Pathology of hypothalamic-pituitary area.
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;
– 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.
– 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
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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.
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.
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
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
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 iormal 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 iearly 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.
I. Constitutional (normal variant) short stature .
II. Nonendocrine disorders (such as chronic disease, malabsorption syndromes, certain hematologic diseases, diseases involving the skeletal system are also common causes of growth retardation).
III. 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.
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.
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.
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.
OBESITY
Obesity is characterized by excessive accumulation of body fat .
Obesity iot 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.)
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.
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Overweight-27,5 – 29,9 I. 30,0 – 34,9 II. 35,0 – 39,9 III. > 40,0
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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
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Waist circumference
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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.
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.
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.
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.
