Radiofrequency ablation of thyroid nodules: "Good Clinical Practice Recommendations" for Austria : An interdisciplinary statement from the following professional associations: Austrian Thyroid Association (ÖSDG), Austrian Society for Nuclear Medicine and Molecular Imaging (OGNMB), Austrian Society for Endocrinology and Metabolism (ÖGES), Surgical Endocrinology Working Group (ACE) of the Austrian Surgical Society (OEGCH).

The present "Good Clinical Practice Recommendations" relate to radiofrequency ablation (RFA) training, execution, and quality control, as well as to pre- and postinterventional standards of care. They are aimed at all physicians who intend to learn to perform, or who are already conducting RFA interventions as well as at thyroid specialists providing pre- and postoperative care to RFA patients in Austria. Adoption of these recommendations is strongly encouraged by the afore-listed professional associations.All RFA interventionists who adhere to these standards shall be listed on a homepage linked to these professional associations entitled "RFA centers in compliance with the GCP recommendations of the ÖSDG/OGNMB/ÖGES/OEGCH-ACE." This will ensure harmonization of RFA training and quality control in the performance of the treatment in Austria.

Factors predicting long-term comorbidities in patients with Cushing's syndrome in remission.

PURPOSE: In Cushing's syndrome, comorbidities often persist after remission of glucocorticoid excess. Here, we aim to identify factors predicting long-term comorbidities in patients with Cushing's syndrome in remission. METHODS: In a retrospective cross-sectional study, 118 patients with Cushing's syndrome in remission (52 pituitary, 58 adrenal, 8 ectopic) were followed for a median of 7.9 years (range 2-38) after the last surgery. Associations between baseline anthropometric, metabolic, hormonal parameters at diagnosis, and comorbidities (obesity, diabetes, hyperlipidemia, hypertension, osteoporosis, depression) at last follow-up, were tested by uni- and multivariate regression analysis. RESULTS: In patients with manifest comorbidities at diagnosis, remission of Cushing's syndrome resolved diabetes in 56% of cases, hypertension in 36% of cases, hyperlipidaemia in 23%, and depression in 52% of cases. In a multivariate regression analysis, age, fasting glucose, BMI, and the number of comorbidities at diagnosis were positive predictors of the number of long-term comorbidities, while baseline 24-h urinary free cortisol (UFC) negatively correlated with the persistence of long-term comorbidities. The negative relationship between baseline UFC and long-term comorbidities was also found when pituitary and adrenal Cushing's cases were analyzed separately. Baseline UFC was negatively related to the time of exposure to excess glucocorticoids. CONCLUSIONS: Long-term comorbidities after remission of Cushing's syndrome depend not only on the presence of classic cardiovascular risk factors (age, hyperglycemia, BMI), but also on the extent of glucocorticoid excess. Lower baseline UFC is associated with a higher number of long-term comorbidities, possibly due to the longer exposure to excess glucocorticoids in milder Cushing's syndrome.

Are hypothyroidism and hypogonadism clinically relevant in patients with malignant gliomas? A longitudinal trial in patients with glioma.

BACKGROUND: So far, the development and course of therapy-induced deficiencies in hypothalamic-pituitary hormones in adult patients with malignant gliomas has not received much attention. However, such deficiencies may impact patient's quality of life substantially. METHODS: In this monocentric longitudinal trial, we examined hormonal levels of TSH, T3, T4, fT3, fT4, FSH, LH, testosterone, estradiol and prolactin in patients with malignant high grade gliomas before the start of radiochemotherapy (RCT), at the end of RCT and then every three months for newly diagnosed patients and every six months in patients diagnosed more than two years before study inclusion. Growth hormone was not measured in this trial. RESULTS: 436 patients (198 female, 238 male) with high-grade gliomas, aged 19-83 years (median 50 years), were included in this study. Low levels of thyroid hormones were observed in around 10% of patients within the first six months of follow up and increasingly after 36 months. Half of premenopausal women at study entry developed premature menopause, 35% showed hyperprolactinemia. Low testosterone levels were measured in 37% of men aged less than 50 years and in 35/63 (55%) of men aged 50 years or older. DISCUSSION: The results of this study show that a significant percentage of patients with malignant gliomas develop hormonal deficiencies mandating regular clinical follow up, state of the art counseling and if clinically necessary substitution therapy.

Calcium-stimulated calcitonin - The "new standard" in the diagnosis of thyroid C-cell disease - clinically relevant gender-specific cut-off levels for an "old test".

INTRODUCTION: Pentagastrin (Pg) stimulated calcitonin (sCT) was used to enhance accuracy in medullary thyroid cancer (MTC) diagnosis. As it is now unavailable, calcium (Ca) has been recommended as an alternative. The aim of this study was to define gender-specific cut-off values to predict MTC in patients with elevated basal CT (bCT) following Pg-sCT and Ca-sCT stimulation and to compare the time courses of CT release during stimulation. MATERIALS AND METHODS: The stimulation tests were applied in 62 consecutive patients with thyroid nodules. Basal calcitonin was measured by chemiluminescent immunometric assay. All patients underwent thyroidectomy and bilateral central neck dissection. C-cell pathology was confirmed by histological and immunohistochemical evaluation. RESULTS: In 39 (0.63) patients MTC was documented while isolated C-cell hyperplasia (CCH) was identified in 23 (0.37) patients. Medullary thyroid cancer was predicted in males with bCT values > 43 pg/mL or sCT concentrations > 470 pg/mL (Pg-sCT) or > 1500 pg/mL (Ca-sCT), and in females with bCT concentrations > 23 pg/mL or sCT concentrations > 200 pg/mL (Pg-sCT) or > 780 pg/mL (Ca-sCT), respectively. Pg-sCT correctly predicted MTC in 16 (0.66) compared to 13 (0.54) after Ca-sCT in males and in 12 (0.80) compared to 11 (0.73) in females; without statistical significance. In patients with CCH or low tumor burden, there was a tendency of faster CT release after Ca stimulation (CT peak after 3min in > 60%) compared to patients with advanced MTC (CT peak after 3min in < 10%). CONCLUSIONS: Using gender-specific cut-off values, Ca could replace Pg to predict MTC with similar diagnostic power.

Total thyroidectomy (Tx) versus thionamides (antithyroid drugs) in patients with moderate-to-severe Graves' ophthalmopathy - a 1-year follow-up: study protocol for a randomized controlled trial.

BACKGROUND: Graves' disease (GD) is characterized by thyrotoxicosis and goiter and arises through circulating autoantibodies that bind to, and stimulate, the thyroid hormone receptor (TSHR). A temporal relation between the onset of hyperthyroidism and the onset of ophthalmopathy, a common extrathyroidal manifestation, has been demonstrated. Graves' ophthalmopathy (GO) is typically characterized by an inflammation and expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered for hyperthyroidism caused by Graves' disease: antithyroid drugs (ATD) (thionamides), radioiodine ablation (RAI) and thyroidectomy (Tx). To date, there is no clear recommendation on the treatment of Graves' disease and GO, mainly due to the individuality of the disease in each patient. The aim of the study is to examine the difference in the outcome of GO in patients with moderate-to-severe GO who receive Tx versus further ATD after suffering their first relapse of GO, or in which GO stays the same following the initial decrease in ATD therapy after 6 months. METHODS/DESIGN: This prospective randomized clinical trial with observer-blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: Clinical Activity Score (CAScore), NOSPECS score, superonasal index measurements via ultrasound, and quality of life score. DISCUSSION: This study should allow for better therapeutic choices in patients with moderate-to-severe GO. In addition, it should demonstrate whether the outcome of GO in patients with moderate-to-severe GO is better in those who receive early Tx versus further ATD. Furthermore, this study will aim to establish a standard glucocorticoid scheme before and after Tx in patients with moderate-to-severe EO. TRIAL REGISTRATION: Eudra-CT: 2015-003515-38; Medical University of Vienna Protocol Record 1839/2015. Date of Ethics Committee approval: 19 January 2017. Registered on 27 January 2017.

Management of Pregnant Women after Bariatric Surgery.

The prevalence of obesity is growing worldwide, and strategies to overcome this epidemic need to be developed urgently. Bariatric surgery is a very effective treatment option to reduce excess weight and often performed in women of reproductive age. Weight loss influences fertility positively and can resolve hormonal imbalance. So far, guidelines suggest conceiving after losing maximum weight and thus recommend conception at least 12-24 months after surgery. As limited data of these suggestions exist, further evidence is urgently needed as well for weight gain in pregnancy. Oral glucose tolerance tests for the diagnosis of gestational diabetes mellitus (GDM) should not be performed after bariatric procedures due to potential hypoglycaemic adverse events and high variability of glucose levels after glucose load. This challenges the utility of the usual diagnostic criteria for GDM in accurate prediction of complications. Furthermore, recommendations on essential nutrient supplementation in pregnancy and lactation in women after bariatric surgery are scarce. In addition, nutritional deficiencies or daily intake recommendations in pregnant women after bariatric surgery are not well investigated. This review summarizes current evidence, proposes clinical recommendations in pregnant women after bariatric surgery, and highlights areas of lack of evidence and the resulting urgent need for more clinical investigations.

PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex.

CONTEXT: Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. CASE DESCRIPTION: Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of PRKAR1A, suggesting a role of this gene in the pituitary adenoma development. CONCLUSION: PRKAR1A loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients.

[Other specific types of diabetes]. / Andere spezifische Diabetesformen.

Numerous endocrine diseases are associated with impaired glucose metabolism and can induce diabetes mellitus. With the exception of hyperthyroidism, where this is uncommon, these diseases are rare. Acromegaly and Cushing syndrome are frequently associated with impaired glucose tolerance and diabetes. In contrast, this is a rare finding in pheochromocytoma and Conn syndrome. Among the many drugs that can induce diabetes this can be observed most frequently with hormones, atypic antipsychotic drugs and immunosuppressives. In addition, diseases of the pancreas such as pancreatitis, pancreatic carcinoma, cystic fibrosis and hemochromatosis can cause diabetes as well as Down syndrome, Klinefelter syndrome, Turner syndrome and Prader Willi syndrome and rare immunmediated or genetic syndromes.

HORMONE SUBSTITUTION AFTER GASTRIC BYPASS SURGERY IN PATIENTS WITH HYPOPITUITARISM SECONDARY TO CRANIOPHARYNGIOMA.

OBJECTIVE: Craniopharyngiomas (CPs) are benign brain tumors presenting frequently in childhood and are treated by surgery with or without radiotherapy. About 50% of cured patients suffer from eating disorders and obesity due to hypothalamic damage, as well as hypopituitarism, necessitating subsequent hormone substitution therapy. Gastric bypass surgery has been reported to be an efficient treatment strategy for morbid hypothalamic obesity. However, so far it is unknown whether oral hormone substitution is affected by impaired intestinal drug absorption, potentially leading to severe hypopituitarism or pituitary crisis. METHODS: Four morbidly obese CP patients with panhypopituitarism treated by gastric bypass surgery were included in this retrospective analysis. Dosages of hormone substitution therapy, blood concentrations of hormones, potential complications of impaired drug absorption, and anthropometric characteristics were investigated pre- and postoperatively after 6 to 14 months and 13 to 65 months. RESULTS: In all CP patients (3 female/1 male; baseline body mass index, 49 ± 7 kg/m(2)), gastric bypass resulted in distinct weight loss (-35 ± 27 kg). In follow-up examinations, mean daily dosage of thyroid hormone (levothyroxinebaseline 156 ± 44 µg/day versus levothyroxinefollow-up 150 ± 30 µg/day), hydrocortisone (hydrocortisonebaseline 29 ± 12 mg/day versus hydrocortisonefollow-up 26 ± 2 mg/day), growth-hormone (somatotropinbaseline 0.9 ± 0.5 mg/day versus somatotropinfollow-up 1.0 ± 0.4 mg/day), and desmopressin (desmopressinbaseline 222 ± 96 µg/day versus desmopressinfollow-up 222 ± 96 µg/day) substitution was unchanged. No patient developed adrenal insufficiency. Oral thyroid/hydrocortisone absorption testing performed in 1 patient indicated sufficient gastrointestinal drug absorption after bariatric surgery. CONCLUSION: Our preliminary results suggest that oral hormone substitution therapy is not impaired following gastric bypass operation in CP patients with morbid obesity, indicating that it might be a safe and effective treatment strategy.

Clinical presentation in insulinoma predicts histopathological tumour characteristics.

BACKGROUND: Insulinomas are rare neuroendocrine tumours (NETs) of the pancreas, characterized clinically by neuroglycopenic symptoms during periods of substrate deficiency. The gold standard test for diagnosing an insulinoma is a 72-h fast. However, the prognostic value of parameters in the standardized 72-h fast on histopathological tumour criteria and clinical presentation has not been examined. METHODS: In thirty-three patients diagnosed with an insulinoma records, and data were investigated retrospectively. Histopathological tumour characteristics, including staging, grading and size, were reviewed. Grading was performed using Ki-67 index. Cut-off values for classical grading (G(clas)) were set at G1(clas) ≤ 2%, G2(clas) 3-20% & G3(clas) >20% and for modified grading (G(mod)) at G1(mod) <5%, G2(mod) 5-20% & G3(mod) >20%. RESULTS: When G(mod) criteria were applied, the initial blood glucose was lower in GII/III(mod) patients compared to GI(mod) (2.8 ± 0.8 vs 3.8 ± 1.3 mmol/l; P = 0.046). Basal and end of fast levels of insulin (basal insulin 71 ± 61 vs 20 ± 16 mU/l; P < 0.001; end of fast insulin 77 ± 51 vs 21 ± 20 mU/l; P < 0.001) and c-peptide (basal c-peptide 5.4 ± 2.4 vs 2.7 ± 1.6 µg/l; P = 0.004; end of fast c-peptide 5.3 ± 2.4 vs 2.5 ± 1.4 µg/l; P = 0.001) were significantly higher in GII/III(mod) than in GI(mod). No differences between the groups were observed when G(clas) criteria were applied. Additionally, close correlations were observed between insulin concentration, Ki-67 index and tumour size. CONCLUSION: This study shows an impact of histopathological tumour characteristics in patients suffering from an insulinoma on clinical presentation during a standardized 72-h fast. Lower initial blood glucose levels and higher concentrations of insulin and c-peptide are associated with worse tumour grading and larger tumour size.

Low-dose calcium versus pentagastrin for stimulation of calcitonin in chronic hemodialysis patients: a pilot study.

CONTEXT: Elevated calcitonin levels occur in up to 46% of patients with chronic hemodialysis (CHD) and frequently reflect benign C-cell hyperplasia rather than medullary thyroid carcinoma. For the differential diagnosis of hypercalcitoninemia, the pentagastrin-stimulated calcitonin test was used until its availability became restricted. OBJECTIVE: This study sought to compare calcium and pentagastrin in terms of their ability to stimulate calcitonin secretion and their side effects in patients with CHD. SETTING AND DESIGN: This prospective pilot study was conducted at the chronic hemodialysis unit of the Medical University of Vienna between December 2012 and September 2013. PATIENTS: We studied six male patients with CHD with elevated basal calcitonin levels. INTERVENTION: The stimulation test was performed first with 0.5 µg/kg pentagastrin and then with 1 mg/kg calcium after a median washout period of 7 (6-9) months. MAIN OUTCOME MEASURES: We measured calcitonin, serum ionized calcium, intact PTH (iPTH), and C-terminal fibroblast growth factor 23 levels before and 2, 5, and 10 minutes after iv infusion of the stimulant and assessed the tolerability of the two substances by a questionnaire. RESULTS: Both pentagastrin and calcium significantly stimulated calcitonin secretion at 2 and 5 minutes. Partial correlation analysis revealed a strong association between calcium- and pentagastrin-stimulated calcitonin levels (r=0.875, P < .0001). Only after calcium infusion serum ionized calcium levels increased from 1.09 (0.91-1.16) mmol/l to 1.4 (1.14-1.65) mmol/l at 2 minutes (P < .01) but returned to baseline levels at 5 minutes. Moreover, calcium infusion led to a significant decrease in iPTH levels from 315 (203-723) pg/ml to 182 (121-415) pg/ml at 5 minutes (P < .05) and 171 (91-346) pg/ml at 10 minutes (P < .001). In general, calcium caused fewer and less severe side effects than pentagastrin. CONCLUSIONS: In patients with CHD, the response of calcitonin to calcium and pentagastrin was comparable, making calcium a potential substitute for pentagastrin in these patients.

Levothyroxine replacement in hypothyroid humans reduces myocardial lipid load and improves cardiac function.

CONTEXT: Hypothyroidism is a common endocrine disorder frequently accompanied by alterations in lipid metabolism, such as hypercholesterolemia and high circulating triglycerides, both risk factors for nonischemic cardiomyopathy. Rodent studies suggest that the hypothyroid state promotes cardiac lipid retention by increasing lipid uptake into cardiomyocytes while reducing fatty acid oxidation. Furthermore, increased cardiac lipid load has been linked to cardiac dysfunction. OBJECTIVE: Dyslipidemia and hypothyroidism frequently coexist; thus, we hypothesized that overt hypothyroidism causes cardiac lipid deposition and ultimately cardiac dysfunction. DESIGN: An interventional prospective study with balanced within-subject comparison. PARTICIPANTS/SETTING/INTERVENTION: Ten patients recruited at an academic center, who underwent a thyroidectomy due to differentiated thyroid carcinoma, were examined 4 weeks postoperatively in the overtly hypothyroid state, right before radioiodine therapy, and 6-8 weeks after initiation of levothyroxine replacement. MAIN OUTCOME PARAMETERS: We measured cardiac lipid content and function in vivo before and after levothyroxine treatment using electrocardiogram-gated (1)H-magnetic resonance spectroscopy and imaging. RESULTS: Levothyroxine therapy reduced cardiac lipid content in nine of the 10 patients (0.35 ± 0.09 vs 0.22 ± 0.06 % water signal; P = .008; n = 10) and improved cardiac index (2 ± 0.2 vs 2.4 ± 0.1 L/min/m(2); P = .047) when comparing the hypothyroid with the euthyroid state, independent of changes in liver fat content (7.5 ± 3.2 vs 7.1 ± 2.6% magnetic resonance spectroscopy signal; P = .60) or body weight. CONCLUSION: Here we show that levothyroxine treatment reduces lipid accumulation in the heart and increases cardiac output in overtly hypothyroid patients. These results could in part explain the increased risk of death and heart failure in hypothyroid patients.

No evidence of ectopic lipid accumulation in the pathophysiology of the acromegalic cardiomyopathy.

CONTEXT: PATIENTS with acromegaly frequently display disturbances of glucose and lipid metabolism, which might contribute to their increased cardiovascular risk. Because insulin resistance and increased lipolysis have been linked to ectopic lipid deposition, altered lipid accumulation in the liver and the myocardium might contribute to metabolic and cardiac complications in these patients. OBJECTIVE: The aim of this study was to investigate myocardial (MYCL) and hepatic lipid content (HCL), insulin sensitivity, and cardiac function in active acromegaly and after control of GH excess through transsphenoidal surgery. PATIENTS: Ten patients with newly diagnosed acromegaly (ACRO_active) were compared with 12 healthy controls (CON), matched for age, body mass index, and gender. In seven patients GH excess was controlled, and they were compared with their active state. METHODS: MYCL and HCL were assessed by (1)H-magnetic resonance spectroscopy, pericardial fat and cardiac function by (1)H-magnetic resonance imaging, and insulin sensitivity and secretion by an oral glucose tolerance test. RESULTS: Although MYCL tended to be lower, HCL was significantly lower in ACRO_active compared with CON (HCL: 1.2% ± 1.2% vs 4.3% ± 3.5% of (1)H-magnetic resonance spectroscopy signal, P < .02). Parameters of systolic function and hypertrophy were significantly increased in ACRO_active compared with CON, as were insulin secretion and resistance. After the control of GH excess, HCL and MYCL remained unchanged, but pericardial fat was increased in the patients in whom GH excess was controlled (from 11.6 ± 5.5 to 14.7 ± 6.2 cm(2), P = .02). CONCLUSION: Acromegaly represents a unique condition characterized by low myocardial and hepatic lipid content despite decreased insulin sensitivity, hyperinsulinemia, and hyperglycemia. Hence, ectopic lipid accumulation does not appear to contribute to cardiac morbidity, and increased lipid oxidation might counteract ectopic lipid accumulation in GH excess.

A Case of "Late-Onset" Idiopathic Infantile Hypercalcemia Secondary to Mutations in the CYP24A1 Gene.

OBJECTIVE: Mutations in the 24-hydroxylase gene, CYP24A1, have recently been reported to cause idiopathic infantile hypercalcemia (IIH), a rare disease presenting in the first year of life that is characterized by increased sensitivity to vitamin D, leading to severe symptomatic hypercalcemia. METHODS: We present a case report and review the relevant literature. RESULTS: A 24-year-old Caucasian man presented with repetitive signs of nephrolithiasis since the age of 18 years, hypercalciuria (17.1 mmol/24 h), slightly elevated serum calcium concentration (2.64 mmol/L), and inappropriately high levels of 1,25-dihydroxyvitamin D (101 pg/mL) in combination with suppressed levels of circulating parathormone (7.9 pg/mL). Exogenous vitamin D intoxication as well as granulomatous disease or malignancy were excluded. Genetic analysis revealed a loss-of-function mutation in CYP24A1. Of note, our patient denied any prior clinical signs of impaired calcium homeostasis during childhood. CONCLUSION: Here, we describe the exceptional case of a patient with hypercalciuria and recurrent nephrolithiasis secondary to mutations in CYP24A1, without any signs of IIH in childhood, indicating that the phenotypic spectrum includes mild "late-onset" disease that becomes symptomatic in adolescence. Therefore, reduced CYP24A1 activity should be considered as a possible reason for recurrent nephrolithiasis in adults.

Adequately adapted insulin secretion and decreased hepatic insulin extraction cause elevated insulin concentrations in insulin resistant non-diabetic adrenal incidentaloma patients.

BACKGROUND: Insulin-resistance is commonly found in adrenal incidentaloma (AI) patients. However, little is known about beta-cell secretion in AI, because comparisons are difficult, since beta-cell-function varies with altered insulin-sensitivity. OBJECTIVES: To retrospectively analyze beta-cell function in non-diabetic AI, compared to healthy controls (CON). METHODS: AI (n=217, 34%males, 57 ± 1 years, body-mass-index:27.7 ± 0.3 kg/m(2)) and CON [n = 25, 32%males, 56 ± 1 years, 26.7 ± 0.8 kg/m(2)] with comparable anthropometry (p ≥ 0.31) underwent oral-glucose-tolerance-tests (OGTTs) with glucose, insulin, and C-peptide measurements. 1mg-dexamethasone-suppression-tests were performed in AI. AI were divided according to post-dexamethasone-suppression-test cortisol-thresholds of 1.8 and 5 µg/dL into 3 subgroups: pDexa<1.8 µg/dL, pDexa1.8-5 µg/dL and pDexa>5 µg/dL. Using mathematical modeling, whole-body insulin-sensitivity [Clamp-like-Index (CLIX)], insulinogenic Index, Disposition Index, Adaptation Index, and hepatic insulin extraction were calculated. RESULTS: CLIX was lower in AI combined (4.9 ± 0.2 mg · kg(-1) · min(-1)), pDexa<1.8 µg/dL (4.9 ± 0.3) and pDexa1.8-5 µg/dL (4.7 ± 0.3, p<0.04 vs.CON:6.7 ± 0.4). Insulinogenic and Disposition Indexes were 35%-97% higher in AI and each subgroup (p<0.008 vs.CON), whereas C-peptide-derived Adaptation Index, compensating for insulin-resistance, was comparable between AI, subgroups, and CON. Mathematical estimation of insulin-derived (insulinogenic and Disposition) Indexes from associations to insulin-sensitivity in CON revealed that AI-subgroups had ~19%-32% higher insulin-secretion than expectable. These insulin-secretion-index differences negatively (r=-0.45, p<0.001) correlated with hepatic insulin extraction, which was 13-16% lower in AI and subgroups (p<0.003 vs.CON). CONCLUSIONS: AI-patients show insulin-resistance, but adequately adapted insulin secretion with higher insulin concentrations during an OGTT, because of decreased hepatic insulin extraction; this finding affects all AI-patients, regardless of dexamethasone-suppression-test outcome.

A Case of simultaneous occurrence of Marine - Lenhart syndrome and a papillary thyroid microcarcinoma.

BACKGROUND: Marine-Lenhart syndrome is defined as the co-occurrence of Graves' disease and functional nodules. The vast majority of autonomous adenomas are benign, whereas functional thyroid carcinomas are considered to be rare. Here, we describe a case of simultaneous occurrence of Marine-Lenhart syndrome and a papillary microcarcinoma embedded in a functional nodule. CASE PRESENTATION: A 55 year-old, caucasian man presented with overt hyperthyroidism (thyrotropin (TSH) <0.01 µIU/L; free thyroxine (FT4) 3.03 ng/dL), negative thyroid peroxidase and thyroglobulin autoantibodies, but elevated thyroid stimulating hormone receptor antibodies (TSH-RAb 2.6 IU/L). Ultrasound showed a highly vascularized hypoechoic nodule (1.1 × 0.9 × 2 cm) in the right lobe, which projected onto a hot area detected in the 99mtechnetium thyroid nuclear scan. Overall uptake was increased (4.29%), while the left lobe showed lower tracer uptake with no visible background-activity, supporting the notion that both Graves' disease and a toxic adenoma were present. After normal thyroid function was reinstalled with methimazole, the patient underwent thyroidectomy. Histological work up revealed a unifocal papillary microcarcinoma (9 mm, pT1a, R0), positively tested for the BRAF V600E mutation, embedded into the hyperfunctional nodular goiter. CONCLUSIONS: Neither the finding of an autonomously functioning thyroid nodule nor the presence of Graves' disease rule out papillary thyroid carcinoma.

Thyroid disorders.

All forms of thyroid diseases are much more frequently observed in women than men, although the reasons are still not completely elucidated.Hyperthyroidism is defined by elevated circulating free thyroid hormones. The prevalence is about 2 % in women and 0.2 % in men. The most frequent causes are various forms of thyroid autonomy in elderly women and Graves' disease, which occurs mostly in younger women.Hypothyroidism is defined by a lack of thyroid hormones. It is a common endocrine disorder caused by autoimmune thyroiditis (Hashimoto thyroiditis), iodine deficiency or following surgery or radioiodine therapy. Thyroxine requirements depend on fat-free mass and are, therefore, somewhat higher in males who are more often undersubstituted. In pregnancy lower TSH-reference ranges have to be considered and thyroid function should be monitored throughout pregnancy to avoid harm to the foetus caused by maternal thyroid dysfunctions. If overtreated women more often feature fractures, whereas males more often develop atrial fibrillation.

Prevalence of endocrine disorders in morbidly obese patients and the effects of bariatric surgery on endocrine and metabolic parameters.

BACKGROUND: Several endocrine abnormalities, including hypothyroidism and Cushing's syndrome (CS), are considered as causative factors of obesity. The aim of this study was to evaluate the prevalence of endocrine disorders and obesity-associated co-morbidities, as well as the impact of substantial weight loss. METHODS: Screening was performed in 433 consecutive morbidly obese patients (age 41 ± 12 years; BMI 47 ± 6.9 kg/m(2); women 76%). A 1-mg dexamethasone suppression test (1-mg DST) was conducted to exclude CS, and thyrotropin (TSH) was measured to exclude hypothyroidism. Insulin sensitivity was estimated from oral glucose tolerance tests employing the Clamp-like index. Examinations were carried out at baseline, as well as at 6 and 12 months postoperatively. RESULTS: The prevalence of CS was below 0.6%. Before surgery, TSH was elevated compared to an age- and sex-matched normal weight control group (2.4 ± 1.2 vs. 1.5 ± 0.7 µU/ml; p < 0.001). The NCEP criteria of metabolic syndrome (MetS) were fulfilled by 39.5% of the patients. Impaired glucose tolerance and diabetes mellitus were observed in 23.5% and 22.6%, respectively. Seventy-two percent were insulin resistant. During follow-up, weight (BMI 47 ± 6.9 vs. 36 ± 6.4 vs. 32 ± 6.6 kg/m(2); p < 0.001) and TSH decreased significantly (2.4 ± 1.2 vs. 1.8 ± 1.0 vs. 1.8 ± 1.0 µU/ml; p < 0.001). Serum cortisol was higher in the MetS(+)-group compared to the MetS(-)-group (15.0 ± 6.3 vs. 13.5 ± 6.3 µg/dl; p = 0.003). CONCLUSIONS: CS appears to be a rare cause of morbid obesity. Normalization of slightly elevated thyrotropin after weight loss suggests that obesity causes TSH elevation rather than the reverse.

Higher frequency of thyroid tumors in the right lobe.

Recently, using ultrasonography, we observed that the right lobe usually is larger compared with the left thyroid lobe. Since the higher cell number in a larger right lobe may confer a higher tumor risk, we investigated the location of benign and malignant lesions to test the hypothesis of a more frequent occurrence in this lobe. In 1,001 consecutive patients with benign thyroid lesions, tumors more frequently occurred in the right lobe (+21.5%, p = 0.0022). Furthermore, in 1,277 thyroid cancer patients with 1,302 thyroid cancers, the right lobe more often harbored the tumor initially (+22.9%, p = 0.0009). Our data show a larger proportion of both benign and malignant tumors in the right thyroid lobe.

Thyrotropin serum concentrations in patients with papillary thyroid microcancers.

BACKGROUND: Recent studies have shown that elevated serum thyrotropin (thyroid-stimulating hormone [TSH]) concentrations are associated with an increased risk of differentiated thyroid cancers in patients with nodular goiter. Therefore, the measurement of TSH concentrations might support the clinical estimation of cancer risk, especially in patients with thyroid nodules that are too small for fine-needle aspiration biopsies. Thus, the objective of this study was to compare preoperative serum TSH concentrations in patients with papillary thyroid microcarcinoma (PTMC) and individuals in whom the presence of even small differentiated thyroid cancers was excluded by thorough histological examination of the thyroid after total thyroidectomy because of medullary thyroid carcinoma or c-cell hyperplasia. METHODS: The study was a retrospective cross-sectional analysis. Thirty-three patients with PTMC who had undergone a hemi- or total thyroidectomy and 54 subjects with medullary thyroid carcinoma or c-cell hyperplasia in whom a total thyroidectomy had been performed between 1994 and 2008 were included. Exclusion criteria were the intake of medication that might affect thyroid function and previous thyroid cancer or thyroid surgery. RESULTS: The mean TSH value was comparable between patients with PTMCs (1.40 +/- 0.92 mLU/L, 95% CI = 1.07-1.72) and the control group (1.43 +/- 1.44 mLU/L; 95% CI = 1.04-1.82, p = 0.912). There was a positive trend in correlation between nodule size and TSH levels in patients with PTMC (p = 0.066). CONCLUSIONS: TSH is not elevated in subjects with PTMCs, indicating that it is not likely involved in the de novo oncogenesis of these small cancers. However, TSH might rather play a role in the progression of preexisting PTMCs.