SUN-429 Primary Bilateral Macronodular Adrenal Hyperplasia with co-secretion of Aldosterone and Cortisol in a Patient with Hyperparathyroidism-Jaw Tumor Syndrome due to a Pathogenic CDC73 Mutation

Abstract Disclosure: L. Martel-Duguech: None. A. Doreille: None. M. Latour: None. M. Thibodeau: None. N. Dumas: None. I. Bourdeau: None. Z. El Haffaf: None. A. Lacroix: None. Background: Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT) is secondary to germline inactivating mutations of the tumor suppressor CDC73 gene. Affected patients often present in addition to severe HPT, lesions in kidney, uterus and thyroid. Primary bilateral macronodular adrenal hyperplasia (PBMAH) can be secondary to mutations in ARMC5 and less frequently in KDM1A, MEN1, APC or FH genes. We now report a patient with HPT-JT and germline CDC73 mutation who later developed PBMAH co-secreting cortisol and aldosterone without ARMC5 or MEN1 gene mutations. Case Presentation: a 54-y.o female was referred in 2013 for bilateral adrenal nodules with weight gain, fatigue, myopathy, hypertension with sleep apnea. Previous history included recurrent kidney stones since age 19, three parathyroidectomies (26, 46, 53 yo) for severe HPT, nephrocalcinosis, near end-stage renal disease and hysterectomy at age 35 for metrorrhagia. Abdominal CT without contrast showed PBMAH (multiple nodules up to 25 mm, 3 to 33 HU), very atrophic kidneys with extensive nephrocalcinosis and renal cysts. Hormonal dynamic testing confirmed suppressed ACTH with aberrant regulation of excess cortisol (443 nmol/L post-dex) and aldosterone production by vasopressin, upright posture and 5-HT4R agonists. Initial genetic testing excluded MEN1 pathogenic variants. Left adrenalectomy was performed in 2015 and pathology confirmed PBMAH; recent CYP11B2 IHC showed heterogeneous high expression of aldosterone synthase in wide portions of outer cortex, but it was negative in several central nodules, while CYP11B1 IHC is pending. Late night salivary cortisol and ACTH levels normalized with mild dysregulated cortisol secretion and residual primary aldosteronism was treated with spironolactone. In 2017, breast ductal carcinoma in situ (DCIS) was resected and she underwent kidney transplantation followed by immunosuppression including prednisone. Recently, progressive increase in cortisol secretion and ACTH suppression may require additional therapy. No jaw tumor was found at recent imaging. Genetic testing: in 2024, expanded panel genetic testing for HPT and PBMAH identified a pathogenic CDC73 pathogenic variant (c.512del, p.Arg171Serfs*31) without mutations in ARMC5, MEN1, RET, CASR, CDKN1B, GCM2. Family testing is currently under way. Conclusion: This is the first case of a patient with HPT-JT with CDC73 gene mutation who developed cortisol- and aldosterone-secreting PBMAH. This finding suggests the possibility that CDC73 mutations may also predispose to development of PBMAH. Presentation: Sunday, July 13, 2025