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Medullary thyroid cancer (MTC) is about 5% of all thyroid carcinomas and is hereditary in 2030% of cases. Multiple endocrine neoplasia syndrome type 2 (MEN2), in addition to medullary thyroid cancer, may include pheochromocytoma, hyperparathyroidism, and some other manifestations. The multidisciplinary data bank (MDB) developed by us is a specialized resource for storing, accumulating and subsequent analysis of data on patients with MTC and MEN2 syndromes. The MDB allows you to collect data from any sources (primary care, medical institutions at various levels, federal centers) and provides internal automated control of the quality and quantity of input data. It is necessary to keep a record of such data to improve the efficiency of diagnostics, treatment and rehabilitation of patients. MDB is an integrated digital platform containing reference materials for doctors, which allows combining evidence-based clinical experience in patients, and provides the opportunity for expert support of medical decisions. In the long run, it will help us organize digitally stored data for machine learning and lays the groundwork for the development of artificial neural networks.

Thyroid cancer is rare in the pediatric population, but thyroid carcinomas occurring in children carry a unique set of clinical, pathologic, and molecular characteristics. In comparison to adults, children more often present with aggressive, advanced stage disease. This is at least in part due to the underlying biologic and molecular differences between pediatric and adult thyroid cancer. Specifically, papillary thyroid carcinoma (which accounts for approximately 90% of pediatric thyroid cancer) has a high rate of gene fusions which influence the histologic subtypes encountered in pediatric thyroid tumors, are associated with more extensive extrathyroidal disease, and offer unique options for targeted medical therapies. Differences are also seen in pediatric follicular thyroid cancer, although there are few studies of non-papillary pediatric thyroid tumors published in the literature due to their rarity, and in medullary carcinoma, which is most frequently diagnosed in the pediatric population in the setting of prophylactic thyroidectomies for known multiple endocrine neoplasia syndromes. The overall shift in the spectrum of histotypes and underlying molecular alterations common in pediatric thyroid cancer is important to recognize as it may directly influence diagnostic test selection and therapeutic recommendations.

Objective We aimed to provide ideas for clinicians, especially radiologists, for the diagnosis of multiple endocrine neoplasia (MEN) syndromes. Background MEN syndromes include MEN1, MEN2, and MEN4 and usually involve 2 or more endocrine tumors. The MEN syndromes are a group of euchromatic dominant genetic diseases, and the main genes involved include MEN1 (MEN1), RET (MEN2), and CDKN1B (MEN4). Methods In this article, involving 8 cases (4 cases of MEN1, 2 cases of MEN2A, 1 case of MEN2B, 1 case of MEN4) from our center, we introduced the disease spectrum, clinical manifestations (especially imaging findings), and related genes involved in each type of MEN syndromes. We also discussed the differential diagnosis between MEN and sporadic tumors and emphasized that MEN should be screened and the relevant required examinations. Conclusions Considering that MEN syndromes involve multiple endocrine gland tumors and nonendocrine organ diseases, it is very important to identify potential patients early and perform multiple examinations on them, including biochemical and multitype, and multisite imaging examinations according to the disease spectrum of each type. Considering that this is a group of genetic diseases, both interviewing patients about their family history and genetic testing are also very important. Only in this way can a comprehensive and accurate diagnosis be made, enabling patients to receive appropriate treatment and improve their prognosis.

Five to ten percent of all pediatric tumors are associated with a genetic predisposition. In this chapter, we will discuss the main imaging examinations used in the evaluation of specific cancer predisposition syndromes (CPS) including Wilms’ tumor predisposition syndromes, Li-Fraumeni syndrome, and neurofibromatosis type 1, as well as more rare syndromes that have specific features, including DICER1 mutations, familial paraganglioma syndromes, and multiple endocrine neoplasia syndromes. Currently, ultrasound (US) and whole-body MRI (WBMRI) are the main modalities utilized for tumor surveillance in these children with cancer predisposition syndromes. Contrast-enhanced ultrasound and WBMRI with positron emission tomography (PET) are emerging as adjunct imaging tools in oncological imaging. In our discussion, we will also highlight the advantages and limitations of US and WBMRI and emphasize the importance of expert imaging interpretation and appropriate communication to clinicians and families.

The diagnosis and treatment of medullary thyroid cancer (MTC) has changed considerably over the past 40 years, although survival has not improved over the past three decades. From the first clinical descriptions of MTC and the multiple endocrine neoplasia syndromes to the identification of the RET proto-oncogene, the concept of prophylactic thyroidectomy has become a reality for some families. The surgery is usually performed by high-volume surgeons in specialized centers with results that rarely leave patients with complications but with maximum survival benefit. For patients with unresectable or metastatic disease, many new targeted agents have been developed, some of which have shown great promise and are close to being approved for a disease which hitherto has had no systemic treatment options. This article highlights the important advances in the diagnosis and management of MTC.

An understanding of the mutations of the proto-oncogenes and tumor suppressor genes that occur in thyroid cancers should eventually explain the diverse clinical characteristics of these tumors and also direct therapy. Some insights have already emerged in the last decade; some abnormalities in tumor genes are consistently associated with specific clinical and pathologic findings. These genetic abnormalities usually represent somatic mutations in tumors of follicular epithelial origin, as opposed to inherited mutations in medullary thyroid cancers of parafollicular C cells origin because most thyroid tumors are sporadic and not familial. This is different from the multiple endocrine neoplasia syndromes in which the primary tumorigenic gene mutations are inherited. This improved understanding of the molecular basis of these diseases has led to the development of novel targeted therapeutic approaches which will be discussed in this paper.

The aim of this review was to summarize the recent developments on the role of positron emission tomography (PET) imaging using different radiopharmaceuticals in patients with multiple endocrine neoplasia (MEN) syndromes. Although most guidelines do not mention the use of PET imaging in patients with MEN syndromes, recent data seem to suggest a relevant diagnostic role of PET imaging in this setting. In particular, latest evidence has shown that somatostatin receptor PET provides a diagnostic accuracy in detecting MEN syndromes-related neuroendocrine tumours (NETs) higher than that of somatostatin receptor scintigraphy, thus influencing patient management in a significant percentage of cases. 18 F-DOPA PET seems to have a potential role in detecting MEN-2-related NETs, whereas 18 F-FDG PET is potentially useful in identifying aggressive NETs with poorer outcomes. More studies are needed to better define the role of different radiotracer-based PET imaging in patients with MEN syndromes.

The aim of this study was to evaluate the role of ⁶⁸Ga DOTANOC PET/CT imaging in patients with multiple endocrine neoplasia (MEN) syndromes.Data of 33 patients (age, 33.5 [13.8] years; male 14/female 19) with MEN syndromes (MEN 1, 9; MEN 2A, 19; MEN 2B, 5) who underwent 41 ⁶⁸Ga DOTANOC PET/CT studies were retrospectively analyzed. Twenty PET/CTs were done for staging and 21 for restating. PET/CT images were evaluated in consensus by 2 nuclear medicine physicians, qualitatively and semiquantitatively (SUV(max)). A combination of histopathology, clinical, and biomarker follow-up was taken as reference standard.Of the total 41 ⁶⁸Ga DOTANOC PET/CTs, 34 were interpreted as positive for neuroendocrine tumors (NETs) and 7 as negative. The patientwise sensitivity of PET/CT was 94% (95% confidence interval [CI], 80-99), specificity was 71% (95% CI, 29-96), positive predictive value was 94% (95% CI, 80-99), negative predictive value was 71% (95% CI, 29-96), and accuracy was 90%. A total of 74 disease sites were demonstrated on PET/CT, including 41 primary NETs (pancreas, 10; stomach, 2; pheochromocytoma, 10; medullary thyroid carcinoma, 19), 31 metastatic sites (lymph node, 15; liver, 10; bone, 4; lung, 1; breast, 1), and 2 parathyroid adenomas. Lesionwise sensitivity, positive predictive value, and accuracy of PET/CT were 93%, 96%, and 90% overall, 89%, 95%, and 85% for primary tumors, and 100%, 97%, and 97% for metastasis, respectively. Among primary tumors, the SUV(max) of medullary thyroid carcinoma was significantly lower than gastro pancreatic NETs (P = 0.003) and pheochromocytomas (P = 0.003). No site-specific difference was seen in SUV(max) of metastatic lesions.⁶⁸Ga DOTANOC PET/CT shows high diagnostic accuracy in MEN syndrome and can demonstrate both primary and metastatic NETs in these patients.

The multiple endocrine neoplasia (MEN) syndromes present a diverse array of challenges to the anesthesiologist. The tumors and their effects are often underdiagnosed and potentially discovered only when the patient is undergoing surgery for either a component of one of the syndromes or another procedure altogether. This can present the anesthesiologist with a life-threatening situation in the operating room. A thorough understanding of the syndromes, as well as management strategies, will enable the anesthesiologist to handle these patients.Advances in the pharmacologic armamentarium available to physicians have enabled patients with MEN, particularly those with the carcinoid syndrome or pheochromocytoma, to undergo surgery safely, with minimal morbidity and mortality.Awareness of the components of the MEN syndromes, as well as careful preoperative preparation, paves the way for a smooth anesthetic and postoperative course in these patients.

The morphologic abnormalities seen in the parathyroid glands are predominantly those related to hyperfunction, i.e., primary hyperparathyroidism (PHP). Thus, the focus in this chapter is on this aspect of parathyroid pathology, because almost all surgical specimens of parathyroid lesions are derived from patients with hyperparathyroidism. Because morphologic abnormalities are an important factor in the surgical treatment of this disease, a review of parathyroid embryologic development, anatomy, and normal histology is included. A brief discussion of parathyroid pathology in hypoparathyroidism is also included, as is discussion of the pathology of the glands in humoral hypercalcemia of malignancy.

Background Primary hyperparathyroidism is one of the most common causes of hypercalcemia. Inherited forms of primary hyperparathyroidism like Multiple Endocrine Neoplasia Type 1, Multiple Endocrine Neoplasia Type 2a, Hyperparathyroidism-Jaw Tumor Syndrome or isolated familial tumors are not common for our population. Results We present a case of primary hyperparathyroidism in a 38-year-old Turkish man with hyperaldosteronism (Conn’s syndrome). Conclusion Genetic studies could not reveal any mutation. We could not identify any inherit form of the diseases. We wanted the first-line relatives examination of the suspected gene mutation, but they refused. Electronic supplementary material The online version of this article (doi:10.1186/s13104-015-1271-0) contains supplementary material, which is available to authorized users.

The identification of the genetic causes of the multiple endocrine neoplasia (MEN) syndromes 1 and 2, and associated genotype–phenotype relationships, has revolutionised the clinical care of affected patients. A genetic diagnosis can be made during infancy and careful clinical surveillance, coupled with early intervention, has the potential to improve both morbidity and mortality. These developments have seen the management of patients with MEN move into the arena of paediatric medicine. In this review article, we consider the genetic causes of MEN together with the clinical manifestations and management of these syndromes.

Lips CJM (University Hospital, Utrecht, The Netherlands). Clinical management of the multiple endocrine neoplasia syndromes: results of a computerized opinion poll at the Sixth International Workshop on Multiple Endocrine Neoplasia and von Hippel–Lindau disease (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 589–94. Objectives and design In order to provide all participants of the Sixth International Workshop on Multiple Endocrine Neoplasia and von Hippel–Lindau Disease with the opportunity to express their opinion on medical, ethical and social issues on clinical management of these hereditary cancer syndromes, a meeting employing an interactive voting system was organized. Results In many aspects, the majority of the participants shared the same opinion. The following percentages of participants felt that, if a specific germline mutation is present in a definitely affected family member, DNA diagnosis should be performed in the offspring of this patient before the age of 10: 78% for MEN-1, 93% for MEN-2, and 71% for VHL. About 71% felt the clinical specialist should provide information about the consequences of DNA analysis and be responsible for disclosing the DNA test results and performing genetic counselling. If possible, selective surgery is preferred to maintain organ function. To make a complete diagnosis in a patient with an apparently sporadic tumour, 89% believed that mutation analysis of germline DNA is mandatory in order to investigate the possibility of inherited disease. In several areas, controversial opinions exist, depending on diversity in discipline, specific research area, experience in the field, and cultural and religious backgrounds. In particular, in vitro fertilization combined with pre-implantation genetic diagnosis is an area which attracts considerable emotion. Conclusions In order to avoid confusion in the families, explicit and common guidelines are needed for the identification, treatment and follow-up of individuals who have predisposing MEN or VHL mutations. Close collaboration between endocrinologists, oncologists, surgeons, pathologists, psychologists and geneticists is required in order to establish and verify such guidelines.

Hypercalcemia is a variable feature of inherited endocrine disorders. In the multiple endocrine neoplasia (MEN) syndromes, generalized hyperparathyroidism is a common feature. It occurs much more frequently in patients with MEN type 1 as compared to patients with MEN type 2A. Unlike the MEN syndromes, patients with familial hypocalciuric hypercalcemia (FHH) have only hypercalcemia with no associated endocrinopathies. The hyperparathyroidism in patients with either of the MEN syndromes is managed by parathyroidectomy, whereas patients with FHH are managed nonoperatively. The specific genetic defects associated with MEN type 2 syndromes and FHH have been identified. They explain, in part, the clinical and pathophysiologic features of these diseases. The genetic defect causative of MEN type 1 will doubtless soon be found and thereby provide further insights into the molecular basis of calcium homeostasis. We will review the clinical presentation and the management of patients with these disorders. We will also review the recent molecular discoveries in MEN 2A, MEN 2B, and FHH, and define how they have altered the management of patients who have these syndromes.

Multiple endocrine neoplasia (MEN) is a term used to describe a group of hereditary carcinoma syndromes. Patients carrying a characteristic autosomal dominant gene aberration exhibit various endocrine carcinomas, as well as other anatomical abnormalities. Unfortunately, familial endocrine carcinoma patients are too often unrecognized by primary care providers, resulting in delayed diagnosis and treatment, with profound consequences related to morbidity and mortality. This article will introduce the various MEN syndromes and the infusion nurse's role in the care of these individuals and their families.

Adbances in the identification and localization of the abnormal genes in the multiple endocrine neoplasia syndromes have provided new methods of identifying "at risk" individuals in these families. Genetic testing using linkage analysis in multiple endocrine neoplasia (MEN) 1 and direct mutation analysis of the RET protooncogene in MEN 2 is now available for these disorders. New management issues for these disorders have resulted, and a practical approach to these issues is discussed.

The multiple endocrine neoplasia syndromes are autosomal dominant proliferative disorders related to an overproduction of hormones. Included in this group are multiple endocrine neoplasias types 1 and 2 (MEN1, MEN2), von Hippel Lindau syndrome, neurofibromatosis, and Carney complex …

Medullary thyroid cancer is a rare neoplasm that arises from the parafollicular C cells. It occurs in a sporadic form, or less commonly as a hereditary form, as part of multiple endocrine neoplasia syndromes types 2A and 2B. The RET proto-oncogene is currently the primary factor that is implicated in the hereditary forms of this neoplasm. The knowledge about the genetic makeup of the neoplasm impacts upon management as it allows for screening, early detection, and prophylactic treatment. Surgery is the main modality that offers a cure. This entails a total thyroidectomy and vigilant management and surveillance of the neck. Prognosis of patients with MTC is variable, but the more constant factors that affect it are the stage of disease and the age of the patient. The emerging molecular genetic understanding of this malignancy will provide the foundation for prognostic and therapeutic decision-making in the future. Interdisciplinary management by surgeons, endocrinologists, pathologists, radiotherapists, radiologists, and medical oncologists should be sought.

Pituitary Tumors Moises Mercado and Mark E. Molitch Hypopituitarism Baha M. Arafah and Mona P. Nasrallah Posterior Pituitary: Disorders of Water Metabolism Lisa L. Wong and Joseph G. Verbalis Hyperthyroidism David S. Cooper Hypothyroidism and Thyroiditis Donald A. Meier and Michael M. Kaplan Thyroid Cancer Richard T. Kloos and Ernest L. Mazzaferri Cushing's Syndrome James W. Findling Adrenal Insufficiency and Adrenal Cancer Erik K. Alexander and Robert Dluhy Pheochromocytoma Mary P. Gillam and Lewis Landsberg Hypercalcemia and Hyperparathyroidism Bart L. Clarke and Sundeep Khosla Hypoparathyroidism and Hypocalcemia Elena I. Barengolts and Subhash C. Kukreja Metabolic Bone Disease Michael Kleerekoper, Hisham Alrefai, Louis Afonso, and Bharat Raman Male Reproductive Endocrinology Shalender Bhasin, Atam B. Singh, and Robert Christiansen Disorders of Female Reproduction Jared C. Robins and Robert Rebar Endocrine Problems in Pregnancy Lisa P. Purdy and Boyd E. Metzger Type 1 Diabetes Mellitus J. Woody Sistrunk and Bruce R. Zimmerman (deceased) Type 2 Diabetes Mellitus Neelima V. Chu and Robert R. Henry Hypoglycemia Neena Natt and F. John Service Disorders of Lipoprotein Metabolism Ira J. Goldberg and Phillip Bukberg Disorders of Puberty Dennis M. Styne Disorders of Growth and Development Erick J. Richmond and Alan D. Rogol Multiple Endocrine Neoplasia Syndromes Kelly L. Wirfel, Douglas B. Evans, Jeffery E. Lee, Helmuth Goepfert, and Robert F. Gagel

Recent progress in molecular biology and genetics has made a major impact on the management of patients with multiple endocrine neoplasia syndromes MEN-1 and MEN-2. The understanding of the mechanisms involved in inherited thyroid and parathyroid tumours also offered valuable answers for other models of neoplasia. In addition, parathyroid surgery has witnessed rapid progress, from the cloning of the calcium receptor to the development of calcimimetics, a new class of drugs that could shift the management of hyperparathyroidism from surgical intervention to medical treatment. Laboratory techniques initially designed for research are more and more being used for clinical diagnosis. For example, the use of the polymerase chain reaction is currently being evaluated in the early diagnosis of metastatic thyroid carcinoma by identifying specific gene products in the local lymph nodes. This chapter attempts to convince the reader that molecular biology is no longer restricted to the laboratory but has an increasing impact on clinical decisions to which an endocrine surgeon is exposed.

Pheochromocytoma is a rare catecholamine-secreting tumor that may present in a protean manner. Gastrointestinal manifestations of pheochromocytoma are common and include nausea, vomiting, and abdominal pain, but megacolon, in the absence of the multiple endocrine neoplasia syndromes (MEN 2A and 2B), has rarely been described. In this report megacolon was the presenting feature of the patient’s pheochromocytoma. We discuss the role of catecholamines in the pathogenesis of a megacolon and emphasize the importance of recognizing this rare, but often lethal, combination.

The multiple endocrine neoplasia (MEN) syndromes are inherited disorders of the neuroendocrine system and are characterized by a predisposition to simultaneous or successive development of neoplasia and/or hyperplasia of several endocrine glands. Transmitted as an autosomal dominant disorder, the endocrine abnormalities in MEN reflect involvement of the amine precursor uptake and decarboxylation (APUD) system.

Background: All patients diagnosed with medullary thyroid carcinoma (MTC) should undergo RET mutation analysis to exclude familial disease – multiple endocrine neoplasia (MEN)-2A and -2B and familial medullary thyroid carcinoma (FMTC). In young patients at risk of genetically determined MTC, the key to a good outcome is an appropriate first operation, and this will depend upon the codon mutation, patient age, calcitonin level and disease extent at presentation. When MTC has already developed, a therapeutic intervention is required. Conclusions: The thyroid, pituitary, adrenal, parathyroid and pancreatic components of MEN-1 and -2 require close collaboration of a specialist and experienced multidisciplinary team.