Frank-Raue K.,Molecular Laboratory |
Haag C.,Molecular Laboratory |
Schulze E.,Molecular Laboratory |
Keuser R.,Endocrine Practice |
And 3 more authors.
European Journal of Endocrinology | Year: 2011
Objective: Hyperparathyroidism-jaw tumour (HPT-JT) syndrome is a rare autosomal dominant cause of benign and malignant parathyroid tumours, ossifying jaw tumours, various cystic and neoplastic renal abnormalities and benign and malignant uterine tumours. Disease-causing mutations have been localised in the tumour suppressor gene CDC73. There is limited information available on the mutations, and resulting phenotypes and long-term follow-up data are especially scarce. Design:We analysed the clinical data from 16 patients (including three families) carrying mutations in the CDC73 gene. We describe five new mutations/gene variants, the corresponding phenotypes of these carriers and the long-term follow-up. Methods: The 16 patients were evaluated at an endocrine outpatient clinic and at a surgical department. DNA samples were obtained for sequence analysis of the CDC73 gene. Results: Clinical features of HPT-JT syndrome were detected in 13 of the 15 carriers with germline CDC73 mutations. The major features were benign (n = 7; 47%) or cancerous (n = 3; 20%) HPT-JT was present in eight cases (53%). Most patients had severe hypercalcaemia, and median serum calcium levels were 3.36 mmol/l. A patient with non-secretory parathyroid carcinoma was included. HPT was diagnosed at a median age of 28.5 years. Mutational analysis of the CDC73 gene identified eight sequence changes, three of them have been reported previously, whereas five are novel: c.1346delG, c.88-94delTTCTCCT, the non-coding variants, c.307+5G>T and c.424-5T>C and c.*12C>A of unknown significance. Conclusions: This study significantly increases the information available on the mutations and phenotypes of HPT-JT syndrome. © 2011 European Society of Endocrinology. Source
Raue F.,Endocrine Practice |
Frank-Raue K.,Endokrinologische Gemeinschaftspraxis
Familial Cancer | Year: 2010
Multiple endocrine neoplasia type 2 (MEN2) is a autosomal dominat inherited tumour-syndrome caused by germline activating mutations of the RET proto-oncogene on chromosome 10. It is clinically characterized by the presence of medullary thyroid carcinoma (MTC), bilateral pheochromocytoma and primary hyperparathyroidism (MEN2A) within a single patient. Three distinct clinical forms have been described depending on the phenotype: the classical MEN 2A, MEN 2B, an association of MTC, pheochromocytoma and mucosal neuroma, (FMTC) familial MTC with a low incidence of other endocrinopathies. Each variant of MEN2 results from different RET gene mutation, with a good genotype phenotype correlation. Genetic testing detects nearly 100% of mutation carriers and is considered the standard of care for all first degree relatives of patients with newly diagnosed MTC. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on a classification into four risk levels utilizing the genotype-phenotype correlations. MEN 2 gives a unique model for early prevention and cure of cancer and for stratified roles of mutation-based diagnosis of carriers. © Springer Science+Business Media B.V. 2010. Source
Raue F.,Endocrine Practice and Molecular Laboratory |
Pichl J.,St Theresien Hospital |
Dorr H.-G.,University Hospital |
Schnabel D.,University Hospital Charite |
And 9 more authors.
Clinical Endocrinology | Year: 2011
Objective Autosomal dominant hypocalcaemia or hypoparathyroidism is caused by activating mutations of the calcium-sensing receptor (CaSR). Treatment with calcium and vitamin D often worsens hypercalciuria and nephrocalcinosis, and renal impairment can result. Our aim was to describe the phenotypic variance of this rare disorder in a large series and to evaluate the outcome after long-term treatment. Design Nationwide retrospective collaborative study. Patients We describe 25 patients (14 men and 11 women), 20 belonging to 11 families and five single cases. Measurements Activating CaSR mutations and clinical and biochemical findings were evaluated. Results Nine different missense mutations of the CaSR, including one novel variant (M734T), were found. Twelve patients (50%) were symptomatic, 9 (36%) had basal ganglia calcifications and 3 (12%) had nephrocalcinosis. Serum calcium was decreased (1·87 ± 0·13 mm), and PTH was decreased (n = 19) or inappropriately low (n = 4). The occurrence of hypocalcaemic symptoms at diagnosis was related to the degree of hypocalcaemia. The occurrence of features like calcification of basal ganglia or kidney calcification did not correlate with the severity of hypocalcaemia or the age at diagnosis. The most common treatment was calcitriol (median dosage 0·6 μg/day), and the mean duration of therapy was 7·1 years (max. 26 years). Hypercalcaemic episodes rarely occurred, and the rate of kidney calcifications was remarkably low (12%). Conclusion This series increases the limited knowledge of mutations and phenotypes of this rare disorder. Mutation analysis of the CaSR gene facilitates patient and family management. Low dosages of calcitriol resulted in less frequent renal calcifications. © 2011 Blackwell Publishing Ltd. Source
Honegger J.,University of Tubingen |
Buchfelder M.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Schlaffer S.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Droste M.,Endocrine Practice |
And 11 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015
Context: The best treatment of primary hypophysitis (PrHy) is a matter of debate. Objective: Our main objective was to analyze the treatment practice for PrHy in Germany and to compare the outcome of the main treatment options. Design: The Pituitary Working Group of the German Society of Endocrinology conducted a nationwide retrospective cross-sectional cohort study. Patients: Seventy-six patients with PrHy were eligible for the study. Main Outcome Measures: Clinical and endocrinological outcomes, side effects and complications of therapy, initial response, and recurrence rates were assessed. Outcome depending on the treatment modality was evaluated. Results: Formereobservation,regressionofspace-occupyinglesionswasobservedin46%,unchangedsize in 27%, and progression reported in 27%. Pituitary function improved in 27% of patients during observation. Deterioration of pituitary function was only found in patients with progressive lesions. The initial response to glucocorticoid pulse therapy was most favorable, with early failure in only 3%. However, the overall failure and recurrence rate was 41%. Recurrence rate was not related to duration of steroid administration. Side effects of steroids occurred in 63%. The surgical approach was transsphenoidal in 94%. The histological subtype was lymphocytic hypophysitis in 70% and granulomatous hypophysitis in 30%. Progression or recurrence was observed in 25% after surgical treatment. Conclusion: Glucocorticoid pulse therapy is associated with a high recurrence rate. Evidence suggests that surgery is not able to prevent recurrence. Considering the favorable results of observation, conservative management is recommended in PrHy unless symptoms are severe or progressive. Copyright © 2015 by the Endocrine Society. Source
Kratzsch J.,University of Leipzig |
Petzold A.,University of Leipzig |
Raue F.,Endocrine Practice |
Reinhardt W.,University of Duisburg - Essen |
And 10 more authors.
Clinical Chemistry | Year: 2011
BACKGROUND: Calcitonin (CT) is a sensitive marker for evaluation of medullary thyroid cancer (MTC). However, CT measurement can vary with assay- and nonassay-dependent factors, and procalcitonin (PCT) measurement has been proposed for evaluating questionable increases in CT. METHODS: We tested 2 fully automated CT assays (Immulite [IL] and Liaison [LIA]) and 1 nonautomated CT assay (IRMA, Medipan) and compared these results with PCT (Brahms Kryptor). We evaluated preanalytical conditions and PCT cross-reactivity in sera of 437 patients with clinical conditions associated with hypercalcitoninemia. Additionally, we determined the true "nil" CT concentration in 60 thyroidectomized patients and defined CT cutoff concentrations for pentagastrin stimulation testing in 13 chronic kidney disease (CKD) patients and 10 MTC patients. RESULTS: Markedly decreased CT concentrations were found after storage of sera for >2 h at room temperature and >6 h at 4°C. Cutoff concentrations for basal and stimulated CT were disease and assay dependent. Proton pump inhibitor therapy was the most frequent reason for increased CT. PCT concentrations were higher in patients with MTC than in patients with CKD without infections (P < 0.001). Whereas IL and LIA demonstrated comparable analytical quality, the IRMA gave increased CT concentrations in nil sera and showed cross-reactivity with PCT in patients with concomitant bacterial infection. CONCLUSIONS: IL, LIA, and IRMA detected increased CT concentrations in non-MTC patients and discriminated MTC from CKD patients in pentagastrin tests. PCT assessment may be helpful in the diagnostic work-up of increased CT concentrations in questionable clinical circumstances. © 2010 American Association for Clinical Chemistry. Source