مجله غدد درون ریز و متابولیسم ایران
سال هفتم شماره 3 (پیاپی 27، پاییز 1384)

Hypercalciemia is one of the endocrine emergency with varing etiologies, such as hyperparathyroidism, malignancies, granulomayous diseases and consumption of certain drugs. Vit D3 intoxication is an uncommon cause of hypercalcemia which is induced by consumption of high doses of Vit D3 (50000-100000 unit per/day). Patients present with nausea, vomiting, weakness and lethargy, and may cause acute renal failure. In laboratory evaluations, high serum calcium and 25(OH)2Vit D3 level and low PTH are detected. Hydration, glucocorticoids and bisphosphonats are used in treatment of these patients. In this paper, three cases of Vit D3 intoxication, who took Vit D3 for athletic purposes and presented with nausea, vomiting and acute renal failure, are reported. High serum calcium and 25(OH) Vit D3, normal level of phosphate and Alkalin phosphatase, low PTH level and severe acute renal failure, were detected in these three patients. Hypercalcemia, renal failure and all the clinical signs and symptoms disappeared after treatment with intravenous fluid, bisphosphonats and glucocorticoid.

The importance of food variety in relation to reduction of chronic disease has not been sufficiently emphasized. This study was conducted to evaluate the relationship between dietary diversity score (DDS) and cardiovascular risk factors in Tehranian adults.

In this population-based cross-sectional study, a representative sample of 581 subjects (295 males and 286 females) aged over 18 years, residents of Tehran, participated. Usual dietary intake was assessed using two 24-hour dietary recall questionnaires. Weight and height were measured according to standard protocols and body mass index was calculated. Blood glucose, serum total cholesterol and triglyceride and HDL-cholesterol concentrations were measured and LDL-cholesterol was calculated. Hypercholestrolemia hypertriglyceridemia, low HDL-C were defined according to Adult Treatment Panel (ATP) III guidelines. Diabetes was defined as a fasting plasma glucose concentration of ≥ 126 mg/dl or a 2-h postchallenge glucose concentration of ≥ 200 mg/dl. Hypertension was defined based on JNC VI. Subjects were categorized based on quartile cut-points of DDS.

Mean±SD of age, body mass index and DDS were 37±12 years 25.7±4.3 kg/m2, and 6.15±1.02 respectively. Mean (±SD) of dietary diversity score was 6.15±1.02. Higher DDS was associated with lower levels of systolic and diastolic blood pressure. The probability of having diabetes and hypertriglyceridemia decreased with quartiles of the diversity score of whole grain (P for trend<0.04). The probability of having hypercholestrolemia decreased with quartiles of the diversity score of vegetables (P for trend<0.03). The probability of having hypercholestrolemia, hypertension and diabetes decreased with quartiles of DDS (P for trend<0.03, <0.03, and 0.04, respectively).

DDS was inversely associated with cardiovascular risk factors. Increasing diversity scores of diets, may be attempted in programs for change of life style.

Hot thyroid nodules are seen in nearly 5% of patients with dominant nodules. The aim of this study was to evaluate the clinical course and results of different modalities of treatment during a ten year period.

The study involved 132 out of 302 patients referring between 1987-1997 with hot thyroid nodules, diagnosed by clinical findings, thyroid function tests, and isotope scanning patients with at least 1-year regular follow-up were included, and were divided into two categories: hyperthyroid and euthyoid at the first presentation according to results of thyroid function tests.

The age range was 15-76 years and the duration of follow up was 1-10 years (4.9 ±3.5 m±SD). Female to male ratio was 7/1 (115 women, and 17 men). Half of the patients (66 cases) were thyrotoxic at the time of presentation. Eighteen of the euthyroid patients developed hyperthyroidism during the follow-up period. Sixty seven patients were treated with 8-25 mCi of I-131. Mean age was 47.5±13 years. Seventy three percent became euthyroid, 10.5% developed subclinical hyperthyroidism, and 16.5% developed clinical and subclinical hypothyroidism. Thyroid noduless disappeared in 21% of patients at the end of the study. Twenty-three patients underwent thyroidectomy. Mean age was 26.4± 7 years. Twenty-two percent of patients developed subclinical hyperthyroidism, and 8.6% developed hypothyroidism. The other half of the patients were euthyroid at the first presentation. Eighteen developed hyperthyroidism, sixteen underwent thyroidectomy. Thirty two patients remained euthyroid during the study, and ten hyperthyroid patients refused surgery or radioiodine treatment and were followed by antithyroid drug therapy.

In this study both the treatments radioactive iodine and surgery were effective. Surgery, was the preferred method of treatment in younger patients. The frequency of hypothyroidism in patients who received radioactive iodine therapy was significantly higher as compared to surgery (p<005).

The distinction between follicular adenoma and follicular carcinoma of the thyroid can be particularly challenging in routine practice of diagnostic surgical pathology. Often examination of several histologic sections is required in order to identify the presence of unequivocal capsular and/ or vascular invasion.

To investigate the role of immunohistochemical markers in the differential diagnosis of follicular lesions of the thyroid, we studied the expression pattern of P53 and Ki-67 in 52 follicular adenomas and 52 follicular carcinomas of the thyroid. Thirty simple goiters were examined as a control.

Ten percent of simple goiters exhibited nuclear P53 expression. P53 positivity was seen in 55.8% and 82.7% of follicular adenomas and carcinomas respectively. Ki-67 nuclear immunoreactivity was observed in 30% of simple goiters, 51.9% of follicular adenomas and 96.2% of follicular carcinomas. Sensitivity and specificity of P53 in diagnosing follicular carcinoma in compaarison with follicular adenomas were 82.7% and 44.2% respectively. Similarly, the results for Ki-67 were 96.2% and 48.1% respectively. Using both P53 and Ki-67 markers had 82.7% sensitivity and 57.7% specificity which shows high sensitivity and a better specificity for diagnosis of follicular carcinoma (compared with follicular adenoma).

The results of this study indicate that immunohistochemical detection of P53 and Ki-67 may have practical application in the differential diagnosis of follicular carcinomas from follicular adenomas in routine surgical pathology (p<0.0005).

Thyroid gland cancers are among the common cancers of endocrine glands in which the role of angiogenesis has not been clearly identified and more research seems necessary. Angiogenesis is an essential factor for growth, viabitily and extension of numerous cancers. The major goal of this research is to investigate the role of angiogenesis in malignant thyroid tumors and its relation with clinical and microscopic findings.

In a descriptive study, 205 paraffin blocks of malignant thyroid lesions were stained with factor 8 by the immunohistochemistry method (avidin-biotin peroxidase). Microvessels in 3 locations having more small vessels were counted, and the mean of microvessels for each case was calculated.

Mean vascular counts were 30.9 in papillary carcinoma (Standard Deviation=11.6) (avidin-bioten peroxidase) 35.7 in medullary carcinoma (Standard Deviation=20.4) 29.5 in follicular carcinoma (Standard Deviation=16.0) and 34.0 in anaplastic carcinoma (Standard Deviation=8.9) these results demonstrate that there is no statistical relationship with regard to microvessel count between the aforementioned groups (p value = 0.263).

There is no significant difference in regard to angiogenesis between the malignant thyroid tumors studied and there is no statistically significant relationship between angiogenesis and microscopic findings (capsular invasion, vascular invasion and lymph node involvement) as well. This study reveals that in sharp contrast to many other common cancers, the role of angiogenesis in thyroid cancers is not so important and further studies for confirmation of this result are necessary.

Graves’ disease is a very common thyroid disease with ophthalmopathy being the most obvious extrathyroid manifestation of this disease. The ocular changes include proptosis, eyelid edema, conjunctivitis, chemosis, extraocular muscle involvement, corneal ulcer, optic neuritis and blindness. This study was conducted to determine the factors that aggravate the severity and activity of the disease.

This is a descriptive study performed on 117 patients (aged 14 to 74 years) with Graves’ ophthalmopathy, referring to a private endocrine clinic in Tehran, between January and November 2002. Following completion of a questionnaire for each patient, thyroid and ophthalmologic examination were done. The second ophthalmologic examinations was conducted after an interval of one to three months, for evaluation of activity. Correlations between severity and activity with factors such as sex, age, duration of disease, smoking, thyroid function and treatment with Iodine were evaluated.

Evaluation of subjects revealed the following prevalences: lid retraction 91.4% only signs, no symptoms 91.4%, soft tissue swelling 17.9%, proptosis 56.4%, extraocular muscle(EOM) involvement 13.7%, optic neuritis 5.1%, and none had corneal ulcer. EOM involvement was higher in men than in women. (27.8% vs. 7.4%) (P<0.05). The prevalence of active ophthalmopathy was higher in men than in women (69.4% compared to 35.8%) (P<0.001) and lower in patient that had iodine ablation 33.3% vs. 62% (P<0.003). Statistics of subjects seen to have autoimmune disease and family histories of thyroid disease were 8.6% and 47.9% respectively. In both sexes smoking was higher than in the general population (P<0.01).

This study revealed that, as compared to other countries, Graves’ ophthalmopathy is seen to occur almost a decade earlier in the Iranian subjects studied. Individuals aged over 40 and males seen to be more at risk as compared to others.

To evaluate thyroid gland dysfunction during interferon alfa (INF-alpha) therapy in patients with the hepatitis B (HBV) and hepatitis C virus (HCV) {BR},

58 patients HCV and 18 patients with HBV were studied prospectively before and at 2 months intervals during INF-alpha therapy. Measurements of serum thyroxine, triiodothyronine, thyrotropine, triiodothyronine resin uptake, thyroid peroxidase antibodies (TPOAbs), and thyroglobulin antibodies (TgAbs) were obtained as were. Thyroid radioactive ioidine uptakes (RAIU) in patients who developed thyroxicosis. Thyroid gland size was evaluated with palpation. {BR}

All patients were clinically and biochemically euthyroid prior to INF-alpha therapy. Before treatment, positive levels of TPOAbs and TgAbs were found in 13.8% and 8.6% of patients with HCV compared with 5.5% and 5.5% of patients with HBV, respectively. Titres of TPOAbs increased significantly at the end of INF -alpha therapy in patients with HCV (!0.3%), among whom 5 patients developed hypothyroidism and 1 patient becamed thyrotoxic secondary to thyroiditis with low thyroid RAIU. Patients who developed thyroid gland dysfunction had a higher prevalence of TPOAbs before treatment. Thyroid gland size increased significantly during the study in patients with HBV (p<0.001) and HCV (p<0.005) respectively. {BR}.

Thyroid gland dysfunction is not infrequently observed in patients with HCV receiving INF alpha therapy. Systematic screening of thyroid function and TPOAbs titers in all patients with HCV before and during INF-alpha therapy seems warranted are recommended, should INF-alpha have goiterogenic effects further studies are recommended.

Etiologic diagnosis of cushing’s syndrome is a major challenge in its investigation and treatment. Classical oral HDDST has shown differing sensitivity and specificity in various studies. The IV DEX suppression test with elimination of intestinal absorption factor has been in use since 1973. This study was designed to evaluate the diagnostic power of IV the DEX test in comparison with classic oral HDDST.

Two hundred and seven consecutively referring patients with Cushing’s syndrome diagnosed by screening and LDDST were enrolled. Two days oral HDDST and 7h-h DEX infusion test were performed in all cases. In the infusion test, decrease in serum cortisol to less than 50% of basal level was consistent with a positive response. In the classic oral test suppression of UFC ≥ 50 % and 90% of basal levels assumed as positive response. Etiologic diagnosis was confirmed by imaging and pathologic specimens.

Mean age of patients with ectopic ACTH (EAS) was (58.2±12.6 vs 31.0±10.0) which was higher than athat of pituitary and adrenal cases (p<0.01). Weight loss, weakness and ecchymosis and hypertension were more prevalent in EAS (p<0.05). Positive response to infusion test was detected in 98% of Cushing’s disease cases and no false positive response was detected in EAS and adrenal cases however oral HDDST (90% cutoff level) had 8.1% false positive. In differential diagnosis of pituitary versus non-pituitary tumors, IV DEX test had sensitivity of 98.1%, specificity of 100% and accuracy of 98.5 compared with classic oral which had sensitivity of 98.1, specificity of 93% and accuracy of 97%. ROC curve showed AUC of 0.99 in infusion test versus 0.96 in the classic oral HDDST with 90% suppression.

In the present study, IV DEX test with its increased rapidity and higher accuracy as well as higher specificity, in comparison the classic oral HDDST, can be a better diagnostic choice in the differential diagnosis of Cushing’s syndrome.

The major consequence of radioiodine therapy for thyrotoxicosis is hypothyroidism and long-term precise management of hypothyroidism may be problematic. In this study, the long-term outcomes were compared in radioiodine treated euthyroid and hypothyroid patients on thyroid hormone treatment.

One hundred and thirty eight patients with diffuse toxic goiter were treated with radioactive iodine. One hundred and seven patients (78%) returned for follow up visits for up to 11.5±0.8 years. Numbers of occurrences of thyroid dysfunction in each patient were recorded and a total cost of management was calculated. At the end, 41 patients (38%) were still euthyroid (group 1) and 66 (62%) became hypothyroid (group 2). Serum, FT4, FT3, TSH, thyroid antibodies, lipid profile, calcium, phosphorus, and PTH were measured and bone mineral density, ECG and echocardiography were performed. There was no significant difference in age, sex, duration of symptoms and thyroid function between the 2 groups. The cost of treatment was lower in group 1 than in group 2. During 11.5 years of follow up, percentage of elevated and suppressed TSH in groups 1 and 2 were 0.02% and 20.5%, p<0.001 and 7.9% and 13.4%, p<0.001, respectively.

At the end of 10 years, goiter rate, serum T4, T3, thyroid antibodies, lipids, Ca, P and PTH and bone mineral density were not significantly different between two groups. In echochardiagraphy left ventricular posterior wall thickness, ejection fraction, left ventricular mass index and other parameters were similar in both groups. However, mean serum TSH and number of TSH above 5 mU/l was greater in group 2 than 1 (p<0.01).

It is concluded that thyroid derangements frequently occur in patients who become hypothyroid after radioiodine therapy while on replacement therapy.

Metabolic disorders including obesity, diabetes and lipid metabolism disorders are the major health problems of today. The aim of this study was to evaluate the prevalence of lipid disorders in Tehranian children and adolescents.

This study was a descriptive-analytic cross-sectional study. 4114 individuals, 3-19 years old, residents of eastern Tehran (Iran) were randomly selected and interviewed. After physical examination, a blood sample was taken for measurement of serum glucose, cholesterol, triglycerides, and HDL.

Of the study population, 1926 (46.8%) were male. Hyperlipidemia was present in 520 (29%) the highest mean of serum cholesterol was found in the 7-10 years old group (17332 mg/dl) and the lowest level was seen in 17-19 year olds (165±33 mg/dl). BMI (body mass index) in hyperlipidemic children was 216 kg/m2 and in the remaining children was 18.74 kg/m2 (P<0.0001). In children with abnormal WHR (waste hip ratio), 174(17.8%) were hyperlipidemic and others 316(11%) (P<0.0001).

This study shows the high prevalence of hyperlipidemia in urban adolescents in Iran. Hyperlipidemia is more prevalent in individuals with higher BMI and abnormal WHR.

Waist and hip circumference play important roles in epidemiologic and clinical studies. The purpose of the present study was to determine the effect of weight loss on the waist and hip circumference of overweight and obese women.

This is a before-after experimental study carried out on 289 women between the ages of 18 and 73 years old. Demographic data were gathered. Weight and height was measured using standard protocols and Body Mass Index (BMI) was also calculated. Waist circumference (WC) –the minimum between the costal margin and iliac crest- and hip circumference (HC) -at the greater trochanters- were measured. Waist to hip ratio (WHR) was also calculated. Obesity was defined with a BMI >30 kg/m², overweight with a 25 ≤ BMI ≤ 30 kg/m² and abdominal obesity with a WHR ≥ 0.8.

The mean age of our subjects was 34.9±11.5 years. At the beginning of the study, mean W and BMI was 81.8±14.6 Kg and 31.8±5.4 kg/m², mean WC was 95.3 ±10.3 cm, mean HC was 114.6±10.8 cm and mean WHR was 0.83±0.06. Two months after the diet recommended for weight reduction, W, BMI, WC, HC and WHR were 77.8±14.5 Kg, 30.4 ±5.4 kg/m², 91.1±10.5 cm, 111.8±11 cm and 0.81±0.06 respectively (P value <0.05 for all).

Our findings suggest that in obese and overweight women a low calorie diet results in a significant weight loss with significant reduction in BMI, WC, HC, WHR. We also demonstrated that these changes in WC and HC have a direct connection with their primary BMI.