Situation: A 46-year-old man with primary adrenal insufficiency (Addison disease) is brought to the emergency department after 2 days of vomiting and diarrhea. He usually takes hydrocortisone 15 mg every morning and 5 mg every afternoon, and fludrocortisone 0.1 mg daily. He was treated for pulmonary tuberculosis 5 years ago. At a follow-up visit, he has been taking his usual doses without illness for 2 months. His findings are shown below. Blood pressure lying: 152/94 mmHg Blood pressure standing: 148/92 mmHg Weight: up 3 kg in 4 weeks Ankles: 2+ pitting edema Potassium: 3.2 mEq/L (3.5–5.0) Fasting glucose: 88 mg/dL (4.9 mmol/L) (70–99) Appearance: no facial rounding or new striae Which change in his therapy do these findings MOST suggest?

Hypertension without an orthostatic drop, weight gain, edema, and low potassium together point to mineralocorticoid excess, so the fludrocortisone dose is too high. A normal fasting glucose and no cushingoid features argue against glucocorticoid excess.

Clinical picture The key findings are blood pressure 152/94 mmHg lying and 148/92 mmHg standing, weight gain of 3 kg in 4 weeks, 2+ pitting ankle edema, and potassium 3.2 mEq/L. Fasting glucose is 88 mg/dL, and there are no cushingoid features. In a patient with primary adrenal insufficiency on both hydrocortisone and fludrocortisone, this combination points to mineralocorticoid excess rather than glucocorticoid excess.

Why these findings indicate fludrocortisone excess Fludrocortisone acts on the mineralocorticoid receptor in the distal nephron to promote sodium and water retention while increasing renal potassium excretion. When the dose is too high, the clinical consequences are exactly what this patient shows: hypertension without a significant orthostatic drop, fluid retention with weight gain and edema, and hypokalemia. The absence of an orthostatic fall is especially informative because patients with undertreated adrenal insufficiency typically have low or posturally dropping blood pressure. Here, the blood pressure remains elevated even when standing, which argues against mineralocorticoid deficiency and supports excess.

Why glucocorticoid excess is less likely Hydrocortisone also has some mineralocorticoid activity, but the normal fasting glucose and the absence of facial rounding or new striae make clinically significant glucocorticoid excess unlikely. Cushingoid appearance, hyperglycemia, and central fat redistribution are the hallmarks of glucocorticoid over-replacement, and none are present. The findings are therefore best explained by excessive mineralocorticoid effect from fludrocortisone.

Therapeutic adjustment The most appropriate change is to lower the fludrocortisone dose. Fludrocortisone is typically given once daily in a range of 0.05–0.2 mg, and the dose is titrated against blood pressure, edema, potassium, and plasma renin activity ^[1]. In primary adrenal insufficiency, mineralocorticoid replacement is required because aldosterone secretion is profoundly impaired, but the dose must be individualized to avoid exactly these signs of overtreatment ^[1]. Reducing the fludrocortisone dose will decrease sodium retention, lower blood pressure, reduce edema, and allow potassium to rise back into the normal range.

Watch out! Adding spironolactone would also oppose mineralocorticoid action, but it is a potassium-sparing diuretic that can cause hyperkalemia in a patient whose adrenal aldosterone production is already absent. Simply lowering the fludrocortisone dose is safer and addresses the root cause. Key point! In primary adrenal insufficiency, mineralocorticoid excess presents as hypertension, edema, weight gain, and hypokalemia without cushingoid features; the corrective step is fludrocortisone dose reduction, not potassium supplementation or a diuretic.