ACTA ENDOCRINOLOGICA (BUC)

Context. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder, which is characterized by renal phosphate wasting, hypercalciuria, increased 1,25-dihydroxyvitamin D, and decreased parathormone (PTH) levels. Objective. Here we report different clinical features of two siblings with HHRH, confirmed with molecular diagnosis. Subjects and methods. 16.4 years old boy (P1), and 8.7 years old girl (P2) were referred to our outpatient clinic due to clinical suspicion of metabolic bone diseases. Results. P1 had severe hypophosphatemia. Additionally, PTH concentration was near to the lower limit, 1,25-dihydroxyvitamin-D concentration was near to the upper limit. P2 had relatively milder clinical and laboratory findings. Bilateral renal calculi were detected on ultrasound in both of them. HHRH was suspected due to their described biochemistry and the presence of bilateral renal calculi. Molecular analysis of SLC34A3 gene revealed a homozygous variant c.756G>A (p.Gln252=) and a splice donor variant c.1335+2T>A. After oral phosphate treatment, clinical and biochemical improvements were observed. However treatment nonadherence of patients was a barrier to reach treatment goal Conclusion. The clinical phenotype due to the same mutation in the SLC34A3 gene may vary even among the members of the same family. An accurate diagnosis is important for the appropriate treatment.

Context. Thyroid cancer is the most common endocrine malignancy. Within various subtypes of thyroid neoplasms, those with follicular growth pattern usually make diagnostic problems. Objectives. To examine ck19 expression as a diagnostic marker in thyroid neoplasms with follicular growth pattern. Design. In this cross sectional study, 86 patients were enrolled. Subjects and Methods. Totally 22 follicular adenoma (FA), 18 well differentiated tumors with undetermined malignant potential (WT-UMP) and 46 follicular variants of papillary thyroid carcinoma (FV-PTC) were enrolled and examined for Ck19 expression by immunohistochemistry staining. Membranous/cytoplasmic staining patterns were considered as positive. Specimens without staining were considered as 0, < 5% positively stained cells as 1+, 5%-25% as 2+, 25%-75% as 3+ and >75% as 4+. Result. CK19 was negative in most cases of FA while positive in most WDT-UMP and FV-PTCs, p<0.001. Additionally, most cases with 2+ and 3+ staining patterns were FV-PTC (75% and 81%, respectively, p<0.001) and none of FAs showed 3+ positivity (p<0.001). Additionally, most of strongly positive results in patients > 45 y/o were PTC (p<0.001). Conclusion. Ck19 is a useful marker in differentiating FA from FV-PTC. We found diffuse and strong (3+) staining pattern in FV-PTC but none of FAs were so. We concluded that diffuse and strong staining for ck19 in a thyroid lesion with follicular pattern of growth, especially in a patient older than 45 y/o should raise the possibility of malignancy.

Background. Thyroid hormone resistance (RTH) is defined as a decrease in response to thyroid hormones in the target tissue. Most patients present with nonspecific findings. In this article, we aimed to represent a 22-yearold female patient who presented with palpitation, fatigue, and heat intolerance. She was thought to have thyroid hormone resistance and her genetic examination revealed NM_001128177.1 (THRβ): c.1034G > A (p.Gly345Asp) pathogenic variation in the THRβ gene. Case report. A 22-year-old female patient presented with complaints of fatigue, heat intolerance and palpitations. She was taking Propranolol twice daily at admission. Her family history revealed hypothyroidism in her grandmother. Her physical examination results were as follows: height 160 cm, weight 65 kg, body mass index 25.4kg/m2, body temperature 36.5˚C, respiratory rate 18/min, heart rate 86 beats/min, blood pressure 120/80 mmHg. Her palms were sweaty. The heart sounds were normal, and no heart murmur was auscultated. The laboratory results were TSH: 5.31uU/mL, fT3: 6.83 pg/mL, and fT4: 2.43 ng/dL. THRβ gene mutation analysis was requested for our patient whose clinical history and laboratory results were compatible with thyroid hormone resistance. The pathogenic variation NM_001128177.1(THRβ):c.1034G>A (p.Gly345Asp) was detected after analysis. Conclusion. A diagnosis of RTH requires high clinical suspicion and a genetic mutation analysis should be requested in the case of clinical suspicion. In this way, unnecessary anti-thyroid treatment can be prevented.

Introduction. Irisin is a recently discovered novel adipomyokine that induces an increase in total body energy expenditure, improves insulin sensitivity and glucose tolerance. It has been shown that circulating levels of irisin are low in patients with obesity, diabetes mellitus and impaired glucose tolerance. However, the information about the level of circulating irisin in gestational diabetes mellitus (GDM) is controversial. Material and Methods. Serum irisin was measured by an ELISA in a longitudinal prospective cohort study in 221 women. There were 156 healthy pregnant and 65 women with GDM. Results. Circulating irisin levels were significantlly higher in the middle pregnancy compared with early pregnancy levels in healthy pregnant women and in women with GDM. Serum irisin levels were found to be lower in GDM compared to healthy pregnant women during first trimester but the difference was not observed throughout the pregnancy and it was comparable in middle pregnancy. There was a significant inverse correlation of BMI with serum irisin (r = -0.193, p = 0.004) and between HbA1c and mean glucose of OGTT with serum irisin (r =-0.377, p =0.0001) and (r = -0.147, p:0.03) in the early pregnancy of pregnant women repectively. Conclusions. The present study shows that serum irisin level increases throughout the gestational period from early to middle pregnancy in women with GDM, but there is no effect of irisin on the development of GDM.

Context. SARS-CoV-2 infection was declared a pandemic in 2020 and affected millions of people worldwide. Angiotensin-converting enzyme-2 receptors, through which coronavirus enters the cells of different organs, have been detected in the thyroid gland. The most common cause of thyrotoxicosis is Graves’ disease in which thyroid-receptors antibodies (TRAb) stimulate the TSH receptor, increasing thyroid hormone production and release. Case presentation. A 22-year-old woman had symptoms of palpitation, tremor, muscle weakness, anxiety and sleep disturbance. 3 weeks before the onset of these symptoms, the patient suffered from COVID-19, which lasted 14 days and was characterized by a course of moderate severity with fever up to 38˚C, general weakness without shortness of breath. The patient had no pre-existing thyroid problems. Her TSH was <0.01 mU/L, FT4, FT3 and TRAb were increased. Antithyroid drugs, glucocorticosteroids and β-blockers were prescribed. During 3 months of treatment doses of methimazole, methylprednisolone and bisoprolol were gradually reduced due to the improvement of the patient’s condition and thyroid tests normalization. Conclusions. COVID-19 infection can cause Graves’ disease and thyrotoxicosis. The onset of this disease after SARS-CoV-2 does not depend on the presence of preexisting thyroid pathology and requires the appointment of glucocortisteroids.

Objective. Osteoporosis is a complex disease and its development is influenced by genetic, epigenetic, metabolic, and environmental factors. However, specific genetic factors associated with osteoporosis are not fully understood. The aim of this study was to identify genetic risk factors for osteoporosis. Methods. This study included 86 females with osteoporosis and 47 healthy females. We analyzed rs1800587, rs16944, rs1799814, rs4988321, rs2228570, and rs35211496 variations in IL1A, IL1B, CYP1A1, LRP5, VDR, and RANK, respectively, using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) analysis. Results. Our analysis revealed that the CT and TT genotype for rs1800587 in IL1A was associated with higher bone mineral density in the lumbar spine, trochanter, Ward's triangle, and femoral neck (p=0.020, p=0.021, p=0.015, and p=0.013, respectively). The rs1800587 variation in IL1A was associated with a reduced risk of osteoporosis in both dominant and codominant inheritance models (CC vs. CT, p=0.016 and CC vs. CT/TT, p=0.035, respectively). However, we did not identify any statistically significant differences in either genotype or allele frequencies between the control group and the patients with osteoporosis for the other genetic variations examined. Conclusion. Our findings suggest that the rs1800587 variation in IL1A gene is associated with a significantly decreased risk of osteoporosis in the Turkish population.

Background. Retinopathy is a common complication of diabetes and strongly related to the duration of the disease and the quality of its management. Despite this relationship, some studies have reported the prevalence of diabetic retinopathy at diagnosis to be 5-30%.\r\nAim. To investigate the prevalence of retinopathy in patients with newly diagnosed type 2 diabetes and its relation to some association factors in Isfahan, Iran.\r\nMethods. During 2001-2004, all newly diagnosed type 2 diabetics (n= 710) attending Isfahan Endocrine and Metabolism Research Center, were enrolled, by consecutive patient selection. Everybody accepted our invitation. The patients were examined by an internist and then by an ophthalmologist for retinopathy. Fasting plasma glucose, glycosylated hemoglobin, lipid profile, and 24-hour urinary albumin and creatinine concentrations were measured.\r\nResults. Of 710 patients, 286 were male. Mean age of the patients was 48.8(9.8) years (31-72 years) and median of diabetes duration was 6 months (0.5-12 months), respectively. Nine percent of patients (CI95%: 7-11) [(9.8% of men (CI95%: 6-13) and 8.5% of women (CI95%: 6-11)] had retinopathy (Odds ratio= 0.85, CI95%: 0.51-1.43, P= 0.5). In the final analysis using logistic regression test, body mass index (OR= 0.9, CI 95%: 0.8-1, P= 0.01), diastolic hypertension (OR= 3.9, CI 95%: 1.33-11.7, P= 0.01) and 24-hour urinary albumin concentration (OR= 1.005, CI 95%: 1-1.01, P= 0.01) were identified as association factors\r\nfor retinopathy.\r\nConclusions. Retinopathy was moderately prevalent in our patients.

Introduction. Diagnosing Cushing Syndrome (CS) remains challenging due to its diverse symptoms and the complexity of its subtypes. This study aimed to optimize diagnostic cut-off values for differentiating CS subtypes using the 1 mg dexamethasone suppression test (DST) in a cohort of 237 patients. Materials and Methods. Retrospective data from patients diagnosed with non-functional adrenal adenomas (NFA), mild autonomous cortisol secretion (MACS), adrenal CS, and pituitary CS at the Dokuz Eylül University Endocrinology and Metabolism Clinic (2005–2016) were analyzed. Sensitivity and specificity of morning cortisol levels after DST were evaluated using receiver operating characteristic (ROC) curve analysis. Results. The analysis identified optimal morning cortisol cut-off levels: 2.14 μg/dL (59.04 nmol/L) for MACS, 2.3 μg/dL (63.4 nmol/L) for adrenal CS, and 2.33 μg/dL (64.28 nmol/L) for pituitary CS. Conclusion. These optimized thresholds demonstrated high sensitivity and specificity, significantly improving diagnostic precision over the conventional threshold of 1.8 μg/dL (50 nmol/L). The findings underscore the importance of tailored cut-off values to address subtype-specific diagnostic challenges, reducing delays and mitigating long-term complications. Personalized diagnostic approaches, incorporating patient demographics and disease-specific characteristics, are essential for enhancing diagnostic accuracy and facilitating timely interventions.

The aim of this study is to analyze and identify the main predictors that may indicate multifocal growth of PTC. Materials and methods. The main and control groups included patients with the category of malignant multifocal process T1-3mN0Mx (n=109) and unifocal T1- T3N0Mx (n=50) respectively, who underwent thyroidectomy with lymphadenectomy. Ultrasound characteristics of the nodes, tissue changes of the thyroid gland were taken into account. Results. Fibrous changes can be considered as one of the risk factors of the presence of additional PTC lesion. Discussion. There is no unambiguity in the definition of predictors of multifocal PTC growth. Conclusions. No clear predictors of multifocal PTC have been identified. It is advisable to improve the quality of ultrasound, to focus on single-focus PTC in patients with fibrinous changes in the thyroid gland at normal levels of TSH.

Context. Some adrenal tumors, such as pheochromocytoma, can be life-threatening. Therefore it is crucial to distinguish them from other lesions, especially prior to surgery. Chromogranin A (CgA) seems to potentially be a good marker for tumors of chromaffin origin. Objective. To assess the differentiating value of CgA in the diagnostic work-up of pheochromocytoma. Design. Retrospective study of operated patients with adrenal incidentaloma with lesions > 10 Hounsfield’s units (HU) on CT. Subjects and Methods. Thirty patients (11 males, 19 females; aged 61.5±21 years) were enrolled in the study. Patients using medications interfering with the assessment of CgA and metanephrines were excluded. Two groups were formed: those with pheochromocytoma (Ph, n=16) and those with non-pheochromocytoma (N-Ph, n=14) lesions. Data included radiological features of masses, serum CgA and 24-hour urine metanephrines (24 - HUM) concentrations. Results. No difference in 24-HUM level nor tumor size or density was found between groups Ph and N-Ph. Median serum CgA concentration was higher in Ph group compared to the N-Ph: 99.35 (68.12-172.73) vs. 52.92 (34.37-101.26) ng/mL, respectively (P=0.04). In Ph group, the size of the lesion correlated negatively with density (r= -0.53, P=0.042). No significant correlation in CgA, 24-HUM, density or size of the lesion was found. Performed curve receiver operating characteristic (ROC) showed AUC=0.7232 for CgA. Taking into account CgA serum value of ≤ 50 ng/mL (sensitivity: 93.75%, specificity: 50.00%, P=0.012), we proposed an algorithm for management of lesions > 10 HU on CT. Conclusion. CgA level ≤ 50 ng/mL might be useful in initial screening evidence for the exclusion of pheochromocytoma. It is crucial to eliminate factors interfering with the measurements.