Increased plasma levels of soluble programmed death ligand 1 (sPD-L1) and fibroblast growth factor 23 (FGF-23) in patients with Graves' ophthalmopathy in comparison to hyperthyroid patients without Graves' ophthalmopathy.

BACKGROUND: Management of Graves' ophthalmopathy (GO) is still a challenge in Graves' disease (GD). Moreover, 40% of GD patients show radiological muscle enlargement without clinically apparent GO. Delayed treatment of GO may lead to deterioration in prognosis. METHODS: Thirty GD patients with overt hyperthyroidism were included in this study, 17 of whom either had GO at diagnosis or developed GO during the study period. Samples were collected at the beginning of the study, at 6 months, and at 24 months. Plasma samples were analyzed for 92 cytokines using the Olink Target 96 inflammation panel. RESULTS: After adjustment for multiplicity testing using the false discovery rate approach, soluble programmed death ligand 1 (sPD-L1) and fibroblast growth factor 23 (FGF-23) were significantly elevated in GO patients. CONCLUSION: Using a broad cytokine panel we show that patients with Graves' ophthalmopathy have elevated PD-L1 and FGF-23 levels. The findings support previous suggestions that PD-L1 may serve as a treatment target.

Comparison Between Thyroid Stimulating Immunoglobulin and TSH-Receptor Antibodies in the Management of Graves' Orbitopathy.

OBJECTIVES: TSH-receptor antibodies (TRAb) targeting the TSH receptor (TSH-R) induce hyperthyroidism in Graves´ disease (GD). Graves´ orbitopathy (GO) is influenced by stimulation of the TSH-R in the orbita. GO has been, among other factors, linked to high TRAb levels. Thyroid stimulating immunoglobulins (TSI) is a relatively new method for assessing TSH-receptor antibodies. The aim of this study was to investigate the role of TSI in the management of GO. METHODS: Patients with newly diagnosed GD (n=30, median age 55 years (range 35-72), 29 women) received pharmacological therapy (methimazole+++thyroxine) for up to 24 months. GO was identified by clinical signs and symptoms. Eleven patients had GO at diagnosis, and another six developed GO during treatment. Blood samples for TSI and other thyroidal biomarkers were obtained at baseline and on five occasions during the 24-month follow-up. Twenty-two subjects completed the drug regimen without surgery or radioiodine treatment. RESULTS: At baseline, TSI was highly correlated with TRAb (r s =0.64, p<0.001), and both assays similarly correlated to fT3 values. TSI and TRAb did not differ significantly between GO and non-GO patients for visit v1 (n=30, 17 GO during the whole study) or at follow-up (n=22, 12 GO during the whole study). During follow-up, levels of TSI and TRAb decreased and normalized in both groups. CONCLUSION: The present study does not support any added benefit of TSI compared to TRAb for the prediction and management of GO.

Vitamin D and bone metabolism in Graves' disease: a prospective study.

PURPOSE: Vitamin D and osteoporosis in Graves' disease (GD) have been examined in cross-sectional studies with divergent results. Here, we prospectively studied vitamin D metabolism and bone health in patients with newly diagnosed GD. METHODS: Thirty consecutive patients with de novo overt thyrotoxicosis diagnosed with GD were included. At diagnosis, none of the patients were treated with vitamin D or anti-osteoporotic drugs. All patients were initially treated with antithyroid drugs. Blood samplings were taken at baseline and at 6 weeks, 3, 6, 12 and 24 months after treatment start. Serum levels of 25OHD3, 1,25OH2D3, calcium, parathyroid hormone (PTH), and C-terminal telopeptides of Type I collagen (CTX-I) were analysed. Bone mineral density (BMD) was measured at baseline, and 1 and 2 years after treatment initiation. RESULTS: At diagnosis, patients with GD did not have vitamin D deficiency. There were no significant correlations between levels of 25OHD3 and thyrotoxicosis. Upon treatment of the thyrotoxicosis, serum calcium fell transiently, and PTH and 1,25OH2D3 increased. 25OHD3 fell within the normal range and stabilised at 6 months. CTX-I fell over 12 months, BMD increased significantly up to 2 years, p = 0.002, < 0.001 and 0.005 in the spine, left total hip and left femoral neck, respectively. CONCLUSIONS: The present data underline that thyrotoxicosis has a negative impact on bone health and demonstrate fine-tuned dynamics in bone and vitamin D metabolism. Upon treatment, bone health improved over a follow-up period of 24 months despite rising PTH. Increased conversion of 25OHD3 to 1,25OH2D3 occurs during treatment of GD.

Time Course of Metabolic, Neuroendocrine, and Adipose Effects During 2 Years of Follow-up After Gastric Bypass in Patients With Type 2 Diabetes.

CONTEXT: Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood. OBJECTIVE: Integrated assessment of neuroendocrine and metabolic changes over time in T2D patients undergoing RYGB. DESIGN AND SETTING: Follow-up of single-center randomized study. PATIENTS: Thirteen patients with obesity and T2D compared to 22 healthy subjects. INTERVENTIONS: Blood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB. RESULTS: After RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P < 0.001). At 4 weeks, morning cortisol (P < 0.05) and adrenocorticotropin (P = 0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P < 0.05) and peaked at 24 weeks (P < 0.01). C-reactive protein (CRP) and white blood cells were rapidly reduced (P < 0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation, and adipogenesis was upregulated (P < 0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (P < 0.01). CONCLUSIONS: We propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (3) body fat and weight loss, increased adipose glucose uptake, and whole-body insulin sensitivity (months-years; similar to healthy controls). Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia.

Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia.

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by 18F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

Serum thyroglobulin is associated with orbitopathy in Graves' disease.

PURPOSE: Serum thyroglobulin levels are often elevated in Graves' disease (GD) and in most cases decrease during treatment. Its relation to Graves' orbitopathy (GO) has not been clarified. Previously, a risk of GO has been linked to smoking, TSH receptor stimulation, high TSH-receptor antibodies (TRAb), low thyroid peroxidase and thyroglobulin antibodies (TPOAb, TgAb). METHODS: We examined Tg levels in 30 consecutive patients with GD were given drug therapy (methimazole + thyroxine) for up to 24 months. GO was identified by clinical signs and symptoms. 17 patients had GO, 11 of whom had it at diagnosis while 6 developed GO during treatment. During the study, 5 subjects were referred to radioiodine treatment, 3 to surgery. The remaining 22 subjects (GO n = 12, non-GO n = 10) completed the drug regimen. RESULTS: At diagnosis, Tg levels in GO patients (n = 11) were higher (84, 30-555 µg/L, median, range) than in non-GO patients (n = 19) (38, 3.5-287 µg/L), p = 0.042. Adding the 6 subjects who developed eye symptoms during treatment to the GO group (n = 17), yielded p = 0.001 vs. non-GO (n = 13). TRAb tended to be higher, while TPOAb and TgAb tended to be lower in the GO group. For the 22 patients who completed the drug regimen, Tg levels were higher in GO (n = 12) vs. non-GO (n = 10), p = 0.004, whereas TRAb levels did not differ. CONCLUSION: The data may suggest that evaluation of thyroglobulin levels in GD could contribute to identify patients at increased risk of developing GO. Possibly, thyroidal release of Tg in GD reflects a disturbance that also impacts retroorbital tissues.

Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery.

OBJECTIVE: To explore the role of hormones and the autonomic nervous system in the rapid remission of diabetes after Roux-en-Y Gastric Bypass (RYGB). RESEARCH DESIGN AND METHODS: Nineteen obese patients with type 2 diabetes, 7 M/12 F, were randomized (2:1) to RYGB or standard-of-care medical treatment (control). At baseline and 4 and 24 weeks post surgery, fasting blood sampling, OGTT, intravenous arginine challenge, and heart-rate variability (HRV) assessments were performed. RESULTS: At both 4 and 24 weeks post-RYGB the following effects were found: arginine-stimulated insulin secretion was reduced. GLP-1, GIP, and glucagon rise during OGTT was enhanced. IGF-1 and GH levels increased. In addition, total HRV and spectral components PLF (power of low frequency) and PHF (power of high frequency) increased. At 4 weeks, morning cortisol was lower than baseline and 24 weeks. At 24 weeks, NEFA levels during OGTT, and the PLF/PHF ratio decreased. None of these changes were seen in the control group. CONCLUSIONS: There were rapid changes within 4 weeks after RYGB: signs of enhanced parasympathetic nerve activity, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose. The findings suggest that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in type 2 diabetes.

Energy restriction in obese women suggest linear reduction of hepatic fat content and time-dependent metabolic improvements.

Energy restriction reduces liver fat, improves hepatic insulin resistance and lipid metabolism. However, temporal data in which these metabolic improvements occur and their interplay is incomplete. By performing repeated MRI scans and blood analysis at day 0, 3, 7, 14 and 28 the temporal changes in liver fat and related metabolic factors were assessed at five times during a low-calorie diet (LCD, 800-1100 kcal/day) in ten obese non-diabetic women (BMI 41.7 ± 2.6 kg/m2) whereof 6 had NAFLD. Mean weight loss was 7.4 ± 1.2 kg (0.7 kg/day) and liver fat decreased by 51 ± 16%, resulting in only three subjects having NAFLD at day 28. Marked alteration of insulin, NEFA, ALT and 3-hydroxybuturate was evident 3 days after commencing LCD, whereas liver fat showed a moderate but a linear reduction across the 28 days. Other circulating-liver fat markers (e.g. triglycerides, adiponectin, stearoyl-CoA desaturase-1 index, fibroblast growth factor 21) demonstrated modest and variable changes. Marked elevations of NEFA, 3-hydroxybuturate and ALT concentrations occurred until day 14, likely reflecting increased tissue lipolysis, fat oxidation and upregulated hepatic fatty acid oxidation. In summary, these results suggest linear reduction in liver fat, time-specific changes in metabolic markers and insulin resistance in response to energy restriction.

Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery.

OBJECTIVES: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP). DESIGN: Experimental hyperinsulinemic-hypoglycemic clamp study. METHODS: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps. RESULTS: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed. CONCLUSIONS/INTERPRETATION: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

Early Changes in Adipose Tissue Morphology, Gene Expression, and Metabolism After RYGB in Patients With Obesity and T2D.

CONTEXT: Roux-en-Y gastric bypass (RYGB) surgery effectively prevents or treats type 2 diabetes (T2D). Adipose tissue (AT) mechanisms may be of importance. OBJECTIVE: To assess the relationship between early changes in whole-body and AT metabolism in surgically treated patients with T2D. DESIGN AND SETTING: A randomized single-center study. PATIENTS: Nineteen patients with T2D with body mass index 30 to 45 kg/m2. INTERVENTIONS: Thirteen patients were assessed at baseline and 4 and 24 weeks after RYGB (preceded by a 4-week low-calorie diet) and compared with 6 control patients continuing standard medical treatment: oral glucose tolerance test, subcutaneous AT biopsies for gene expression, adipocyte size, glucose uptake, lipolysis, and insulin action. RESULTS: At 4 and 24 weeks post-RYGB, all patients but one had stopped diabetes medication. Fasting glucose, HbA1c, and insulin levels decreased and the Matsuda index increased compared with baseline (P < 0.01 for all), indicating improved whole-body insulin sensitivity. Mean adipocyte size significantly reduced, more at 4 than at 24 weeks; at 4 weeks, glucose uptake per adipocyte was lowered, and isoproterenol-stimulated lipolysis tended to increase, whereas the fold insulin effects on glucose uptake and lipolysis were unchanged. Expression of genes involved in fatty acid oxidation, CPT1b and adiponectin, was increased at 4 weeks, whereas leptin and E2F1 (involved in cell proliferation) were reduced (P < 0.05 for all). CONCLUSION: Glycemic control and in vivo insulin sensitivity improved 4 weeks after RYGB, but adipocyte insulin sensitivity did not change despite a marked reduction in adipocyte size. Thus, mechanisms for a rapid improvement of T2D after RYGB may occur mainly in other tissues than adipose.

Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia.

Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

[Insufficient knowledge about mild TSH elevation during pregnancy. Still too early for screening within the Swedish maternity health system]. / Otillräcklig kunskap om lindrig TSH-stegring under graviditet - Ännu för tidigt för screening inom mödravårdsprogrammet.

Guidelines of the Swedish Society of Obstetricians and Gynecologists suggest screening for thyroid disease in early pregnancy in accordance with some international guidelines. A recommendation to treat all pregnant women with an increase of serum TSH above the trimester specific reference limit with levothyroxine is included. In a commentary on these guidelines from the authors, published in this issue of Läkartidningen, a more cautious approach to this controversial standpoint is noticed. Until further experience is gained and the scientific problem is resolved it is unjustified to implement a broad sceening procedure for thyroid disease in the Swedish maternity health system.

Limited value of cabergoline in Cushing's disease: a prospective study of a 6-week treatment in 20 patients.

CONTEXT AND OBJECTIVE: The role of cabergoline in Cushing's disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after ≥1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD. DESIGN: Twenty patients (19 naïve and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5-5 mg/week over 6 weeks. METHODS: Urinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end. RESULTS: At study end, the median cabergoline dose was 5 mg, range 2.5-5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a >50% decrease of UFC, three had a >50% rise of UFC. Salivary cortisol at 2300 h showed a congruent >50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study. CONCLUSIONS: Cabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.

Hypoglycemia in everyday life after gastric bypass and duodenal switch.

DESIGN: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. METHODS: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. RESULTS: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (<3.3  mmol/l, or 60  mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P<0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. CONCLUSION: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

Health-Related Quality-of-Life (HRQoL) on an Average of 12 Years After Gastric Bypass Surgery.

BACKGROUND: It is evident that morbidly obese patients have a low health-related quality-of-life (HRQoL), and this low HRQoL has become a common reason for them to seek bariatric surgery. Several HRQoL studies demonstrate a dramatic postoperative improvement, but most of these have had a short follow-up period. MATERIAL AND METHODS: An observational, cross-sectional study for HRQoL was conducted to study 486 patients (average age of 50.7 ± 10.0 years, with 84 % of them being female) operated with gastric bypass (GBP) in the period 1993 to 2003 at the University Hospitals of Örebro and Uppsala. Mean follow-up after gastric bypass was 11.5 ± 2.7 years (range 7-17). Two HRQoL instruments were used, SF-36 and the Obesity-related Problems scale (OP). The study group was compared with two control groups, both matched for age and gender, one from the general population and one containing morbidly obese patients evaluated and awaiting bariatric surgery. RESULTS: The study group scored better in the SF-36 domains (all four physical domains and the vitality subscore) and OP scale compared to obese controls, but their HRQoL scores were lower than those of the general population. HRQoL was better among younger patients and in the following subgroups: men, patients with satisfactory weight loss, satisfied with the procedure, free from co-morbidities and gastrointestinal symptoms, employment, good oral status and those not hospitalised or regularly followed up for non-bariatric reasons. CONCLUSION: Long-term follow-up after GBP for morbid obesity showed better scores in most aspects of HRQoL compared to obese controls but did not achieve the levels of the general population. Patients with better medical outcome after gastric bypass operation had better HRQoL.

Prevalence of anemia and related deficiencies 10 years after gastric bypass--a retrospective study.

BACKGROUND: Bariatric surgery has gained wide acceptance as treatment for severe obesity and is associated with decreased overall mortality. The aims of this study were to evaluate the prevalence of anemia long term after Roux-en-Y gastric bypass (RYGB) and to search for factors predicting anemia. METHODS: All 745 patients who underwent RYGB between 1993 and 2003 at either Örebro or Uppsala University Hospital and who were living in Sweden were invited to participate by providing a fasting blood sample and completing a questionnaire about their health status. Full blood count, serum iron, transferrin, vitamin B12, and folic acid were determined. RESULTS: Follow-up was completed in 431 patients (58 %) with mean age 51.3 ± 10 years. Of all patients, 27 % had anemia postoperatively and related deficiencies; iron, folic acid, and vitamin B12 were seen in 20, 12, and 2 %, respectively. There was no correlation between anemia and sex, follow-up time, 25-OH vitamin D level, and preoperative or postoperative BMI. An inverse correlation was found between anemia and regular medical checkups concerning gastric bypass surgery. CONCLUSION: Twenty-seven percent of patients had anemia more than 10 years after RYGB. Anemia does not seem to progress with time and was less common in patients with regular medical checkups. Thus, improved long-term follow-up is needed.

Changes in liver volume and body composition during 4 weeks of low calorie diet before laparoscopic gastric bypass.

BACKGROUND: Weight loss before laparoscopic Roux-en-Y gastric bypass (LRYGB) is desirable, because it can reduce liver volume and thereby facilitate the procedure. The optimal duration of a low-calorie diet (LCD) has not been established. The objective of this study was to assess changes in liver volume and body composition during 4 weeks of LCD. METHODS: Ten women (aged 43±8.9 years, 114±12.1 kg, and body mass index 42±2.6 kg/m(2)) were examined on days 0, 3, 7, 14, and 28 after commencing the LCD. At each evaluation, body composition was assessed through bioelectric impedance analysis, and liver volume and intrahepatic fat content were assessed by magnetic resonance imaging. Serum and urine samples were obtained. Questionnaires regarding quality of life and LCD-related symptoms were administered. RESULTS: In total, mean weight decreased by 7.4±1.2 kg (range 5.7-9.1 kg), and 71% of the weight loss consisted of fat mass according to bioelectric impedance analysis. From day 0 to day 3, the weight loss (2.0 kg) consisted mainly of water. Liver volume decreased by 18%±6.2%, from 2.1 to 1.7 liters (P<.01), during the first 2 weeks with no further change thereafter. A continuous 51%±16% decrease was seen in intrahepatic fat content. Systolic blood pressure, insulin, and lipids improved, while liver enzymes, glucose levels, and quality of life were unaffected. CONCLUSION: A significant decrease in liver volume (18%) occurred during the first 2 weeks of LCD treatment, and intrahepatic fat gradually decreased throughout the study period. A preoperative 2-week LCD treatment seems sufficient in similar patients.

A rare case of dyshormonogenetic fetal goiter responding to intra-amniotic thyroxine injections.

Fetal goiter was detected by routine ultrasound in early pregnancy, gestational week (GW) 18, in a 28-year-old woman with no thyroid history, normal thyroid hormone levels and no TSH receptor or thyroid peroxidase antibodies. An umbilical cord blood sample was drawn in GW 23. The analysis indicated fetal hypothyroidism with TSH >100 mU/l (reference value 6.8 ± 2.9, mean ± SD), fT4 3.8 pmol/l (reference value 16.5 ± 5.3, mean ± SD). Intra-amniotic injections of thyroxine were given in conjunction with ultrasound every 7-10 days, in total nine times during GW 24-33. A dose of 10 µg thyroxine/kg of estimated fetal weight per day was administered on six occasions, and 5 µg/kg/day the last three times. Upon injections of thyroxine further growth of the goiter was reduced. Elevated amniotic TSH levels fell from 13 to 2.5 mU/l (reference range 0.04-0.51). Throughout pregnancy, fetal heart rate and skeletal maturation were within normal limits. In week 34, chorioamnionitis was suspected and the child was delivered by cesarean section. Cord blood revealed TSH 596 mU/l (reference value 8.0 ± 5.12, mean ± SD), fT4 4.4 pmol/l (reference value 19.3 ± 4.3, mean ± SD) and total T3 1.18 nmol/l (reference value 0.5 ± 0.3, mean ± SD); the newborn was put on thyroxine supplementation. Psychomotor development of the child, now 3 years old, has been uneventful. The reported experience of treating dyshormonogenetic fetal goiter is limited but growing, creating a need for guidelines on administration of intra-amniotic thyroxine and monitoring treatment.

Twelve-year results for revisional gastric bypass after failed restrictive surgery in 131 patients.

BACKGROUND: Gastric banding (GB) and vertical banded gastroplasty (VBG) may result in unsatisfactory weight loss or intolerable side effects. Such outcomes are potential indications for additional bariatric surgery, and Roux-en-Y gastric bypass is frequently used at such revisions (rRYGB). The present study examined long-term results of rRYGB. METHODS: In total, 175 patients who had undergone rRYGB between 1993 and 2003 at 2 university hospitals received a questionnaire regarding their current status. The questionnaire was returned by 131 patients (75% follow-up rate, 66 VBG and 65 GB patients). Blood samples were obtained and medical charts studied. The reason for conversion was mainly unsatisfactory weight loss among the VBG patients and intolerable side effects among GB patients. RESULTS: The 131 patients (112 women), mean age 41.8 years at rRYGB, were evaluated at mean 11.9 years (range 7-17) after rRYGB. Mean body mass index of those with prior unsatisfactory weight loss was reduced from 40.1 kg/m(2) (range 28.7-52.2) to 32.6 kg/m(2) (range 19.1-50.2) (P<.01). Only 2 patients (2%) underwent additional bariatric surgery after rRYGB. The overall result was satisfactory for 74% of the patients. Only 21% of the patients adhered to the recommendation of lifelong multivitamin supplements while 76% took vitamin B12. Anemia was present in 18%. CONCLUSIONS: rRYGB results in sustained weight loss and satisfied patients when VBG or GB have failed. Subsequent bariatric surgery was rare but micronutrient deficiencies were frequent.

Vitamin D status 10 years after primary gastric bypass: gravely high prevalence of hypovitaminosis D and raised PTH levels.

BACKGROUND: The primary aim of this study was to evaluate the prevalence of vitamin D deficiency and secondary hyperparathyroidism after Roux-en-Y gastric bypass. Secondly, we have tried to assess predictors for vitamin D deficiency. METHODS: Five hundred thirty-seven patients who underwent primary Roux-en-Y gastric bypass surgery between 1993 and 2003 at the Örebro University Hospital and Uppsala University Hospital were eligible for the study. Patients were asked to provide a blood sample between November 2009 and June 2010 and to complete a questionnaire about their postoperative health status. Serum values of 25-OH vitamin D, parathyroid hormone (PTH), alkaline phosphatase (ALP) and calcium were determined. RESULTS: Follow-up was completed in 293 patients, of which 83 % were female, with an age of 49 ± 9.9 years after a median time of 11 ± 2.8 years. Vitamin D, PTH and albumin-corrected calcium values were 42 ± 20.4 nmol/L, 89.1 ± 52.7 ng/L and 2.3 ± 0.1 mmol/L, respectively. Of all patients, 65 % were vitamin D deficient, i.e. 25-OH vitamin D <50 nmol/L, and 69 % had PTH above the upper normal reference range, i.e. >73 ng/L. Vitamin D was inversely correlated with PTH levels (p < 0.001) and positively correlated with calcium (p = 0.016). Vitamin D did not correlate with ALP. The only factor found to predict vitamin D deficiency was high preoperative body mass index (BMI) (p = 0.008), whereas gender, age, time after surgery and BMI at follow-up did not. CONCLUSIONS: Vitamin D deficiency and secondary hyperparathyroidism after Roux-en-Y gastric bypass (RYGB) were confirmed in our study because 65 % of patients had vitamin D deficiency, and 69 % had increased PTH levels more than 10 years after surgery. These data are alarming and highlight the need for improved long-term follow-up. Vitamin D deficiency does not seem to progress with time after surgery, possibly due to weight loss. Only preoperative BMI, cutoff point 43 kg/m(2), was a predictor of vitamin D deficiency at follow-up. Improved long-term follow-up of patients that undergo RYGB is needed.