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). Automimmune hypophysitis has been associated with checkpoint inhibitor cancer immunotherapy. The most common cause of hypopituitarism is neoplastic in origin (pituitary mass, or following hypophysectomy or radiation therapy). Pituitary hormone failure due to compression, destruction, or radiation therapy follows a sequential pattern, though this is highly variable: 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 hypothalamic and pituitary damage.
Each hormone deficiency is associated with specific findings:
- GH:growth disorders in children; increased intraabdominal fat, reduced lean body mass, hyperlipidemia, reduced bone mineral density, decreased stamina, and social isolation in adults
- FSH/LH: menstrual disorders and infertility in women (Chap. 178 Disorders of the Female Reproductive System); hypogonadism in men (Chap. 177 Disorders of the Male Reproductive System)
- ACTH: features of hypocortisolism (Chap. 174 Adrenal Gland Disorders) without mineralocorticoid deficiency
- TSH: growth retardation in children; features of hypothyroidism in children and adults (Chap. 173 Thyroid Gland Disorders)
- PRL: failure to lactate postpartum
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. Note that TSH levels are often inappropriately low or normal in the setting of low free T4. 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 | ||
HypopituitarismHormonal replacement should aim to mimic physiologic hormone production. Effective dose schedules are outlined in Table 171-1 Hormone Replacement Therapy for Adult Hypopituitarisma . 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. |