Effects of Acute Recombinant Human TSH on Serum Ghrelin Levels

Recent findings showed the presence of a reciprocal relationship between thyroid hormones and ghrelin, although the exact mechanism is not known. Design: Our study is addressed to evaluate the effect of acute exogenous rhTSH administration on serum ghrelin levels in athyreotic patients on replacement l-thyroxine therapy. The study group included 50 patients (16 males and 34 females) submitted to total thyroidectomy and 131-iodine remnant ablation for differentiated thyroid cancer on l-thyroxine therapy. Mean age was 47.5 ± 16.5 years and mean BMI was 25.6 ± 5.01 kg/m2. rhTSH was administrated at the dosage of 0.9 mg i.m. once daily for two consecutive days. Blood samples were taken between 08.00 and 09.00 after a overnight fasting for measurement of TSH, FT3, FT4, and ghrelin before the first administration of rhTSH and for measurement of TSH and ghrelin 24, 48, 72, and 96 h after the first administration of rhTSH. Results: Mean ± SD values of basal TSH were 0.54 ± 0.77 μU/ml without significant difference between females and males. As expected, after rhTSH administration TSH concentrations increased at 24 and 48 h with peak TSH values ranging from 20.20 to 313 μU/ml (mean ± SD 98.4 ± 66.7 μU/ml). Mean ± SD values of basal ghrelin were 1085 ± 373 pg/ml without significant difference between males and females. After rhTSH administration ghrelin concentrations decreased significantly (p < 0.01) at 24 h (mean ± SD 934 ± 314 pg/ml p < 0.01) and returned to pre-treatment levels at 96 h. Conclusion: Our study demonstrates that acute exogenous TSH administration has a suppressive effect on ghrelin secretion independent from changes in thyroid status

Follow-up after bariatric surgery: is it time to tailor it? Analysis of early predictive factors of 3-year weight loss predictors of unsuccess in bariatric patients

Bariatric surgery (BS) is the most effective treatment strategy for obesity. Nevertheless, a subset of patients does not reach a successful weight loss or experience long-term weight regain. Conflicting evidence exists regarding predictors of BS outcomes. We aimed to define the early factors linked to 3 year unsuccessful weight loss in order to promote a tailored close follow-up. We enrolled 443 patients who underwent BS from January 2014 to December 2018 with a 3 year follow-up. An unsuccessful BS outcome was defined as a percentage of total weight loss (%TWL) &lt;20. We compared the characteristics between successful and unsuccessful patients in order to identify predictor factors of unsuccess after surgery. We found that the proportion of patients with unsuccessful weight loss progressively increased from one to three years after BS. In a multiple regression model, only 1 month %TWL and sleeve gastrectomy (SG) were significantly associated with 3 year unsuccessful weight loss. We stratified our cohort in four groups according to the risk of BS unsuccess, in terms of 1 month %TWL and type of surgery (SG vs gastric bypass). Interestingly, groups showed a significant difference in terms of %TWL at each follow-up point. Patients submitted to SG with lower 1 month %TWL must be considered at higher risk of future weight regain; consequently, they require a tailored and closer follow-up.[GRAPHICS]. © 2022, The Author(s)

RARE POMC MUTATION IN A PATIENT WITH MYOTONIC DYSTROPHY TYPE 1 AND ADRENOCORTICOTROPIN HYPERRESPONSE TO CORTICOTROPIN-RELEASING HORMONE

Objective: Myotonic dystrophy (DM) is a monogenic disorder. It is caused by expansion of a cytosine-thymineguanine triplet in the DMPK gene which encodes for myotonic dystrophy protein kinase (DMPK). Methods: A 24-year-old man with DM and the DMPK mutation presented with elevated adrenocorticotropic hormone (ACTH) levels twice (152 and 185 pg/mL; normal value is 10 to 52 pg/mL) with normal cortisol levels (134.6 and 113.0 ng/mL, or 371.3 and 311.7 nmol/L; normal values are 67 to 226 ng/mL or 184.8 to 623.5 nmol/L). ACTH, corticotropin-releasing hormone (CRH) and insulin tolerance test (ITT) demonstrated normal cortisol response to ACTH and partial response to CRH and ITT tests, and ACTH hyperresponse to CRH and ITT. We suspected ACTH and/or ACTH receptor (ACTHR) mutations and evaluated the genetic profile for pro-opiomelanocortin (POMC), melanocortin 2 receptor (MC2R) and follicle-stimulating hormone receptor (FSHR) genes. Results: No mutations were found in either the MC2R or FSHR genes. The patient was heterozygous for the c.614A&gt;G mutation corresponding to a p.53D&gt;G substitution with a glycine instead of an aspartate in position 53 in POMC gene. This mutation was outside the sequence for ACTH (which spans amino acids 138 to 176) but was included in the part originating the N-terminal peptide of pro-opiomelanocortin (also called pro-γ-melanocyte stimulating hormone) which spans amino acids 27 to 102 and is involved in the regulation of adrenal steroidogenesis. Conclusion: The pathologic expansion of the cytosine-thymine-guanine triplet repeat in the 3' noncoding region of DMPK could explain the hyperresponse of ACTH typical of DM. The mutation of pro-γ-melanocyte-stimulating hormone could be associated with the abnormal response of cortisol, compatible with a partial adrenal insufficiency. Other studies are necessary to demonstrate this hypothesis

Feasibility, Adherence and Efficacy of Liraglutide Treatment in a Sample of Individuals With Mood Disorders and Obesity

Background: Liraglutide is a once-daily injectable medication approved for the treatment of obesity. Hereby we report the feasibility, adherence and efficacy of liraglutide treatment in a sample of individuals with mood disorders and obesity.Methods and Sample: Twenty-nine patients with Bipolar or Major Depressive Disorder received liraglutide once daily subcutaneously at a dose gradually titrated from 0.6 to 3 mg. All patients were obese and had previously failed multiple healthy lifestyle interventions, including exercise and diet programs. Patients' weight was recorded before liraglutide treatment (T0) and then 1 (T1), 3 (T3), and 6 months (T6) following T0.Results: Mean baseline (T0) weight was 110.54 Kg (±24.95). Compared to baseline, the percentage of weight loss was 3.37% at T1, 7.85% at T3, and 10.20% at T6. Thirty-one percent (n = 9) of patients had no side effects, 34.48% (n = 10) had one, 24.14% (n = 7) had two, and 10.34% (n = 3) had three side effects. All 29 subjects were still on liraglutide at T1; 79.31 and 48.28% were on liraglutide at T3 and T6. No significant relationship was found between liraglutide dose and likelihood to continue the medication. No patient showed a worsening of the psychiatric condition due to liraglutide treatment. Acceptability and satisfaction with treatment were good for the 48% that completed the study.Conclusions: Liraglutide treatment was efficacious, accepted and tolerated by ~50% of our sample, followed up for a period of 180 days. Larger, longer, controlled, prospective studies are warranted

CONUT Score: A New Tool for Predicting Prognosis in Patients with Advanced Thyroid Cancer Treated with TKI

(1) Background: The Controlling Nutritional Status (CONUT) score is an immuno-nutritional screening tool based on serum albumin, total cholesterol, and lymphocyte count. The aim of the study was to assess the CONUT score as a potential prognostic factor of response to therapy in patients with advanced thyroid cancer treated with tyrosine kinase inhibitors (TKIs). (2) Methods: We retrospectively evaluated 42 metastatic thyroid cancer patients (54.8% female). The median age at the time of TKI treatment was 69 years. Histological diagnosis was differentiated thyroid cancer in 66.7%, poorly differentiated thyroid cancer in 21.4%, and medullary thyroid cancer in 11.9% of patients. CONUT score was assessed before starting TKI therapy. (3) Results: Progression-free survival (PFS) and overall survival (OS) were significantly influenced by baseline CONUT score. The best CONUT cut-off able to predict the response to treatment was 3. Both PFS and OS were better in patients with CONUT score &lt;3 than in those with CONUT score &ge;3 (p &lt; 0.0001). CONUT score was the only independent prognostic factor associated with PFS (p = 0.021) and OS (p = 0.007). (4) Conclusions: CONUT score represents a relatively new screening tool, easily applicable in clinical practice and potentially useful in predicting prognosis in thyroid cancer patients treated with TKIs

Novel Pathogenic Variants of the AIRE Gene in Two Autoimmune Polyendocrine Syndrome Type I Cases with Atypical Presentation: Role of the NGS in Diagnostic Pathway and Review of the Literature

Background. Autoimmune polyglandular syndrome type 1 (APS-1) with or without reversible metaphyseal dysplasia is a rare genetic disorder due to inactivating variants of the autoimmune regulator, AIRE, gene. Clinical variability of APS-1 relates to pleiotropy, and the general dysfunction of self-tolerance to organ-specific antigens and autoimmune reactions towards peripheral tissues caused by the underlying molecular defect. Thus, early recognition of the syndrome is often delayed, mostly in cases with atypical presentation, and the molecular confirm through the genetic analysis of the AIRE gene might be of great benefit. Methods. Our methods were to investigate, with a multigene panel next generation sequencing approach, two clinical cases, both presenting with idiopathic hypoparathyroidism, also comprising the AIRE gene; as well as to comment our findings as part of a more extensive review of literature data. Results. In the first clinical case, two compound heterozygote pathogenic variants of the AIRE gene were identified, thus indicating an autosomal recessive inheritance of the disease. In the second case, only one AIRE gene variant was found and an atypical dominant negative form of APS-1 suggested, later confirmed by further medical ascertainments. Conclusions. APS-1 might present with variable and sometimes monosymptomatic presentations and, if not recognized, might associate with severe complications. In this context, next generation diagnostics focused on a set of genes causative of partially overlapping disorders may allow early diagnosis

Is sleeve gastrectomy a therapeutic procedure for all obese patients?

Background: Laparoscopic sleeve gastrectomy (LSG) is a worldwide surgical procedure for morbid obesity. However patients selection is still anecdotal. The aim of this study is to analyse clinical and anthropometric parameters correlated with LSG and to check the validity of this procedure for different categories of obese patients. Methods: Two-hundred one consecutive patients were submitted to LSG as a primary bariatric procedure between 2008 and 2014. One year follow-up was completed in 159 patients. Smaller groups of patients completed 2 and 3 years follow-up (78, 46 patients respectively). Median preoperative body mass index (BMI) was 45.4 kg/m2 (range: 34.8-73.8); 135 patients (80%) had one or more comorbidities. Potential correlations between age, gender, preoperative BMI, preoperative excess weight, early excess weight loss (EWL) and 1 and 3 year-EWL were investigated. Results: All procedures were regularly completed with laparoscopic approach without conversion to laparotomy. Postoperative complications occurred in six patients (3.7%); no postoperative mortality was observed. Median one-year BMI and EWL were 32.8 kg/m2 and 55.34%, respectively. Three year-EWL was significantly influenced by age, and early EWL. A complete normalization of glycemic levels after the three-year follow-up was also observed in high percentage of diabetic patients. In patients with preoperative BMI>50 kg/m2 we observed most failure cases in terms of EWL and the worst metabolic results. Conclusions: Our experience indicates that LSG is a safe procedure with satisfactory three-year late weight loss in patients with preoperative BMI <50 kg/m2. Promising results, in terms of improvements of comorbidities, were also observed. These results make LSG one of the most attractive first stage surgical procedure for morbid obesity