Cushing's conundrum: an unusual case of primary pigmented nodular adrenal disease in a 60-year-old woman

Abstract

A 60-year-old woman with resistant hypertension, poorly controlled type 2 diabetes, and chronic obstructive pulmonary disease requiring inhaled corticosteroids was referred for investigation of Cushing’s syndrome. She had a BMI of 31 kg/m2, abdominal obesity, and proximal muscle wasting. Investigations showed a normal aldosterone-to-renin ratio, plasma metanephrines, and renal artery Doppler ultrasound fi ndings, but increased 24 h urine free cortisol concentration (454 nmol/L [normal range <350 nmol/L]). Adrenocorticotropic hormone remained undetectable on several occasions for 12 months, during the diagnostic workup (<5 pg/mL). Because of diffi culty in ceasing use of inhaled corticosteroids, an overnight 1 mg dexa methasone suppression test was done while the patient was taking fl uticasone, showing an 8 am cortisol concentration of 278 nmol/L (compared with a normal range of <120 nmol/L). Persistent hypercortisolism was then confi rmed with intravenous dexamethasone suppression testing done after inhaled fl uticasone was withheld for several days. An adrenal CT scan showed an enlarged left adrenal gland, with an 8 mm nodule at the inferior pole (fi gure A), insuffi cient to account for the patient’s hypercortisolism. Functional imaging with iodo cholesterol under dexamethasone suppression showed bilateral uptake of labelled cholesterol (fi gure B). Adrenal vein sampling under dexamethasone supp ression was consistent with bilateral autonomous cortisol secretion (appendix). The patient underwent a bilateral adrenalectomy. The macroscopic and histological appearance was consistent with primary pigmented nodular adrenal hyperplasia (also known as primary pigmented nodular adrenal disease [PPNAD]; fi gure C, D). PPNAD is associated with Carney’s complex in 90% of white patients. Carney’s complex is an autosomal dominant multiple neoplasia syndrome, typically presenting with the classic triad of myxomas, spotty skin pigmentation, and endocrine overactivity. 60% of Carney’s complex in the white population is associated with germline-inactivating mutations in regulatory subunit 1α of protein kinase A (PRKAR1A). To our knowledge, this patient is the oldest reported person to be diagnosed with PPNAD—most patients are diagnosed before age 40 years. She has no other manifestations of Carney’s complex and is currently undergoing genetic testing for mutations in the PRKAR1A gene. This case shows that PPNAD can be latent for many years and should be considered in diff erential diagnosis of adrenocorticotropic hormoneindependent Cushing’s syndrome in elderly individuals.