Mehmet Muhittin Yalcin

A Case With Immunoassay Interferences in the Measurement of Multiple Hormones

CONTEXT Commonly used immunoassays are not free from interference, which can be a confounder in the interpretation of test results. We present a case with extremely high multiple hormone levels due to such interference. CASE DESCRIPTION A 33-year-old woman with no specific symptoms had markedly elevated TSH with normal free T4 and free T3 levels. Repeated measurements revealed discordantly high TSH, ACTH, FSH, PTH, IGF-1, prolactin, β-human chorionic gonadotropin, and calcitonin levels without the associated clinical pictures. The measurements were repeated with the same patient sample on four different analytical platforms using chemiluminescence immunoassays/electrochemiluminescence immunoassays, and the results were divergent on each platform. Serial dilutions of serum samples revealed nonlinearity, suggesting assay interference. All hormonal measurements were in the normal range when heterophile antibody blocking tubes were used. The serum of the patient was then subjected to polyethylene glycol precipitation. The post-polyethylene glycol recovery resulted in hormone levels in the normal range. The patient did not receive any medications and has been under follow-up without any signs and symptoms for 24 months. CONCLUSIONS This report illustrates a rare case of falsely elevated hormone levels due to assay interference caused by heterophile antibodies. We point out the importance of a close collaboration between clinicians and the laboratory to avoid unnecessary clinical investigations as well as inappropriate treatments.

Is thyroid autoimmunity itself associated with psychological well-being in euthyroid Hashimoto's thyroiditis?

Recent studies imply that euthyroid Hashimotos thyroiditis (HT) might be related with impaired HRQoL, depression and anxiety. Ninety three patients with euthyroid HT and 31 age- and gender-matched euthyroid control subjects were enrolled into this study. SF-36 questionnaire, Beck Depression Inventory and Beck Anxiety Inventory tests were used for evaluating HRQoL, depression and anxiety. Beck Depression Inventory scores were higher in patients with HT compared to control subjects (7.5 (4.0-14.75) vs. 5.0 (2.25-9.0), p=0.008). Beck Anxiety Questionnaire scores were also higher in patients with HT than controls (9.50 (5.0-17.0) vs. 5.0 (2.0-11.75), p=0.021). In SF-36 questionnaire; physical functioning (26.0 (20.0-28.0) vs. 29.0 (26.0-30.0), p=0.038), general health (16.4 (13.4-20.4) vs. 19.4 (16.3-21.2), p=0.026) and mental health (20.5 (16.0-23.0) vs. 23.0 (21.0-25.0), p=0.001) scores were lower in patients with HT than control subjects. There were no significant differences between patients with HT under levothyroxine replacement therapy compared to those without therapy in terms of depression and anxiety scores and components of SF-36 questionnaire. Beck Depression Inventory scores were positively correlated with TSH (r=0.250, p=0.01). In SF-36, role physical (r=0.192, p<0.05) and vitality (r=0.181, p<0.05) were positively correlated with fT4. Role emotional was negatively correlated with TSH (r=-0.185, p<0.05) and anti-TPO (r=-0.234, p<0.05). Mental health was negatively correlated with anti-TPO (r=-0.287, p<0.01). HRQoL is impaired and depression and anxiety scores are high in patients with euthyroid HT independent of levothyroxine replacement. Therefore, our results indicate that thyroid autoimmunity itself may have an impact on psychological well-being in euthyroid patients with HT.

GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance

Aims. Growth Differentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory peptide for iron deposition. Current data is conflicting about the relationship between hepcidin and disorders of glucose metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose tolerance (NGT). Methods. Thirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body mass index- (BMI-) matched, were included in the study. Results. Serum GDF-15 levels were significantly higher in IGT compared to NGT. There were no differences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We found a positive correlation between GDF-15 and hepcidin levels. There were also positive correlations between GDF-15 and age, uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G. Conclusions. Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are not significantly altered in prediabetic state.

Fıbroblast growth factor 21 and ıts relatıonshıp wıth ınsulın sensıtıvıty ın fırst-degree relatıves of patıents wıth type 2 dıabetes mellıtus.

INTRODUCTION Fibroblast growth factor 21 (FGF 21) has been suggested as a predictor for the development of type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS We aimed to determine FGF 21 levels in normoglycaemic (Group 1) and prediabetic (Group 2) first-degree relatives (FDR) of patients with T2DM in comparison with normoglycaemic subjects without a history of T2DM in their FDR (Group 3). RESULTS There was a significant difference between Group 1, 2, and 3 with respect to plasma FGF 21 concentrations (143.3 ± 93.8, 221.9 ± ± 171.7 and 121.2 ± 119.8 pg/mL, respectively, p = 0.01). FGF 21 levels were significantly increased in prediabetic FDR of patients with T2DM compared to normoglycaemic subjects without a history of T2DM in their FDR (p = 0.02). FGF 21 levels did not differ between normoglycaemic FDR of patients with T2DM and normoglycaemic subjects without a history of T2DM in their FDR (p > 0.05). In the whole group, FGF 21 correlated positively with age (r = 0.31, p = 0.003), BMI (r = 0.38, p < 0.001), systolic blood pressure (r = 0.38, p = 0.001), diastolic blood pressure (r = 0.26, p = 0.02), fasting blood glucose (r = 0.24, p = 0.02), HOMA-IR (r = 0.23, p = 0.03), AUC glucose (r = 0.35, p = 0.001), and AUC insulin (r = 0.32, p = 0.003) and negatively with HDL cholesterol (r = -0.24, p = 0.02) and Matsuda ISI (r = -0.33, p = 0.002). In the regression analysis, BMI was the most predictive factor for FGF 21 levels (beta = 0.41, r2 = 0.17, p < 0.001). CONCLUSIONS We showed that FGF 21 concentrations are increased in prediabetic FDR of patients with T2DM and that there is a significant association between FGF 21 and obesity and insulin sensitivity. (Endokrynol Pol 2016; 67 (3): 260-264).

Proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and ankle brachial index in patients with differentiated thyroid cancer.

The cardiovascular effects of short-term overt hypothyroidism are not well known. We investigated proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and the ankle brachial index (ABI) in thyroid cancer patients with short-term overt hypothyroidism due to thyroid hormone withdrawal (THW). Twenty-one patients requiring radioactive iodine (RAI) ablation or scanning and 36 healthy control subjects were enrolled. Patients were evaluated in the subclinical thyrotoxic phase when they were on suppressive levothyroxine therapy and in the overt hypothyroid phase due to THW for four weeks. PCSK9, sLOX-1, lipids and ABI were measured in the patient and control groups. Total cholesterol, LDL cholesterol, triglycerides and Apo B levels were increased in short overt hypothyroidism compared with the control group (p<0.001). PCSK9 levels increased before THW and after THW in the patients compared to control group (p<0.001, p=0.004, respectively). sLOX-1 levels were not different between patients with short term overt hypothyroidism and control group (p=0.27). ABI was found to be significantly decreased in patients with thyroid cancer before and after THW compared to control group (p=0.04, p=0.002 respectively). PCSK9 levels were correlated negatively with ABI (r=-0.38, p=0.004). In conclusion; our study demonstrated that patients with differentiated thyroid cancer both before and after THW which is a short term overt hypothyroid phase, had increased PCSK9 levels and decreased ABI. Short term overt hypothyroidism also leads to increased HDL, LDL, total cholesterol, Apo A and Apo B levels.

Eleven patients with primary thyroid lymphoma: a single center experience

Background/aim: Primary thyroid lymphoma (PTL) is a very rare thyroid malignancy. It should be diagnosed and treated immediately and accurately. Our aim was to evaluate the diagnostic methods and treatment results for patients with PTL.Materials and methods: We retrospectively evaluated the records of 11 patients with PTL from 2009 to 2015, diagnosed at our institute. Age, sex, stage, histopathologic type, presence of Hashimotos thyroiditis, diagnostic methods, treatment types, and recurrence were examined.Results: Six patients were female, 5 were male, and the median age of the patients was 61 years (range: 15-76 years). All patients had a large palpable mass in the neck. Fine needle aspirate (FNA) biopsy was performed in all patients; however, it was useful only in the diagnosis of 7 patients. Excisional and surgical biopsy was performed in 4 patients. All patients had non-Hodgkin B-cell lymphoma, including 9 cases of diffuse large B-cell lymphoma (DLBCL), and 2 patients had mucosa-associated lymphoid tissue (MALT) lymphoma. Recurrence was observed in one patient. Median survival was 34 months.Conclusions: The preferred option for the diagnosis of PTL should be FNA biopsy, and the treatment should be decided on according to whether the disease is limited to the thyroid gland or not, its histological type, and its stage.

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.

Lymph node fine-needle aspiration washout thyroglobulin in papillary thyroid cancer: Diagnostic value and the effect of thyroglobulin antibodies

ABSTRACT Purpose: Thyroglobulin (Tg) assessment in the needle washout after fine-needle aspiration biopsy (FNAB) of a suspicious neck lymph node (LN) is known to improve the diagnostic accuracy in patients with papillary thyroid cancer (PTC). However, there is still controversy on the best diagnostic cut-off levels for FNAB-Tg and whether thyroglobulin antibody (TgAb) positivity affects FNAB-Tg. The objectives of this study were to determine (i) the diagnostic power of different cut-offs for FNAB-Tg and (ii) if serum TgAb(+) negatively affects the FNAB-Tg evaluation. Methods: This was a retrospective cohort study analyzing PTC patients with suspicious neck LNs, in a university hospital setting, from October 2009 to October 2013. In total, 103 patients with PTC (226 LNs) undergoing ultrasound-guided FNAB for LNs were included. Cytology and FNAB-Tg levels were compared in reference to LN histopathology and the effect of TgAb(+) on FNAB-Tg levels was evaluated. Results: The diagnostic accuracies of FNAB-Tg cut-off of 1 and 10 ng/mL were 94.1% and 88.2%, respectively. Raising the cut-off from 1 to 10 ng/mL led to decreased sensitivity rates (91.9% vs. 83.9%). The receiver operating characteristic curve analysis demonstrated that the best FNAB-Tg cut-off was 1.2 ng/mL. There were no LNs with an FNAB-Tg ≥ 10 ng/mL that turned out to be cytologically or histopathologically benign. FNAB-Tg levels of the histopathologically malignant LNs were similar between TgAb (+) and TgAb (−) patients (p = 0.546). Serum Tg predicted FNAB-Tg levels above 1 ng/mL (p = 0.002) and FNAB-Tg predicted malignant histopathology (p = 0.004), both independently of the TgAb status of the patient. Conclusions: FNAB-Tg ≥ 1 ng/mL has a superior diagnostic power, irrespective of TgAb (+), in PTC patients with suspected LN involvement.

Metastatic Papillary Thyroid Carcinoma Arising from Thyroglossal Duct Cysts

ABSTRACT Objective: We report a rare case of a patient who developed papillary thyroid carcinoma (PTC) arising from thyroglossal duct cysts (TGDCs) with lateral lymph node metastasis who had a normal thyroid gland and benign central compartment lymph nodes. Methods: We present a case with metastatic PTC arising from TGDC together with a brief review of the relevant literature. Results: A 38-year-old man patient was admitted with a cystic lesion in the midline of his neck. There was also an easily palpable lymph node on the left neck, which was suspected of being metastatic PTC on ultrasonography (USG). There was no nodule in the thyroid gland. A fine-needle aspiration cytology of the lymph node was positive for metastases of PTC. We performed an excision of the cystic lesion and total thyroidectomy with the central and left neck lymph node dissection. The cystic lesion pathology was reported as PTC, 10 mm in size. There was a metastatic lymph node in the lateral left neck compartment (regions III–IV), 7 c...

Destructive thyroiditis followed by hypothyroidism associated with infliximab therapy.

OBJECTIVE To present the rare case of a patient who developed destructive thyroiditis accompanied by transient thyrotoxicosis resulting from infliximab therapy for the treatment of psoriasis. METHODS The clinical presentation and management of a case with infliximab-associated thyroiditis is described with a brief review of the literature. RESULTS A 57-year-old male who suffered from psoriasis was treated with infliximab therapy for 4 years. Thyroid function tests were normal before infliximab therapy. When the patient presented in our clinic, he had thyrotoxicosis and was using propylthiouracil. A 99m Technetiumpertechnetate thyroid scintigraphy scan showed no visualization of either thyroid lobe or decreased thyroid iodine uptake. Thyroid-stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody (anti-TPO Ab) and thyroglobulin antibody (anti-Tg Ab) were negative. Thyroid ultrasonography revealed a heterogeneous thyroid gland without nodules. After stopping propylthiouracil therapy, we advised monitoring of his thyroid function tests in the following weeks, and infliximab therapy for psoriasis was continued. Four weeks later, his thyroid function tests showed an elevated TSH level with normal levels of free triiodothyronine and thyroxine (FT3 and FT4, respectively), and levothyroxine treatment was administered to the patient. Thyroid function tests normalized after levothyroxine treatment. One year later, infliximab therapy was stopped because of clinical remission. Simultaneously, levothyroxine treatment was also stopped. His thyroid function tests were normal 6 weeks after the cessation of levothyroxine treatment. CONCLUSION To our knowledge, the present report is the third infliximab-associated thyroid disorder case. Periodic follow-up of thyroid function tests is necessary during infliximab therapy.