Cesar Esteves

A polymorphism in the promoter region of the selenoprotein S gene (SEPS1) contributes to Hashimoto's thyroiditis susceptibility.

CONTEXT The association between selenium and inflammation and the relevance of selenoproteins in follicular thyroid cell physiology have pointed to a putative role of selenoproteins in the pathogenesis of autoimmune thyroid diseases. OBJECTIVE The aim of this study was to evaluate the role of a promoter variation in SEPS1, the selenoprotein S gene, in the risk for developing Hashimotos thyroiditis (HT). DESIGN A case-control study was performed to assess the association of genetic variation in the SEPS1 gene (SEPS1 -105G/A single-nucleotide polymorphism, rs28665122) and HT. SETTING The study was conducted in north Portugal, Porto, in the period of 2007-2013. PATIENTS OR OTHER PARTICIPANTS A total of 997 individuals comprising 481 HT patients and 516 unrelated controls were enrolled in the study. MAIN OUTCOME MEASURES Genetic variants were discriminated by real-time PCR using TaqMan single-nucleotide polymorphism genotyping assays. RESULTS There is a significant association between the SEPS1 -105 GA and AA genotypes and HT [odds ratio (OR) 2.24, confidence interval (CI) 1.67-3.02, P < 5.0 × 10(-7), and OR 2.08, CI 1.09-3.97, P = .0268, respectively]. The A allele carriers are in higher proportion in the patient group than in the control population (46.2% vs 28.1%, P < 5.0 × 10(-7)) with an OR (CI) of 2.22 (1.67-2.97). The proportion of patients carrying the A allele is significantly higher in male patients with HT, representing a 3.94 times increased risk (P = 7.9 × 10(-3)). CONCLUSION Our findings support the existence of a link between SEPS1 promoter genetic variation and HT risk.

A challenging coexistence of central diabetes insipidus and cerebral salt wasting syndrome: a case report

BackgroundCombined central diabetes insipidus and cerebral salt wasting syndrome is a rare clinical finding. However, when this happens, mortality is high due to delayed diagnosis and/or inadequate treatment.Case presentationA 42-year-old white man was referred to neurosurgery due to a non-functional pituitary macroadenoma. He underwent a partial resection of the tumor on July 2, 2015. On the day following surgery he presented polyuria with sodium 149 mEq/L, plasma osmolality 301 mOsm/kg, and urine osmolality 293 mOsm/kg. He started nasal desmopressin 0.05 mg/day with good response. He was already on dexamethasone 4 mg and levothyroxine 75 mcg due to hypopituitarism after surgery. On July 9 he became confused. Cerebral computed tomography was performed with no significant changes. His natremia dropped to 128 mEq/L with development of polyuria despite maintenance of desmopressin dose. His hemoglobin and hematocrit rose from 9.1 g/L to 11.6 g/L and 27.5 to 32.5, respectively. His thyroid function was normal and he was on hydrocortisone 30 mg/day. At 12 p.m. 150 mg/hydrocortisone infusion was initiated, but sodium did not increase. Plasma and urine osmolality were 264 mOsm/kg and 679 mOsm/kg, respectively. At 4 p.m. hydrocortisone was increased and hypertonic saline replacement started. Two hours later he was dehydrated with polyuria and vomiting, and natremia of 124 mEq/L. Hyponatremia was very resistant to treatment despite hypertonic saline replacement, hence desmopressin was suspended. The following day, urine spot analysis showed that natriuresis was 63 mEq/L with serum sodium 132 mEq/L. This was interpreted as a cerebral salt wasting syndrome and control was achieved with aggressive hypertonic saline replacements and fludrocortisone 0.1 mg/three times a day. ConclusionsWe present a rare case of a patient with diabetes insipidus and cerebral salt wasting syndrome, who was successfully treated. Hyponatremia in a patient with diabetes insipidus may erroneously be interpreted as inadequate diabetes insipidus control or as syndrome of inappropriate antidiuretic hormone secretion, leading to therapeutic errors. Thus, all clinical and analytical data should be evaluated together for early and correct diagnosis.

Evaluation of interrelationships between thyroid function, autoimmunity, insulin resistance and lipid profile in Graves' disease

Introduction: Thyroid hormones modulate the lipoprotein and glucose metabolisms. In hyperthyroidism, insulin resistance is a frequent finding. The aim of our study was to assess the interrelationships between thyroid function, autoimmunity, lipid profile, glucose metabolism and other cardiovascular risk factors in patients with Graves’ disease. Material & Methods: We recorded free T3, free T4, TSH, TSH receptor antibodies, parameters of the lipid profile, glucose metabolism (including insulin resistance markers like homeostasis model assessment for insulin resistance - HOMA-IR), C reactive protein and homocysteine in 126 patients with Graves’ disease in the first cycle of treatment with methimazole (92.9% females, mean age 44.9 ± 15.2 years). Patients were divided in subgroups according to: TSH receptor antibodies [positive (n = 57) or negative (n = 69)] and thyroid function [euthyroidism (n = 74), subclinical (n = 29) or clinical hyperthyroidism (n = 22)]. Spearman correlations, t-tests and Mann-Whitney tests were performed for statistical analysis. Results: Comparing the positive and negative TSH receptor antibodies groups, significantly lower apolipoprotein B (80.3 ± 23.9 vs 89.7 ± 23.8 mg/dL; p = 0.047) and TSH [0.180 (0.002-1.080) vs 1.020 (0.235-2.055) μUI/mL; p < 0.001] were found in the positive TSH receptor antibodies group. Comparing with the normal thyroid function group, patients in the clinical hyperthyroid group presented significantly lower apolipoprotein B (70.9 ± 25.8 vs 89.8 ± 24.0 mg/dL; p = 0.007] and higher fasting glucose (96.0 ± 24.4 vs 86.4 ± 10.0 mg/dL; p = 0.019), insulin [10.4 (6.2-15.8) vs 7.5 (4.8-9.7) μUI/mL; p = 0.021], HOMA-IR [2.09 (1.29-4.53) vs 1.55 (0.96-2.13); p = 0.023] and C reactive protein [0.57 (0.20-0.93) vs 0.20 (0.07-0.38) mg/L; p = 0.005]. No significant differences were found between the subclinical hyperthyroid and the normal groups. There was a negative correlation between TSH and the TSH receptor antibodies (r = -0.386; p < 0.001). Apolipoprotein B was positively correlated with TSH (r = 0.236; p = 0.016), and negatively with the TSH receptor antibodies (r = -0.211; p = 0.030). Both free T3 and free T4 were positively correlated with fasting insulin (r = 0.268; p = 0.008 and r = 0.226; p = 0.025, respectively) and HOMA-IR (r = 0.258; p = 0.010 and r = 0.259; p = 0.010, respectively). Free T4 was also positively correlated with fasting glucose (r = 0.269; p = 0.008). Conclusion: In patients with Graves’ disease, the interrelationships between thyroid function, autoimmunity, insulin resistance and lipid profile may contribute to the increased cardiovascular risk. The lipid profile suggests a hypolipidemic effect.

Cardiovascular risk factors in patients with autoimmune thyroiditis

Introduction: Thyroid dysfunction has been related to an increased cardiovascular risk resulting from alterations in lipid profile, insulin resistance, homocysteine levels and low grade systemic inflammation. The impact of normal TSH levels and subclinical hypothyroidism and autoimmunity in the increased cardiovascular risk remains controversial. Our objective was to evaluate the interrelations between thyroid function, thyroid autoimmunity and cardiovascular risk factors, in patients with autoimmune thyroiditis. Methods: 353 subjects with autoimmune thyroiditis were evaluated. We defined three groups based on TSH levels: TSH 0.5-2.5 μUI/mL, TSH 2.5-5.0 μUI/mL and TSH 5.0-10.0 μUI/mL. We recorded thyroid function tests, thyroid autoimmunity, insulin resistance markers including HOMA-IR (Homeostasis Model Assessment for Insulin Resistance), lipid profile, homocysteine, high-sensitivity C-reactive protein (hs-CRP) and vitamin B12 levels. Statistical analysis was performed using KruskalWallis test and Spearman correlations. Results: Our sample comprised 94% females with a mean age of 47.0 ± 16.3 years. The group TSH 5.0-10.0 μUI/mL presented higher levels of HOMA-IR when compared to the other two groups [2.96 (1.76-4.59) in TSH 5.0-10.0 μUI/mL vs 1.86 (0.97-2.56) in TSH 2.5-5.0 μUI/mL and 1.58 (1.06-2.46) in TSH 0.5-2.5 μUI/mL, p = 0.002]. In the total group we observed positive correlations between free T3 and both HDL (r = 0.118, p = 0.028) and apolipoprotein A-I (Apo A-I) (r = 0.129, p = 0.024); TSH was positively correlated with HOMA-IR (r = 0.146, p = 0.018) while free T4 was negatively correlated with homocysteine (r = -0.119, p = 0.041). In the group TSH 0.5-2.5 μUI/mL, positive correlations were found between TSH and both HDL (r = 0.136, p = 0.031) and homocysteine (r = 0.147, p = 0.028), between free T4 and CRP (r = 0.136, p = 0.037) and between anti-thyroglobulin antibodies and apolipoprotein B (r = 0.165, p = 0.013); anti-thyroglobulin antibodies were negatively correlated with homocysteine (r = -0.186, p = 0.006). Negative correlations between anti-thyroglobulin antibodies, total cholesterol (r = 0.371, p = 0.004), LDL (r = -0.325, p = 0.011), apolipoprotein B (r = -0.342, p = 0.022) and lipoprotein(a) (r = -0.470, p = 0.001) were revealed in the group TSH 2.5-5.0 μUI/mL. Regarding the group TSH 5.0-10.0 μUI/mL, we found positive correlations between free T3 and HDL (r = 0.358, p = 0.030), vitamin B12 (r = 0.398, p = 0.024) and HOMA-IR (r = 0.424, p = 0.031), and between anti-thyroglobulin and homocysteine (r = 0.383, p = 0.033). Conclusion: We observed significant correlations between thyroid function, thyroid autoimmunity, insulin resistance, lipid profile and homocysteine that may contribute to an increased cardiovascular risk in patients with autoimmune thyroiditis.

Subclinical hypothyroidism, autoimmune thyroiditis, and cardiovascular risk factors

Background and objectives: There is increasing evidence that subclinical hypothyroidism is related with an increased cardiovascular risk. The objective is to evaluate the relationship between autoimmune thyroiditis, subclinical hypothyroidism and cardiovascular risk factors. Methods: We recorded thyroid function tests, anti-TPO and antithyroglobulin antibodies, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoproteinA1, apolipoproteinB, lipoprotein(a), homocysteine, high sensitivity CRP, folic acid, vitamin B12, HOMA-IR, HOMA-β, QUICKI, HISI, WBISI, IGI in 185 subjects with autoimmune thyroiditis and in euthyroid state and in 69 subjects with autoimmune thyroiditis and subclinical hypothyroidism. Statistical analysis was performed with Mann-Whitney test, logistic regression and Spearman correlations. The results were adjusted for age and body mass index. Statistical significance was considered for a bilateral value of p<0.05. Results: 94% of subjects were female. The median age was significantly higher in the euthyroid group. Patients with higher levels of total cholesterol (OR=1.008; p=0.034), CRP (OR=1.684; p=0.041) or anti-thyroglobulin antibodies (OR=1.002; p=0.021) had an increased likelihood of having subclinical hypothyroidism. In the total group of patients, we observed positive correlations between TSH, CRP and HOMA-IR, between free T3 and HDLcholesterol and between free T4 and IGI. TSH levels correlated negatively with QUICKI, HISI and WBISI. In the group with subclinical hypothyroidism, we found negative correlations between free T3 and homocysteine and between free T4 and anti-TPO antibodies.