A 26-year-old woman comes to the clinic due to worsening generalized weakness, myalgias, and unintentional weight loss. She has primary hypothyroidism for which she takes levothyroxine. Blood pressure is 110/70 mm Hg supine and 90/60 mm Hg standing. She appears mildly emaciated. Cardiopulmonary examination reveals no abnormalities. Laboratory studies show mild normochromic, normocytic anemia; eosinophil count of 15%; and serum glucose of 65 mg/dL. Which of the following additional changes is most likely in this patient?

Question

Quizplus · Accepted Answer

This patient has multiple clinical features that suggest primary adrenal insufficiency (PAI) (also known as Addison disease). PAI most commonly results from autoimmune destruction of the bilateral adrenal cortex and often occurs in patients with a preexisting history of autoimmune disease (eg, hypothyroidism, type 1 diabetes mellitus). Reduced mineralocorticoid (mainly aldosterone) production leads to renal salt wasting with consequent hypovolemia and orthostasis (systolic blood pressure decrease ≥20 mm Hg with standing). Reduced cortisol can lead to hypoglycemia, normocytic anemia, and eosinophilia. In the renal collecting tubule principal cells, reduced aldosterone leads to markedly decreased sodium absorption and increased potassium absorption; therefore, there is high urine sodium and low urine potassium. Serum potassium is elevated (hyperkalemia) due to the increased tubular absorption. Although the tubular salt wasting reduces total body sodium, it does not directly affect serum sodium concentration. However, because hypovolemia provides nonosmotic stimulus for antidiuretic hormone (ADH) secretion and ADH secretion is normally inhibited by cortisol, ADH levels are increased in PAI. The increased ADH levels lead to increased water retention and low serum sodium (hyponatremia). (Choice B) Hyponatremia in the setting of high urine sodium is characteristic of the syndrome of inappropriate ADH secretion (SIADH). SIADH has no significant effect on serum and urine potassium levels. (Choices C and D) In hypovolemic states (eg, severe vomiting, diabetic ketoacidosis), restoration of blood volume is the highest priority. Therefore, the kidneys respond by stimulating increased aldosterone secretion, which decreases urine sodium and increases urine potassium. The hypovolemia also provides nonosmotic stimulus for ADH release, which leads to hyponatremia. Both total body and serum potassium are low in severe vomiting due to both gastrointestinal and renal losses. Although total body potassium is low in diabetic ketoacidosis, serum potassium is high because potassium is unable to enter cells in the absence of insulin. (Choice E) Primary hyperaldosteronism causes potassium wasting by the renal principal cells, leading to high urine potassium and low serum potassium (hypokalemia). There is renal sodium retention that leads to increased blood volume, but any significant change in serum or urine sodium concentration is avoided due to aldosterone escape. Educational objective: Reduced aldosterone production in primary adrenal insufficiency leads to renal sodium wasting with consequent hypovolemia, orthostasis, and potassium retention (hyperkalemia). Low cortisol stimulates increased antidiuretic hormone secretion, which leads to water retention and hyponatremia.

A 26-Year-Old Woman Comes to the Clinic Due to Worsening