Diagnosis of persistent galactorrhea-amenorrhea syndrome

If the diagnosis of typical forms of persistent galactorrhea-amenorrhea syndrome seems quite simple today, then the differential diagnosis of “erased”, “incomplete” forms from symptomatic forms of persistent galactorrhea-amenorrhea syndrome, as well as from various unclearly defined and poorly studied clinical syndromes, in which galactorrhea develops against the background of normal serum prolactin levels and its correction does not change the course of the underlying disease and does not alleviate the patient’s condition, is very complex.

Laboratory and instrumental examination required to confirm the presence of persistent galactorrhea-amenorrhea syndrome consists of 4 stages:

1. confirmation of the presence of hyperprolactinemia by determining the serum level of prolactin;
2. exclusion of symptomatic forms of persistent galactorrhea-amenorrhea syndrome (determination of the functional state of the thyroid gland, exclusion of Stein-Leventhal syndrome, liver and kidney failure, neuroreflex and drug effects, etc.);
3. clarification of the condition of the adenohypophysis and hypothalamus (X-ray of the skull, computed tomography or magnetic resonance imaging of the head, with additional contrast if necessary), carotid angiography;
4. clarification of the state of various organs and systems against the background of chronic hyperprolactinemia (determination of the level of gonadotropins, estrogens, DHEA sulfate, study of the state of carbohydrate and fat metabolism, the skeletal system, etc.).

When assessing prolactin levels in the case of minor deviations from the norm, it is advisable to conduct three to five studies to avoid erroneous conclusions, since the very manipulation of blood sampling is often the cause of moderate hyperprolactinemia.

A special group should include patients with galactorrhea against the background of a normal ovulatory and menstrual cycle, who have clinical manifestations of asthenoneurotic syndrome, sometimes with elements of cancerophobia, who constantly check for discharge from the mammary glands and reflexively maintain galactorrhea with this self-palpation. In these patients, in contrast to patients with persistent galactorrhea-amenorrhea syndrome with high prolactin levels, galactorrhea is the main complaint persistently presented to the doctor in combination with other complaints of a neurasthenic nature. Cessation of self-palpation in many of these patients helps eliminate galactorrhea.

Determination of serum prolactin level has not only diagnostic but also differential diagnostic value. Moderate increase is more common in "idiopathic" forms, significantly increased hormone level in prolactinomas. It is generally accepted that prolactinemia over 200 mcg/l reliably indicates the presence of prolactinoma even with radiologically intact sella turcica. To detect "latent", "transient", hyperprolactinemia, dynamic determination of prolactin during the day and in different phases of the menstrual cycle is used. "Exaggerated", hyperergic night rise of prolactin level exceeding the normal maximum, as well as periovulatory hyperprolactinemia are typical.

Until recently, specialists were puzzled by the discrepancy observed in a number of patients between the fairly high serum prolactin levels and the extremely poorly presented clinical symptoms of HG, combined with resistance to the therapy with dopamine agonists. Recent studies aimed at studying prolactin isoforms have made it possible to find an answer to this question. As it turned out, the total pool of immunoreactive prolactin includes forms with different molecular weights. In patients with classical symptoms of HG, prolactin with a molecular weight of 23 kDa is detected in the blood serum by gel filtration, while in women without the typical symptom complex of persistent galactorrhea-amenorrhea, the predominant form (80-90% of the total pool) is prolactin with a molecular weight of over 100 kDa (big-big-prolactin), which has low biological activity (the phenomenon of macroprolactinemia). It is assumed that the origin of high-molecular prolactin is heterogeneous. This form of the hormone may be the result of aggregation of monomeric prolactin or its association with other proteins, such as immunoglobulin. It is possible that big-big-prolactin may directly represent a specific immunoglobulin that exhibits the ability to imitate the presence of prolactin in immunochemical analysis systems. Macroprolactinemia accounts for up to 20% of all cases of hyperprolactinemia.

A number of tests have been proposed to study prolactin secretion under stimulation conditions (with thyrotropin-releasing hormone, chlorpromazine, insulin, sulpiride, cerucal, cimetidine, domperidone). For micro- and macroprolactinomas, a decrease in the response to stimulating effects is typical, directly correlating in most patients with the size of the adenoma. However, the probability of a false-positive or false-negative conclusion about the form of the disease based on the results of stimulation tests in each individual patient is up to 20%.

The level of other hormones in persistent galactorrhea-amenorrhea syndrome is quite typical: unchanged or decreased levels of LH and FSH with a good response to luliberin, decreased levels of estrogens and progesterone, increased levels of dehydroepiandrosterone (DHEA) sulfate.

No biochemical changes specific to persistent galactorrhea-amenorrhea syndrome have been identified, despite numerous experimental data on the effect of prolactin on various types of metabolism. Often there are only signs of impaired lipid metabolism, increased levels of NEFA and triglycerides.

Serum electrolyte levels are usually normal. ECG may show signs of myocardial dystrophy: negative or biphasic T wave in the chest leads. Hyperventilation, orthostatic, and potassium or obsidan load tests reveal the non-coronary nature of these disorders. Chronic uncorrected hyperprolactinemia leads to the development of osteoporosis. The leading role in the pathogenesis of osteoporosis in persistent galactorrhea-amenorrhea syndrome belongs to the slowdown in bone formation, which is confirmed by a decrease in the level of osteocalcin in the blood.

Patients with this syndrome have elevated serum insulin levels. Given their normal glucose levels, they are considered to have some insulin resistance.

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