Phaeochromocytoma: inherited associations, bilaterality and cortex preservation

Abstract

Abstract Background Hereditary phaeochromocytoma (HP) is characterized by early onset, bilateral adrenal involvement, low malignancy rate and genetic linkage with certain familial syndromes. This retrospective review was intended to show the high yield of surveillance, predictable bilaterality and the challenge of cortex-sparing adrenalectomy. Methods From 1964 to 1999, 32 patients with HP (mean age 29 years) were treated at a single institution and followed for a mean of 7 (range 0·5–24) years. There were 15 patients with multiple endocrine neoplasia type 2A (MEN2A), 12 with von Hippel–Lindau disease (VHLD), three with von Recklinghausen's disease (VRD) and two patients with familial phaeochromocytoma (FP). Twenty-six of 32 patients underwent bilateral adrenalectomy (12 metachronous). Subtotal resection with orthotopic cortex preservation was performed in four patients and heterotopic autografting in 14 patients. Subcapsular segments were harvested and implanted into the rectus muscle after histological confirmation of the absence of medullary tissue. The following variables were assessed: presenting signs, interval of metachronous disease, recurrence, outcome of cortex preservation and survival. Results Phaeochromocytoma was the first manifestation in six of 12 patients with VHLD and four of 15 with MEN2A. Surveillance uncovered medullary thyroid cancer in five of 15 patients with MEN2A, and haemangioblastomas, renal cell carcinoma and islet cell tumours in seven of 15 patients with VHLD and VRD. HP was bilateral in 26 of 32 cases (14 of 15 MEN2A, eight of 12 VHLD, two of three VRD and both FP). In 12 cases of metachronous HP, the mean interval between adrenalectomy was 67 (range 9–156) months. Three of four patients who underwent orthotopic preservation of the adrenal cortex developed recurrence compared with none of 14 patients with heterotopic autotransplantation of cortical tissue. Four patients in this latter group had normal serum cortisol levels and required no exogenous replacement therapy. There was one case of malignant HP and there was no surgical death. Conclusion Inherited bilateral phaeochromocytoma is derived from medullary hyperplasia. The long interval of metachronous phaeochromocytoma argues against prophylactic removal of the contralateral ‘normal’ adrenal gland. Phaeochromocytoma frequently heralds coexisting silent VHLD or MEN-2, mandating surveillance for inherited associations. Total adrenalectomy and heterotopic autotransplantation of medulla-free cortex may diminish the need for lifelong steroid substitution and eliminates recurrence.