Several nonneoplastic diseases (see Table 4) may induce hypogonadotropic hypogonadism (19). In these disorders, hypogonadism primarily results from gonadotropin deficiency secondary to hypothalamic-pituitary damage. In addition, GH/IGF-1, thyroid hormone, and CRF/ACTH/cortisol play a permissive role in the spermatogenesis and testosterone production regulation. In fact, these hormones regulate the gonadotrophin responsiveness of Leydig and Sertoli cells. Therefore, deficiency of all or some anterior pituitary hormones, together with the increase in PRL, may induce hypogonadism.
Pituitary apoplexy results in anterior pituitary failure secondary to hemorrhagic or ischemic infarction. In men, hemorrhage usually occurs into a pituitary tumor, whereas ischemia may involve a normal pituitary gland in the setting of increased intracranial pressure or during anticoagulation therapy. Hormone deficiencies after apoplexy include GH (88%), gonadotropins (58-76%), ACTH (66%), TSH (42-53%), and PRL (67-100%) (90).
Empty sella is defined as a sella that is completely or partially filled by CSF, owing to arachnoid herniation into the pituitary fossa. This herniation remodels and enlarges the bony sella and flattens the pituitary gland against the sella floor. Empty sella is usually an incidental anatomical finding, and functional pituitary damage is infrequent, particularly in primary empty sella. That patients are usually asymptomatic derives from the large functional reserve of the adenohypophysis. However, hypogonadism is not rare, and hyperprolactinemia occurs in approx 15% of cases (90).
Aneurysms of the cavernous sinus, as well as infectious (bacterial or fungal abscesses, tuberculosis, and toxoplasmosis) and inflammatory processes (sarcoidosis, giant cell granuloma, lymphocytic hypophysitis, and histiocytosis X) can mimic a pituitary adenoma, causing mass effect and hypothalamic-hypophyseal endocrine dysfunction secondary to infiltration of normal tissue (91).
Arachnoid cyst is a diverticulum of the arachnoidal membrane of Liliequist. Of these cysts, 15% occur in the sellar and parasellar regions. This mass may compress the hypothalamic-pituitary unit, inducing endocrine disorders, including hypogonadism-producing impotence or low libido (88).
Mucoceles are slowly expanding, mucous-filled cystic lesions that arise in the paranasal sinuses. These cysts result from the accumulation and retention of mucous secretions in a sinus secondary to the occlusion of the ostium draining the sinus. Sphenoid mucocele with suprasellar extension can also increase prolactin levels by compressing the pituitary stalk (92).
Radiation of the head for treatment of primary central nervous system (CNS) tumors or brain metastases may cause the gradual onset of hypothalamic-pituitary failure. The most frequent endocrine abnormalities after cranial radiotherapy are hypothyroidism (65%), hypogonadism (61%), and mild hyperprolactinemia (50%). Although the mechanism of radiation damage to the hypothalamus and pituitary gland is not known, it must involve a direct injury to the secreting cells or to the stroma or its microvasculature or damage the vascular channels that transfer the hypothalamic hormones to the pituitary (93).
Head trauma may induce hypogonadism. This is a common event. Lee et al. observed hypotestosteronemia in 67% of patients within 1 wk of severe traumatic brain injury (94). The gonadotropins are the most fragile hormones (95), with deficiency occurring in almost 100% of cases with post-head trauma hypopituarism. ACTH, TSH, and GH deficiency occur in 53%, 44%, and 24% of cases, respectively. In addition, stalk lesions may increase PRL levels in approx 50% of the cases, further worsening gonadal function (96).
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