Multiple Endocrine Neoplasia Type 2B Research Articles

Multiple Endocrine Neoplasia Type 2B: Early Diagnosis by Multiple Mucosal Neuroma

Multiple Endocrine Neoplasia Type 2B: Early Diagnosis by Multiple Mucosal Neuroma

7109 "My Stomach hurts": A Rare Case of Adrenal Cortical Carcinoma

Abstract Disclosure: R.C. Attah: None. I. Sirisena: None. Pheochromocytoma/Paragangliomas are rare neurogenic tumors that arise from chromaffin cells present in the adrenal medulla or extra-adrenal paraganglia, these cells produce catecholamines. Typically, these tumors are discovered as incidentalomas. They can be hereditary as seen in genetic syndromes like multiple endocrine neoplasia type 2A or 2B, neurofibromatosis type 1 or Von Hippel Lindau syndrome but can occur sporadically. Patients typically present with hormonal hypersecretion signs or symptoms like abdominal pain, episodic headaches, sweating, hypertension and tachycardia, but some patients are asymptomatic. Patient is a 37-year-old female with past medical history of hypertension, type 2 diabetes mellitus and fatty liver who presented to the ED with abdominal pain for a few weeks. On arrival, her vitals were BP 205/124, HR 102, RR 14 and SpO2 100% on room air. CT abdomen was obtained which showed a 7.6 x 4.7 x 5.7 cm mass replacing left adrenal gland with small left retroperitoneal hemorrhage worrisome for adrenal cortical carcinoma, metastatic disease or pheochromocytoma. Hormonal workup revealed elevated 24-hr urine cortisol 124.2mcg (ref 4.0-50.0mcg/24h), normal aldosterone/renin ratio 10.63ng/dL (ref <30ng/dl), failed low dose dexamethasone suppression test with post-dex AM cortisol 7.20ug/dL (ref <1.8ug/dL), slightly elevated serum total catecholamine 1256pg/mL (242-1125 pg/mL), norepinephrine 1155pg/mL (ref 217-1109 pg/mL), total metanephrine and normetanephrine 341pg/mL (reg <205 pg/mL), normetanephrine 244.1 (ref <210.1pg/mL), elevated 24-hr urine normetanephrine 700ug/L (ref 131-612ug/L), metanephrine 136ug/L (ref 36-209ug/L) and DHEA-s level 285ug/dl (ref 23-266ug/dL). Due to elevation in cortisol, adrenal cortical carcinoma was suspected as these tumors are frequently associated with cortisol secretion. However, pheochromocytoma with co-secretion of ACTH could not be excluded. She was started on doxazosin for alpha blockade and eventually started on beta blockade with Metoprolol. She underwent a left adrenalectomy and was started on steroid taper post-op due to concern of cortisol co-secretion. Surgical pathology was positive for Left adrenal malignant pheochromocytoma and ganglioneuroma. Genetic panel was negative with no mutation identified in the 54 gene Hereditary paraganglioma-pheochromocytoma panel. This patient had a large adrenal tumor (>4cm mass) but mildly elevated catecholamines which could have led to misdiagnosis as her catecholamine levels were less than 2-3x ULN which is unusual for pheochromocytomas. Roughly 25% of people with pheochromocytoma are undiagnosed throughout their lifespan. This condition can be life-threatening, hence early diagnosis and intervention can be lifesaving. Prognosis of malignant pheochromocytoma is dependent on tumor size, presence of SDHB gene mutation or visceral metastases. Presentation: 6/1/2024

Exploring Multiple Endocrine Neoplasia Type 2B: Key Findings from a Case Report

Multiple endocrine neoplasia type 2B (MEN 2B) is an autosomal dominant syndrome primarily caused by the germline M918T RET mutation. It is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PC), and non-endocrine features. Symptoms depend on the glandular elements present. The initial diagnosis of MEN 2B is relatively late, and the diagnosis by non-endocrine components is extremely weak. The initial management consists of a total thyroidectomy with dissection of the lymph nodes. If PC is present, its treatment is surgical removal, which should be performed before thyroidectomy for MTC. The prognosis of MTC in MEN 2B depends on the stage at diagnosis, and only early diagnosis and intervention offer a chance of cure. It is necessary to underline the need to treat the extra-endocrine signs in these patients. We present below a case of MEN 2B who consulted late for a cervical tumor and morphological abnormalities of the lips and tongue.

Laryngeal Neuromas in a 5-Year-Old With MEN2B: A Case Report and Literature Review.

Multiple endocrine neoplasia type 2B (MEN2B) syndrome is a rare genetic disorder primarily driven by mutations in the RET proto-oncogene. MEN2B exhibits diverse symptoms affecting multiple organ systems, with mucosal neuromas being a prominent feature. These benign tumors contribute to the syndrome's clinical variability, alongside medullary thyroid carcinoma and pheochromocytoma. The article presents a case study of a young girl diagnosed with MEN2B, complicated by laryngeal neuromas leading to respiratory distress post-thyroidectomy. Laryngeal neuromas are exceedingly rare, underscoring the importance of recognizing such manifestations for proper airway management, especially during surgical interventions. Despite its rarity, MEN2B presents significant clinical challenges, requiring early detection, genetic counseling, and multidisciplinary management for improved outcomes. Clinicians must remain vigilant for rare manifestations like laryngeal neuromas to prevent serious complications, particularly during surgical procedures.

Clues for Early Diagnosis of MEN2B Syndrome Before Medullary Thyroid Carcinoma.

Early onset medullary thyroid carcinoma, later pheochromocytomas, and nonspecific extra-endocrine features (hypermobility and persistent constipation) are part of the clinical phenotype of Multiple Endocrine Neoplasia type 2B (MEN2B). A de novo pathogenic M918T variant in the rearranged during transfection proto-oncogene is usually identified. Affected children are often seen by multiple clinicians over a long period before consideration of a diagnosis of MEN2B, with metastatic medullary thyroid carcinoma often the precipitator. We describe the clinical presentation and course of 5 children ultimately diagnosed with MEN2B in New South Wales and the Australian Capital Territory, Australia between 1989 and 2021. All cases had intestinal ganglioneuromatosis that could have prompted an earlier diagnosis. Population wide newborn genomic screening for rare diseases is on the horizon. We propose that MEN2B genomic screening should be included in newborn screening programs and that careful exclusion of intestinal ganglioneuromatosis would allow earlier identification leading to improved clinical outcomes.

Multiple endocrine neoplasia type 2B diagnosed after small intestinal volvulus with progressive megacolon in an adolescent

Multiple endocrine neoplasia type 2B is a rare autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, Marfan-like fatigue, a peculiar face with thickening of the lips, mucosal neuromas on the lips and tongue, and gastrointestinal phenomena. Most patients harbor pathological variants of the RET gene. Herein, we present the first case of a 14 year-old boy who experienced small intestinal volvulus along with a megacolon, and he was diagnosed with multiple endocrine neoplasia type 2B. The patient complained of constipation since he was 2 years old and slowly progressive abdominal distension at school age. At 14 years of age, he presented with remarkable megacolon mimicking Hirschsprung’s disease and complicated with small intestinal volvulus. The volvulus was successfully repaired, and the particularly dilated transverse colon was resected following a rectal biopsy. Histopathological evaluation of the resected transverse colon revealed to be compatible with ganglioneuromatosis. After emergency surgery, the patient was diagnosed with multiple endocrine neoplasia type 2B with medullary thyroid carcinoma, and a de novo variant of RET was confirmed. Gastroenterologists should consider it when treating patients with constipation, especially those with megacolon. Therefore, timely diagnosis may lead to appropriate treatment of medullary thyroid carcinoma and improve mortality.

Developing Dynamic Structure-Based Pharmacophore and ML-Trained QSAR Models for the Discovery of Novel Resistance-Free RET Tyrosine Kinase Inhibitors Through Extensive MD Trajectories and NRI Analysis.

Activation of RET tyrosine kinase plays a critical role in the pathogenesis of various cancers, including non-small cell lung cancer, papillary thyroid cancers, multiple endocrine neoplasia type 2A and 2B (MEN2A, MEN2B), and familial medullary thyroid cancer. Gene fusions and point mutations in the RET proto-oncogene result in constitutive activation of RET signaling pathways. Consequently, developing effective inhibitors to target RET is of utmost importance. Small molecules have shown promise as inhibitors by binding to the kinase domain of RET and blocking its enzymatic activity. However, the emergence of resistance due to single amino acid changes poses a significant challenge. In this study, a structure-based dynamic pharmacophore-driven approach using E-pharmacophore modeling from molecular dynamics trajectories is proposed to select low-energy favorable hypotheses, and ML-trained QSAR models to predict pIC50 values of compounds. For this aim, extensive small molecule libraries were screened using developed ligand-based models, and potent compounds that are capable of inhibiting RET activation were proposed.

Spontaneous and Treatment-Related Changes of Serum Calcitonin in Medullary Thyroid Cancer: Long-Term Experience in a Patient With Multiple Endocrine Neoplasia Type 2B.

Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.

Solving the puzzle of MEN2B syndrome in an adolescent girl

Solving the puzzle of MEN2B syndrome in an adolescent girl

SAT335 Bilateral Pheochromocytomas In Multiple Endocrine Neoplasia Type 2B: A Frozen Abdomen, A Slow Growing Mass, And A Backdoor Solution

Abstract Disclosure: O.A. Shariq: None. T.J. McKenzie: None. W.F. Young: None. Background: Multiple endocrine neoplasia type 2B (MEN2B) is most commonly caused by a germline methionine-to-threonine substitution at codon 918 (M918T) of the RET proto-oncogene. The syndrome is characterized by medullary thyroid carcinoma, pheochromocytoma, and extra-endocrine manifestations (intestinal ganglioneuromas, mucosal neuromas, and skeletal and ophthalmic abnormalities). We describe a patient with MEN2B and bilateral pheochromocytomas, in whom the slow-growing nature of the lesions, and previous history of an extra-endocrine manifestation, precluded the typical approach to surgical resection. Clinical Case: A 58-year-old-male with MEN2B, diagnosed at age 15, presented with a 6-month history of episodic palpitations and labile blood pressures. His past surgical history included a total abdominal colectomy and ileorectal anastomosis at age 7 years for megacolon, secondary to intestinal ganglioneuromatosis. He subsequently required multiple laparotomies and adhesiolysis procedures for recurrent small bowel obstructions. During his most recent laparotomy at age 44, he was noted to have a ‘frozen’ abdomen with dense adhesions involving the small bowel. CT abdomen revealed bilateral adrenal masses, measuring 2.9 cm and 1.5 cm on the right and left, respectively. Review of previous imaging revealed that the right adrenal mass had been present 16 years prior, measuring 1.0 cm at that time, while the left-sided mass was not seen. Biochemical workup was negative previously, but now showed elevated plasma metanephrine (4.1 nmol/L [N<0.5 nmol/L ]) and normetanephrine 2.3 nmol/L [N<0.9 nmol/L ]) levels. In the setting of extensive intra-abdominal adhesions and the slow-growing nature of both masses, the decision was made to perform a unilateral right adrenalectomy through a retroperitoneoscopic, rather than a transabdominal, approach. Pathology confirmed a 4.4 cm pheochromocytoma. The patient was discharged on postoperative day 1 and was symptom free at 1 year follow-up. His most recent plasma metanephrine and normetanephine levels were 0.7 nmol/L and 0.5 nmol/L, respectively. Clinical Lessons: Patients with MEN2B have a 50% lifetime risk of developing pheochromocytoma. Unlike medullary thyroid cancer, which exhibits an aggressive phenotype in this syndrome, MEN2B-associated pheochromocytomas may be slow growing, thereby avoiding the need for an initial bilateral adrenalectomy. Many patients with MEN2B develop gastrointestinal manifestations, including megacolon during infancy, for which multiple surgical interventions may be required. These procedures carry a risk of adhesion formation, which presents a challenge if further abdominal surgery is required later in life for pheochromocytoma. Retroperitoneoscopic adrenalectomy provides a safe approach in such patients, as the need to perform risky adhesiolysis and mobilize adjacent organs is obviated. Presentation: Saturday, June 17, 2023

SAT309 Clinical And Genetic Profiling Of Patients With Multiple Endocrine Neoplasia Type 2 Syndrome And Screening for Medullary Thyroid Carcinoma In Asymptomatic First-degree Relatives

Abstract Disclosure: K. Kumar P: None. Y. Gupta: None. A. Goyal: None. D. Kandasamy: None. N. Tandon: None. Background: Multiple endocrine neoplasia type 2 (MEN2) syndrome is a rare disorder with autosomal dominant inheritance, characterised by the presence of two of the following three endocrine manifestations: medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and primary hyperparathyroidism (PHPT) [1-2]. There is a paucity of data on clinical and genetic profile of MEN2 syndrome in the Indian subcontinent. Objectives: We aimed to evaluate the clinical and genetic profile of patients with MEN2 syndrome and perform screening for MTC among asymptomatic family members with serum calcitonin. Materials and Methods: This was an ambispective study conducted in the Department of Endocrinology at AIIMS New Delhi, involving diagnosed patients of MEN2 syndrome between January 2016 and December 2022. Results: We evaluated a total of 24 families with MEN2 syndrome comprising 61(MEN2A, n=56; MEN2B, n=5) patients, 18 patients were diagnosed as index cases. Data were derived retrospectively for 46 patients (MEN2A, n=43 MEN2B, n=3) and prospectively for 15 patients (MEN2A, n=13; MEN2B, n=2). The mean age at presentation of MEN2A and MEN2B were 28.6 ± 13.52 years and 22 ± 4.44 years, respectively. Of the study patients, 35 (57.38%) were females, among them 32 were MEN2A. Among 18 index patients 67% were synchronously detected to have MTC and PCC while 33% had MTC preceding PCC. Among patients with MEN2A syndrome 33 (59%) had MTC, 21(38%) had simultaneous PCC and MTC and one patient had PCC as presentation. We noted PHPT in 5 (9%) patients with MEN2A syndrome. Of the 5 patients with MEN2B syndrome, 4 (80%) presented with synchronous MTC and PCC and one (20%) presented with MTC aloneMetastatic MTC was noted in six patients with MEN2A syndrome and two patients with MEN2B syndrome. Median baseline Sr calcitonin level was 42 (4-1721) pg./ml in non-Metastatic group vs 3945(928-35572) pg./ml in distant metastasis group. 1 patient had metastasis from PCC to liver. Mutational analysis data are available for 40 patients. The most common mutations in MEN2A and MEN2B groups were C634R (exon 11 of RET gene, n=21) and M918T (exon 16 of RET gene, n=4), respectively.A total of 177 eligible family members of index patients with MEN2A syndrome were contacted, of whom 83 turned up for screening and 42 (50.6%) had elevated serum calcitonin levels (>10 pg./ml). Of the 26 eligible family members of index patients with MEN2B syndrome, only 9 could be screened and all had normal serum calcitonin levels (<10 pg./ml). Discussion & Conclusion: 1) This is the largest study comprising 61 patients after screening 24 family members in India. 2) Synchronous presentation of MEN2 with PCC and MTC is 67% vs 17% in western literature in Index patients. 3) MEN2 syndrome should be suspected in patients with MTC and young-onset PCC and all first-degree relatives of index patients with this syndrome. Presentation: Saturday, June 17, 2023

SAT555 Utility of 18F-DOPA PET/CT in the Diagnosis of Medullary Thyroid Cancer in a Patient with Multiple Endocrine Neoplasia Type 2B

Abstract Disclosure: D.G. Varghese: None. S. Akshintala: None. A. Jha: None. S. Gubbi: None. A. Reno: None. J. Klubo-Gwiezdzinska: None. K. Pacak: None. J. Glod: None. J. Del Rivero: None. Background: MEN2B is a cancer predisposition syndrome caused by an activating mutation in the RET proto-oncogene. It is characterized by medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and extra endocrine features. U/S, CT, MRI and 18F-fluorodeoxyglucose (18F-FDG), 18F-fluorodihyroxyphenylalanine (18F-FDOPA), 68Ga-DOTA-(0)-Tyr(3)-octreotate (68Ga-DOTATATE) PET/CT scans have been used for the diagnosis and follow up of MTC. However, there is increasing evidence of 18F-FDOPA PET as more specific imaging modality in the diagnosis of MTC since L-type amino acid transporters have shown to be present in MTC cells.Clinical Case: 26-year-old female presented with HTN at the age of 17. The patient developed episodes of nausea/vomiting, intermittent headaches with systolic BP in the 190’s. Further work-up revealed bilateral adrenal nodules with elevated plasma metanephrines. The patient underwent left adrenalectomy and a year later, right adrenal nodule resection confirming PHEO. On follow up, calcitonin was elevated, and the patient underwent a total thyroidectomy with bilateral central lymph node dissection. At age 19 she was diagnosed with MEN2B (RET mutation, p.Met918Thr). With rising calcitonin, she was referred to our institution for further evaluation. Her serum calcitonin was 31986(<7.6 pg/ml), CEA 631 (0.8-3.4 ng/ml), fractionated plasma normetanephrine 565 (18-112 pg/ml), and metanephrine 304 (12-61 pg/mL). MRI of the abdomen showed enlarging adrenal masses. 18F-FDG PET/CT scan showed a focus of uptake (SUVmax of 8.5) in posterior right thyroid bed, uptake in the liver (SUVmax of 7.5) and uptake in the right adrenal gland and left adrenal bed; 68Ga-DOTATATE PET/CT scan showed a faint uptake in the right thyroid lobe (SUVmax of 2.7) and an 18F-FDOPA PET/CT scan showed intense uptake in both lobe of the thyroid, multiple lesions in the liver and suspicious focus in the right adrenal bed. The patient underwent bilateral adrenalectomy for recurrent PHEO and her plasma metanephrines normalized. Conclusion: This case adds to the mounting evidence in the usage of 18F-FDOPA PET/CT scan as a useful imaging modality for MTC especially in the setting of MEN2B syndrome. A head-to-head comparison in 18 patients, both per patient and per lesion sensitivity by 18F-FDOPA PET/CT (72%, 85%) was found to be statistically superior compared to 68Ga-DOTATATE PET/CT (33%, 20%), and 18F-FDG PET/CT (17%, 28%). A meta-analysis conducted in MTC consisting of 306 patients from 14 studies, 18F-FDOPA compared to 18F-FDG and 68Ga-DOTATATE showed the highest surface under the cumulative ranking curve (SUCRA) value in both patient and lesion-based analyses irrespective of serum calcitonin/CEA values or calcitonin doubling time. The potential for use of 18F-FDOPA as a diagnostic agent and the potential to provide insight into possible therapeutic targets are unknown and should be further studied. Presentation Date: Saturday, June 17, 2023

SAT521 Predictive Value of Tumor Volumetrics in Patients with Medullary Thyroid Cancer

Abstract Disclosure: N. Behairy: None. S. Gubbi: None. M.G. Pascoal: None. A. Bharadwaj: None. E.C. Wright: None. T. Abijo: None. N. Uttarkar Vikram: None. P. Veeraraghavan: None. C. Cochran: None. J. Glod: None. J. Klubo-Gwiezdzinska: None. Predictive Value of Tumor Volumetrics in Patients with Medullary Thyroid Cancer Background Medullary thyroid cancer (MTC) is a rare endocrine malignancy that can present either as a sporadic disease or as a part of inherited autosomal dominant multiple endocrine neoplasia type 2A (MEN2A) and 2B (MEN2B) syndromes. There is limited data on the prognostic value of the tumor volume (TV) doubling time (TVDT) in patients with sporadic and familial MTC. Therefore, the goal of this study was to examine the association between TVDT and disease-specific survival (DSS) in patients with metastatic MTC. Material and Methods This cohort study included patients with metastatic MTC for whom at least 3 follow-up CT/MRI scans revealed ≥2 measurable lesions and up to the 5 largest lesions in each affected organ were analyzed. The tumor volumes were measured in 2 dimensions (2D) per standard practice reporting and 3 dimensions (3D) using an ellipsoid formula. The average TVDT of all measured lesions in each organ with metastatic deposits was calculated using a previously reported formula. Calcitonin (Ct-DT) and CEA doubling times (CEA-DT) were assessed using the American Thyroid Association Guidelines calculator. The association between DSS and TVDT, Ct-DT, and CEA-DT was tested using Cox regression. Correlations were assessed using a Spearman correlation coefficient. The study was approved by the Institution Review Board. Results The study cohort consisted of 51 patients (27 women, 53%) with age at the initial scan 24 ± 17 years and an average primary tumor size of 3.3±2.0 cm. Seven patients presented with sporadic MTC, 12 with MEN2A and 32 with MEN2B. During a follow-up of 8.0±4.3 years, 28/51 (55%) patients had disease progression and required systemic or local therapies and 9/51 (18%) patients died. A total of 456 scans were analyzed documenting that the organs with the most rapid TVDT were neck masses in 25/51 (49%), liver metastases in 16/51 (31%), lung nodules in 7/51 (14%) and prostate lesions in 3/51 (6%) patients. There was a strong correlation between 2D and 3D TVDT (r = 0.96) as well as between Ct-DT and CEA-DT (r = 0.82). However, the correlation between 2D TVDT and Ct-DT and CEA-DT were low (r = 0.45 for both). The DSS hazard ratios (HR) for DT <1 year compared to ≥3 years were 8.2 (1.5-45.4) for 2D TVDT, 8.7 (1.6-48.2) for 3D TVDT, 15.9 (1.72-146.7) for Ct-DT, and 11.72 (2.0-68.7) for CEA-DT. DSS was not associated with either familial or sporadic etiology of MTC (p = 0.38), gender (p = 0.12), or age at initial scan (p = 0.85). Conclusions Apart from Ct-DT and CEA-DT, TVDT is a valuable prognostic factor in metastatic MTC. Given a strong correlation between 2D and 3D TVDT, standard 2D-based TVDT measurements might be used as an easily obtained and clinically feasible prognostic marker of DSS in MTC patients. Presentation Date: Saturday, June 17, 2023

Coexistence of Slipped Capital Femoral Epiphysis and multiple endocrine neoplasia type 2B (MEN2B) - a case report

Introduction: MEN 2B syndrome is distinguished by the occurrence of medullary thyroid cancer, pheochromocytoma, mucosal neuromas, marfanoid features, and skeletal anomalies, including kyphoscoliosis, joint laxity, pes cavus, and, in a smaller number of cases, slipped capital femoral epiphysis (SCFE).
 Case report: We describe a case report of a 15-years-old patient with the diagnosis of the MEN2B syndrome with a rare manifestation of Slipped Capital Femoral Epiphysis (SCFE). A 15-year-old female presented to the orthopedics out-patient department (OPD) with complaints of pain around the right hip and knee and walking with a limp for approximately four months. Additionally, the feeling of enlarged thyroid gland was reported. X-ray confirmed the presence of the SCFE, while thyroid biopsy revealed the presence of medullary thyroid cancer (MTC). Thus, the diagnosis of MEN2B was made.
 Conclusion: Slipped capital femoral epiphysis (SCFE) can occasionally be a manifestation of MEN 2B syndrome. It is important for physicians to be aware of this association, as it can contribute to the early detection of a potentially life-threatening condition.

Are kidney malformations an additional feature of MEN2B syndrome? – Case report and literature review

Are kidney malformations an additional feature of MEN2B syndrome? – Case report and literature review

Medullary thyroid cancer: epidemiology

Epidemiology of medullary thyroid cancer is presented in the literature review. Thyroid cancer is the most common form of endocrine oncological pathology. It accounts for 96–97 % of all malignant tumors of endocrine organs. According to the Surveillance, Epidemiology, and End Results Program (USA), the incidence of thyroid cancer in 1975–2009 increased approximately threefold, from 4.9 to 14.3 cases per 100,000 population. At the same time, the mortality rate remained low, approximately at the same level, 0.5 cases per 100,000. Such a situation can be explained to some extent by the improvement of diagnostic capabilities of the early, often preclinical, stage of thyroid tumors. Medullary thyroid cancer ranks third after papillary and follicular cancer, but surpasses them in terms of aggressiveness. It is a re­latively rare disease. This type of tumor makes up 1–9 % of all thyroid cancers. Against the background of the general tendency to increase the incidence of thyroid cancer, the absolute number of cases of medullary cancer according to various data remains relatively stable. Epidemiological characteristics of medullary thyroid cancer deserve attention in the age aspect, as well as when considering the frequency of detecting these tumors at autopsy of people who had no signs during their lifetime. In clinical practice, medullary thyroid cancer occurs in two main forms — sporadic and hereditary. The latter is represented as part of the combined syndrome of multiple endocrine neoplasia type 2 (MEN-2), which, in turn, is divided into two subtypes: MEN-2A and MEN-2B syndromes. MEN-2 syndrome is a rare combined hereditary pathology. Sporadic medullary thyroid cancer accounts for approximately 70–80 % of such tumors. It is accompanied by other types of endocrinopathies. Most cases of medullary thyroid cancer occur in the fifth decade of life. The presented data on the epidemiology of medullary thyroid cancer allow for a more detailed and in-depth study of this pathology and contain a certain amount of useful and necessary information.

Lived experiences of undergoing regular tumor screening in patients with multiple endocrine neoplasia types 1 and 2 (MEN1/MEN2).

Targeted screening programs for individuals with an increased risk for cancer have become increasingly available. Patients with multiple endocrine neoplasia (MEN), rare genetic conditions associated with the development of tumors in the endocrine glands, undergo intensive surveillance from an early age. Quantitative research has shown that patients with MEN experience fear of disease occurrence in themselves and their family members. However, little is known about the role that intensive, lifelong screening plays in the lives of individuals. This study investigates the lived experiences of patients with MEN undergoing regular tumor screening through an interpretative phenomenological analysis of interviews with 12 patients with MEN1, MEN2A, or MEN2B syndrome. Four experiential group themes are identified: coming to the foreground/fading into the background, relating to uncertainty, experiencing control, and familial context. Screening is characterized as an ambiguous experience that brings MEN to the foreground and may both exacerbate MEN-related uncertainty as well as provide a sense of control over the disease. The experience of undergoing screening is strongly influenced by the familial context, as participants care for and are cared for by family members and understand their disease through familial experiences. Good care according to patients with MEN includes providing family-centered care, addressing the impact on daily functioning and the meaning of illness, support in the interpretation of physical complaints, facilitation of patient experiences of control, and careful attunement to patient needs within a good doctor-patient relationship.

An unexpected discovery of MEN 2B Syndrome in an adolescent - a case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Difficult situation in treatment of medullary thyroid carcinoma in patient with multiple endocrine neoplasia type 2 B(MEN2B)

Abstract Introduction Multiple endocrine neoplasia type 2B (also known as ‘MEN2B’,‘Multiple endocrine neoplasia type 3′ or ‘Wagenmann–Froboese syndrome’) is a genetic disease characterized by the presence of medullary carcinoma of the thyroid, pheochromocytoma, mucosal neuromas, marfanoid features and multiple skeletal abnormalities such as kyphoscoliosis and pes cavus. Clinical Case A 16 years male presented with neck swelling and dysmorphic feature in the form of marfanoid habitus, including multiple tongue and oral mucosal swelling with mucosal neuromas on the anterior third of the tongue, the lips and the inner eyelid. Lips are thickened and bumpy. Visible neck swelling, palpable solid neck mass, high arm span to height ratio at >1.05, elongated fingers, pes cavus and positive wrist sign which is defined as when the distal phalanges of the thumb and fifth finger overlap on encircling the opposite wrist, were present. Ultrasound of the neck revealed a left solid irregular mass (57mmx33mm), that is hypoechoic, has coarse calcification, hypervascularity, that is mostly central, Multiple cervical lymph node(abnormal nodes include shape (round), absent hilum, intranodal necrosis, reticulation, calcification, peripheral vascularity),Investigation at beginning, Normal thyroid function test and biochemical and electrolyte were observed, Chest x ray was normal, FNAC done for thyroid nodule that showed multiple clumps of large hyperchromatic oval cells picture suggesting high suspicion of thyroid malignancy, thyroid biopsy advised, The patient was referred the FDEMC center for further evaluation and investigation prior to the surgery. During investigation at FDEMC center, thyroid function test normal, biochemistry normal, including PTH and electrolytes, Calcitonin was very high 465 pg/mL (0.2–27.7 pg/mL),GH under GTT was normal, IGF 1 182µg/L (150–350),Plasma metanephrine 40 pg/ml(<90pg/ml),and Plasma normetanephrine 27pg/ml(<196pg/ml) were normal. The patient referred to surgery, total thyroidectomy with radical neck dissection with multiple lymph node resection was performed. The biopsy revealed medullary thyroid carcinoma with cervical lymph node secondaries (bilateral multiple foci in both lobes). The patient kept on levothyroxine tab 100mcg.The follow up of the patient after one month by ultrasound and calcitonin level revealed residual thyroid tissue and two large cervical LN in the the ultrasound and a calcitonin level of 322 pg/mL Another surgical neck dissection to the metastatic LN <multiple LN 7×5cm, multiple suprasternal mass dissection 3×2.5cm,remnant of thyroid tissue 0.8cm,Follow up the patient after one month by ultrasound and calcitonin level still showed that there is residual pathological cervical LN, while the calcitonin level still high 412 pg/mL. PET scan done for him showed there is uptake in the head, neck and chest. The calcitonin was repeatedly was high.

Frequency and impact of musculoskeletal symptoms on quality of life in MEN2B.

To investigate the impact of musculoskeletal (MSK)-related symptoms on the quality of life of patients with multiple endocrine neoplasia Type 2b (MEN2B). An online survey was distributed by the Association for Multiple Endocrine Neoplasia Disorders (AMEND) to their members and worldwide via a social media group for MEN2B patients. The survey consisted of a detailed questionnaire analysing the MSK-related symptoms and structural deformities of MEN2B patients and their impact on patient's lives. Forty-eight participants completed the survey. Participants reported several musculoskeletal complaints; the most prevalent being musculoskeletal weakness at 73% (n = 35) and pain 58% (n = 28). The median pain score was 7 (interquartile range [IQR]: 5-8) and the frequency of pain was daily in 44% (n = 15) and constant in 21% (n = 7). Structural complaints were common with 63% (n = 30) stating their physique was 'different' and 40% (n = 19) describing marfanoid body features. Spinal curvature and foot deformities were the commonest structural abnormalities with scoliosis 70% (n = 16) and pes cavus 63% (n = 22) prevailing. Dental problems were mentioned by 69% (n = 33) with interdental spacing being the most common complaint at 61% (n = 20). The musculoskeletal symptoms of MEN2B had a median impact of 6 (IQR: 3-9) on quality of life (QOL) with structural deformities 53% (n = 18) and pain 26% (n = 9) listed as having the highest impact. Poor MSK health affected exercise, work and mobility. We report a high prevalence of musculoskeletal-related complaints in MEN2B which significantly affects QOL. This suggests a need to provide better holistic care including a multidisciplinary team with physiotherapist, orthopaedic and dental specialist input.