Transition medicine aims at the coordinated transfer of young patients with a chronic disease from paediatric to adult care. The present study reflects 20 years of experience in transitioning patients with congenital adrenal hyperplasia (CAH) in a single center setting. Our endocrine transition-clinic was established in 2002 and offers joint paediatric and adult consultations. Data were evaluated retrospectively from 2002 to 2005 and 2008 to present. Fifty-nine patients (29 males) were transferred. Median age was 18.4 years (17.6-23.6). Ninety percent of the patients presented with 21-hydroxlase-deficiency (21-OHD), 38 patients (23 m) with salt-wasting (sw), 7 (1 m) with simple-virilising (sv) and 8 (3 m) with the non-classic (nc) form. Rarer enzyme deficiencies were found in 6 cases: 17 alpha-OHD (2 sisters), P450-oxidoreductase-deficiency (2 siblings), 3 beta-hydroxysteroid-dehydrogenase-deficiency (1 m) and 11 beta-OHD (1 female). Thirty-four patients (57.6%, 20 m) are presently still attending the adult clinic, 1 patient (1.7%, m) moved away and 24 (40.7%, 8 m) were lost to follow-up (13 sw-21-OHD, 6 sv-21-OHD, 5 nc-21-OHD). Thirty-seven patients (62.7%) attended the adult clinic for >2 years after transfer, 17 (28.8%) for >10 years. In the lost to follow-up group, median time of attendance was 16.3 months (0-195.2). Defining a successful transfer as two or more visits in the adult department after initial consultation in the transition clinic, transfer was efficient in 84.7% of the cases. A seamless transfer to adult care is essential for adolescents with CAH. It requires a continuous joint support during the transition period, remains challenging, and necessitates adequate funding.

Die Begriffe benignes und malignes Phäochromzytom sollten nicht mehr verwendet werden, da jedes Phäochromozytom das Potenzial zur Metastasierung in sich trägt. Man spricht von einem metastasierten Phäochromozytom oder Paragangliom. Bei Tumoren >5 cm sowie bei extraadrenaler Lokalisation steigt das Risiko metastasierter Formen wie auch bei postoperativ persistierendem Hypertonus. Zur Beurteilung des Metastasierungspotenzials können der PAS-Score und GAPP-Score eine einschätzende Beurteilung erlauben. Konventionelle Schnittbildgebung (CT/MRT) wird zur Umfelddiagnostik primär eingesetzt und kann durch eine [123I] MIBG-Szintigrafie und [124I] MIBG PET/CT ergänzt werden kann. Die chirurgische Resektion stellt den Goldstandard dar. Sollte der Befund nicht resektabel sein, so stehen [123I] MIBG oder radiomarkierte Somatostatin Analoga zur Verfügung. Die Chemotherapie ergänzt die Therapie im fortgeschrittenen Stadium und in therapierefraktären Situationen.

This article is written in remembrance of Karl Valentin's 70th anniversary of his death. He was a comedian and song writer suffering from vegetative dystonia and depression lifelong. This hypochondriac developed extreme self observation and had anxiety to get ill permanently. As one year old, his brother died of diphteria and he was close to death himself. After jumping in an ice cold river in Munich as a young man he caught a pneumonia. From that day he had a undefined long lasting lung disease. His performances and pieces of literature in Bavarian dialect are characterized by critical thoughts about the world in general and human vulnerability including his own in a philosophical way. His sarcastic view of the world, which was rarely pleasant for the counterpart still induced admiration of many audiences and was satisfying for Karl Valentin's egocentrism. He has been the most famous Bavarian comedian during world war II and during the early days of the Republic of Germany.

Patients with dedifferentiated and anaplastic thyroid carcinomas that do not take up radioiodine are resistant to chemotherapeutic treatment and external irradiation and thus are difficult to treat. Direct induction of apoptosis is a promising approach in these apoptosis-resistant tumor cells. The BH3 mimetic ABT-737 belongs to a new class of drugs that target anti-apoptotic proteins of the BCL-2 family and facilitate cell death. The purpose of this study was to investigate the effect of ABT-737 alone or in combination with chemotherapeutic drugs on thyroid carcinoma cell lines.

Zusammenfassung Die Diskussion darüber, welcher TSH-Wert die Grenze zur Hypo-thyreose markiert, ist noch im Gange. Eine Tendenz zu strengeren Schwellenwerten wird deutlich. Bereits die subklinische Hypothyreose soll künftig therapiert werden, wenn sie mit erhöhten TPO-Antikör-pern einhergeht, Kinderwunsch, Schwangerschaft oder Infertilität be-stehen oder der Patient über spezifische Symptome klagt.

High resting heart rate (RHR) predicts cardiovascular outcomes in patients with vascular disease and heart failure. We evaluated the prognostic value of RHR in a large contemporary population-based, prospective cohort of individuals without known coronary artery disease.

Endocrine disorders may have an important influence on fertility, the course of a pregnancy and fetal development. For example, fertility is decreased and the risk of miscarriage is increased in women with autoimmune disorders, such as Addison's disease or autoimmune thyroiditis. Treatment of endocrine diseases in many cases has to be adapted during the course of a pregnancy. In patients with Addison's disease the dosage of hydrocortisone necessarily has to be increased. This is also valid for the time of delivery. Disorders of the thyroid gland are of great importance during pregnancy. If hypothyroidism is diagnosed in early pregnancy, immediate treatment with levothyroxine should be initiated. Iodine supplementation is strongly recommended in all pregnant and breast-feeding women. Treatment of Graves's disease will be performed during the first trimenon with propylthiouracile, afterwards with methimazole (thiamazole). In contrast, thyrotoxicosis due to hCG should not be treated with methimazole. In this paper, we present an overview on the most important endocrine disorders during pregnancy.

This study aimed at investigating predicting factors for therapy response under growth hormone receptor antagonist therapy with a focus on subjective and patient-oriented measures.

The evasion of cell death is one of the hallmarks of cancer, contributing to both tumor progression and resistance to therapy. Dedifferentiated and anaplastic thyroid carcinomas that do not take up radioiodine are resistant to conventional anticancer treatments and patients with these tumors are difficult to treat. BH3 mimetics are a new class of drugs that target anti-apoptotic proteins of the BCL-2 family and promote cell death. The purpose of this study was to analyze the molecular effects of the BH3 mimetic GX15-070 on thyroid carcinoma cell lines and to characterize cell death induced by GX15-070.

Patients with dedifferentiated or anaplastic thyroid carcinomas currently lack appropriate treatment options. Kinase inhibitors are among the most promising new agents as alternative strategies. The BRAF- and multi-kinase inhibitor, sorafenib, has already shown antitumor effects in thyroid carcinoma patients in a phase III clinical trial. In this study we aim to better characterize molecular effects and efficacy of sorafenib against thyroid carcinoma cells with various histological origins and different BRAF mutational status. Analysis of different signaling pathways affected by sorafenib may contribute to assist a more specific therapy choice with fewer side effects. Twelve thyroid carcinoma cell lines derived from anaplastic, follicular and papillary thyroid carcinomas with wildtype or mutationally activated BRAF were treated with sorafenib. Growth inhibition, cell cycle arrest, cell death induction and inhibition of intracellular signaling pathways were then comprehensively analyzed.

BACKGROUND:The indirubin derivative 7-bromoindirubin-3'-oxime (7BIO) has already shown anticancer properties by causing cell death in some tumour cell lines and may be a new therapeutic option for treatment-resistant tumour cells. Since dedifferentiated and anaplastic thyroid carcinomas do not take up radioiodine and are insensitive to chemotherapeutic treatment and external radiation, direct cell death induction in these tumour cells may be a promising approach. We thus investigated the effect of 7BIO on thyroid carcinoma cell lines of different histological origins and characterized the type of cell death induction by 7BIO.METHODS:Cell viability was measured with MTT assay. Cell death was analysed by caspase 3/7 activity, lactate dehydrogenase liberation, caspase cleavage products, DNA fragmentation, cell cycle phase distribution and LC3B analysis.RESULTS:After 7BIO treatment, cell viability was reduced in all 14 thyroid carcinoma cell lines investigated. Treated cells showed DNA fragmentation, cell cycle arrest and lactate dehydrogenase liberation but no LC3B cleavage. Caspase activation following 7BIO treatment was found in five of six cell lines investigated. Interestingly, inhibition of caspases had no effect on viability of the cells after 7BIO incubation.CONCLUSIONS:Our results indicate that 7BIO efficiently killed dedifferentiated thyroid carcinoma cells. It induced a non-classical kind of cell death that was caspase-independent and includes DNA fragmentation. 7BIO and related indirubin components thus may have value as a new therapeutic option for dedifferentiated thyroid cancer irrespective of the exact target molecules and the kind of cell death they induce.

Background: Coronary artery calcium (CAC) indicates coronary atherosclerosis and can be present in very early stages of the disease. The conversion from no CAC to any CAC reflects an important step of the disease process as cardiovascular risk is increased in persons even with mildly elevated CAC. We sought to identify risk factors that determined incident CAC>0 in men and women from an unselected general population with a special focus on the role of smoking.Methods: All 4814 persons that were initially studied in the Heinz Nixdorf Recall Study were invited to participate in the follow-up examination after 5.1 +/- 0.3 years. All traditional Framingham risk factors were quantified using standard techniques. Smokers were categorized in never, former and present smokers. The CAC scores were measured from EBCT using the Agatston method.Results: Overall, out of 342 men and 919 women with zero CAC at baseline, 107 (31.3%) men and 210 (22.9%) women had CAC>0 at second examination. In multivariable analysis, age (OR estimate per 5 years: 1.34 (95% CI: 1.21-1.47)), LDL cholesterol (per 10 mg/dL: 1.05 (95% CI: 1.01-1.10)), systolic blood pressure (per 10 mmHg: 1.19 (95% CI: 1.11-1.28)) and current smoking (1.49 (95% CI: 1.04-2.15)) were independent predictors of CAC onset. The probability of CAC onset steadily increased with age from 23.3% (men) and 15.3% (women) at age 45-49 years to 66.7% (men) and 42.9% (women) at age 70-74 years. The difference in age-dependent conversion rates was quantified by years between reaching a given level of CAC onset probability. We found a consistent pattern with respect to smoking status: presently (formerly) smoking middle-aged men convert to positive CAC 10 (5) years earlier than never smokers, for women (middle-aged to elderly) this time span is 8 (5) years.Conclusion: Several traditional CVD risk factors are associated with CAC onset during 5 years follow-up. CAC onset is accelerated by approximately 10 (5) years for present (former) compared to never smokers. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Objective: Acromegaly is associated with an increased prevalence of glucose metabolism disorders. Clinically confirmed diabetes mellitus is observed in approximately one quarter of all patients with acromegaly and is known to have a worse prognosis in these patients.Design: Of 514 acromegalic patients treated with pegvisomant and recorded in the German Cohort of ACROSTUDY, 147 had concomitant diabetes mellitus. We analysed these patients in an observational study and compared patients with and without concomitant diabetes.Results: Under treatment with pegvisomant, patients with diabetes mellitus rarely achieved normalisation (64% in the diabetic cohort vs 75% in the non-diabetic cohort, P=0.04) for IGF1. Diabetic patients normalised for IGF1 required higher pegvisomant doses (18.9 vs 15.5 mg pegvisomant/day, P<0.01). Furthermore, those diabetic patients requiring insulin therapy showed a tendency towards requiring even higher pegvisomant doses to normalise IGF1 values than diabetic patients receiving only oral treatment (22.8 vs 17.2 mg pegvisomant/day, P=0.11).Conclusions: Hence, notable interdependences between the acromegaly, the glucose metabolism of predisposed patients and their treatment with pegvisomant were observed. Our data support recent findings suggesting that intra-portal insulin levels determine the GH receptor expression in the liver underlined by the fact that patients with concomitant diabetes mellitus, in particular those receiving insulin therapy, require higher pegvisomant doses to normalise IGF1. It is therefore important to analyse various therapy modalities to find out whether they influence the associated diabetes mellitus and/or whether the presence of diabetes mellitus influences the treatment results of an acromegaly therapy.

OBJECTIVE:Malignant phaeochromocytomas are rare and highly aggressive tumours. This retrospective study evaluated the outcome of combined chemotherapy with cyclophosphamide, vincristine and dacarbazine (also known as CVD regimen).METHODS:Patients with histologically and radiologically confirmed malignant phaeochromocytoma who were treated with the CVD regimen for progressive disease were retrospectively identified from chart review. Treatment cycles were usually repeated at 21-day intervals, with cyclophosphamide (750 mg/m(2) ), vincristine (1·4 mg/m(2) ) and dacarbazine (600 mg/m(2) ) on day 1, and dacarbazine only (600 mg/m(2) ) on day 2. The main outcome measures were best response during treatment and progression-free survival.RESULTS:Eight patients (4 males; median age 55·5 (range 31-77) years) with progressive disease underwent a median of 6 (range 3-11) cycles. Best treatment responses were as follows: partial response, n = 2 (25%); stable disease, n = 3 (38%); and progressive disease, n = 3 (38%). The median progression-free survival was 5·4 (range 2·5-26·8) months. After the initial administration of 6 cycles, two patients received a second course of chemotherapy with another 6 cycles after new progressive disease had been detected. Subsequently, these patients were progression-free for another 6·0 and 6·4 months. Mild gastrointestinal symptoms and fatigue were the most common adverse events.CONCLUSION:Although objective tumour response rates were lower than previously reported in small series, the CVD regimen allowed disease stabilization for a substantial period of time and may therefore be considered as a treatment option in advanced stages. To improve disease outcome, however, new therapeutic approaches and larger multicentre studies are needed.

BackgroundEarly identification of patients at risk for thoracic aortic aneurysm (TAA) has the potential of improving prognosis. So far, however, “normal” aortic dimensions are not well defined, rendering identification of patients with enlarged aortas difficult. In the present study we aimed to (1) establish age- and gender-specific distribution of thoracic aortic diameters and (2) to determine the prevalence of asymptomatic TAA in a population-based European cohort.MethodsDiameters of ascending thoracic aorta (ATA) and descending thoracic aorta (DTA) were measured from electron beam computed tomography (EBCT) scans of 4129 participants aged 45 to 75years from the Heinz Nixdorf Recall study. Age- and gender-specific percentiles were calculated for body-surface adjusted aortic diameters. Multivariable linear regression was used to evaluate the association between aortic diameters and cardiovascular risk factors including age, gender and body-surface area (BSA).ResultsAortic diameters were generally greater in the ATA than in the DTA, and were greater in men than in women (ATA: 3.71±0.4cm vs. 3.45±0.4cm, p<0.0001; DTA: 2.82±0.3cm vs. 2.54±0.3cm, p<0.0001). Age, male gender, blood pressure and body-surface area were independently associated with aortic diameters in both ATA and DTA. Based on our measurements age- and gender-specific percentiles for indexed ATA and DTA diameters were computed. Aneurysms≥5cm were found in 12 (0.34%) out of the total of 4129 subjects.ConclusionSince BSA was independently associated with increasing aortic diameters, correction of aortic diameters for BSA may be more helpful in order to reliably identify patients at risk for aneurysm formation. Based on the normal distribution of body-surface adjusted thoracic aortic diameters displayed in age- and gender-specific percentiles we suggest a cut-off point for aneurismal aortic diameter at the 95th percentile.

Background: Coronary atherosclerosis can be detected by computed tomography. The amount of coronary artery calcification (CAC) is related to cardiovascular risk factors, the strength of the gender specific relation between lipoprotein parameters and CAC has not extensively been studied. Especially, the role of routinely determined lipoproteins in contrast to less common and computed lipid parameters (e. g. ratios) remains to be clarified.Methods and results: The study cohort (n = 3956, 52% women, age 45-75 years) was randomly selected from three cities of a German metropolitan area. Lipoproteins-low-and high density lipoprotein (LDL-C/HDL-C), total cholesterol, apolipoprotein A-1 and B (apoA-1/apoB) as well as lipoprotein (a) (Lp(a)) were measured, while non-HDL-C was calculated. All participants received an electron-beam computed tomography (EBCT) for quantification of CAC. Adjusted for age and cardiovascular risk factors, CAC increased by a factor of 1.97 (1.51-2.57, 95% CI) and 1.94 (1.53-2.45, 95% CI) comparing the fourth to the first quartile of LDL-C for men and women, respectively. This association with LDL-C was also found after dichotomization of CAC at thresholds >0, >= 100 and >= 400. The best association of CAC was, however, found to be apoB and the second best was non HDL-C, in both men and women. For apoB, the model including all risk factors reached an explained variance for CAC of 20.2% in men and of 21.6% in women. When using LDL-C as a given parameter according to the current practice and advice, HDL-C in men and apoB in women provided an additional but small benefit.Conclusion: ApoB showed the best association with CAC compared to all other tested lipoproteins. Neither the ratio LDL-C/HDL-C nor apoB/apoA-1, or Lp(a) revealed a closer association with CAC. While lipoproteins are related to CAC more closely in women than in men, their association with CAC is, however, not particularly strong. Our results may influence primary and secondary prevention advices in order to improve detection of subclinical atherosclerosis, for which lipoprotein parameters can only play a minor role. (C) 2013 Elsevier Ireland Ltd. All rights reserved.