مجله غدد درون ریز و متابولیسم ایران
سال پنجم شماره 3 (پیاپی 19، پاییز 1382)

Androgen deficiency leads to bone loss and contributes to osteoporotic fractures in men. Yet, the long-term effects of androgen replacement therapy on bone mineral density (BMD) are not well defined. We therefore reviewed the effect of testosterone treatment on BMD and its effect modifiers from prospectively collected dual energy xـray absorptiometry (DXA) of the lumbar spine and proximal femur. Men (n=137, aged 39±1 years, range 17 to 79 years) with established androgen deficiency (58% with primary hypergonadotropic hypogonadism) requiring regular androgen replacement therapy (ART) were treated with testosterone implants (800 mg, 4-6 month intervals) and had DXA scan at 2 to 3-year intervals. Patients were classified into four subgroups according to adequacy of prior treatment at the time of first DXA study comprising those (a) never treated, (b) well treated, (c) poorly treated (<1 year of inadequate treatment) and (d) off treatment (off all treatment >1 year). In the cross sectional analysis, none had fractures but WHO-defined osteoporosis and osteopenia were present in 8% and 29% in the lumbar spine and 5% and 31%, in the femoral neck, respectively. Testosterone treatment was associated with higher BMD but there was no significant difference between those well treated and recently off treatment. Adjustment for age, physique or type of hypogonadism did not modify the findings. In a longitudinal analysis of 48 men who had two BMD measurements at a median of 3 years (range 1-7 years) apart, BMD was significantly increased in lumbar spine (2. 0±0. 5% per year) and trochanter (1. 1±0. 5% per year) but did not change in femoral neck or Ward’s triangle. 22 of these patients had osteopenia and osteoporosis at their 1st BMD measurement. With a follow up period of 1ـ-5 (median 2) years, increases in their bone mineral density was observed at all bone sites. The present study confirms that androgen deficiency reduces, and ART improves BMD in men at lumbar spine and trochanter but not at femoral neck or Ward’s triangle. It increases BMD at all bone sites in those patients with osteopenia or osteoporosis at 1st DXA scan. These observations suggest that reversing the effects of androgen deficiency requires adequate testosterone treatment and that beneficial effects of testosterone are durable despite even short-term interruption of treatment. The consequences of these findings for he potential androgen treatment to prevent bone loss and fractures related to male ageing and chronic diseases associated with mild androgen deficiency remain to be determined. Keywords: BMD, Bone, Osteoporosis, Men, Testosterone, Androgen, Hypogonadism, Osteopeina

Following screening of newborns for congenital hypothyroidism (CH) in Tehran for 49 months and in Damavand for 21 months, a question was raised as to whether there are any differences between the recall rates and CH incidences in metropolitan and district populations. The present study was conducted to address the aforementioned issue. From February 1998 to March 2002, cord blood spot samples from 8 hospitals and a rural birth center in Tehran (the capital) and Damavand (district) were collected and tested for TSH measurement using a two site IRMA method. TSH values  20 mU/L were recalled. The diagnosis of CH was confirmed using age-adjusted reference values for serum TSH and T4 levels. The frequency distribution of recalls and CH cases in Tehran and Damavand were compared using 2 and Fisher’s exact tests, respectively. Of 30085 (Tehran: 28001 and Damavand: 2084) screened neonates, 319 (Tehran: 297 and Damavand: 22) had cord TSH values  20 mU/L. The recall rate was 1. 06% (Tehran: 1. 06% and Damavand: 1. 06%). Thirtyـtwo (Tehran: 30 and Damavand: 2) neonates had CH. The CH incidence was 1 in every 940, 933, and 1042 live births in total, Tehran, and Damavand populations, respectively. A total of 5119 out of 18260 (28%) neonates had parental consanguinity. This was 4582 out of 16178 (28. 3%) in Tehran and 537 out of 2082 (25. 8%) in Damavand. The recall rates and CH incidences were not significantly different in Tehran and Damavand. Preliminary findings of CH screening program showed that recall and CH occurrence do not have significantly different distributions in Tehran and Damavand and CH was prevalent in both regions. It could be concluded that CH might be prevalent in other parts of the country.

Due to the relationship between structure and function, the study of glomerular volume is important to understand initiation and progression of diabetic glomerulopathy. The aims of the present study were to estimate renal volume as well as absolute glomerular volume and total glomerular number in diabetic rats following administration of different doses of streptozotocin (STZ), by using unbiased morphometric methods. Male Wistar rats with an average weight of 110 gr were randomly divided into 5 groups. Diabetes was induced by an IP injection of Stereptozotocin 15mg/kg, 45mg/kg and 90 mg/kg. Fifty-six days after IP injection, the animals were anesthetized by ketamine hydrochloride and the kidneys were excised, decapsulated and fixed in modified Lilli´s solution. After tissue processing and staining, new morphometric methods were used to estimate the volumes of different zones of kidney, absolute glomerular volume and total glomerular number. This experiment showed increased cortical tissue volume in all groups whereas medullary volume increased only in the group which received 90mg/kg of STZ (P<0.01). Glomerular volume was increased significantly in all groups (P<0.01) but no changes in total glomerular number were detected (P>0.05). This study revealed that, at least, after short periods of inducing diabetes mellitus, administration of more STZ might have more effects on kidneys and cause more imbalances in cells turnover.

It is well recognized that the pathogenesis of thyroid diseases is complex and different factors such as heredity, iodine deficiency, sex, age, radiation therapy in childhood, growth stimulating antibodies, and other epithelial growth factors can influence it. Epidemiological features of thyroid tumors and experimental evidences suggest that female sex hormones may exert effects on this gland and its neoplasms. This possibility was addressed by investigating the expression of estrogen receptor protein in 351 thyroid lesions. 351 cases of human thyroid tissues comprising 130 nodular goiters and 221 neoplastic lesions were used for the present immunohistochemical study of estrogen receptor expression. Positive control was estrogen receptor positive breast cancer tissues. The prevalence of estrogen receptor positive cases was 24% (31/130) for nodular goiters, 22% (8/37) for follicular adenomas, 11% (2/18) for follicular carcinomas, 31% (37/119) for papillary carcinomas, 0% (0/35) for medullary carcinomas, and 0% (0/12) for undifferentiated carcinomas. The prevalence of estrogen receptor positivity is more in well differentiated thyroid lesions. It is in parallel with other investigations. Estrogen receptor reactivity does not significantly differ between females and males, different age groups and does not correlate with lymph node status and vascular or capsular invasion. The relative high estrogen receptor positivity in goiters, follicular adenomas and papillary carcinomas and strong statistical association between estrogen receptor positivity and papillary carcinomas (P<0.0005), suggests that the incidence of estrogen receptor reactivity tends to increase with better differentiation of thyroid lesions. The use of these findings in treating the patients merits more clinical investigations.

Many studies performed on nonـtraditional risk factors have proposed a metabolic triad including increased serum level of apolipoprotein B, hyperinsulinemia and high small dense LDLـC as a risk factor of cardiovascular disease. Hypertriglycemic waist (increased waist circumference as well as high fasting triglycerides) can be used as a simple criterion to predict metabolic triad. The aim of this study was to investigate the prevalence of hypertriglycemic waist and the frequency of cardiovascular risk factors in the affected population The study was performed on 18-70 year-old males of the population of Tehran Lipids and Glucose Study (TLGS). The subjects fell into four groups with respect to serum level of fasting triglycerides (Tg) and waist circumference (W). Subjects of TgHWH group had serum Tg >160 mg/dl as well as WC >95 cm while those of TgHWL group had Tg>160 mg/dl and W<95 cm. Triglycerides level was less than 160 mg/dl in TgLWH and TgLWL groups whereas waist circumference was higher than 95 cm in TgLWH and lower than 95 cm in TgLWL. Cardiovascular risk factors, anthropometric and laboratory variables were compared between groups. A total of 4169 subjects were enrolled of whom 784 had high serum levels of triglycerides as well as increased waist circumference. The prevalence of cardiovascular risk factors was significantly highest in TgHWH group. Mean age of subjects was significantly higher in TgHWH compared to others (37±15, 48±14, 41+13 and 46±13 years in TgLWL, TgLWH, TgHWL and TgHWH, respectively, p<. 001). Systolic and diastolic blood pressures and body mass index were significantly higher in TgHWH than others. Serum total cholesterol, triglycerides and LDL-C were significantly higher in TgHWH compared to others whereas HDL-C was significantly lower in this group. The prevalence of subjects who had at least four risk factors was 75% and 10% in TgHWH and TgLWH, respectively. Hypertriglycemic waist can be used as a simple criterion to predict cardiovascular risk factors.

Growth and puberty disorders and endocrine abnormalities are seen in major thalassaemia in the background of chronic anemia or iron retention following transfusion. In a case-control study, 109 thalassaemic patients, aged 8 to 18 years, were compared with 107 healthy individuals in the same age range in order to evaluate growth and puberty state and detecting high risk age groups. Thalassaemic patients were divided into good control (ferritin <1500 ng/dl) and poor control (ferritin >1500 ng/dl) groups. Only 14% of thalassaemic patients were in good control group. Short stature [SDS (Standard Deviation Score) less than -2.5] was seen in 64% of patients. Statistically significant differences were found between SDS of height and weight in healthy individuals and thalassaemic patients (P<0.01). SDS for height was -3.2 vs -0.89 and SDS for weight was -2.91 vs -1.16 for thalassaemic and healthy individuals, respectively. Furthermore, SDS for weight and SDS for height were positively correlated in both thalassaemic patients and healthy individuals. This correlation was stronger in thalassaemic patients (r=0.86). From another point of view, in those older than 14 years, there was a significant difference between height and weight of thalassaemic patients and healthy individuals (P<0.01). The prevalence of hypogonadism in this study was about 60%. The mean ages of puberty onset in thalassaemic and healthy boys were 16.5 ±1 and 11.6 ± 2 years and for girls were 16±3 and 10 ± 1 years, respectively (P<0.01). There was no difference in onset of puberty in 8 to 11 year-old thalassaemic patients in both good and poor control groups, whereas it was statistically significant in 12 to 14 years old patients of both groups (P<0.05). This study reveals a strong relationship between growth retardation and weight loss in thalassaemic patients, especially above the age of 14, as well as the role of poor control of plasma ferritin in puberty delay. It was also shown that, because of the equal prevalences of short stature and hypogonadism in thalassemic patients, hypogonadism can be an important factor in short stature of these patients.

Human studies investigating the relationship between obesity and diet composition, have failed to achieve consistent findings. This study was undertaken to assess the relationship between macronutrient intake and body mass index in a group of Tehranians. From among participants of TLGS, 1290 subjects over 10 years old (565 males and 725 females) were selected randomly for dietary survey. Anthropometric indices were measured according to standard protocols and BMI was calculated. Dietary data were collected by trained interviewers using two non-consecutive 24-hour dietary recalls. Under-and over-reporting of energy intake were defined as energy intake to BMR<1.35 and >=2.4, respectively. Calorie-adjusted amounts of macronutrients were calculated by the residual method, following which energy intakes from all calorie-adjusted macronutrients were simultaneously included in the multiple regression model controlling for confounding variables and mutual effects of macronutrients. Total energy intake was not included to avoid co-linearity. After excluding under and over-reporters, BMI did not change in males but decreased in females. Misreporting of energy intake increased with age and BMI. Excluding misreporters caused significant changes in actual amounts of macronutrient intakes of women, but not of men. In all cases, adjusting for energy caused a significant increment in the amounts of protein. Controlling for confounding variables, energy intake from fat was positively associated with BMI in males and females (β= 0.61, P<0.01 and β=0.75, P<0.01, respectively). This relationship remained after excluding misreporters (β= 0.66, P<0.01 and β=0.78, P<0.01, respectively). No association was seen between energy intake from protein and carbohydrate with BMI in subjects before and after excluding misreporters. We have found evidence indicating that energy from fat is positively associated with obesity. No other association was observed between energy from protein and carbohydrates with BMI.

Prcision and stable control of blood glucose level is an essential requirement for Diabetic patients. On the other hand, biological systems (e.g. Insulin-glucose interaction) act as a non-deterministic and nonlinear complex model. Therefore, we need to use intelligent control. In this paper we use a practical model (instead of the patient) and simulate a neural-fuzzy controller for blood glucose adjustment. Neural network estimates the future of the model then generates the control signal (insulin injection rate). This is a Model Prediction Control (MPC). Fuzzy controller acts as a supervisor system and guarantees the stable and robust control.

Nowadays with the current treatments, survival and life expectancy has increased in acute lymphoblastic leukemia (ALL) and hence researchers have focused more on long term quality of life in these patients. Some of the long-term problems of ALL patients include biochemical disturbances of vitamin D and minerals, reduction in mineral content of bone and pathological fractures due to osteoporosis. The aim of the current study is to establish and compare biochemical indices of mineral and bone metabolism in ALL patients before and after chemotherapy. The patient studied were children between one to ten years of age with ALL who visited the Department of Pediatric Oncology of Shiraz University of Medical Sciences in two consecutive years, and received the same chemotherapy regimens. Blood samples (to measure serum calcium, phosphorous, albumin and alkaline phosphatase) as well as urine samples (for calcium and creatinine) were collected immediately after the diagnosis and before the beginning of chemotherapy. Similar samples were also collected and tested four to eight months after the completion of induction of chemotherapy. Total number of 20 patients aged 8±2.4 years (50% boys and 50% girls) were studied. Average serum calcium level was 9 mg/dL before chemotherapy, and 9.4 mg/dL after it (p<0.05). Average difference of phosphorous (p>0.4) and Alkalin phosphatase (p>0.3) before and after chemotherapy were not significant. Sixty five percent of patients had hypercalciuria before chemotherapy but this proportion declined to 25%, four to eight months after completion of chemotherapy. It seems that disturbances of mineral and especially calcium metabolism are common in ALL patients. On the other hand, chemotherapy has not had a considerable effect in long term on indices of mineral and calcium metabolism and moreover it seems that with induction of chemotherapy, and hence, control of the disease process (after four to eight months) the above mentioned indices improve, i.e reduction of rate of hypercalciuria and significant increase in serum calcium so, the role of the disease process itself in the disturbances observed in mineral and bone metabolism is probably greater than the effect of chemotherapy.