REGULATION OF FUNCTIONS OF ORGANISM BY HYPOTALAMIC – PITUITARY SYSTEM AND ADRENAL GLANDS.
BIOCHEMICAL PRINCIPLES OF INFERTILITY.
Role of endocrine system in vital activity of the organism
The endocrine system relates the most important regulatory systems. It carries out regulatory influence with the help of hormones practically on all functions of an organism – metabolism , growth, reproduction, mental activity, adaptation, functional activity of all organs.
Hormones can be synthesized:
· by epithelial cells (one’s own glandular ephithelium );
· by neuroendocrine cells (hypothalamic cells);
· by myoendocrine cells (muscular fibres of heart atriums).
According to chemical nature they differentiate:
· steroid hormones (mineral – and glucocorticoids, female and male sexual hormones);
· derivatives of aminoacids (thyreoid hormones, catecholamines, melatonine);
· protein peptide hormones (releasing-hormones, vasopressin, oxytocin, hormones of adenohypophysis, insuline, glucagone, parathyrin, calcitonine).
According to functional effects hormones can be:
· affectors (act directly on organs – targets);
· tropic (regulate synthesis of effecting homones);
· releasing–hormones (regulate synthesis and secretion of tropic hormones).
Etiology of endocrine disorders
Reasons and kinds of endocrine disorders. Among numerous ethiological factors of endocrine disorderss it is possible to select the following main ones: a mental trauma, necrosis, tumour, inflamatory process, bacterial and viral infections, intoxications, local disorders of blood circulation (hemorrhage, thrombosis), alimentary disorders (deficiency of iodine and cobalt in food and drinking water, redundant consumption of carbohydrates), ionising radiation, inherent chromosome and gene defects.
There are three variants of endocrine functions disorders :
1. Hyperfunction of endocrine glands
2. Hypofunction of endocrine glands
3. Disfunction of endocrine glands.
Disfunction is characterized by different changes of hormonal production and production physiologic active precursors of their biosynthesis in the same endocrine gland or synthesis and entering in blood of atypical hormonal products.
Pathogenesis of endocrine disorders
The mechanisms of function disorders of an endocrine gland can be various depending on localization and character of process.
In pathogenesis of endocrine disorders it is possible to select three main mechanisms:
1) Disorders of regulation of endocrine glands – disregulatory disorders;
2) Disorders of biosynthesis of hormones and their secretion – glandular disorders;
3) Disorders of the transport, reception and metabolism of hormones – peripheral disorders.
Disorders of endocrine gland regulation
Regulation of endocrine gland activity can be carried out with the help of four mechanisms:
1. Nervous (impulse-mediators) or parahypophysis regulation. With the help of direct nervous influences the activity of following structures is regulated: а) adrenal medulla; b) neuroendocrine structures of hypothalamus; c) epiphysis.
2. Neuroendocrine or transhypophysar regulation. It is carried out by neuroendocrine cells of hypothalamus, which transform nervous impulses in specific endocrine process. Along releasing-hormones, which regulate activity of adenohypophysis are synthesized and get secreted in the system of portal vessels of hypophysis .
3. Endocrine regulation. It is that some hormones influence on synthesis and other influence secretion of the others. An example of this mechanism is the influence of adenohypophysis tropic hormons on activity of adrenal cortex, thyroid gland, sexual glands.
4. Non-endocrine humoral regulation is carried out by unspecific humoral factors, in particular by metabolites, ions.
Pathological processes which are primarity developed in hypothalamus lead to disorders of transhypophysar and parahypophysar regulation of endocrine glands function. The activity of hypothalamic centres can be disturbed also secondarily in connection with disorders in limbic system (hypocampus, tonsil, olfactory brain) and upper parts of central nervous system which are closely connected with hypothalamus. At that the large role belongs to mental trauma and other stress influences.
Transhypophysar regulation includes synthesis of peptides which are moving by axons and reach adenohypophysis in neurosecretory cells of mediobasal part of hypothalamus. Here they either stimulate or inhibit formation of tropic hormones. Stimulating peptides have received the name of liberins or releasing-factors, they are: thyroliberin, gonadoliberin, somatoliberin etc. inhibiting peptides are named statins – thyrostatin, somatostatin etc. Their ratio among themselves is determined formation of appropriate tropic hormone. Then formation of tropic hormones begins in adenohypophysis – somatotropic (STH), gonadotropic (GTH) etc. Tropic hormones act on appropriate targets and stimulate derivation of hormones in appropriate glands, and STH stimulates formation of somatomedines in tissues – polipeptide hormones, through which they act.
By means of parahypophysar mechanism secretory, vessel and trophic influence of CNS on the function of endocrine glands is carried out . For adrenal medulla, Langerhans’ islets and parathyroid glands it is a major pathway of their regulation. In realization of the function of other glands both pathways of regulation take place. So, the function of thyroid gland is determined not only by TTH, but also by sympathetic impulsation. The direct irritation of sympathetic nerves increases absorption of iodine by the gland, synthesis of thyroid hormones and their secretion. Denervation of ovaries causes their atrophy and weakens response on gonadotropic hormones.
The disorders of trans– and parahypophysar regulation leads to disfunction of endocrine glands. The disturbanc of one gland function is called monoglandular process, several glands – pluriglandular process. The disorders of the glandular function can be partial, when production of only one hormone is disturbed, or total, when secretion of all hormones is changed .
Role of mechanisms feedback bond in endocrine disturbances
The mechanism of feedback bond is obligated link in self regulation of glandular activity. The essence of negative adverse effects is that formed hormones oppress activity of structures which carry out the previous stages of regulation. Therefore the increase of secretion of effectory hormone through certain parts causes decrease of its formation and entering in blood, and on the contrary, the decreasing of the hormone contents in blood causes increase of intensity of its formation and secretion. In this way regulation of cortizol secretion, thyroid and sexual hromones is carried out.
By the principle of the mechanism of feedback bond inhibition of the function (even atrophy) of the gland during treatment by their or other hormones can occur.
Disorders of hormones biosynthesis and their secretion
Strictly glandular disorders of endocrine functions can be conditioned:
1. By changes of functionally active endocrine cells amount :
a) by decrease of their amount (removal of gland or its part, damage, necrosis), that results to endocrine hypofunction;
b) by increase of their amount (benignt and malignant tumors of glandular epithelium) that is accompanied by features of endocrine hyperfunction.
2. Qualitative changes in cells:
a) by disorders of biosynthesis of hormones;
b) by disorders of processes of their secretion.
The main possible reasons of protein-peptide hormones synthesis disorders are:
1) disorders of transcription;
2) disorders of translation;
3) deficiency of essential aminoacids;
4) deficiency of ATP;
5) disorders of posttranslatory modification and activation.
Disorders of transport, reception and hormones metabolism.
The peripheral mechanisms determine activity of hormones excreted into blood , development of peripheral disorders of endocrine functions occurs due to:
1. Disorders of the hormones transport in organism.
2. Disorder of metabolic inactivation of hormones.
3. Disorders of interaction of hormones with peripheral cells – targets.
All hormones is excreted from gands associate with proteins in blood and circulate in two forms – connected and free. From these two forms connected hormone is biologically inactive. The activity is peculiar only to free form of hormone.
The disorders of the hormone transport in an organism can appear in two types of endocrine function disorders:
а) hypofunction – increase of hormone binding and decrease of its contents in the free form;
b) hyperfunction – decrease of hormone binding and increase in blood of concentration of the free form.
Disorders of endocrine functions, connected with disturbances of interaction of hormones with peripheral cells
The influence of hormones on cells – targets is carried out through their action on specific proteins – receptors and is performed in three ways:
1) influences on permeability of biological membranes;
2) stimulation or oppression of enzymes activity;
3) influences on the genetic apparatus of a cell.
There are two types of cytoreception of hormones.
1. Membrane type of cytoreception. It is the main mechanism of action of protein- peptide hormones and catecholamines. Nowadays we known secondary intermediaties which are represented by the following substances: a) cyclic nucleotides – cAMP, cGМP; b) ions of Са++; c) phospholipide messangers– diacilglycerol (DAG) and inozitoltriphosphate (ITP). The specificity of the answer of a cell on this or other hormone is determined by specificity of the receptor, which is connected only with a certain hormone, and also by nature of specific to a cell proteinkinase and protein substrats.
2. Intracellular type of cytoreception. It is in the base of mechanism of steroid and thyroid hormones action.
The blockade of hormonal receptor is the widespread mechanism, which results to hormonal insufficiency: active hormone does not find receptor on a cell or in it because of receptor loss or fixing on its surface of antagonist, conformation changes of the receptor, which interfere connection with the hormone. Usually concentration of hormone in such cases is normal or increased. The introduction of the hormones with the medical purpose is not accompanied by appropriate effect.
Disorder of endocrine functions, connected with disturbances of hormones metabolism
The destruction of protein-peptide hormones is realized in liver with the help of peptidase enzymes. The disturbances of metabolic hormones transformations can stimulate development of peripheral disorders of endocrine function. So, in case of slowing– down of hormones inactivation their contents in blood is increased, that appears in glands hyperfunction. And on the contrary, the accelerated transformation of hormones in their inactive forms is accompanied by development of endocrine hypofunction. In hepatitis and cyroses of a liver hormones metabolism is oppressed.
PATHOPHYSIOLOGY OF HYPOPHYSIS AND SUPRARENAL GLANDS
Disturbances of functions of hypophysis.
Role of pituitary gland in peripheral endocrine gland function
Hypofunction of adenohypophysis (hypopituitaritism)
There are panhypopituitarity and partial hypopituitariti.
Panhypopituitarity – is the decrease of formation of all adenohypophysis hormones. The following clinical forms of panhypopituitarity are known:
1) Hypophysar cachecsia of Simonds;
2) Afterbearing necrosis of hypophysis – syndrome of Schegan;
3) Chromophobe hypophysis adenomas, i.e. tumors, which grow from chromophobe cells. For want of it the tumour squeezes and damages glandular cells of adenohypophysis.
The clinical manifestations of panhypopituitarity are connected with deficiency of adenohypophysis hormones and disorders of activity of peripheral endocrine glands (thyroid gland, cortex of adrenal, sexual glands). The first symptoms of lesion of adenohypophysis occur in damage of 70-75 % of gland tissue, and for development of complete picture of panhypopituitarity destruction of 90-95 % of adenohypophysis is necessary. Vessels disorders in hypophysis and hypothalamus (most frequently afterbearing longtime spasm of vessels of brain and hypophysis owing of haemorrhage), trauma of the skull basis, tumour of hypophysis and hypothalamus, inflammatory damage (tuberculosis,sepsis) of hypophysis, inherent aplasia and hypoplasia can lead to development of panhypopituitarity. The most frequently gonadotropic function of hypophysis and secretion of STH is damaged with the consequent connection of nonsufficient secretion of ТТH, ACTH and prolactine.
Partial hypopituitarity is the disorder of formation of separate hormones of adenohypophysis (not all). The following variants of partial hypopituitarity are described:
1) Hypophysar nanism (dwarfishness) – deficiency of STH;
2) Secondary hypohonadism – deficiency of FSH and LH;
3) Secondary hypothyrosis – deficiency of TTH;
4) Secondary hypocorticism – deficiency of ACTH.
The insufficiency of STH results to development of hypophysar dwarfishness, or nanism and appears by such disorders:
1) decrease of intensity of protein synthesis that leads to delay and stop of growth (more than 30 % from average) and development of bones, internal organs, muscles. The disorders of protein synthesis in connective tissue results in loss of its elasticity;
2) decrease of inhibiting action of STH on an absorption of glucose with predominance of insulinic effect and development of hypoglycemia;
3) fallout of fat mobilizing action and tendency to obesity.
Nanism
The insufficiency of ACTH leads to secondary partial insufficiency of adrenal cortex. The glucocorticoid function suffers mainly. Mineralocorticoid function practically does not vary.
Insufficiency of TTH causes secondary decrease function of thyroid gland and development of secondary hypothyrosis symptoms. As against in case of primary hypofunction of thyroid gland the introduction of TTH can restore its function.
Insufficiency of gonadotropic hormones results in decrease of ability of Sertoli cells to accumulate androgens and oppression of spermatogenesis and ability to impregnation in men. In case of defect of LG hormone the function of Leidig’s cells is infringed, the formation of androgens ceases and develops eunuchoidism with preservation of partial ability to impregnation, as the process of spermatozoids maturing does not stop.
Hyperfunction of adenohypophysis (hyperpituitarism)
The main reasons of hyperpituitarism development are the benign tumours – adenomas of endocrine cells.
There are two groups of adenomas.
1. Eosinofilic adenoma, develops from acidophilic cells of adenohypophysis forming STH. Clinically hyperproduction of STH appears by giantism (if adenoma develops in children and young people before closing of epiphysar cartilages) and acromegalia (in adult). Giantism is characterized by the proportional increase of all body components.
Acromegalia appears by increased growth of hands, legs, chin, nose, tongue, liver, kyphoscoliosis.
Acromegalia
Besides that increased metabolic activity of STH –hyperglycemia, insulin resistanse, even to development of metahypophysar diabetes, fatty infiltration of liver develop.
2. Basophilic adenoma, grows from basophilic cells of adenohypophysis which more often produce ACTH. During this the Itsenko-Cushing disease develops. It is characterized by: а) secondary hypercorticism; b) strengthened pigmentation of skin. There are tumors which produce other hormones of adenohypophysis less often: TTH, gonadotropic hormones, prolactin, MSH.
The increased level of ACTH during this disease is combined with increase of level of other products of proopiomelanocortin.
Hyperfunction of neurohypophysis
Leads to redundant production vasopressin and oxytocin.
Their main effects:
Vasopressin (antidiuretic hormone) renders the following influence through V1 and V2 receptors:
1) Acting on tubulus contortus distalis and collective tubules of kidneys, strengthens reabsorption of water;
2) Causes contraction of smooth muscles of blood vessels;
3) Strengthens glycogenolysis and gluconeogenesis in liver;
4) Stimulates consolidation of memory traces and mobilization of saved information (hormone of memory);
5) Endogenic analgetic (depresses pain).
Oxytocin renders the following functional influences:
1) Stimulates secretion of milk (lactation) causing contraction of myoepithelial cells of small-sized ducts of mammary glands;
2) Initiates and strengthens contractions of uterus of pregnant woman;
3) Worsens storing and mobilization of information (amnestic hormone).
Redundant secretion of vasopressin arises in tumors of different tissues forming vasopressin, and also in disorders of hypothalamic endocrine function regulation. Its main manifestation is hypervolemia leading to development of constant arterial hypertension.
Hypofunction of neurohypophysis
Insufficient production of vasopressin results to development of diabetes insipidus. There are two pathogenetic variants: central (neurogenic) during which will a little quantity of vasopressin, is formed and nephrogenic during which the sensitivity of epithelial cells receptors of distal nephron parts and collective tubules to vasopressin action (absence or a little quantity receptors) is reduced. The decreasing of water reabsorption in kidneys results to poliuria and decreasing of circulatting blood volume (hypovolemia), falling of arterial pressure and hypoxia.
The decreasing of oxitocin production appears by disorders of lactation, weakness of labor activity.
Disorders of adrenal gland function
The most frequently there are following manifestations:
1) Hypofunction of adrenal cortex – hypocorticism
2) Hyperfunction of fascicular zone – syndrome of Itsenko-Kushing
3) Hyperfunction of glomerulose zone – hyperaldosteronism
4) Dysfunction of adrenal cortex – adrenogenital syndrome
Insufficiency of adrenal cortex
According to etiology there are primary and secondary kinds of adrenal cortex insufficiency. Primary insufficiency arises as a result of adrenals injury, secondary is connected with the defeat of hypotalamus (deficiency of corticoliberin), or with hypofunction of adenohypophysis (deficiency of ACTH). Insufficiency of corticosteroids can be total when the operation of all hormones drops out, and partial fallout of activity of one adrenal hormone. Insufficiency of adrenal cortex can be acute and chronic.
Examples of acute insufficiency are:
а) state after removal of adrenals;
b) hemorrhage in adrenals which arises during sepsis, meningococci infection (syndrome Waterhouse-Friderixan);
c) syndrome of cancellation of glucocorticoides preparations.
Fast falling of the adrenals function causes development of collaps and the patients can die during the first day.
The chronic insufficiency of adrenals cortex is characterized for Adison’s disease (bronzed disease). The most often reasons of it are: а) tuberculose destruction of adrenals; b) autoimmune process.
І. Manifestation, connected with the falling of mineralocorticoids functions of adrenal cortex:
1) dehydration develops owing to loss of sodium ions (decreases rearbsortion) with the loss of water (poliuria);
2) arterial hypotension is stipulated by decrease of circulating blood volume;
3) hemoconcentration (condensation of blood) is connected with liquid loss, results to disorders of microcirculation and hypoxia;
4) decreasing of kidney blood circulation is stipulated by increase of arterial pressure with disturbances of glomerular filtration and development of intoxication (nitrogenemia);
5) hyperpotassiumemia is stipulated by decrease of canales secretion of potassium ions and their output from the damaged cells. It causes disorders of function of arousing tissues;
6) distal canales acidosis. It is connected with disorders of acidogenesis in distal nephron canales;
7) gastro-intestinal disorders (nausea,vomiting, diarrhea).
Loss of sodium (osmotic diarrhea) and intoxication have significant meaning. This disorders without appropriate correction result to death.
ІІ. Manifestations stipulated by disorders of glucocorticoid function of adrenals. To such manifestations concern:
1) hypoglycemia which results to starvation;
2) arterial hypotension (permissive reaction on catecholamines);
3) decrease reaction of fat tissue on lipotropic stimules;
4) decrease resistance of an organism on action of different pathogenic factors;
5) decrease of ability to remove water during water load (water poisoning);
6) muscular weakness and fast tiredness;
7) emotional disorders (depression);
8) delay of growth and development of children;
9) sensor disorders – loss of ability to distinguish separate shades gustatory osmetic acoustical sensations;
10) distress-syndrome of a newborn (hyalinic membranosis). It is stipulated by disorders of surfactant formation in lungs owing to what lungs are not straightened after birth of a child.
Increase of adrenals cortex function
Hyperaldosteronism. Arises during hyperfunction of glomerular zone of adrenals cortex, which produce mineralcorticoides.
There are primary and secondary hyperaldosteronism.
Primary hyperaldosteronism (Conn syndrome) arises in adenoma of zone glomerular, which secretes high quantity of aldosteron. Main manifestations of this disease:
1) arterial hypertension. It is connected with increase of sodium contents in blood and in wall of blood vessels, after what the sensitivity of their smooth muscles to action of pressore factors, particularly cathecholamines increases.
2) hypopotassiumaemia (result of hypersecretion of potassium ions in canals of kidneys). It causes disorders of arousing organs and tissues (disorders of heart activity, miostenia, pareses);
3) ungas alcalosis. It is connected with amplification of acidogenesis in distall nephron canaliculas;
4) polyuria arises as a consequence sensitivity of kineys canales epithelium loss to action of vasopressin. It explains absence of volume increase of circulatting blood and edema.
Secondary hyperaldosteronism is a result of renin-angiotensin system activation. This state appears by:
a) arterial hypertension;
b) aedemas;
c) hypopotassiumaemia;
d) ungas alcalosis.
There are two clinical forms of hypercorticism with hyperproduction of glucocorticoides:
1. Cushing’s disease – basophil adenoma of anterior hypophysis part.
2. Cushing’s syndrome:
· tumoral – adenoma of zona fasticulata of adrenal cortex;
· ectopic production of АCТH by some malignant tumors (pulmonar cancer);
· iatrogenic – introduction of glucocorticoides in an organism with the medical purpose.
Glucocorticoid hypercorticism appears by:
1) arterial hypertension
2) hyperglycaemia – metasteroid diabetes mellitus
3) obesity
4) development of infectious diseases without signs of an inflammation
5) gastric hypersecretion and formation of ulcers in stomach and duodenum
6) osteoporosis
7) muscular weakness
8) slow of wounds healing
Cushing’s syndrome
Adrenogenital syndrome results from the hereditary stipulated blockade of cortisole synthesis and amplified formation of androgens from general intermediate products.
Depending on the level of blockade of cortisole synthesis there are three variants of adrogenital syndrome.
І. Disorders of early stages of synthesis – deficiency of glucocorticoides, mineralcorticoides and androgens hyperproduction. Manifestations: signs of insufficiency of gluco- and mineralocorticoidal functions of adrenal cortex features of early sexual maturing in males, virilization in women (appearance of man’s sexual features).
ІІ. Disorders of intermediate stages – deficiency of glucocorticoides, surplus of androgens, formation of mineralocorticoides is not infringed (classical androgenic syndrome). Manifestations are the same, as in the first case, only without signs of insufficiency of mineralocorticoidal function.
ІІІ. Disorders at final stages of cortirol synthesis – deficiency of glucocorticoides, hyperproduction of androgens and mineralocorticoide. Features of hyperaldosteronism are connected with manifestations of classical androgenital syndrome.
Disorders of adrenal medulla function
Hypofunction of adrenal medulla happens seldom because of the fact that these functions can be accepted by other chromaphine cell.
Hyperfunction of adrenal medulla arises during tumors of chromaphine cells – pheochromocytome. Appears by arterial hypertension, tachycardia, extrasystole, flatering of atriums, hyperglycaemia, hyperlipidaemia, hyperthermia. Development of moderately expressed diabetus, thyreotoxicosis is possible. In time of paroxizm vertigo, headache, hallucinations, increased excitability of the nervous system, cramps appear.
Sex hormones.
Sex hormones are synthesized in testicles, ovaries. Smaller amount of sex hormones are produced in adrenal cortex and placenta. Small amount of male sex hormones are produced in ovaries and female sex hormones – in testicles.
Male sex hormones are called androgens and female – estrogens.
Chemical structure – steroids.
Synthesis and secretion of the sex hormones are controlled by the pituitary honadotropic hormones. Sex hormones act by means of the activation of gene apparatus of cells. Catabolism of sex hormones takes place in liver. The time half-life is 70-90 min.
The main estrogens: estradiol, estrole, estriole (are produced by follicles) and progesterone (is produced by yellow body and placenta). The main biological role of estrogens – conditioning for the reproductive female function (possibility of ovum fertilization). Estradiol results in the proliferation of endometrium and progesterone stimulates the conversion of endometrium in decidual tissue which is ready for ovum implantation. Estrogens also cause the development of secondary sexual features.
The main androgen is testosterone. Its synthesis is regulated by the luteinizing hormone. Testosterone forms the secondary sexual features in males.
Effect of sex hormones on protein metabolism:
1. stimulate the processes of protein, DNA, RNA synthesis;
2. cause the positive nitrogenous equilibrium.
Effect of sex hormones on carbohydrate metabolism:
1. activate the Krebs cycle;
2. activate the synthesis of glycogen in liver.
Effect of sex hormones on lipid metabolism:
1. enhance the oxidation of lipids;
2. inhibit the synthesis of cholesterol.
Effect of sex hormones on energy metabolism:
– stimulate the Krebs cycle, tissue respiration and ATP production.
Sex hormones are used for treatment of variety diseases. For example, testosterone and its analogs are used as anabolic remedies; male sex hormones are used for the treatment of malignant tumor of female sex organs and vice versa.
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.
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).
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 10 in males).
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;
– cardiovascular disorders.
