A 44-year-old woman comes to the office due to fatigue, nausea, and weight loss for the last 3-4 months. She also has noticed her freckles becoming darker and reports frequent dizziness upon standing. Temperature is 36.8 C (98.2 F) , blood pressure is 120/80 mm Hg when sitting and 95/65 mm Hg when standing, and pulse is 77/min. Hyperpigmentation of the vermillion border of the lips is noted. The remainder of the physical examination is unremarkable. Comprehensive diagnostic workup reveals a diagnosis of idiopathic primary adrenal insufficiency. The patient is started on hydrocortisone and fludrocortisone. Fludrocortisone is most likely to cause which of the following effects in this patient?

Question

Quizplus · Accepted Answer

This patient's fatigue, nausea, hyperpigmentation, and orthostatic hypotension are due to primary adrenal insufficiency (PAI). PAI results from reduced levels of both mineralocorticoid (mainly aldosterone) and glucocorticoid (mainly cortisol), typically due to autoimmune destruction of the bilateral adrenal cortex. Orthostasis in PAI is due primarily to hypovolemia from reduced mineralocorticoid production. Reduced mineralocorticoid activity in the renal collecting tubule principal cells leads to markedly decreased sodium absorption (ie, renal salt wasting) and increased potassium absorption. The decreased sodium reabsorption leads to decreased fluid retention, overall decreased circulating blood volume, and hypovolemia-induced orthostasis. Fludrocortisone, a synthetic adrenal steroid with high mineralocorticoid activity, is used to treat mineralocorticoid deficiency. It works by 2 primary mechanisms: Increased sodium reabsorption in the distal convoluted tubule and collecting ducts, causing increased fluid retention and circulating blood volume. This leads to decreased urine sodium. Increase vascular sensitivity to multiple endogenous vasoconstrictors (eg, angiotensin II, norepinephrine), causing a potentiation of their pressor effects (Choices D, E, and F). The increased circulating plasma volume and increased sensitivity to vasoconstricting mediators leads to an increase in blood pressure and improvement in orthostatic hypotension (Choices A and B). Educational objective: Fludrocortisone improves hypovolemia and orthostatic hypotension in primary adrenal insufficiency by decreasing urine sodium excretion (thereby increasing circulating blood volume) and increasing the sensitivity of the vasculature to endogenous vasoconstrictors (eg, norepinephrine). __________ References: Adrenal insufficiency - recognition and management. (http://www.ncbi.nlm.nih.gov/pubmed/28572228)

A 44-Year-Old Woman Comes to the Office Due to Fatigue