Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant disorder characterized by tumors of the pituitary, parathyroid, and endocrine-gastrointestinal tract. Pituitary neuroendocrine tumors (PitNETs) occur in about 40% of MEN1 cases, with 10% being the first manifestation. Recent studies show a slight female predominance, with microPitNETs (<1 cm) being more common than macroPitNETs (>1 cm). Functional PitNETs (FPitNETs) are more frequent than non-functional ones (36% to 48%), with prolactinomas being the most common FPitNETs. MEN1-associated PitNETs are often plurihormonal, larger, and more invasive compared to sporadic types, though patient age and FPitNET proportions are similar. MEN1 mutation-negative patients tend to have larger, symptomatic PitNETs at diagnosis. Six patients with MEN1 have been reported to have pituitary carcinomas, including a mutation- negative patient. Treatment approach between PitNETs in MEN1 and sporadic types appears to be similar. PitNETs also occur in MEN4, but their epidemiology is less understood. In patients with a MEN1-like phenotype and negative genetic testing, MEN4 should be considered.

Multiple endocrine neoplasia type 1 is a rare genetic neuroendocrine syndrome caused by over 1500 different germline mutations. It can cause 20 different endocrine tumors affecting primarily the parathyroid glands, gastroenteropancreatic tract, and the anterior pituitary gland. Multiple endocrine neoplasia type 2A (MEN2A) and Multiple endocrine neoplasia type 2B (MEN2B) are autosomal dominant genetic syndromes because of a germline variant in the \'rearranged during transfection\' (RET) proto-oncogene. There are common RET mutations causing receptor hyperactivation and induction of downstream signals that cause oncogenesis. Common conditions with MEN2A are medullary thyroid cancer (MTC), pheochromocytoma, and primary hyperparathyroidism. Common conditions with MEN2B include MTC, pheochromocytomas, and benign ganglioneuromas.

A man, in his 30s, with a history of obesity and hypothyroidism planned to begin taking a new Glucagon-like peptide-1 (GLP-1) agonist for weight loss. As these medications have been associated with C-cell hyperplasia, a calcitonin level was checked as evaluation prior to starting the drug. This returned at 131 pg/mL (upper limit of normal<10 pg/mL), and a subsequent carcinoembryonic antigen was 5.2 ng/mL (ref<3 ng/mL). Thyroid ultrasound was performed and demonstrated bilateral subcentimeter nodules. After total thyroidectomy, final pathology demonstrated bilateral 0.8 cm medullary thyroid carcinoma. Genetic testing revealed a NM_020975.6: c.1826G > A; p.Cys609Tyr. germline RET mutation, confirming the diagnosis of multiple endocrine neoplasia 2 syndrome. The patient recovered well from treatment. His first-degree relatives also underwent genetic testing. This case represents a surprising diagnosis of familial multiple endocrine neoplasia 2A prior to starting a Glucagon-like peptide-1 agonist.

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Multiple endocrine neoplasia (MEN) syndromes are rare autosomal dominant diseases that are associated with a mixture of both endocrine and non-endocrine tumors. Traditionally, there are 2 types of MEN that have unique clinical associations: MEN 1 (parathyroid hyperplasia, pancreatic neuroendocrine tumors, and pituitary tumors) and MEN 2 (medullary thyroid carcinoma and pheochromocytoma), which is further classified into MEN 2A (adds parathyroid adenomas) and 2B (adds ganglioneuromas and marfanoid habitus). Many of the endocrine tumors are resected surgically, and the pre, intra, and postoperative management strategies used must take into account the high recurrence rates asscioated with MEN tumors.

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BACKGROUND: Jeffrey A. Norton could have been a professional football player but instead he chose to pursue a career in medicine and in the process became an outstanding academic surgeon. This story recounts his ascent from a small town in Massachusetts to the pinnacle of academic surgery.
METHODS: After graduating from high school in Albany, New York, Jeff continued his education at Dartmouth University, the State University of New York Upstate Medical University at Syracuse (SUNY Upstate Medical University), and the Department of Surgery at the Duke University School of Medicine. When he completed the surgical residency, he spent 10 years at the National Cancer Institute (NCI) where he and his colleagues made significant contributions to the diagnosis and treatment of patients with endocrine tumors. After leaving the NCI, he had highly productive years as a Professor in Departments of Surgery at Washington University, the University of California at San Francisco, and Stanford University. He became a member of every major academic surgical society and won numerous awards for his accomplishments in research. His expertise in educating medical students and surgical residents is legendary.
RESULTS: In addition to his academic accomplishments, Jeff trained legions of young surgeons who subsequently made significant contributions in surgical investigation and clinical surgery.
CONCLUSIONS: It is most fitting that the Stanford University School of Medicine has assembled a group of Jeffrey Norton\'s colleagues in academic medicine and surgery to pay tribute to his achievements as a surgical scientist.

Understanding genetic predisposition has a significant impact on the management of patients with endocrine tumours, including therapy, early detection and prevention. These tumours, which develop as part of a familial predisposition, often manifest early in life and frequently affect several endocrine organs. In the following article, both common syndromes, such as multiple endocrine neoplasia (MEN) syndromes, and rare syndromes, such as familial isolated pituitary adenoma (FIPA), are presented based on their indicator diseases.
ENDOKRINOLOGISCHE TUMORPRäDISPOSITIONEN: Die Kenntnis über eine genetische Tumorprädisposition hat einen wesentlichen Einfluss auf die Behandlung sowie die Früherkennung und Prävention bei Patient*innen mit endokrinen Tumoren. Die im Rahmen einer familiären Prädisposition entstehenden Tumore manifestieren sich oft früh und betreffen häufig mehrere endokrine Organe. Im folgenden Artikel werden die innerhalb der Tumorsyndrome häufig vorkommenden Krankheitsbilder wie die MEN-Syndrome (Multiple Endokrine Neoplasien) sowie seltenere Manifestationen wie das familiäre isolierte Hypophysenadenom (FIPA) anhand ihrer jeweiligen Indikator-Erkrankungen vorgestellt.

Genetic testing for germline RET pathogenic variants, which cause the Multiple Endocrine Neoplasia Type 2 (MEN2) syndrome, has become crucial in managing patients with medullary thyroid carcinoma (MTC). Classically, RET heterozygous missense pathogenic variants are transmitted in a Mendelian autosomal dominant pattern, of which germline/gonadal mosaicism has never been reported. We report the novel occurrence of a MEN2A patient\'s family in which the siblings inherited three different RET 634 genotypes: wild type (p.Cys634), p.Cys634Gly or p.Cys634Arg heterozygous pathogenic variants. We hypothesized that germline/gonadal mosaicism, derived from an inherited + early somatic mutation in the mother or a double de novo mutation during maternal embryogenesis, led to this rare event in the RET gene. Exome analysis of the proband\'s deceased mother\'s paraffin-embedded thyroid tissue confirmed the three nucleotides in the same 634 codon position. For the first time, we describe germline/gonadal mosaicism in RET, generating a second pathogenic amino acid change in the same codon causing MEN2A. Our finding shows that RET parental mosaicism, confirmed by somatic exome sequencing, might explain discrepant genotype cases in siblings with inherited cancers.

Multiple endocrine neoplasia (MEN) are tumors that involve two or more endocrine glands. It can also involve other organs and tissues as well. Out of the four types of MEN type 2 is the most common. In MEN type 2 or type 3, paraganglioma is rare, but in our case, medullary thyroid carcinoma (MTC), hyperparathyroidism, and pheochromocytoma were associated with the paraganglioma.