A 35-year-old man comes to the office after a year of weakness, fatigue, and weight loss. He has experienced reduced appetite and intermittent diarrhea. The patient had no improvement after several sessions with a clinical psychologist, who suggested evaluation for a physiological cause of his symptoms. His medical history is unremarkable, and he takes no regularly scheduled medications. The patient does not use tobacco, alcohol, or illicit drugs. Family history is notable for hypothyroidism (sister). Temperature is 37.2 C (99 F), blood pressure is 106/66 mm Hg, pulse is 94/min, and respirations are 14/min. On physical examination, the patient does not appear to be in acute distress. His neck shows no thyromegaly or lymphadenopathy. Cardiopulmonary examination is normal, and the abdomen is soft with normal bowel sounds and no organomegaly. Motor strength and deep tendon reflexes are normal and symmetric. Laboratory results are as follows: Which of the following is the most appropriate next step in management of this patient?

Question

A 35-year-old man comes to the office after a year of weakness, fatigue, and weight loss.  He has experienced reduced appetite and intermittent diarrhea.  The patient had no improvement after several sessions with a clinical psychologist, who suggested evaluation for a physiological cause of his symptoms.  His medical history is unremarkable, and he takes no regularly scheduled medications.  The patient does not use tobacco, alcohol, or illicit drugs.  Family history is notable for hypothyroidism (sister).  Temperature is 37.2 C (99 F), blood pressure is 106/66 mm Hg, pulse is 94/min, and respirations are 14/min.  On physical examination, the patient does not appear to be in acute distress.  His neck shows no thyromegaly or lymphadenopathy.  Cardiopulmonary examination is normal, and the abdomen is soft with normal bowel sounds and no organomegaly.  Motor strength and deep tendon reflexes are normal and symmetric.  Laboratory results are as follows:  Which of the following is the most appropriate next step in management of this patient?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d39c_3797_bc81_f5427669541c_MD0003_00 This patient has chronic weakness, weight loss, hyponatremia, and hyperkalemia associated with a low-normal cortisol level. This is a typical presentation of primary adrenal insufficiency (PAI), also known as Addison disease. PAI can be due to autoimmune adrenalitis, infections (eg, tuberculosis), malignancy, or adrenal hemorrhage. The initial symptoms are nonspecific and include fatigue, weakness, and weight loss. Gastrointestinal symptoms occur in most patients. Aldosterone deficiency causes volume depletion, which can manifest as hypotension or syncope. Skin signs can include hyperpigmentation or vitiligo. Almost all patients have hyponatremia due to salt wasting, volume depletion, and increased antidiuretic hormone release. Most also have hyperkalemia due to aldosterone deficiency. The initial evaluation should include an 8 AM serum cortisol and plasma ACTH. A low cortisol level (<5 µg/dL) with high ACTH confirms PAI, and a low cortisol level with low ACTH suggests central (pituitary [secondary] or hypothalamic [tertiary]) adrenal insufficiency. A high or high-normal cortisol level (>15 µg/dL) essentially rules out PAI. Some patients with manifestations strongly suggestive of PAI may have low-normal cortisol levels (5-15 µg/dL) that fall within the normal range, as seen here. Because of this, and because the ACTH assay can take several days, an ACTH stimulation test (cosyntropin test) is usually performed concurrently to rapidly confirm the diagnosis. Cosyntropin is a synthetic ACTH analog. Infusion of a 250-µg bolus of cosyntropin normally triggers a rapid increase in serum cortisol. In contrast, patients with PAI will not have a significant rise. In addition, most patients with central adrenal insufficiency have a blunted (minimal or suboptimal) response due to adrenal atrophy from chronically low ACTH. If results are indeterminate, further pituitary function testing can be considered. (Choice A) Urinary cortisol levels are decreased in severe PAI, but sensitivity is too low for use in the initial diagnosis. Urinary 24-hour cortisol is one of the first line tests in Cushing syndrome (eg, facial plethora, striae, hypertension at a young age). (Choice C) Cortisol is synthesized in response to hypoglycemia. In the insulin hypoglycemia test, insulin is given to induce hypoglycemia, and cortisol levels are measured. However, this test is technically cumbersome and can be hazardous in some patients. (Choice D) Intravenous hydrocortisone is given for adrenal crisis (ie, abdominal pain, fever, hemodynamic instability). This patient has chronic, stable symptoms, and the diagnosis should be confirmed prior to treatment. (Choice E) Dexamethasone suppresses release of ACTH from the pituitary, which subsequently reduces adrenal cortisol production. The dexamethasone suppression tests are used to evaluate hypercortisolism (eg, Cushing) but are not used in PAI. Educational objective: The evaluation of adrenal insufficiency should include an 8 AM serum cortisol and plasma ACTH. In addition, an ACTH stimulation test (cosyntropin test) can identify patients with primary adrenal insufficiency (and most patients with central adrenal insufficiency) and should be performed in the initial evaluation. References: Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline (http://www.ncbi.nlm.nih.gov/pubmed/26760044)

A 35-Year-Old Man Comes to the Office After a Year