This is a complex investigation and I will repeat the explanation several times to the patient on each subsequent visit to assure his under standing. The major objectives of the initial assessment of a patient with possible hypo-gonadism are to distinguish primary gonadal failure (hyper-gonadotropic hypo-gonadism with low testosterone and increased FSH and LH levels) from hypothalamic-pituitary disorders (hypo-gonadotropic hypo-gonadism with low testosterone and low to normal FSH and LH levels) and to make a specific diagnosis. The initial clinical manifestations may vary, depending on whether the onset of the disorder was pre-pubertal or post-pubertal. Men with hypo-gonadotropic disorders may achieve fertility with gonadal stimulation. Men with hyper-gonadotropic disorders are treated with testosterone to achieve virilization and are usually, but not invariably, incapable of achieving fertility.
History and Physical Examination
A history of major medical problems, medications, toxic exposures, fertility problems, and developmental milestones should especially be noted. Low libido, impotence, fatigue, impaired concentration, and sexual dysfunction are important presenting problems and need to be asked about specifically because most men will not seek medical attention for these symptoms alone. • The degree of pubertal development, eunuchoid proportions, anosmia, hyposmia, gynecomastia, abnormal hair growth and distribution, abnormal genitalia, presence of varicocele, findings on prostate examination, and testicular size and consistency, in particular, are important physical manifestations for differential diagnosis.
Laboratory and Ancillary Evaluation
Laboratory testing is directed toward determining whether the patient has abnormalities of reproductive hormones and whether the abnormalities are indicative of testicular or hypothalamic-pituitary disease. The initial laboratory testing should include a morning blood sample for testosterone, prolactin, FSH, and LH levels. A semen analysis is needed if fertility potential is at issue. • If testosterone levels are low-normal and the symptoms and signs indicate hypo-gonadism, the testosterone 452 AACE Hypogonadism Guidelines, Endocr Pract. 2002;8(No. 6) study should be repeated, and SHBG or a free testosterone level by equilibrium dialysis should be determined to help diagnose a hypo-gonadal state because total testosterone levels may be normal in the setting of hypo-gonadism if the SHBG levels are increased. • For the diagnosis of hyper-gonadotropic hypo-gonadism, FSH is especially important because FSH has a longer half-life, is more sensitive, and demonstrates less variability than LH. Pooled LH samples (three preferred) may help reduce problems with LH variability associated with a short half-life and pulsatile secretion. • Dynamic testing of the hypothalamic-pituitary-testicular axis should be done by an endocrinologist and reserved for patients in whom the results of baseline diagnostic testing are equivocal, although interpretation of the results of dynamic testing may be poorly defined. • In acquired hypo-gonadotropic hypo-gonadism, a prolactin level and pituitary imaging study should be done to assess the patient for a possible hypothalamic-pituitary disorder such as a pituitary tumor. Testing of the thyroid, adrenal, and growth hormone axes is also indicated. • Chromosomal analysis should be considered in men with pre-pubertal-onset hyper-gonadotropic hypo-gonadism to evaluate for Klinefelter’s syndrome and related disorders. • Bone densitometry should be done in men with chronic, untreated hypo-gonadal disorders to aid in decision making about treatment options to prevent and treat osteoporosis. • Testicular ultrasonography should be done in patients with clinical findings suggestive of a scrotal or testicular mass. • In the evaluation of abnormal semen findings, testicular biopsy should be reserved for patients with normal results of hormonal studies and azoospermia to evaluate for obstruction or congenital absence of the vasa and possible surgical repair or for possible use of in vitro fertilization with intra-cytoplasmic sperm injection. Diagnosis and Treatment An overall summary of clinical and laboratory findings, potential diagnoses, and recommended evaluation or treatment strategies in adult male patients with hypo-gonadism is presented in Table 1.
The recognition, evaluation, and treatment of hypo-gonadism in the male patient are often dismissed by the patient and overlooked by the physician. The symptoms and signs of hypo-gonadism should be identified through appropriate questioning of the patient and a directed physical examination. Hormonal and ancillary testing should be performed in a cost-efficient and clinically appropriate manner to allow pertinent treatment considerations. Testosterone replacement therapy can often enable the patient to function in a more normal manner and decrease the risk of future problems with fertility, mood disturbances, fatigue, impaired virilization, and osteoporosis. Further studies are needed to determine the influence of testosterone replacement therapy on cardiovascular risk. Of importance, these guidelines demonstrate the need for meaningful, long-term studies of hypo-gonadal disorders in general and of aging men in particular. The ultimate goals are to improve not only the duration but also the quality of life and to allow people to reach their full potential regardless of age. Patients with acquired hypo-gonadotropic hypo-gonadism may require assessment for a possible pituitary tumor with appropriate pituitary imaging studies, such as MRI, and determination of a prolactin level. Depending on the presence or absence of a tumor, other hormonal testing may be indicated, including thyroid and adrenal function tests. Further evaluation and treatment options would depend on what hormonal deficits are present, the size and site of the tumor, the operability of the tumor, and the patient’s preferences in specific circumstances. If a prolactinoma is present, therapy would be directed toward correcting this problem before initiation of other therapy. Medical therapy with bromocriptine, pergolide, or cabergoline may effectively reduce prolactin levels sufficiently to allow gonadal function to resume or allow stimulation with gonadotropins. Even when prolactin levels cannot be normalized, hCG therapy alone or in conjunction with human menopausal gonadotropin (or FSH) therapy may stimulate spermatogenesis in treated prolactinomas and result in pregnancies (77). Surgical therapy should especially be considered for significant pituitary tumors that are not prolactin-secreting microadenomas. Surgical treatment may also be an option in prolactin-secreting microadenomas if patients have severe side effects from medications or prefer this approach after being appropriately informed of the risks and benefits of medical versus surgical management
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