Treatment of functional adrenal tumors: From preoperative work-up to postoperative follow-up in patients with aldosterone-producing adenoma or pheochromocytoma

Abstract

Primary aldosteronism and pheochromocytoma are important endocrine causes of hypertension and are associated with substantial cardiovascular morbidity and mortality if left untreated. Although adrenalectomy remains the cornerstone of treatment for many patients, important challenges remain regarding diagnosis, patient selection, preoperative counseling, postoperative follow-up, and long-term management. The overall aim of this thesis was to improve the care of patients with functional adrenal tumors through more personalized treatment strategies and optimized clinical decision-making. The first part of this thesis focused on primary aldosteronism. Despite being one of the more common causes of secondary hypertension, PA remains substantially underdiagnosed. For patients with unilateral disease, adrenalectomy offers a high likelihood of biochemical cure; however, complete resolution of hypertension is less predictable. To improve preoperative counseling and shared decision-making, we externally validated a simplified version of the Primary Aldosteronism Surgical Outcome (PASO) score in a large international cohort. The simplified model retained moderate to good predictive performance while improving clinical applicability, supporting its use as a practical tool for individualized risk stratification and expectation management. A second objective was to optimize postoperative follow-up after adrenalectomy for primary aldosteronism. A systematic review demonstrated that blood pressure typically improves within weeks to months after surgery and remains largely stable thereafter. These findings were confirmed in a longitudinal cohort study, which showed that the greatest reductions in blood pressure and antihypertensive medication use occur during the first postoperative month, with limited changes thereafter. Together, these studies provide evidence that outcome assessment can be performed earlier than commonly assumed and support individualized follow-up schedules based on clinical response. The second part of this thesis focused on pheochromocytoma. A comprehensive review of the rapidly evolving molecular landscape of pheochromocytoma and paraganglioma demonstrated how advances in genomics, molecular pathology, and immunohistochemistry are reshaping disease classification, risk assessment, and personalized management. These developments are expected to improve prognostication and facilitate more individualized treatment strategies. In parallel, this thesis explored the clinical potential of the novel functional imaging tracer [18F]mFBG PET/CT. A clinical case illustrated its added value in detecting recurrent disease when conventional imaging was inconclusive. Furthermore, this thesis identified optimal standard uptake-value normalization techniques and reference tissues, contributing to future standardization and reproducibility of [18F]mFBG PET/CT across centers and supporting ongoing studies evaluating its diagnostic accuracy. Finally, long-term outcomes following partial versus total adrenalectomy in patients with MEN2-associated pheochromocytoma were evaluated. Partial adrenalectomy was associated with a tenfold higher recurrence rate and substantially shorter time to recurrence, while preservation of adrenal function was achieved in only a subset of patients. These findings challenge current assumptions regarding adrenal-sparing surgery in MEN2 and support a more individualized surgical approach that carefully balances oncological safety and preservation of adrenal function. Overall, this thesis contributes to more evidence-based and personalized care for patients with primary aldosteronism or pheochromocytoma through improved prediction of surgical outcomes, optimized follow-up strategies, advances in molecular and imaging diagnostics, and critical evaluation of surgical management.