Association between inadequate weight gain according to the institute of medicine 2009 guidelines and pregnancy outcomes in women with thyroid disorders.

PURPOSE: Gestational weight gain (GWG) is an important contributor to pregnancy outcomes in the general obstetric population and different subgroups. The corresponding information in women with thyroid conditions is limited. We aimed to evaluate the relationship between GWG according to institute of medicine (IOM) and pregnancy outcomes in women with thyroid disorders. METHODS: We performed a retrospective analysis of 620 pregnant women either treated with levothyroxine (N = 545) or attended because of hyperthyroidism during pregnancy (N = 75). RESULTS: The associations between GWG according to IOM and pregnancy outcomes were present both in women treated with thyroid hormone and women followed by hyperthyroidism, most of them related to the fetal outcomes. In women treated with levothyroxine, insufficient GWG was associated with gestational diabetes mellitus (GDM) (odds ratio (OR) 2.32, 95% confidence interval (CI) 1.18, 4.54), preterm birth (OR 2.31, 95% CI 1.22, 4.36), small-for-gestational age newborns (OR 2.38, 95% CI 1.09, 5.22) and respiratory distress (OR 6.89, 95% CI 1.46, 32.52). Excessive GWG was associated with cesarean delivery (OR 1.66, 95% CI 1.10, 2.51) and macrosomia (OR 2.75, 95% CI 1.38, 5.49). Large-for-gestational age newborns were associated with both insufficient GWG (OR 0.25, 95% CI 0.11, 0.58) and excessive GWG (OR 1.80, 95% CI 1.11, 2.92). In women followed by hyperthyroidism, excessive GWG was associated with large-for-gestational age newborns (OR 5.56, 95% CI 1.03, 29.96). CONCLUSION: GWG according to IOM is associated with pregnancy outcomes both in women treated with thyroid hormone and women followed by hyperthyroidism.

Frailty in outpatients with cirrhosis: A prospective observational study.

BACKGROUND AND AIM: Frailty is increasingly recognized as a major prognostic factor in cirrhosis in addition to conventional liver insufficiency scores. The aim was to compare the prevalence and characteristics of frailty between patients with cirrhosis and controls, and to analyse its prognostic value. METHODS: We included outpatients with cirrhosis and age- and gender-matched non-cirrhotic controls. Frailty was defined according to the Fried frailty criteria. In patients with cirrhosis, we analysed the ability of the degree of frailty to predict a composite endpoint, consisting of hospitalization, admission to a long-term care centre, falls or death. RESULTS: We included 135 patients with cirrhosis and 135 controls. The prevalence of frailty was higher among patients with cirrhosis: 35 (25.9%) frail, 74 (54.8%) pre-frail and 26 (19.2%) robust vs 14 (10.4%) frail, 67 (49.6%) pre-frail and 54 (40%) robust (P < .001) in controls. This difference was mainly as a result of decreased muscle strength in patients with cirrhosis. During follow-up, frail patients with cirrhosis showed a higher probability of composite endpoint, hospitalization and falls than pre-frail and robust cirrhotic patients but mortality was similar. MELD-Na score and frailty were independent predictive factors for hospitalization, frailty for falls, and MELD-Na score and albumin for survival. Vitamin D deficiency and increased cystatin C were associated with frailty. CONCLUSIONS: Frailty was more frequent in outpatients with cirrhosis than in controls, mainly because of a decrease in muscle strength, and it could be a predictive factor for hospitalization and falls in these patients.

Cystatin-C and epicardial adipose tissue as noninvasive predictors of cardiovascular risk in acromegaly.

BACKGROUND: Acromegaly (ACRO) is associated with elevated cardiovascular risk, although the prevalence of coronary artery disease (CAD) is unclear. Increased epicardial adipose tissue (EAT) and elevated cystatin-C (Cys-C) levels are cardiovascular risk factors, also related to the progression of CAD in several populations. AIMS: To measure the severity and extent of CAD in patients with ACRO and to determine whether either EAT or Cys-C reflect higher cardiovascular risk in patients with ACRO than in healthy controls. SUBJECTS AND METHODS: Case-control study, of 35 patients with ACRO (19 males, 17 with active disease) and 35 age-, gender- and body mass index (BMI)-matched healthy controls; mean age was 48·1 ± 8·1 years and mean BMI was 27·6 ± 4·8 kg/m2 . Cys-C was measured by an immunoturbidimetric assay. The 10-year risk of developing a coronary event was calculated using the Framingham Risk Score (FRS). EAT index (volume indexed to body surface area), and severity and extent of CAD were measured using a 256-slice multidetector computed tomography scanner (iCT-256 Philips Healthcare, Amsterdam). RESULTS: Coronary artery disease lesions, EAT index and severity/extent of CAD were similar between patients with ACRO and controls. Forty-four per cent of patients with ACRO had mild coronary lesions associated with greater EAT index (ß = 0·022, P = 0·036). Cys-C levels correlated with both EAT index (ρ = 0·386, P = 0·031) and FRS (ρ = 0·477, P = 0·004) in patients with ACRO only, despite similar prevalence of traditional cardiovascular risk factors. In a multiple linear regression model, both Cys-C levels (ß = 0·369, P = 0·007) and EAT index (ß = 0·29, P = 0·025) predicted FRS (R2 = 0·613). CONCLUSIONS: In patients with ACRO, both Cys-C and EAT index might be used as noninvasive predictors of cardiovascular risk.

Pituitary response profile following metoclopramide administration in women with different forms of hyperprolactinemia.

AIMS: To test the hypothesis that macroprolactinemia is an extra-pituitary phenomenon by showing that the pituitary production of prolactin in patients with hyperprolactinemia due to macroprolactin is comparable to that in normoprolactinemic women and different from that in women with monomeric hyperprolactinemia. METHODS: Twenty-five women were studied: eight with macroprolactin hyperprolactinemia, eight with monomeric hyperprolactinemia, and nine controls. Prolactin levels were measured before and after precipitation with polyethylene glycol at baseline and at 5, 10,15, 30, and 60 min after metoclopramide administration (10 mg i.v.) in the three groups. RESULTS: The response profile of total and monomeric prolactin following the administration of metoclopramide was similar in women with monomeric hyperprolactinemia and normoprolactinemia but different in women with macroprolactinemia. The areas under the curve for total and monomeric prolactin were higher in patients with macroprolactinemia than in the other two groups (p < 0·0001). The maximal concentration of monomeric prolactin was reached before that of total prolactin in macroprolactinemic patients but the differences were not significant. DISCUSSION: Our findings support the hypothesis that prolactin secretion is comparable in women with macroprolactinemia and in normoprolactinemic women. The dynamics of the secretion suggest that the formation of prolactin complexes is an extra-pituitary process.

Relative adrenal insufficiency in severe acute variceal and non-variceal bleeding: influence on outcomes.

BACKGROUND & AIMS: Relative adrenal insufficiency (RAI) is common in critical illness and in cirrhosis, and is related with worse outcomes. The prevalence of RAI may be different in variceal and non-variceal bleeding and whether it may influence outcomes in these settings is unclear. This study assesses RAI and its prognostic implications in cirrhosis with variceal bleeding and in peptic ulcer bleeding. METHODS: Patients with severe bleeding (systolic pressure <100 mmHg and/or haemoglobin <8 g/L) from oesophageal varices or from a peptic ulcer were included. Adrenal function was evaluated within the first 24 h and RAI was diagnosed as delta cortisol <250 nmol/L after 250 µg of i.v. corticotropin. RESULTS: Sixty-two patients were included, 36 had cirrhosis and variceal bleeding and 26 without cirrhosis had ulcer bleeding. Overall, 15 patients (24%) had RAI, 8 (22%) with variceal and 7 (24%) with ulcer bleeding. Patients with RAI had higher rate of bacterial infections. Baseline serum and salivary cortisol were higher in patients with RAI (P < 0.001) while delta cortisol was lower (P < 0.001). There was a good correlation between plasma and salivary cortisol (P < 0.001). The probability of 45-days survival without further bleeding was lower in cirrhotic patients with variceal bleeding and RAI than in those without RAI (25% vs 68%, P = 0.02), but not in non-cirrhotic patients with peptic ulcer bleeding with or without RAI (P = 0.75). CONCLUSION: The prevalence of RAI is similar in ulcer bleeding and in cirrhosis with variceal bleeding. Cirrhotic patients with RAI, but not those with bleeding ulcers, have worse prognosis.

Hypovitaminosis D in type 2 diabetes: relation with features of the metabolic syndrome and glycemic control.

AIM: To assess the association of hypovitaminosis D with clinical and biochemical characteristics of type 2 diabetic patients and to determine the effect of glycemic control optimization on 25-hydroxyvitamin D (25(OH)D) concentrations. METHODS: Cross-sectional study of 63 patients with type 2 diabetes (mean age 60 ± 9.8 years, 69.8% men). Twenty of the 63 patients were also studied before and after glycemic control optimization. RESULTS: Mean 25(OH)D concentrations were 63.64 ± 25.51 nmol/L and 74.6% of patients had hypovitaminosis D. Compared with patients with vitamin D sufficiency, patients with hypovitaminosis D had higher prevalence of overweight or obesity (72.3% versus 37.5%; p = 0.012) and higher VLDL cholesterol (VLDL-c) (0.71 (0.24-3.59) versus 0.45 (0.13-1.6) mmol/L; p = 0.011) and C-reactive protein (3.28 (0.36-17.69) versus 1.87 (0.18-17.47) mg/L; p = 0.033) concentrations. The composition of HDL particles also differed in both groups, with higher relative content of triglycerides and lower of cholesterol in patients with hypovitaminosis D. After adjustment for age, seasonality and BMI, differences remained significant for VLDL-c and triglyceride content of HDL. No differences were found regarding other diabetes characteristics. Improvement of glycemic control (HbA1c 9.4 (7.6-14.8) versus 7.3 (6.2-8.7)%; p = 0.000) was accompanied by a decrease in 25(OH)D concentrations (72.7 ± 33.3 to 59.0 ± 21.0 nmol/L; p = 0.035). Correlation analysis revealed that changes in 25(OH)D concentrations were negatively associated to changes in HbA1c (r - 0.482; p = 0.032). CONCLUSION: Hypovitaminosis D is associated with features of the metabolic syndrome in type 2 diabetes and improvement of glycemic control decreases 25(OH)D concentrations.

Home exercise, branched-chain amino acids, and probiotics improve frailty in cirrhosis: A randomized clinical trial.

BACKGROUND: Frailty is a predictive factor of hospitalization, falls, and mortality in patients with cirrhosis, regardless of the degree of liver failure. The aim was to analyze whether a multifactorial intervention consisting of home-based exercise, branched-chain amino acids, and a multistrain probiotic can improve frailty in these patients. METHODS: Outpatients with cirrhosis were classified according to the Liver Frailty Index (LFI). Prefrail and frail patients were randomized into 2 groups. The intervention group was assigned to a multifactorial intervention consisting of exercise at home, branched-chain amino acid supplements, and a multistrain probiotic for 12 months. The control group received standard care. All patients were prospectively followed up every 3 months for 1 year to determine LFI, incidence of falls, emergency room visits, hospitalizations, and mortality. RESULTS: Thirty-two patients were included: 17 patients were assigned to the intervention group and 15 to the control group. In the intervention group, the baseline LFI decreased at 3, 6, 9, and 12 months (p = 0.019 for overall change with respect to the control group). The change in LFI (ΔLFI) at 12 months was -0.71 ± 0.24 in the intervention group and -0.09 ± 0.32 in the control group (p<0.001). During follow-up, patients in the intervention group had a lower 1-year probability of falls (6% vs. 47%, p = 0.03) and emergency room visits (10% vs. 44%, p = 0.04) than patients in the control group. CONCLUSIONS: A long-term multifactorial intervention that included exercise at home, branched-chain amino acids, and a multistrain probiotic improved frailty in outpatients with cirrhosis and was associated with a decrease in the incidence of clinical events such as falls and emergency room visits.

Clinical and outcome comparison of genetically positive vs. negative patients in a large cohort of suspected familial hypocalciuric hypercalcemia.

OBJECTIVE: Biochemical suspicion of familial hypocalciuric hypercalcemia (FHH) might provide with a negative (FHH-negative) or positive (FHH-positive) genetic result. Understanding the differences between both groups may refine the identification of those with a positive genetic evaluation, aid management decisions and prospective surveillance. We aimed to compare FHH-positive and FHH-negative patients, and to identify predictive variables for FHH-positive cases. DESIGN: Retrospective, national multi-centre study of patients with suspected FHH and genetic testing of the CASR, AP2S1 and GNA11 genes. METHODS: Clinical, biochemical, radiological and treatment data were collected. We established a prediction model for the identification of FHH-positive cases by logistic regression analysis and area under the ROC curve (AUROC) was estimated. RESULTS: We included 66 index cases, of which 30 (45.5%) had a pathogenic variant. FHH-positive cases were younger (p = 0.029), reported more frequently a positive family history (p < 0.001), presented higher magnesium (p < 0.001) and lower parathormone levels (p < 0.001) and were less often treated for hypercalcemia (p = 0.017) in comparison to FHH-negative cases. Magnesium levels showed the highest AUROC (0.825, 95%CI: 0.709-0.941). The multivariate analysis revealed that family history and magnesium levels were independent predictors of a positive genetic result. The predictive model showed an AUROC of 0.909 (95%CI: 0.826-0.991). CONCLUSIONS: The combination of magnesium and a positive family history offered a good diagnostic accuracy to predict a positive genetic result. Therefore, the inclusion of magnesium measurement in the routine evaluation of patients with suspected FHH might provide insight into the identification of a positive genetic result of any of the CaSR-related genes.

11-Deoxycorticosterone Producing Adrenal Hyperplasia as a Very Unusual Cause of Endocrine Hypertension: Case Report and Systematic Review of the Literature.

Background and Objectives: 11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of. Design and Methods: We report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021. Results: We identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions. Conclusions: 11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable. Systematic Review Registration: Open Science Framework, 10.17605/OSF.IO/NR7UV.

Obesity Surgery Improves Hypogonadism and Sexual Function in Men without Effects in Sperm Quality.

(1) Background: Obesity is associated with hypogonadism, sexual dysfunction, and impaired fertility in men. However, its effects on semen parameters or sexual function remain debatable. (2) Methods: This paper involves a longitudinal study in men submitted for obesity surgery at a university tertiary hospital. Patients were studied at baseline and at 6, 12, and 18 months after obesity surgery. At each visit, anthropometry measures were collected and hormonal and semen parameters were studied. Sexual function was evaluated with the International Index of Erectile Function (IIEF). (3) Results: A total of 12 patients were included. The average body mass index of patients decreased from 42.37 ± 4.44 to 29.6 ± 3.77 kg/m2 at 18 months after surgery (p < 0.05). Hormonal parameters improved after obesity surgery. The proportion of sperm cells with normal morphology tended to decrease from baseline and became most significant at 18 months (5.83 ± 4.50 vs. 2.82 ± 2.08). No significant changes were found in the remaining semen parameters. Erectile function improved significantly at six months after surgery. (4) Conclusions: The authors believe that, in general, the effects of obesity surgery on fertility may be limited or even deleterious (at least in the short and midterm follow-up).

Comprehensive Genetic Testing of CYP21A2: A Retrospective Analysis in Patients with Suspected Congenital Adrenal Hyperplasia.

The most common form of congenital adrenal hyperplasia (CAH) results from a deficiency of the 21-hydroxylase enzyme (21-OHD), presenting with a broad spectrum of clinical phenotypes according to the CYP21A2 gene mutations. Of the 59 patients with suspected CAH, 62.7% presented a positive genetic result. Of them, 78.4% and 18.9% presented with non-classical and classical forms, respectively. An overall phenotype-genotype correlation of 88.9% was observed. Biochemically, 17-hydroxiprogesterone concentrations were significantly higher in genetically confirmed patients. Genetically, 36 patients presented with previously reported pathogenic variants, and one presented a new variant in homozygosis. Among the 74 alleles tested, point mutations were found in 89.2% and large rearrangements were found in the rest. The most prevalent pathogenic variant was p.(Val282Leu). The inclusion of relatives revealed one further case. Interestingly, 87.5% of relatives were carriers of a pathogenic variant, including two siblings initially classified as genetically positive. In addition, the study of male partners with gestational desire identified several carriers of mild mutations. Studying the allelic distribution of the variants also allowed for reclassifying one patient. In conclusion, a genetic approach including Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) analysis, and allelic distribution of the pathogenic variants represents a beneficial tool for better classifying patients with 21-OHD.

Phase angle by electrical bioimpedance is a predictive factor of hospitalisation, falls and mortality in patients with cirrhosis.

The phase angle is a versatile measurement to assess body composition, frailty and prognosis in patients with chronic diseases. In cirrhosis, patients often present alterations in body composition that are related to adverse outcomes. The phase angle could be useful to evaluate prognosis in these patients, but data are scarce. The aim was to analyse the prognostic value of the phase angle to predict clinically relevant events such as hospitalisation, falls, and mortality in patients with cirrhosis. Outpatients with cirrhosis were consecutively included and the phase angle was determined by electrical bioimpedance. Patients were prospectively followed to determine the incidence of hospitalisations, falls, and mortality. One hundred patients were included. Patients with phase angle ≤ 4.6° (n = 31) showed a higher probability of hospitalisation (35% vs 11%, p = 0.003), falls (41% vs 11%, p = 0.001) and mortality (26% vs 3%, p = 0.001) at 2-year follow-up than patients with PA > 4.6° (n = 69). In the multivariable analysis, the phase angle and MELD-Na were independent predictive factors of hospitalisation and mortality. Phase angle was the only predictive factor for falls. In conclusion, the phase angle showed to be a predictive marker for hospitalisation, falls, and mortality in outpatients with cirrhosis.

Web Support for Weight-Loss Interventions: PREDIRCAM2 Clinical Trial Baseline Characteristics and Preliminary Results.

An ongoing clinical trial is testing the efficacy of web telematic support in a structured program for obesity treatment and diabetes prevention. Participants were recruited from two tertiary-care hospitals and randomized to receive either a telematic intervention (TI) supported by PREDIRCAM2 web platform or a non-telematic intervention (NTI). All receive 1-year follow-up. Both interventions consist of tailored dietary and exercise prescriptions, based on a Mediterranean dietary pattern and general WHO exercise recommendations for adults. At 6 months, both groups have received 7 contacts, 3 exclusively telematic for the TI group. This is a preliminary result intention-to-treat analysis. One hundred eighty-three participants were recruited, with a mean body mass index of 34.75 ± 2.75 kg/m2. General dropout rate at 6 months was 26.8%. Weight changes were statistically significant at months 3 and 6 compared to baseline, -2.915 ± 0.24 kg, -3.29 ± 0.36 kg, respectively (P < 0.001), but not statistically significant between the 3- and 6-month time points -0.37 ± 0.21 kg (P = 0.24). Mean group differences showed that the TI group lost 1.61 ± 1.88 kg more than the NTI group (P = 0.39). Waist, waist/hip ratio, resting heart rate, blood pressure, HbA1c, and low-density lipoprotein cholesterol also showed statistically significant changes at 6 months, with no significant differences between groups. Weight loss in the TI group shows similar results as the usual care NTI group for weight loss and control of obesity comorbidities. At completion of the clinical trial, these results will be reevaluated to assess the potential role of web support in weight-loss maintenance and its cost-effectiveness.

Severe ectopic cushing syndrome caused by adenoid cystic carcinoma of a salivary gland.

OBJECTIVE: We present a rare case of Cushing syndrome due to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS). To our knowledge only two similar cases have been previously reported. METHODS: This is a case report of EAS by a metastatic lingual adenoid cystic carcinoma (ACC). RESULTS: The patient was diagnosed of a Cushing syndrome caused by tumoral EAS two years after initial cancer diagnosis. Clinical presentation included asthenia, insomnia, hypertension, acne, and hyperpigmentation developing in a period of two months. Laboratory and imaging testing revealed hypokalemic metabolic alkalosis, hypercortisolemia, high ACTH, nonsuppresion by 8 mg dexamethasone, and a normal pituitary magnetic resonance imaging (MRI). With a high clinical suspicion of EAS, combined medical treatment was started but was unsuccessful. Bilateral adrenalectomy could not be performed given the patient's rapid deterioration. Immunostained tissue from the original tumor was positive for synaptophysin. CONCLUSION: This rare case of EAS illustrates the challenge that this condition may confer regarding diagnosis and management.