endocrine and metabolic disorders
Generalized Hypopituitarism
Diagnosis of Generalized Hypopituitarism
MRI or CT Pituitary hormone levels: TSH, prolactin, LH, FSH, Target organ hormone levels: Free thyroxine (T4),testosterone(in men) orestradiol(in women), andcortisollevels plus provocative testing of pituitary-adrenal axis Sometimes other provocative testing Clinical features are often nonspecific, and the diagnosis must be established with certainty before committing the patient to a lifetime of hormone replacement therapy. Pituitary dysfunction must be distinguished from Anorexia Nervosa , chronic liver disease, myotonia dystrophica, polyglandular autoimmune disease , and disorders of the other endocrine glands (see table Patients should undergo high-resolution CT or MRI, with contrast agent as required (to rule out structural abnormalities, such as pituitary adenomas). Positron emission tomography (PET) is a research tool used in a few specialized centers and therefore is rarely done. When no modern neuroradiologic facilities are available, a simple cone-down lateral x-ray of the sella turcica can identify pituitary macroadenomas with a diameter>10 mm. Cerebral angiography is indicated only when other imaging tests suggest perisellar vascular anomalies or aneurysms. Initial evaluation should include testing for TSH and ACTH deficiencies, because both conditions are potentially life threatening. Selective Pituitary Hormone Deficiencies is also discussed elsewhere. Dynamic or provocative testing of pituitary function is seldom done except in the evaluation of adrenal insufficiency with the short ACTH stimulation test, and with testing to diagnose GH deficiency. Agents used in many tests, including thyrotropin-releasing hormone, growth hormone–releasing hormone, Free T4 and TSH levels should be determined. TSH is typically inappropriately low or normal in relation to low levels of circulating T4. The most common manifestation of central hypothyroidism is a pattern of normal TSH level with low free T4. In contrast, elevated TSH levels with low free T4 indicates a primary abnormality of the thyroid gland. Synthetic thyrotropin-releasing hormone (TRH), 200 to 500 mcg IV given over 15 to 30 seconds, may help identify patients with hypothalamic as opposed to pituitary dysfunction, although this test is not often done due to lack of commercial availability. Serum TSH levels are generally measured at 0, 20, and 60 minutes after injection. If pituitary function is intact, TSH should rise by>5 mIU/L, peaking by 30 minutes after injection. A delayed rise in serum TSH levels may occur in patients with hypothalamic disease. However, some patients with primary pituitary disease also show a delayed rise. Serum ACTH levels are not helpful in the diagnosis of ACTH deficiency. Similarly, serum cortisol levels alone are not reliable indicators of ACTH-adrenal axis function, although a very low morning serum cortisol level (< 3.5 mcg/dL [96.6 nmol/L] between 7:30 and 9:00 AM) strongly suggests cortisol deficiency. One of several provocative tests should be done unless a morning level>18 mcg/dL [500 nmol/L] obtained using polyclonal radioimmunoassays or a morning level > 15 mcg/dL (415 nmol/L) using monoclonal antibodies or liquid chromatography with tandem mass spectrometry (LC-MS/MS) rules out adrenal insufficiency. Theshort ACTH stimulation testis a safer and less labor-intensive test for cortisol deficiency than theinsulintolerance test. In the short ACTH stimulation test, synthetic ACTH 250 mcg IV or IM (standard-dose test) or 1 mcg IV (low-dose test) is given, and the blood cortisol level is measured immediately before and 30 and 60 minutes after administration of the synthetic ACTH. Cortisol should rise significantly; a peak of<18 mcg/dL (500 nmol/L) using polyclonal assays or < 15 mcg/dL (414 nmol/L) using monoclonal antibody assays or LC-MS/MS is abnormal. However, the short ACTH stimulation test is abnormal in secondary cortisol deficiency only when the test done at least 2 to 4 weeks after onset of the deficiency; before this time, the adrenal glands have not atrophied and remain responsive to exogenous ACTH. Usually, only transient perspiration, tachycardia, and nervousness occur. If the patient complains of palpitations, loses consciousness, or has a seizure, the test should be stopped promptly and Treatment by giving IV glucose. tolerance test alone will differentiate between primary (Addison disease) and secondary (hypopituitary) adrenal insufficiency. Tests to make this distinction and to evaluate the hypothalamic-pituitary-adrenal axis are described under Addison Disease . Thecorticotropin-releasing hormone(CRH) test is done to distinguish between primary, secondary (pituitary), and tertiary (hypothalamic) causes of adrenal insufficiency. CRH 1 mcg/kg IV is given by rapid injection. Serum ACTH and cortisol levels are measured 15 minutes before, then at baseline, and 15, 30, 60, 90, and 120 minutes after the injection. Adverse effects include temporary flushing, a metallic taste in the mouth, and slight and transient hypotension. Use of this test is limited by cost and availability of CRH. Ease of administration of the short ACTH stimulation test has largely replaced this test. Prolactin levels are routinely measured. These levels are often elevated up to 5 times normal values when a large pituitary tumor is present, even if it does not produce prolactin. The tumor compresses the pituitary stalk, preventingdopamine, which inhibits pituitary prolactin production and release, from reaching the pituitary. Patients with such hyperprolactinemia often have hypogonadotropism and secondary hypogonadism. Measurement of basal levels of LH and FSH is most helpful in evaluating hypopituitarism in postmenopausal women not taking exogenousestrogensin whom circulating gonadotropin concentrations are normally high (>30 mIU/mL [> 30 IU/L]). In premenopausal women, menstrual history is superior to measurement of gonadotropins in determining pituitary function. Although gonadotropin levels tend to be low in other patients with panhypopituitarism, overlap exists with the normal range. Levels of both hormones should increase in response to synthetic gonadotropin-releasing hormone (GnRH) at a dose of 100 mcg IV, with LH peaking about 30 minutes and FSH peaking 40 minutes after GnRH administration, but normal increases in LH and FSH in response to GnRH vary. However, normal, diminished, or absent responses to GnRH may occur in hypothalamic-pituitary dysfunction. Administration of exogenous GnRH is not helpful in distinguishing primary hypothalamic disorders from primary pituitary disorders. Dynamic testing of the gonadal axis is rarely indicated in adults and is rarely helpful in distinguishing gonadal axis deficiencies and delayed puberty in adolescents. GnRH is also not widely commercially available. -like growth factor 1 (IGF-1) level. Because GH levels vary by time of day and other factors and are difficult to interpret, levels of IGF-1, which reflect GH, are used; low levels suggest GH deficiency, but normal levels do not rule it out. A Diagnosis may be necessary. 