The Prognostic Role of Metabolic and Endocrine Parameters for the Clinical Severity of COVID-19.

OBJECTIVE: An outbreak of coronavirus disease-19 (COVID-19) began in December 2019 and spread globally, overwhelming the entire world. COVID-19 is a public health emergency of international concern. Due to its high morbidity and mortality rate, recognition of its risk and prognostic factors is important. We aimed to understand the relationship between metabolic and endocrine parameters and the prognosis of COVID-19. METHODS AND MATERIALS: This was a cross-sectional clinical study. A total of 70 patients with severe COVID-19 were enrolled. Laboratory results at the first admission time (including complete blood count, C-reactive protein, lactate dehydrogenase, blood glucose, calcium, phosphate, albumin, creatinine, magnesium, lipid profiles, liver enzymes, thyroid hormones, cortisol, and vitamin D) and outcome data were recorded. We divided patients into (1) intensive care unit- (ICU-) admitted and non-ICU-admitted and (2) survivors and nonsurvivors for estimation of severity and prognosis. We determined the risk factors associated with critical illness and poor prognosis. RESULTS: Patients with higher white blood cell (WBC) count and phosphate levels had significantly higher ICU admission rates. According to univariate analysis, serum levels of T3, phosphate, and WBC as well as the duration of hospitalization were associated with mortality. Multivariate analysis revealed that only WBC and duration of hospitalization were independent predictors for mortality rate in COVID-19 patients. CONCLUSION: Our findings suggest that longer duration of hospitalization and higher WBC count are associated with poor outcomes in patients with COVID-19.

The Effect of Levothyroxine in Comparison with Placebo on Serum Osteocalcin Levels in Patients with Subclinical Hypothyroidism.

BACKGROUND AND OBJECTIVE: Subclinical hypothyroidism can potentially develop into overt hypothyroidism. Thyroid hormones have substantial roles in metabolism and glucose homeostasis and thus, are closely related to determinant factors of metabolic syndromes, such as obesity and insulin resistance. Osteocalcin is considered a predictor of metabolic conditions in thyroid diseases. This study aimed to investigate the effect of levothyroxine vs. placebo on serum osteocalcin levels in patients with subclinical hypothyroidism. METHODS: This randomized clinical trial was performed on 30 patients with subclinical hypothyroidism, who were referred to the endocrine clinics of Ghaem and Imam Reza hospitals in Mashhad, Iran. After giving informed consent, patients were randomly divided into intervention (50 µg/- day levothyroxine for 2 months) and control (placebo) groups. Serum levels of osteocalcin, thyroid hormones, lipid profile, insulin, and fasting glucose, as well as other clinical and anthropometric data, were measured at baseline and at the end of the study. SPSS was used to analyze the data, and p < 0.05 was considered significant. RESULTS: Mean age in the intervention and control groups was 35.07 ± 9.94 and 31.30 ± 4.30, respectively (p = 0.20). There was no significant difference between osteocalcin levels before and after the intervention in either of the groups (p = 0.54). TSH level was significantly decreased in the levothyroxine group after the intervention (p < 0.01). T4 level was significantly increased in the intervention group (p = 0.02). CONCLUSION: Levothyroxine had no significant effect on the increasing levels of serum osteocalcin in patients with subclinical hypothyroidism.

Assessment of insulin resistance in patients with primary hyperparathyroidism before and after Parathyroidectomy.

BACKGROUND: Primary hyperparathyroidism (PHPT) can lead to renal and skeletal disorders, as well as insulin resistance and impaired glucose metabolism. The current study aimed to assess the effects of parathyroidectomy on insulin resistance in patients with PHPT. MATERIALS AND METHODS: The present study was conducted on 65 patients with PHPT and indications for parathyroidectomy who were referred to the endocrinology clinics of Mashhad University of Medical Sciences. Thereafter, the demographic characteristics of the patients were recorded. Blood tests, including haemoglobin A1c (HbA1c), fasting blood glucose (FBG) and insulin levels, were assessed one week before and three months after the surgery. The insulin resistance score (HOMA-IR) was calculated and compared using the relevant formula. RESULTS: A total of 65 participants with a mean age of 45.44 ± 9.59 years were included in the current study. In one-month postoperative tests, mean scores of FBG (p < .05), insulin level (p < .05) and HbA1c (p < .05) were significantly reduced. Moreover, the HOMA-IR index decreased in 51 patients after the surgery. CONCLUSION: According to our findings, parathyroidectomy can be effective in the reduction of insulin resistance and corresponding complications in patients with PHPT in the present short-term study. However, it has yet to be confirmed as a treatment method for insulin resistance in these patients. Future long-term studies are required to be done to investigate the effect of parathyroidectomy on insulin resistance.

Evaluation of Serum Level of FGF23 and 1,25(OH)2D3 in Primary Hyperparathyroidism Patients Before and After Parathyroidectomy.

PURPOSE: Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) play critical roles in phosphate homeostasis. To the best of our knowledge, there are limited data on the impact of FGF23 and PTH on serum calcium, 1,25(OH)2D3, and phosphate in patients with primary hyperparathyroidism (PHPT). We examined these parameters and their correlations in PHPT patients before and after parathyroidectomy (PTX). PATIENTS AND METHODS: In this prospective cohort study, 29 PHPT patients who met the inclusion criteria were selected. The patient's blood samples were taken three times: before the operation, 24 h after the operation, and 1 week after the operation. The concentrations of serum calcium, FGF23, 1,25(OH)2D3, phosphate, PTH, and alkaline phosphatase were measured in a referral laboratory at each of the three steps. Moreover, 25(OH)D was primarily measured just before the surgery. RESULTS: Of 29 patients included in this study with a mean age of 52.37±12.3 years, majority were females (75.8%). Serum FGF23 and 1,25(OH)2D3 levels were high before PTX and decreased after the operation; however, the difference was not statistically significant. FGF23 levels were significantly correlated with 1,25(OH)2D3 at each of the three steps (r=0.964, P <0.01; r=0.985, P <0.0; and r=0.976, P <0.05). The variations in calcium, phosphate, creatinine, and PTH were preoperatively and postoperatively significant. CONCLUSION: Although 1,25(OH)2D3 and FGF23 levels were preoperatively higher in PHPT, their variations were not meaningful. There was a statistically direct significant relationship between 1,25(OH)2D3 and FGF23 preoperatively and postoperatively; however, the correlations between FGF23 and calcium, phosphate, and PTH were not significant.

Effect of high-dose vitamin D supplementation on antibody titers to heat shock protein 27 in adolescent girls.

Background Although vitamin D deficiency is associated with several inflammatory conditions, there have been few studies on the effects of vitamin D supplementation on markers of oxidative stress (OS) and inflammation. The aim of the current study was to evaluate the effects of high-dose vitamin D supplementation on heat shock protein 27 antibody (anti-Hsp27) titers in adolescent girls. Methods Five hundred and fifty adolescent girls received vitamin D3 at a dose of 50,000 IU/week for 9 weeks. Demographic, clinical and biochemical markers including serum fasting blood glucose (FBG), lipid profile and anti-Hsp27 titers as well as hematological parameters including white blood cell (WBC) count and red blood cell (RBC) distribution width (RDW) were determined in all the subjects at baseline and at the end of the study. Results Serum vitamin D significantly increased from 6.4 (4.2-9.6) ng/mL to 35.6 (25.8-47.5) ng/mL (p < 0.001) following the intervention. Furthermore, serum anti-Hsp27 titers were significantly lower after the 9-week vitamin D administration period (0.22 [0.12-0.33] optical density [OD] vs. 0.19 [0.11-0.31] OD; p = 0.002). A significant correlation was found between serum anti-Hsp27 and RDW (r = 0.13, p = 0.037). The reduction in RDW values after intervention was particularly evident in subjects with the greatest increase in serum vitamin D levels. Conclusions High-dose vitamin D supplementation was found to reduce antibody titers to Hsp27. Further randomized placebo-controlled trials are warranted to determine the long-term effect of vitamin D administration on the inflammatory process especially that associated with chronic disease.

Childhood Sex-Typed Behavior and Gender Change in Individuals with 46,XY and 46,XX Disorders of Sex Development: An Iranian Multicenter Study.

Disorders of sex development (DSD) are congenital conditions in which the typical genetic and hormonal profiles are affected and thereby the usual process of sexual differentiation. Most of these studies, however, have been conducted in Western countries. In the present study, preschool sex-typed activities of Iranian individuals with DSD and their age-matched non-affected male and female relatives were assessed using the Pre-School Activities Inventory (PSAI) modified for retrospective self-report. A total of 192 individuals participated in our study, including 33 46,XX individuals with congenital adrenal hyperplasia (CAH; M age = 10.36, SD = 5.52), 15 46,XY individuals with complete androgen insensitivity syndrome (CAIS; M age = 19.8, SD = 7.14), and 16 46,XY individuals with 5-alpha reductase deficiency type-2 (5α-RD-2; M age = 17.31, SD = 7.28), as well as one age-matched non-affected male and female relative for each patient. With regard to PSAI scores, male-identifying participants with 5α-RD-2 and male controls reported similar levels of male-typical childhood play. Female-identifying participants with 5α-RD-2 and CAH showed comparable scores: significantly less masculine and more feminine than male controls, but significantly more masculine and less feminine than females with CAIS and female controls. These findings support the role of androgens in the development of sex-typical childhood play behavior, with those being exposed to higher levels of fetal functional androgens expressing more masculine behavior at preschool ages.

Menstrual disorders and premenstrual symptoms in adolescents: prevalence and relationship to serum calcium and vitamin D concentrations.

There have been several studies evaluating the association between vitamin and mineral status and menstrual disturbance. In the present study, we aimed to assess the relationship between the menstrual bleeding pattern and premenstrual syndrome (PMS) symptoms with serum 25-hydroxyvitamin D, and calcium levels in adolescent girls. A cross-sectional study was carried out in 897 high school girls from northeastern Iran. The prevalence of hypocalcaemia, normal serum calcium and hypercalcaemia was 27.1, 59.8 and 13.1%, respectively. The menstrual flow of participants differed significantly between the calcium status groups (p = .005). There was no significant association between the symptoms of PMS, as assessed by the questionnaire and serum vitamin D status, or serum calcium concentrations, apart from the irritability. There appears to be an association between serum calcium, menstrual blood loss and irritability in adolescent girls. Impact statement What is already known on this subject? Several studies have evaluated the association of vitamin and mineral status with menstrual disturbance, although these relationships are not consistent, specifically among calcium and vitamin D levels with a menstrual bleeding pattern. What do the results of this study add? In the present study, we investigated the correlation of menstrual bleeding patterns and PMS with calcium and vitamin D levels in a large population in adolescent girls. We found that the level of calcium was associated with the level of menstrual blood loss and irritability. However, no significant association was observed between the menstrual bleeding pattern or the PMS symptoms with a vitamin D status. What are the implications of these findings for future clinical practise/research? Further studies are required to assess the value of a calcium adequate intake or a calcium supplementation for the amelioration of PMS and a better understanding the role of calcium in PMS.

Prenatal testosterone and theory of mind development: Findings from disorders of sex development.

Women on average perform better than men on the "Reading the Mind in the Eyes" test (RMET) which is a measure of Theory of Mind (ToM). The aim of this study was to assess whether these sex differences are influenced by differences in prenatal testosterone levels through a study on individuals with Disorders of Sex Development and matched controls. ToM performance was examined using the RMET in female-assigned-at-birth individuals with increased prenatal testosterone exposure (Congenital Adrenal Hyperplasia (CAH) and 5-alpha Reductase type-2 Deficiency (5α-RD-2)), female-assigned-at-birth individuals with testosterone insensitivity (Complete Androgen Insensitivity Syndrome (CAIS)), and their age-matched unaffected male and female relatives. A total number of 158 individuals participated in the study; 19 with 5α-RD-2, 17 with CAH, 18 women with CAIS, 52 matched unaffected men and 52 matched unaffected women. All subgroups were around 20 years of age. Women with CAH scored significantly lower on RMET than control women and CAIS individuals. CAIS individuals scored significantly higher than control men and participants with 5α-RD. Statistically, CAIS individuals' performance on RMET was similar to control women's, women with CAH did not differ significantly from control men and 5α-RD-2 individuals scored significantly lower than control men. These results, which are in line with previous theories, illustrate that performance on the RMET, as an index of ToM, may be influenced by variations in prenatal androgens levels.

A Western dietary pattern is associated with elevated level of high sensitive C-reactive protein among adolescent girls.

BACKGROUND: Serum high sensitive C-reactive protein (hs-CRP), is an indicator of low-grade inflammation, and is associated with several non-communicable diseases. The effects of diet on inflammation have not been extensively investigated, particularly among adolescents. We aimed to examine the association between major dietary patterns and elevated serum level of hs-CRP among Iranian adolescent girls. MATERIALS AND METHODS: In this cross-sectional study, a total of 670 adolescent girls were recruited from several schools in different areas of Mashhad and Sabzevar cities, Iran. The dietary intakes of study participants were collected using a 147-item food frequency questionnaire. To identify major dietary patterns based on the 40 food groups, we used principal component analysis. Serum concentration of hs-CRP was measured using commercial kits and the BT-3000 auto-analyser. To investigate the association between dietary patterns and elevated serum level of hs-CRP, we used logistic regression analysis. RESULTS: Three specific dietary patterns were identified: (i) healthy, (ii) traditional and (iii) western dietary patterns. A significant association was found between more adherence to Western dietary pattern and elevated serum level of hs-CRP (OR: 1.58; 95% CI: 1.02-2.42, P-trend = .03); these association remained significant after adjustment for potential confounders. However, there was no significant relationship between healthy and traditional dietary patterns and elevated serum level of hs-CRP. CONCLUSION: Our results indicate that there is a significant positive association between more adherence to Western dietary pattern and higher serum levels of hs-CRP among Iranian adolescent girls. Further studies, particularly longitudinal intervention studies may be required to clarify these relationships.

Topical propolis improves wound healing in patients with diabetic foot ulcer: a randomized controlled trial.

In this randomized controlled trial, diabetic patients with foot ulcers (Wagner grades 1 and 2) were randomly assigned to conventional therapies for diabetic foot ulcer plus topical propolis ointment (5%; twice daily) or conventional therapies alone. The process of ulcer healing was observed during 4 weeks and compared between the two groups regarding the size, erythema, exudates, white blood cell (WBC) count and erythrocyte sedimentation rate (ESR). The process of ulcer size reduction during the four-week period of study was significantly different between the groups. However, this difference was not significant between the third and fourth weeks. There was no significant difference between two groups regarding erythema and exudate reduction as well as WBC count and ESR. Administration of topical propolis ointment in addition to the conventional treatments of diabetic foot ulcer could reduce the size of ulcers with Wagner grades 1 and 2.

Sexual orientation and medical history among Iranian people with Complete Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia.

OBJECTIVE: To report sexual orientation, relationship status and medical history of Iranian people with Differences of Sex Development (DSD) who were raised female. METHODS: Our participants consisted of nineteen 46,XY individuals with Complete Androgen Insensitivity Syndrome (CAIS) and eighteen 46,XX individuals with Congenital Adrenal Hyperplasia (CAH) who were raised as females and older than 13years. As well as their relationship status and detailed medical history, an expert psychiatrist assessed their sexual orientation by a semi-structured psychiatric interview with them and, where applicable, their parents. RESULTS: Five percent of CAH participants and 42% of CAIS participants were in a relationship, which was significantly different. All CAH individuals had been diagnosed at birth; 89% of CAIS had been diagnosed after puberty and due to primary amenorrhea and 11% were diagnosed in childhood due to inguinal hernia. Genital reconstructive surgery had been performed in 100% of CAH participants and 37% of CAIS. Regarding sexual contact experiences and sexual fantasies (androphilic, gynephilic or both), no significant differences were found. However, CAH females had significantly more gynephilic dreams (P=0.045). CONCLUSION: This study, notable as one of the rare from a non-western culture, described sexual, medical and socioeconomic status of 46,XX CAH and 46,XY CAIS individuals living in Iran. Although broadly in line with previous findings from Western cultures, Iranian CAH individuals had fewer romantic relationships, but in contrast to previous studies their sexual orientation was only different from CAIS in the contents of sexual dreams.

Psychosexual Outcome Among Iranian Individuals With 5α-Reductase Deficiency Type 2 and Its Relationship With Parental Sexism.

INTRODUCTION: Few studies exist on the psychosexual outcome of homogeneous groups of individuals with 5α-reductase deficiency type 2 (5α-RD-2) and the relation between gender changes and parental hostile and benevolent sexism, which are two components of ambivalent sexism that assume a stereotypical approach toward women in an overtly negative way or a chivalrous, seemingly positive way. AIM: To report on the psychosexual outcome of individuals with 5α-RD-2 and to investigate its relation to the level of parental sexism in a relatively large sample of Iranians with 5α-RD-2. METHODS: Twenty participants (mean age = 19.5 years, SD = 6.345) with a molecularly confirmed diagnosis of 5α-RD-2 who were assigned the female gender at birth and raised as female were included in the study. Participants and their parents were interviewed and their medical records were assessed. Parents also completed the Ambivalent Sexism Inventory (ASI), which includes hostile and benevolent sexism subscales. MAIN OUTCOME MEASURES: Psychosexual outcome and parental hostile and benevolent sexism measurements. RESULTS: Twelve of 20 participants (60%) were diagnosed with gender identity disorder not otherwise specified (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision). Ten of these transitioned to the male gender. The other 10 participants (50%), including the two diagnosed with gender identity disorder not otherwise specified, continued living in a female gender role. When comparing the ASI subscale scores between families of participants who changed their gender and those who did not, no significant difference was found for ASI total and hostile sexism scores, but there was a difference for benevolent sexism (P = .049): those whose daughters had changed their gender had higher benevolent sexism scores. CONCLUSION: The high prevalence of gender change and gender dysphoria reported in the literature was confirmed in this relatively large and homogeneous sample of Iranians with 5-α-RD-2 raised as female. Prenatal exposure to testosterone is hypothesized to play a role in the development of gender identity and sexual orientation, but parental attitudes also might be important. Although gender change in individuals with 5-α-RD-2 is often attributed to high levels of hostile sexism in some cultures, our findings show this to be associated with benevolent sexism.

The "Reading the Mind in the Eyes" Test: Investigation of Psychometric Properties and Test-Retest Reliability of the Persian Version.

The psychometric properties of the Persian "Reading the Mind in the Eyes" test were investigated, so were the predictions from the Empathizing-Systemizing theory of psychological sex differences. Adults aged 16-69 years old (N = 545, female = 51.7 %) completed the test online. The analysis of items showed them to be generally acceptable. Test-retest reliability, as measured by Intra-class correlation coefficient, was 0.735 with a 95 % CI of (0.514, 0.855). The percentage of agreement for each item in the test-retest was satisfactory and the mean difference between test-retest scores was -0.159 (SD = 3.42). However, the internal consistency of Persian version, calculated by Cronbach's alpha (0.371), was poor. Females scored significantly higher than males but academic degree and field of study had no significant effect.

Morning melatonin serum values do not correlate with disease activity in rheumatoid arthritis: a cross-sectional study.

Rheumatoid arthritis (RA), the most prevalent autoimmune arthritis worldwide, usually presents with a circannual manner and, meanwhile, follows a circadian rhythm for symptoms like morning stiffness. Therefore, association between RA and some hormones such as melatonin (MLT) and vitamin D, whose serum values are related to body circadian rhythms or seasonal variations, has become more noticeable recently. Since some studies proposed that RA patients show altered MLT circadian rhythms, especially in concordance with symptoms, in this research, we present the correlation between MLT serum values and RA disease activity score (DAS28ESR). The current cross-sectional study was carried out on 80 volunteers (60 patients and 20 healthy controls). Fifty percent of the participants in each group were sampled in cold, and the same percentage were sampled in warm seasons at 8 a.m. Disease activity was estimated utilizing DAS28ESR. Patients with possible known confounders of MLT secretion were excluded. A commercial MLT ELISA kit was employed to measure MLT. Statistical analysis was conducted by SPSS-11 software. This study outlined higher serum values of MLT in RA patients compared with controls (P = 0.006, z = -2.73). However, MLT did not correlate with DAS in patients (P = 0.45, r = -0.09). GLM analysis demonstrated that DAS28ESR, age, disease duration, medications, gender, and season of sampling had no influence on serum MLT. However, newly diagnosed RA patients presented higher MLT values than established ones (P = 0.03, t = -2.2). A cutoff point value of 23 pg/mL (63.3 % sensitivity and 90 % specificity) for MLT was computed between patients and controls. This study denoted that morning MLT serum values are higher in RA patients than in healthy volunteers. However, MLT and RA disease activity or other disease characteristics do not correlate. MLT serum values were higher in newly diagnosed RA patients than established ones.