[Other specific types of diabetes and exocrine pancreatic insufficiency (update 2023)]. / Andere spezifische Diabetesformen und exokrine Pankreasinsuffizienz (Update 2023).

The heterogenous category "specific types of diabetes due to other causes" encompasses disturbances in glucose metabolism due to other endocrine disorders such as acromegaly or hypercortisolism, drug-induced diabetes (e.g. antipsychotic medications, glucocorticoids, immunosuppressive agents, highly active antiretroviral therapy (HAART), checkpoint inhibitors), genetic forms of diabetes (e.g. Maturity Onset Diabetes of the Young (MODY), neonatal diabetes, Down­, Klinefelter- and Turner Syndrome), pancreatogenic diabetes (e.g. postoperatively, pancreatitis, pancreatic cancer, haemochromatosis, cystic fibrosis), and some rare autoimmune or infectious forms of diabetes. Diagnosis of specific diabetes types might influence therapeutic considerations. Exocrine pancreatic insufficiency is not only found in patients with pancreatogenic diabetes but is also frequently seen in type 1 and long-standing type 2 diabetes.

[Gestational diabetes mellitus (Update 2023)]. / Gestationsdiabetes (GDM) (Update 2023).

Gestational diabetes (GDM) is defined as any degree of glucose intolerance with onset during pregnancy and is associated with increased feto-maternal morbidity as well as long-term complications in mothers and the offspring. Women detected to have diabetes early in pregnancy receive the diagnosis of overt, non-gestational, diabetes (glucose: fasting ≥ 126 mg/dl, spontaneous ≥ 200 mg/dl or HbA1c ≥ 6.5% before 20 weeks of gestation). GDM is diagnosed by an oral glucose tolerance test (oGTT) or increased fasting glucose (≥ 92 mg/dl). Screening for undiagnosed type 2 diabetes at the first prenatal visit is recommended in women at increased risk (history of GDM/pre-diabetes; malformation, stillbirth, successive abortions or birth weight > 4500 g previously; obesity, metabolic syndrome, age > 35 years, vascular disease; clinical symptoms of diabetes (e.g. glucosuria) or ethnic origin with increased risk for GDM/T2DM (Arab, South- and Southeast Asian, Latin American)) using standard diagnostic criteria. Performance of the oGTT (120 min; 75 g glucose) may already be indicated in the first trimester in high-risk women but is mandatory between gestational week 24-28 in all pregnant women with previous non-pathological glucose metabolism. Following WHO recommendations, which are based on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, GDM is defined, if fasting venous plasma glucose is ≥ 92 mg/dl or 1 h ≥ 180 mg/dl or 2 h ≥ 153 mg/dl after glucose loading (international consensus criteria). In case of one pathological value a strict metabolic control is mandatory. After bariatric surgery we do not recommend to perform an oGTT due to risk of postprandial hypoglycemia. All women with GDM should receive nutritional counseling, be instructed in blood glucose self-monitoring and motivated to increase physical activity to moderate intensity levels-if not contraindicated (Evidence level A). If blood glucose levels cannot be maintained in the therapeutic range (fasting < 95 mg/dl and 1 h after meals < 140 mg/dl, Evidence level B) insulin therapy should be initiated as first choice (Evidence level A). Maternal and fetal monitoring is required in order to minimize maternal and fetal/neonatal morbidity and perinatal mortality. Regular obstetric examinations including ultrasound examinations are recommended (Evidence level A). Neonatal care of GDM offspring at high risk for hypoglycaemia includes blood glucose measurements after birth and if necessary appropriate intervention. Monitoring the development of the children and recommendation of healthy lifestyle are important issues to be tackled for the whole family. After delivery all women with GDM have to be reevaluated as to their glucose tolerance by a 75 g oGTT (WHO criteria) 4-12 weeks postpartum. Assessment of glucose parameters (fasting glucose, random glucose, HbA1c or optimally oGTT) are recommended every 2-3 years in case of normal glucose tolerance. All women have to be instructed about their increased risk of type 2 diabetes and cardiovascular disease at follow-up. Possible preventive meassures, in particular lifestyle changes as weight management and maintenance/increase of physical activity should be discussed (evidence level A).

Increased ATP synthesis might counteract hepatic lipid accumulation in acromegaly.

Patients with active acromegaly (ACRO) exhibit low hepatocellular lipids (HCL), despite pronounced insulin resistance (IR). This contrasts the strong association of IR with nonalcoholic fatty liver disease in the general population. Since low HCL levels in ACRO might be caused by changes in oxidative substrate metabolism, we investigated mitochondrial activity and plasma metabolomics/lipidomics in active ACRO. Fifteen subjects with ACRO and seventeen healthy controls, matched for age, BMI, sex, and body composition, underwent 31P/1H-7-T MR spectroscopy of the liver and skeletal muscle as well as plasma metabolomic profiling and an oral glucose tolerance test. Subjects with ACRO showed significantly lower HCL levels, but the ATP synthesis rate was significantly increased compared with that in controls. Furthermore, a decreased ratio of unsaturated-to-saturated intrahepatocellular fatty acids was found in subjects with ACRO. Within assessed plasma lipids, lipidomics, and metabolomics, decreased carnitine species also indicated increased mitochondrial activity. We therefore concluded that excess of growth hormone (GH) in humans counteracts HCL accumulation by increased hepatic ATP synthesis. This was accompanied by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a metabolomic profile, reflecting the increase in mitochondrial activity. Thus, these findings help to better understanding of GH-regulated antisteatotic pathways and provide a better insight into potentially novel therapeutic targets for treating NAFLD.

Ectopic Cushing's syndrome in a patient with inferior petrosal sinus sampling indicating pituitary-dependent ACTH secretion.

In an unclear case of Cushing's syndrome, IPSS identifies the origin of ACTH secretion, and together with MRI enables the localization of an ectopic corticotroph adenoma in the parasellar or cavernous sinuses region.

MARKEDLY DELAYED INSULIN SECRETION AND A HIGH RATE OF UNDETECTED OVERT DIABETES CHARACTERIZE GLUCOSE METABOLISM IN ADULT PATIENTS WITH CYSTIC FIBROSIS AFTER LUNG TRANSPLANTATION.

OBJECTIVE: Cystic fibrosis-related diabetes (CFRD) is associated with adverse clinical outcomes and should be screened for by an annual oral glucose tolerance test (OGTT). Since pathophysiologic studies have mainly been performed in a pediatric/adolescent, nontransplanted collective, we aimed to assess parameters of insulin secretion and sensitivity in adult cystic fibrosis (CF) patients after lung transplantation (LT). METHODS: Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index [BMI] 21.5 ± 3.3 kg/m2) and 8 control subjects matched by age (36.0 ± 6.6 years; P>.05), BMI (22.3 ± 1.5 kg/m2; P>.05), and gender (CON group) underwent a 3-hour OGTT with glucose, insulin, and C-peptide measurements. Parameters of insulin secretion and sensitivity as well as lipid profiles were assessed. RESULTS: In the CF group, 4 patients were diagnosed with overt diabetes (CFRD) compared to CF patients without diabetes (CF-noDM), of whom 6 had indeterminate glycemia with 1-h glucose values >200 mg/dL. The insulin peak after glucose load occurred after 30 minutes in CON, after 90 minutes in CF-noDM, and was missing in CFRD. Insulin sensitivity was comparable between the groups. Beta-cell glucose sensitivity was markedly reduced in CFRD (10.7 ± 5.8 pmol/min*m2*mM), higher in CF-noDM (39.9 ± 23.4 pmol/min*m2*mM), but still significantly lower compared to CON (108.3 ± 53.9 pmol/min*m2*mM; P = .0008). CFRD patients exhibited increased triglyceride levels and decreased high-density lipoprotein levels. CONCLUSION: Adult CF patients after LT have profound disturbances in glucose metabolism, with a high rate of undetected diabetes and markedly delayed insulin secretion. Curbed beta-cell glucose sensitivity rather than insulin resistance explains postprandial hyperglycemia and is accompanied by abnormalities in lipid metabolism. ABBREVIATIONS: AUC = area under the curve; BMI = body mass index; CF = cystic fibrosis; CFRD = cystic fibrosis-related diabetes; CFTR = cystic fibrosis transmembrane-conductance regulator; CF-TX = cystic fibrosis patients who underwent lung transplantation; CGM = continuous glucose monitoring; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; INDET = indeterminate glycemia; LDL = low-density lipoprotein; LT = lung transplantation; OGIS = oral glucose sensitivity index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index.

Absolute Quantification of Phosphor-Containing Metabolites in the Liver Using 31 P MRSI and Hepatic Lipid Volume Correction at 7T Suggests No Dependence on Body Mass Index or Age.

BACKGROUND: Hepatic disorders are often associated with changes in the concentration of phosphorus-31 (31 P) metabolites. Absolute quantification offers a way to assess those metabolites directly but introduces obstacles, especially at higher field strengths (B0 ≥ 7T). PURPOSE: To introduce a feasible method for in vivo absolute quantification of hepatic 31 P metabolites and assess its clinical value by probing differences related to volunteers' age and body mass index (BMI). STUDY TYPE: Prospective cohort. SUBJECTS/PHANTOMS: Four healthy volunteers included in the reproducibility study and 19 healthy subjects arranged into three subgroups according to BMI and age. Phantoms containing 31 P solution for correction and validation. FIELD STRENGTH/SEQUENCE: Phase-encoded 3D pulse-acquire chemical shift imaging for 31 P and single-volume 1 H spectroscopy to assess the hepatocellular lipid content at 7T. ASSESSMENT: A phantom replacement method was used. Spectra located in the liver with sufficient signal-to-noise ratio and no contamination from muscle tissue, were used to calculate following metabolite concentrations: adenosine triphosphates (γ- and α-ATP); glycerophosphocholine (GPC); glycerophosphoethanolamine (GPE); inorganic phosphate (Pi ); phosphocholine (PC); phosphoethanolamine (PE); uridine diphosphate-glucose (UDPG); nicotinamide adenine dinucleotide-phosphate (NADH); and phosphatidylcholine (PtdC). Correction for hepatic lipid volume fraction (HLVF) was performed. STATISTICAL TESTS: Differences assessed by analysis of variance with Bonferroni correction for multiple comparison and with a Student's t-test when appropriate. RESULTS: The concentrations for the young lean group corrected for HLVF were 2.56 ± 0.10 mM for γ-ATP (mean ± standard deviation), α-ATP: 2.42 ± 0.15 mM, GPC: 3.31 ± 0.27 mM, GPE: 3.38 ± 0.87 mM, Pi : 1.42 ± 0.20 mM, PC: 1.47 ± 0.24 mM, PE: 1.61 ± 0.20 mM, UDPG: 0.74 ± 0.17 mM, NADH: 1.21 ± 0.38 mM, and PtdC: 0.43 ± 0.10 mM. Differences found in ATP levels between lean and overweight volunteers vanished after HLVF correction. DATA CONCLUSION: Exploiting the excellent spectral resolution at 7T and using the phantom replacement method, we were able to quantify up to 10 31 P-containing hepatic metabolites. The combination of 31 P magnetic resonance spectroscopy imaging data acquisition and HLVF correction was not able to show a possible dependence of 31 P metabolite concentrations on BMI or age, in the small healthy population used in this study. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:597-607.

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.

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.

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.

The impact of recurrent gestational diabetes on maternal metabolic and cardiovascular risk factors.

OBJECTIVE: The development of overt diabetes in women with prior gestational diabetes mellitus (priorGDM) has been linked to several risk factors including age, obesity and insulin therapy during pregnancy; the role of recurrent GDM as a further risk factor remains unclear. As studies examining detailed metabolic consequences of recurrent GDM are missing and the role of recurrent GDM on cardiovascular risk is unknown, our aim was to investigate the impact of recurrent GDM (within 5 years after an index pregnancy) on metabolic and cardiovascular parameters. METHODS: Oral and intravenous glucose tolerance tests as well as assessment of cardiovascular risk factors were performed at baseline (6 months after index pregnancy) and 5 years thereafter in 21 prior GDM with recurrent GDM (recGDM), 41 prior GDM with no additional pregnancy (nonrecGDM) and 10 healthy controls [CON]. RESULTS: Despite weight gain in recGDM (2·3 ± 5·1 vs. -1·3 ± 6·7 kg, P < 0·04), glucose tolerance, insulin sensitivity and secretion did not differ compared with nonrecGDM at baseline and follow-up. Furthermore, recGDM did not exhibit increased cardiovascular risk factors. Metabolic deterioration in (19% of) the total priorGDM group was associated with decreased insulin sensitivity (OGIS:367·4 ± 89·6 vs. 436·4 ± 75·5 mL/min*m², P = 0·01), hyperinsulinaemia (TIS:37·9 ± 9·7 vs. 28·0 ± 10·2 nM, P < 0·006) and postchallenge hyperglycaemia at 5 years postpartum. CONCLUSIONS: Recurrence of gestational diabetes was not associated with deterioration of glucose metabolism, insulin sensitivity and secretion nor with increased cardiovascular risk. Consequently, priorGDM should not be recommended to refrain from subsequent pregnancies, but be encouraged to regain and maintain normal body weight after delivery and regularly undergo OGTTs to early detect metabolic deterioration.

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.