Multiple Endocrine Neoplasia PDF

Multiple Endocrine Neoplasia, Primary Endocrine Neoplasia, SIADH CLINICAL Medicine Misty T. Justus, DMSc, MS, PA-C  Outline Multiple Endocrine Neoplasia Subtypes SIADH 3 Major Types of Hormone Diseases: (1) hormone excess, (2) hormone deficiency, & (3) Hormone Resistance Multiple Endocrine...

Multiple Endocrine Neoplasia, Primary Endocrine Neoplasia, SIADH CLINICAL Medicine Misty T. Justus, DMSc, MS, PA-C  Outline Multiple Endocrine Neoplasia Subtypes SIADH 3 Major Types of Hormone Diseases: (1) hormone excess, (2) hormone deficiency, & (3) Hormone Resistance Multiple Endocrine Neoplasia Type 1 Multiple Endocrine Neoplasia -1  Multiple Endocrine Neoplasia type I, (MEN 1) originally called Wermer’s Syndrome Rare autosomal dominant disorder Predisposition for tumors of the 3 P’s : Parathyroid Anterior Pituitary Pancreatic islet cells Pituitary adenomas occur in about 15- 20% (as found on imaging) of these patients MEN1 also includes a predisposition to gastrinomas in the duodenum, bronchopulmonary & thymic neuroendocrine tumors, gastric carcinoids, adrenal adenomas (occasionally carcinomas), angiofibromas, lipomas, & other tumors MEN1  Most common manifestation is hyperparathyroidism (found as hypercalcemia incidentally)  Pituitary adenomas — Clinically apparent pituitary adenomas have been found in approximately 15-20% of patients with MEN1. The MC type of pituitary adenoma in MEN1 is a lactotroph adenoma, but somatotroph, corticotroph, gonadotroph, & clinically nonfunctioning adenomas can also occur  Pancreatic islet cell/gastrointestinal endocrine tumors — Enteropancreatic neuroendocrine tumors (NETs) is the primary life-threatening manifestation of MEN1. The MC cause of symptomatic disease is the Zollinger-Ellison (gastrinoma) syndrome (ZES)  Thymic NETs – Thymic NETs (formerly known as thymic carcinoid tumors) occur with increased frequency in MEN1  Bronchopulmonary NETs – Bronchopulmonary NETs occur in at least 20-30% of MEN1 patients with equal sex distribution  Gastric carcinoids  Adrenal tumors — Adrenocortical tumors are reported to occur in 20 -75% of MEN1 patients  Cutaneous tumors — Cutaneous tumors are common in MEN1  Breast cancer risk doubles  MEN 1 Diagnosis:  The clinical diagnosis of MEN1 is based upon the occurrence of two or more primary MEN1 tumor types (parathyroid gland, anterior pituitary, & enteropancreatic)  In family members of a patient with a clinical diagnosis of MEN1, the occurrence of one of the MEN1-associated tumors is consistent with familial MEN1  Testing MEN1 mutation: If the diagnosis is not clear or in an asymptomatic family member without evidence of disease  Carefully monitor all patients with MEN1, known MEN1 mutation carriers, for symptoms or signs of MEN1-associated tumors, such as nephrolithiasis, amenorrhea (females), galactorrhea, erectile dysfunction (males), peptic ulcer disease, diarrhea, symptoms from hypoglycemia  Measure serum calcium, PTH, & prolactin annually Multiple Endocrine Neoplasia Type 2 A & 2 B MEN 2  Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder  The genetic defect in these disorders involves the RET proto-oncogene on chromosome 10  Prevalence of 1 per 30,000 in the general population  MEN2 is subclassified into two distinct syndromes -  Type 2A (MEN2A)  MEN2A is characterized by medullary thyroid cancer (MTC), pheochromocytoma, & primary parathyroid hyperplasia  Within MEN2A, there are four variants: Classical MEN2A, MEN2A with cutaneous lichen amyloidosis (CLA), MEN2A with Hirschsprung disease (HD), & familial medullary thyroid cancer (FMTC)  Type 2B (MEN2B)  Multiple endocrine neoplasia type 2B (MEN2B): Autosomal dominant disorder characterized by MTC & pheochromocytoma but not hyperparathyroidism.  MTC occurs in almost all patients MEN 2 Diagnosis Multiple endocrine neoplasia type 2 (MEN2) should be suspected in any patient with medullary thyroid cancer (MTC) or pheochromocytoma* The diagnosis of MEN2 is based upon the presence of the classical clinical features, family history, & genetic testing (identification of a germline RET mutation)  Particularly when the tumors occur at a young age ( 100mOsm/kg H2O; Urine Na > 40 mEq/L (nml 20mEq/L)  ↑ Serum AVP during time of ↓Na+  AM Cortisol normal (rules out Addison disease)  SIADH Treatment Goals Severity of symptoms determines urgency of treatment Correct hyponatremia Salt administration &/or water restriction Block V2 receptors in renal collecting ducts Selective Vasopressin receptor (V2) antagonists (tolvaptan)  SIADH Treatment If Severe Sx or Na 125 mEq/L: Tx underlying cause Fluid restriction  SIADH Prevention  Avoid hypotonic preoperative IVFs  Ex. = ½ NS, ¼ NS etc.  Closely monitor pts. on SIADH-associated medications:  SSRIs  NSAIDs  Chemo Tx  Amiodarone (antiarrhythmic)  Seizure medications