A 34-year-old woman comes to the office after a recent hospitalization. Over the past several months, the patient has had worsening weakness, anorexia, nausea, and abdominal discomfort. Two weeks ago, she had a syncopal episode; evaluation found a low serum cortisol level and subnormal response to ACTH stimulation. The patient was treated in the hospital and was discharged on oral hydrocortisone therapy. Since discharge, she has had intermittent episodes of light-headedness and nausea but reports improvement in other symptoms. Her husband adds that the patient consumes excessive amounts of salty foods. Temperature is 36.9 C (98.4 F), blood pressure is 108/66 mm Hg supine and 98/60 mm Hg upright, and pulse is 88/min supine and 102/min upright. Physical examination reveals hyperpigmentation of the oral mucosa and palmar creases. Cardiopulmonary and abdominal examination shows no abnormalities. Laboratory results are as follows: Which of the following is the most appropriate next step in management of this patient?

Question

A 34-year-old woman comes to the office after a recent hospitalization.  Over the past several months, the patient has had worsening weakness, anorexia, nausea, and abdominal discomfort.  Two weeks ago, she had a syncopal episode; evaluation found a low serum cortisol level and subnormal response to ACTH stimulation.  The patient was treated in the hospital and was discharged on oral hydrocortisone therapy.  Since discharge, she has had intermittent episodes of light-headedness and nausea but reports improvement in other symptoms.  Her husband adds that the patient consumes excessive amounts of salty foods.  Temperature is 36.9 C (98.4 F), blood pressure is 108/66 mm Hg supine and 98/60 mm Hg upright, and pulse is 88/min supine and 102/min upright.  Physical examination reveals hyperpigmentation of the oral mucosa and palmar creases.  Cardiopulmonary and abdominal examination shows no abnormalities.  Laboratory results are as follows:  Which of the following is the most appropriate next step in management of this patient?

Quizplus · Accepted Answer

Explanation: 11ec2b69_c12f_0fe0_8f63_01f8718ab520_MD0005_00 This patient likely has primary adrenal insufficiency (PAI) given her low serum cortisol level, abnormal ACTH stimulation test, and hyperpigmentation (increased melanocyte-stimulating hormone, which, along with ACTH, is derived from proopiomelanocortin). The resultant loss of both glucocorticoid and mineralocorticoidproduction from the adrenal glands leads to hypotension, orthostatic syncope, hyponatremia (salt craving), and hyperkalemia. adrenal glands The patient received appropriate initial treatment with hydrocortisone, which has glucocorticoidand mild mineralocorticoid activity. However, most patients who have PAI and are treated with hydrocortisone alone may continue to have signs of mineralocorticoid deficiency, including hyponatremia, hyperkalemia, and orthostatic hypotension. Fludrocortisone is a synthetic mineralocorticoid analog that can be given in small doses with hydrocortisone to replace mineralocorticoid activity. In contrast, patients with central (ie, hypothalamic, pituitary) adrenal insufficiency usually have adequate mineralocorticoid activity (aldosterone secretion is regulated by the renin-angiotensin system) and are treated with glucocorticoids alone. (Choice B) Midodrine is an alpha-adrenergic agonist used to treat orthostatic hypotension. It may improve this patient's orthostatic symptoms but would not correct the other features of mineralocorticoid deficiency (eg, hyperkalemia). (Choice C) Switching to dexamethasone would not correct this patient's mineralocorticoid deficiency because this medication has only glucocorticoid and no mineralocorticoid activity. Furthermore, hydrocortisone is generally preferred over dexamethasone for PAI because it has a shorter duration of action and can be given in divided doses to better mimic the circadian rhythm of endogenous cortisol secretion. (Choice D) Although hydrocortisone has both glucocorticoid and mineralocorticoid properties, increasing the dose to get more mineralocorticoid activity is likely to result in toxicity from excessive glucocorticoid exposure (eg, weight gain, hyperglycemia, bone loss). (Choice E) Glucocorticoids in PAI are given in the lowest dose necessary to correct the clinical features of deficiency, although some experts measure morning ACTH to confirm that the dose is not excessive. However, ACTH stimulation testing is primarily used in diagnosis of adrenal insufficiency, and the diagnosis in this patient is already established. Educational objective: Patients with primary adrenal insufficiency have glucocorticoid and mineralocorticoid deficiency. Most patients require replacement of both glucocorticoid (eg, hydrocortisone) and mineralocorticoid (eg, fludrocortisone) activity. References: Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. (http://www.ncbi.nlm.nih.gov/pubmed/26760044) Diagnosis and management of adrenal insufficiency. (http://www.ncbi.nlm.nih.gov/pubmed/25098712)

A 34-Year-Old Woman Comes to the Office After a Recent