A variety of disorders may cause deficiencies of one or more pituitary hormones. These disorders may be genetic, congenital, traumatic (pituitary surgery, cranial irradiation, head injury), neoplastic (large pituitary adenoma, parasellar mass, craniopharyngioma, metastases, meningioma), infiltrative (hemochromatosis, lymphocytic hypophysitis, sarcoidosis, histiocytosis X), vascular (pituitary apoplexy, postpartum necrosis, sickle cell disease), or infectious (tuberculous, fungal, parasitic). The most common cause of hypopituitarism is neoplastic in origin (macroadenomatous destruction, or following hypophysectomy or radiation therapy). Pituitary hormone failure due to compression, destruction, or radiation therapy typically follows a sequential pattern: GH>FSH>LH>TSH>ACTH. Genetic causes of hypopituitarism may affect several hormones (e.g., pituitary dysplasia, PROP-1 and PIT-1 mutations) or be restricted to single pituitary hormones or axes (e.g., isolated GH deficiency, Kallmann syndrome, isolated ACTH deficiency). Hypopituitarism following cranial irradiation develops over 5-15 years. Varying degrees of partial to complete hormone deficiencies occur during evolution of pituitary destruction.
Each hormone deficiency is associated with specific findings:
Biochemical diagnosis of pituitary insufficiency is made by demonstrating low or inappropriately normal levels of pituitary hormones in the setting of low target hormone levels. Initial testing should include an 8 A.M. cortisol level, TSH and free T4, IGF-I, testosterone in men, assessment of menstrual cycles in women, and PRL level. Provocative tests are required for definitive diagnosis of GH and ACTH deficiency. Adult GH deficiency is diagnosed by demonstrating a subnormal GH response to a standard provocative test (insulin tolerance test, L-arginine + GHRH). Acute ACTH deficiency may be diagnosed by a subnormal response in an insulin tolerance test, metyrapone test, or corticotropin-releasing hormone (CRH) stimulation test. Standard ACTH (cosyntropin) stimulation tests may be normal in acute ACTH deficiency; with adrenal atrophy, the cortisol response to cosyntropin is blunted.
Treatment: Hypopituitarism Hormonal replacement should aim to mimic physiologic hormone production. Effective dose schedules are outlined in Table 168-1. Doses should be individualized, particularly for GH, glucocorticoids, and L-thyroxine. GH therapy, particularly when excessive, may be associated with fluid retention, joint pain, and carpal tunnel syndrome. Glucocorticoid replacement should always precede L-thyroxine therapy to avoid precipitation of adrenal crisis. Pts requiring glucocorticoid replacement should wear a medical alert bracelet and should be instructed to take additional doses during stressful events such as acute illness, dental procedures, trauma, and acute hospitalization. |
For a more detailed discussion, see Melmed S, Jameson JL: Anterior Pituitary: Physiology of Pituitary Hormones, Chap 401e; Hypopituitarism, Chap 402, p. 2255; Anterior Pituitary Tumor Syndromes, Chap 403, p. 2261, in HPIM-19. |
Section 13. Endocrinology and Metabolism