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.

Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

Cellular immunity in subacute thyroiditis: a new perspective through neopterin.

Subacute thyroiditis (SAT) is an inflammatory disorder of the thyroid gland. Although its etiology is not fully understood, it is believed to occur shortly after viral infections and is mostly associated with human leukocyte antigen (HLA)-B*35. Cellular immunity is prominent in SAT. Neopterin is produced by activated monocytes/macrophages and is a marker of cellular immunity. Its production is stimulated by interferon gamma (IFN-γ), provided mainly by activated helper T lymphocytes type 1 (Th1) in the adaptive immune system. Therefore, with these cells' activation, an increase in serum neopterin levels is expected. We aimed to evaluate neopterin levels in demonstrating cellular immunity in SAT and compared 15 SAT patients with 16 healthy controls. Since all SAT patients were in the active thyrotoxic phase, we found a significant difference in thyroid functions. Classical inflammatory markers, erythrocyte sedimentation rate, and C-reactive protein were markedly elevated in the patient group. Although we expected to find an increase considering that cellular immunity is at the forefront in the pathogenesis of SAT, we found serum neopterin levels significantly lower in the patient group than in the control group. There is an increase in CD8+ T cells in the thyroid tissue in SAT. The possible relationship with HLA-B*35- major histocompatibility complex class I in SAT, and the antigen presentation to CD8+ T cells may be the reason why we observed low serum neopterin levels in patients due to the cytokine imbalance. Neopterin provides unique and independent data from classical acute phase response indicators.

Assesment of attainment of recommended TSH levels and levothyroxine compliance in differentiated thyroid cancer patients.

OBJECTIVE: Thyroid-stimulating hormone (TSH) suppression treatment can induce signs and symptoms of hyperthyroidism and hypothyroidism due to inappropriate treatment or poor compliance to the treatment. The current study aimed to investigate TSH levels, frequency of being on target TSH, adherence to levothyroxine (LT4) suppression treatment in differentiated thyroid cancer (DTC) patients after surgery in a multicentric setting. DESIGN AND PATIENTS: This multicentric cross-sectional study was conducted at 21 medical centres from 12 cities in Turkey. DTC patients followed at least one year in the same center included in the study. Clinical data, serum TSH, free thyroxine (FT4), thyroglobulin (Tg) and anti-Tg levels were recorded during the most recent visit. Body mass index, systolic and diastolic blood pressures, pulse rate were measured. LT4 doses were recorded and doses per kilogram of bodyweight were calculated. Pill ingestion habits recorded and adherence to the therapy were evaluated using the Morisky Medication Adherence Scale and categorized as good, moderate or poor compliant based on their scores. Risk stratification forpredicting the disease persistance and/or reccurence was assessed using the American Joint Committee on Cancer-7th edition thyroid cancer staging calculator. TSH serum concentrations were classified as severe suppression (TSH < 0.01 mU/L), moderate suppression (TSH: 0.01-0.1 mU/L), mild suppression (TSHL 0.1-0.5 mU/L), euthyroid (TSH: 0.5-4 mU/L) and hypothyroid (TSH > 4 mU/L). TSH levels can also be classified as on being on target, under the target, or beyond over the target, according to the American Thyroid Association recommendations. RESULTS: A group of 1125 patients (F/M: 941/184, 50.7 ± 11.7 years) were included in the study. The mean LT4 daily dosage was 132.4 ± 39.6 mcg/day. TSH levels showed severe suppression in 99 (%8.8) patients, moderate suppression in 277 (%24.6) patients and mild suppression in 315 (%28) patients and euthyroid range in 332 (%29.5) patients and hypothyroid range in 97 (8.6%). TSH levels were in target in 29.2% of the patients 20.4% of the patients were undertreated, 50.4% overtreated. The daily LT4 dose and LT4 dose/kg were significantly higher in the severe suppression group (p < .001, p < .001). According to the Morisky scale, 564 patients (50.1%) were good compliant, 368 patients (32.7%) were moderate compliant, and 193 patients (17.1%) were noncompliant. Patients with poor compliance need a higher dose of LT4 compared to the good compliance group (p < .001). TSH levels of patients with good compliance were 0.67 ± 1.96 mU/L and TSH with poor compliance was 2.74 ± 7.47 mU/L (p < .001). TSH levels were similar in patients on fixed and alternating dosages. CONCLUSION: In 29.2% of the DTC patients, serum TSH levels were at target levels. Remaining of the study group have TSH levels under or over treatment range, exposing the patient to medication side effects. Majorty of the study group 82.8% have good or moderate adherence to LT4 therapy. Reaching TSH targets requires simplified and applicable guidelines and following the guideline recommendations.

Subacute thyroiditis following COVID-19 vaccination in a 67-year-old male patient: a case report.

Subacute thyroiditis is the most common cause of painful thyroid gland diseases. It is characterized by inflammation of the thyroid gland and usually occurs after viral upper respiratory tract infections. Coronavirus disease 2019 (COVID-19) can lead to subacute thyroiditis. There are also vaccine-related subacute thyroiditis cases in the literature. Here, we describe a 67-year-old male patient developing subacute thyroiditis following COVID-19 vaccination.

Effect of hyperparathyroidism on coagulation: a global assessment by modified rotation thromboelastogram (ROTEM)

Background/aim: Hyperparathyroidism is an endocrine disorder characterized by hypercalcemia. Because of calcium's effects on parathyroid glands, bone, intestines, and kidneys, it has an important place in homeostasis. The results of studies regarding hyperparathyroidism hemostasis are conflicting. Thromboelastography helps to evaluate all steps of hemostatic system. Our aim in this study was to investigate the possible role of hemostatic mechanisms in the development of thrombosis in hyperparathyroid patients with the modified rotation thromboelastogram (ROTEM). Materials and methods: Twenty-two patients with primary hyperparathyroidism (PHPT) and 20 healthy controls were involved. This study was conducted in Eskisehir Osmangazi University Faculty of Medicine, Endocrinology and Hematology clinics for 2 years. The complete blood count, fibrinogen, D-dimer levels, prothrombin time, activated prothrombin time, and ROTEM parameters [clot formation time (CFT), clotting time (CT), and maximum clot formation (MCF)] were determined by two activated tests, INTEM and EXTEM analyses. A thromboelastographic evaluation was performed in the preoperative and postoperative (3 months after surgery) periods. Results: In INTEM assay, the CT (p = 0.012) and CFT (p = 0.07) values were increased in preoperative PHPT patients compared with the control group. Although there was a decrease in the postoperative CT and CFT values, no statistical difference was found. Conclusion: The prolongation of the CT and CFT values were consistent with a hypocoagulable state in patients with PHPT. Hyperparathyroidism causes a hypocoagulable state that can be successfully assessed by ROTEM. Hemostatic changes, do not seem to have an effect on increased cardiovascular mortality.

Coexistence of Ectopic Posterior Pituitary and Sellar/Suprasellar Arachnoid Cyst: A Case Report.

BACKGROUND: The ectopic posterior pituitary (EPP) is a rare condition characterized by the ectopic location of the posterior pituitary lobe associated with varying degrees of stalk anomalies. The arachnoid cysts (AC) are benign lesions of the arachnoid, which account for 1% of all intracranial space-occupying lesions. Sellar/suprasellar ACs account for approximately 1% of all ACs. This is the first case of coexistence EPP with sellar/suprasellar AC. CASE REPORT: A 67-year-old woman presented with 6 months history of fatigue. Her medical history was positive for irregular menstruation. Her endocrine examinations indicated low free thyroxine level with low TSH level, low oestradiol with low gonadotrophin level, slightly elevated prolactin level. Her Insulin-like growth factor-1 was below the normal levels. Dynamic contrast hypophysis MRI revealed a sellar cystic lesion with a dimension of 18 × 14 × 14 mm, extending from the suprasellar cistern, traversing the diaphragma sellae and reaching the level of the floor of the 3rd ventricle, consistent with sellar/suprasellar AC. There was no wall enhancement. The optic chiasm was compressed. The precontrast T1-weighted magnetic resonance images did not demonstrate the characteristic bright spot of posterior pituitary within the sella, which was higher in position, in the region of the median eminence. The pituitary stalk was not present. CONCLUSION: Although speculative, we have a hypothesis to explain how the EPP and sellar/- suprasellar AC coexist in this patient. Due to the absence of stalk, CSF may enter the sella tursica from the central aperture of the diaphragma sellae through which normally the stalk passes.

An Evaluation of Clinicopathological Factors Effective in the Development of Central and Lateral Lymph Node Metastasis in Papillary Thyroid Cancer.

INTRODUCTION AND AIM: Papillary thyroid cancer (PTC) constitutes more than 90% of newly emerging differentiated thyroid cancers. Lymph node metastasis is often seen in PTC. There is a high risk of central metastasis in the presence of clinicopathological factors such as extrathyroidal extension, multifocality and lymphovascular invasion. The aim of this study is to evaluate the clinicopathological features that are effective in the development of lymph node metastasis. MATERIAL AND METHOD: A retrospective examination was made of the records of patients diagnosed with papillary thyroid cancer and followed up in our clinic. Patients with and without lymph node metastasis were compared in respect of demographic features such as age, gender, pathology, histopathology, tumor size, lymph node metastasis, lymphovascular invasion, multifocality, capsule invasion, extrathyroidal extension and bilaterality. RESULTS: Lymph node metastasis was determined in 52 of 419 papillary thyroid cancers. In the logistic regression analysis, a statistically significant relationship was determined between cervical lymph node metastasis and age <45 years (p < 0.001, OR:4.193), lymphovascular invasion (p < 0.001, OR:7.762), capsule invasion (p < 0.002, OR:3.054), extrathyroidal extension (p < 0.001, OR:6.450) and bilaterality (p < 0.001, OR: 0.217). CONCLUSION: The risk of cervical lymph node metastasis was determined to be high in the presence of clinicopathological factors such as extrathyroidal extension, multifocality and lymphovascular invasion. Although lymph node metastasis does not clinically develop in all patients, knowing the risk factors related to lymph node metastasis can contribute to the evaluation of prophylactic central neck dissection in high-risk patients and follow-up of the patient in respect of recurrence.

The Effect of Hyperparathyroid State on Platelet Functions and Bone Loss.

OBJECTIVE: Coagulation and fibrinolysis defects were reported in primary hyperparathyroid patients. However, there are not enough data regarding platelet functions in this group of patients. Our aim was to evaluate the platelet functions in primary and secondary hyperparathyroid patients and to compare them with healthy subjects. MATERIALS AND METHODS: In our study 25 subjects with primary hyperparathyroidism (PHPT), 25 subjects with secondary hyperparathyroidism (SHPT), and 25 healthy controls were included. Platelet functions of the subjects were evaluated by using platelet-rich plasma and platelet aggregation tests induced with epinephrine, adenosine diphosphate (ADP), collagen, and ristocetin. Serum P selectin levels, which indicate platelet activation level, were measured in all subjects. Bone mineral densitometry was performed for all patients. RESULTS: There was no significant difference between the groups with PHPT and SHPT and the control group regarding the platelet aggregation tests and serum P selectin levels. There was also no significant correlation between parathormone levels and aggregation parameters (ristocetin, epinephrine, collagen, and ADP: respectively p=0.446, 0.537, 0.346, and 0.302) and between P selectin (p=0.516) levels. When we separated the patients according to serum calcium levels, there was also no significant difference between aggregation parameters and serum P selectin levels between the patients with hypercalcemia and the patients with normocalcemia. We could not find any significant correlation between aggregation parameters, P selectin levels, and serum calcium levels in this group of patients. Bone loss was greater in patients with PHPT. CONCLUSION: There is no significant effect of PHPT or SHPT and serum calcium levels on platelet functions when evaluated by aggregation tests.

Clinical effectiveness of thyroidectomy on the management of locally advanced laryngeal cancer.

OBJECTIVE: The incidence of thyroid gland invasion in patients with advanced laryngeal cancer was reported to be 0-50%. However there is a controversy in necessity and extent of routine thyroidectomy in these patients due to the difficulty in diagnosis of tumor invasion to thyroid gland and the risk of possible postoperative hypothyroidism and hypocalcemia. METHODS: The medical files of 47 patients who underwent thyroidectomy as part of surgical treatment for advanced laryngeal cancer were reviewed. RESULTS: Fourty-four (93.6%) patients underwent hemithyroidectomy, 3 (6.3%) patients underwent total thyroidectomy. Thyroid gland invasion was found in 2 (4.2%) patients. Hypothyroidism occurred in 15 (31.9%) patients, and their hormone levels were regulated with medical treatment during follow-up. Hypocalcemia was not found in any patients. CONCLUSION: We recommend that at least a hemithyroidectomy should be performed in patients with advanced laryngeal cancer, if they have any predictive factor (subglottic extension more than 1cm, invasion of paraglottic space, thyroid cartilage, cricoid cartilage and prelaryngeal tissue detected by radiological examination) for thyroid gland invasion.