Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

Menstrual Changes after COVID-19 Infection and COVID-19 Vaccination.

Background: Several factors such as stress, depression, infection, and vaccination influenced the menstrual cycle in women during the coronavirus disease 2019 (COVID-19) pandemic. We investigated whether there were changes in the menstrual cycle in women after COVID-19 vaccination or infection and, if so, the nature of the change. Methods: This study was designed as a descriptive, cross-sectional study. A face-to-face survey was conducted among menstruating women aged 18-50 years from May 31 to July 31, 2022. Women were inquired about their first three menstrual cycles that occurred after COVID-19 infection or vaccination. Results: Of 241 women with COVID-19 infection, 86 (35.7%) mentioned that they experienced various changes in their menstrual patterns in the first three cycles after infection. Of 537 participants who received various COVID-19 vaccines, 82 (15.1%) stated that they experienced changes in their menstrual patterns after vaccination. The incidence of postvaccination menstrual change was higher in women who received Pfizer-BioNTech and Sinovac (CoronaVac) vaccines. Only 10.9% of women who reported a change in their menstrual pattern after vaccination or infection consulted a physician. Conclusion: COVID-19 infection and vaccination can affect the menstrual cycle in women. It is important to be aware of the menstrual changes after COVID-19 infection and vaccination and to warn and inform women about this issue.

Severe chronic periodontitis is not common in Acromegaly: Potential protective role of gingival BMP-2

Background/aim: Advanced chronic periodontitis is observed rarely in acromegaly. Periodontal tissue including the alveolar bone is seemed to be spared from the systemic metabolic derangements of bone in this patient population. Chronic elevation of growth hormone, IGF-1, and bone morphogenetic proteins may play a role in periodontal tissue regeneration in acromegalics. In this study, we aimed to evaluate the potential roles of local gingival bone morphogenetic proteins (BMP) in periodontal tissue pathology in acromegaly. Materials and methods: Thirty-five patients with acromegaly and 22 healthy subjects were recruited. All the participants were examined by the same periodontologist for the diagnosis of periodontal diseases. BMP-2 and -4 were studied in gingival crevicular fluid. Results: Gingival BMP-2 and BMP-4 levels were similar in acromegaly and control groups in general, with and without chronic periodontitis. For all the participants, gingival BMP-2 levels were statistically lower in those participants with chronic periodontitis then those without periodontitis (29.4 ± 11.2 vs. 41.2 ± 23.2, respectively, p = 0.027). Causal relation between the gingival BMP levels and periodontal tissue health status was tested with one way ANOVA which revealed a significant difference between gingival BMP- 2 levels in those with different degrees of periodontal tissue pathology (p = 0.025). When analyzed separately, gingival BMP-2 levels revealed a causal relation with the degree of periodontal pathology with borderline significance only in patients with acromegaly (p = 0.057). Conclusion: Acromegaly is a disease with an unexpectedly low frequency of advanced periodontitis, irrespective of the long disease duration and pathognomonic oral manifestations. BMP-2 might have a protective role against chronic advanced periodontitis in these patients.

The effect of iatrogenic subclinical hyperthyroidism on anxiety, depression and quality of life in differentiated thyroid carcinoma

Background/aim: Overt thyroidism is known to cause neuropsychiatric disorders but studies on subclinical hyperthyroidism (SCH) are limited. Subclinical hyperthyroidism induction by administering L-Thyroxine (LT4) is the standard treatment method in differentiated thyroid carcinoma (DTC) follow-up. Our aim was to investigate whether anxiety, depression and quality of life are affected in DTC patients followed-up with exogenous SCH. Materials and methods: The patients were divided into exogenous SCH by LT4-DTC (n = 127), euthyroid-DTC (n = 66) and exogenous euthyroid-benign thyroid noduüle (BTN) who underwent thyroidectomy for benign thyroid pathology (n = 85) groups. Results: The rate of moderate/severe anxiety was significantly higher in SCH-DTC than euthyroid-BTN group (27.5%, n = 35 vs. 9.4%, n = 8) (P = 0.001). TSH levels and Beck anxiety inventory (BAI) scores were significantly negatively correlated(P = 0.009 r = ­0.16). Free T4 and BAI were significantly positively correlated (P = 0.04 r = 0.4). The groups were similar in terms of depression severity (P = 0.15). Subclinical hyperthyroid-DTC group scored significantly lowerthan euthyroid-BTN group in all scales of SF-36 quality of life survey. Conclusion: LT4-induced SCH, which is a part of traditional DTC treatment, can exacerbate the anxiety symptoms in patients and disrupt their quality of life, depending on the level of fT4.

Value of shear wave elastography by virtual touch tissue imaging quantification in patients with diffuse thyroid gland pathology

Background/aim: This study was performed to assess the diagnostic accuracy of shear wave elastography by virtual touch tissue imaging quantification in patients with diffuse thyroid gland pathology and to differentiate Graves' disease from Hashimoto's thyroiditis. Materials and methods: Thirty patients with Hashimoto's thyroiditis and 22 patients with Graves' disease were evaluated with conventional ultrasonography and shear wave elastography by virtual touch tissue imaging quantification. Thirty healthy participants formed the control group. Ten elastographic measurements of each thyroid lobe were performed in all three study groups. The mean shear wave velocity was calculated and compared between the patients and controls. Results: The mean shear wave velocity of the controls (1.92 ± 0.14 m/s) was significantly lower than that of the patients with Graves' disease (2.71 ± 0.22 m/s) and Hashimoto's thyroiditis (2.50 ± 0.20 m/s). Patients with Graves' disease had significantly higher shear wave velocities than those with Hashimoto's thyroiditis (P < 0.001). Conclusion: Shear wave elastography by virtual touch tissue imaging quantification can be used to discriminate a normal thyroid gland from diffuse thyroid gland pathology after conventional sonography and may assist in the diagnosis of Graves' disease and Hashimoto's thyroiditis.

Circulating Th17 cytokine levels are altered in Hashimoto's thyroiditis.

The disrupted autoimmune response in Hashimoto's thyroiditis (HT) has long been considered to be dominantly T helper type 1 (Th1) mediated. Recent advances in the field of immunology have introduced a new class of effector T cells, named 'Th17', which plays important roles in autoimmune disorders once thought to be merely Th1 mediated. We aimed to examine the levels of major Th17 cytokines in patients with HT in this study. We studied serum interleukin 17 (IL-17) and interleukin 23 (IL-23) levels in 46 newly diagnosed, untreated patients with HT (40 women and 6 men, aged 40.0 ± 11.8 years) divided into euthyroid (n=22) and hypothyroid (n=24) groups and compared them with age and sex matched 26 healthy euthyroid controls without HT (21 women and 5 men; aged 36.0 ± 12.9 years). Serum IL-17 and IL-23 levels were significantly different among euthyroid and hypothyroid HT patients and controls, with highest levels obtained in the euthyroid HT group (p=0.041 for IL-17 and p<0.001 for IL-23). TSH was negatively and FT4 was positively correlated with IL-17 (p=0.016 for TSH and p=0.004 for FT4) and IL-23 (p<0.001 for TSH and p=0.003 for FT4) levels. There were no correlations between thyroid volumes calculated on thyroid ultrasonography and IL-17 (p=0.630) or IL-23 (p=0.321) levels. In conclusion, the levels of IL-17, one of the major effector cytokines of the Th17 system, and IL-23, which had been implicated in the generation, survival and expansion of Th17 cells, are altered in HT. How thyroid hormone status and the course of disease affect Th17 system in chronic autoimmune thyroiditis needs to be determined with further studies.

RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.

Evaluation and follow-up of patients diagnosed with hypophysitis: a cohort study.

OBJECTIVE: Primary hypophysitis might be challenging to diagnose, and there is a lack of evidence regarding optimal treatment strategies due to rarity of the disease. We aim to investigate the clinical features and compare the outcomes of different management strategies of primary hypophysitis in a large group of patients recruited on a nationwide basis. DESIGN: A retrospective observational study. METHODS: The demographic, clinical, and radiologic features and follow-up data were collected in study protocol templates and analyzed. RESULTS: One hundred and thirteen patients (78.8% female, median age: 36 years) were included. Lymphocytic (46.7%) and granulomatous hypophysitis (35.6%) were the prevailing subtypes out of 45 patients diagnosed after pathologic investigations. Headache (75.8%) was the most common symptom, and central hypogonadism (49.5%) was the most common hormone insufficiency. Of the patients, 52.2% were clinically observed without interventions, 18.6% were started on glucocorticoid therapy, and 29.2% underwent surgery at presentation. Headache, suprasellar extension, and chiasmal compression were more common among glucocorticoid-treated patients than who were observed. Cox regression analysis revealed higher hormonal and radiologic improvement rates in the glucocorticoid-treated group than observation group (hazard ratio, 4.60; 95% CI, 1.62-12.84 and HR, 3.1; 95% CI, 1.40-6.68, respectively). The main indication for surgery was the inability to exclude a pituitary adenoma in the presence of compression symptoms, with a recurrence rate of 9%. CONCLUSION: The rate of spontaneous improvement might justify observation in mild cases. Glucocorticoids proved superior to observation in terms of hormonal and radiologic improvements. Surgery may not be curative and might be considered in indeterminate, treatment-resistant, or severe cases.

Evaluation of ambulatory arterial stiffness index in hyperthyroidism

Background/aim: Hyperthyroidism causes hemodynamic changes that are associated with adverse cardiovascular outcomes. Twenty-four-hour ambulatory blood pressure monitoring recordings provide us with some essential data: BP variability and ambulatory arterial stiffness index (AASI). In this study, we aimed to investigate AASI and short-term BP variability in both overt and subclinical hyperthyroidism and their relationship with thyroid hormones. Materials and methods: We enrolled 36 patients with subclinical hyperthyroidism, 23 patients with overt hyperthyroidism, and 25 healthy euthyroid controls. ABPM recording was performed for 24 h for all patients. Results: There were no statistically significant differences among the overt hyperthyroidism, subclinical hyperthyroidism, and control groups in terms of AASI (0.43 ± 0.15, 0.38 ± 0.12, 0.42 ± 0.13, respectively; P = 0.315). Variability of diastolic BP was significantly higher in patients with overt hyperthyroidism than in patients with subclinical hyperthyroidism (14.8 ± 2.6 vs. 12.8 ± 2.5%, P = 0.023). There were significant positive correlations between AASI and fT3 (r = 0.246, P = 0.02) and fT4 (r = 0.219, P = 0.04) while TSH was not correlated with AASI (r = 0.023, P = 0.838). After adjusting for confounders, age, 24-h systolic and diastolic BP, variability of systolic and diastolic BP, and fT4 were independent predictors of AASI (r2 = 0.460, P < 0.001). Conclusion: Although AASI did not differ between overt and subclinical hyperthyroidism, there was a positive relationship between AASI and free thyroid hormone levels. Furthermore, short-term BP variability was higher in overt hyperthyroidism than in subclinical hyperthyroidism.

A Case Report of Bilateral Adrenal Sarcomatoid Carcinoma.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Sarcomatoid adrenal carcinoma is even more aggressive type of ACC. Bilateral malignant adrenal tumors are extremely rare except for those that represent metastasis from an extra-adrenal organ. Here we report a 53-year-old woman who presented with abdominal pain and weight loss. Abdominal computed tomography revealed bilateral adrenal masses and a mass in her liver. Surgical specimens showed pleomorphic tumor cells with epithelial and spindle cell morphology and immunohistochemical staining was compatible with sarcomatoid carcinoma. Sarcomatoid adrenal carcinoma should be kept in mind during the management of bilateral adrenal masses.

The effect of thyroid autoimmunity on T-cell responses in early pregnancy.

Thyroid autoimmunity (TAI) is common in women of reproductive age. There is a relationship between TAI and recurrent pregnancy loss and infertility. In pregnant patients with thyroid autoimmunity, the T helper-1 (Th1)/T helper-2 (Th2) ratio may shift to a Th1-type response and these activated T lymphocytes may lead to implantation failure. The aims of this study were to investigate the serum levels of Th1-, Th2-, and T-helper-17-(Th17)-associated cytokines in pregnant patients with TAI, and to evaluate how these cytokines change with l-thyroxin treatment during pregnancy. Twenty pregnant women with TAI diagnosed in the first trimester of pregnancy who were not on l-thyroxine treatment, 14 pregnant women with known TAI before pregnancy already been on l-thyroxine treatment, and 19 pregnant patients without TAI were included in this study. Thyroid function tests, thyroid autoantibodies, and cytokine levels were measured at the first and the second trimesters. In pregnant patients who were diagnosed with TAI in the first trimester, both serum IL-2 levels and IL-17 levels were significantly higher than those of the control group. There were no significant differences between groups for serum IL-4, IL-6, IL-23, IL-10, and IFNγ levels. In the second trimester, no significant differences were found between groups for all the cytokines measured. There are significant differences in Th1- and Th17-associated cytokine levels between patients with TAI and the control group in the first trimester. In the second trimester cytokine levels were similar among all groups. This pattern may be associated with the clinical benefits of l-thyroxine treatment.

Diffuse amyloid deposition in thyroid gland: a cause for concern in familial Mediterranean fever.

Thyroid gland is among the many organs that could be infiltrated in systemic amyloidosis. However, diffuse infiltration of the thyroid gland secondary to systemic amyloidosis associated with Familial Mediterranean fever (FMF) is rare. Here, we present a 49-year-old woman diagnosed with FMF and systemic amyloidosis, who had a large goiter and multiple nodules that developed slowly through the years and was complicated by tracheal compression symptoms and a mild thyroid dysfunction. Multiple fine needle aspiration biopsies of the nodules and the thyroid parenchyma revealed amyloid deposits. We would like to point out that amyloidosis may have a significant impact on the thyroid gland and fine needle aspiration biopsy is a valuable tool for diagnosis.