Endocrine Disorders for the USMLE, Step One: Multiple Endocrine Neoplasia Type 1 (MEN-1 Syndrome) Howard J. Sachs, MD www.12DaysinMarch.com Endocrine Disorders for the USMLE, Step One: Multiple Endocrine Neoplasia Type 1 View MEN2 Syndromes BEFORE (MEN-1 Syndrome) this video Howard J. Sachs, MD www.12DaysinMarch.com MEN-1 Syndrome Pituitary Parathyroid Pancreas MEN-1 Syndrome Pituitary Parathyroid Pancreas 3-P’s MEN-1 Syndrome Pituitary Parathyroid Pancreas 3-P’s MEN-1 Syndrome Before proceeding, we need to change the name into something more memorable and informative. Once we move from MEN-1 and the 3-P’s, the rest is a breeze. Pituitary ParathyroidReally. Pancreas 3-P’s MEN-1 Syndrome Parathyroid Pancreas Pituitary ~100% ~60% ~20% MEN-1 Syndrome Parathyroid Pancreas Pituitary ~100% ~60% ~20% Multiple Adenomas Gastrinoma (ZE) Prolactinoma MEN-1 Syndrome Pituitary Pancreas Parathyroid ~20% ~60% ~100% Prolactinoma Gastrinoma (ZE) Ca+2 MEN-1 Syndrome Pituitary Pancreas Parathyroid ~20% ~60% ~100% Prolactinoma Gastrinoma (ZE) Ca+2 Pro-ZE-Ca Syndrome MEN 1: Pro-ZE-Ca Syndrome Pituitary Pancreas Parathyroid ~20% ~60% ~100% Prolactinoma Gastrinoma (ZE) Multiple Adenomas Mass Effect Multiple/Atypical Ca+2 Hormonal Dysfunction Ulcers MEN 1: Pro-ZE-Ca Syndrome What are the take homes? Background: A. High penetrance B. Initial presention in majority of MEN C. Compared with sporadic: • PituitaryMultiple adenomas and earlyPancreas age Parathyroid ~20% Presentation: ~60% ~100% D. SameProlactinoma as any other patientGastrinoma with hyperPTH (ZE) Multiple Adenomas • Ca, PTH, PO4- • MassStones, Effect Constipation Multiple/Atypical Ca+2 Hormonal• X- Dysfunctionray: subperiosteal bone Ulcersresorption MEN 1: Pro-ZE-Ca Syndrome What are the take homes? Background: A. High penetrance B. Initial presention in majority of MEN C. Compared with sporadic: • PituitaryMultipleOn USMLE, adenomas any patient and early diagnosedPancreas age or presentingParathyroid with HyperPTH, you need be HyperVigilent for an ~20% MENPresentation Syndrome: (Type~60% 1 or 2a) ~100% D. SameProlactinoma as any other patientGastrinoma with hyperPTH (ZE) Multiple Adenomas • Ca, PTH, PO4- • MassStones, Effect Constipation Multiple/Atypical Ca+2 Hormonal• X- Dysfunctionray: subperiosteal bone Ulcersresorption MEN 1: Pro-ZE-Ca Syndrome What are the take homes? Background (Pancreatic Endocrine Tumors): A. Gastrinoma most common • May present in duodenal location B. Insulinoma, VIPoma, Glucagonoma • Hypoglycemia, WDHA, NME (bronze skin) C. Carcinoid (bronchial, thymus) Pancreas Pituitary Pancreas Presentation: ~60% ~20% ~60% D. Multiple or Atypical Ulcers Gastrinoma (ZE) • ProlactinomaDuodenal beyond D1 Gastrinoma (ZE) • Epigastric pain despite rx Multiple/Atypical E. DiarrheaMass Effect (inactivates lipase/acidicMultiple/Atypical lumen) Ulcers Hormonal Dysfunction Ulcers MEN 1: Pro-ZE-Ca Syndrome What are the take homes? Diagnostics (Gastrinoma): 1. High gastric basal acid secretion Pancreas 2. GastrinPituitary Level Pancreas 3. Secretin Stimulation Test ~60% • Rise~20% in Gastrin Level ~60% Gastrinoma (ZE) Prolactinoma Gastrinoma (ZE) Multiple/Atypical Mass Effect Multiple/Atypical Ulcers Hormonal Dysfunction Ulcers MEN 1: Pro-ZE-Ca Syndrome WhatBe on are the the lookout take homes? with any question that includes Gastrinoma , VIPoma, or Insulinoma. Diagnostics (Gastrinoma): If they include Ca+2, you have two components 1. High gastric basal acid secretionof MEN-1… Pancreas 2. GastrinPituitary Level Pancreas 3. Secretin Stimulation…they will Test most assuredly come after you on the ~60% • Rise~20% in Gastrin Level third component…~60% Gastrinoma (ZE) Prolactinoma Gastrinomathe Pituitary (ZE) Multiple/Atypical Mass Effect Multiple/Atypical Ulcers Hormonal Dysfunction Ulcers MEN 1: Pro-ZE-Ca Syndrome What are the take homes? Background: 1. Adenomas of Anterior Pituitary follow same pattern as in non-MEN syndromes • Prolactin > Growth Hormone > Null Pituitary • HormonePancreas product versus MassParathyroid Effect ~20% ~60% ~100% Presentation: Prolactinoma 1. PituitaryGastrinoma mass (ZE) lesion: HA, visualMultiple field Adenomas cut 2. Prolactinoma: hypogonadotropic hypogonadism Mass Effect • Male:Multiple/Atypical libido/ ED Ca+2 Hormonal Dysfunction Ulcers • Female: menses, galactorrhea MEN 1: Pro-ZE-Ca Syndrome What are the take homes? Diagnostics: 1. Prolactin level 2. Men: LH, testosterone Pituitary 3. ImagingPancreas for mass effect orParathyroid PRL ~20% ~60% Note: ~100% Prolactinoma FrequencyGastrinoma (ZE) of pituitary Multiplelesion in Adenomas MEN-1 depends on how hard you look Mass Effect Multiple/Atypical(20% clinical, 60% by MRI screen) Ca+2 Hormonal Dysfunction Ulcers MEN 1: Pro-ZE-Ca Syndrome What are the take homes? Interestingly, I’ve mentioned you should Diagnosticsbe hypervigilant: looking for MEN1 in patients with1. hyperPTH Prolactin and/or level pancreatic masses or neuroendocrine tumors. 2. Men: LH, testosterone Pituitary On the other hand,3. questionsImagingPancreas involving for mass pituitary effect adenomas orParathyroid PRL are usually focused on the adenoma and secretions. ~20% ~60% Note: ~100% Prolactinoma FrequencyGastrinoma (ZE) of pituitary Multiplelesion in Adenomas MEN-1 depends on how hard you look Mass Effect Multiple/Atypical(20% clinical, 60% by MRI screen) Ca+2 Hormonal Dysfunction Ulcers MEN-1 Syndrome • Reviewed major components – Endocrinopathy (PTH, Pancreas, Pituitary) – Derm Manifestations Angiofibroma (90%) Collagenoma Lipoma MEN-1 Syndrome Lip/Tongue Neuromas seen in MEN2b • Reviewed major components – Endocrinopathy (PTH, Pancreas, Pituitary) – Derm Manifestations Angiofibroma (90%) Collagenoma Lipoma MEN-1 MEN-2 (Pro-ZE-Ca) 1. MTC (100%) 2. Pheochromocytoma (50%) 1. Pituitary (Prolactinoma) 2. Pancreas (Gastrinoma; ZE) 2a 2b 3. Parathyroid (100%; Ca+2) HyperPTH Marfanoid, Neuromas The most difficult part of an MEN Syndrome is knowing you are in one… Autosomal Dominant MEN-1 MEN-2 (Pro-ZE-Ca) 1. MTC (100%) 2. Pheochromocytoma (50%) 1. Pituitary (Prolactinoma) 2. Pancreas (Gastrinoma; ZE) 2a 2b 3. Parathyroid (100%; Ca+2) HyperPTH Marfanoid, Neuromas Autosomal Dominant MEN-1 MEN-2 (Pro-ZE-Ca) 1. MTC (100%) 2. Pheochromocytoma (50%) 1. Pituitary (Prolactinoma) 2. Pancreas (Gastrinoma; ZE) 2a 2b 3. Parathyroid (100%; Ca+2) HyperPTH Marfanoid, Neuromas Gain of function Loss of Suppressor MEN1 RET Mutation Mutation MEN-1 MEN-2 (Pro-ZE-Ca) 1. MTC (100%) 2. Pheochromocytoma (50%) 1. Pituitary (Prolactinoma) 2. Pancreas (Gastrinoma; ZE) 2a 2b 3. Parathyroid (100%; Ca+2) HyperPTH Marfanoid, Neuromas Gain of function Loss of Suppressor MEN1 RET Mutation Mutation MEN-1 MEN-2 (Pro-ZE-Ca) 1. MTC (100%) 2. Pheochromocytoma (50%) 1. Pituitary (Prolactinoma) 2. Pancreas (Gastrinoma; ZE) 2a 2b 3. Parathyroid (100%; Ca+2) HyperPTH Marfanoid, Neuromas Autosomal Dominant MEN-1 MEN-2 (Pro-ZE-Ca) 1. MTC (100%) 2. Pheochromocytoma (50%) 1. Pituitary (Prolactinoma) 2. Pancreas (Gastrinoma; ZE) 2a 2b 3. Parathyroid (100%; Ca+2) HyperPTH Marfanoid, Neuromas Endocrine Disorders for the USMLE, Step One: Multiple Endocrine Neoplasia Type 1 (Pro-ZE-Ca or MEN-1 Syndrome) Pro-ZE-Ca Howard J. Sachs, MD Email: [email protected] .