Landscape of congenital adrenal hyperplasia cases in adult endocrinology clinics of Türkiye-a nation-wide multicentre study.

BACKGROUND AND AIMS: Congenital adrenal hyperplasia (CAH) is a group of disorders that affect the production of steroids in the adrenal gland and are inherited in an autosomal recessive pattern. The clinical and biochemical manifestations of the disorder are diverse, ranging from varying degrees of anomalies of the external genitalia to life-threatening adrenal insufficiency. This multicenter study aimed to determine the demographics, biochemical, clinical, and genetic characteristics besides the current status of adult patients with CAH nationwide. METHODS: The medical records of 223 patients with all forms of CAH were evaluated in the study, which included 19 adult endocrinology clinics. A form inquiring about demographical, etiological, and genetic (where available) data of all forms of CAH patients was filled out and returned by the centers. RESULTS: Among 223 cases 181 (81.16%) patients had 21-hydroxylase deficiency (21OHD), 27 (12.10%) had 11-beta-hydroxylase deficiency (110HD), 13 (5.82%) had 17-hydroxylase deficiency (17OHD) and 2 (0.89%) had 3-beta-hydroxysteroid-dehydrogenase deficiency. 21OHD was the most prevalent CAH form in our national series. There were 102 (56.4%) classical and 79 (43.6%) non-classical 210HD cases in our cohort. The age of the patients was 24.9 ± 6.1 (minimum-maximum: 17-44) for classical CAH patients and 30.2 ± 11.2 (minimum-maximum: 17-67). More patients in the nonclassical CAH group were married and had children. Reconstructive genital surgery was performed in 54 (78.3%) of classical CAH females and 42 (77.8%) of them had no children. Thirty-two (50.8%) NCAH cases had homogenous and 31 (49.2%) had heterogeneous CYP21A2 gene mutations. V281L pathological variation was the most prevalent mutation, it was detected in 35 (55.6%) of 21OHD NCAH patients. CONCLUSION: Our findings are compatible with the current literature except for the higher frequency of 110HD and 17OHD, which may be attributed to unidentified genetic causes. A new classification for CAH cases rather than classical and non-classical may be helpful as the disease exhibits a large clinical and biochemical continuum. Affected cases should be informed of the possible complications they may face. The study concludes that a better understanding of the clinical characteristics of patients with CAH can improve the management of the disorder in daily practice.

Case Series: Exposure to Glucagon-like Peptide-1 Receptor Agonist in the First Trimester of Pregnancy in Two Siblings.

BACKGROUND: The safety of glucagon-like peptide-1 receptor agonists in pregnancy is under investigation. In this report, we want to share the results of a patient with polycystic ovary syndrome who applied to our outpatient clinic for diabetes and had two unplanned pregnancies following the initiation of exenatide for obesity treatment. CASE PRESENTATION: A 40-year-old woman with diabetes was admitted to the endocrinology outpatient clinic. On physical examination, the body mass index was over 35 kg/m ², therefore, exenatide treatment was started. Four weeks later, she came to suspicion of pregnancy, and obstetric ultrasound revealed a fetus at 17 weeks of gestation. Exenatide was interrupted. At 37 weeks of gestation, she gave birth to a female baby with atrial septal defect. The baby was followed with echocardiography annually until spontaneous closure of ASD when she was three years old. Two years later, the patient consulted us again for weight gain. Exenatide was prescribed again. After 6 months, an abdominal ultrasound revealed a fatty liver and detected a pregnancy compatible with 13 weeks of gestation. Two siblings are healthy now, 7 and 5 years old, respectively. CONCLUSION: This report contributes to our knowledge of fetal exposure to exenatide. Large-scale randomized studies are needed for its safe use in pregnancy.

A Case Presenting with Neck Pain and High Sedimentation Rate: Amyloid Goiter.

INTRODUCTION: Amyloid goiter is a rare disease characterized by amyloid deposits that cause sudden growth in the thyroid gland. CASE PRESENTATION: Here we present a case of a 26-year-old woman with euthyroid amyloid goiter who presented with subacute granulomatous thyroiditis clinic. Amyloid goiter was detected as a result of core biopsy from the thyroid parenchyma of the patient with sudden thyroid enlargement. Surgery was not applied to the patient who had no pressure symptoms or signs. In systemic amyloidosis secondary to Familial Mediterranean fever, involvement was found in the heart, kidney, liver, and intestines, except for the thyroid. CONCLUSION: Amyloid accumulation should be considered in addition to anaplastic thyroid cancer and lymphoma in patients with sudden thyroid enlargement. It should not be overlooked that amyloid goiter may mimic subacute thyroiditis clinic. Systemic amyloidosis should be considered in patients with amyloid goiter, and an examination should be made to assess the presence of amyloid accumulations in other organs.

Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.

CONTEXT: The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. METHODS: This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. RESULTS: Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. CONCLUSION: Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism.

Evaluation of management of patients with postoperative permanent hypoparathyroidism. How close are we to the targets?

BACKGROUND: Postoperative hypoparathyroidism (PO-HypoPT) is a complication usually seen after thyroid surgery. PO-HypoPT, which lasts longer than 6 months is defined permanently. The aim of this study was to evaluate how close permanent PO-HypoPT patients can approach target values. METHODS: One hundred seven patients who were followed-up with permanent diagnosis of PO-HypoPT between 2016-2020 were included in the study. The study protocol includes serum albumin corrected total calcium (Alb-sCa), phosphate (P), Ca-P product, and 24 h urine calcium measurements. Laboratory measurements of the patients include the values recorded in 4-year visits and in the last visit. In addition, radiological reports of renal/abdominal ultrasound and cranial tomography examinations performed in our hospital for any reason during this period were also reviewed. RESULTS: When looking at the total measurements in the 4-year period, the Alb-sCa level was below the target in most of the measurements (68.1%). P level was higher than normal in 296 (46.2%) measurements. Twenty-four h urine ca excretion was measured 185 times in total visits, and 81 (43.7%) of these measurements showed hypercalciuric values. The patient's latest visit measurements were evaluated on 4 targets (Alb-sCa, P, Ca-P product and 24 h urine Ca excretion). The number of patients meeting all four targets was only 21 (19.6%). Six (7.5%) patients had kidney stones or nephrocalcinosis. Three (0.09%) patients with imaging had calcification in the basal ganglia. CONCLUSIONS: Our study shows that the management of the patients with PO-HypoPT is suboptimal with active vitamin D and cholecalciferol treatment.

Intensifying Iodine Deficiency Throughout Trimesters of Pregnancy in a Borderline Iodine-Sufficient Urban Area, Ankara, Turkey.

Iodine has long been recognized as an essential micronutrient for maternal thyroid function, as well as fetal growth and development during pregnancy. The current study aimed to evaluate thyroid hormone status, urinary iodine concentration (UIC), thyroid volume, and nodularity in pregnant women, throughout trimesters, in a borderline iodine sufficient, urban area with mandatory table salt iodization. Two-hundred-sixty-five pregnant women ranging from 17 to 45 years participated in this prospective longitudinal study. Thyroid function tests, thyroid volume, nodule growth, and UIC were recorded throughout the first, second, and third trimesters with no intervention. Median UIC was 96, 78, and 60 µg/L in the first, second, and third trimester of pregnancy, respectively (p < 0.001). Mean TSH values increased significantly (i.e. 0.65 mIU/ml, 1.1 mIU/ml, and 1.3 mIU/ml in the first, second, and third trimesters, respectively) (p < 0.001). Mean ± s.d. thyroid volume was significantly higher in the third trimester (14.72 ± 6.8 ml) compared with the first trimester (13.69 ± 5.31 ml) (p < 0.001). An intensifying iodine deficiency (ID) was reported throughout trimesters in this cohort of pregnant women from Ankara. A significant percentage of pregnant women from a borderline iodine sufficient, urban area in Turkey were iodine deficient during all trimesters, and the deficiency increased throughout the pregnancy. Pregnant women should receive iodine supplementation, besides consuming iodized salt in borderline iodine sufficient areas.

Ameliorating effects of N-acetyl cysteine against early liver damage of radioiodine in rats.

OBJECTIVE: The present study was aimed to explore the potential ameliorating effects of N-acetyl cysteine (NAC) against radioiodine (RAI)-induced early liver damage. METHODS: Thirty Wistar Albino male rats were arbitrarily allocated into three groups each containing 10 rats: the control group (group 1); the RAI group (group 2), oral 111 MBq/kg radioiodine was administered to rats; the RAI + NAC group (group 3), 150 mg/kg/day intraperitoneal NAC treatment was initiated 3 days prior to the RAI administration and continued for 10 days. Liver samples were obtained 24 h after the last dose of NAC therapy for biochemical and histopathologic evaluation. RESULTS: In the RAI + NAC group, the histopathologic damage was found significantly less than in the RAI group for whole parameters except inflammatory cell infiltration (P < 0.05). Unlike the RAI group which had marked histopathologic damage, the RAI + NAC group had only mild histologic activity index scores with no granuloma formation observed. Oxidative stress parameters were demonstrated that the NAC treatment significantly decreased the tissue malondialdehyde (MDA) and catalase levels and increased the total sulfhydryl (total sulfhydryl) levels when compared to the RAI group (P < 0.01). CONCLUSION: The outcomes of the study exhibited that the NAC treatment improved RAI-induced early liver damage. This improving effect considered to be caused by its antioxidant, anti-inflammatory, and likely vasodilator properties of NAC. Having advantages such as inexpensive, easy access, and tolerability, the NAC can be used as a radioprotective agent, especially in patients with liver diseases and requiring RAI treatment.

Evaluation of spatio-temporal gait parameters and gait symmetry in diabetic polyneuropathic patients with burn injury: A pilot study.

PURPOSE: The purpose of this study was to investigate the effects of burn injury on spatio-temporal gait parameters and gait symmetry in individuals with diabetic polyneuropathy (DPN)-related lower extremity burn injury. METHODS: Demographic information and the physical examinations of the lower extremities of 14 patients with unilateral lower extremity burn injury due to DPN (DPNB) and 14 uninjured patients with DPN (DPN0) were recorded. The GAITRite computerized gait analysis system was used to evaluate the spatio-temporal parameters of gait. Symmetry Index (SI) was calculated to determine gait symmetry. The Mann Whitney U test was used to determine the demographical and clinical differences between the groups, the Wilcoxon's test was used to compare both sides of all the participants for all gait parameters and linear regression analysis was used to find the variables that affect gait parameters. RESULTS: The groups were similar in terms of their demographic information except for age. Compared with the DPN0 group, DPNB group had increased extent of area with sensory loss and severity of DPN, decreased ankle joint range of motions and intrinsic foot muscles strength and they displayed lower gait speed, step length, stride length and swing percentage but their double support and stance percentage were increased. CONCLUSION: This study results have shown that, spatio-temporal gait parameters of DPNB patients are different. These differences in spatiotemporal parameters are found on both sides, probably owing to the symmetric and bilateral sensory loss is superior to unilateral burn injury due to symmetrical and bilateral sensory loss. Gait analysis should be considered in order to reveal the changes in gait parameters and to improve appropriate healing process of patients with DPN-related lower extremity burn injury.

Neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-tolymphocyte ratio in different etiological causes of thyrotoxicosis

Background/aim: The most common causes of thyrotoxicosis include Graves' disease (GD), toxic multinodular goiter (TMNG), toxic adenoma (TA), and subacute granulomatous thyroiditis (SAT). In our study, we aimed to see whether neutrophil­to­lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet­to­lymphocyte ratio (PLR), and mean platelet volume (MPV) may be helpful in the differential diagnosis of these diseases. Materials and methods: We retrospectively analyzed the hospital records of the Endocrinology Clinic of our hospital between 2016 and 2019. We included data from 66 GD, 37 TA, and 35 SAT patients. We compared the data with those of 35 healthy subjects as controls. Results: NLR, MLR, and PLR were found to be higher in the SAT group when compared to other groups. The post hoc analysis of comparison of NLR, MLR, and PLR in each group showed that NLR and PLR were significantly different in the SAT group when compared to the GD, TA, and controls groups (P < 0.001, P = 0.003, and P < 0.001 for NLR respectively and P < 0.001 for PLR in all groups). MPV levels were different between groups (P = 0.007). However, the intergroup analysis (Tukey's test) failed to show a statistically significant difference for any of the groups. In patients with SAT, PLR and NLR were significantly higher than in the GD, TA, and control groups. MLR was also higher in SAT when compared to other groups, but the difference was not statistically significant. Conclusion: High PLR and NLR may be helpful to differentiate SAT from GD and TA, the other common causes of thyrotoxicosis.

Is There a Tendency for Thrombosis in Gestational Diabetes Mellitus?

CONTEXT: Impact of gestational diabetes mellitus (GDM) on the coagulation system, dynamics involved at a pathophysiological level and the exact mechanism remain unclear. AIMS: To evaluate the association between diabetes-related parameters and hemostatic factors to search for a tendency of thrombosis in GDM. SETTINGS AND DESIGN: Nineteen pregnant women who had GDM, 16 healthy pregnant and 13 healthy nonpregnant controls admitted to the Endocrinology outpatient clinics were enrolled in the study. SUBJECTS AND METHODS: Fasting and postprandial glucose, hemoglobin A1c and insulin levels, and insulin resistance; fructosamine, thrombin activatable fibrinolysis inhibitor (TAFI), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor Type-1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, plasminogen and hemoglobin levels, platelet counts, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were studied. STATISTICAL ANALYSIS USED: One-way analysis of variance, Kruskal-Wallis, and post hoc Tukey honestly significant difference or Conover's nonparametric multiple comparison tests for comparison of the study groups. RESULTS: PT and aPTT were significantly lower in GDM patients compared to controls (P < 0.05), whereas fibrinogen and plasminogen levels were significantly higher in this group compared to both nonpregnant and healthy pregnant controls (P < 0.05 for each). TAFI, TFPI, PAI-1, and tissue t-PA levels were not significantly different among groups. CONCLUSIONS: Our findings indicate tendency to develop thrombosis in GDM similar to diabetes mellitus; but more comprehensive studies with larger sample size are needed to determine the relationship between GDM and hemostasis.

Higher levels of circulating CXCL-9 and CXCL-11 in euthyroid women with autoimmune thyroiditis and recurrent spontaneous abortions.

BACKGROUND: We aimed to measure serum CXCL-9 and CXCL-11 levels in patients with autoimmune thyroiditis (AIT) and recurrent spontaneous abortions (RSA). METHODS: Forty-one euthyroid, non-pregnant women with AIT and a history of unexplained first trimester RSA, 35 euthyroid women with AIT, and 29 healthy controls matched for age and body mass index were enrolled. Serum CXCL-9 and CXCL-11 were measured. RESULTS: Serum CXCL-9 and -11 levels were significantly higher (p < 0.001 for both) in the antibody-positive women with a history of abortions than in both control groups. Additionally, CXCL-9 levels were higher in patients with AIT without RSA than in healthy controls. No significant differences were found in CXCL-9 and -11 levels in subjects with a history of RSA in relation to the number of previous abortions. In multiple linear regression analyses, abortions were significantly related to CXCL-9 (ß-coefficient = 0.174, p < 0.001), CXCL-11 (ß-coefficient = 0.490, p < 0.001). CONCLUSION: Higher circulating levels of CXCL-9 and -11 have been shown in non-pregnant AIT patients with a history of RSA as compared to both control groups, suggesting that this subgroup produce a more dominant Th-1 cytokine profile.

The relationship of PON1 QR 192 and LM 55 polymorphisms with serum paraoxonase activities of Turkish diabetic patients.

Paraoxonase (PON1) is a serum esterase responsible for the protection against xenobiotics toxicity such as paraoxon. Alterations in PON1 concentrations have been reported in a variety of diseases including diabetes mellitus (DM). It has been shown that the serum PON1 concentration and activity are decreased in patients with both type 1 and type 2 DM. This study aimed to investigate the lipid profiles and the relationship between PON1 activity and PON1, QR192 and LM55 polymorphisms in Turkish type 2 diabetic patients and non-diabetic control subjects. According to our results, RR variant had significantly higher PON activity than QQ and QR variants (p < 0.01) and LL variant had significantly higher PON activity than MM variant in both control and patient groups (p < 0.05). In conclusion, we found that PON1 192RR and 55LL genotypes are associated with higher PON activity than QQ and MM genotypes. This may be more protective to lipid peroxidation.

Are PON1 Q/R 192 and M/L 55 polymorphisms risk factors for diabetes complications in Turkish population?

OBJECTIVES: We investigated whether the human serum paraoxonase (PON1) Q/R 192 and M/L 55 polymorphisms are associated with the complications of the type 2 diabetes (T2D). DESIGN AND METHODS: Study group was consisted of 50 healthy subjects and 100 type 2 diabetes mellitus (DM) patients. Following measuring of serum PON1 activity, isolation of DNA and genotyping analyses were performed. RESULTS: PON1 activity of the patients with complications was significantly reduced by 23.5% compared to the group of diabetic patients and by 26.3% than the controls. According to multivariate analysis, we observed a three times significant effect of Q/R 192 polymorphism on the susceptibility to the occurrence of complications. CONCLUSIONS: Protective effects of paraoxonase against peroxidation of LDL particles are important in T2D complications. Although both of the two polymorphisms are associated, 192 polymorphism seems to be stronger predictor of the risk of diabetic complications.

Migraine in metabolic syndrome.

OBJECTIVES: Recent studies suggest that insulin resistance is more common in patients with migraine. Insulin resistance underlies the pathogenesis of obesity, diabetes, and hypertension that are components of metabolic syndrome. As migraine is associated with an increased risk of vascular disorders, such as stroke, and migraine patients have higher diastolic blood pressure than healthy individuals, we aimed to investigate the 1-year prevalence of migraine in metabolic syndrome. METHODS: Two hundred ten patients with metabolic syndrome were enrolled in the study. Migraine was diagnosed according to International Classification of Headache Disorders-II criteria. RESULTS: Migraine prevalence was estimated as 11.9% in men and 22.5% in women with metabolic syndrome. Of the metabolic syndrome components, diabetes, increased waist circumference, and body mass index were significantly more frequent in patients with migraine in contrast to those without migraine (P<0.05). Hypertension and dyslipidemia frequencies showed no difference between 2 groups. CONCLUSIONS: Our results demonstrate that migraine prevalence in metabolic syndrome was higher than in the general population.

Association of hypoadiponectinemia with metabolic syndrome in patients with polycystic ovary syndrome.

Patients with polycystic ovary syndrome (PCOS) have an increased prevalence of metabolic syndrome (MBS). Hypoadiponectinemia is closely associated with MBS. The aim of our study was to evaluate the association of adiponectin levels with MBS in patients with PCOS. We studied 60 patients with PCOS and 60 age-matched control subjects. Serum adiponectin, fasting glucose, triglycerides, high-density lipoprotein (HDL) levels, blood pressure and waist circumference were measured for each subject. The results showed that 33% of patients with PCOS were diagnosed with MBS; this was 11.7% in the control group (p<0.01). Adiponectin levels were significantly lower in PCOS patients with MBS than PCOS patients without MBS (p<0.001). After adjustment for body mass index (BMI), adiponectin levels were correlated negatively with waist circumference, triglycerides, diastolic blood pressure, homeostasis model assessment (HOMA) and positively with HDL. PCOS patients with adiponectin levels lower than median value had 10.5-fold higher risk of having MBS. Logistic regression analysis revealed that adiponectin levels were independently associated with the risk of having MBS, and the significance did not change after adjusting for each component of MBS. We concluded that patients with PCOS had an increased prevalence of MBS and thus an increased risk of cardiovascular disease. Hypoadiponectinemia was independently associated with MBS in these patients. Adiponectin as an endogenous biologically relevant modulator of vascular remodeling may have a role in the development of MBS in PCOS patients.

Plasma homocysteine levels in hyperthyroid patients.

Hyperhomocysteinemia is a risk factor for premature atherosclerotic vascular diseases. It is known that plasma homocysteine levels are higher in hypothyroid patients compared to healthy subjects. The aim of our study was to assess plasma total homocysteine concentrations in hyperthyroid patients before and after treatment when euthyroid status was reached and compare them with control group. Thirteen hyperthyroid patients (age, 42.9 +/- 15.6 year) and eleven healthy subjects (age, 39.9 +/- 12.5 year) were involved in the study. Plasma levels of homocysteine and serum cholesterol, triglyceride, HDL cholesterol, urea, creatinine, vitamin B12, folate were measured before and after treatment. LDL cholesterol and creatinine clearances were calculated. Pretreatment homocycteine levels of the hyperthyroid patients were significantly lower than healthy controls (11.5 +/- 3.6 micromol/L vs. 15.1 +/- 4.5 micromol/L, respectively, p<0.05). Posttreatment homocysteine levels were significantly higher than pretreatment levels (13.9 +/- 6.3 micromol/L vs. 11.5 +/- 3.6 micromol/L, respectively, p<0.05) and posttreatment creatinine clearance were lower than pretreatment level (103.5 +/- 12.7 ml/min vs. 114.2 +/- 9.3 ml/min, respectively, p<0.01). Lower homocysteine levels in hyperthyroidism can be partially explained with the changes in creatinine clearance.

Acute adrenal crisis together with unilateral adrenal mass caused by isolated tuberculosis of adrenal gland.

OBJECTIVE: To describe a patient admitted with acute adrenocortical failure and a right adrenal mass without evidence of tuberculosis, who was ultimately diagnosed with isolated adrenal tuberculosis after postoperative histopathologic evaluation. METHODS: A case report is presented, with clinical, laboratory, and imaging findings. We also discuss potential factors that may complicate the diagnosis of tuberculosis. RESULTS: A 61-year-old man was admitted with symptoms and signs of acute adrenal crisis. The patient had an erythrocyte sedimentation rate of 30 mm in 1 hour, a negative tuberculin skin test, a 6-cm right adrenal mass, and left adrenal nodularity in conjunction with normal findings on a computed tomographic scan of the chest. He recovered dramatically after intravenous corticosteroid treatment. Investigation, including acid-fast staining and cultures for tuberculosis of all available specimens, gastroduodenoscopy and rectosigmoidoscopy, intestinal x-ray imaging, and autoantibody studies, did not disclose the diagnosis. Subsequently, bilateral adrenalectomy revealed isolated tuberculosis of the adrenal glands on histopathologic evaluation. Quadruple antituberculous therapy was initiated, and continued follow-up of the patient is scheduled. CONCLUSION: Our case indicates that acute or chronic adrenocortical failure can occur as a result of tuberculosis of the adrenal gland, despite the absence of clinical and laboratory evidence of tuberculosis.