Evolution of Adrenocortical Carcinoma Leading to Primary Aldosteronism

While 60-80% of adrenocortical carcinomas (ACCs) are functional, only 2.5% produce aldosterone. Aldosterone-producing adrenocortical carcinomas (APACs) are poorly understood and require further study.

Case Description :

A 35-year-old man presented with night sweats, abdominal pain, and >20 lb. weight loss. Computed tomography imaging revealed a 26 cm left-sided malignant-appearing retroperitoneal mass with surrounding adenopathy and pulmonary masses, later biopsy-confirmed to be metastatic ACC. Initial work-up revealed a plasma renin activity (PRA) of 7 ng/mL/hr (ref. 0.5-4 ng/mL/hr), plasma aldosterone concentration (PAC) of 7 ng/dL (ref. 4-31 ng/dL), serum sodium concentration of 135 mEq/L, (ref. 135-145 mEq/L), and serum potassium concentration of 4.7 mEq/L (ref. 2.2-5.3 mEq/L). Levels of dehydroepiandrosterone sulfate and androstenedione were elevated at 2668.6 mcg/dL (ref. 84.9-476.1 mcg/dL) and 4.060 ng/mL (ref. 0.330-1.340 ng/mL), respectively, while the total testosterone level was low at 98.8 ng/dL (ref. 241-827 ng/dL). A late morning cortisol level was elevated at 21.6 mcg/dL (ref. 6-18.4 mcg/dL), while adrenocorticotropic hormone and 24-hour urinary free cortisol levels were normal at 18 pg/mL (ref. 7.2-63.3 pg/mL) and 32 ug/24h (ref. < 60 ug/24h), respectively. 

Given the high-risk of surgery, the patient was initiated on mitotane along with combination etoposide, cisplatin, and doxorubicin. Hydrocortisone was started for mitotane-induced primary adrenal insufficiency. Disease progression required a switch to combination immunotherapy and second line chemotherapy. Three years after diagnosis, he developed worsening hypertension and hypokalemia in the setting of continued cancer progression. Repeat PRA and PAC were 0.5 ng/mL/hr and 34.3 ng/dL, respectively, confirming primary aldosteronism (PA). Despite potassium replacement and escalating doses of spironolactone, he was later hospitalized for refractory hypertension and hypokalemia, prompting discussions of tumor embolization and microwave ablation.

Discussion :

Immature steroidogenesis typically predominates over the production of terminal pathway hormones in functional ACCs, particularly as the cancer progresses. This is the first reported case of an ACC that developed aldosterone hypersecretion years after diagnosis, leading to severe hypertension and hypokalemia. Although APACs are rare, periodic biochemical evaluation for PA should be considered even if the initial screen is negative, and while such patients are on mitotane. Earlier detection and treatment of APACs may prevent significant morbidity and mortality.