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1.  Effect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes: A randomized placebo-controlled clinical trial 
The people with prediabetes have insulin resistance (IR). IR may affect thyroid function, size and nodules. We investigated the effects of metformin on the thyroid gland in prediabetic people.
Materials and Methods:
In a randomized, double-blind placebo-control clinical trial, 89 people with prediabetes, aged 18-65 years were studied for 3 months. They were divided into two, metformin (n = 43) and placebo (n = 46) treated groups. Serum thyroid stimulating hormone (TSH) was measured and thyroid nodules and volume was studied by ultrasonography. The data were compared between and within groups, before and after the study.
Mean of the baseline characteristics in metformin and placebo-treated groups had no statistically significant difference. At the end of the study, serum TSH was not significantly different between the two groups. However, if the TSH range was divided into two low normal (0.3-2.5 μU/ml) and high-normal (2.6-5.5 μU/ml) ranges, significant decrease was observed in metformin-treated group with a high-normal basal serum TSH (P = 0.01). Thyroid volume did not change in metformin-treated group. However, in placebo-treated group, the thyroid was enlarged (P = 0.03). In 53.9% of participants, thyroid nodule was observed. There was just a decrease in the volume of small solid (not mixed) nodules from median of 0.07 ml to 0.04 ml in metformin-treated group (P = 0.01).
In prediabetic people, metformin decreases serum TSH, only, in those people with TSH >2.5 μU/ml and reduces the size of small solid thyroid nodules. It also prevents an increase in the thyroid volume.
PMCID: PMC4310072  PMID: 25657744
Insulin resistance; metformin; prediabetes; thyroid; thyroid nodule; thyroid volume
2.  Carney complex presenting with a unilateral adrenocortical nodule: a case report 
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.
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.
PMCID: PMC3927851  PMID: 24499519
Carney; Cushing’s syndrome; Myxoma; PPNAD; Schwannomas
3.  The effects of oral vitamin D on insulin resistance in pre-diabetic patients 
Some epidemiological and interventional studies have shown the role of vitamin D on insulin secretion and resistance. A previous study in our center showed that intramuscular vitamin D decreases insulin sensitivity in pre-diabetic patients. We investigated the role of oral vitamin D on the insulin sensitivity index and insulin resistance in pre-diabetic patients.
Materials and Methods:
In a randomized clinical trial, we divided 45 people with pre-diabetes aged 47.4 ± 6.6 (range 33-61) years into three groups: group A subjects treated with 50,000 IU oral vitamin D and 500 mg calcium carbonate (n = 21), group B subjects treated with a single 300,000 IU intramuscular vitamin D and 500 mg calcium carbonate (n = 9), and group C subjects treated with 500 mg calcium carbonate alone (n = 15). Serum 25-hydroxyvitamin D [25(OH) D] was measured at baseline. If it was less than 75 nmol/l, 50,000 IU vitamin D was given weekly, and if serum 25(OH) D was more than that, vitamin D was administered every 2 weeks. Before and after 12 weeks of treatment, a 75-g glucose tolerance test was performed. We used paired t-test and analysis of variance (ANOVA) to analyze the data. P values less than 0.05 were considered significant.
Mean (SD) of serum vitamin D increased from 77.5 ± 39.2 to 118.8 ± 56.3 nmol/l (P = 0.009) in group A and from 80 ± 36 to 102.8 ± 43.3 nmol/l (P = 0.053) in group B, and decreased from 44.8 ± 18.3 to 34.6 ± 13.9 nmol/l (P = 0.06) in group C. Insulin sensitivity index (Matsuda) decreased from 11.4 ± 3 to 9.9 ± 3.2 (P = 0.046) in group A, but in comparison with other groups, it was not significant.
Oral vitamin D had no effect on insulin sensitivity in pre-diabetes patients in 12 weeks treatment. A randomized double-blind study with a longer duration of treatment is suggested to investigate the effect of vitamin D on insulin resistance.
PMCID: PMC3719226  PMID: 23900423
Glucose tolerance test; insulin resistance; pre-diabetes; vitamin D; vitamin D deficiency
4.  Comparison of ox-LDL Levels in Diabetic Patients with Normo-, Micro-, and Macroalbuminuria with Their First Degree Relatives and the Healthy Control Group 
Oxidized low density lipoprotein (ox-LDL) is a product of oxidative stress. In this cross-sectional study, we compared the ox-LDL concentrations in diabetic patients with normoalbuminuria (n = 28), microalbuminuria (n = 28), and macroalbuminuria (n = 28) with their first degree relatives (n = 28) and healthy control people (n = 31). They were selected by consecutive patient selection method. The ox-LDL level was assayed using ELISA. We measured blood pressure, lipid profile, fasting plasma glucose (FPG), and HbA1c in all groups. There was no significant difference in ox-LDL concentrations among normoalbuminuric, microalbuminuric, and macroalbuminuric diabetic groups. In diabetic patients with micro- and macroalbuminuria, ox-LDL concentration was higher than their first degree relatives (P = 0.04 and P = 0.03) and control group (P = 0.001 and P = 0.03, resp.). In normoalbuminuric diabetic persons, ox-LDL concentration was just higher than that of healthy people (P = 0.02). There was no statistically significant difference in ox-LDL levels between normoalbuminuric diabetic patients and their first degree relatives. In conclusion, the presence and progression of albuminuria in diabetic patients are not related to ox-LDL concentration and genetic predisposition influences the plasma OX-LDL level. Larger sample size is needed to confirm this conclusion in future studies.
PMCID: PMC3501829  PMID: 23193400
5.  Is uric acid an indicator of metabolic syndrome in the first-degree relatives of patients with type 2 diabetes? 
To determine whether uric acid levels are associated with the components of metabolic syndrome and whether uric acid is a significant factor for development of metabolic syndrome in the first-degree relatives of type 2 diabetic patients as high risk group.
Materials and Methods:
A total of 694 (182 male and 512 female, aged 30-69 years) first-degree relatives of type 2 diabetic patients during 2007-2011 were enrolled. The height, weight, waist circumference, blood pressure, fasting plasma glucose, lipid profile and uric acid concentrations were measured. Metabolic syndrome was defined by NCEP-ATP III.
Uric acid was associated with waist circumference, blood pressure, triglyceride and HDL-cholesterol level in both sexes (r = 0.1-0.3, P < 0.05). The prevalence of metabolic syndrome in the fourth quartile of uric acid (64.4% of male and 60.2% of female population) was significantly more than those in the first (25.5% of male and 31.2% of female population) and second quartiles (33.3% of male and 32.0% of female population). The mean of uric acid in people with metabolic syndrome was significantly higher than in those without (6.6 ± 1.2 mg/dL vs. 5.8 ± 1.2 mg/dL; P = 0.0001). The age-adjusted odds ratios (95% confidence interval) of uric acid for metabolic syndrome in univariate analysis were [1.60 (1.23-2.07); P = 0.008] for men and [1.61 (1.34-1.92); P = 0.0001] for women but the effect of uric acid in multivariate logistic regression was not significant.
Uric acid is associated with majority of the metabolic syndrome components. People with metabolic syndrome have higher uric acid levels. However, uric acid probably is not an independent factor to predict the metabolic syndrome.
PMCID: PMC3702079  PMID: 23833572
Cardiovascular disease; insulin resistance; metabolic syndrome; obesity; type 2 diabetes
6.  Does the intramuscular injection of vitamin D increase insulin resistance? 
Considering the physiologic roles of vitamin D on insulin regulation, the effects of vitamin D treatment on insulin sensitivity and resistance indexes and beta cell function in pre-diabetic vitamin D deficient patients were investigated.
In a randomized open clinical trial, 61 pre-diabetic vitamin D deficient patients who were the first degree relatives of type 2 diabetic patients, were enrolled and randomized into three groups (A, B and C). Group A (n = 21) were treated with intramuscular injection of 300,000 units of vitamin D at the beginning of the study and one month later. In group B (n = 20), injection of vitamin D plus 500 mg/d calcium and in group C (n = 20), just calcium was administered for two months. At baseline and two months later, oral glucose tolerance test was done. Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR), insulin resistance index, Homeostasis Model of Assessment-B (HOMA-B) which is a beta cell function index, and Matsuda index, an insulin sensitivity index, were calculated and compared before and after intervention and between three groups.
In vitamin D treated groups (A + B), the mean (SD) of HOMA-IR increased from 2.46 (1.36) to 3.1 (2.3) (P = 0.02), and Matsuda index decreased from 11 (3) to 9.0 (2.3) (P = 0.001).
Injection of vitamin D increased insulin resistance and decreased insulin sensitivity indexes.
PMCID: PMC4076860  PMID: 24991591
Vitamin D; pre-diabetic state; diabetes mellitus type 2; oral glucose tolerance test
7.  The impact of acute hypothyroidism on lipid levels in athyreotic patients 
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.
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.
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.
PMCID: PMC3687877  PMID: 23798937
Cholesterol-HDL; hypothyroidism; lipid metabolism; thyroid hormones; thyroid neoplasms
8.  The prevalence of hypogonadism in diabetic men in Isfahan Endocrine and Metabolism Research Center, Isfahan, Iran 
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.
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.
Hypogonadism is highly prevalent in type 2 diabetes men.
PMCID: PMC3685773  PMID: 23798917
Hypogonadism; male; Iran; prevalence; Type 2 diabetes mellitus
9.  Prevalence of Vitamin D Deficiency among Adult Population of Isfahan City, Iran 
Determination of vitamin D status in different age-groups in a community and in different climates of a country is necessary and has important implications for general health. The study was conducted to determine the prevalence of vitamin D deficiency among the adult population of Isfahan, a centrally-located city in Iran. In this cross-sectional study, 1,111 healthy people—243 men and 868 women—aged 41.4 (mean 14 and range 20-80) years, who attended a single-consultation outpatient clinic, were selected. Serum 25-hydroxy vitamin D (25-OHD), parathyroid hormone (PTH), calcium and phosphorus concentrations were measured. Mild, moderate and severe vitamin D deficiencies were defined as 25-OHD values of 20-30 ng/mL, 10-20 ng/mL, and <10 ng/mL respectively. The median (range) concentrations of 25-OHD were 21 (4.0-105.0) ng/mL in males and 18 (1.5-117) ng/mL in females (p=0.05). The prevalence of mild, moderate and severe vitamin D deficiencies among the adult population was 19.6%, 23.9%, and 26.9% respectively. Vitamin D deficiency was more prevalent among women (p=0.001) and younger age-group (p=0.001). Medians of 25-OHD in spring-summer and autumn-winter were 21 ng/mL and 18 ng/mL respectively (p=0.005). The prevalence of severe vitamin D deficiency was higher in autumn-winter than in spring-summer (odds ratio=1.6, 95% confidence interval 1.2-2.2, p=0.001). The prevalence of vitamin D deficiency was high in a sunny city—Isfahan— especially among women and younger population. The high prevalence of vitamin D deficiency in this city emphasizes the necessity of vitamin D supplementation as more exposure to sun is limited due to the type of clothing required by current law.
PMCID: PMC3126987  PMID: 21608424
Adult; Cross-sectional studies; Parathyroid hormone; Seasonal variation; Vitamin D deficiency; Iran
10.  Should the first degree relatives of type 2 diabetic patients with isolated impaired fasting glucose be considered for a diabetes primary prevention program? 
The aim of this study is to investigate the need for diabetes primary prevention program in isolated impaired fasting glucose (i-IFG) of the first degree relatives of type 2 diabetics.
In a cross sectional study, 793 individuals with prediabetes [543 with i-IFG and 250 with isolated impaired glucose tolerance (i-IGT)] who were the first degree relatives of type 2 diabetic patients, were enrolled. Isolated IFG was considered as fasting plasma glucose between 100-125 mg/dl and 2 hour plasma glucose < 140 mg/dl and isolated IGT as FPG < 100 mg/dl and 2 hour plasma glucose between 140-199 mg/dl during an overnight fasting 75 g oral glucose tolerance test. Mean of the age, weight, waist circumference, body mass index, systolic and diastolic blood pressure, plasma glucose, HbA1C, and lipid profile were compared between two groups (i-IFG and i-IGT). The prevalence of cardiometabolic risk factors (BMI ≥ 25 kg/m2, hypertension, cholesterol ≥ 200 mg/dl, LDL-C ≥ 100 mg/dl, HDL-C ≤ 40 mg/dl, and triglyceride ≥ 150 mg/dl) adjusted by age, sex and BMI were compared.
The prevalence of cardiometabolic risk factors is higher in i-IFG group than i-IGT. The mean level of LDL-C is significantly higher in i-IFG than i-IGT group.
First degree relatives of T2DM with isolated impaired fasting glucose should probably be included in the primary preventive program for diabetes. However, longitudinal cohort study is required to show high progression of i-IFG to T2DM.
PMCID: PMC3082819  PMID: 21526094
Prediabetic States; Diabetes Mellitus; Type II; Oral Glucose Tolerance Test; Primary Prevention; Dyslipidemia; Risk Factor; Iran
11.  Zinc status in goitrous school children of Semirom, Iran 
Iodine deficiency produces the spectrum of iodine deficiency disorders (IDDs) including 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. An association between zinc and goiter has previously been reported.
A cross sectional study investigating an association between goiter and serum zinc status was performed in 2003 in a mountainous region of Iran. One thousand eight hundred twenty-eight children were selected by multistage cluster sampling. Goiter staging was performed by inspection and palpation. Serum zinc, total thyroxine, thyroid stimulating hormone and urinary iodine concentration were measured in a group of these children.
Thirty six and seven tenth percent of subjects were classified as goitrous. Serum zinc level in goitrous and nongoitrous children was 82.80 ± 17.85 and 83.38 ± 16.25 μg/dl, respectively (p = 0.81). The prevalence of zinc deficiency (serum zinc ≤65 μg/dl) in goitrous and nongoitrous children did not differ significantly (9.3 % vs. 10.8%, p = 0.70).
Goiter is still a public health problem in Semirom. According to the present study zinc status may not play a role in the etiology of goiter in Semirom school children. However, the role of other goitrogens or micronutrient deficiencies should be investigated in this region.
PMCID: PMC3129056  PMID: 21772878
Goiter; Iodine Deficiency; Zinc Deficiency; Child

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