Poster Presentation ESA-SRB 2023 in conjunction with ENSA

Heterogeneity of clinical behaviour of phaeochromocytomas in an MEN 5 kindred (#254)

Gregory I Hockings 1 2 , Amanda J Love 3 , Sofia B Velosa 4 , Roderick J Clifton-Bligh 5 6 , Emma L Duncan 7 8
  1. Endocrinology Unit, Greenslopes Private Hospital, Brisbane, Qld , Australia
  2. School of Medicine, University of Queensland, Brisbane, Qld , Australia
  3. Department of Endocrinology, Royal Brisbane & Women's Hospital, Brisbane, Qld , Australia
  4. Department of Endocrinology, Sunshine Coast University Hospital, Birtinya, Qld , Australia
  5. Department of Endocrinology, Royal North Shore Hospital, Sydney, NSW , Australia
  6. Faculty of Medicine and Health, The University of Sydney, Sydney, NSW , Australia
  7. Department of Endocrinology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK
  8. Faculty of Life Sciences and Medicine , King’s College , London SE1 7EH, UK

MEN51, caused by germline mutations in the MAX gene, has been added to the 2022 revision of the WHO international diseases classification2. We describe the clinical, biochemical and radiological features of pheochromocytomas (PCCs) in nine affected family members from a single large MEN5 kindred, and the clinical course of these tumours.

Although all these patients have the same MAX mutation, they show considerable heterogeneity in their catecholamine and hormonal secretory  profiles, nuclear medicine characteristics and the clinical behaviour of their tumours over an extended period of follow-up.

Eight of the affected family members had predominantly noradrenergic catecholamine secretion and presented with hypertension, while the ninth showed a predominantly adrenergic catecholamine profile and presented with paroxysmal symptoms and myocardial ischaemia. These secretory patterns did not change with recurrences in individual patients.

One patient has chronic acromegaly; their GH excess occurred synchronously with their catecholamine excess, and persisted after pituitary surgery, suggesting ectopic GHRH secretion. Another does not have phenotypic features of acromegaly, but has an intermittently elevated IGF-1 and a markedly asymmetric pituitary gland; her PCC tissue stained positive for GHRH.

The radionuclide scanning agents used varied because of the long time span involved in the diagnosis and follow-up of the various family members. I-MIBG uptake was variable among these patients. Ga-DOTATATE and/or F-DOPA were always taken up by the PCCs, but with some difficulties in interpretation regarding possible lymph node metastases.

Three of the nine patients have developed recurrences in an adrenal bed, plus/minus lymph node metastases; one of these has died from progressive metastatic disease. Two more have possibly abnormal isotope uptake in lymph nodes, of uncertain significance. The clinical variability, difficulties in interpretation of nuclear medicine imaging and relatively high malignancy risk should be carefully considered in the diagnosis and management of PCCs in patients with MEN5.