Publications by authors named "Davide Carvalho"

136 Publications

Characterization of a transgender population in Portugal.

Ann Endocrinol (Paris) 2021 Dec 3. Epub 2021 Dec 3.

Department of Endocrinology, Diabetes and Metabolism of Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal; Faculty of Medicine and Instituto de Investigação e Inovação em Saúde of Universidade do Porto, Porto, Portugal.

Introduction: Gender dysphoria (GD) is a condition in which the individual's gender identity does not correspond to their biological sex, causing significant distress. Biological males who identify as females are referred to as transgender females or as showing male-to-female GD (MtF GD) and biological females who identify as males are referred to as transgender males or as showing female-to-male GD (FtM GD). In our center, there is a multidisciplinary consultation to approach and follow patients with GD.

Aim: We aimed to analyze the characteristics of the individuals who attend this consultation.

Methods: Retrospective study of individuals attending the Sexual Medicine Group Consultation. Age, comorbidities, symptom onset, and hormonal and surgical treatment were analyzed.

Results: In total, 114 patients were diagnosed with GD: 68.4% FtM GD and 31.6% MtF GD. Median age was 30.2±12years. Among the patients, 63.2% reported symptom onset in childhood: 14.9% between 10 and 18years, and 4.4% later than 18years. Median age at treatment initiation was 23.1±7.1years. Several individuals had concomitant medical conditions, notably smoking (n=37; 32.5%) and depression (n=26; 22.3%). The majority of (92.3% FtM GD and 88.9% MtF GD) were under hormone treatment, and about one-third had undergone some sex reassignment surgery.

Discussion: We found higher prevalence of FtM than MtF, in contrast with most other studies. The reasons for this are not clear. A high percentage of our patients were self-medicated. Other characteristics were similar to those previously reported.

Conclusion: Medical requests by individuals with GD are increasing worldwide. To our knowledge, this is the first study to portray a case series in a consultation center dedicated to the diagnosis, treatment and follow-up of individuals with GD in Portugal.
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http://dx.doi.org/10.1016/j.ando.2021.11.004DOI Listing
December 2021

Quality of Life in Children Diagnosed With Non-classic Congenital Adrenal Hyperplasia.

Cureus 2021 Oct 21;13(10):e18937. Epub 2021 Oct 21.

Pediatrics, Sao Joao Hospital Center, Porto, PRT.

Background Non-classical congenital adrenal hyperplasia (NC-CAH) is a chronic disease characterised byexcessive androgen production that may negatively affect the quality of life (QoL) of affected patients. Pediatric Quality of Life Inventory 4.0 (PedsQL™) is a validated tool to assess health-related QoL (HRQoL). Methods A cross-sectional study including 19 patients with NC-CAH was carried out in the pediatric endocrinology department. NC-CAH patients who agreed to participate were included. Anthropometric datawas collected. PedsQL™ was applied to the patients and their parents. Patients were divided into four groups according to age: 2-4, 5-7, 8-12, and 13-18 years old. The control group consisted of healthy individuals from the instrument's validation studies for the Portuguese population and the standard control population used in the PedsQL™ validation study. Results The only difference found concerns the parents' score results for children aged 8-12, which showed physical health and emotional dimension scores significantly higher (86.16±9.86 vs.68.90±23.02 p=0.004, 69.17±14.14 vs. 65.82±19.24 p=0.004), while psychosocial health's score and total scale score were significantly lower than the control group (59.99±9.90 vs. 69.34±14.07 p=0.047, 73.11±4.65 vs.78.86±16.61 p=0.017). Conclusion HRQoL scores are not negatively affected by NC-CAH in most group ages, with the exception of the parents' reports on HRQoL for children aged 8-12. Further studies with a greater number of patients are needed to determine the impact of this chronic disease on the HRQoL of children.
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http://dx.doi.org/10.7759/cureus.18937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604433PMC
October 2021

Adequate magnesium level as an associated factor of pre-diabetes and diabetes mellitus remission in patients with obesity submitted to bariatric surgery.

Sci Rep 2021 10 27;11(1):21223. Epub 2021 Oct 27.

Departamento de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar Universitário São João, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.

Bariatric surgery (BS) can lead to remission of type 2 diabetes mellitus (T2DM), however, the evidence on the influence of preoperative serum magnesium levels on this reversal is scarce. To study the influence of preoperative serum magnesium levels on the pre-T2DM and T2DM remission one year after BS. Retrospective study carried out among 1656 patients with obesity who underwent BS in the Centro Hospitalar Universitário São João. T2DM and pre-T2DM remission were defined as being normal glycaemic measures of at least one year's after BS and without pharmacological therapy. To assess the association between preoperative serum magnesium levels and pre- and T2DM remission, logistic regression models, crude and adjusted for sex, age and body mass index were computed. Patients with normoglycaemia presented hypomagnesaemia less often than those patients with pre-T2DM and T2DM (17.0% vs. 21.3% vs. 39.9%) (p < 0.001). One year after BS, 62.9% of patients with pre-T2DM or T2DM before BS showed remission. Adequate magnesium levels were positively associated with T2DM and pre-T2DM remission, one year after BS (OR 1.79; 95% CI 1.34-2.38), independently of sex, age, and body mass index. Adequate preoperative serum magnesium levels showed to be an important clinical parameter for pre-T2DM and T2DM remission.
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http://dx.doi.org/10.1038/s41598-021-00584-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551299PMC
October 2021

Correction to: Avascular femoral necrosis as part of Cushing syndrome presentation: a case report.

J Med Case Rep 2021 Sep 23;15(1):483. Epub 2021 Sep 23.

Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, 4200-319, Porto, Portugal.

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http://dx.doi.org/10.1186/s13256-021-03105-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461890PMC
September 2021

Beta Cell Function as a Baseline Predictor of Weight Loss After Bariatric Surgery.

Front Endocrinol (Lausanne) 2021 12;12:714173. Epub 2021 Aug 12.

Serviço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Porto, Portugal.

Background: Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain.

Aim: To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity.

Methods: Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery).

Results: There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (β = -1.04 [-1.82 to -0.26], p<0.01; β = -1.16 [-2.13 to -0.19], p=0.02; β = -1.29 [-2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery.

Conclusion: β-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.
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http://dx.doi.org/10.3389/fendo.2021.714173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387593PMC
August 2021

Obesity and Cancer: the Profile of a Population who Underwent Bariatric Surgery.

Obes Surg 2021 11 9;31(11):4682-4691. Epub 2021 Aug 9.

Faculdade de Medicina, Universidade do Porto, Porto, Portugal.

Introduction: Obesity is a significant risk factor for cancer incidence and mortality. The number of patients with obesity who undergo bariatric surgery is increasing; however, the impact of such a procedure in affecting the risk of cancer is not completely understood yet.

Methods: We conducted a retrospective unicentric cohort study to characterize the occurrence of cancer in patients who underwent bariatric surgery from January 2010 to December 2018. For cases of cancer identified after bariatric surgery, we performed a cancer-free survival analysis over time. We also performed a cross-sectional analysis of demographic and clinical characteristics at the time of surgery and compared patients with or without a cancer diagnosis.

Results: Of the 2578 patients who underwent bariatric surgery, 117 patients (4.5%) were diagnosed with a cancer. Fifty-nine cases were diagnosed before surgery, and the remaining 58 cases occurred after the bariatric procedure. The prevalence of cancer was more accentuated in women (4.9%) than among men (2.7%). Thyroid and breast cancer were the most frequent before and after bariatric surgery, respectively. On average, patients with cancer diagnosis were older (49.0 vs 43.3 years, p<0.001) and with a lower level of education (7.4 vs 8.6 school years, p=0.002).

Conclusion: Almost all the cases of cancer identified in this study were obesity-related cancers. Further prospective studies are needed to extend the current knowledge regarding the cancer risk profile of patients who undergo bariatric surgery.
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http://dx.doi.org/10.1007/s11695-021-05626-0DOI Listing
November 2021

Predictors of the effectiveness of insulin pumps in patients with type 1 diabetes mellitus.

Endocrine 2022 Jan 2;75(1):119-128. Epub 2021 Aug 2.

Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal.

Purpose: Insulin pump therapy has become the preferential treatment for type 1 diabetes (T1D) as it mimics the physiological secretion of insulin better than multiple daily injections. However, not all patients improve with insulin pump therapy. This study aims to determine the predictors of the effectiveness of insulin pumps in T1D.

Methods: We conducted a retrospective observational study of patients who started insulin pumps. Data from four timepoints (before, at 6, 12, and 36 months) were evaluated for outcomes of glycemic control and safety. The association of baseline predictors with outcomes was analyzed using linear and logistic regression models.

Results: We evaluated 136 patients (57.4% females, age 36 ± 12 years, duration of T1D 14 ± 9 years). During the follow-up, there was a mean decrease of HbA1c of 0.9 ± 1.2%. The improvement in HbA1c was independent of sex, age, and duration of T1D. Higher baseline HbA1c, family history of diabetes, and not being treated with statins were predictors of improvement in HbA1c. Not being treated with statins and higher baseline HbA1c predicted improvement in HbA1c without worsening hypoglycemia. History of hypoglycemia was a predictor of severe hypoglycemia. Family history, higher baseline HbA1c, and psychological/psychiatric disorders were predictors of ketoacidosis.

Conclusion: Benefits of insulin pump were independent of sex, age, and duration of T1D. Baseline HbA1c, family history of diabetes, treatment with statins, history of hypoglycemia, and psychological/psychiatric disorders were predictors of outcomes, and may allow the identification of patients who benefit most from insulin pump therapy or who are at increased risk of complications.
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http://dx.doi.org/10.1007/s12020-021-02837-4DOI Listing
January 2022

Heterogeneity amongst GLP-1 RA cardiovascular outcome trials results: can definition of established cardiovascular disease be the missing link?

Diabetol Metab Syndr 2021 Jul 27;13(1):81. Epub 2021 Jul 27.

Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar E Universitário S. João, Porto, Portugal.

Atherosclerotic cardiovascular diseases are the leading cause of adverse outcomes in patients with type 2 diabetes, and all new anti-diabetic agents are mandated to undergo cardiovascular outcome trials (CVOTs). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are incretin mimetics that reduce blood glucose levels with a low associated risk of hypoglycaemia. CVOTs with different GLP-1 RAs yielded different results in terms of major cardiovascular composite outcome (MACE), with some trials showing superiority in the treatment arm, whereas other simply displayed non-inferiority. More importantly, the significance of each component of MACE varied between drugs. This begs the question of whether these differences are due to dissimilarities between drugs or other factors, namely trial design, are at the root of these differences. We analyse the trial designs for all CVOTs with GLP-1 RAs and highlight important differences between them, namely in terms of definition of established cardiovascular disease, and discuss how these differences might explain the disparate results of the trials and preclude direct comparisons between them. We conclude that a fair comparison between GLP-1 RA CVOTs would involve post-hoc analysis re-grouping the patients into different cardiovascular risk categories based upon their baseline clinical parameters, in order to even out the criteria used to classify patients.
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http://dx.doi.org/10.1186/s13098-021-00698-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317280PMC
July 2021

Secondary Hyperparathyroidism Among Bariatric Patients: Unraveling the Prevalence of an Overlooked Foe.

Obes Surg 2021 08 12;31(8):3768-3775. Epub 2021 Jun 12.

Serviço de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar e Universitário de S. João, Porto, Portugal.

Introduction: Bariatric surgery (BS) is the most effective therapeutic approach to obesity. It is associated with great gastrointestinal anatomic changes, predisposing the patients to altered nutrient absorption that impacts phosphocalcium metabolism. This study aimed to clarify the prevalence of secondary hyperparathyroidism (SHPT) and its predictors in patients submitted to BS.

Methods: Retrospective study of 1431 patients who underwent metabolic surgery between January 2010 and June 2017 and who were followed for at least 1 year. We compared the clinical and biochemical characteristics of patients with and without secondary hyperparathyroidism (considering SHPT a PTH ˃ 69 pg/mL). Two different analyses were performed: (1) paired analysis of participants before and 1 year after surgery (N = 441); (2) Cross sectional analysis of participants submitted to bariatric surgery before (N = 441), 1 year after (N = 1431) and 4 years after surgery (N = 333). Multiple logistic regression models were used to evaluate possible predictors of SHPT after BS.

Results: The overall prevalence of SHPT was 24.9% before surgery, 11.2% 1 year after surgery and 21.3% 4 years after surgery. Patients submitted to LAGB had the highest prevalence of SHPT 1 year after surgery (19.4%; vs RYGB, 12.8%, vs SG, 5.3%). Four years after surgery, RYGB had the highest prevalence of SHPT (27.0%), followed by LAGB (13.2%) and SG (6.9%). Higher body mass index and age, decreased levels of vitamin D and RYGB seem to be independent predictors of SHPT 1 year after surgery. The only independent predictor of SHPT 4 years after surgery was RYGB.

Conclusion: The prevalence of SHPT is higher before and 4 years after BS than 1 year after surgery. This fact raises some questions about the efficacy of the implemented follow-up plans of vitamin D supplementation on the long term, mainly among patients submitted to RYGB.
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http://dx.doi.org/10.1007/s11695-021-05495-7DOI Listing
August 2021

Mixed medullary-papillary thyroid carcinoma with mixed lymph node metastases: A case report.

Clin Case Rep 2021 May 24;9(5):e04165. Epub 2021 May 24.

Serviço de Endocrinologia do Instituto Português de Oncologia do Porto Francisco Gentil Porto Portugal.

Mixed medullary-follicular-derived carcinoma is a very rare event. It is extremely important to make the correct diagnosis, due to prognostic and treatment implications. A genetic study of these patients is advisable to exclude the presence of MEN 2.
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http://dx.doi.org/10.1002/ccr3.4165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142802PMC
May 2021

Avascular femoral necrosis as part of Cushing syndrome presentation: a case report.

J Med Case Rep 2021 May 26;15(1):287. Epub 2021 May 26.

Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, 4200-319, Porto, Portugal.

Background: The clinical characteristics and complications of Cushing syndrome (CS) are well known and described in the literature. Nevertheless, rare, atypical presentations may go unnoticed. Osteonecrosis is a well-documented complication of glucocorticoid therapy. However, endogenous hypercortisolism is a rare, but relevant, cause of bone avascular necrosis. We describe the case of a woman with CS undiagnosed for 2 years after presenting with femoral avascular necrosis.

Case Presentation: A 38-year-old Caucasian woman was referred for evaluation of secondary amenorrhea, associated with oral contraception withdrawal in the context of deep venous thrombosis (DVT). She had a previous right hip arthroplasty for treatment of avascular necrosis of the femoral head, diagnosed after 3 years of progressive right hip pain and limited mobility. She also had high blood pressure (HBP) of 5 years' duration, and reported weight gain (4 kg in 2 years). There was no history of infertility (gravida 2, para 2). Physical examination revealed buffalo hump, truncal obesity, facial plethora, muscular atrophy and proximal myopathy, and easy bruising (under anticoagulant treatment for DVT). Workup showed abnormal overnight dexamethasone suppression test (DST) (serum cortisol 21.5 µg/dL; normal < 1.8 µg/dL), elevated 24-hour urinary free cortisol (UFC) (728.9 µg/day; reference range 36.0-137.0 µg/day), and suppressed plasma adrenocorticotropic hormone (ACTH) (< 1.0 pg/mL), findings consistent with ACTH-independent CS. Urinary metanephrines and catecholamines were normal, and the remaining analytical study showed no major changes, apart from glycated hemoglobin (HbA1c) of 6.8%. Adrenal computed tomography (CT) scan showed a 25 mm lesion in the left adrenal gland, with density non-suggestive of adenoma. The patient underwent unilateral adrenalectomy and started steroid replacement. Histology revealed an adrenal cortex adenoma. Three months after surgery the patient presented with resolution of HBP and hypercortisolism (UFC 37.4 µg/day; reference range 36.0-137.0 µg/day).

Conclusion: In some cases, CS signs may go unnoticed and the diagnosis postponed. Avascular necrosis is a rare presenting feature of endogenous hypercortisolism, and, if left untreated, complete collapse of the femoral head may ensue, rendering the need for hip replacement in up to 70% of patients. Suspicion and recognition of atypical features is therefore important in avoiding complications and delay in treatment of CS.
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http://dx.doi.org/10.1186/s13256-021-02882-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152328PMC
May 2021

Hyperandrogenism, oligomenorrhea, and erythrocytosis caused by an ovarian Leydig cell tumor: A case report.

Clin Case Rep 2021 May 26;9(5):e04001. Epub 2021 Mar 26.

Serviço de Endocrinologia Diabetes e Metabolismo Centro Hospitalar e Universitário de S. João Porto Portugal.

Leydig cell tumors are rare ovarian neoplasms. Affected individuals typically present with amenorrhea/oligomenorrhea and rapidly progressive features of virilization. Erythrocytosis can also occur as a result of high testosterone levels.
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http://dx.doi.org/10.1002/ccr3.4001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117810PMC
May 2021

Gut microbiota changes after metabolic surgery in adult diabetic patients with mild obesity: a randomised controlled trial.

Diabetol Metab Syndr 2021 May 21;13(1):56. Epub 2021 May 21.

Integromics, Institute of Cardiometabolism and Nutrition, ICAN, Paris, France.

Background: Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30-35 kg/m).

Methods: DM was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass-RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing.

Results: Twenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p < 0.001) and HbA1c was 6.2 vs. 7.7% (p < 0.001) respectively. We observed a continuous increase of genus richness after RYGB up until M12. In the medical arm, genus richness ended-up being significantly lower at M12. Composition analysis indicated significant changes of the overall microbial ecosystem (permanova p = 0.004, [R = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages.

Conclusions: This was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level.

Trial Registration: ISRCTN53984585.
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http://dx.doi.org/10.1186/s13098-021-00672-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139007PMC
May 2021

Thyroid Hormones within the Normal Range and Cardiac Function in the General Population: The EPIPorto Study.

Eur Thyroid J 2021 Apr 8;10(2):150-160. Epub 2020 Jul 8.

EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.

Background: Hypothyroidism and hyperthyroidism are associated with marked changes in cardiac structure and function. However, the association of thyroid function within the normal range with cardiac structure and function in the general population remains uncertain.

Methods: Eight hundred thirty-five subjects aged ≥45 years from the EPIPorto cohort (evaluation between 2006 and 2008) were cross-sectionally analyzed. We excluded participants with TSH, free T4 (FT4), or free T3 (FT3) outside of the reference range or with self-reported cardiovascular or thyroid disease. Cardiac structure and function were evaluated by echocardiography. We used linear regression models unadjusted and adjusted for sex and age (model 1), and sex, age, BMI, diabetes, hypertension, and smoking (model 2). Nonlinear associations were assessed using restricted cubic splines.

Results: The mean age was 61.5 years (SD 10.5); 61.1% of the patients were women. In the adjusted model 2, heart rate was positively associated with FT3; diastolic blood pressure was positively associated with TSH; LV end-diastolic and end-systolic volumes were inversely associated with TSH, and ejection fraction was nonlinearly associated with FT3, with higher ejection fractions near the limits of the reference range. Left ventricle (LV) posterior wall thickness was nonlinearly associated with FT4 in the adjusted model 1, with a greater thickness near the limits of the reference range. Regarding diastolic function, no significant associations were observed in adjusted models.

Conclusions: Thyroid function within the reference range was associated with heart rate, blood pressure, cardiac structure, and function. Increasing thyroid function (lower TSH, higher FT4, or higher FT3) was associated with a higher heart rate, a lower diastolic blood pressure, and larger LV volumes. LV wall thickness and ejection fraction had a U-shaped association with thyroid hormones.
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http://dx.doi.org/10.1159/000508407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077596PMC
April 2021

Evaluation of Thyroid Function in Patients Hospitalized for Acute Heart Failure.

Int J Endocrinol 2021 31;2021:6616681. Epub 2021 Mar 31.

Departamento de Cirurgia e Fisiologia, Unidade de Investigação Cardiovascular, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.

Background: Thyroid hormones (TH) are crucial for cardiovascular homeostasis. Recent evidence suggests that acute cardiovascular conditions, particularly acute heart failure (AHF), significantly impair the thyroid axis. Our aim was to evaluate the association of thyroid function with cardiovascular parameters and short- and long-term clinical outcomes in AHF patients.

Methods: We performed a single-centre retrospective cohort study including patients hospitalized for AHF between January 2012 and December 2017. We used linear, logistic, and Cox proportional hazard regression models to analyse the association of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) with inpatient cardiovascular parameters, in-hospital mortality, short-term adverse clinical outcomes, and long-term mortality. Two models were used: (1) unadjusted, and (2) adjusted for age and sex.

Results: Of the 235 patients included, 59% were female, and the mean age was 77.5 (SD 10.4) years. In the adjusted model, diastolic blood pressure was positively associated with TSH [ = 2.68 (0.27 to 5.09); = 0.030]; left ventricle ejection fraction (LVEF) was negatively associated with FT4 [ = -24.85 (-47.87 to -1.82); = 0.035]; and a nonsignificant trend for a positive association was found between 30-day all-cause mortality and FT4 [OR = 3.40 (0.90 to 12.83); = 0.071]. Among euthyroid participants, higher FT4 levels were significantly associated with a higher odds of 30-day all-cause death [OR = 4.40 (1.06 to 18.16); = 0.041]. Neither TSH nor FT4 levels were relevant predictors of long-term mortality in the adjusted model.

Conclusions: Thyroid function in AHF patients is associated with blood pressure and LVEF during hospitalization. FT4 might be useful as a biomarker of short-term adverse outcomes in these patients.
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http://dx.doi.org/10.1155/2021/6616681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026290PMC
March 2021

The Impact of Vitamin D in Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Patients with Morbid Obesity.

Diabetes Metab Syndr Obes 2021 3;14:487-495. Epub 2021 Feb 3.

Serviço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Porto, Portugal.

Purpose: We aimed to evaluate the association between vitamin D status and hepatic function parameters and scores: Fatty Liver Index (FLI, predictor of hepatic steatosis) and BARD (BMI, AST/ALT ratio and DM, predictor of hepatic fibrosis) in patients with morbid obesity.

Patients And Methods: Cross-sectional study including patients with morbid obesity followed in our centre between January 2010 and July 2018. Patients with missing vitamin D levels or hepatic profile parameters were excluded. We divided the population according to two cut-offs of vitamin D levels (12ng/mL and 20ng/mL).

Results: The included population (n=1124) had an average age of 43.3±10.7 years and 84.3% were female. Seventy-point eight percent of the population had vitamin D levels lower than 20ng/mL and 34.8% lower than 12ng/dL. Patients with lower vitamin D levels (<12ng/mL) had higher BMI, hip and waist circumferences and higher prevalence of hypertension. Higher FLI scores [OR= 0.77 (0.07), p<0.01] and ALP levels [β= -0.03 (-0.06, -0.01), p<0.01] associated to lower vitamin D levels.

Conclusion: Vitamin D deficiency is associated with a higher risk of hepatic steatosis in individuals with morbid obesity. Correction of vitamin D deficiency may have a beneficial role in the management of NAFLD in patients with morbid obesity.
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http://dx.doi.org/10.2147/DMSO.S286334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868234PMC
February 2021

The Glucocorticoid Receptor Gene () 9β SNP Is Associated with Posttraumatic Stress Disorder.

Healthcare (Basel) 2021 Feb 5;9(2). Epub 2021 Feb 5.

i3S-Instituto de Investigação e Inovação em Saúde (Institute for Research and Innovation in Health), Universidade do Porto, 4200-135 Porto, Portugal.

Posttraumatic stress disorder (PTSD) has been associated with glucocorticoid (GC) hypersensitivity. Although genetic factors account for 30-46% of the variance in PTSD, no associations have been found between single nucleotide polymorphisms (SNPs) of the GC receptor (GR) gene () and risk for this disorder. We studied the association of five SNPs in the GR gene (rs10052957, rs6189/rs6190, rs6195, rs41423247, and rs6198) and haplotypes with PTSD, in a group of Portuguese male war veterans (33 with lifetime PTSD, 28 without). To determine whether the 9β SNP (rs6198) was associated with chronically altered cortisol levels, we evaluated hair cortisol concentrations (HCC) in a sample of 69 veterans' offspring. The 9β variant (G allele) was significantly associated with lifetime PTSD under a dominant model of inheritance. The 9β variant was also significantly associated with severity of current PTSD symptoms. The haplotype analysis revealed an association between a common haplotype comprising the 9β risk allele and lifetime PTSD. Carriers of the 9β risk allele had significantly lower HCC than non-carriers. We found the 9β risk allele and a haplotype comprising the 9β risk allele of the GR gene to be associated with PTSD in veterans. This 9β risk allele was also associated with lower HCC in their offspring.
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http://dx.doi.org/10.3390/healthcare9020173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915937PMC
February 2021

Bariatric Surgery Impact on Cardiovascular Risk Factors: Is Age a Factor to Consider?

Obes Facts 2021 15;14(1):72-77. Epub 2020 Dec 15.

Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de S. João, Porto, Portugal.

Introduction: Despite the abundance of data addressing the influence of patient's age on surgery-related complications, its impact on cardiometabolic outcomes following bariatric surgery has been overlooked.

Methods: Retrospective unicentric study of 1,728 obese patients who underwent bariatric surgery between January 2010 and June 2015. Patients were divided in 3 age groups, according to their age at surgery: ˂40 (n = 751), 40-59 (n = 879), and ≥60 years (n = 98). Parameters with cardiometabolic impact, such as body anthropometric measures, lipid profile, and glycemic status, before and 24 months after surgery, were compared between these groups. A multiple linear regression was performed, adjusting differences between groups for sex, surgery type, and body mass index variation.

Results: The group ˂40 years presented more weight loss (-35.4 ± 9.0 kg, p ˂ 0.001), greater BMI reduction (-15.8 ± 6.1 kg/m2, p ˂ 0.001), and larger changes in waist (-34 ± 13.8 cm, p ˂ 0.001) and hip circumferences (-28.7 ± 11.9 cm, p ˂ 0.05). The group of ≥60 years presented the heaviest reduction in fasting glucose (-17.7 ± 32.8 mg/dL, p ˂ 0.001) and HbA1c (0.7 ± 1.0, p ˂ 0.001), and also had a tendency to have the biggest changes in systolic blood pressure (-14.7 ± 18.7 mm Hg, p = 0.071).

Conclusion: Patients with ≥60 years benefit the most from bariatric surgery regarding cardiometabolic parameters, presenting heavier reductions in fasting glucose, as well as HbA1c and a tendency towards a higher decrease in systolic blood pressure. No clinically significant differences in lipid profile were observed between groups.
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http://dx.doi.org/10.1159/000511737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983533PMC
July 2021

ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.

Eur J Endocrinol 2020 Dec 1. Epub 2020 Dec 1.

T Kocjan, Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Ljubljana, Slovenia.

Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform.

Aims: 1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD.

Design: On-line survey in endocrine centres throughout Europe.

Patients And Methods: Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018.

Results: Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved.

Conclusion: Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.
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http://dx.doi.org/10.1530/EJE-20-1180DOI Listing
December 2020

Thyroid Function and the Risk of Non-Alcoholic Fatty Liver Disease in Morbid Obesity.

Front Endocrinol (Lausanne) 2020 28;11:572128. Epub 2020 Oct 28.

Serviço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Porto, Portugal.

Background: An association between hypothyroidism and the risk of Non-alcoholic Fatty Liver Disease (NAFLD) has been suggested. This association remains to be elucidated in patients with morbid obesity.

Aim: To evaluate the association between thyroid function and parameters of liver function and hepatic scores in patients with morbid obesity.

Methods: Patients with morbid obesity followed in our center between January 2010 and July 2018 were included. The ones without evaluation of liver and thyroid functions were excluded. (FLI) and BARD scores were used as predictors of hepatic steatosis and fibrosis, respectively.

Results: We observed a positive association between TSH and both BARD (OR 1.14; p = 0.035) and FLI (OR 1.19; p = 0.010) in the unadjusted analysis. We found a negative association between free triiodothyronine levels and BARD (OR 0.70; p<0.01) and a positive association between free triiodothyronine levels and FLI (OR 1.48; p = 0.022). Concerning liver function, we found a positive association between total bilirubin and free thyroxine levels (β = 0.18 [0.02 to 0.35]; p = 0.033) and a negative association between total bilirubin and free triiodothyronine levels (β = -0.07 [-0.14 to -0.002]; p = 0.042).

Conclusion: Higher levels of TSH and free triiodothyronine may be associated with a higher risk of NAFLD, particularly steatosis, in patients with morbid obesity.
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http://dx.doi.org/10.3389/fendo.2020.572128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655985PMC
May 2021

Thyroid hormones and modulation of diastolic function: a promising target for heart failure with preserved ejection fraction.

Ther Adv Endocrinol Metab 2020 4;11:2042018820958331. Epub 2020 Oct 4.

Departamento de Cirurgia e Fisiologia, Unidade de Investigação Cardiovascular, Faculdade de Medicina, Universidade do Porto, Alameda Hernâni Monteiro, Porto, 4200-319, Portugal.

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome with high mortality for which there is no proven therapy to improve its prognosis. Thyroid dysfunction is common in heart failure (HF) and is associated with worse prognosis. In this review, we discuss the cardiovascular effects of thyroid hormones, the pathophysiology of HFpEF, the prognostic impact of thyroid function, and the potential of thyroid hormones for treatment of HFpEF. Thyroid hormones have a central role in cardiovascular homeostasis, improving cardiac function through genomic and non-genomic mechanisms. Both overt and subclinical hypothyroidism are associated with increased risk of HF. Even when plasmatic thyroid hormones levels are normal, patients with HF may have local cardiac hypothyroidism due to upregulation of type 3 iodothyronine deiodinase. Thyroid hormones improve several pathophysiological mechanisms of HFpEF, including diastolic dysfunction and extra-cardiac abnormalities. Supplementation with thyroid hormones (levothyroxine and/or liothyronine), modulation of deiodinase activity, and heart-specific thyroid receptor agonists are potential therapeutic approaches for the treatment of HFpEF. Further preclinical and clinical studies are needed to clarify the role of thyroid hormones in the treatment of HFpEF.
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http://dx.doi.org/10.1177/2042018820958331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543162PMC
October 2020

Clinical characteristics and incidence of glucose metabolism disorders during the follow-up of surgically treated insulinomas.

Endocrine 2021 02 17;71(2):351-356. Epub 2020 Oct 17.

Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal.

Purpose: Insulinomas are pancreatic endocrine tumors characterized by hypoglycemia resulting from hypersecretion of insulin. The long-term impact of surgical treatment of insulinomas, particularly the risk of glucose metabolism disorders, remains largely unknown.

Methods: We retrospectively evaluated all patients with insulinoma submitted to surgery at Centro Hospitalar Universitário de São João (Porto, Portugal) between 1980 and 2016. We evaluated baseline characteristics of patients at presentation, imaging evaluation, surgical treatment, characteristics of the tumors, perioperative complications, disease remission, and long-term follow-up and metabolic outcomes.

Results: Twenty-eight patients with insulinomas submitted to surgical treatment were included. Sixty-one percent were female, and the average age was 46.4 years. The most reported symptoms were confusion (72%) and diaphoresis (56%). The most used imaging technique was abdominal CT (72%), and the test with the highest percentage of positive results was endoscopic ultrasound (80%). The most used surgical procedure was partial pancreatic resection (71%). The mean tumor diameter was 2.1 cm and 11% of the tumors had lymph node involvement at diagnosis. Pancreatic fistula was the most common postoperative acute complications (21%). After surgery, patients were followed for a median time of 80 months (25th-75th percentile: 20-148 months). Eight patients (32%) developed glucose metabolism disorders (seven developed diabetes and one prediabetes). One of these patients developed albuminuria, and no macrovascular complications were observed during the follow-up.

Conclusions: Disorders of glucose metabolism are a frequent complication during follow-up of surgically treated insulinomas. The prevention, early diagnosis, and treatment of diabetes should be a priority in the follow-up of these patients.
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http://dx.doi.org/10.1007/s12020-020-02520-0DOI Listing
February 2021

The Pathways between Cortisol-Related Regulation Genes and PTSD Psychotherapy.

Healthcare (Basel) 2020 Oct 1;8(4). Epub 2020 Oct 1.

Department of Endocrinology, Diabetes and Metabolism, São João Hospital University Centre, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.

Post-traumatic stress disorder (PTSD) only develops after exposure to a traumatic event in some individuals. PTSD can be chronic and debilitating, and is associated with co-morbidities such as depression, substance use, and cardiometabolic disorders. One of the most important pathophysiological mechanisms underlying the development of PTSD and its subsequent maintenance is a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis. The corticotrophin-releasing hormone, cortisol, glucocorticoid receptor (GR), and their respective genes are some of the mediators of PTSD's pathophysiology. Several treatments are available, including medication and psychotherapies, although their success rate is limited. Some pharmacological therapies based on the HPA axis are currently being tested in clinical trials and changes in HPA axis biomarkers have been found to occur in response not only to pharmacological treatments, but also to psychotherapy-including the epigenetic modification of the GR gene. Psychotherapies are considered to be the first line treatments for PTSD in some guidelines, even though they are effective for some, but not for all patients with PTSD. This review aims to address how knowledge of the HPA axis-related genetic makeup can inform and predict the outcomes of psychotherapeutic treatments.
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http://dx.doi.org/10.3390/healthcare8040376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712185PMC
October 2020

Hair Cortisol as a Marker of Intergenerational Heritage of War? A Study of Veterans and Their Offspring.

Psychiatry Investig 2020 Oct 6;17(10):976-986. Epub 2020 Oct 6.

i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.

Objective: Posttraumatic stress disorder (PTSD) has been associated with lower circulating cortisol levels in specific subgroups, which have also been found in the offspring of people with PTSD. The analysis of hair cortisol concentrations (HCC) is a recent methodology which is used to assess long-term systemic cortisol levels. We aimed to study veterans with war-related lifetime PTSD and their respective offspring with regards to HCC. We also studied the influence of lifetime major depressive disorder (MDD), war experiences, and childhood adversities on HCC in these groups.

Methods: 31 male veterans with PTSD and 28 without PTSD and 69 adult offspring were studied. HCC were quantified by liquid chromatography tandem-mass spectrometry.

Results: No differences in HCC were found between veterans with and without PTSD, or between their respective offspring. Veterans without MDD showed a positive association between total war exposure and HCC. Veterans reporting more frequent childhood physical abuse had lower HCC. Veterans-with-PTSD's offspring with MDD had increased HCC compared to offspring without MDD. Offspring's exposure to more frequent childhood physical abuse was negatively associated with HCC in those without MDD.

Conclusion: HCC did not appear to constitute a marker of intergenerational heritage of war-related PTSD, except in the case of veteranswith-PTSD's offspring with MDD. Our data suggest that HCC is a marker of adult reported childhood physical abuse.
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http://dx.doi.org/10.30773/pi.2020.0212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596280PMC
October 2020

Effects of sodium-glucose co-transporter 2 inhibitors on liver parameters and steatosis: A meta-analysis of randomized clinical trials.

Diabetes Metab Res Rev 2021 09 12;37(6):e3413. Epub 2020 Oct 12.

Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.

Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in Western countries and a common comorbidity with type 2 diabetes (T2D). It lacks effective pharmacotherapy. We aimed to summarize the evidence on the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on liver structure and function.

Materials And Methods: Meta-analysis of randomized clinical trials in PubMed, Web of Science and ClinicalTrials.gov from their inception to April 2019. Trials evaluating liver function and/or structure and comparing SGLT2 inhibitors with placebo or other oral antidiabetic drugs in patients with T2D were included. Twenty studies (from 3033) were included. A total of 1950 patients with T2D, with or without NAFLD, were treated with SGLT2 inhibitors for at least 8 weeks, and 1900 patients were used as controls. Independent extraction was carried out by two observers. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis.

Results: SGLT2 inhibitors induced a significant decrease in serum alanine (-7.43U/L, [95%CI -12.14, -2.71], p < 0.01), in aspartate aminotransferases (-2.83U/L, [-4.71, -0.95], p < 0.01), as well as in gamma glutamyl transferase (-8.21U/L, [-9.52, -6.91], p < 0.01), and an increase in total plasma bilirubin (8.19% [0.79, 15.59], p < 0.01), comparing with placebo or other oral antidiabetic drugs. SGLT2 inhibitors treatment was associated with a decrease in liver steatosis (-3.39% [-6.01, -0.77], p < 0.0.1).

Conclusions: Treatment with SGLT2 inhibitors improves liver structure and function in patients with T2D. This meta-analysis suggests that SGLT2 inhibitors are a promising pharmacological approach for treatment of NAFLD.
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http://dx.doi.org/10.1002/dmrr.3413DOI Listing
September 2021

Vulnerability Factors Associated with Lifetime Posttraumatic Stress Disorder among Veterans 40 Years after War.

Healthcare (Basel) 2020 Sep 24;8(4). Epub 2020 Sep 24.

i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal.

Vulnerability factors for posttraumatic stress disorder (PTSD) development are still controversial. Our aim was to study the vulnerability factors for the development of war-related PTSD over a period of 40 years after exposure. A cross-sectional, observational study was carried out on 61 male traumatized war veterans, taking into consideration adverse childhood experiences (ACE), attachment orientations, number of non-war-related traumatic events, and war experiences. Lifetime PTSD was assessed by using the Clinician-Administered PTSD Scale. Insecure attachment styles were significantly associated with lifetime PTSD and even after adjustment for war exposure this was still significant. Non-war-related traumatic events were not associated with lifetime PTSD, whereas ACE were associated with lifetime PTSD. War-related experiences were also associated with lifetime PTSD, except for injury or disease. The results for our sample show that, 40 years after war, the intensity of war-related experiences and ACE were significantly and independently associated with the development of lifetime PTSD. Insecure attachment was significantly associated with lifetime PTSD, which, in turn, are both positively associated with war exposure. These findings may have implications for patient care, as they constitute a strong argument that attachment-focused therapies could well be necessary 40 years after trauma.
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http://dx.doi.org/10.3390/healthcare8040359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711782PMC
September 2020

Effectiveness of lanreotide autogel 120 mg at extended dosing intervals for acromegaly.

Endocrine 2020 12 28;70(3):575-583. Epub 2020 Jul 28.

Endocrinology and Nutrition Department, Hospital Universitario La Paz, Madrid, Spain.

Purpose: Recent data indicate that extended dosing intervals (EDIs) with lanreotide autogel 120 mg are effective and well-received among patients with acromegaly who have achieved biochemical control with monthly injections of long-acting somatostatin analogues (SSAs). We further evaluated the effectiveness of lanreotide autogel 120 mg delivered at EDIs (>4 weeks) in routine clinical practice.

Methods: Cross-sectional, multicentre, observational study conducted to determine the effectiveness-measured by control of serum insulin-like growth factor 1 (IGF-1)-of lanreotide autogel 120 mg at dosing intervals >4 weeks for ≥6 months in selected patients with acromegaly treated in routine clinical practice (NCT02807233). Secondary assessments included control of growth hormone (GH) levels, treatment adherence, patient satisfaction, and quality of life (QoL) using validated questionnaires (EQ-5D, AcroQoL, and TSQM-9). Patients who received radiotherapy within the last 6 months were excluded.

Results: Among 109 patients evaluated, mean (SD) age was 59.1 (13.2) years. IGF-1 values were normal (mean [SD]: 175.0 [74.5], 95% CI: 160.8 -189.1) in 91.7% of cases and normal in 91.4% of patients without previous radiotherapy treatment (n = 81). GH levels were ≤2.5 and ≤1 ng/mL, respectively, in 80.6% and 58.3%. Most patients were treated either every 5-6 (57.8%) or 7-8 weeks (38.5%), with 2.8% treated greater than every 8 weeks. The mean AcroQoL score was 63.0 (20.1). The mean global treatment satisfaction score (TSQM-9) was 75.1 (16.6). Treatment adherence (defined as no missed injections) was 94.5%.

Conclusion: Lanreotide autogel 120 mg at intervals of >4 weeks provided IGF-1 control in more than 90% of patients with acromegaly. Treatment satisfaction and adherence were good. These findings support use of extended dosing intervals in patients who have achieved good biochemical control with long-acting SSAs.
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http://dx.doi.org/10.1007/s12020-020-02424-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674328PMC
December 2020

Association between Serum Vitamin D and Diabetic Retinopathy in Portuguese Patients with Type 1 Diabetes.

Acta Med Port 2020 Jul 1;33(7-8):459-465. Epub 2020 Jul 1.

Department of Ophthalmology. Centro Hospitalar de São João. Porto. Department of Surgery and Physiology. Faculty of Medicine. University of Porto. Porto. Portugal.

Introduction: Recently, vitamin D has gained importance as a diabetes risk modifier. Our aim was to assess the association between serum vitamin D levels and the prevalence of diabetic retinopathy in patients with type 1 diabetes.

Material And Methods: Retrospective review of a population of patients with type 1 diabetes followed in a Portuguese tertiary center. Patients were included if they had an ophthalmological evaluation and a serum 25-hydroxyvitamin D level determination within the same year. Logistic regression analysis was used to adjust for possible confounders.

Results: We included 182 patients (47% male), and 57% (n = 103) had signs of diabetic retinopathy. We found a significant association between lower circulating levels of 25-hydroxyvitamin D levels and a greater prevalence of diabetic retinopathy after adjusting for confounders (duration of diabetes, estimated glomerular filtration rate, age, sex, metabolic control, season, dyslipidemia and hypertension) (OR = 0.94; 95% CI 0.90 - 0.99, p = 0.023). Longer duration of diabetes and worse metabolic control also remained associated with diabetic retinopathy in the multivariate analysis (OR = 1.20; 95% CI 1.13 - 1.27, p < 0.001 and OR = 4.13; 95% CI 1.34 - 12.7, p = 0.013, respectively).

Conclusion: Lower levels of vitamin D were associated with an increased prevalence of diabetic retinopathy in patients with type 1 diabetes, after adjusting for possible confounders. Future controlled studies may elucidate the molecular routes for this association as well as the role of supplementation in the prevention of diabetes microvascular complications.
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http://dx.doi.org/10.20344/amp.12890DOI Listing
July 2020

Multivariable Prediction Model for Biochemical Response to First-Generation Somatostatin Receptor Ligands in Acromegaly.

J Clin Endocrinol Metab 2020 09;105(9)

Department of Medicine, Endocrinology section, Pituitary Center Rotterdam, Erasmus University Medical Center, Rotterdam, the Netherlands.

Context: First-generation somatostatin receptor ligands (fg-SRLs) represent the mainstay of medical therapy for acromegaly, but they provide biochemical control of disease in only a subset of patients. Various pretreatment biomarkers might affect biochemical response to fg-SRLs.

Objective: To identify clinical predictors of the biochemical response to fg-SRLs monotherapy defined as biochemical response (insulin-like growth factor (IGF)-1 ≤ 1.3 × ULN (upper limit of normal)), partial response (>20% relative IGF-1 reduction without normalization), and nonresponse (≤20% relative IGF-1 reduction), and IGF-1 reduction.

Design: Retrospective multicenter study.

Setting: Eight participating European centers.

Methods: We performed a meta-analysis of participant data from 2 cohorts (Rotterdam and Liège acromegaly survey, 622 out of 3520 patients). Multivariable regression models were used to identify predictors of biochemical response to fg-SRL monotherapy.

Results: Lower IGF-1 concentration at baseline (odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.72-0.95 IGF-1 ULN, P = .0073) and lower bodyweight (OR = 0.99, 95% CI 0.98-0.99 kg, P = .038) were associated with biochemical response. Higher IGF-1 concentration at baseline (OR = 1.40, (1.19-1.65) IGF-1 ULN, P ≤ .0001), the presence of type 2 diabetes (oral medication OR = 2.48, (1.43-4.29), P = .0013; insulin therapy OR = 2.65, (1.02-6.70), P = .045), and higher bodyweight (OR = 1.02, (1.01-1.04) kg, P = .0023) were associated with achieving partial response. Younger patients at diagnosis are more likely to achieve nonresponse (OR = 0.96, (0.94-0.99) year, P = .0070). Baseline IGF-1 and growth hormone concentration at diagnosis were associated with absolute IGF-1 reduction (β = 0.90, standard error (SE) = 0.02, P ≤ .0001 and β  = 0.002, SE = 0.001, P = .014, respectively).

Conclusion: Baseline IGF-1 concentration was the best predictor of biochemical response to fg-SRL, followed by bodyweight, while younger patients were more likely to achieve nonresponse.
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http://dx.doi.org/10.1210/clinem/dgaa387DOI Listing
September 2020

Which Factors Are Associated with a Higher Prevalence of Anemia Following Bariatric Surgery? Results from a Retrospective Study Involving 1999 Patients.

Obes Surg 2020 09;30(9):3496-3502

Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.

Introduction: Anemia in obese patients is common and multifactorial and is also a complication of bariatric surgery. The aim of this study is to establish which variables are associated with a higher prevalence of post-bariatric surgery anemia.

Methods: Retrospective cohort study involving 1999 patients submitted to bariatric surgery with a follow-up period of 4 years. Anthropometric, laboratorial parameters and the presence of comorbidities were evaluated before surgery and during follow-up. Patients were divided into two groups, according to whether they developed anemia, or not. Groups were compared using independent sample T-tests or Chi-squared tests, as appropriate. Univariate binary logistic regression models were used to test the association between the diagnosis of anemia during follow-up and all the possible explanatory variables. Independent variables with an association with the outcome (p < 0.1) were included in multivariate binary logistic regression models, as well as possible confounders (age, BMI, and supplementation).

Results: Anemia was diagnosed in 24.4% of the patients. Females present a two-fold increased risk of developing anemia (OR 2.11, 95% CI 1.48-3.01, p < 0.001). Patients subjected to gastric sleeve and gastric band surgery present approximately half the risk of anemia when compared with gastric bypass surgery (RYGB) (OR 0.46, 95% CI 0.35-0.59, p < 0.001; OR 0.51, 95% CI 0.36-0.72, p < 0.001). None of the other variables evaluated showed association with the outcome.

Conclusion: In our study, the only factors associated with an increased risk of developing anemia were female gender and RYBG surgery. Prospective studies evaluating the risk factors for anemia in patients undergoing bariatric surgery are needed.
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http://dx.doi.org/10.1007/s11695-020-04673-3DOI Listing
September 2020
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