How is hypopituitarism diagnosed?
In the setting of typical and overt manifestations of hypopituitarism, basal serum hormone measurements may suffice. However, in patients with more subtle manifestations, dynamic endocrine testing may be indicated.
• ACTH deficiency: Nonspecific laboratory findings include hyponatremia, normochromic, normocytic anemia, and eosinophilia. In the noncritical setting, morning (7–9 am) serum cortisol levels < 3 mcg/dL and > 15 mcg/dL practically rule in and rule out adrenal insufficiency, respectively. When cortisol values are between 3 and 15 mcg/dL or if there is any doubt about the diagnosis, standard-dose corticotropin (ACTH) stimulation testing should be performed. An ampule of cosyntropin (250 mcg) is administered intramuscularly or intravenously, and serum cortisol is obtained at 0, 30, and 60 minutes. Adrenal insufficiency is excluded if either the 30-minute or the 60-minute cortisol level is > 18 mcg/dL. If it is not obvious that the etiology is central in origin, an inappropriately low or normal morning (7–9 AM ) plasma ACTH level will confirm this suspicion.
• TSH deficiency: Hyponatremia, macrocytic anemia, hyperlipidemia, and elevated creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) can be seen. However, central hypothyroidism is confirmed when the serum free thyroxine (T 4 ) level is below the laboratory reference range in conjunction with a low, normal, or slightly elevated TSH concentration in the setting of pituitary disease.
• Gonadotropin deficiency: Normochromic, normocytic anemia may be seen in men with hypogonadism. Decreased fasting morning (before 10 am) testosterone levels in men and low estradiol concentrations in premenopausal normoprolactinemic women with oligomenorrhea or amenorrhea, in conjunction with inappropriately low or normal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, are indicative of central hypogonadism. In postmenopausal women, the absence of high serum FSH and LH is consistent with gonadotropin deficiency.
• GH deficiency: In patients with clear-cut features of GH deficiency, ≥ three pituitary hormone deficits, and insulin-like growth factor 1 (IGF-1) level below the lower limit of normal for age and gender is indicative of GH deficiency. Otherwise, GH stimulation testing, using appropriately controlled body mass index (BMI) cut-offs to assess peak GH values, is required to make this diagnosis. Because growth hormone–releasing hormone (GHRH) is presently unavailable in the United States and the insulin tolerance test is not commonly performed for fear of complications associated with hypoglycemia, the glucagon stimulation test has become increasingly utilized to rule out GH deficiency. Glucagon 1 mg (1.5 mg if weight > 90 kg) is administered intramuscularly and blood for GH and glucose is collected at 0, 30, 60, 90, 120, 150, 180, 210, and 240 minutes. A peak GH level < 3 mcg/L is indicative of GH deficiency.
• PRL deficiency: Low or undetectable serum PRL concentration.