(click for larger image)Pituitary gland in the brain. Computer artwork of a person’s head showing the left hemisphere of the brain inside. The highlighted area (center) shows the pituitary gland. The pituitary gland is a small endocrine gland about the size of a pea protruding off the bottom of the hypothalamus at the base of the brain. It secretes hormones regulating homoeostasis, including trophic hormones that stimulate other endocrine glands. It is functionally connected to and influenced by the hypothalamus.Image Credit: Roger Harris / Science Source
Case
A 53-year-old woman with a history of a suprasellar meningioma resected nine years ago with recurrence of a 4.5×2 cm mass one year ago and recent ventriculoperitoneal (VP) shunt placement for hydrocephalus presented with altered mental status (AMS) and hallucinations. She was admitted for radiation therapy to the mass. The patient had little improvement in her mental status four weeks into a six-week, 4860 cGy course of photon therapy.
The internal medicine service was consulted for new onset tachycardia (103), hypotension (83/55), and fever (38.6 C). Laboratory data revealed a white blood cell count 4.8 x 109 cells/L, sodium 137 mmol/L, potassium 4.1 mmol/L, chloride 110 mmol/L, bicarbonate 28 mmol/L, blood urea nitrogen 3 mg/dl, creatinine 0.6 mg/dl, and glucose 91 mg/dl. Thyroid-stimulating hormone (TSH) was low at 0.38 mIU/mL. Urine specific gravity was 1.006. Workups for infectious and thromboembolic diseases were unremarkable.
Discussion
Hypopituitarism is a disorder of impaired hormone production from the anterior and, less commonly, posterior pituitary gland. The condition can originate from several broad categories of diseases affecting the hypothalamus, pituitary stalk, or pituitary gland. In adults, the etiology is often from the mass effect of tumors or from treatment with surgery or radiotherapy. Other causes include vascular, infectious, infiltrative, inflammatory, and idiopathic. Well-substantiated data on the incidence and prevalence of hypopituitarism is sparse. It has an estimated prevalence of 45.5 cases per 100,000 and incidence of 4.2 cases per 100,000 per year.1
Clinical manifestations of hypopituitarism depend on the type and severity of hormone deficiency. The consequences of adrenal insufficiency (AI) range from smoldering and nonspecific findings (e.g. fatigue, lethargy, indistinct gastrointestinal symptoms, eosinophilia, fever) to full-fledged crisis (e.g. AMS, severe electrolyte abnormalities, hemodynamic compromise, shock). The presentation of central AI (i.e., arising from hypothalamic or pituitary pathology) is often more subtle than primary AI. In central AI, only glucocorticoid (GC) function is disrupted, leaving the renin-angiotensin-aldosterone system and mineralocorticoid (MC) function intact. This is in stark contrast to primary AI resulting from direct adrenal gland injury, which nearly always disrupts both GC and MC function, leading to more profound circulatory collapse and electrolyte disturbance.2
Aside from orthostatic blood pressure or possible low-grade fever, few physical exam features are associated with central AI. Hyperpigmentation is not seen due to the lack of anterior pituitary-derived melanocortins that stimulate melanocytes and induce pigmentation. As for laboratory findings, hyperkalemia is a feature of primary AI (due to hypoaldosteronism) but is not seen in central AI. Hyponatremia occurs in both types of AI and is vasopressin-mediated. Hyponatremia is more common in primary AI, resulting from appropriate vasopressin release that occurs due to hypotension. Hyponatremia also occurs in secondary AI because of increased vasopressin secretion mediated directly by hypocortisolemia.3,4
In summary, hyperpigmentation and the electrolyte pattern of hyponatremia and hyperkalemia are distinguishing clinical characteristics of primary AI, occurring in up to 90% of cases, but these features would not be expected with central AI.5
In the hospitalized patient with multiple active acute illnesses and infectious risk factors, it can be difficult to recognize the diagnosis of AI or hypopituitarism. Not only do signs and symptoms frequently overlap, but concomitant acute illness is usually a triggering event. Crisis should be suspected in the setting of unexplained fever, dehydration, or shock out of proportion to severity of current illness.5