Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Cause-Specific Risk Factors of Death in Individuals with Diabetes: A Competing Risks Modeling.

BACKGROUND: Diabetes is on the rise worldwide. OBJECTIVES: This study aimed to evaluate the risk factors of various causes of death in people with type 2 diabetes (T2D). METHODS: In this cohort study on 2638 people with T2D, we applied cause-specific and sub-distribution hazards models to assess the impact of various factors on the risk of death. Moreover, we plotted a cumulative incidence curve to summarize cumulative failure rates over time. RESULTS: About 75% of individuals with T2D died from cardiovascular disease (CVD) and cerebrovascular accidents (CVA). Death from CVD was associated with the increased risk of hypertension (hazard ratio (HR) = 1.83, 95% CI: 1.37 - 2.46), hypercholesterolemia (HR = 1.58, 95% CI: 1.17 - 2.14), and diabetes duration. The risk of death from CVA was related to hypertension (HR = 2.76, 95% CI: 1.67 - 4.55) and hyperglycemia (HR = 4.34, 95% CI: 1.75 - 10.79). The CVA risk in patients with diabetes duration of 10 - 20 years was higher than the risk in patients with diabetes duration > 20 years (diabetes duration of ≤ 10 years as the reference category). Diabetes duration of longer than 20 years was associated with a higher risk of death from cancer (HR = 2.65, 95% CI: 1.05 - 6.68). The risk of death from foot infection and diabetic nephropathy increased in patients with longer diabetes duration after adjustment for sex, age, and body mass index. CONCLUSIONS: Regardless of the cause, death rates in people with T2D increase over time and risk factors have different impacts on death from each cause. This should be acknowledged in risk management in individuals with T2D.

Assessment of the Early and Late Complication after Thyroidectomy.

BACKGROUND: The complications in thyroid surgery have been reported variable in literature. The aim of this study was to evaluate the early and late (3 months after surgery) complication rates of thyroidectomy in a cohort of patients undergoing thyroid surgery at two hospitals of Isfahan University of Medical Science, Iran. MATERIALS AND METHODS: This study included 204 patients who candidates for thyroidectomy presenting at Medical Educational Centers of Al-Zahra and Kashani hospitals in Isfahan between March 2016 and March 2017. Clinical data are collected for all patients by continuous enrollment. The patients examined before and after thyroid surgery and the findings were recorded. RESULTS: The highest prevalence of thyroidectomy was in women (81.9%). The most frequent thyroid surgery was total thyroidectomy and the most common indication for thyroid surgery was suspicious fine-needle aspiration for thyroid malignancy. Hypocalcemia was the most common complication with a frequency of 54.4%. The odds ratios for early complications were 2.375 and 2.542 for intermediate- and low-volume surgeons, respectively, compared to high-volume surgeons. CONCLUSIONS: According to the results of this study, the high level of surgeon's skill is effective to reduce the likelihood of late and early complications; furthermore, the chance of late complications increases with age.

The Role of Intraoperative Thyroglobuline Level of Lymph Node in the Management of Papillary Thyroid Cancer (Determination of a Cutoff Point).

BACKGROUND: Some studies have shown that a preoperative high concentration of thyroglobulin (Tg) in wash out of fine-needle aspiration cytology of cervical lymph nodes mandate therapeutic lymph node dissection. However, there is disagreement about the minimum concentration of Tg which could have diagnostic value. Hence, according to our literature review, this study is the first one which designed to do intraoperatively. Therefore, this study was conducted and aimed to determine the clinical diagnostic value of Tg lymph nodes in the diagnosis of metastatic thyroid cancer. METHODS: In a cross-sectional study, 65 patients with papillary thyroid carcinoma (PTC) who were thyroidectomy candidates were chosen and during surgery, before the removal of lymph nodes in the neck, fine-needle sampling was performed and the level of Tg in the samples, nature of the sample sent for biopsy and Tg levels in affected and unaffected lymph nodes were determined. RESULTS: The mean levels of washout Tg in malignant and nonmalignant lymph nodes were 622.1 ± 66.2 and 1.38 ± 0.43 ng/ml, respectively, and the difference between the two groups was significant (P < 0.001). The Tg cut-off point for the detection of lymph node metastases was 0.7 ng/dl, and according to it, Tg washout sensitivity was 93.8%, specificity of 92.4%, false positives 7.76%, false negatives 6.3%, positive predictive value was 92.3%, and negative predictive value was 93.8% and accuracy was 93.1%. CONCLUSION: Based on the results, Tg level of cervical lymph nodes in patients with PTC is a suitable criterion for the diagnosis of lymph node which can be determined through fine-needle biopsy. Therefore, it is suggested that in patients with suspicion of lymph nodes involvement during surgery, fine-needle biopsy and determination of the Tg level performed.

Two rare manifestations of primary hyperparathyroidism: paralysis and peptic ulcer bleeding.

Primary hyperparathyroidism revealed by thoracic spine brown tumor and peptic ulcer bleeding is rare. We presented a case of 33-year-old male patient who was admitted with paraplegia. Thoracic spine magnetic resonance imaging (MRI) showed extradural lesion at T4 level. He underwent surgical decompression in T4. According to histopathologic finding and elevated serum parathormone (PTH) and hypercalcemia (total serum calcium 12.1 mg/dL), the diagnosis of brown tumor was down. Ultrasonography of his neck showed a well-defined lesion of 26 × 14 × 6 mm. The day after surgery, he experienced 2 episodes of melena. Bedside upper gastrointestinal endoscopy showed gastric peptic ulcer with visible vessel. Treatment with intragastric local instillation of epinephrine and argon plasma coagulation was done to stop bleeding. After stabilization of the patient, parathyroidectomy was performed. Histologic study showed the parathyroid adenoma without any manifestation of malignancy. At discharge, serum calcium was normal (8.6 mg/dL). On 40th day of discharge, standing and walking status was normal. LEARNING POINTS: Thoracic spine involvement is a very rare presentation of primary hyperparathyroidism.The issue of whether primary hyperparathyroidism increases the risk of peptic ulcer disease remains controversial. However, gastrointestinal involvement has been reported in association with classic severe primary hyperparathyroidism.The treatment of brown tumor varies from case to case.

Carney complex presenting with a unilateral adrenocortical nodule: a case report.

INTRODUCTION: Carney complex is an autosomal dominant syndrome with multiple neoplasms in different sites, including myxomas, endocrine tumors and lentigines lesions. To the best of our knowledge, this is the first report of Carney complex presenting with a unilateral adrenal adenoma associated with a pituitary incidentaloma. CASE PRESENTATION: A 27-year-old Iranian woman was referred to our endocrinology clinic with amenorrhea and hirsutism, further confirming a diagnosis of adrenocorticotropic hormone-independent Cushing's syndrome. The cause was believed to be a right adrenocortical adenoma based on a computed tomography scan. Our patient underwent a right laparoscopic adrenalectomy and pathological examination revealed pigmented micronodular adrenal hyperplasia. Pituitary magnetic resonance imaging also documented a microadenoma that was considered to be an incidentaloma based on normal pituitary function tests. Recurrence of hypercortisolism led to a left laparoscopic adrenalectomy, providing further evidence for the diagnosis of primary pigmented nodular adrenocortical disease. Carney complex was established in light of her history of cardiac myxomas. CONCLUSION: We present what we believe to be the first case of Carney complex presenting with a unilateral adrenocortical adenoma in association with a pituitary incidentaloma. Although primary pigmented nodular adrenocortical disease is rare as a component of Carney complex, it should be considered in the differential diagnosis of Cushing's syndrome. Rarely, adrenal and pituitary imaging can be misleading.

The prevalence of hypogonadism in diabetic men in Isfahan Endocrine and Metabolism Research Center, Isfahan, Iran.

OBJECTIVE: Low testosterone, with or without symptoms, reported in diabetic men in some studies. We investigated the prevalence of hypogonadism in Iranian type 2 diabetic men. MATERIALS AND METHODS: Total testosterone (TT) and sex hormone binding globulin (SHBG) concentrations were measured in 247 diabetic men >30 years who had symptoms of androgen deficiency, according to ADAMs questionnaire. The correlation between some parameters and total, free and bioavailable testosterone levels was determined using Pearson correlation coefficient. Free and bioavailable testosterone were calculated by electronic calculator. Four patients were excluded because of high testosterone level, due to unreported androgen use. Overt hypogonadism was defined as total testosterone ≤8 nmol/l or calculated bioavailable testosterone (cBT)≤2.5 nmol/l and borderline hypogonadism was considered as TT 8-12 nmol/l or cBT 2.5-4nmol/l. RESULTS: The mean and SD of age was 59 (9.3) years. The mean TT, calculated free testosterone (cFT), and cBT and SHBG levels were 4.81 (1.7) nmol/l, 0.11 (0.06) nmol/l, 2.42 (1.17) nmol/l and 36.15 (18.3) nmol/l, respectively. According to TT and cBT, overt hypogonadism observed in 7.4% and 61.6% of men, respectively, and the prevalence of borderline hypogonadism was 9.9% and 36%, respectively. cFT ≤0.16 nmol/l found in 227 diabetic men (96%). Hypogonadism (TT ≤12 nmol/l) was not correlated with obesity, smoking, age,duration of diabetes, blood pressure, and HbA1c. CONCLUSION: Hypogonadism is highly prevalent in type 2 diabetes men.

The impact of acute hypothyroidism on lipid levels in athyreotic patients.

BACKGROUND: We investigated the effect of acute hypothyroidism on lipid concentrations especially on high density lipoprotein (HDL-cholesterol) level in athyroatic patients. MATERIALS AND METHODS: Thirty-one patients, with a history of differentiated thyroid carcinoma and total thyroidectomy, who were candidates of radioiodine therapy, enrolled in the study. Their lipid profiles and serum thyrotropin stimulating hormone (TSH) levels were measured before and two-to-six weeks after thyroid hormone withdrawal. The lipid concentrations were compared with the paired t test and serum TSH using the Wilcoxon singed rank test. P values < 0.05 were considered statistically significant. RESULTS: The median of TSH concentration was 0.06 mU / liter on thyroid hormone suppressive therapy and 102 mU / liter at the thyroid hormone withdrawal phase (P < 0.0001). The serum concentrations of all lipids were significantly increased after withdrawal (P < 0.0001). The mean (SD) of the HDL-cholesterol concentration rose from 44 ± 9 mg / dL to 58 ± 17 mg / dL. The levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride increased by 58, 75, 30, and 59%, respectively, during acute hypothyroidism. CONCLUSION: The present study showed that thyroid hormone withdrawal altered the lipid concentrations significantly, in a short period of time. The levels of both atherogenic (LDL-cholesterol) and cardioprotective (HDL-cholesterol) particles increased concurrently. Their clinical importance should be investigated in future.

Sonographic and functional characteristics of thyroid nodules in a population of adult people in Isfahan.

INTRODUCTION: The aim of this study was to investigate the current status of sonographic characteristics of thyroid nodules in Isfahan, a previously iodine deficient area in central Iran. MATERIAL AND METHODS: In a cross-sectional study conducted in 2006, 2523 adult people (age > 20 years) were selected by a multistage clustering sampling method. Of these people, 263 volunteered persons were underwent sonographic evaluation. Thyroid examination was done by two expert sonographers. Serum T(3), T(3), T3RU, TSH, TPO Ab and Tg Ab, and urinary iodine were measured. RESULTS: Forty-six per cent of the 263 people were women. Their mean age was 35.5 years with a range of 20-64 years. Median urinary iodine was 19.4 microg/dL. The prevalence of thyroid nodules on sonography was 22.4% in the whole group; 30% in women and 16.3% in men (OR = 2.2, P = 0.01). The prevalence of thyroid nodules increased with age (P = 0.006). The prevalence of thyroid nodules was higher in hypothyroid people than in euthyroid people (35.1% v. 20.5%, OR = 2.1, P = 0.04). Neither urinary iodine nor autoantibody concentrations correlated with the prevalence of thyroid nodules in sonography. CONCLUSIONS: The prevalence of thyroid nodule by sonography is still high despite relatively normal urinary iodine in this population.

Prevalence of polycystic ovary syndrome in reproductive-aged women with type 2 diabetes.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are at higher risk of type 2 diabetes and cardiovascular disease. The present study was conducted to investigate the prevalence of PCOS in type 2 diabetic patients. METHODS: Type 2 diabetic women (n = 157) of reproductive age were selected by a convenience sampling method. PCOS was confirmed using the clinical diagnosis criteria proposed in 1990 by the National Institute of Child Health and Human Development Conference of PCOS. The diabetic patients were divided into two groups according to the presence of PCOS. Baseline demographic characteristics were obtained by questionnaire, and body weight, height, waist circumference, blood pressure and some biochemical indices were measured in both groups. RESULTS: The prevalence of PCOS was high (8.3%, 95% confidence interval 4.5-13.4%) in these type 2 diabetic women. The onset of diabetes occurred at a lower age in the PCOS group, who also displayed significantly greater waist circumference and body mass index (p<0.05). No difference in lipid profile, glycosylated hemoglobin or blood pressure was observed between the two groups. CONCLUSIONS: PCOS is highly prevalent in type 2 diabetic patients. Hence, focusing the treatment on insulin sensitizers in these patients should improve both the metabolic and non-metabolic complications of PCOS.

Thyroid incidentaloma in Isfahan, Iran - a population-based study.

INTRODUCTION: Thyroid nodules not detected in palpation but diagnosed following a radiological procedure or during surgery are called thyroid incidentalomas. We designed this study to investigate the prevalence of sonographic thyroid incidentaloma in Isfahan, Iran, for the first time. MATERIAL AND METHODS: By a multistage cluster sampling method, 2523 adults were selected randomly. From this group, 2045 had normal thyroid examination. 234 out of the 2045 were selected randomly for thyroid sonography. Thyroid stimulating hormone (TSH), urinary iodine concentrations (UIC) and antithyroid antibodies were measured. RESULTS: The prevalence of thyroid incidentaloma was 13.2% [Confidence interval (CI) 95% = 8-18]. The average age of subjects with and without incidentaloma was 46.1 (12.4) and 38.4 (12.1), respectively (P = 0.002). It was more prevalent in females than in males (19% vs. 10%) [Odds ratio (OR) = 2.59, CI 95% = 1.17-5.76, P value (P) = 0.01]. Median UIC in the incidentaloma group (14 microg/dl) was significantly lower than in the group of subjects without nodules (20 microg/dl) (OR = 0.9, CI 95% = 0.91-0.99, P = 0.02). There was no difference in the levels of TSH and antithyroid antibodies between the two groups (P > 0.05). Mean diameter of nodules was 8.14 (3.43) mm. CONCLUSIONS: The prevalence of thyroid incidentaloma was 13.2% in Isfahan. It was higher in females than males and increased with age.

High prevalence of goiter in an iodine replete area: do thyroid auto-antibodies play a role?

INTRODUCTION: Despite long standing iodine supplementation in Iran the prevalence of goiter remains high in some areas. This may suggest that causes other than iodine deficiency, such as autoimmune thyroid diseases, should also be considered. We therefore assessed the prevalence of anti-thyroid antibodies in children living in an inland area in Iran and correlated these findings with prevalence of goiter within this region. METHODS: In a cross-sectional study, 1948 students were selected by multistage random cluster sampling from the 108 primary schools (age, 7-13 year-old) of the urban and rural areas of Semirom. After obtaining written consent from their parents, the children were examined by endocrinologists for goiter grading. Grade 2 goitrous children (108 cases) were compared with non-goitrous children (111 children as control group) for anti-thyroid antibodies. RESULTS: Overall, 36.7% of 1948 students had goiter. The mean urinary iodine excretion level was 1.49+/-0.7 micromol/L. This was within normal limits. Of 219 children studied, 4.3% presented with subclinical hypothyroidism, and 7.3% had positive anti-thyroid antibodies. There was non-significant difference of positive thyroperoxidase antibody (anti-TPO) (Odds Ratio= 3.2, p= 0.13) but significant difference of anti Tg between goitrous and non goitrous children (Odds Ratio: 5.6, 95% CI: 1.18-26.0, p: 0.015). CONCLUSION: This study suggests that autoimmunity may be one of the mechanisms responsible for goiter persistence after iodine replenishment in this iodine deficient region, but the role of other factors should also be considered.

Iron deficiency in goitrous schoolchildren of Semirom, Iran.

BACKGROUND: Iodine deficiency produces the spectrum of iodine deficiency disorders (IDDs): endemic goiter, hypothyroidism, cretinism, and congenital anomalies. Other factors, including goitrogens and micronutrient deficiencies, may influence the prevalence and severity of IDDs and response to iodine supplementation. This cross-sectional, descriptive study was performed in 2003 on elementary school children of Semirom, a mountainous region of Iran, where goiter was hyper-endemic in 1994, but the goiter prevalence had not decreased as expected many years after salt iodization and iodine injection. Some possible risk factors associated with goiter in that area were evaluated, and the results of iron study are presented here. METHODS: 1,869 cases were selected by a multistage cluster sampling procedure. Grade 2 goitrous children were compared with equal number of nongoitrous children for serum iron, ferritin, transferrin, thyroxin, TSH and urine iodine concentrations (UIC). RESULTS: 210 children (105 goiter grade 0 and 105 goiter grade 2) entered this sub-study. Of 210 participants, 70 children had low transferrin saturation, 13 had low serum ferritin and 9 children had both problems. There was no significant difference in goiter rate between children with low iron indices and others. There was no significant correlation between serum iron, ferritin or transferrin saturation with other variables including T4, UIC and goiter stage. CONCLUSION: The present study reveals that in the area studied, iron deficiency cannot explain the high prevalence of goiter, so other responsible factors should be investigated.