SAT-507 - Biochemically Silent Bilateral Adrenal Nodules in an SDHB Mutation Carrier

Background: Succinate dehydrogenase subunit B (SDHB) mutations cause a hereditary pheochromocytoma-paraganglioma (PCC/PGL) syndrome associated with aggressive tumor behavior, increased metastatic risk, and frequent bilateral or extra-adrenal disease. Importantly, SDHB-associated tumors may present with minimal or absent biochemical activity, limiting the sensitivity of catecholamine-based screening and posing diagnostic challenges during adrenal nodule evaluation.

Clinical

Case: A 48-year-old woman with a history of hypertension was evaluated for adrenal nodules. She had been incidentally diagnosed with a right adrenal nodule five years earlier and followed with serial imaging demonstrating progression. She denied episodic hypertension, headaches, diaphoresis, palpitations, pallor, or anxiety.

Family history was notable for a son diagnosed with pheochromocytoma at age 4 who died at age 28, and a maternal grandmother diagnosed with pheochromocytoma in her 50s. Given this history, genetic testing was pursued and revealed a heterozygous pathogenic SDHB mutation, c.136C>T (p.R46*), confirming hereditary PCC/PGL syndrome.

Biochemical evaluation for pheochromocytoma demonstrated largely normal results. Plasma free metanephrine was 29.9 pg/mL (reference < 57), plasma free normetanephrine 69.8 pg/mL (reference < 148), and plasma norepinephrine 569 pg/mL (reference 115–524). Twenty-four-hour urinary catecholamines showed dopamine 202 µg (reference 52–480), epinephrine < 7 µg (reference ≤24), and norepinephrine 37 µg (reference ≤100), without evidence of catecholamine excess. Additional hormonal evaluation did not reveal alternative functional adrenal disorders.

Initial imaging demonstrated a 2.4 cm right adrenal nodule with attenuation of 14 Hounsfield units. Follow-up CT revealed progression to bilateral adrenal nodules, with a dominant right-sided lesion measuring 2.8 cm and a left-sided lesion measuring 1.3 cm. No of extra-adrenal disease or metastatic lesions was identified.

Despite largely normal biochemical testing, the presence of bilateral adrenal nodules in the setting of a pathogenic SDHB mutation raised concern for high-risk hereditary PCC/PGL, prompting intensified surveillance.


Conclusion: This case highlights the critical role of genetic testing in adrenal nodule evaluation. Biochemically silent tumors are characteristic of SDHB-associated PCC/PGL, limiting the sensitivity of catecholamine-based screening. Guidelines recommend lifelong surveillance with annual biochemical testing in adults (every two years in childhood) and imaging from skull base to pelvis every 2-3 years, preferably with MRI. SSTR-based PET may be considered given higher sensitivity. Post-surgical cases require intensified surveillance. These recommendations have important implications for long-term management and family screening.

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