Omair A Shariq1, Kate E Lines2, Katherine A English3, Bahram Jafar-Mohammadi4, Philippa Prentice5, Ruth Casey6, Benjamin G Challis6, Andreas Selberherr7, Hannah Boon8, Treena Cranston8, Fiona J Ryan9, Radu Mihai10, Ultan Healy4, Tom Kurzawinski11, Mehul T Dattani5, Irina Bancos12, Benzon M Dy13, Melanie L Lyden13, William F Young14, Travis J McKenzie13, Duncan Richards15, Rajesh V Thakker16. 1. Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, United Kingdom; Department of Surgery, Mayo Clinic, Rochester, MN. Electronic address: https://twitter.com/@omairshariq. 2. Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, United Kingdom. Electronic address: https://twitter.com/@klines500. 3. Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, United Kingdom. Electronic address: https://twitter.com/@Katie__English. 4. Department of Endocrinology Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, United Kingdom. 5. Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children and UCL Great Ormond Street Institute of Child Health, London, United Kingdom. 6. Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, United Kingdom. 7. Department of Surgery, Medical University of Vienna, Austria. 8. Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, United Kingdom. 9. Department of Paediatric Endocrinology, Oxford Children's Hospital, University of Oxford, United Kingdom. 10. Department of Endocrine Surgery, University of Oxford, United Kingdom. Electronic address: https://twitter.com/RaduMiSurgeon. 11. Centre for Endocrine Surgery, Great Ormond Street Hospital for Children, London, United Kingdom. 12. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN. Electronic address: https://twitter.com/@IrinaBancos. 13. Department of Surgery, Mayo Clinic, Rochester, MN. 14. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN. 15. Oxford Clinical Trials Research Unit, Botnar Research Centre, United Kingdom. 16. Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, United Kingdom. Electronic address: rajesh.thakker@ndm.ox.ac.uk.
Abstract
BACKGROUND: Clinical manifestations and treatment outcomes in children and adolescents with multiple endocrine neoplasia type 1 are not well characterized. METHODS: We conducted a retrospective cohort study of 80 patients with multiple endocrine neoplasia type 1 who commenced tumor surveillance at ≤18 years of age. RESULTS: Fifty-six patients (70%) developed an endocrine tumor by age ≤18 years (median age = 14 years, range = 6-18 years). Primary hyperparathyroidism occurred in >80% of patients, with >70% undergoing parathyroidectomy, in which less-than-subtotal (<3-gland) resection resulted in decreased disease-free outcomes versus subtotal (3-3.5-gland) or total (4-gland) parathyroidectomy (median 27 months versus not reached; P = .005). Pancreaticoduodenal neuroendocrine tumors developed in ∼35% of patients, of whom >70% had nonfunctioning tumors, >35% had insulinomas, and <5% had gastrinomas, with ∼15% having metastases and >55% undergoing surgery. Pituitary tumors developed in >30% of patients, and ∼35% were macroprolactinomas. Tumor occurrence in male patients and female patients was not significantly different. Genetic analyses revealed 38 germline MEN1 mutations, of which 3 were novel. CONCLUSION: Seventy percent of children aged ≤18 years with multiple endocrine neoplasia type 1 develop endocrine tumors, which include parathyroid tumors for which less-than-subtotal parathyroidectomy should be avoided; pancreaticoduodenal neuroendocrine tumors that may metastasize; and pituitary macroprolactinomas.
BACKGROUND: Clinical manifestations and treatment outcomes in children and adolescents with multiple endocrine neoplasia type 1 are not well characterized. METHODS: We conducted a retrospective cohort study of 80 patients with multiple endocrine neoplasia type 1 who commenced tumor surveillance at ≤18 years of age. RESULTS: Fifty-six patients (70%) developed an endocrine tumor by age ≤18 years (median age = 14 years, range = 6-18 years). Primary hyperparathyroidism occurred in >80% of patients, with >70% undergoing parathyroidectomy, in which less-than-subtotal (<3-gland) resection resulted in decreased disease-free outcomes versus subtotal (3-3.5-gland) or total (4-gland) parathyroidectomy (median 27 months versus not reached; P = .005). Pancreaticoduodenal neuroendocrine tumors developed in ∼35% of patients, of whom >70% had nonfunctioning tumors, >35% had insulinomas, and <5% had gastrinomas, with ∼15% having metastases and >55% undergoing surgery. Pituitary tumors developed in >30% of patients, and ∼35% were macroprolactinomas. Tumor occurrence in male patients and female patients was not significantly different. Genetic analyses revealed 38 germline MEN1 mutations, of which 3 were novel. CONCLUSION: Seventy percent of children aged ≤18 years with multiple endocrine neoplasia type 1 develop endocrine tumors, which include parathyroid tumors for which less-than-subtotal parathyroidectomy should be avoided; pancreaticoduodenal neuroendocrine tumors that may metastasize; and pituitary macroprolactinomas.
Authors: Kreepa G Kooblall; Victoria J Stokes; Omair A Shariq; Katherine A English; Mark Stevenson; John Broxholme; Benjamin Wright; Helen E Lockstone; David Buck; Simona Grozinsky-Glasberg; Christopher J Yates; Rajesh V Thakker; Kate E Lines Journal: Endocr Relat Cancer Date: 2022-08-04 Impact factor: 5.900