Persistent galactorrhea-amenorrhea syndrome: causes, symptoms, diagnosis, treatment

Syndrome of persistent galactorrhea-amenorrhoea (synonyms: Chiari-Frommel syndrome, Ahumada-Argons-del Castillo syndrome-by the authors who first described this syndrome: in the first case, in those giving birth and in the second case for nulliparous women). Galactorrhea in men is sometimes referred to as O'Connell syndrome. The main clinical symptom is the galactorrhea, which can be observed both against the background of hyperprolactinemia and with normoprolactinemia. Normoprolactinemic galactorrhea usually occurs without concomitant amenorrhoea. Hyperprolactinemic galactorrhea is combined with two other clinical manifestations of the disease - a violation of the menstrual cycle and infertility.

The causes of the syndrome of persistent galactorrhea-amenorrhea

One of the main causes of the syndrome of persistent galactorrhea-amenorrhea are adenomas of the pituitary gland - micro- and macrocloractinomas. Tumors of parasellar and hypothalamic localization can provoke a syndrome of persistent galactorrhea-amenorrhea. There are also traumatic genesis of the disease (rupture of the pituitary foot) and inflammatory-infiltrative genesis (sarcoidosis, histiocytosis-X).

Hyperprolactinemic hypogonadism can be observed with intracranial hypertension and with the syndrome of the "empty" Turkish saddle.

Knowledge of these etiological causes determines the initial tactics of the physician with the obligatory neurological examination of the patient (radiography of the skull, eye fundus, visual field, computed tomography). In addition, a frequent cause of the syndrome of persistent galactorrhea-amenorrhea is the long-term use of neurochemistry-modifying pharmacological agents, monoamines (tx-methyldopa) synthesis inhibitors, monoamine (reserpine) reducing agents, dopamine receptor antagonists (phenothiazines, butyrophenones, thioxanthenes), inhibitors reverse neuronal capture of mediator monoamines (tricyclic antidepressants), estrogens (oral contraceptives), drugs.

One of the common causes of the development of the syndrome of persistent galactorrhea-amenorrhea is decompensation of the constitutional biochemical hypothalamic defect with the development of dopaminergic deficiency in the tuberoinfundibular region. In these cases, the terms "idiopathic hyperprolactinemia", "functional hypothalamic hyperprolactinemia" are sometimes used.

Reducing the inhibitory effects of the CNS on the secretion of prolactin as a result of unfavorable external influences (emotional stress - acute or chronic, debilitating prolonged physical exertion) can lead to hyperprolactinaemia with the formation of the SSC syndrome.

Pathogenesis of the syndrome of persistent galactorrhea-amenorrhea

The disease is based on hyperprolactinaemia, which is the result of a violation of hypothalamic-pituitary dopaminergic mechanisms. Dopamine is a physiological inhibitor of prolactin secretion. Insufficiency of dopaminergic systems in the tuberoinfundibular region of the hypothalamus leads to hyperprolactinaemia; it may also be due to the presence of a prolactin secretory tumor of the pituitary gland. In the formation of the macrophage and microadenomas of the pituitary gland, great importance is attached to hypothalamic disorders of catecholamine control of prolactin secretion, which can cause excessive proliferation of crolactophors in the pituitary gland with the possible formation of prolactinoma in the future.

Symptoms of persistent galactorrhea-amenorrhea syndrome

Galactorrhea should be considered a different degree of secretion of milk-like secretion from the mammary glands, which lasts more than 2 years after the last pregnancy or occurs regardless of it. The degree of expression of the galactorrhea can vary significantly - from single drops of secretion with strong pressure on the mammary glands in the nipple region before spontaneous discharge of milk. Violations of the menstrual cycle are manifested in the form of secondary amenorrhea or oligomenorrhoea; rarely, primary amenorrhea can be observed. Most often, galactorrhea and amenorrhea develop simultaneously. As a rule, patients have atrophy of the uterus and appendages, monotonous rectal temperature. It should be borne in mind that in the first years of the disease atrophic changes in the internal genital organs may be absent.

There is a lack of orgasm and difficulty in sexual intercourse due to a significant reduction in vaginal secretions. There can be both a decrease and an increase in body weight. Hirsutism, as a rule, is moderate. Pale skin, pastosity of the face, lower extremities, propensity to a bradycardia are marked. Syndrome of persistent galactorrhea-amenorrhea can be combined with other neuro-exchange-endocrine syndromes - cerebral obesity, diabetes insipidus, idiopathic edema.

In the emotional-personal sphere, undefined anxiety-depressive disorders prevail. As a rule, the disease begins at the age of 20 to 48 years. Spontaneous remissions are possible.

Differential diagnosis

It is necessary to exclude the pathology of peripheral endocrine glands, which can lead to secondary hyperprolactinaemia and symptoms characteristic of the syndrome of persistent galactorrhea-amenorrhoea. These include diseases such as primary hypothyroidism, estrogen-producing tumors, Stein-Levental syndrome (polycystic ovary syndrome), congenital adrenal cortex dysfunction. Chronic renal failure should also be excluded. It is known that 60-70% of people with this disease have prolactin levels. Its increase is also observed with cirrhosis of the liver, especially in hepatic encephalopathy. It is necessary to exclude tumors of nonendocrine tissues with ectopic production of prolactin (lungs, kidneys). If the spinal cord and chest walls are damaged (with burns, incisions, shingles), if IV-VI intercostal nerves are involved in the process, a galactorrhea may develop.

Treatment of the syndrome of persistent galactorrhea-amenorrhea

Therapeutic tactics depend on the causes that caused hyperprolactinemia. When the tumor is verified, surgical intervention is used or radiation therapy is performed. In the absence of tumor or inflammatory-infiltrative lesion of the central nervous system, the use of anti-inflammatory, resorptive, dehydrating therapy or X-ray therapy is not indicated. The main drugs for the treatment of the syndrome of persistent galactorrhea-amenorrhea are derivatives of ergot alkaloids: parlodel (bromocriptine), fenil (lizard), metergoline, and also L-DOPA, clomiphene.

Parlodel is a semisynthetic ergot alkaloid, which is a specific dopamine receptor agonist. In connection with the stimulating effect on the dopamine receptors of the hypothalamus, the parlodel has a retarding effect on the secretion of prolactin. Assign usually at a dose of 2.5 to 10 mg / day., Apply daily for 3-6 months. Lisenil is prescribed in a dose of up to 16 mg / day. Other ergot alkaloids are also used: ergometrine, metisergide, metergoline, however the therapeutic tactics of their application are under development.

The therapeutic effect of L-DOPA is based on the principle of increasing the content of dopamine in the central nervous system. L-DOPA is used in a daily dose of 1.5 to 2 g, the course of treatment is usually 2-3 months. There are indications of the effectiveness of the drug in the normoprolactinemic galactorrhea. It is believed that this drug can directly affect the secreting cells of the breast and reduce lactorrhea. In the absence of effect during the first 2-3 months. Application of further therapy is impractical.

Clomiphen (clomid, klostilbegit) is prescribed in a dose of 50-150 mg / day. From the 5th to the 14th day of the menstrual cycle, induced by the previous administration of infecondin. Spend 3-4 courses of treatment. The drug is less effective than parlodel.

To treat the syndrome of persistent galactorrhea-amenorrhea, a serotonin receptor blocker, peritol (cicroheptadine, deseril) is used. The effectiveness of the drug is controversial: it does not help all patients, there are no clear criteria for its use. Preferred treatment tactics with parlodel or lisenil.