scholarly journals The RET C611Y mutation causes MEN 2A and associated cutaneous lichen amyloidosis

2018 ◽  
Vol 7 (9) ◽  
pp. 998-1005 ◽  
Author(s):  
Xiao-Ping Qi ◽  
Jian-Zhong Peng ◽  
Xiao-Wei Yang ◽  
Zhi-Lie Cao ◽  
Xiu-Hua Yu ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia Type ◽  
Elevated Serum ◽  
Hirschsprung Disease ◽  
Skin Lesions ◽  
Normal Serum ◽  
Serum Calcitonin ◽  
Cutaneous Lichen Amyloidosis ◽  
Interscapular Region ◽  
Scapular Region ◽  
Men 2A

Background Cutaneous lichen amyloidosis (CLA) has been reported in some multiple endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical manifestation in ‘MEN 2A with CLA’, one of four variants of MEN 2A, which was strictly located in the scapular region of the upper back. Patient Findings This study reports a large south-eastern Chinese pedigree with 17 individuals carrying the MEN 2A-harboring germline C611Y (c.1832G>A) RET mutation by Sanger sequencing. One individual presented MEN 2A-related clinical features, including typical CLA in the interscapular region; another individual exhibited neurological pruritus and scratching in the upper back but lacked CLA skin lesions. Both subjects presented with CLA or pruritic symptoms several years before the onset of medullary thyroid carcinoma (MTC) and/or pheochromocytoma. The remaining 15 RET mutation carriers did not exhibit CLA; of these, one presented with MTC and pheochromocytoma, nine with MTC only, two with elevated serum calcitonin and three younger subjects with normal serum calcitonin levels. This family’s clinical data revealed a later diagnosis of MTC (mean age, 45.9 (range: 23–73) years), a lower penetrance of pheochromocytoma (2/17, 11.8%) and CLA (1/17, 5.9%). However, no hyperparathyroidism and Hirschsprung disease were reported in this family. Summary and Conclusions This is the first description of a family with MEN 2A-related CLA due to a germline RET C611Y mutation, which might exhibit a novel and diversified genotype–phenotype spectrum in MEN 2A.

scholarly journals Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634)

2014 ◽  
Vol 142 (1-2) ◽  
pp. 72-74 ◽  
Author(s):  
Maja Jesic ◽  
Milina Tancic-Gajic ◽  
Milos Jesic ◽  
Vladan Zivaljevic ◽  
Silvija Sajic ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Prophylactic Thyroidectomy ◽  
Urinary Catecholamines ◽  
Serum Calcitonin ◽  
Long Term Outcome ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2A

Introduction. The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. Case Outline. This is a case report of 3-year-old boy from the MEN 2A family (the boy?s father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is <2 pg/ml (normal <13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Conclusion. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

Hepatitis G Viral RNA in Serum and in Peripheral Blood Mononuclear Cells and Its Relation to HCV-RNA in Patients with Clotting Disorders

1997 ◽  
Vol 77 (05) ◽  
pp. 0868-0872 ◽  
Author(s):  
Li Sheng ◽  
Ann Soumillion ◽  
Kathelijne Peerlinck ◽  
Chris Verslype ◽  
Lan Lin ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Elevated Serum ◽  
Normal Serum ◽  
Hcv Rna ◽  
Peripheral Blood Mononuclear ◽  
Hepatitis G Virus ◽  
Blood Mononuclear Cells ◽  
Hepatitis G

SummaryThe hepatitis G virus (HGV) has recently been identified as a new member of the Flaviviridae family. Infection by this virus is thought to be associated with blood borne hepatitis. In this study, the presence of HCV- and HGV-RNAs in serum or plasma (175 patients) and in peripheral blood mononuclear cells (PBMC) (133 patients) was investigated in patients with clotting disorders using a sensitive reverse transcriptase polymerase chain reaction (RT-PCR). HGV-RNA was detected in serum of 26 patients (14.8%). In apparently healthy blood donors, serum HGV-RNA was detected in 4 of 358 individuals investigated (1.12%). Ninety two percent of the 26 serum HGV-RNA positive patients had coinfection with the hepatitis C virus (HGV), especially with HCV genotype lb, the most common genotype in Belgium. Of these coinfected patients, 15 (62.5%) showed elevated serum ALT levels. Two patients who were solely infected with HGV had normal serum ALT. HGV-RNA in PBMC was found in 18 patients, of whom 3 were negative for serum HGV-RNA. As in case of HCV, HGV-RNA in PBMC is preferentially sensitive to interferon treatment. Nevertheless, rapid reappearance of HGV-RNA in PBMC was observed after cessation of treatment. In one patient, persistent serum ALT elevation seems to be associated with continued HGV viremia, despite the disappearance of serum HCV-RNA.

Molecular diagnosis and treatment of multiple endocrine neoplasia type 2B in Ethnic Han Chinese

2020 ◽  
Vol 20 ◽  
Author(s):  
Zhe-Wei Zhang ◽  
Xiao Guo ◽  
Xiao-Ping Qi
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Histopathological Examination ◽  
Diagnosis And Treatment ◽  
De Novo Mutation ◽  
Neck Lymph Node ◽  
Serum Calcitonin ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2B

Background: Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and non-endocrine features. However, the diagnosis and treatment are usually delayed. Materials & Methods: This study reports 5 Chinese pedigrees with 5 individuals harboring germline RET-M918T, and systematically reviewed previous Chinese literatures. Results: All 5 patients initially presented MTC, but none had biochemically cured postoperatively. 2 also presented bilateral PHEO after adrenal-sparing surgery, 1 needed steroid replacement. Further, totally 32 MEN 2B patients from literatures were clustered with 28 available for analysis. 26 (92.8%) were diagnosed by endocrine-related symptoms; the remaining 2 (7.2%) due to RET testing and oral symptoms respectively. 25 patients underwent thyroidectomy with/without neck lymph node dissection at mean age of (23.3 ± 10.4) years. Histopathological examination revealed MTC (100%). Of them, 17 had definite TNM stage, with 1 in stage Ⅲ and others in Ⅳ. Other information of MEN 2B-related symptoms included penetrance of PHEO (60.7%), constipation (32.1%), Hirschsprung disease (25%), alacrima (17.8%), mucosal ganglioneuroma (96.4%) and marfanoid habitus (71.4%). 19 patients were verified harboring RET-M918T (c.2753T>C), of whom 15 (78.9%) were de novo mutation. The other 9 were clinically diagnosed as MEN 2B. Discussion & Conclusion : The initial diagnosis of MEN 2B is relatively later, and diagnosed by non-endocrine components is extremely lower. Recognition of MEN 2B and its non-endocrine-related components is still the utmost requirement for a Chinese physician. Combined RET screening and serum calcitonin detection can facilitate early diagnosis.

scholarly journals POS0826 SKIN LIMITED IGA VASCULITIS IN ADULTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 666.1-666
Author(s):  
A. Hočevar ◽  
J. Ostrovrsnik ◽  
K. Perdan-Pirkmajer ◽  
M. Tomsic ◽  
Z. Rotar
Keyword(s):  
Clinical Characteristics ◽  
Systemic Disease ◽  
Elevated Serum ◽  
Skin Lesions ◽  
Current Smoker ◽  
P Value ◽  
Symptom Duration ◽  
Iga Vasculitis ◽  
Reactive Protein

Background:IgA vasculitis (IgAV) could be limited to skin or evolve into a systemic disease, affecting characteristically joints, gastrointestinal tract and/or kidneys.Objectives:We aimed to look for differences between adult IgAV patients with disease limited to skin compared to systemic IgAV.Methods:Medical records of histologically proven adult IgAV cases, diagnosed between January 2010 and December 2020 at our secondary/tertiary rheumatology centre were analyzed.Results:During the 132-month observation period we identified 328 new IgAV cases (59.5% males, median (IQR) age 64.3 (45.1; 76.1) years). Ninety-four (40.2%) patients had skin limited disease, and the rest systemic IgAV.Clinical differences between skin limited and systemic adult IgAV are presented in table 1. Adults with IgAV limited to skin were significantly older, had less commonly skin lesions above the waistline and a lower level of C reactive protein compared to patients with a systemic disease. There were no differences in the frequency of skin necroses between the compared IgAV subgroups. The frequency of potential vasculitis triggers (prior infections, new medications, malignancy) was similar between the compared subgroups.Table 1.Clinical characteristics of IgA vasculitis patients with skin limited and systemic diseaseClinical characteristicsSkin limited IgAV (94)Systemic IgAV (234)P valueMale gender (%)54.361.50.263Age (years)*68.0 (55.0-80.5)61.5 (41.7-75.8)0.007Current smoker (%)13.821.80.123Antecedent infection (%)28.733.80.434New medication23.423.51.0History of cancer12.810.70.569Symptom duration (days)*7 (5-21)8 (5-14)0.756Purpura above waistline36.255.60.002Skin necroses (%)52.145.70.329ESR /mm/h) *32 (18-52)34 (17-53)0.873CRP (g/l) *13.5 (1-32)30 (11-68)<0.001Elevated serum IgA (%)50.649.10.892Legend: * median and IQR;Follow up data were available for 250 (76.2%) patients. During the follow up of median (IQR) 12.5 (6.8 – 22.4) months 35 patients relapsed (13/70 (18.6%) with skin limited IgAV and 22/180 (12.2%) with systemic IgAV, p= 0.224).Conclusion:Skin limited IgAV was associated with older age and less extensive skin puprura in adults. However, relapses of purpura were as common as in systemic IgAV.Disclosure of Interests:None declared

scholarly journals Usefulness of preoperative serum calcitonin in patients with nodular thyroid disease without suspicious history or cytology for medullary thyroid carcinoma

2013 ◽  
Vol 57 (4) ◽  
pp. 312-316 ◽  
Author(s):  
Pedro Weslley Rosário ◽  
Gustavo Cancela Penna ◽  
Kamilla Brandão ◽  
Bárbara Érika Souza
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Serum Calcitonin ◽  
Medullary Thyroid ◽  
Endocrine Neoplasia ◽  
Preoperative Serum ◽  
History Of

OBJECTIVE: To evaluate the usefulness of preoperative serum calcitonin (sCT) in patients with nodular disease without suspicion of medullary thyroid carcinoma (MTC) in history or cytology. PATIENTS AND METHODS: sCT was measured before thyroidectomy in 494 patients with nodular disease who had no family history of MTC or multiple endocrine neoplasia type 2, and no cytological suspicion of MTC. RESULTS: Basal sCT was < 10 ng/mL in 482 patients and none of them had MTC. One patient with basal sCT > 100 pg/mL had MTC. Among the 11 patients with basal sCT between 10 and 100 pg/mL, MTC was diagnosed in only one. The two patients with MTC were submitted to total thyroidectomy, combined with elective lymph node dissection indicated exclusively based on hypercalcitoninemia, and sCT was undetectable after six months. CONCLUSIONS: Preoperative sCT is useful for the detection of sporadic MTC in patients with nodular disease, even in the absence of suspicious history or cytology.

scholarly journals Surgical approach to medullary thyroid cancer

2007 ◽  
Vol 51 (5) ◽  
pp. 818-824 ◽  
Author(s):  
Catharina Ihre Lundgren ◽  
Leigh Delbridg ◽  
Diana Learoyd ◽  
Bruce Robinson
Keyword(s):  
Thyroid Cancer ◽  
Total Thyroidectomy ◽  
Medullary Thyroid Cancer ◽  
Prophylactic Surgery ◽  
Surgical Removal ◽  
Serum Calcitonin ◽  
Medullary Thyroid ◽  
Central Lymph Node Dissection ◽  
Familial Form ◽  
Men 2A

Medullary thyroid cancer (MTC) compromises 3-5% of all thyroid cancers and arises from parafollicular or calcitonin-producing C cells. It may be sporadic (75% of cases), or may occur as a manifestation of either the hereditary syndrome Multiple Endocrine Neoplasia type 2 (MEN 2A or MEN 2B) (25% of cases), or rarely as an isolated familial syndrome (FMTC). Complete surgical resection comprising in most cases total thyroidectomy with central lymph node dissection at an early stage of the disease is the only potential cure for MTC. The familial form of the disease, MEN-2A occupies a unique place in surgical history, having been the first disease where surgical removal of an affected organ was undertaken before the development of malignancy, solely on the basis of genetic testing. Total thyroidectomy prior to the development of invasive cancer completely avoids an otherwise lethal malignancy. Timing of prophylactic surgery is based on models that utilise genotype-phenotype correlations, which have now been stratified into three risk groups based on the specific codon involved. MTC should be followed with postoperative serial serum calcitonin levels to survey for persistent or recurrent disease as indicated by detectable levels. The challenge however, if calcitonin levels are increased, is to find the source of its production. The first localisation technique recommended would be ultrasound of the neck, since there is a high frequency of local recurrence and cervical node metastasis, followed by a total body CT scan and bone scintigraphy.

scholarly journals Normal levels of serum pancreatic enzymes in patients with progressive familial intrahepatic cholestasis type 2.

2010 ◽  
Vol 57 (4) ◽  
Author(s):  
Jaroslaw Walkowiak ◽  
Irena Jankowska ◽  
Aleksandra Lisowska ◽  
Maciej Biczysko ◽  
Aldona Wierzbicka ◽  
...  
Keyword(s):  
Intrahepatic Cholestasis ◽  
Elevated Serum ◽  
Normal Serum ◽  
Pancreatic Enzymes ◽  
Serum Lipase ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Elastase 1 ◽  
Pancreatic Damage ◽  
High Prevalence

High prevalence of elevated serum pancreatic enzymes in children with cholestasis with normal fecal elastase-1 concentrations has been documented. However, this state is related predominantly to biliary atresia. Therefore, we aimed to assess pancreatic damage by measuring serum pancreatic enzymes in patients with progressive familial intrahepatic cholestasis type 2 (PFIC type 2). Twenty PFIC type 2 patients with normal serum bilirubin and bile acid concentrations were included in the study. Thirty pancreatic insufficient cystic fibrosis (PI-CF) patients, thirty patients with acute pancreatitis (AP) and thirty healthy subjects (HS) served for the purpose of comparison. In all subjects, serum lipase and elastase-1 levels were measured. In all but one PFIC type 2 patients and all HS normal lipase activities were found. Serum elastase-1 concentrations were normal in all PFIC type 2 patients and HS. The enzyme levels were very similar in both groups studied. Lipase activities in PFIC type 2 patients were significantly higher than in PI-CF patients (p < 0.00001) and lower than in patients with AP (p < 0.00001). Serum elastase-1 levels in PFIC type 2 patients were significantly lower than in patients with AP (p < 0.00001) and not different from those in PI-CF patients. In conclusion. serum pancreatic enzymes in patients with PFIC type 2 are normal. No pancreatic damage in these patients could be detected.

scholarly journals Hypophosphatemia Gene Panel Sponsored Program: A High Yield of Molecular Diagnoses from Clinically Confirmed XLH and Suspected Genetic Hypophosphatemia

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A263-A263
Author(s):  
Kathryn Dahir ◽  
Eric Rush ◽  
Daniel Beltran ◽  
Scott Eisenbeis ◽  
Britt Johnson ◽  
...  
Keyword(s):  
Copy Number ◽  
Diagnostic Yield ◽  
Elevated Serum ◽  
Clinical Signs ◽  
Normal Serum ◽  
Hypophosphatemic Rickets ◽  
High Yield ◽  
Molecular Diagnostic ◽  
Single Nucleotide Variants ◽  
Limb Deformity

Abstract X-linked hypophosphatemia (XLH), a dominant disorder caused by a disease-associated variant in the PHEX gene, affects males and females of all ages. Rickets and osteomalacia may be present along with short stature, lower limb deformity, muscle pain and/or weakness/fatigue, bone pain, joint pain/stiffness, hearing difficulty, enthesopathy, osteoarthritis, and dental abscesses. Patients with XLH have below-normal serum phosphate and elevated serum FGF23. XLH is one of multiple etiologies of hypophosphatemia; depending on genetic cause, management may differ. Acquired hypophosphatemia (e.g. tumor induced osteomalacia) is non-hereditary in nature. This program provides a no-charge genetic test to confirm a clinical XLH diagnosis or to aid suspected genetic hypophosphatemia diagnosis. Patients aged &gt;/= 6 months with either a clinical XLH diagnosis or suspicion of genetic hypophosphatemia, as evidenced by 2 or more clinical signs/ symptoms, were eligible for testing. The next generation sequencing panel includes 13 genes: ALPL, CLCN5, CYP2R1, CYP27B1, DMP1, ENPP1, FAH, FAM20C, FGF23, FGFR1, PHEX, SLC34A3 and VDR. Copy number variant detection was performed. 831 unrelated individuals were tested as of June 30, 2020. 569 (68.5%) of these subjects had a PHEX variant: 519 (91.2%) were either pathogenic or likely pathogenic (P/LP) and 50 (8.8%) were variants of uncertain significance (VUS). Of the 312 (37.5%) cases where no PHEX molecular diagnosis was found, 38 (12.2%) had molecular diagnoses associated with other genes/disorders: 4 had a variant (P/LP) in FGF23 (autosomal dominant [AD] hypophosphatemic rickets), 2 had two variants (P/LP) in CYP27B1 (autosomal recessive [AR] vitamin D dependent rickets), 1 had P/LP variants in ENPP1 (AR hypophosphatemic rickets Type 2). There were 27 cases with single P or LP variants in ALPL (AD hypophosphatasia, HPP); 4 cases carried two variants (P/LP) in ALPL (AR form). Of 237 unique P/LP PHEX variants detected: 59 were deletions, duplications or insertions; 37 were copy number variants; 52 were splice-site variants; 89 were single nucleotide variants. Additional family member testing/clinical information resulted in 48 cases having VUS reclassified to P/LP, highlighting the value of cascade family testing/clinical info to resolve VUS. RNA analyses to resolve VUS may further improve molecular diagnostic yield. Program results demonstrate a high diagnostic yield for XLH/ genetic hypophosphatemia and new insight into XLH-associated PHEX variants.

Hypergonadotropism in Peripubertal Boys with Chronic Renal Failure

PEDIATRICS ◽  
1983 ◽  
Vol 72 (3) ◽  
pp. 384-389
Author(s):  
Harold K. Marder ◽  
Laxmi S. Srivastava ◽  
Stephen Burstein
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Elevated Serum ◽  
Serum Testosterone ◽  
Normal Serum ◽  
Adult Men ◽  
Testicular Dysfunction ◽  
Serum Luteinizing Hormone ◽  
Serum Lh ◽  
Serum Gonadotropin

Serum gonadotropin and testosterone concentrations were measured in ten peripubertal boys to assess the effects of uremia on pubertal maturation. Serum luteinizing hormone (LH) concentrations were elevated for stage of puberty in eight boys, whereas in most boys serum follicle-stimulating hormone and testosterone concentrations were normal. Serum LH concentrations correlated with the severity of uremia. LH levels declined when measured 1 year after the initial measurements in four boys who received renal allografts, but were further elevated in two boys who were treated conservatively. Elevated serum LH concentrations in the presence of normal serum testosterone concentrations imply limited testicular sensitivity to the effects of LH in these peripubertal boys, as has been documented for adult men with chronic renal failure. Alternatively, there may be accumulation of an immunoreactive LH molecule that lacks bioactivity. A testicular dysfunction may explain the pubertal delay experienced by some uremic adolescent boys.

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