Usefulness of Ultrasound in Assessing the Impact of Bariatric Surgery on Body Composition: a Pilot Study.

BACKGROUND: Bariatric surgery (BS) has a significant impact on body composition. The purpose of the study is to evaluate the usefulness of musculoskeletal ultrasound (MUS) to bioelectrical impedance (BIA) in the follow-up of patients undergoing BS in terms of body composition and quality of life (QoL). METHODS: This is a prospective pilot study including 32 subjects (75% female, mean age: 49.15 ± 1.9 years) who underwent BS. Fat mass (FM), lean mass (LM), and skeletal muscle index (SMI) were calculated by BIA. MUS measured subcutaneous fat (SF) and thigh muscle thickness (TMT) of the quadriceps. QoL was assessed by the Moorehead-Ardelt questionnaire. All these measurements were performed 1 month prior to BS and at 12-month follow-up. RESULTS: The mean BMI decreased by 6.63 ± 1.25 kg/m2 (p=0.001). We observed significant reductions in FM (p=0.001) and SF (p=0.007) and in LM (p=0.001) but not in SMI and TMT. We found a correlation between the FM and SF (pre-surgical, r=0.42, p=0.01; post-surgical, r=0.52, p=0.003) and between SMI and TMT (pre-surgical, r=0.35, p=0.04; post-surgical, r=0.38, p=0.03). QoL test showed significant improvement (p=0.001). In addition, a correlation between the QoL questionnaire and TMT post-surgery (r=0.91, p=0.019) was observed. However, we did not find any statistically significant correlation between QoL assessment and SMI or LM. CONCLUSIONS: Our results suggest that MUS can be complementary to BIA for the evaluation and the follow-up of body composition after BS. TMT of quadriceps can provide relevant information about regional sarcopenia and has a significant correlation with QoL.

GLUT2 expression by glial fibrillary acidic protein-positive tanycytes is required for promoting feeding-response to fasting.

Feeding behavior is a complex process that depends on the ability of the brain to integrate hormonal and nutritional signals, such as glucose. One glucosensing mechanism relies on the glucose transporter 2 (GLUT2) in the hypothalamus, especially in radial glia-like cells called tanycytes. Here, we analyzed whether a GLUT2-dependent glucosensing mechanism is required for the normal regulation of feeding behavior in GFAP-positive tanycytes. Genetic inactivation of Glut2 in GFAP-expressing tanycytes was performed using Cre/Lox technology. The efficiency of GFAP-tanycyte targeting was analyzed in the anteroposterior and dorsoventral axes by evaluating GFP fluorescence. Feeding behavior, hormonal levels, neuronal activity using c-Fos, and neuropeptide expression were also analyzed in the fasting-to-refeeding transition. In basal conditions, Glut2-inactivated mice had normal food intake and meal patterns. Implementation of a preceeding fasting period led to decreased total food intake and a delay in meal initiation during refeeding. Additionally, Glut2 inactivation increased the number of c-Fos-positive cells in the ventromedial nucleus in response to fasting and a deregulation of Pomc expression in the fasting-to-refeeding transition. Thus, a GLUT2-dependent glucose-sensing mechanism in GFAP-tanycytes is required to control food consumption and promote meal initiation after a fasting period.

Efficacy and feasibility of basal-bolus insulin regimens and a discharge-strategy in hospitalised patients with type 2 diabetes--the HOSMIDIA study.

AIMS: Guidelines recommend use of basal-bolus insulin in hospitalised patients with hyperglycaemia, but information about implementation and medication reconciliation at discharge is scarce. The HOSMIDIA study evaluated a management program involving basal-bolus insulin and an algorithm for medication reconciliation at discharge in non-critically ill hospitalised patients with type 2 diabetes in clinical practice. METHODS: HOSMIDIA was a prospective, observational study performed during routine clinical practice at 15 Spanish hospitals during hospitalisation, with follow-up 3 months postdischarge. Study patients (n = 134) received a basal-bolus regimen with insulin glargine during hospitalisation and treatment at discharge was adjusted according to a simple algorithm. The control group (n = 62) included patients with similar characteristics hospitalised during the month before study initiation and had no follow-up after discharge. RESULTS: Compared with control subjects, patients in the prospective study achieved lower mean total (167.7 ± 41.1 vs. 190.5 ± 53.3 mg/dl) preprandial (164.2 ± 42.4 vs. 189.6 ± 52.6 mg/dl; p < 0.001) and fasting (137.0 ± 42.2 vs. 165.8 ± 56.5 mg/dl) blood glucose levels while hospitalised, without increased hypoglycaemic episodes (17.7% vs. 19.3% patients). In the prospective study, glycaemic control improved from admission to discharge, with control maintained 3 months after discharge. The main treatment modification at discharge compared with admission was addition of basal insulin, and treatment at discharge was maintained at 3 months in 89% of patients. CONCLUSION: The HOSMIDIA study confirmed that management of hyperglycaemia with basal-bolus insulin is feasible and effective in routine clinical practice, and that a simple strategy facilitating the reconciliation of medication on discharge can improve glycaemic control postdischarge.

Diagnosis of cure in Cushing's syndrome: lessons from long-term follow-up.

It is generally assumed that endocrine 'cure' of hypercortisolism after successful treatment for Cushing's syndrome (CS) is associated with reversal of increased morbidity and mortality, typical of the active disease. However, recent data do not support this idea; increased cardiovascular risk is still present 5 years after endocrine cure, and health-related quality of life (HRQoL), although improved when compared to the active phase of hypercortisolism, is still impaired when compared to normal population. Abnormal body composition typical of hypercortisolism (i.e., increased total and trunk fat, reduced bone mass and lean body mass) is not completely normalized, even years after controlling hypercortisolism. Thus, control of hypercortisolism in CS does not normalize HRQoL, long-term cardiovascular risk and morbidity, body composition nor some metabolic parameters. Whether the same occurs in patients exposed to pharmacological doses of exogenous glucocorticoids, and whether the body composition abnormalities associated with the exposure to exogenous glucocorticoids are reversible or not, are worth considering.

Body composition after endogenous (Cushing's syndrome) and exogenous (rheumatoid arthritis) exposure to glucocorticoids.

Exposure to chronic glucocorticoid (GC) excess determines changes in body composition. The aim of the study was to compare body composition in women exposed to endogenous hypercortisolism (Cushing's syndrome, CS), exogenous glucocorticoid treatment (rheumatoid arthritis, RA) and controls. Fifty-one CS women, 26 RA women treated with low-dose prednisone (5 mg/day or 10 mg/2 days), and 78 female controls were included. Fourteen CS patients were hypercortisolemic, 37 in remission (10 required hydrocortisone substitution after surgery). Body composition parameters were measured by dual-energy X-ray absorptiometry scanning (DEXA). RA patients had a greater waist-hip ratio (WHR) (p<0.01), less lean body mass (LBM) (p<0.01), and lumbar bone mineral density (BMD) (p<0.01) than controls. CS patients, globally and those with cured disease, had more total fat (both percentage and kg) and trunk fat percentage, and less whole body-BMD than RA patients (p<0.05, p<0.01, p<0.05, respectively). Active CS patients had less whole body-BMD and more LBM than RA patients (p<0.05, p=0.01, respectively). Cured CS patients not taking hydrocortisone had more total fat [both percentage (p<0.05) and kg (p<0.05)], trunk fat percentage (p<0.05), lumbar BMD (p<0.01) than RA patients. Cured CS patients requiring hydrocortisone only differed from RA patients by smaller WHR (p<0.01). All the differences in BMD disappeared when the data were reanalyzed including only the estrogen-deficient groups. Hypercortisoliof CS determines an irreversible increase in body fat, greater than in RA. Endogenous and exogenous exposure to GC negatively affects body composition by increasing the WHR. There appears to be no additional effect on BMD in estrogen-deficient women.

Thyrotoxic periodic paralysis: a case report and literature review.

We describe a 37-year-old man with a 4-month history of episodic muscular weakness, involving mainly lower-limbs. Hypokalemia was documented in one episode and managed with intravenous potassium chloride. Hyperthyroidism was diagnosed 4 months after onset of attacks because of mild symptoms. The patient was subsequently diagnosed as having thyrotoxic periodic paralysis associated with Graves' disease. Treatment with propranolol and methimazol was initiated and one year later he remains euthyroid and symptom free. Thyrotoxic periodic paralysis is a rare disorder, especially among Caucasians, but it should always be considered in patients with acute paralysis and hypokalemia, and thyroid function should be evaluated.

Gender dimorphism in body composition abnormalities in acromegaly: males are more affected than females.

BACKGROUND: Acromegaly changes body composition (BC), but long-term gender differences have not been reported. OBJECTIVE: To evaluate BC in active and controlled acromegalic patients. DESIGN AND METHODS: Clinical and biochemical variables and BC (by dual-energy X-ray absorptiometry) were evaluated in 60 acromegalic patients (19 active, 41 controlled) and 105 controls, matched for age and gender. RESULTS: Acromegalic males (n=24) had more total mass (89+/-13 vs 76.5+/-15.3 kg, P<0.001), lean body mass (LBM; 64.6+/-8.7 vs 56.4+/-5.8 kg, P<0.001), and bone mineral content (BMC; 2.9+/-0.5 vs 2.6+/-0.3 kg, P<0.05) than controls (n=33). Controlled male patients (n=14) had more total mass (89+/-14.7 vs 76.5+/-15.3 kg, P<0.05) and a trend to have more LBM (61.8+/-9.4 vs 56.4+/-5.8 kg, P=0.065) than controls. Only in active disease was a decrease in fat mass (FM) observed, compared with controlled patients and controls (males: 19.5+/-5.3 vs 27+/-6.2 and 25.9+/-4%, P<0.001; females: 30.3+/-6.7 vs 37.1+/-5.8 and 36.5+/-6.6%, P<0.01). In females, no further differences were observed. No differences in BMC were found between eugonadal and hypogonadal acromegalic patients, but in hypogonadal females, acromegaly appeared to prevent the BMC loss seen in hypogonadal postmenopausal controls. GH and IGF1 levels were negatively correlated with FM (males, P<0.05; females, P<0.001), but in the regression analysis GH was a predictor of FM only in women. CONCLUSIONS: Control of acromegaly reverts decreased FM in both genders; only in males more total mass and a trend for more LBM persist. The anabolic effect of GH on bone reverted in cured males, but persisted in females and appeared to override the bone loss of menopause.

Evaluation of health-related quality of life in patients with Cushing's syndrome with a new questionnaire.

UNLABELLED: Chronic exposure to hypercortisolism has significant impact on patient's health and health-related quality of life (HRQoL), as demonstrated with generic questionnaires. We have developed a disease-generated questionnaire to evaluate HRQoL in patients with Cushing's syndrome (CS; CushingQoL). OBJECTIVE: Validate the CushingQoL questionnaire in patients with CS in clinical practice conditions. DESIGN: Observational, international, cross-sectional study. METHODS: A total of 125 patients were recruited by 14 investigators from Spain, France, Germany, The Netherlands, and Italy over a 2-month period. Clinical and hormonal data were collected and correlated with results of the generic short form 36 (SF-36) questionnaire, a question on self-perceived general health status and the CushingQoL score. RESULTS: A total of 107 patients were pituitary-dependent and 18 adrenal-dependent CS; 104 (83%) were females, mean age 45 years (range 20-73 years); 39 (31%) were currently hypercortisolemic; and 47 (38%) adrenal insufficient. In clinical practice, CushingQoL was feasible (117; 94% of patients fully responded to the questionnaire in a mean time of 4 min), reliable (Crohnbach's alpha=0.87), and valid (factorial analysis demonstrated unidimensionality and Rasch analysis lead to a final version with 12 items). A significant (P<0.001) correlation was observed between CushingQoL score and patients self-perceived general health status and dimensions of SF-36 (Pearson's correlation coefficient > or =0.597). Patients with current hypercortisolism scored worse (lower) than those without (44+/-22 vs 56+/-21, P=0.004). Linear regression analysis identified female gender and hypercortisolism as significant predictors for worse QoL. CONCLUSION: CushingQoL is useful to evaluate HRQoL in patients with CS and correlates with clinical parameters.

Determinants of neurosurgical outcome in pituitary tumors.

OBJECTIVE: Neurosurgery is one of the main therapies for pituitary tumors; optimising outcome is highly desirable for the patient and the health system. We have analysed predictors of outcome in surgically treated pituitary adenomas operated in this centre. DESIGN AND PATIENTS: A total of 289 patients underwent neurosurgery for a pituitary tumor, by the same two neurosurgeons, between 1982 and 2001. Their records were examined to find predictors of post-surgical outcome. Thirty-eight percent were males, with a median age of 40.8 (8-82.7) yr; 51.9% had been operated since 1992, 92.2% by the transsphenoidal route. Most tumors (70.2%) were macroadenomas; 28.4% were non-functioning, 27.3% secreted PRL, 26.3% GH of which 14 (4.8%) also secreted PRL, 17.3% ACTH, 0.3% FSH and 0.3% TSH. RESULTS: A stepwise, forward logistic regression analysis revealed tumor size as the only significant predictor of radiological cure [odds ratio (OR) for macroadenoma 0.16 vs microadenoma, p=0.0005]. Hormonally, PRL-secretion by the tumor was a predictor of poor prognosis (OR 3.29 for cure of non-PRL-secreting tumors, p=0.005), as was tumor size (OR 0.45 for cure of macroadenomas, p=0.005). Considering simultaneous radiological and hormonal remission, tumor size (OR 0.35 for macroadenoma, p=0.0002), and operation date (OR 0.40 for up to 1991, p=0.0002) were the only significant predictors. CONCLUSIONS: PRL secretion, tumor size and operation date are the main predictors of neurosurgical outcome in pituitary tumors, the latter suggesting that neurosurgical experience plays an important role.

Biochemical evidence in favor of revising Cortina criteria.

There is evidence that the Cortina criteria for the cure of acromegaly are not strict enough if the aim is to predict patients where cure will be successful as opposed to patients who will suffer disease recurrence or will have mortality and morbidity return to disease-like levels. These criteria depend on biochemical measurements of GH and IGF-I that are not universally standardised or comparable, even when excluding the older, less sensitive polyclonal radio immuno assay (RIA). The biochemical evidence suggesting a revision of the criteria for curing acromegaly and derived proposals can be summarised as follows: A) Using immunoradiometric assay (IRMA) for GH measurement, no acromegalic patient with elevated IGF-I suppressed GH after 100 g oral glucose tolerance test (OGTT) to < or = 0.14 microg/l, but 50% suppressed to <1microg/l. B) With hourly GH measurements using IRMA, cured acromegalic patients exhibit basal GH values < or = 0.33 microg/l (x +/- 2 SD). C) In patients with normal IGF-I having GH after OGTT suppressed to < or = 0.14microg/l no recurrences were observed, while in 19% with GH >0.14 microg/ showed recurrences (4, 5); however, this was not the experience of others. D) Polyclonal assays for GH exhibit overlap of GH suppression after OGTT between normal subjects and active patients and should therefore be avoided. E) A recent agreement for implementing universal rhGH reference standards by September 2006 will hopefully facilitate the comparison of different assays in the future. F) Reliable IGF-I assays require age- and sex-matched reference ranges. G) For evaluation of long-term biochemical assessment after treatment, both GH and IGF-I should be undertaken. H) In order to monitor treatment with GH-receptor antagonists, a reliable IGF-I assay is of critical importance, since GH measurements cannot be used to evaluate treatment efficacy.

Growth hormone (GH) insensitivity syndrome due to a GH receptor truncated after Box1, resulting in isolated failure of STAT 5 signal transduction.

Congenital GH insensitivity syndrome (GHIS) is usually the result of a mutation in the extracellular domain of the GH receptor (GHR). We report one of only a small number of mutations so far identified within the intracellular domain of the GHR. The probands are a 53-yr-old woman, height 114 cm (SD score, -8.7), peak GH 45 microg/liter during hypoglycemia, IGF-I 8.0 microg/liter [normal range (N) N 54-389], IGF binding protein-3 16 nmol/liter (N 61-254), GHBP 6.8% (N > 10); and her 57-yr-old brother, height 140 cm (SD score, -6), IGF-I 38.8 micro g/liter (N 54-290), IGF binding protein-3 30 nmol/liter (N 61-196). Both patients were homozygous for a 22-bp deletion in the DNA encoding the cytoplasmic domain of the GHR, resulting in a frameshift and premature stop codon. The resultant GHR is truncated at amino acid 449 (GHR1-449) after Box1, the Janus kinase 2 binding domain of the receptor. Functional studies in HEK293 and Chinese hamster ovary cells show GHR1-449 to have a cellular distribution similar to that of the wild-type GHR, judged by binding of iodinated GH, FACS analysis, and immunocytochemistry. Western blot analysis showed GH-induced phosphorylation of Janus kinase 2, signal transducer and activator of transcription (Stat)3, and Erk2 for both GHR1-449 and wild-type GHR. However, no Stat5 activity was detected in cells expressing GHR1-449, consistent with the fact that GHR1-449 contains no Stat5 binding site. In conclusion, we report two adult siblings with GHIS due to a mutation in the intracellular domain of GHR resulting in a selective loss of Stat5 signaling. Results are consistent with the hypothesis that the loss of signaling through the Stat5 pathway results in GHIS.