PMID- 38152133 OWN - NLM STAT- MEDLINE DCOM- 20231229 LR - 20240229 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - An aggressive cabergoline-resistant, temozolomide-responsive macroprolactinoma due to a germline SDHB pathogenic variant in the absence of paraganglioma or pheochromocytoma. PG - 1273093 LID - 10.3389/fendo.2023.1273093 [doi] LID - 1273093 AB - CONTEXT: Germline succinate dehydrogenase subunit B (SDHB) pathogenic variants are characteristic of familial paraganglioma (PGL) syndrome type 4. This syndrome frequently presents with abdominal PGL and has high tendency for locally aggressive behavior and distant metastasis. The vast majority of pituitary adenomas (PAs) are sporadic. However, PAs can be part of a number of familial tumor syndromes such as multiple endocrine neoplasia type 1 (MEN 1) or more rarely in association with pheochromocytoma and PGL (referred to as 3P syndrome). Only a limited number of PAs in association with SDHB-related PGL has been reported and the vast majority occurred subsequently or simultaneously with pheochromocytoma/PGL (collectively abbreviated as PPGL). In this report, we describe a young patient who had a giant pituitary macroprolactinoma resistant to large doses of cabergoline (CBG) and external beam radiotherapy (XRT). The patient did not have personal history of PPGL but was found to carry a germline SDHB pathogenic variant. CASE REPORT: A 38-year-old woman presented with headache, visual disturbances and galactorrhea and was found to have a 34-mm macroprolactinoma. She was treated with CBG 3-4 mg per week but PA continued to grow and caused significant cranial pressure symptoms. She underwent two transsphenoidal surgeries with rapid tumor recurrence after each one. She received XRT but PA continued to grow. She was finally treated with temozolomide with excellent response. Whole exome and subsequent Sanger sequencing confirmed that she has a pathogenic monoallelic SDHB mutation (NM_003000:c.C343T, p.R115*). PA tissue showed loss of heterozygosity for the same mutation and absent SDHB immunostaining confirming the pathogenic role of this SDHB mutation. CONCLUSION: Germline SDHB mutations can rarely cause PA in the absence of PPGL. They should be considered as a possible cause of aggressiveness and resistance to dopamine agonists in similar cases. CI - Copyright (c) 2023 Alzahrani, Bin Nafisah, Alswailem, Moria, Poprawski, Al-Hindi and Pacak. FAU - Alzahrani, Ali S AU - Alzahrani AS AD - Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. AD - Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Bin Nafisah, Abdulghani AU - Bin Nafisah A AD - Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. AD - College of Science, King Saud University, Riyadh, Saudi Arabia. FAU - Alswailem, Meshael AU - Alswailem M AD - Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Moria, Yosra AU - Moria Y AD - Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Poprawski, Dagmara AU - Poprawski D AD - Oncology Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. AD - College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia. FAU - Al-Hindi, Hindi AU - Al-Hindi H AD - Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Pacak, Karel AU - Pacak K AD - Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States. LA - eng PT - Case Reports PT - Journal Article DEP - 20231213 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - LL60K9J05T (Cabergoline) RN - YF1K15M17Y (Temozolomide) RN - EC 1.3.5.1 (SDHB protein, human) RN - EC 1.3.99.1 (Succinate Dehydrogenase) SB - IM MH - Female MH - Humans MH - Adult MH - *Pheochromocytoma/genetics MH - Cabergoline MH - Temozolomide/therapeutic use MH - *Prolactinoma/drug therapy/genetics MH - Neoplasm Recurrence, Local MH - *Paraganglioma/drug therapy/genetics/diagnosis MH - *Adenoma/genetics MH - *Pituitary Neoplasms/drug therapy/genetics MH - *Adrenal Gland Neoplasms/genetics MH - Succinate Dehydrogenase/genetics PMC - PMC10751293 OTO - NOTNLM OT - SDHB OT - cabergoline OT - macroprolactinoma OT - pituitary adenoma OT - temozolomide COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2023/12/28 06:42 MHDA- 2023/12/29 06:43 PMCR- 2023/01/01 CRDT- 2023/12/28 03:58 PHST- 2023/08/05 00:00 [received] PHST- 2023/10/24 00:00 [accepted] PHST- 2023/12/29 06:43 [medline] PHST- 2023/12/28 06:42 [pubmed] PHST- 2023/12/28 03:58 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1273093 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Dec 13;14:1273093. doi: 10.3389/fendo.2023.1273093. eCollection 2023.