SYNDROME OF THE GIPERPROLAKTINEMICHESKY HYPOGONADISM (Greek syndrome confluence, accumulation; Greek hyper-+ prolactin + Greek haima blood; a hypogonadism) — the symptom complex developing at women and men owing to long hypersecretion of hormone of a hypophysis of prolactin.
Fiziol. the effects rendered by prolactin on a human body are diverse (see. Prolaktin ). Its influence on reproductive system is fullestly studied. At women prolactin together with gonadotropic and sex hormones supports a two-phase menstrual cycle, promotes formation of a yellow body, supports pregnancy, provides development of mammary glands and a puerperal lactation. At men prol actin stimulates growth and development of a prostate and seed bubbles. In fiziol. doses, promoting accumulation in seed bubbles cyclic 3', 5 '-AMF, to utilization of carbohydrates, providing reserves of cholesterol, prolactin supports genital function. Prolactin takes part in regulation of function of adrenal glands, kidneys, a liver and other bodies and functional systems of an organism. Long hypersecretion of prolactin (giperprolaktinemiya) induces at women secretion of milk (galactorrhoea) and the menstrual cycle (amenorrhea) suppresses. Excess of prolactin causes characteristic clinic in men hypogonadism (see).
Patol. forms of a lactation are known since the most ancient times. This disease is defined by Hippocrates in its aphorism: «If the nonpregnant woman lactates, its periods are stopped».
At men is This year, proceeding with a galactorrhoea, call sometimes O'Konelli's syndrome. At women the typiform This year carries the name of a syndrome of a persistent hectare-lactorrhea-amenorrhea.
The long time a syndrome of a persistent galactorrhoea amenorrhea was subdivided into various forms depending on whether pregnancy and childbirth preceded it or not. So, by name the researchers who for the first time described this syndrome at the giving birth women it was called Kiari's syndrome — Frommelya (see. Kiari — Frommelya a syndrome ), at not giving birth — Argons's syndrome — del Castillo, at persons with adenoma of a hypophysis — Forbes's syndrome — Albright. Meanwhile, it was noticed that quite often one form of a disease is transformed to another. So, persons with Argons's syndrome — del Castillo after short-term remission with recovery of genital function have strong indications of growth of adenoma of a hypophysis. In a crust, time it is accepted to call all listed syndromes This year
the Aetiology and a pathogeny
the Pathogeny This year is defined first of all by the reciprocal relations in regulation of gonads between prolactin and gonadotropic a follicle about stimulating (FSG) and luteinizing (L G) hormones of a hypophysis. At L G women and FSG (see. Luteinizing hormone , Follicle-stimulating hormone ) are responsible for development of follicles in an ovary and an ovulation, i.e. provide the first phase menstrual cycle (see), and prolactin dominates in the second phase when it together with progesterone (progesterone) stimulates development of a parenchyma of a mammary gland and secretion of milk (after the delivery). Therefore, at women gonadotropic hormones and prolactin dominate in different phases of a menstrual cycle. And if the hypophysis begins to throw out constantly excess of prolactin, then the last suppresses secretion of FSG and L G and, therefore, development of follicles in an ovary; the menstrual cycle is as a result broken, arises infertility (see). At men excess products of prolactin also suppress secretion of FSG and L G responsible for spermatogenesis (see) and biosynthesis androgens (see), as leads to a hypogonadism.
Biosynthesis and release of all hypophyseal hormones is controlled by the special peptide gino-thalamic factors called by rileasing-hormones — liberina and statines (see. Hypothalamic neurohormones ). The first stimulate, the second slow down secretion of hypophyseal hormones. In regulation of hormones of a hypophysis an important role is played also by such monoamines of a hypothalamus as noradrenaline, adrenaline, dopamine, serotonin. From all hypophyseal hormones the most difficult and the system of regulation which still is finally not found out prolactin has. The constant hypothalamic inhibiting control is the cornerstone of it. A role prolactin - the inhibiting factor, according to E. Fluckiger with sotr. (1982), plays dopamine. Existence of special peptide rileasing-hormones — a prolaktosta-tpna and a prolaktoliberina is allowed.
The system of regulation of prolactin is closely connected with hypothalamic control of the tireotroiny hormone of a hypophysis (THH) responsible for function of a thyroid gland (see. Thyritropic hormone ). Tiroliberin stimulating thyritropic hormone of a hypophysis possesses at the same time and powerful prolactin - the stimulating activity owing to what its direct participation in regulation of secretion of prolactin is allowed. Serotoninergichesky, noradrenergichesky and cholinergic structures of a hypothalamus, as well as endogenous opiates (see. Opiates endogenous ), prostaglandins (see) and sexual steroids, participate in regulation of biosynthesis of prolactin.
Nature patol. giperprolaktinemiya it is heterogeneous. Allocate two main forms of a syndrome: primary This year, caused by defeat gipotalamo-pituitary system (see), and secondary This year, developing at nek-ry endocrine and not endocrine diseases, and also the iatrogenic influences which are followed hron. giperirolaktinemiya.
This year it can be induced etiol. factors of extremely broad range of action. Primary This year are the cornerstone of a pathogeny as the functional changes which are followed by deficit of monoamines and first of all dopamine (e.g., at long stressful states), and the organic lesions of a hypophysis (prolaktii-cosecreting tumors of a hypophysis — a prolaktinoma). Primary This year develops against the background of intracranial hypertensia (see. Intracranial pressure ) and «a syndrome of the empty Turkish saddle» arising, as a rule, at weakness of its diaphragm (e.g., at hydrocephaly) and the skull diagnosed on pneumoencephalograms but to defect of filling of the Turkish saddle with tissue of hypophysis.
Disturbance of the dofaminergichesky inhibiting control of secretion of prolactin leads at first to a hyperplasia of laktotropotsit, or pro-lactotrophs (the cells of a hypophysis cosecreting prolactin), and then to formation micro and macro-prolactin of a hypophysis.
Secondary This year develops against the background of other diseases of gipotalamo-pituitary system (an acromegalia, Itssnko's disease — Cushing, Nelson's syndrome, hormonal and inactive tumors of a hypophysis — a cranyopharyngioma, a meningioma, a glioma, a chondroma of area of the Turkish saddle), and also at such general diseases as sarcoidosis (see), xanthomatosis (see). Combination This year and acromegalias (see) prolactin and somatotropic hormone (see), or the pluripotential adenoma consisting of one generation of cells, but producing both of these hormones can be caused by existence or the mixed adenoma of a hypophysis (see) consisting of two types of cells sekretpruyushchy. Find coexistence of two or more adenomas less often — prolactin and Somatotropinum, producing prolactin and somatotropic hormone. Sometimes supersecretion of prolactin is caused by the hyperplasia of laktotropotsit caused by a prelum of a leg of a hypophysis the adenomas consisting of various cells of a hypophysis (eosinophilic at an acromegalia, basphilic at Itsenko's disease — Cushing, the chromophobic cells making hormonal and inactive adenomas). These tumors, squeezing capillaries of a leg hypophysis (see), on the Crimea rileasing-hormones and monamina are transported from a hypothalamus in a front share of a hypophysis, as if remove the inhibiting control over secretion of prolactin. The hyperplasia of laktotropotsit which is followed by hypersecretion of prolactin results. The giperprolaktinemiya has identical genesis at cranyopharyngiomas (see), gliomas (see. Brain ) and other tumors of hypothalamic area squeezing a leg of a hypophysis.
Secondary This year it is observed also at the states which are followed by excess products of sexual steroids (a sclerocystosis of ovaries, estrogenprodutsiruyushchy tumors, inborn dysfunction of bark of adrenal glands) at primary hypothyroidism, at reception of nek-ry pharmaceuticals, neurogenic disturbances, at hron. liver and renal failure. Development of a giperprolaktinemiya at excess products of sexual steroids is caused as their direct stimulating influence on synthesis of prolactin, and disturbance in these conditions of the inhibiting dofaminergicheeky control from a hypothalamus.
Deficit of hormones of a thyroid gland by the principle of the return positive communication leads to a gi-iyerproduktion of thyritropic hormone of a hypophysis and prolactin. It is supposed that the main role in such superproducts of both hormones is played not only by surplus of a hypothalamic tiroliberin, but also naru-ineHPie exchange of dopamine and estrogen, caused by a lack of thyroid hormones.
The medicinal giperprolaktinemiya develops owing to administration of drugs, breaking synthesis of dopamine (dopegit), exhausting a reserve of dopamine (Reserpinum), blocking effect of dopamine in postsynaptic receptors (a haloperidol, Sulpiridum, cerucal, etc.). Oral contraceptives (see. Contraceptives ), the containing estrogen, causes considerable hyperproduction of prolactin in nek-ry women.
The pathogeny of a giperprolaktinemiya at somatopathies is difficult and insufficiently studied. Content of prolactin at a liver and renal failure increases both owing to decrease in its removal, and because of the increased its secretion as a result of disturbance of exchange of biogenic amines, estrogen, endogenous opiates (endorphines, enkephalins).
A clinical picture
At women since This year. amenorrhea (see), as a rule, carries secondary, is more rare — primary character. Degree of a galactorrhoea (see the Lactation) varies from plentiful spontaneous to single drops at strong pressing on mammary glands. In the latter case patients, as a rule, do not note a galactorrhoea, it is found by the doctor at purposeful survey. In mammary glands the regressive changes which are not corresponding to age often are found. Not proliferative fibroznokistozny mastopathy (see) and cancer mammary gland (see) at This year meet not more often than on average in population. The syndrome is characterized by decrease in a libido, lack of an orgasm, an atrophy of a uterus and mucous membrane of a vagina. Quite often moderate obesity, a hypertrichosis (the raised pilosis), such symptoms of dysfunction of a hypothalamus as «dirty» elbows and a neck (a hyperkeratosis and a hyperpegmentation), nacreous striya (a strip of stretching of skin) on hips, a breast, a stomach come to light. At women allocate also various incomplete forms This year when the giperprolaktinemiya is not followed by a galactorrhoea, it is combined not with an amenorrhea, and with the opsomenorrhea or a polymenorrhea shortened or a defective lyutei-new phase of a menstrual cycle (see. Menstrual cycle ).
At This year at men are noted oligo-and an asthenospermia (see. Sperm ), impotence, decrease in a libido; the gynecomastia and a galactorrhoea meet rather seldom.
A wedge, the manifestation This year caused by reception of pharmaceuticals vary from the minimum galactorrhoea and (or) disturbance of a menstrual cycle before typical manifestations of a syndrome; a giperprolakti-nemiya at the same time it is long proceeds asymptomatically.
The wedge, a picture This year developing at primary hypothyroidism depends on time of its emergence. If primary hypothyroidism (see) develops in the dopubertatny period, at girls the so-called syndrome of Van Vick — Grambakh forms, to-ry it is characterized by premature puberty (see. Hypergenitalism ), a galactorrhoea, menometrorrhagias (see. Menstrual cycle); deficit of thyroid hormones causes oppression of physical and intellectual development in boys, brakes sexual development. At reproductive age primary hypothyroidism involves disturbance of a menstrual cycle up to an amenorrhea, is more rare — polymenorrheas. The galactorrhoea is usually expressed more at young women.
At patients with a sclerocystosis of ovaries (see. Matte — Leventalya a syndrome ) This year it is found in 30 — 60% of cases. At the same time the galactorrhoea can be absent.
At persons with somatic pathology, in particular with a renal and liver failure, the wedge, manifestations This year vary that is caused not only by hypogonadotropic influence of prolactin, but also direct action on gonads of the toxicants collecting owing to an abnormal liver function and kidneys.
At women the diagnosis This year is made on the basis of characteristic a wedge. the picture confirmed with tests of functional diagnosis, napr, the basal temperature, reaction of vulval smears and, surely, determination of level of prolactin in blood. The hormonal background, typical for This year, is characterized by significant increase in content of prolactin in blood, decrease in level of luteinizing and follicle-stimulating hormones, decrease in concentration of estrogen (at women) and testosterone (at men).
For confirmation of the diagnosis, as a rule, rather single determination of level of prolactin. The content of hormone exceeding 200 ng! the ml, in most cases indicates existence of a prolaktinoma of a hypophysis. Determination of content of prolactin in blood is obligatory in all cases of infertility and (or) disturbance of a menstrual cycle. Timely carrying out this inspection provides early diagnosis This year.
Considerable difficulties are connected with identification of the specific reason This year, in particular, with an exception micro and macroadenomas of a hypophysis, including and about l actin, and also a syndrome of «an empty Turkish saddle». Macroadenomas of a hypophysis diagnose by means of a rentgenokraniografiya (see. Kraniografiya ), and microadenomas — by means of hypocycloidal political homography (in two projections — from the right and left side) and a computer tomography (see the Tomography computer). For diagnosis of a syndrome of «an empty Turkish saddle» use a pneumoencephalography or a computer tomography with ventrikulografiya (see).
Tests with tiroliberiny or the block that Rami Dofaminergicheskikh of structures (haloperidol) apply to differential diagnosis of gipotalamo-pituitary genesis and This year at a sclerocystosis of ovaries This year. For This year of gipotalamo-pituitary genesis in response to administration of these substances of increase in secretion of prolactin it is not observed, at a sclerocystosis of ovaries giperergichesky reaction (strengthening of secretion of hormone) comes to light.
For diagnosis This year, caused by deficit of thyroid hormones, determine the level of thyritropic hormone of a hypophysis and hormones of a thyroid gland in blood.
Till 70th 20 century of reliable methods of treatment This year was not. The large adenomas of a hypophysis which are followed This year deleted. At the functional disturbances of gipotalamo-pituitary system which are followed This year used therapy by sexual steroids, edges it is carried out by cycles. Later it became clear that such therapy at This year is undesirable since estrogen strengthens a gi-perprolaktinemiya. At a small number of patients it is possible to recover reproductive function by Clostilbegytum (clomifene) or gonadotropic hormones (pergonal, ho-riogonin). However danger of development during pregnancy of the adenoma of a hypophysis induced by similar treatment, and also weak therapeutic effect of these drugs at This year limit their use.
The most effective drug for treatment This year is semi-synthetic alkaloid of an ergot Parlodelum, to-ry raising a susceptibility of receptors of cells of a hypophysis (laktotropotsit) to dopamine, blocks synthesis and release of prolactin as In fiziol. conditions, and at various patol. the states proceeding with hyper-prolaktinemiyey. Parlodelum reduces the frequency of mitoses in laktotropo-tsita and inhibits growth by prolactin. Normalization of secretion of prolactin at most of patients since This year leads to recovery of cyclic activity of the sexual centers of a hypothalamus, increase in products of gonadotropic hormones, recovery of a two-phase menstrual cycle and genital function. Parlodelum is widely used at treatment of hypotala-mo-pituitary genesis This year. In a complex with other means Parlodelum is successfully used at treatment of a sclerocystosis of the ovaries and nek-ry forms This year caused by reception medicinal средств.^
Parlodelum appoint in a dose 2,5 — B of mg, less often it is increased to 10 mg a day. When This year it is combined with an acromegalia, reception of Parlodelum is increased to 20 mg a day. It is accepted during food, since 1,25 mg, gradually bringing a dose to therapeutic effective. The ovulation comes on 4 — 8 week of treatment more often though cases of induction of an ovulation are described also in 10 days from an initiation of treatment. At approach of pregnancy many clinical physicians cancel Parlodelum. However activation of products of prolactin during pregnancy and the period of a lactation, and also the observed cases of progressing of growth by prolactin during pregnancy force to reconsider this point of view recently. At the same time perhaps total disappearance of the symptoms This year after the delivery induced by Parlodelum. At cancellation of Parlodelum, as a rule, there is a recurrence This year, including and at patients with macro-irolaktinomami therefore therapy by Parlodelum shall be carried out constantly. Drug does not possess abortal or teratogenic action. Overseeing by the children who were born at women, treated Parlodelum did not reveal at them aberrations. By-effects at treatment by Parlodelum (nausea, orthostatic hypotension, locks) are usually short-term and disappear at reduction of a dose.
Until recently for treatment This year, caused a macro-prolaktinomami hypophysis, generally remote radiation therapy, implantation of radioelements in a hypophysis, and also an operational oncotomy were applied. These methods seldom lead to full remission of a disease. Parlodelum is capable to recover completely reproductive function at persons about macroprolactin ohms. Due to the danger of growth of a tumor during pregnancy it is recommended to appoint Parlodelum after preliminary radiation or an oncotomy.
As high antimitotic activity of Parlodelum leads to delay of growth and a rassasyvaniye prolactin, on condition of careful protection from pregnancy Parlodelum can be used for treatment This year at persons about poppy roprol by aktiioma without preliminary inhibition of growth of a tumor by other methods.
Small prolaktinoma delete in the operational way. The pregnancy which arose after treatment by Parlodelum at persons with Mick Roprol of an aktinomama, as a rule, is not followed by significant growth in a tumor. Extra care is required only from patients with rather large, to dia. 7 — 10 mm, prolaktinomam.
At the become pregnant women with prolaktinomy at emergence of a hiaz-malny syndrome (loss of peripheral fields of vision owing to pressure the growing adenoma of a hypophysis on an optic chiasm) treatment by Parlodelum is recommended to be continued before delivery. After the delivery, as a rule, the sizes of a tumor of a hypophysis decrease, and the hiazmalny syndrome regresses.
At persons with expressed by hyper pro-laktinemiyey and extremely low level of gonadotropic hormones of a hypophysis and estrogen treatment by Parlodelum least effectively. At achievement of normalization of content of prolactin at such patients treatment by Clostilbegytum — the drug stimulating emission of the follicle-stimulating and luteinizing hormones deposited in a hypophysis, and also administration of directly gonadotropic hormones like the chorionic gonadotrophin or pergonal containing the follicle-stimulating and luteinizing hormones in the ratio 1:1 can be in addition used.
At men at treatment This year Parlodelum activates a spermatogenesis, recovers the level of gonadotropic hormones and testosterone, raises a libido and a potentiality.
At primary hypothyroidism This year successfully gives in to replacement therapy by thyroid hormones.
Decrease in content of prolactin at secondary This year is reached at treatment of a basic disease. Methods of treatment This year at patients with somatic pathology (hron. a liver and renal failure) are in a stage of scientific development.
The forecast and Prevention
the Forecast for life and preservation of genital function at modern methods of treatment favorable.
Prevention primary This year is not developed, the prevention of a giperprolaktinemiya at secondary This year consists in treatment of a basic disease.
Bibliography: Anosova of L. N. Galak-torrey, Probl. endocrinins., t. 4, No. 4, page 34, 1939; Dubnov M. V. To an etiology of a galactorrhoea, Akush. and ginek., No. 2, page 41, 1945; Starkov and N. T. and Melnichenko G. A. Use of blockers and secretagogues of prolactin at a syndrome of a persistent lactorrhea amenorrhea, Probl. endocrinins., t. 24, No. 6, page 42, 1978, bibliogr.; Th orner M. O. and. lake of Long-term treatment of galactorrhoea and hypogonadism with bromocriptine, Brit. med. J., v. 2, p. 419. 1974.
I. I. Dedov, G. A. Melnichenko.