MON-471 - Primary Bilateral Macronodular Adrenal Hyperplasia with Discordant Aldosterone and Cortisol Secretion: An Adrenal Venoussampling-Guided Surgical Approach

Primary Bilateral Macronodular Adrenal Hyperplasia (PMAH) is a heterogeneous adrenal disorder, with challenging management due to the absence of standardized clinical guidelines. We present a case of PMAH with concomitant aldosterone excess and mild autonomous cortisol secretion (MACS).

61-year-old female with history of hypertension, hyperlipidemia, prediabetes with A1C 5.8%, hypokalemia ranging 2.7 -3.5 mmol/L, and overweight with BMI 27.1kg/m² presented with bilateral adrenal incidentalomas. Biochemical evaluation confirmed primary hyperaldosteronism, with aldosterone 23 ng/dL, suppressed renin activity 0.13 ng/mL, and ARR 176.9. Unsuppressed serum cortisol of 2.8 µg/dL and dexamethasone levels of 168, following a 1 mg dexamethasone suppression test, with an elevated 24-hour urinary free cortisol at 162.6 µg/day, AM random ACTH of 10 pg/mL, and low DHEA-S 12 µg/dL, was suggestive for MACS. Adrenal CT confirmed a 3.4 cm right adrenal nodule measuring –19 HU and two left adrenal nodules up to 1.8 cm with attenuation values of –14 and –6 HU. Adrenal venous sampling using metanephrines demonstrated lateralization of aldosterone secretion to the left adrenal gland with contralateral suppression, while cortisol secretion lateralized to the right gland. Hypokalemia resolved and blood pressure improved significantly following left adrenalectomy.

PBMAH is a clinical condition characterized by variable degrees of cortisol, and aldosterone, or other steroid excess, produced by bilateral benign adrenocortical macronodules. Hormonal hypersecretion is linked to activation of the cAMP/PKA pathway. Activation of the cAMP/PKA pathway can also be stimulated through aberrantly expressed G-protein-coupled receptors (GPCRs) enabling non-ACTH ligands to mimic ACTH action. Another mechanism involves local ACTH production by adrenal steroidogenic cells, creating an autocrine/paracrine loop. Although considered sporadic, family cases have suggested a hereditary contribution, with identified somatic mutations, leading to inactivation of ARMC5 and KDM1A genes.
Standardized management guidelines remain lacking, contributing to delays in diagnosis and variability in therapeutic decision making. Current approaches recommend active surveillance for patients without overt hypercortisolism, while bilateral or unilateral adrenalectomy or medical treatment is suggested for those with overt hypercortisolism or related complications. However, key questions remain regarding the optimal timing of intervention, predictors of disease progression, the role of medical versus surgical therapy, and the utility of AVS. These unresolved issues underscore the need for well-defined, evidence-based clinical guidelines. In our case, an AVS-guided surgical approach enabled lateralization, led to clinical improvement, and avoided bilateral adrenalectomy.

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