Two cases of MACS due to PBMAH associated with an in vivo aberrant response to LHRH treated with leuprolide acetate

Abstract

We describe two rare cases of primary bilateral macronodular adrenal hyperplasia (PBMAH) with mild autonomous cortisol secretion (MACS), incidentally discovered and further evaluated for aberrant cortisol responses to various stimuli. In both patients, morning serum cortisol levels remained elevated following 1 mg dexamethasone suppression test (DST) and 4 mg intravenous DST, while basal adrenocorticotropic hormone (ACTH) levels were suppressed. However, 24 h urinary free cortisol and nocturnal salivary cortisol levels were within normal limits. The first case involved a 69-year-old woman who exhibited significant increases in cortisol in response to luteinizing hormone-releasing hormone (LHRH; +142%), vasopressin (+66%) and metoclopramide (+98%). Treatment with the long-acting GnRH agonist leuprolide acetate led to decreased cortisol production and normalization of ACTH levels. The second case, a 54-year-old woman, showed cortisol increases following stimulation with LHRH (+58%), cosyntropin (+1,016%) and vasopressin (+46%). However, leuprolide acetate treatment did not successfully control her hypercortisolism. These cases highlight the clinical relevance of identifying aberrant cortisol responses to specific stimuli in patients with PBMAH and MACS. Such findings may inform the use of targeted medical therapies as alternatives to unilateral or bilateral adrenalectomy. In addition, a more pronounced cortisol response to LHRH compared to other stimuli may predict a favorable response to GnRH agonist therapy.