By Julio Libman and Jesús Ramón Giraudo

Gynecomastia is defined as the exaggerated, non-immoral development of the mammary gland in the male. It can be unilateral, although it is usually bilateral. Its size ranges from a small concentric button of tissue to breasts similar to those of an adult woman.

Physiology and pathophysiology.

Under normal conditions it is rarely possible to observe the existence of palpable breast tissue in normal adult males. Gynecomastia may be a physiological manifestation at certain stages of life, or it may be due to a wide variety of disease states. In any of these circumstances, its development would result from an absolute increase in plasma estrogens, or more frequently, from a relative increase in said hormones in relation to androgens, as a consequence of a decrease in the synthesis or peripheral action of testosterone. , an increase in the production of estrogens, or a combination of both mechanisms. When gynecomastia is not associated with galactorrhea, plasma prolactin levels are normal. Once established, gynecomastia may retrograde or persist even in the absence of a subsequent hormonal stimulus. To explain the pathophysiology of gynecomastia in patients with normal hormonal levels, a local metabolic alteration has been postulated, with increased aromatization of androgens and increased production of estrogens.

An increase in estradiol, either endogenously or by exogenous administration, induces the growth, division and elongation of the duct system, increased stroma, and maturation of the areola of the nipple. In later stages, there is progressive fibrosis with hyalinization, together with regression of epithelial proliferation.

Gynecomastia causes

  1. Physiological
    1. Of the newborn. It is transitory and disappears after a few weeks of life. It results from the action of maternal or placental estrogens.
    2. From adolescence. It occurs in most males in the course of normal pubertal development. It can be asymmetric and sometimes unilateral. Sometimes a certain degree of tenderness is observed. Frequently returns spontaneously upon completion of sexual development.
    3. Of senescence. It is observed in up to 40% of autopsies of healthy elderly individuals. It is due to increased peripheral conversion of androgens to estrogens and decreased production of the former, observable with age.
  2. Pathological
    1. Poor production or peripheral action of testosterone with or without a secondary increase in estrogen production. They include congenital anomaly, Klinefelter syndrome, androgen resistance (as in testicular feminization and Reifenstein syndrome), defects in testosterone synthesis and secondary testicular deficiencies as in kidney failure, neurological and granulomatous diseases, orchitis. viral etc.
    2. Congenital abnormality is an example of the development of gynecomastia due to deficiency in testosterone production with normal or slightly decreased levels of estradiol. In Klinefelter syndrome, decreased testosterone production causes an increase in luteinizing hormone (LH), which determines increased synthesis of estradiol by the testes. In testicular feminization syndrome, deficiency in androgenic action is associated with increased testicular production of estrogens.
    3. Increased production of estrogens. They include testicular tumors and bronchogenic adenocarcinomas that, by ectopic production of chorionic gonadotropin (HCG), stimulate testicular production of estrogens. Some testicular tumors can synthesize estrogens directly. Increased estrogen production may result from increased substrate availability for peripheral aromatization due to increased production of androstenedione, as in congenital 11B-hydroxylase deficiency adrenal hyperplasia, hyperthyroidism, and adrenal feminizing tumors, or decreased metabolism of it by normal routes, as occurs in various liver diseases. Another cause is true hermaphroditism.
    4. The administration of estrogens or gonadotrophins, the latter through a stimulus in the production of estrogens by the testicle, can cause gynecomastia. Digitalis act as estrogens or enhance their action. Spironolactone and cimetidine block the binding of testosterone to cytosolic receptors, while alkylating agents interfere with testosterone synthesis. Methyldopa, isoniazid, amitriptyline, diazepam, D-penicillainin, etc., cause gynecomastia by unclear mechanisms.

Interrogation and study methodology

The evaluation of a gynecomastia patient begins with a detailed questioning about the previous intake of medications. The physical examination should be careful, with special emphasis on the lungs, liver, adrenals, thyroid, cardiovascular system, as well as nutritional status. The testicular examination is essential. If both testicles are small, the indicated is a study of nuclear chromatin and the obtaining of a karyotype (Kiinefelter syndrome); if they are asymmetric, the probable existence of a tumor (choriocarcinoma or Leydig cell tumor) should be evaluated. Endocrine evaluation should include the determination of 17-ketosteroids, dehydroepiandrosterone, estradiol, testosterone, LH, and the B subunit of HCG. A high LH with low testosterone indicates testicular failure. If both parameters are low, it is probable that there is an autonomous tumor source of estrogens. If LH and testosterone are elevated, the data points to a state of resistance to androgens or to a tumor producing gonadotro fines.

Liver function tests should be performed to detect symptoms of cirrhosis, hemochromatosis, hepatitis, or congestion as in heart failure, and adequate studies should be performed to rule out bronchogenic adenocarcinoma.