DISEASES OF THE TESTES & MALE BREAST MALE HYPOGONADISM
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ESSENTIALS OF DIAGNOSIS
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Diminished libido and erections Decreased growth of body hair Testes may be small or normal in size Serum testosterone is usually decreased Serum gonadotropins (LH and FSH) are decreased in hypogonadotropic hypogonadism; they are increased in testicular failure (hypergonadotropic hypogonadism)
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Male hypogonadism is caused by deficient testosterone secretion by the testes It may be classified according to whether it is due to (1) insufficient gonadotropin secretion by the pituitary (hypogonadotropic) or (2) pathology in the testes themselves (hypergonadotropic) (Table 26 14)
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A Hypogonadotropic Hypogonadism
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A deficiency in FSH and LH may be isolated or associated with other pituitary hormonal abnormalities (See Hypopituitarism) Patients must be evaluated for signs of Cushing s syndrome or adrenal insufficiency, growth hormone excess or deficiency, and thyroid hormone excess or deficiency Acquired hypogonadotropic hypogonadism may be due to pituitary or hypothalamic factors but may be idiopathic Hyperprolactinemia (see Table 26 2) may also induce hypogonadism Hypogonadotropic hypogonadism can develop in men receiving GnRH agonist therapy for prostate cancer and can persist following cessation of therapy
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B Hypergonadotropic Hypogonadism
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A failure in testicular secretion of testosterone causes a rise in LH If testicular Sertoli cell function is deficient, FSH will be elevated Conditions that can cause testicular failure include viral infection (eg, mumps), irradiation, cancer chemotherapy, autoimmunity, myotonic dystrophy, uremia, XY gonadal dysgenesis, partial 17-ketosteroid reductase deficiency, Klinefelter syndrome, and male climacteric Klinefelter syndrome (seminiferous tubule dysgenesis) is a common cause of male hypogonadism that is due to the expression of an abnormal karyotype, classically 47,XXY Other forms are common, eg, 46,XY/47,XXY mosaicism, 48,XXYY, 48,XXXY, or 46,XX males The manifestations of Klinefelter syndrome are variable Testes feel normal during childhood, but during adolescence they usually become firm, fibrotic, small, and nontender to
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Table 26 14 Causes of male hypogonadism
Hypogonadotropic (Low or Normal LH) Alcohol Chronic illness Congenital syndromes Constitutional delay Cushing s syndrome Drugs Estrogen-secreting tumors (testicular, adrenal) GnRH agonist (leuprolide) Hemochromatosis Hypopituitarism Hypothyroidism Idiopathic Kallmann s syndrome Ketoconazole 17-Ketosteroid reductase deficiency Malnourishment Marijuana Obesity (BMI > 40) Prader-Willi syndrome Prior androgens Spironolactone LH, luteinizing hormone; GnRH, gonadotropin-releasing hormone; BMI, body mass index Hypergonadotropic (High LH) Antitumor chemotherapy Bilateral anorchia Idiopathic Klinefelter syndrome Leprosy Lymphoma Male climacteric Mumps Myotonic dystrophy Noonan s syndrome Orchitis Radiation therapy Sertoli cell-only syndrome Testicular trauma Tuberculosis Uremia
Table 26 15 Causes of gynecomastia
Idiopathic Physiologic causes Neonatal period Puberty Aging Obesity Endocrine diseases Androgen resistance syndromes Aromatase excess syndrome (sporadic or familial) Diabetic lymphocytic mastitis Hyperprolactinemia Hyperthyroidism Klinefelter s syndrome Male hypogonadism Partial 17-ketosteroid reductase deficiency Systemic diseases Chronic liver disease Chronic renal disease Neurologic disorders Refeeding after starvation Spinal cord injury Neoplasms Adrenal tumors Bronchogenic carcinoma Carcinoma of the breast Hepatocellular carcinoma (rare) Testicular tumors Drugs (partial list) Alcohol Alkylating agents Amiodarone Anabolic steroids Androgens Bicalutamide Busulfan Chorionic gonadotropin Cimetidine Clomiphene Cyclophosphamide Diazepam Diethylstilbestrol Digitalis preparations Estrogens (oral or topical) Ethionamide Finasteride Flutamide Goserelin HAART (highly active antiretroviral therapy) Haloperidol Hydroxyzine Isoniazid Ketoconazole Leuprolide Marijuana Meprobamate Methadone Methyldopa Metoclopramide Mirtazapine Molindone Nilutamide Omeprazole Opioids Penicillamine Phenothiazines Progestins Protease inhibitors Reserpine Risperidone Somatropin (growth hormone) Spironolactone Testosterone Thioridazine Tricyclic antidepressants
palpation Although puberty occurs at the normal time, the degree of virilization is variable About 85% of patients have some gynecomastia at puberty Other common findings include tall stature and abnormal body proportions that are unusual for hypogonadal men (height greater than arm span; crown-pubis length greater than pubis-floor) Patients with multiple X or Y chromosomes are more apt to have mental deficiency and other abnormalities such as clinodactyly or synostosis They may also exhibit problems with coordination and social skills Other problems include a higher incidence of breast cancer, chronic pulmonary disease, varicosities of the legs, and diabetes mellitus (8% of patients); impaired glucose tolerance occurs in an additional 19% of patients Most men (about 95%) have azoospermia, but men with 46,XY/47,XXY mosaicism may be fertile The diagnosis is confirmed by karyotyping or by determining the presence of RNA for X-inactive-specific transcriptase (XIST) in peripheral blood leukocytes by polymerase chain reaction All causes of gynecomastia (see Table 26 15) must be differentiated from Klinefelter syndrome