Multiple Endocrine Neoplasia
Multilpe endocrine neoplasia (MEN) are rare fimilial (inherited) conditions affecting the glands of the endocrine system:
- Multiple endocrine neoplasia 1 (MEN type I) also known as Wermer's syndrome
- Multiple endocrine neoplasia 2A (MEN type IIa) also known as Sipple Syndrome
- Multiple endocrine neoplasia 2B (MEN type IIb)
- Familial medullary thyroid carcinoma, (FMTC) is a similar inherited condition were medullary thyroid carcinoma may occur in several family members, though not necessarily with the other endocrine tumours seen in MEN.
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MeSH term: Multiple Endocrine Neoplasia
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Gallium-68 Dotatate PET/CT is superior to other imaging modalities in the detection of medullary carcinoma of the thyroid in the presence of high serum calcitonin.
Hell J Nucl Med. 2015 Jan-Apr; 18(1):19-24 [PubMed] Related Publications
SUBJECTS AND METHODS: Seven patients (age range 31-66 years, M:F 3:4) with raised calcitonin (mean=7,143pg/mL) were referred for (68)Ga-Dotatate PET/CT scan for localisation of persisting recurrent MTC. Six patients were known to have MTC treated with thyroidectomy and one patient was presenting for the first time. All patients had multiple imaging including ultrasound (US), CT, magnetic resonance imaging (MRI), fluorine-18-fluorodeoxyglucose ((18)F-FDG) PET/CT and iodine-123-metaiodobenzylguanidine ((123)I-MIBG). Positive findings were defined as areas of increased uptake other than the organs of normal distribution and were correlated with results of biopsies, other imaging, long term monitoring of calcitonin and clinical follow up.
RESULTS: In 6/7 patients with very high serum calcitonin (range= 672-37,180, mean=8,320pg/mL) (68)Ga-Dotatate PET/CT confirmed the presence of active disease seen on other modalities or detected hitherto unsuspected lesions. In at least 3 cases, (68)Ga-Dotatate PET/CT showed many more lesions compared to other imaging combined. In 1/7 patient (68)Ga-Dotatate PET/CT was negative in line with a relatively low calcitonin level (80pg/mL) and negative disease on fine needle aspiration.
CONCLUSION: (68)Ga-Dotatate PET/CT is an effective tool for localising metastatic spread of MTC. It appears to be most effective in the presence of higher levels of serum calcitonin, probably in excess of 500pg/mL. The results of our small cohort had an impact on staging and management with the introduction of peptide receptor radionuclide therapy for inoperable disease.
Thyroid incidentalomas in patients with multiple endocrine neoplasia type 1.
Eur J Endocrinol. 2015; 172(4):337-42 [PubMed] Related Publications
DESIGN: A cross-sectional study.
METHODS: The study included two groups: patients with MEN1 and a matched non-MEN1 control group without known thyroid disease, who underwent an ultrasound of the neck for the localization of parathyroid adenoma. Ninety-five MEN1 patients underwent ultrasound of the neck and were matched on gender and age with non-MEN1 patients. The prevalence of thyroid incidentalomas described in the ultrasound report was scored. Multinodular goiters, solitary nodes, and cysts were scored as incidentalomas. Presence of nuclear menin expression was evaluated by menin immunostaining of the thyroid tumors.
RESULTS: In the MEN1 group, 43 (45%) patients had a thyroid incidentaloma compared with 48 (51%) in the non-MEN1 group, of which 14 (15%) and 16 (17%), respectively, were solitary nodes. Menin was expressed in the nuclei of all evaluated thyroid tumors.
CONCLUSIONS: MEN1 patients do not have a higher prevalence of thyroid incidentalomas compared with primary hyperparathyroidism patients without the diagnosis of MEN1. Menin was expressed in the thyroid tumors of MEN1 patients.
Long-term results of the surgical management of insulinoma patients with MEN1: a Groupe d'étude des Tumeurs Endocrines (GTE) retrospective study.
Eur J Endocrinol. 2015; 172(3):309-19 [PubMed] Related Publications
DESIGN AND METHODS: Consecutive insulinoma-MEN1 patients operated on for a nonmetastatic insulinoma between 1957 and 2010 were retrospectively selected from the MEN1 database of the French Endocrine Tumor Group. The type of surgery was categorized as distal pancreatectomy (DP), total pancreatectomy/cephalic duodenopancreatectomy (TP/CDP), or enucleation (E). Primary endpoint was time until recurrence of hypoglycemia after initial surgery. Secondary endpoints were post-operative complications.
RESULTS: The study included 73 patients (median age=28 years). Surgical procedures were DP (n=46), TP/CDP (n=9), or E (n=18). After a median post-operative follow-up of 9.0 years (inter-quartile range (IQR): 2.5-16.5 years), 60/73 patients (82.2%) remained hypoglycemia free. E and TP/CDP were associated with a higher risk of recurrent hypoglycemia episodes (unadjusted hazard ratio: 6.18 ((95% CI: 1.54-24.8); P=0.010) for E vs DP and 9.51 ((95% CI: 1.85-48.8); P=0.007) for TP/CDP vs DP. After adjustment for International Union against Cancer pTNM classification, enucleation remained significantly associated with a higher probability of recurrence. Long-term complications had occurred in 20 (43.5%) patients with DP, five (55.6%) with TP/CDP, but in none of the patients who have undergone E (P=0.002).
CONCLUSION: In the French Endocrine database, DP is associated with a lower risk for recurrent hypoglycemia episodes. Due to lower morbidity, E alone might be considered as an alternative.
RET Cys634Arg mutation confers a more aggressive multiple endocrine neoplasia type 2A phenotype than Cys634Tyr mutation.
Eur J Endocrinol. 2015; 172(3):301-7 [PubMed] Related Publications
DESIGN: The study was retrospective and multicentric.
METHODS: We collected data included in the Spanish Online National Database from patients with MEN2A carrying a RET proto-oncogene mutation on codon 634. The mean follow-up time was 7.6±6.9 years (1-32).
RESULTS: Patients (n=173) from 49 unrelated families were C634Y carriers, and 26 patients from eight different families had C634R mutation. We found higher penetrance of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (P<0.001, P=0.007 and P<0.001 respectively) in C634R carriers than in C634Y carriers. The Kaplan-Meier estimate of cumulative lymph node and distant metastases rates showed that these events occurred earlier in patients harbouring the C634R mutation (P<0.001). A multivariate adjusted Cox regression analysis indicated that the C634R mutation was an independent factor for persistent/recurrent disease (hazard ratio, 3.17; 95% CI: 1.66-6.03; P<0.001).
CONCLUSIONS: Our results suggest that there could be clinical differences caused by different amino acid substitutions at codon 634; specifically, the C634R mutation was associated with a more aggressive MEN2A phenotype than the C634Y mutation.
Preliminary whole-exome sequencing reveals mutations that imply common tumorigenicity pathways in multiple endocrine neoplasia type 1 patients.
Surgery. 2014; 156(6):1351-7; discussion 1357-8 [PubMed] Related Publications
METHODS: Whole-exome sequencing was performed on blood and tissue from HPT patients (MEN1 and sporadic) and somatic single nucleotide variants (SNVs) were identified. Stop-gain and stop-loss SNVs were analyzed with Ingenuity Pathways Analysis (IPA). Loss of heterozygosity (LOH) was also assessed.
RESULTS: Sequencing was performed on 4 MEN1 and 10 sporadic cases. Eighteen stop-gain/stop-loss SNV mutations were identified in 3 MEN1 patients. One complex network was identified on IPA: Cellular function and maintenance, tumor morphology, and cardiovascular disease (IPA score = 49). A nonsynonymous SNV of TP53 (lysine-to-glutamic acid change at codon 81) identified in a MEN1 patient was suggested to be a driver mutation (Cancer-specific High-throughput Annotation of Somatic Mutations; P = .002). All MEN1 and 3/10 sporadic specimens demonstrated LOH of chromosome 11.
CONCLUSION: Whole-exome sequencing revealed somatic mutations in MEN1 associated with a single tumorigenic network, whereas sporadic pathogenesis seemed to be more diverse. A somatic TP53 mutation was also identified. LOH of chromosome 11 was seen in all MEN1 and 3 of 10 sporadic patients.
Multiple endocrine neoplasia type 2B: maxillofacial significance in 5 cases.
J Oral Maxillofac Surg. 2014; 72(12):2498.e1-17 [PubMed] Related Publications
PATIENTS AND METHODS: The findings in five individuals with confirmed diagnoses of MEN2B are arranged to demonstrate the various manifestations of the disorder, and together represent the largest single group in the oral and maxillofacial surgery literature to date.
RESULTS: Tabulation of the patients' individual findings demonstrates the variants and severity of the disorder, discloses findings not previously emphasized in the literature, and stresses the significance of early recognition of medullary thyroid carcinoma.
CONCLUSION: The evidence in this study group suggests that the oral mucosal lesions are more commonly neurofibromas than neuromas as previously reported, that the characteristic dental central diastemas may occur independent of tongue size or the presence of oral soft tissue lesions, and that the characteristic apertognathia potentially requires surgical correction.
Metastasectomy of neuroendocrine tumors in patients with multiple endocrine neoplasia type 1.
Am J Surg. 2014; 208(6):1047-53; discussion 1052-3 [PubMed] Related Publications
METHODS: A review of MEN1 patients undergoing surgery for NE tumors from 1994 to 2010 at a single tertiary care center was performed. Tumor function, the extent of metastasis, R0 resection, and survival were analyzed.
RESULTS: We identified 30 patients who underwent resection including synchronous and metachronous metastasectomy. Synchronous metastases were identified in 19 patients (63%), whereas 11 (37%) had metachronous disease. R0 resection was achieved in 93% of patients. Estimated 10-year survival is 86.4% (95% confidence interval, 60% to 100%) with no factors predictive of overall survival. The disease-free interval at 1, 5, and 10 years was 89%, 50%, and 19%, respectively, with recurrence occurring at a median of 5.4 years (95% confidence interval, 77.7% to 100%). Synchronous metastasis (P = .0072; hazard ratio [HR], 3.4) and nonfunctioning tumors (P = .014; HR, 3.3) were more likely to recur, whereas age (P = .09; HR, 1.5), gender (P = .49; HR, 1.3), and the site of metastasis (P = .81; HR, 1.1) did not influence recurrence.
DISCUSSION: Patients with MEN1 benefit from resection of metastatic NE disease. Despite a high recurrence rate, survival and disease-free interval is favorable vs patients without MEN1.
Adrenal medullary hyperplasia is a precursor lesion for pheochromocytoma in MEN2 syndrome.
Neoplasia. 2014; 16(10):868-73 [PubMed] Free Access to Full Article Related Publications
Safety and efficacy of percutaneous parathyroid ethanol ablation in patients with recurrent primary hyperparathyroidism and multiple endocrine neoplasia type 1.
J Clin Endocrinol Metab. 2015; 100(1):E87-90 [PubMed] Related Publications
OBJECTIVE: This study sought to evaluate the safety and efficacy of percutaneous ethanol ablation (PEA) for the treatment of recurrent PHP in patients with MEN1. DESIGN, SETTING, PATIENTS, INTERVENTION, OUTCOME MEASURED: We performed an electronic search to identify patients with a billing code for MEN1 who were seen at Mayo Clinic between 1977 and 2013. Patients with recurrent PHP who underwent PEA were identified and their clinical information was collected. We performed t test analyses to compare mean values.
RESULTS: Thirty-seven patients underwent 80 PEA treatments that included 123 sessions of ethanol administration. Twenty-one patients were women (56.8%) and the mean age at diagnosis of PHP was 33.8 years. The mean preprocedure calcium level was 10.7 mg/dl ± 0.57 (SD) and the mean postprocedure calcium level was 9.6 mg/dl ± 0.76 (P < .01). In 14 treatments (18.9%) the postprocedure calcium was greater than 10.1 mg/dl. Postprocedure hypocalcemia occurred in six treatments (8.1%). Normocalcemia was achieved in 54 of the treatment episodes (73%) and the mean duration of normocalcemia was 24.8 months. PEA was safe with transient hoarseness occurring in four of the treatments (5%).
CONCLUSION: The treatment of recurrent PHP in patients with MEN1 represents a challenge that is associated with increased morbidity. PEA is an effective treatment option for achieving normocalcemia in the majority of the patients with MEN1. PEA is associated with low rates of hypocalcemia and no permanent complications.
A newly identified missense mutation in RET codon 666 is associated with the development of medullary thyroid carcinoma.
Endocr J. 2014; 61(11):1141-4 [PubMed] Related Publications
Mixed medullary-papillary carcinoma of the thyroid: report of two cases and review of the literature.
Indian J Pathol Microbiol. 2014 Oct-Dec; 57(4):598-602 [PubMed] Related Publications
A randomized, prospective trial of operative treatments for hyperparathyroidism in patients with multiple endocrine neoplasia type 1.
Surgery. 2014; 156(6):1326-34; discussion 1334-5 [PubMed] Related Publications
METHODS: Patients were assigned randomly to either SP or TP/AT and data were collected prospectively. The rates of persistent HPT, recurrent HPT, and postoperative hypoparathyroidism were compared.
RESULTS: The study cohort included 32 patients randomized to receive either SP or TP/AT (mean follow-up, 7.5 ± 5.7 years). The overall rate of recurrent HPT was 19% (6/32). Recurrent HPT occurred in 4 of 17 patients (24%) treated with SP and 2 of 15 patients (13%) treated with TP/AT (P = .66). Permanent hypoparathyroidism occurred in 3 of 32 patients (9%) overall. The rate of permanent hypoparathyroidism was 12% in the SP group (2/17) and 7% in the TP/AT group (1/15). A second operation was performed in 4 of 17 patients initially treated with SP (24%), compared with 1 of 15 patients undergoing TP/AT (7%; P = .34).
CONCLUSION: This randomized trial of SP and TP/AT in patients with MEN 1 failed to show any difference in outcomes when comparing results of SP versus TP/AT. Both procedures are associated with acceptable results, but SP may have advantages in that is involves only 1 surgical incision and avoids an obligate period of transient postoperative hypoparathyroidism.
Incidental angiofibromas prompt a diagnosis of multiple endocrine neoplasia type-1 (MEN-1).
Dermatol Online J. 2014; 20(9) [PubMed] Related Publications
OBSERVATIONS: The patient is a 28-year-old man who was referred to the dermatology department for evaluation and removal of skins lesions, later confirmed by biopsy to be facial angiofibromas and a truncal collagenoma. This combination of cutaneous findings was suspicious for a genodermatosis and genetic testing subsequently confirmed the diagnosis of MEN-1. The patient was referred for appropriate follow up and surveillance.
CONCLUSIONS AND RELEVANCE: This case highlights the importance of vigilance on the part of dermatologists to be aware of subtle skin findings that may be characteristic of rare disorders and may have gone unrecognized by other providers and the patients themselves. In this respect, dermatologists are in a unique position given their specialized training in the recognition of inherited skin disorders. An early diagnosis of an inherited disorder, especially one with increased risk of malignancy, can allow for appropriate surveillance and potentially alter the course of the disease.
Endocrine cancer syndromes: an update.
Minerva Pediatr. 2014; 66(6):533-47 [PubMed] Related Publications
Medullary thyroid carcinoma in children.
Endocr Dev. 2014; 26:202-13 [PubMed] Related Publications
Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with MEN1 mutations affecting the CHES1 interacting MENIN domain.
J Clin Endocrinol Metab. 2014; 99(11):E2387-91 [PubMed] Related Publications
OBJECTIVE: The objective of the study was the evaluation of an association between MEN1 mutations in different interacting domains of Menin and the phenotype of pNENs.
DESIGN: This was a retrospective analysis of a prospectively collected cohort of 71 genetically confirmed MEN1 patients at a tertiary referral center.
MAIN OUTCOME MEASURES: Analysis of patients' characteristics and clinical phenotype of pNENs regarding the mutation type and its location in Menin interacting domains was measured.
RESULTS: Sixty-seven patients (93%) developed pNENs after a median follow-up of 134 months. Patients with mutations leading to loss of interaction (LOI) with the checkpoint kinase 1 (CHES1) interacting domain codons (428-610) compared with patients with mutations resulting in LOI with other domains (eg, JunD, Smad3) had significantly higher rates of functioning pNENs (70% vs 34%), malignant pNENs (59% vs 16%), and aggressive pNENs (37% vs 9%), respectively. Patients with CHES1-LOI also had an increased pNEN-related mortality (20% vs 4.5%). Neither gender, age, nor the ABO blood types were associated with the phenotype of pNENs.
CONCLUSIONS: MEN1 patients with MEN1 mutations leading to CHES1-LOI have a higher risk of malignant pNENs with an aggressive course of disease and disease-related death.
Menin immunoreactivity in secretory granules of human pancreatic islet cells.
Appl Immunohistochem Mol Morphol. 2014 Nov-Dec; 22(10):748-55 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
An esophageal gastrointestinal stromal tumor in a patient with MEN1-related pancreatic gastrinoma: an unusual association and review of the literature.
J Cancer Res Ther. 2014 Apr-Jun; 10(2):443-5 [PubMed] Related Publications
p.Ala541Thr variant of MEN1 gene: a non deleterious polymorphism or a pathogenic mutation?
Ann Endocrinol (Paris). 2014; 75(3):133-40 [PubMed] Related Publications
OBJECTIVE: The aim of this study was to evaluate the pathogenic influence of the p.Ala541Thr variant on clinical and functional outcomes.
PATIENTS AND METHODS: We analysed a series of 55 index patients carrying the p.Ala541Thr variant. Their clinical profile was compared to that of 117 MEN1 patients. The biological impact of the p.Ala541Thr variant on cell growth was additionally investigated on menin-deficient Leydig cell tumour (LCT)10 cells generated from Men1+/Men1- heterozygous knock-out mice, and compared with wild type (WT).
RESULTS: The mean age at first appearance of endocrine lesions was similar in both p.Ala541Thr carriers and MEN1 patients, but no p.Ala541Thr patient had more than one cardinal MEN1 lesion at initial diagnosis. A second MEN1 lesion was diagnosed in 13% of MEN1 patients and in 7% of p.Ala541Thr carriers in the year following preliminary diagnosis. Functional studies on LCT10 cells showed that overexpression of the p.Ala541Thr variant did not inhibit cell growth, which is in direct contrast to results obtained from investigation of WT menin protein.
CONCLUSION: Taken together, these data raise the question of a potential pathogenicity of the p.Ala541Thr missense variant of menin that commonly occurs within the general population. Additional studies are required to investigate whether it may be involved in a low-penetrance MEN1 phenotype.
The association between Hirschsprung's disease and multiple endocrine neoplasia type 2a: a systematic review.
Pediatr Surg Int. 2014; 30(8):751-6 [PubMed] Related Publications
METHODS: A systematic literature-based search for relevant articles was conducted using three online databases. After exclusion of ineligible publications, we recorded data on all patients with a diagnosis of HSCR or MEN2A with a "Janus" RET mutation, as well as those who carried the mutation but were unaffected. Statistical analysis was performed using SPSS.
RESULTS: The literature search yielded 885 publications, of which 36 articles, incorporating data on 341 individuals, were eligible for inclusion in the final analysis. Co-occurrence of HSCR and MEN2A was recorded in 84 cases (24.6 %). HSCR occurred alone in 64 carriers of a "Janus" mutation (18.8 %) and MEN2A occurred in isolation in 173 cases (50.7 %). Twenty individuals (5.9 %) were found to carry a "Janus" mutation after screening on the basis of family history but were unaffected by either MEN2A or HSCR. The most common mutation recorded was the C620 mutation [114 cases (48.1 %)]. There was a relatively high incidence of long-segment aganglionosis (29.3 %) and total colonic aganglionosis (17.3 %) in this cohort. This trend was particularly notable in those with C620 mutations, only 33 % of whom had short-segment disease.
CONCLUSION: While the overall incidence of HSCR co-occurring with MEN2A is low, both conditions occur with a relatively high frequency in families with a RET mutation at exon 10. The proportion of cases of long-segment HSCR and total colonic aganglionosis is higher than that in the general population with HSCR in those with C620 and C618 mutations. These findings reinforce the importance of RET mutation testing in HSCR when a family history of either HSCR or MEN2 is present. In families with MEN2A and known exon 10 RET mutations, the threshold for investigation for HSCR in those with gastrointestinal symptoms should be very low. High-quality prospective longitudinal studies of large HSCR populations are required to shed greater light on this rare but important phenomenon.
Diagnostic correlation between RET proto-oncogene mutation, imaging techniques, biochemical markers and morphological examination in MEN2A syndrome: case report and literature review.
Rom J Morphol Embryol. 2014; 55(2):389-400 [PubMed] Related Publications
Multiple endocrine neoplasia (MEN) syndromes.
Semin Pediatr Surg. 2014; 23(2):96-101 [PubMed] Related Publications
Association between the p27 rs2066827 variant and tumor multiplicity in patients harboring MEN1 germline mutations.
Eur J Endocrinol. 2014; 171(3):335-42 [PubMed] Related Publications
DESIGN: As the CDKN1B (p27) gene causes MEN4 syndrome and it is transcriptionally regulated by the product of the MEN1 gene (menin), we sought to analyze whether p27 influences the phenotype of MEN1-mutated patients. The cohort consisted of 100 patients carrying germline MEN1 gene mutations and 855 population-matched control individuals.
METHODS: Genotyping of the coding p27 c.326T>G (V109G) variant was performed by sequencing and restriction site digestion, and the genotypes were associated with clinical parameters by calculating odds ratios (ORs) and their 95% CIs using logistic regression.
RESULTS: There were significant differences in p27 V109G allele frequencies between controls and MEN1-mutated patients (OR=2.55, P=0.019, CI=1.013-5.76). Among patients who are ≥30 years old carrying truncating MEN1 mutations, the T allele was strongly associated with susceptibility to tumors in multiple glands (three to four glands affected vs one to two glands affected; OR=18.33; P=0.002, CI=2.88-16.41). This finding remained significant after the Bonferroni's multiple testing correction, indicating a robust association. No correlations were observed with the development of MEN1-related tumors such as hyperparathyroidism, pituitary adenomas, and enteropancreatic and adrenocortical tumors.
CONCLUSIONS: Our study suggests that the p27 tumor suppressor gene acts as a disease modifier for the MEN1 syndrome associated with MEN1 germline mutations. If confirmed in independent patient cohorts, this finding could facilitate the management of this clinically complex disease.
Multiple endocrine neoplasia type IIa associated with Cushing's syndrome.
Arch Iran Med. 2014; 17(6):451-4 [PubMed] Related Publications
Natural course and survival of neuroendocrine tumors of thymus and lung in MEN1 patients.
J Clin Endocrinol Metab. 2014; 99(9):3325-33 [PubMed] Related Publications
OBJECTIVE: Our objective was to assess prevalence, tumor growth, and survival of Th and lung NETs in an unselected MEN1 population with long-term follow-up.
DESIGN: This was an observational study.
PATIENTS AND METHODS: A longitudinal study was performed using the Dutch national MEN1 database, including >90% of the Dutch MEN1 population >16 years of age. Patients under care of the Dutch University Medical Centers (1990-2011) (n = 323) were included.
MAIN OUTCOME MEASURES: The prevalence and survival of Th and lung NETs were assessed. Linear mixed-models analysis was applied to assess tumor growth with age as a possible confounder and gender, genotype and baseline tumor size as possible effect modifiers.
RESULTS: Th NETs occurred in 3.4% of patients, almost exclusively in males with a 10-year survival of 25% (95% confidence interval = 8%-80%). A thoracic computed tomography scan was available in 188 patients (58.2%). A lung NET was identified in 42 patients (13.0%) with a 10-year survival of 71.1% (95% confidence interval = 51%-100%). Tumor volume of lung NETs increased 17% per year (P < .001) (tumor doubling time 4.5 years). Tumor doubling time in males was 2.5 vs 5.5 years in females (P = .05). Lung NET growth was not associated with genotype or with baseline tumor size (<1 vs ≥1 cm).
CONCLUSION: In MEN1 patients, Th NETs almost exclusively occurred in males and had a very low prevalence and a high mortality. Lung NETs occurred more often than previously thought, had an indolent course, and occurred equally in both sexes. Tumor growth in males was double compared with female patients.
Cognitive behavioural therapy for depression in multiple endocrine neoplasia type IIB: a 1-year follow-up.
BMJ Case Rep. 2014; 2014 [PubMed] Related Publications
Diagnosis and preoperative imaging of multiple endocrine neoplasia type 2: current status and future directions.
Clin Endocrinol (Oxf). 2014; 81(3):317-28 [PubMed] Related Publications
Sarcomatoid carcinoma of the kidney in a MEN1 patient: case report and genetic profile.
Endocr J. 2014; 61(8):781-7 [PubMed] Related Publications
Ectopic Cushing syndrome secondary to metastatic medullary thyroid cancer in a child with multiple endocrine neoplasia syndrome type 2B: clues to early diagnosis of the paraneoplastic syndromes.
J Pediatr Endocrinol Metab. 2014; 27(9-10):993-6 [PubMed] Related Publications
The rare intracellular RET mutation p.S891A in a Chinese Han family with familial medullary thyroid carcinoma.
J Biosci. 2014; 39(3):505-12 [PubMed] Related Publications