Endocrine Abstracts

Introduction: Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) represents <2% of causes of Cushing’s Syndrome (CS). Clinical course is insidious, with adrenal bilateral macronodules and gradual cortisol excess, only rarely presenting with overt CS. The pathophysiology remains unclear, however, hyperactivation of the cAMP/PKA pathway, in 77-87% of cases through aberrantly expressed G-protein coupled receptors (GPCRs), has been described. Despite being a benign entity, PBMAH associated hypercortisolism may require aggressive management.

Objectives: To present a case of PBMAH diagnosed due to hypertension and overt CS, successfully treated with unilateral adrenalectomy.

Case Report: A 34-year-old woman presented with progressive weight gain, facial hair growth and headaches for 14 months. She had been diagnosed with prediabetes and hypertension, which motivated additional study. She had round plethoric face and hypertrichosis, dorsocervical and supraclavicular fat pads and easy bruising. Her weight was 66.5 kg with a body mass index of 24.4 kg/m². Laboratory evaluation showed a 9 am serum cortisol of 46.1 µg/dl (n:6.2-18), with circadian rhythm, as demonstrated by the measurement of salivary cortisol at 8 am and 11 pm; ACTH <1 pg/ml and 24 h urinary cortisol 6825 µg/24 h (n:124-581). Serum cortisol after 1 mg dexamethasone suppression test was 37.9 µg/dl, while salivary cortisol kept circadian rhythm. Androgen and mineralocorticoid hypersecretion were excluded. Adrenal CT scan documented evident bilateral adrenal enlargement with multiple hypodense macronodules which reached a maximum diameter of 67 mm and 49 mm. Considering a PBMAH diagnosis, the stimulation tests to assess aberrant receptors were performed following Lacroix et al protocol, but there was no evidence of positive response. The patient initiated metyrapone, controlling the hypercortisolism with 250 mg twice daily. Unilateral adrenalectomy of the largest adrenal gland was considered and uneventfully performed. Histopathologic evaluation revealed an adrenal cortex macronodular hyperplasia, compatible with the PBMAH diagnosis. After surgery, blood pressure returned to normal levels, allowing antihypertensive medication to be suspended two weeks afterwards, and 24 h urinary cortisol normalized. The patient also reported improved well-being and weight loss was documented. One month after surgery, she remained on hydrocortisone replacement, under close surveillance.

Discussion and Conclusions: In this case, secondary hypertension evaluation revealed hypercortisolism and documented adrenal macronodules favouring PBMAH diagnosis. Despite being frequent, aberrant receptors were not present, precluding targeted medical treatment. Unilateral adrenalectomy may offer clinical and biochemical benefits while avoiding hormone replacement, nevertheless, long term follow-up is required since disease recurrence has been reported with this approach.