Management
of patients with pathology of hypothalamic-pituitary area.
THE
HYPOTHALAMIC – PITUITARY RELATIONSHIPS
Hypothalamus
The
hypothalamus modulates the activity of the pituitary gland (hypophysis) via 2
distinct routes, one to the posterior and other to the anterior pituitary. The
hypothalamus is connected with the posterior pituitary (neurohypophysis) by the
supraopticohypophyseal nerve tract (peptidergic neurons). No nervous connection
with the anterior pituitary (adenohypophysis) exists, but blood coursing
through the hypothalamus gathers into a portal venous system which traverses
the anterior pituitary and thus serves as a channel for direct transmission of
the hypothalamic neurohormones. By these 2 routs, the hypothalamus is able to
stimulate or release pituitary hormones.
Neurohypophyseal
function.
The
supraoptic and paraventricular nuclei of the hypothalamus secrete 2 octapeptide
hormones – vasopressin and oxytocin. Both hormones are transported down axons bound
as granules to carrier proteins, and are stored in the nerve endings of the
posterior pituitary. They are released from these endings into the general
circulation, where the granules dissociate, releasing free hormone and
proteins.
Vasopressin (antidiuretic hormone, ADH)
regulates water balance by stimulating resorption in the distal renal tubule.
Secretion of ADH is controlled by increased osmotic pressure and decreased
effective plasma volume.
Oxytocin stimulates uterine contractions
(more so as pregnancy progresses), causes the myoepithelial cells of the breast
to contract, expressing milk into the ducts. Secretion of oxytocin is
controlled by suckling.
Adenohypophyseal
function.
The hypothalamus plays an important
role in hormone regulation by secreting a
series of small peptides which stimulate or inhibit the synthesis and
release of hormones by the anterior pituitary. Traditionally, these hypothalamic
peptides have been known as releasing factors or
as hypophysiotropic hormones (because
they affect not only hormone release but also secretion).
The neurons that secrete the hypothalamic
peptides are located in the ventromedial
nucleus nearby the median eminence. Secretion of
these peptides is intimately related to the
release of neurotransmitters by neurosecretory
cells which are located in the same anatomical area (the
best known neurotransmitters are the catecholamines
dopamine and
norepinephrine and the indoleamine serotonin).
The corticotropin-releasing
hormone (CRH) stimulates the synthesis and release of corticotropin (ACTH)
by the anterior pituitary.
The
thyrotropin-releasing hormone (TRH) controls the secretion of thyrotropin
(TSH) and also causes release of prolactin.
The gonadotropin-releasing
hormone (GnRH), or luteinizing hormone-releasing hormone (LHRH) stimulates
pituitary secretion of luteinizing hormone (LH) and to lesser extent that of
follicle-stimulating hormone (FSH).
The growth-hormone-releasing
hormone (GRH) stimulates and growth-hormone-inhibiting hormone (GIH, or
somatotropin release-inhibiting factor (SRIF), or somatostatin) inhibits growth
hormone (somatotropin) secretion from the anterior pituitary. GIH also inhibits
insulin and glucagon secretion, gastrointestinal secretion of water, bicarbonate,
pancreatic enzymes, gastric acid gastrin; glucose absorption and calcium
transport.
The prolactin-inhibiting
factor (PIF) controls prolactin secretion.
Pituitary gland
The pituitary gland lies in a bony structure, the sella turcica, located at
the base of the skull. The gland is a small organ about I
cm long; it weighs 500 mg and is divided into two parts, anterior (adenohypophysis) and
posterior (neurohypophysis). Both parts derive from the ectoderm, but their origins differ. The anterior
pituitary
originates from Rathke's pouch, an evagination from the roof of the embryonic oral region, whereas the posterior
pituitary is formed from an extension of the floor of the third ventricle.
Secretory granules can be demonstrated in the fetal pituitary by the end of the 12th week. The blood
supply reaches the anterior pituitary through the superior hypophyseal artery (a branch or the internal
carotid) and through the venous portal system, which originates in the median
eminence and ends in the sinusoidal capillaries of the anterior lobe. Hypothalamic peptides reach the
adenohypophysis by way of the portal system. Thin nerve fibers from the carotid plexus
surround the arterioles.
The anterior pituitary secretes several
important hormones, some of which in turn control hormone secretion by other
glands: they are corticotropin (ACTH), somatotropin
(growth hormone), prolactin, gonadotropins [follicle-stimulating
(FSH) and luteinizing (LH) hormones], thyrotropin
(TSH), and melanocyte-stimulating hormones
(MSH).
FEEDBACK :
Hormone secretion → delivery to target cells → hormone recognition
by receptors in target cells → biologic effect → hormone
degradation → signal from target cells to slop further hormone secretion
.
ACTH
stimulates adrenal growth and the secretion of cortisol. ACTH secretion is under
dual control: by the hypothalamus through CRH (stress provokes serotonin
secretion, and last stimulates secretion of GRH) and by adrenals through
cortisol (by negative feedback). ACTH is secreted episodically, in a circadian
pattern, with higher plasma concentrations in the early morning hours.
Somatotropin
(growth hormone) stimulates protein
synthesis and lipolysis, and increases blood glucose concentration (by
decreasing of glucose utilization by the peripheral tissues and stimulating of
hepatic gluconeogenesis). Somatotropin is under the control of GRH and GIH.
Prolactin function is
initiation and maintenance of lactation. (Before pregnancy, the development and
differentiation of the breast are influenced by estrogen, progesterone, and
prolactin, but steroids are not effective in the absence of prolactin).
Prolactin is under the control of TRH, PIF and physiologic stimulus for
prolactin secretion is suckling.
Gonadotropins:
FSH stimulates follicular growth in
the female and spermatogenesis in the male; LH induces ovulation and maintains the corpus luteum after
ovulation has occurred in the female and stimulates testosterone secretion by
the Leydig cells of the testes.
Gonadotropins secretion is under dual control from the hypothalamus
(GnRH production is stimulated by norepinephrine and inhibited by dopamine) and
the gonads (feedback mechanism).
TSH stimulates
the vascularity of the gland and the hypertrophy of the follicular cells, it also has extrathyroid actions, e.g. stimulation of
lipolysis. TSH secretion is under the control of TRH and the thyroid hormones
(feedback mechanism).
MSH stimulates hyperpigmentation. MSH secretion is under the
control of ACTH.
Hypopituitarism. Diagnostic criteria and treatment.
It
is the syndrome, which is characterized by deficiency of one or more anterior
pituitary hormones.
Etiology
Several pathologic processes may play an etiologic
role in the development of the; syndrome:
1. Tumors:
-
chromophobe
adenomas can cause hypopituitarism by
destroying the anterior pituitary cells that secrete the trophic hormones.
Hormone deficiencies in order of frequency are growth-hormone, gonadotropins,
TSH, ACTH, and
prolaclin;
This
photograph is a high power view of the adenoma itself
-
craniopharyngiomas
arise from remnants of Rathke's pouch and
can be either cystic or solid. This tumor is more common in younger people
(with peak incidence in the second decade) who present with signs and symptoms
of increased intracranial pressure; visual field defects, particularly bitemporal
hemianopsia; hypogonadism;
growth retardation; diabetes insipidus; and suprasellar calcifications;
-
pituitary
cysts are very common, with a frequency as
high as 25 % in autopsy series. The cysts vary considerably in size. Some produce
little change in the sella, while others may show moderate supraseliar
extension or even massive sellar erosion.
2. Ischemia:
-
postpartum
uterine hemorrhage (Sheehan's syndrome) is the most common cause of
hypopituitarism in females. The clinical manifestations result from pituitary
necrosis, which is believed to be caused by ischemia. Anterior pituitary
hormone deficiencies appear during the puerperium.
The neurohvpophysis is seldom affected. Failure to lactate and involution of
the breasts are followed
by loss of axillary and pubic hair. The amenorrhea of pregnancy persists and
the symptoms of TSH and ACTH deficiency appear later.
Although gonadotropins and
growth-hormone deficiency may be the earliest to occur, there is variability in
the order in which the hormones fail and in the type of hormones. affected.
This
photograph contrasts the residual viable pituitary (on the right) with the
infarcted necrotic area (on the left).
Notice
the ghost architecture and the acellular area of infarction in this case of
Sheehan'ssyndrome.
-
less
frequently, involvement of the vascular supply to the anterior piluitary
in patients with diabetes mellitus, sickle-cell
disease, and collagen vascular diseases can result in the development of
pituitary insufficiency.
3. Many
cases of hypopiluilarism that were considered idiopalhic probably represent an autoimmune
process in which antipituiatary antibodies are
present. Lymphocytic hypophysitis
is a syndrome reported in women only during pregnancy or the postpartum period.
Signs and symptoms resemble those seen in
patients with pituitary tumors. Light microscopic
studies reveal extensive cellular infiltration of the pituitary by lymphocytes.
Antipituitary
antibodies, particularly to prolactin, have been detected in some of the
patients. The entity is considered to be autoimmune and it is associated
with other endocrine autoimmune
processes, notably chronic thyroiditis.
4. Hypopituitarism
frequently results from pituitary irradiation. Eighty-three % of
patients who receive radiotherapy for tumors of the head and neck, usually 5000
rads, develop pituitary insufficiency.
Hormone deficiencies may develop within a year or more after irradiation. The hypothalamus, the pituitary, or both may
be affected.
5. Infiltration
of the pituitary gland by iron, histiocytes,
or granulomatous processes is a relatively rare cause of
hypopituitarism:
-
hemochromatosis;
-
histiocytosis;
-
sarcoidosis.
6. Infectious
processes:
-
tuberculosis;
-
bacteria;
-
fungus.
7. Pituitary
insufficiency can be caused by traumatic
or surgical destruction
of the hypothalamic-pituitary area.
Clinical presentation.
Many patients with pituitary tumors are asymptomatic,
and the diagnosis is made accidentally by plain x-rays of the skull obtained.
Usually, clinical manifestations of hypopituitarism are not present unless 75 %
of the gland is destroyed.
Some patients present with signs
and symptoms of increased intracranial pressure,
such as headaches,
vomiting, and papilledema. Compression
of the optic chiasm results in visual impairment, notably bitemporal
hemianopsia.
In the classic case of hypopituitarism,
clinical manifestations of ACTH, TSH, and gonadotropin deficiency are presen:
1. Weakness,
dizziness, weight loss, and abdominal symptoms are
secondary to decreased corlisol secretion
by the adrenals. Symptoms of hypoglycemia may predominate. Dehydration,
hypotension, and prostration may be found on physical examination.
2. Gonadotropin
deficiency is responsible for decreased libido in patients of both sexes and
for amenorrhea in females. Decreased
libido, impotence, and hair loss are caused by
testosterone deficiency, and amenorrhea is
caused by estrogen deficiency. In males, a sallow
complexion of the face, prominent
wrinkles of the forehead, and loss of body hair,
particularly pubic and axillary hair, may be very striking.
3. Patients
with unexplained anemia should be investigated for hypopituitarism.
Erythropoiesis is hormone-dependent, and is particularly dependent upon testosterone,
which stimulates erythropoietin production
by the kidney.
4. Secondary
hypothyroidism is characterized by tiredness,
cold intolerance,
constipation, tingling and numbness of the extremities,
and anorexia. Pale, dry skin and slow relaxation phase of the deep tendon
reflexes are observed on examintion
of the patient.
The symptoms of hypopituitarism mimic those of many
diseases. The diagnosis can often be missed unless it is suspected. Watch for
pituitary insufficiency:
Diagnosis.
1. The presence of pituitary insufficiency should be
suspected from the history and physical examination and confirmed by laboralory lesling. There are two types of
diagnostic procedures: those designed to identify the cause of the problem
(usually a radiologic procedure) and those intended for evaluation of pituitary
function.
2. Laboratory findings:
-
anemia, hypercholesterolemia, tendency
to hypoglycemia;
-
hormonal assessment (decreased levels
of pituitary and peripheral endocrine glands).
3. Instrumental investigations.
X-ray
diagnosis of the abnormal sella turcica.
The sella turcica can be evaluated by plain x-ray films of the skull, multidirectional polytomography,
pneumoencephalography, computerized cranial axial tomography (CT scan), magneto – resonance investigation (MRI (pict.)) and cerebral angiography.
Plain films of the sella are useful in evaluating patients for the possibility
of a pituitary tumor. The sella may be abnormal in size, volume, or
configuration. The upper limits of normal for sellar dimensions are length
17mm, depth 13mm, and width 15mm. Sellar enlargement is seen in 90 % of
patients with endocrine deficiency caused by a pituitary tumor, but it may also
be seen in patients with increased intracranial pressure, the empty sella
syndrome, internal carotid artery aneurysm, primary hypothyroidism, and
juxtasellar tumors. Likewise, a normal sella does not rule out pituitary
pathology because microadenomas which are less than
Adenoma
Cerebral angiography is useful in establishing the presence of parasellar
lesions, determining the degree of suprasellar or parasellar extension of a
pituitary tumor, excluding the presence of an aneurysm, and determining whether
major vessels are involved by the tumor.
Visual fields.
A search for visual-field defects is important. Visual impairment in patients
with hypopituitarism suggests the presence of a pituitary tumor compressing the
optic chiasm. Bitemporal hemianopsia is the typical finding but other
visual-field defects may be present. This ophthalmologic procedure can also
help to monitor the response to therapy and to evaluate patients for possible
tumor recurrences.
Treatment
The treatment of patients with pituitary
insufficiency consists of
1)
eliminating the underlying cause and
2)
replacing the
deficient hormones.
Pituitary tumors should be removed surgically,
although irradiation and drug therapy (bromocriptine) are also available.
Hypothalamic
peptides or pituitary hormones are not suitable for hormone replacement for several reasons:
(1) The human hormones are difficult to oblain in
pure form;
(2) because of their nature and short halh-life they
have to be given parenterally and frequently; and
(3) since they stimulate antibody formation, their
activity is lost a few weeks after initiation of therapy.
Under these circumstances the usual practice is to
administer the hormones produced by the target glands. They are available in pure form and are relatively
inexpensive.
Adrenal
insufficiency. Hydrocortisone is given orally in a total daily
dose of 20 to 30 mg. Many physicians give one 20-mg tablet in the morning and
half a tablet in the afternoon to try to stimulate the normal diurnal variation
of plasma cortisol. This practice is not necessary, the local amount can be
given as a -single dose in the morning. Other steroids with glucocorticoid
activity can be used. Prednisone is preferred by some physicians because of its
lower cost.
Hypothyroidism. Symptoms are
easily controlled with synthetic l.-thyroxine. Most patients need 0.15 mg/day.
In women the replacement dose is usually lower, and many do well on 0.1 mg/day.
Hypogonadism
replacement with gonodal steroids is never indicated until puberty
normally occurs. These agents in high doses can hasten bone maturation and
epiphyseal closure, thereby limiting the height which may ultimately be
reached.
In males
testosterone therapy is recommended. (Testosterone
enanthate, a long-acting preparation at a dose which is equivalent to 50 to
100 mg/week. This is given as an intramuscular injection of 100 to 200 mg every
2 to 4 weeks. At the beginning of therapy, it is useful to administer 200 mg IM
every 2 weeks until a good androgenic response is obtained. Side effects
of testosterone include gynecomastia, acne, and occasionally hypertension,
presumably secondary to stimulation of sodium
retention by testosterone. The indications
for testosterone therapy include decreased
libido and anemia). Methyltestosterone
or fluoxymesterone
(10 to 40 mg/day) can also be used. They
have the advantage of convenience, since
they can be given orally, but development of cholesiatic jaundice and liver
disease are potential problems with their use.
Premenupausal
females
with ovarian failure should be treated with estrogens. It can be
ethinyl estradiol, which is administered orally in a dose of 0,025 to 0,05 mg
once a day for 25 days of each month. Although this is the usual replacement
dose. some patients may need a smaller or a
larger dose. The benefits of estrogen
therapy
include return of menstruation, improvement of secondary sex characteristics
such as skin texture and breast development, increased libido, and prevention
of osteoporosis.
Side effects. Estrogen therapy
is not without risk, e.g., the increased incidence of thrombophlebitis and
pulmonary embolus.
Hypertension, glucose intolerance, liver disease and
hyperlipoproteinemia
are also potential problems. There is also some controversial evidence that
estrogens predispose to carcinoma of the endometrium,
To minimize all these side effects,
it is recommended that the minimum
effective estrogen dose be used, that estrogens be prescribed cyclically rather
than on an everyday basis, that periodic pelvic examinations be performed, and
that an endometrial biopsy be done at the first sign of unexpected uterine
bleeding.
Acromegaly. Gigantism. Pituitary dwarfism.
Increased secretion of growth hormone
(GH) by pituitary tumors or increased sensitivity of peripheral tissues to GH
leads to gigantism before puberty and to acromegaly after
puberty.
Etiology
1.
Acidophilic adenoma of the pituitary.
2.
Chromophobe adenoma of the pituitary
Gross
of a large chromophobe adenoma. Notice the location of
the
tumorin relation to the optic chiasm to explain visual field changes
3.
Ectopic
GH-producing tumors.
Clinical
features
The
signs and symptoms which appear in these patients are of two types:
1)
those secondary to the presence of
tumor: mass effect (Headaches and visual impairment are present in 90 and 60 %
of the patients respectively. Typically one finds bilateral loss of peripheral
vision (bitemporal hemianopsia), which may be progressive.) and
2)
those secondary to increased
circulating growth-hormone levels.
Gigantism
is
characterized by height more than
Leonid Stadnyk - 7 feet 7 inches (231.1 cm) with
Yushchenko V. (president of Ukraine 2005-2010), 183 sm.
Leonid Stadnyk (full name Leonid Ivanovych
Stadnyk), (born 1971 in Zhytomyr Oblast, Ukraine) is a living man renowned for
his stature. He was formerly listed as the world's tallest living man according
to Guinness World Records. On August 20, 2008, editor-in-chief of Guinness
World Records, Craig Glenday, announced that the title of world's tallest man
had been returned to China's Bao Xishun after Stadnyk refused to be measured
under new guidelines, which required him to be independently measured by
Guinness World Records adjudicators.
Differential
diagnosis have to be made with
-
constitutional high height
- Klainfelter’s syndrome
-
Marphan syndrome
Acromegaly
GH
hypersecretion after closure of epiphyses leads to periostal overgrowth and
cortical thickening. Overgrowth of the mandible leads to protrusion of the jaw
(prognatism). There is an overbite and the teeth become separated (diastema).
Bone overgrowth and soft tissue thickening lead to characteristic coarsening of
the facial features. The hands are widened and the fingers become broad,
requiring a larger ring size.
Similiar changes in the feet require a larger
shoe size. This increase in dimension of the acral (distal) parts of the body
has led to the term acromegaly.
Hepatomegaly
and cardiomegaly are consistent findings. Thyromegaly is present in about 25 %
of the patients. Hyper- and hypothyroidism occurs rarely. The kidney may also
become enlarged, and renal clearance of phosphate is frequently impaired.
Hypertension
is present in 40 % of patients with acromegaly, although its cause is unknown.
It is unclear whether the increase in blood pressure is caused by growth
hormone per se or whether it is part of the generalized cardiovascular
involvement seen in patients with the disease. Plasma renin may be high,
normal, or low. The association of primary aldosteronism with acromegaly has
been reported in a few cases.
Other
manifestations of the disease are secondary to the abnormalities in glucose
metabolism which result from growth-hormone excess. Thus, symptoms of diabetes
mellitus, which include polyuria, polydipsia, polyphagia, and tiredness, may be
present.
Increased
perspiration is common among 90 % of patients. The skin is thickened, and
females may note hypertrichosis.
Joint
manifestations are common (70 %) in patients with acromegaly. In some patients,
for example, arthralgias and arthritis may be the presenting complaints.
Amenorrhea,
which occurs in as many as two-thirds of female patients, may be the chief complaint.
Decreased libido is experienced by one-third of the patients.
Hyperfunction
or deficiency of other pituitary trophic hormones may be present. Of note is
the frequency among women with acromegaly (15 % of cases) of galactorrhea which
is caused by increased secretion of prolactin by the pituitary tumor.
Diagnosis
The
diagnosis of acromegaly is usually suspected from:
1)
the
patient's history and
2) physical
examination (The head is large, the mandible is prominent, and the tongue is
enlarged. The skin is thick and hard. Large hands and feet and increased
subcutaneous tissue are evident on examination. Carpal tunnel syndrome occurs
in as many as 44 % of the patients. Deformed joints can be confused with other arthritic
syndromes.).
3)
The role of the laboratory is to
assist in the confirmation of the diagnosis. Since the syndrome is caused by
excessive growth-hormone production, one wants to demonstrate increased
circulating levels of this hormone. An occasional blood sample drawn at
-
some patients with acromegaly have
normal growth-hormone concentrations, and
-
in normal subjects growth-hormone levels vary
greatly. Stress, sleep, exercise, food ingestion, and diurnal variation can
significantly affect growth-hormone concentrations. Thus, a normal serum
growth-hormone level does not exclude acromegaly, and an elevated
growth-hormone level does not always mean acromegaly.
To
eliminate this problem one takes advantage of the concepts of feedback and
autonomy to screen patients for acromegaly. Normally, glucose suppresses
growth-hormone secretion. In patients with acromegaly the pituitary tumor is
autonomous; that is, it does not respond to hyperglycemia. The recommended
procedure consists of a glucose tolerance test with concomitant growth-hormone
determinations; serum growth-hormone concentration falls in normal subjects 1 h
after the oral glucose load. Patients with acromegaly not only have elevated
values but also fail to suppress in response to glucose ingestion.
4)
Somatomedin-C, the tissue mediator of
some of the effects of growth hormone, has been measured by radioimmunoassay
in the blood of patients with acromegaly. Because somalomedin-C binds to plasma
protein, its serum concentrations are more stable than those of growth hormone.
The values are evaluated in patients with acromegaly and they correlate well
with growth hormone values 1 h post glucose administration.
5)
A paradoxical growth-hormone increase
in response to TRH is seen in some patients with acromegaly, and when this
abnormality is found, it can be used to follow the response to therapy.
6)
Glucose intolerance is seen in about
40 % of the patients. This information becomes available at the time the
glucose tolerance test is ordered to obtain growth-hormone levels.
7)
An important part of the evaluation
in patients with acromegaly is the search for visual-field defects. As
mentioned earlier, because of the anatomical location of the tumor, the typical
finding is the presence of bitemporal hemianopsia. However, other visual-field defects
may be present.
8)
The sella turcica is enlarged in at least 90 % of patients with acromegaly.
(MRI , CT) Because of the slow progression of the disease, the sella is usually
enlarged when the patient is first seen.
9)
One should also be interested in
determining whether suprasellar extension of the tumor is present, and the best
procedure for this purpose is computed tomography. This information can help
the surgeon to decide what approach to use when removing the tumor.
Treatment.
Three
therapeutic modalities—surgery, irradiation, and drugs—have been used to treat
patients with acromegaly.
The
surgical
techniques of craniotomy, transsphenoidal hypophysectomy, and stereotaxic
surgery, particularly cryosurgery, have been used to treat acromegaly, and all
of them have met with some success.
At
present, transsphenoidal hypophysectomy is the procedure of choice. An incision is
made in the inner aspect of the upper lip and the pituitary gland is entered
through the nasal septum and the sphenoid sinus. With this procedure,
improvement or cure of the acromegaly can be achieved in nearly 90 % of the
patients. Advantages of transsphenoidal hypophysectomy, besides its
effectiveness, include simplicity and low morbidity. Hypupituitarism and
diabetes insipidus are extremely uncommon, since the remainder of the
pituitary gland is left intact. Perhaps the major difficulty of transsphenoidal
hypophysectomy is the fact that some patients need a second operation because
of recurrence of symptoms.
Craniotomy
is reserved for large tumors with suprasellar extension and involvement of the
optic chiasm. Cryohypophysectomy (destruction of the pituitary by cold
injury) can reduce the secretion of growth hormone without causing
hypopituitarism in 88 % of the patients.
External irradiation
has been reported by some to control the activity of the disease in as many as 80
% of the patients, but other reports indicate that the procedure has not been
too successful. One of the limitations is the amount of radioactivity that can
be delivered, which should not exceed 5500 roentgens (R). Another difficulty
with irradiation is its slow onset of action, the full effects requiring as
long as 10 years to appear.
Irradiation
with accelerated proton beams, which can be focused on the
pituitary, delivers 10,000 or more rads without damaging the surrounding
tissues. Results with this technique and those obtained with alpha particle
irradiation are similar.
Drugs.
A
dopaminergic agonist and ergot derivative, 2a-bromergocriptine (bromocriptine),
causes a paradoxical inhibition of growth-hormone secretion in patients with
acromegaly. In doses of 10 to 60 mg/day, the drug has induced clinical
remissions in 73 % of the treated patients. However, return of normal
growth-hormone suppressibility in response to glucose is seen in only 22 % of
patients. Side effects include nausea, orthostatic hypotension, constipation,
digital vasospasm, and peptic ulcer.
PITUITARY DWARFISM (GROWTH FAILURE) -
it is the disease caused by decreased
secretion of GH by pituiatary gland or decreased sensitivity of peripheral
tissues to this hormone and leads to growth retardation.
The
height of adult men is less than
Etiology
Children
with pituitary dwarfism most commonly have either a craniopharyngioma or no demonstratable etiology (idiopathic
hypopituitarism). The latter is more frequent in males than in females. Before
the diagnosis of pituitary dwarfism can be made, all other etiologies must be
ruled out (look differential diagnosis).
Classification.
A. Organic (trauma, neoplasms,
infection).
B.
Idiopatic (primary or secondary, due
to hypothalamic deficiency).
1.
Panhypopituitarism.
2.
Isolated GH deficiency (may be
hereditary and transmitted as an autosomal recessive trait, in other instances
a hereditary basis cannot be established).
Clinical manifestations
1.
Child is born with normal weight and
height.
2.
Growth retardation can be observed
since 3 – 4 years (the increasing of the height is not more than
3.
The patient, despite small size, has
normal body proportions.
4.
Mental
develoment is normal.
5. Secondary hypothyroidism.
6. Secondary adrenal insufficiency.
7.
Puberty will not appear because of a
lack of gonadotropic hormons (secondary hypogonadism).
8.
The passport age is not corresponding
with biologic age.
9.
In patients with isolated GH
deficiency the patients have normal pituitary function (other than lack og GH),
undergo normal puberty, and have normal reproductive capacity.
Diagnosis
Clinical
picture (carefully recorded growth charts may disclose the time of onset of the
disease); level of GH; X-ray examination of the skull and hands can be helpfull
in diagnosis.
Differential diagnosis
have to be made with other causes of short stature:
I.
Endocrine:
1.
Primordial (Lorrain – Levi) dwarfism (is an
ill-defined diagnosis which presupposes normal hormonal activity in an
individual with limited potential for tissue growth. Because the infants in
this category are often small for gestation age, the term intrauterine dwarfism
has also been used to designate those who have
growth retardation at birth. While patients with hypopituitarism are
normal of size at birth (probably because of maternal Ghand somatomedin),
patients with premordial dwarfism are already dwarfed at thus time because
maternal somatomedin is not available or is ineffective. Characteristically,
growth is slow from earliest infancy, although epiphyseal maturation and sexual
development occur normally or at only a slightly retarded rate. No definite
abnormalies have been reported. Intellect may be affected and other congenital
anomalies may be present.)
2.
Hypothyroidism (primary or secondary)
3.
Precocious puberty.
4. Cushing’s syndrome.
II.
Constitutional
(normal variant) short stature .
III.
Nonendocrine
disorders (such as chronic disease, malabsorption
syndromes, certain hematologic diseases, diseases involving the skeletal system
are also common causes of growth retardation).
![dwe00215g02[1]](20.Managment%20of%20patients%20with%20pathology%20of%20pituitary%20gland.files/image059.gif)
IV.
Psychosocial
dwarfism (is associated with severe emotional
deprivation, and is alleviated by the removal of the child from the adverse
situation).
Treatment.
I.
Balanced
diet.
II.
Complex
of physical exercises.
III.
Pharmacotherapy.
1.
GH (synthetic). Indications: a low
level of GH or a low level of somatomedin in patients with biologic age less
than 12 – 13 years and passport age more than 3 years. Doses of 2 – 4 IU of GH given IM at night
time three times a week for 2 – 3 months with 2 – 3 months break have
accelerated the rate of linear growth, through often this therapeutic effect is
not sustained.
2.
Anabolic steroids under the control
of biologic (osteal) age.
3.
Thyroid
replacement.
4.
Replacement with gonodal steroids is
never indicated until puberty normally occurs. These agents in high doses can
hasten bone maturation and epiphyseal closure, thereby limiting the height
which may ultimately be reached.
5.
Vitamintherapy.
IV.
Surgical therapy (a craniopharyngioma
presents special therapeutic problems, usually necessitating removal of tumor
tissue or drainage of fluid from tumor cysts.
DIABETES
INSIPIDUS
Diabetes insipidus is a clinical disorder characterized by the excretion
of large quantities of diluted urine and caused either by failure of ADH
release (hypothalamic diabetes insipidus) or by lack of response of the tubules
to normal quantities of circulating ADH (nephrogenic diabetes insipidus).
Criteria for the diagnosis of hypothalamic diabetes insipidus
include:
(1) insufficient ADH
release despite serum hyperosmolality and
(2) an increase in
urine osmolality in response to exogenous ADH.
Etiology
Causes of hypothalamic diabetes insipidus:
1.
Surgery:
section of the supraopticohypophyseal tract above the median eminence.
Disruption of the tract at the level of the pituitary stalk leads 10 transient
diabetes insipidus which disappears in 1 to 2 weeks.
2.
Trauma to the hypothalamus or the median eminence.
Most commonly, diabetes insipidus resulting from trauma is transient, but it
may be permanent.
3.
Tumors
that destroy the site of production and release of ADH are either primary, such
as craniopharyngioma or metastatic, the most common being carcinoma of the
breast.
4.
Infiltration
of the hypothalamus by leukemic cells, granuloma (sarcoidosis, tuberculosis),
histiocytes (Hand-Schuller-Christian disease), or infections. All these are
rare causes of diabetes insipidus.
5.
Idiopathic.
6.
Familial.
Diabetes insipidus can be masked by a
concomitant deficiency of the anterior pituitary hormones. In the absence of
cortisol, there may be enhanced release of ADH as well as increased sensitivity
of the tubules to ADH, both of which lead to an impairment in water excretion.
In addition, growth hormone, cortisol, and thyroxin increase the glomerular
filtration rate. In patients with panhypopituitarisrn, diabetes insipidus
becomes clinically manifest when cortisol and thyroxin replacement begin.
Causes of nephrogenic diabetes insipidus:
1.
Hereditary
factors: X-linked transmission with predominance in males.
2.
Acquired
factors:
Dietary factors: With marked
restrictions of protein intake, there is decreased availability of urea, which
normally accounts for 50 percent of medullary
interstitial hypertonicity during antidiuresis. Dietary sodium
deficiency causes a concentrating defect by enhancing proximal salt
reabsorption, thereby limiting sodium delivery to the loop of Henle.
Electrolyte disorders. Patients with
chronic hypokalemia or chronic hypercalcemia may develop both polyuria and the
inability to concentrate the urine. In both conditions, medullary tonicity is
diminished but the identity of the primary pathophysiologic mechanism is
unclear. The urine of patients with hypokalemia and polyuria is usually
isotonic (osmolalily 300), in contrast to the hypotonic urine found in patients
with diabetes insipidus.
Drugs: Lithium carbonate,
demeclocycline. methoxyflurane. and amphotericin B interfere with the action of
ADH on the tubules. Patients on these drugs can develop marked hypotonic
polyuria. The presence of massive polyuria a few days after anesthesia with
methoxyflurane may lead to severe dehydration if it is not recognized and
treated promptly. Massive polyuria is usually reversible.
Renal disease Chronic renal disease of different types may
produce isotonic mild polyuria, which is resistant to the action of ADH
Clinical picture.
The hallmark of diabetes insipidus is
the excretion of large quantities of urine (usually 5 to 10 L/day, but the amount can be more).
In mild forms of diabetes insipidus,
polyuria may be minimal with urine volumes of 2 to 4 L/day.
Source: www.1tv.ru
Polydipsia (ingesting of large amounts of mostly cold water).
Insomnia, decreasing
of appetite, dryness of skin and mucous membranes, pharyngitis, gastritis, constipation are common in
patients.
In situations in which
the patient has no access to water, is unconscious, or has an abnormality of
the thirst mechanism, severe dehydration may ensue.
Source:www.darmedcenter.ru
Diagnosis
A careful study of the patient's
history, a physical examination, and an awareness of previous laboratory
abnormalities are required in evaluating patients with polyuria.
Typically, in severe
diabetes insipidus the urine has a specific gravity of less than 1,005 and an
osmolality of less than 100 mosmol/kg; serum osmolality is increased. Patients
with partial diabetes insipidus can concentrate the urine to isotonic or moderately
hypertonic levels. Some patients with diabetes insipidus are able to compensate
for the urine loss by ingesting large amounts of fluids so that serum
osmolalily, which is usually elevated, may be normal or only slightly
increased.
Differential diagnosis.
First it is necessary to determine
whether one is dealing with diabetes insipidus or other types of polyurea, such
as diabetes mellitus, or increased fluid intake. Then a distinction between
hypothalamic and nephrogenic diabetes insipidus must be made. The so-called
psychogenic polydipsia, a condition which occurs in patients who ingest large
quantities of water and other fluids, is the most important these responses to
keep in mind.
|
|
Psychogenic polydipsia |
Hypothalamic diabetes insipidus |
Nephrogenic diabetes insipidus |
|
History |
Insidious onset |
Abrupt
onset, brain surgery, tumor present, steroid therapy |
Family
history, chronic hypokalemia, chronic hypercalcemia, postanesthesia |
|
Physical examination |
Normal hydration |
Dehydration may be present |
Dehydration may be present |
|
Laboratory: -
serum osmolality; -
urine osmolality |
270 – 290 (↓ to N) < 200 (↓) |
285 – 320 (N to ↑) < 200 (↓) |
285 – 320 (N to ↑) < 200 (↓) |
|
Pituitrin administration |
Patient
feels ill; no change in serum osmolality; increase in urine osmolality |
Patient
feels better; decrease in serum osmolality; increase in urine osmolality |
No
change in serum or urine osmolality |
Treatment.
In an acute situation when a rapid
effect is desirable, Pituitrin (aqueous
Pitressin) should be given intravenously
at a rate of 5 mU/min or subcutaneously in doses of 5 to 20 U every 4 to 6 h.
The preparation is available in vials containing 20 U/ml.
In the chronic management of
hypothalamic diabetes insipidus, the following drugs have been used:
Adiurecrin powder nasal spray0,03 g 1
– 3 times a day was formerly used (nasal irritation and bronchopulmonary
allergic reactions, however, are considerable problems).
Adiuretin in drops 1 – 3 times a day.
Synthetic lysine vasopressin is available
as a nasal spray in 5-ml vials containing 50 U/ml of the drug. The usual dose
is 1 to 2 sprays three or four times a day.
Pituitrin 0,5 – 1 ml subcutaneous 2 –
3 times a day. The patient's body weight, urine, and serum osmolality should be
monitored at weekly or monthly intervals depending upon the clinical response.
The oral hypoglycemic agent
chlorpropamide has been effective in controlling polyuria in as many as 80
percent of patients with hypothalamic diabetes insipidus. The major action of the
drug is potentiation of the effect of ADH on the tubules. An additional effect
on stimulation of ADH release is controversial. It is given in doses similar to
those employed in patients with diabetes mellitus—that is, doses of 100 to 500
mg/day. The hypolipidemic agent clofibrate can also stimulate release of ADH
and is useful in treatment of some patients with hypothalamic diabetes
insipidus. The dose is similar to that used for hyperlipidemia, namely 500 mg
four times daily. Chlorpropamide and clofibrate are synergistic. This allows
usage of lower doses of each drug in combination.
Because of lack of response of the
tubules to ADH, none of the agents listed above is effective in the treatment
of nephrogenic diabetes insipidus. This entity is treated by means of dietary
protein and sodium restriction in order to minimize the osmotic load that must
be excreted and, hence, minimize the urine flow. A thiazide diuretic (50 to 100
mg/day of hydrochlorothiazide) is added to enhance the sodium depletion and impair
the ability of the tubules to generate a dilute urine. Inhibitors of
prostaglandin synthesis, particularly indomethacin, have effected a decrease in
urine flow in a few patients with nephrogenic diabetes insipidus. The E
prostaglandins (PGEs) have been shown to inhibit ADH action on the renal
tubules by decreasing cAMP formation.
Cushing's syndrome
Cushing syndrome is caused by prolonged exposure to elevated levels of
either endogenous glucocorticoids or exogenous glucocorticoids.
The source of cortisol excess can be:
-
the adrenal gland (endogenous
Cushing's syndrome);
Pict. Adrenal
adenoma
-
administration of supraphysiologic
doses of a glucocorticoid (exogenous Cushing's syndrome).
Endogenous Cushing's syndrome can be:
1)
ACTH
– dependent, caused by:
-
increased pituitary ACTH secretion
(it has frequently been reffered to as Cushing’s disease, implying a partucular
physiologic abnormality. Patients with Cushing’s disease may have a basophilic adenoma
of the pituitary, or a chromophobe adenoma. In some cases, no histologic
abnormality is found in the pituitary despite clear evidence of ACTH
overproduction. Microadenomas, which are difficult to visualize
radiographically, are often the cause);
. 
Pict. Pituitary
MRI - basophilic adenoma of the pituitary
-
nonpituitary ACTH secretion by
nonendocrine tumors;
2)
Non
– ACTH – dependent:
-
caused by cortisol secretion by
benign or malignant adrenal tumors;
-
micronodular or macronodular
dysplasia of the adrenal (the condition occurs most commonly in children and
young adults).
In
pituitary-dependent Cushing's syndrome, increased secretion of endogenous ACTH
leads to bilateral adrenal hyperplasia and cortisol overproduction. ACTH
secretion continues despite high circulating cortisol, indicating an abnormality
in the feedback mechanism. A good number of these patients harbor a pituitary
microadenoma which secretes ACTH. Despite normal x-rays of the sella, including
tomograms, the neurosurgeon often finds and removes the microadcnoma through
the transsphenoidal route. Pituitaty – dependent adrenal hyperplasia accounts
for about 60 to 70 percent of endogenous Cushing’s syndrome cases.
A
polypeptide that resembles pituitary ACTH in its biologic and immunologic action
can be secreted by a great variety of nonendocrine tumors, particularly oat
cell carcinoma of the lung, but also by carcinoid bronchial adenomas, and by
carcinomas of the prostate, ovaries, and pancreas, as well as others.
Nonpituitary ACTH stimulates the adrenals to hypertrophy and to overproduce
cortisol. Because the feedback mechanism is intact, pituitary ACTH secretion is
suppressed by cortisol.
In
patients with adrenal tumors, the excessive production of cortisol suppresses
endogenous secretion of ACTH by the pituitary gland. An adrenal tumors is foud
in 20 percent of the patients.
Exogenous, or
iatrogenic, Cushing’s syndrome is
caused by administration of supraphysiologic doses of glucocorticoids. Besides
cortisol, other synthetic steroids with glucocorticoid activity have the
ability to suppress ACTH secretion by the anterior pituitary. Adrenal atrophy
and a decrease in cortisol secretion then result. Although the patients exibits
the clinical manifestations of Cushing’s syndrome, adrenal insufficiency may
actually occur if the steroid is discontinued abruptly. Because of the
widespread use of glucocorticoids, iatrogenic Cushing’s syndrome is the most
common type.
History:
·
Patients with Cushing
syndrome may complain of weight gain, especially in the face, supraclavicular
region, upper back, and torso.
·
Frequently, patients
notice changes in their skin, including purple stretch marks, easy bruising,
and other signs of skin thinning.
·
Women may complain of
irregular menses and hirsutism.
·
Because of progressive
proximal muscle weakness, patients may have difficulty climbing stairs, getting
out of a low chair, and raising their arms.
·
Psychological problems
such as depression, cognitive dysfunction, and emotional lability may develop.
·
New-onset or worsening of
hypertension and diabetes mellitus, difficulty with wound healing, increased
infections, osteopenia, and osteoporotic fractures may occur.
·
Patients with an
ACTH-producing pituitary tumor (Cushing disease) may develop headaches,
polyuria and nocturia, visual problems, or galactorrhea.
·
If sufficient mass effect
from the tumor is present on the anterior pituitary, hyposomatotropism,
hypothyroidism, hyperprolactinemia or hypoprolactinemia, and hypogonadism may
develop.
·
In addition, look for the
following:
o
Irregular menses or
amenorrhea in women and decreased libido, infertility, and impotence in men
o
Polyuria or polydipsia
from diabetes mellitus or diabetes insipidus
o
Impaired wound healing or
predisposition to infections from immunosuppression
·
When rapid onset of
glucocorticoid excess occurs, virilization in women or feminization in men may
be seen. This scenario suggests an adrenal carcinoma as the underlying cause of
the Cushing syndrome.
Physical:
Obesity
o
Patients may have increased
adipose tissue in the face (moon facies), upper back at the base of the neck
(buffalo hump), and above the clavicles (supraclavicular fat pads).
Pict.Moon face.
o
Central obesity with increased adipose tissue in the
mediastinum and peritoneum; increased waist-to-hip ratio greater than
Pict. Central obesity
Skin
o
Facial plethora may be
present, especially over the cheeks.
Pict. Facial plethora
o
Violaceous striae,
usually more than
Pict. Striae.
o
Ecchymoses may be
present.
o
Patients may have
telangiectasias and purpura.
o
Cutaneous atrophy with
exposure of subcutaneous vasculature tissue and tenting of skin may be evident.
o
Hirsutism and male
pattern balding may be present in women.
o
Patients may have increased
lanugo facial hair.
o
Steroid acne, consisting
of papular or pustular lesions over the face, chest, and back, may be present.
o
Acanthosis nigricans,
which is associated with insulin resistance and hyperinsulinism, may be
present. The most common sites are axilla and areas of frequent rubbing, such
as over the elbows, around the neck, and under the breasts.
Cardiovascular and renal
o
Hypertension may be present.
o
Volume expansion may
occur, with edema from sodium and water retention.
o
Diabetes mellitus may be
present.
Gastroenterologic
o
Peptic ulceration may
occur with or without symptoms.
o
Particularly at risk are
patients given high doses of glucocorticoids (rare in endogenous
hypercortisolism).
Endocrine
o
Hypothyroidism may occur
from anterior pituitary tumors, which can interfere with proper
thyroid-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) function.
o
Galactorrhea may occur
when anterior pituitary tumors compress the pituitary stalk, leading to
elevated prolactin levels.
o
Other pituitary function
may be interrupted. Possibilities include polyuria and nocturia from diabetes
insipidus.
o
Menstrual irregularities,
amenorrhea, and infertility may occur due to inhibition of pulsatile secretion
of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which
likely is due to interruption of luteinizing hormone-releasing hormone (LHRH)
pulse generation.
o
Low testosterone levels
in men may lead to decreased testicular volume from inhibition of LHRH and
LH/FSH function.
o
Low estrogen levels in
women may result from inhibition of LHRH and LH/FSH function.
o
Increased synthesis of
high-density lipoprotein (HDL), low-density lipoprotein (LDL), and
triglycerides may occur.
o
With severe
hypercortisolism, hypokalemic metabolic alkalosis may occur.
Skeletal/muscular
o
Proximal muscle weakness
may be evident.
.
Atrophy of muscles
o
Osteoporosis may lead to
incident fractures and kyphosis, height loss, and axial skeletal bone pain.
Avascular necrosis of the hip also is possible from glucocorticoid excess.
Neuropsychological
o
Patients may experience
emotional liability, fatigue, and depression.
o
Visual-field defects,
often bitemporal, and blurred vision may occur in individuals with large
ACTH-producing pituitary tumors that impinge on the optic chiasm.
o
Adrenal crisis
o
Patients with cushingoid
features may present to the emergency department in adrenal crisis. Adrenal
crisis may occur in patients on steroids who stop taking their glucocorticoids
or neglect to increase their steroids during an acute illness. It also may
occur in patients who have recently undergone resection of an ACTH-producing or
cortisol-producing tumor.
o
Physical findings that occur in a patient
in adrenal crisis include hypotension, abdominal pain, vomiting, and mental
confusion (secondary to low serum sodium level or hypotension). Other findings include hypoglycemia, hyperkalemia,
hyponatremia, and metabolic acidosis.
o
Diagnosis.
There are two phases of
investigation:
-
confirmation of the presence or
absence of Cushing’s syndrome;
-
differential diagnosis of its case.
1.
Exogenous
Cushing's syndrome should offer no problems in diagnosis since a history of
chronic ingestion of suprapliysiologic doses of glucocorlicoids is usually
present. However, occasionally patients deny, either deliberately or because of
ignorance, that they have been taking the glucocorticoid. In this case, the
diagnosis can easily be made by obtaining a blood sample at
2.
Single-dose
dexamethasone suppression test. This is the preferred procedure for screening
patients for Cushing's syndrome. The patient ingests 1.0 mg of dexamethasone at
bedtime (10 to 12 p.m.), and a blood sample for plasma cortisol is obtained
the following morning at
(There are a
few clnical situations in which failure of dexamethasone suppression occurs in
the absence of Cushing's syndrome. Patients who are under acute stress,
particularly those with fever and infections, and depressed individuals may not
respond to dexamelhasone. Therapy with estrogen, and occasionally phenobarbital
or phenothiazines may alter the response to dexamethasone. To some extent, all
these drugs induce the hepatic microsomal enzymes that metabolize
dexamethasone, and acceleration of the hepatic metabolism of the steroid
results in insufficient plasma levels to yield a normal response. In these conditions, and in any others in
which an abnormality in the metabolism of dexamethasone is suspected,
simultaneous quantitation of the plasma dexamethasone concentration offers
extremely useful information. Compared with individuals who exhibit no
abnormalities in the metabolism of the steroid, individuals with altered
hepatic metabolism have a much lower plasma concentration. Estrogens also
increase the synthesis of corticusteroid-binding globulin (CBG) by the liver.
Since plasma cortisol assays measure both bound and free cortisol, values are
high in people on estrogen medication.)
3.
48
– hour low dose dexamethasone test. The results obtained with the single-dose
dexamethasone suppression test are comparable to those of the first suppression
test developed by Liddle. In this procedure, eight 0.5-mg doses of
dexamethasone at 6-h intervals are given orally; 24-h urine samples for
17-hydroxycorticosteroids (17-OHCS) excretion are collected before and during
dexamethasone administration. In normal subjects, 17-OHCS values are below 3 mg
per 24 h on the second dexamethasone day. Patients with Cushing's syndrome fail
to suppress. Not only is this test less convenient and more expensive but it
may not be accurate if incomplete urine collections have been obtained.
4.
High-dose
dexamethasone suppression test. After the oral administration of a single dose
of 4.0 mg of dexamethasone between 10 p.m. and midnight, the measured
5.
radiologic diagnosis includes X-ray examination for a pituitary tumor, and
computed tomography which is the most popular procedure for visualizing the
adrenals in patients with Cushing's syndrome.
Treatment.
surgery. If
clinical manifestations are severe and definitive correction is immediately
required, surgery will be the procedure of choice for most patients with Cushing's
syndrome. Pituitary surgery is the preferred therapeutic modality for
pituilary-dependent Cushing's syndrome. The transsphenoidal route is most
commonly utilized, but transfruntal exploration may be required for large
tumors or areas where there is extrasellar extension. There is general
agreement that once the diagnosis of pituitary-dependent Cushing's syndrome has
been established the pituitary should be explored with or without radiologic
evidence of a pituitary tumor. Operative morbidity of pituitary surgery is 2 to
5 %. Transphenoidal hypophysectomia is usually successfulwhen carried out by an
experienced neurosurgeon. While the
majority of patients may be cured by this operation and normal pituitary function
will remain intact, recurrences occur and may appear months or years after the
operation.
Because
a pituitary adenoma is not found in all cases, complete tumor removal is
difficult, and recurrences arise following adenomectomy, partial or even total
hypophysectomy has been recommended by some clinicians. With partial
hypophyseclomy best results are obtained by removing the central mucoid zone
which contains most of the ACTH-secreting cells. With total hypophysectomy, the
problem of recurrences is resolved but hypopituitarism develops, necessitating
permanent hormone-replacement therapy. Therefore, indiscriminate use of total
hypophysectomy is not justified. Adrenalectomy is the treatment of choice in
patients with adrenal tumors. Since the lesion is unilateral in most cases,
only one adrenal is removed. Therapy with glucocorticoids, is required for as
long as a year because of chronic suppression of ACTH secretion and atrophy of
the contralaleral adrenal.
Bilateral
adrenalectomy is utilized to treat patients with primary adrenocortical nodular
dysplasia. although a few patients with this condition have responded to
hypophyseclomy. Bilateral adrenalectomy is a difficult procedure, with an
operative mortality of 4 to 10 percent of patients. There is a recurrence of
the disease as the result of hyperplastic remnant in 10 percent of patients,
and development of hyperpigmentation with rapid growth of pituitary tumors in
10 to 20 percent.
In patients with nonpituitary tumors
that are secreting ACTH, surgery or chemotherapy my be helpful. In patients
with severe hypercortisolism that is not controlled by surgery or drugs,
bilateral adrenalectomy may be necessary . The changes produced by Cushing's disease are partially reversible
(after several months).
Pict.
Female before and after adrenalectomy
pituitary irradiation. If clinical manifestations are not severe, pituitary
irradiation may be tried initially. Pituitary irradiation is delivered by means
of conventional cobalt radiotherapy (4500 rads), by proton-beam irradiation, or
by pituitary implantation of radioactive material. Conventional cobalt
radiotherapy has a cure rate in 46 to 83 percent of patients. Two-thirds of
these patients experience a complete resolution of the signs and symptoms, and
the others manifest some degree of improvement. The response is better in
younger individuals. Improvement, however, is slow and may take 6 to 18 months.
Radiation effects continue for many years, and the incidence of hypopituitarism
is 80 percent at 20 years. If there is no response to pituitary irradiation
after 6 month, adrenalectomy is indicated.
drugs. Several
drugs have been used to treat patients with Cushing's syndrome. Improvement of
the clinical manifestations is the result of a decrease in ACTH secretion by
the pituitary gland or cortisol secretion by the adrenals.
Cyproheptadine
(Periactin) and peritol have been helpful in some patients with
pituitary-dependent Cushing's syndrome. Cyproheptadine has peripheral and central
antiserotonergic, antihistaminergic, anticholinergic, and antidopaminergic
actions, but the inhibition on ACTH secretion is the result off its
antiserotonin effect on the hypothalamus. The drug is administered orally at an
initial dose of 4 mg three times a day, which is increased to a maximum dose of
4 mg every 4 h over 2 to 4 weeks. Clinical and biochemical responses occur
within 2 to 3 months after initiation of therapy, and the return of
dexamethasone suppressibility and ACTH and cortisol periodicity are observed by
6 to 12 months. Remission of the disease occurs in 30 to 50 percent of the
patients and the longest duration of remission has been 5 years. Although a few
cases of permanent remission after discontinuation of the drug have been reported,
relapse is the rule. Cyproheptadine can be used in combination with pituitary
irradiation. The drug is given for 4 to 6 months to control symptoms before the
effects of irradiation are manifested. The two major side effects are
hyperphagia (with weight gain) and somnolence. The dopamine agonist bromocriptine
is very useful. The usual dose is 2.5 mg three times a day. But the therapy has
to be began from the ¼ of a tablet (2.5 mg) at a bedtime for 3 to 4 days
(because of its side effect such as somnelence), then it has to be increased on
¼ of a tablet each 3 days to 7.5 mg.
Several
adrenal cortisol inhibitors are available to treat patients with Cushing's
syndrome, particularly those with adrenal carcinomas or nonpi-tuitary
ACTH-secreting tumors. Mitotane, Lysodren inhibit adrenal growth and interferes
with cortisol synthesis by blocking the conversion of cholesterol into
pregnenolone. The dose is 1 to 10 g/day. Side effects include gastrointestinal
complaints, sedation, depression, and adrenal insufficiency. Because of its
inhibitory effect on adrenal growth, the drug is preferred for the treatment of
adrenal cancer. Aminoglutethimide (Cytadren, Elipten) inhibits the conversion
of cholesterol into pregnenolone as well, but it does not have any effect on adrenal
growth. The usual dose is 250 to 500 mg four times a day. Side effects are
gastrointestinal complaints, drowsiness, skin rash, goiter, and adrenal
insufficiency. Metyrapone (Metopirone) inhibits the last step in cortisol
synthesis - the conversion of 11-deoxycortisol into cortisol. Effective doses
range from1 to 4 g/day. Better results are obtained when metyrapone is
administered every 2 h rather than every 4 h. Hirsutism is the most frequent
problem with prolonged metyrapone usage. Trilostane, at a dosage of 0.25 to 1.0
g/day, can reduce cortisol synthesis effectively. A combination of two drugs,
such as aminoglutethimide and metyrapone, usually is more effective than any
drug alone. Problems shared by all of these drugs are (1) the fact that their effects
cease as the result of both a compensatory increase in ACTH secretion and of
stimulation of partially suppressed adrenals and (2) the development of adrenal
insufficiency. These problems can be minimized by administering physiologic
amounts of a glucocorticoid, such as 0.5 mg/day of dexamethasone. If
hypotension and electrolyte problems develop, 0.1 mg/day of the
mineralocorticoid 9-alfa-fluorohydrocortisone (Florinef) should be given.
Hypothalamic syndrome of pubertal period.
Particularities.
1. Obesity
is not cushingoid (not central).
2. Striae
(pink and not very large).
3. Hypertension (constant or permanent).
4.
Glucose
intolerance.
Treatment.
1.
Diet 8.
2.
Parlodel
(2.5 – 5 mg for 3 – 6 month).
3. Peritol
(4 mg 2 times a day for 1 month).
4. Dehydration
therapy (hypothiasid 50 – 100 mg/day MgSO4 25 % solution intramuscular 10 – 15 times).
5. Nonsteroid antiinflammatory drugs
(indometacine).
6.
Biogenic
stimulators (aloe, plasmol).
7. Increasing
of microcirculation of the blood in the
brain (cavinton, piracetam).
8. Vitamintherapy.
9.
Symptomatic
therapy (hypotensive therapy).
10.
Phisiotherapy.
THE
SYNDROME OF INAPPROPRIATE SECRETION OF ADH.
Normally,
serum hyperosmolality stimulates and hypoosmolality suppresses ADH release.
Increased ADH promotes renal water reabsorption, thereby increasing urine
concentration, and decreased ADH results in increased renal water excretion and
the production of a dilute urine. Thus. in normal subjects, changes in urine
osmolality parallel those in serum osmolality.
The syndrome of inappropriate ADH
secretion is characterized by persistent ADH secretion and the excretion of a
concentrated urine despite serum hypoosmolality.
Etiology.
The
syndrome of inappropriate ADH secretion may develop under a wide variety of
clinical settings. It should be understood that inappropriate ADH secretion is
associated with numerous conditions: the syndrome occurs following surgery and
trauma, with many drugs, in patients with pulmonary and central-nervous-system
diseases, and in association with cancer and tuberculosis. (ADH activity has
been found in tuberculous lesions, and it is believed that the tuberculomas
secrete ADH or an ADH-like substance). Abnormalities which are similar to those
observed in the syndrome of inappropriate ADH secretion are seen in certain
other endocrine disorders, notably hypothyroidism and pituitary insufficiency,
and in patients with congestive heart failure and cirrhosis of the liver.
Pathogenesis.
Hyponatremia
and serum hypoosmolality result from excessive water retention, Suppression of
aldosterone and inhibition of proximal tubular sodium reabsorption, by volume
expansion, lead to increased urinary sodium excretion. However, caution should
be exercised in interpreting urinary sodium excretion in patients with [he
syndrome of inappropriate ADH secretion. Urine sodium excretion is a reflection
of the amount ingested or the amount given parenterally. For this reason, a
high urinary sodium excretion is not always seen, and a low urinary sodium does
not exclude the diagnosis of the syndrome. The quantities of water retained in
patients with the syndrome rarely exceeds
Diagnostic criteria
The characteristic features of the
syndrome include:
1.
Hyponatremia.
2.
Serum
hypoosmolality.
3.
Continuous
urinary sodium excretion despite hyponatremia.
4.
Urine
osmolalily usually greater than the serum osmolality.
5.
Absence
of clinical edema.
6.
Reversal
of the abnormalities following water restriction.
7.
Symptoms
are usually not present unless the serum sodium concentration falls below 120
meq/L. When this occurs, headaches, anorexia, nausea, and vomiting may ensue.
With marked hyponatremia (100 to 110 meq/L), symptoms related to the central
nervous system, such as confusion, disorientation, hostility, convulsions, and
coma, may predominate. Arrhythmia may also occur.
Differential diagnosis
It is
recommended that cardiac, hepatic, adrenal, and renal disease be ruled out
before making the diagnosis of inappropriate ADH secretion.
The
differential diagnosis of the syndrome of inappropriate ADH secretion is that
of
dilutional hyponatremia. The most important diagnosis to be considered because
of its therapeutic implications is that of adrenal insufficiency.
Treatment
Identification of the underlying
cause and measures to correct it are important therapeutic goals.
The mainstay of therapy for the
syndrome of inappropriate ADH secretion is water restriction to less than 1
L/day. Weight loss and an increase in serum sodium concentration will occur 3
to 7 days after therapy has been started.
In patients who present with marked
hyponatremia (less than 110 meq/L) and neurologic symptoms, particularly
seizures, infusion of 250 ml of hypertonic saline (3 % NaCI) over 2 to 4 h is
indicated.
Furosemide in combination with intravenous or
oral sodium chloride sometimes is effective. The therapeutic goal is to
increase free water clearance and at the same time to replace the sodium
urinary losses .
Sexual disorders.
Primary and secondary hypogonadism. The hermaphroditism. The menopause.
TESTOSTERONE DEFICIENCY SYNDROMES
Testosterone
has a role in the development of fetus and its absence will result in female
phenotype. A lack of testosterone at the expected time of pubescence is manifest
by delayed closure of epiphysis and eunuchoidal skeletal proportions, no
deepening of the voice, delayed and scanty growth of pubic and axillary hair,
absence of beard and mustache growth, small prostate, small penis and a
nonpigmented, nonrugated scrotum, low testicular volume with absent
spermatogenesis, poor muscular development, and usually, psychosocial
immaturity. The patients are usually brought to the physician by their parents,
who are worried about poor growth and development.
Classification:
Primary hypogonadism (due to Leydig cell dysfunction.
GnRHs in serum or urine are elevated because of decreased feedback at the
pituitary – hypothalamic unit).
Secondary (due to disorders of the hypothalamic – pituitary
unit. Pituitary and hypothalamic hypogonadism may be differentiated by
appropriate testing with GnRH)
Primary hypogonadism
Leydig
cell function is depressed in malnutrition, in renal failure, myotonic
dystrophy, in chronic disease, to a variable extent with aging, and by certain
toxins such as lead and alcohol.
Klinefelter’s
syndrome
This
most frequent cause of primary hypogonadism is defined as the presence of one
or more extra X chromosomes in at least one tissue.
The
hallmark of the Klinefelter’s syndrome is the presence of small and firm
testes, containing sclerosed tubules with only rare sertoli cells, and there is
thus usually azoospermia. Eunochoidal habitus, gynecomastia, female
distribution of body fat, particularly around the hips, and female distribution
of pubic hair, lack of temporal recession of the hairline, arched palate,
mental retardation constitute the typical findings. Many of these clinical
findings may be absent and the disease manifests itself only by infertility or
decreased fertility.
Laboratory
studies include azoospermia, chromatin-positive buccal smear, and the elevated
plasma FSH and LH. An XXY chromosomal pattern is most characteristic, but may
be XXY/XX, XYY, XXYY, and multitude of others are known. Plasma testosterone
levels are in the low range or slightly depressed.
Sertoli-cell-only
syndrome (germinal aplasia).
These
patients present as essentially normal men with slightly reduced testicular
volume and infertility. There is an absence of germinal cells in the tubules.
Plasma testosterone is normal, and elevated serum FSH concentrations. There are
no chromosomal abnormalities in this syndrome, and the buccal smear is
negative.
Noonan’s
syndrome (male Turner’s)
These
boys have a normal XY karoytype, some of the features of Turner’s syndrome (such as hypertelorism, short stature,
epicanthal folds, and right – sided congenital heart disease), and various
skeletal malformations. In contrast to Turner’s syndrome, mental retardation is
often present. Leydig cell function may be normal or decreased and some
patients may have cryptorchism.
Secondary hypogonadism.
Delayed
pubescence.
The
prepubertal male is hypogonadotropic. FSH stimulation of tubular development is
the first evidence of pubescence. At the present, there is no reliable test to
distinguish between delayed puberty and hypogonadotropic hypogonadism.
Kallman’s
syndrome (hypogonadotropic hypogonadism).
It
is the most frequent cause of secondary hypogonadism. It is inherited as an autsomal dominant with
variable penetrance and is characterized by low FSH, LH levels, anosmia or
hypoosmia, and the variable occurrence of short fourth metacarpals, syndactyly,
midline skeletal defects, and mental retardation. Inadequate secretion of FSH
and LH may occur as an isolated defect as well. In both cases the disease can
be shown to be hypothalamic in origin, since repeated injections o GnRH will
eventually elicit a normal gonadotropin response. Boys remain sexually prepubescent
until either testosterone secretion is induced by HCG (chorionic gonadotropin)
or androgen is given.
Isolated
LH deficiency (fertile eunuch syndrome).
This
is a rare syndrome, the boys having pubertal testicular size and some
spermatogenesis in the absence of signs of androgen effect. The deficiency of
LH is not complete and HCG will virilization and increased sperm counts.
Laboratory
assessment of Leydig cell function
In
the adult male, cessation or diminution of testosterone secretion is difficult
to appreciate clinically. The symptoms of loss of libido and impotence are not
specific for androgen lack and the most often occur in men with normal Leydig
cell function. A decrease in frequency of shaving, early soft wrinkling of the
face, and a softening of the testis may be present.
serum testosterone levels,
serum gonadotropins,
GnRH stimulation;
Karyotype;
HCG stimulation.
Treatment
Patients with primary hypogonadism can be virilized
with exogenous androgens (testosterone enanthate). They cannot become fertile
and gonadotropin treatment need not be considered.
Patients with secondary hypogonadism can be treated by
androgens and HCG.
Syndromes of androgen resistance.
Syndromes
manifested by feminine habitus and the presence of testes, and is characterized
by an absolute or varying degrees of resistance to androgen action as a result
of absent or decreased amounts of intracellular receptor for
dinydrotestosterone.
Patients
present in their teenage years as girls with primary amenorrhea, this
pseudohermaphroditism is inherited, with transmission as an X-linked recessive
or autosomal dominant trait. In the most extreme form, testicular feminization,
the women have well-developed breasts, absent pubic and axillary hair, normal
external genitalia, a short blind vaginal pouch, an absent uterus, and
testes(palpable “masses”) present either in the labial folds or inguinal canal.
The tests have small tubules and lack germ cells.
Laboratory
data are X, Y genotype, testosterone, and estradiol levels at the upper limits
of the normal adult male range, high LH (due to androgen resistance), and
usually normal FSH (due to persistent Sertoli cells).
Treatment
of these patients consists of removal of the testes to obviate the increased
risk of testicular neoplasm, and replacement of estrogens. Patients are
irreversibly infertile.
Precocious puberty -
is
activation of the hypothalamic-pituitary axis with a consequent enlargement and
maturation of the gonads, and the development of the secondary sexual
characteristics, adult serum testosterone levels, and spermatogenesis (the
onset of sexual maturation before age
The
incidence of true precocious puberty is greater in females (2:1), and about 80
% of female cases have no identifiable abnormality. In contrast, 60 % of male
cases have underlying organic disease.
Boys
exhibit facial, axillary, and pubic hair, penile growth, and increased
masculinity. Linear growth is initially rapid in both sexes, but the adult
height is shortened by premature closure of the epiphysis.
Laboratory
evaluation should include skull x-rays, 24-h urinary 17-KS measurement, and the
serum LH, FSH levels, CT scanning of the brain.
Treatment
include therapy of the organic factor and suppressing of gonadotropins.
Sexual
disorders in the female are often presented with menstrual abnormalities such
as primary (Turner’s syndrome, congenital adrenal hypoplasia) and secondary
amenorrea.
Turner’s syndrome
(ovarian dysgenesis)is characterized by 45,X karyotype and chromatin-negative
buccal swear, streak gonads, infertility, primary amenorrhea, short stature,
sexual infantilism, a variety of phenotypic abnormalities (webbing of the neck,
high-arched palate, low posterior hairline, low-set ears, cubitus valgys, chest
deformities, shortening of metacarpal, metatarsal, and phalangeal bones,
hypoplastic nails, pigmented nevi, small mandible, epicanthol folds, lymphedema
of the hands and feet, tendency for keloid formation) plasma gonadotropins are
usually elevated.
True hermaphroditism
It
is the presence of male and female gonads in the same individual.
The
exact origin of true hermaphroditism is not known.
The
external genitalia are ambiguous, with either male or female predominance. A
penis with hypospadia and cryptorchism is often present. Breast development and
menses occur in about 70 % of the patients ovulation and spermatogenesis are
uncommon most patient are raised as males. 2/3 of patients are
chromatin-positive, and the most common karyotype is 46,XX. Mosaic patterns
such as XX/XY and XY/XXY are often found.
The menopause.
It
is discontinuation of menstruation. It may be natural (results from
age-related declining ovarian function and usually occurs between ages 40 and
50. As the ovary becomes atrophic and ceases to respond to gonadotropin
stimulation, the few remaining follicles undergo atresia and urinary
gonadotropin excretion increases sharply), premature (refers to
cessation of ovarian function before the age 40, and must be distinguished from
gonadal dysgenesis and hypopituitarism), artificial (follows
ovariectomy, irradiation of the ovaries).
Menopause
may be asymptomatic or symptoms primarily due to estrogen deficiency and autonomic
nervous system responses may be severe and last a few months or year.
Menopausal
symptoms:
1)
early:
- vasomotor effects (hot flushes and sweating);
- psychological (anxiety, emotional lability,
irritability);
2)
middle:
- genitourinary (dyspareunia (senile vaginitis),
vaginal infections, urgency of micturation);
- changes of the skin and hair (dryness, hair loss);
3)
late:
- Osteoporosis Video;
- cardiovascular disorders.
Treatment include
nonmedicamentous (diet, physical exertions, massage), medicamentous (vitamins,
sedative, calcium preparations), hormonal therapy (estrogens).
OBESITY
Obesity is characterized by excessive accumulation of body fat .
Obesity in not a condition for which a precise
definition is particularly useful. Unlike many “real” diseases, obesity
represents one arm of distribution curve of body fat or body weight, with no
sharp cut-off point. Its importance lies in the many, often serious,
complications to which obese people are subject. In these complications that
warrant undertaking a treatment that is so often unsuccessful.
Etiology
The cause of obesity is simple –
consuming more calories than are expended as energy. However, we usually do not
know why persons consume more calories than they expend.
Predisposing
factors
1. Social
factors (obesity is prevalent among lower-class people than among upper-class.
Other social factors, particularly ethnic and religious are also closely linked
to obesity, how these factors lead to obesity, or its control, has not been
established, but differences in life style, dietary and exercise patterns, probably
play a major role).
2. Sex
(female have greater tendency to gain weight particularly at puberty and during
pregnancy), age (at middle aged people have more tendency to become obese.
Anyhow, obesity is present among all age groups).
3. Endocrine
factors. (Certain diseases of endocrine glands are associated with obesity i.e.
hypothyroidism, Cushing’s disease, hypogonadism.)
4. Psychological
factor (many obese persons report that they overeat when emotionally upset, but
many nonobese persons also overeat in such conditions. Two deviant eating
patterns based on stress and emotional disturbance, however, may contribute to
the obesity of a few patients. Bulemia is the sudden, compulsive ingestion of
very large amounts of food in a very short time, usually followed by agitation,
self-condemnation, and often by self-induced vomiting. The night-eating
syndrome consists of morning anorexia, evening hyperphagia, and insomnia.
Attempts at weight reduction in these 2 conditions are usually unsuccessful and
may cause the patient unnecessary distress.)
5. Genetic
factors (It is widely recognized that obesity runs in families: 80 % of the
offspring of 2 obese parents are obese, compared with 40 % of the children of 1
obese parent and only 10 % of the offsprings of 2 nonobese parents.).
6. Physical
activity. (Decreased physical activity in affluent societies is often sited as
a major factor in the rise obesity.)
7. Development
factors.(The increased adipose tissue mass in obesity can result from either an
increase in size of fat cells (hypertrophic obesity), from an increase in the
number of fat cells (hyperplastic obesity), or from an increase in both
(hypertrophic-hyperplastic obesity). Most persons whose obesity began in adult
life suffer from hypertrophic obesity. They lose weight solely by the decrease
in the size of their fat cells; the number of fat cells does not change.
Persons whose obesity began in childhood are more likely to suffer from
hyperplastic obesity, usually of the combined hypertrophic-hyperplastic type.
They may have up to 5 times as many fat cells as either persons of normal
weight or those suffering from pure hypertrophic obesity. As a result, they may
be able to reach a normal body weight only by marked depletion of the lipid
content of each fat cell.)
![19267[1]](20.Managment%20of%20patients%20with%20pathology%20of%20pituitary%20gland.files/image113.jpg)
8. Brain
damage. (Brain damage, particularly to the hypothalamus, can lead to the
obesity.)
Classification
by Egorov
1. Alimentary.
2. Endocrine.
3. Cerebral.
Classification
due to stages of obesity
A.
According
to Brock’s index (N: weight = height – 100).
I.
Weight excess < 30 %.
II.
Weight excess 30 – 50 %.
III.
Weight excess 50 – 100 %.
IV. Weight
excess > 100 %.
B.
According
to Kettle’s index or body
mass index .
Experts believe that a person's body
mass index (BMI) is the most accurate measurement of body fat for children and
adults.
Adults with a BMI greater
than 30 are considered obese. Adults with a BMI between 25 and 29.9
are considered overweight.
|
|
Overweight-27,5 – 29,9 II. 35,0 – 39,9 III. > 40,0 |
![figure7[1]](20.Managment%20of%20patients%20with%20pathology%20of%20pituitary%20gland.files/image118.gif)
There are exceptions. For example, an
athlete may have a higher BMI but not be overweight .
Classification
due to deposition of fat tissue.
-
lower type (gluteofemoralis).
-
upper type (abdominal): Waist/hip
ration
>
>
Waist
circumference
>
>
Both methods identify those with increased CVD risk;
Clinical
manifestations.
Obese people come to the doctor not only complain about
their fitness but also with complications (cardiovascular, pulmonary,
orthopedic and others).
Clinical
particularities of hypothalamic obesity.
1. Fast
gain weight (20 –
2. More
frequent dysplastic localization of the fat.
3. The
presence of the striae.
4. Symptoms
associated with increased intracranial pressure and neurologic picture
(somnolence, raised appetite and others).
5. Signs
of hypothalamic dysfunction (palpitation, hyperhydrosis, hypertension).
Differential diagnosis
have to be made between different
types of obesity.
Alimentary
obesity
1. Genetic
(family) factor.
2. Eating
habits (ingestion of large amounts of food).
3. Slow
progressing.
Pickwickian
syndrome
It can occur in the massively obese persons. Pressure
on the thorax from the encompassing sheath of the fatty tissue combined with
pressure on the diaphragm from below by large intra-abdominal accumulations may
lead to reducing of the respiratory capacity, hypoventilation, retention of CO2
leading to decreased effects of CO2 as respiratory stimulant and
resultant hypoxia and somnolence
Hypothalamic-pituitary
disorders.
Barraquer–Simons
syndrome (progressing lipodystrophia)
1. More
frequent is in young women.
2. Atrophy
of the subcutaneous adipose tissue in the region of face neck, thorax;
increased quantity of adipose tissue in the lower part of body, thighs, legs
(“riding-breeches” type).
3. Duration
of the disease, as a rule, without any changes in nervous and endocrine system
and patients have only cosmetic defect.
Dercum disease (generalized painful
lipomatosis).
1. More
frequent is in women in menopause.
2. There
is localized, painful nodes (knots) in the subcutaneous adipose tissue. These
nodes are painful, itch, the skin over nodes is red.
3. Patient
can have normal weight or be obese.
4. Person
has nervous changes (CNS asthenia, neuroses) and endocrine disturbances
(decreasing of function of sexual glands).
Babinski-Fröhlich syndrome
(adipose-genital dystrophy)
1. More
frequent is observed in boys.
2. Characterized
by obesity (dysplastic type) and hypogenitalism (development of primary and
secondary sexual signs is stopped: small sizes of scrotum, penis, may be
criptorchism).
3. There
is often lack in growth.
Postnatal
neuroendocrine syndrome (PNES)
.
1. Increasing
of the weight during 3 – 12 months after abortion or labor (Kettle’s index
usually is more than 30).
2. Subcutaneous
adipose tissue is localized like in patients with Cushing’s syndrome.
3. Striae
are present.
4. There
is moderate hirsutism, tendency to hypertension and hyperglycemia.
5. Ovary
unovulatory hypofunction is present. PNES may lead to endocrine sterility.
Endocrine
pathology.
Laurence-Moon-Biedl syndrome or Laurence-Moon-Biedl-Bardet .
1. Obesity,
hypogenitalism like in patients with Babinsky-Frelych’s disease.
2. Decreased
mental activity or debility.
3. Pigmental
retinitis.
4. Bones
or inner organs abnormalities (polydactylia, syndactylia and others)
Morgagni Stewart Morel syndrome.
1. More
frequent in young women or in climacteric female.
2. Adipose
tissue localized in the region of chin, abdomen (like apron) mammary glands
(mastoptosis), skin is flabby, striae are absent.
3. Hirsutism
is present (beard, moustache).
4. Hypertension.
5. Diabetes
mellitus.
6. Increased
thickness of lamina interna of frontal bone.
Hyperostosis Frontalis Interna
Treatment.
The
prognosis for obesity is poor, particularly for obese children, and the course
tends to progress throughout the life. Obesity is a chronic condition resistant
to treatment and prone to relapse. Most obese persons will not participate in
outpatient treatment, and those who do will not lose a significant amount of
weight. Most of those who do lose weight will regain it. These results are
poor, not because of failure to implement any therapy of known effectiveness,
but because no simple or generally effective therapy exists. The numerous
people who try to reduce without medical assistance, on diets and advice from
magazines, may have more success.
The
basis of weight reduction in all treatment regimens is to establish a caloric
deficit by reducing intake below output.
Diet
The simplest way to reduce caloric
intake is with a low-calorie diet. Optimal long-term effects are achieved with
a balanced diet containing readily available foods. For most people, the best
reducing diet consists of their usual foods in amounts limited with the aid of
standard tables of food values. Such a diet gives the best chance of long-term
maintenance of the weight loss, although it is the most difficult diet to
follow during weight reduction. Consequently, many people turn to novel or even
bizarre diets, of which there are many. The effectiveness of these diets, if
any, results, in large part, from monotony - nearly everyone will tire of
almost any food if that is all they get to eat. Consequently, when they stop
the diet and return to their usual fare, the incentives to overeat are
increased. Fasting has had considerable vogue as a treatment for obesity, but
it is now rarely used. Most patients promptly regain most of the weight they
lose. Since fasting is not without complications, it should be carried out in a
hospital.
Several recommendations. Patient
has to:
1)
eat 4 – 5 times a day, only in a
direct time, not to eat between basic meal receptions;
2)
eat
only one portion;
3)
limit a free liquid to 1,0 – 1,2
l/day;
4)
not to eat with the aim of decreasing
depression, not to eat “for a company”;
5)
the total daily energy intake should
be between 1600 – 800 Kcal.
Physical activity
It
is frequently recommended in weight reduction regimens and its usefulness has
probably been underestimated even by its proponents. Since caloric expenditure
in most forms of physical activity is directly proportional to body weight,
with the same amount of activity obese persons expend more calories than do
those of normal weight.
Physical
activity has to be: 1) regular; 2) bring
only positive emotions; 3) it is better to work in a group of the patients.
Medications
Many
preparations (amphetamines, fenfluramine, others) are used as anorectic drugs.
Their efficacy and side effects seem comparable and their potential to abuse
limited. However, to an even greater degree than after other conservative
treatment, weight is regained after drug treatment and the use of appetite
suppressants is currently out of favor.
We
have to use medications in patients with endocrine and cerebral pathology:
anti-inflammatory drugs (to treat encephalitis, arachnoiditis), bromcreptin,
peritol (to treat hypothalamic and pituitary disorders) and others.
Physiotherapy.
Massage, automassage, circulating shower-massage are very effective in the
treatment of the patients.
Surgery.
Radical
surgical treatment may offer some hope
to persons with morbid obesity (100 % overweight) in whom all others treatments
have failed.
For the dangerously overweight, it’s the
only way to lose pounds and keep them off.
Morbid obesity leads to
hypertension, type 2 diabetes, obstructive sleep apnea, depression,
incontinence, arthritis and other significant health problems.
Worried about their health and tired of being socially
isolated, some morbidly obese individuals turn to bariatric surgery.
"Obesity is a complex problem, and successful treatment is based on a
healthy diet, counseling, increased physical activity and, when indicated,
surgery," says Raul J. Rosenthal, M.D., one of three bariatric surgeons at
Cleveland Clinic Florida.
Limiting intake or altering digestion.
The are two types of bariatric surgery, both of which are
effective for significant, long-term weight loss. Gastric (stomach) restrictive
procedures limit food intake by decreasing the size of the stomach so that the
sensation of "fullness" (or pain) occurs after a small amount of food
is ingested. Malabsorptive procedures alter the digestion process, thus causing
food to be poorly digested and incompletely absorbed. The excess is eliminated
in the stool.
"Most patients who choose bariatric surgery have tried
all kinds of diets with little success, and this is their last option. If they
don’t have the surgery, they have a 50 to 100 percent chance of dying
prematurely from obesity-related problems," says Dr. Rosenthal. "Our
goal is to help patients live longer."
Getting around the stomach.
Several types of bariatric surgery have been developed, but
the two favored by Dr. Rosenthal and his colleagues are adjustable gastric
banding (also called gastric banding), a restrictive procedure, and proximal
roux-en-y gastric bypass, a malabsorptive procedure that
involves bypassing a large portion of the stomach.
Gastric banding involves no stapling or cutting of the
stomach; rather an implantable hollow band is used to isolate a small portion
of the upper stomach to make a pouch that serves as a "new" stomach.
The pouch fills quickly with solid food and empties slowly to relieve hunger
and produce a feeling of fullness. Overeating results in pain or vomiting.
The roux-en-y gastric bypass procedure is an alternative
means of achieving malabsorption, and is the most commonly performed and
successful malabsorptive surgery. It also involves creating a separate gastric
pouch while leaving the rest of the stomach in place. Unlike bypass procedures
that involve removal of the stomach, the roux-en-y approach poses fewer
operative risks.
New approaches help reduce pain, shorten recuperation.
Traditional or "open" bariatric surgery requires a
6- to 8-inch incision and approximately four weeks of recuperation. Using
minimally invasive surgical techniques in select patients, however, Dr.
Rosenthal and colleagues can perform restrictive or malabsorptive bariatric
procedures without opening the abdomen. The minimally invasive approach
achieves results comparable to those associated with open surgery, but with
less post-operative pain and swifter recovery. Patients who undergo minimally
invasive bariatric surgery can return to work one week after undergoing gastric
banding and two weeks after gastric bypass.
Malabsorptive bypass procedures such as roux-en-y bypass
produce more weight loss than restrictive operations and are more effective in
reversing the health problems associated with severe obesity. Patients who have
malabsorptive operations generally lose two-thirds of their excess weight
within 2 years. According to Dr. Rosenthal, gastric bypass procedures account
for 90 percent of the bariatric operations performed today. "It has been
done for 40 years, so it is well understood. Doing them laparoscopically,
however, is rather new," he says.
Patients who undergo a gastric bypass feel full after eating
about two tablespoons of food. Due to some malabsorption, nutritional
supplements are necessary. In the three months following surgery, patients can
expect to lose about
Patients who undergo gastric banding can lose up to
Risks are significant, but rare.
In gastric banding, complications include kinking of the
stomach, leaking from the site of banding or band breakage, all of which
require surgical intervention to resolve. Side effects of gastric bypass
surgery include internal bleeding, pulmonary embolism and unidentified leakage.
Such serious side effects, however, are rare, says Dr. Rosenthal; and the risk
can be further reduced by seeking care from an experienced bariatric surgeon
who offers a comprehensive program of care. "The surgeon should offer
safe, proven procedures, a thorough preoperative workup, and a postoperative
program consisting of nutritional consultation, support groups and mental
health counseling. This helps ensure an optimal outcome," says Dr.
Rosenthal.
Roux-en-Y stomach surgery for weight loss
The
Roux-en-Y gastric bypass procedure involves creating a stomach pouch out of a
small portion of the stomach and attaching it directly to the small intestine,
bypassing a large part of the stomach and duodenum. Not only is the stomach
pouch too small to hold large amounts of food, but by skipping the duodenum,
fat absorption is substantially reduced.
Restrictive gastric operations, such
as an adjustable gastric banding
procedure, serve only to restrict and decrease food intake and do not
interfere with the normal digestive process.
In this
procedure, a hollow band made of special material is placed around the stomach
near its upper end, creating the small pouch and a narrow passage into the
larger remaining portion of the stomach. This small passage delays the emptying
of food from the pouch and causes a feeling of fullness.
The band
can be tightened or loosened over time to change the size of the passage.
Initially, the pouch holds about
Adjustable gastric banding
Vertical
banded gastroplasty
Restrictive
gastric operations, such as vertical banded gastroplasty (VGB), serve only to
restrict and decrease food intake and do not interfere with the normal
digestive process.
In this
procedure the upper stomach near the esophagus is stapled vertically to create
a small pouch along the inner curve of the stomach. The outlet from the pouch
to the rest of the stomach is restricted by a band made of special material.
The band delays the emptying of food from the pouch, causing a feeling of
fullness.
Biliopancreatic diversion (BPD )
Malabsorptive
operations, such as biliopancreatic diversion (BPD), restrict both food intake and
the amount of calories and nutrients the body absorbs.
In a BPD
procedure, portions of the stomach are removed. The small pouch that remains is
connected directly to the final segment of the small intestine, completely
bypassing the upper part of the small intestines. A common channel remains in
which bile and pancreatic digestive juices mix prior to entering the colon.
Weight loss occurs since most of the calories and nutrients are routed into the
colon where they are not absorbed.
References.
А.
1.
Davidson's Principles and
Practice of Medicine (1st Edition) / Edited by N. R. Colledge,
B. R. Walker, S. H. Ralston. - Philadelphia
2.
Harrison’s Principles of Internal
Medicine (18th edition) / D. Longo,
A. Fauci,
D. Kasper,
S. Hauser,
J. Jameson,
J. Loscalzo,. – New York : McGraw-Hill
Education - Europe, 2011. – 4012 p.
3.
Kumar and Clark's Clinical Medicine
(8th Revised edition) (With studenrconsult Online Access) / P. KumarM. L. Clark . –
B. Additional
1.
Greenspan's Basic and Clinical Endocrinology ( 9th Revised edition) / David G. Gardner, Dolores M. Shoback. –
2.
Oxford Handbook of Endocrinology and Diabetes ( 2nd
Revised edition) / John A. H. WassHelen Turner. –
3.
Williams Textbook of Endocrinology (12th Revised edition) / Shlomo Melmed, Kenneth S. Polonsky, P. Reed Larsen, Henry M. Kronenberg, 2011. – 1897 p.
4.
5.
Oxford Textbook of Endocrinology and Diabetes2nd
Revised edition) / John A. H. WassPaul StewartStephanie A. AmielMelanie J. Davies. –
6. Web-sites:
http://emedicine.medscape.com/endocrinology