Arash Ordookhani

Sustainability of a well-monitored salt iodization program in Iran: Marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations without alteration in iodine content of salt

Objective: Two yr after legislation of salt iodization of 40 parts per million (ppm) in 1994, goiter was still endemic and urinary iodine concentration (UIC) remained elevated in many provinces of Iran. Goiter prevalence and UIC were compared 2 and 7 yr after sustained consumption of uniformly iodized salt by Iranian households. Methods: Schoolchildren (7–10 yr) of all provinces were randomly selected by cluster sampling from December 2000 to June 2001. Goiter rate, UIC, and household salt iodine values were compared to those in 1996. Factory salt iodine was also compared in 2001 vs 1996. Ultrasonographically determined thyroid volumes of 7–10 yr old children were compared in 2001 vs 1999. Results: In 2001 (no.=33600) vs 1996 (no.=36178), total, grade 1, and grade 2 goiter rates were 13.9 vs 53.8%, 11.0 vs 44.8%, and 2.9 vs 9.0%, respectively (p<0.0001). Weighted total goiter rate was 9.8% in 2001. Median (range) UIC in 2001 (no.=3329) was 165 (18–499) μg/l and in 1996 (no.=2917) was 205 (10–2300) μg/l (p<0.0001). In 2001 vs 1996, mean±SD for iodine salt content was 32.7±10.1 vs 33.0±10.2 ppm (p=0.68) in households and was 33.2±13.4 and 33.8±13.2 ppm (p=0.57) in factories, respectively. Among 7–10 yr old children in 2001 (no.=400) vs 1999 (no.=396), only 7-yr-old children in 2001 (the only group with probably no history of iodine deficiency) showed significant smaller thyroid volumes by ultrasonography compared to those in 1999. Conclusions: After 7 yr of optimized iodized-salt supplementation in Iran, adequate UIC values and marked reduction in goiter rate have been achieved.

A High Prevalence of Consanguineous and Severe Congenital Hypothyroidism in an Iranian Population

To determine the incidence of permanent congenital hypothyroidism (CH) in Tehran and Damavand, cord blood spots were collected from February 1998-August 2002 and infants with TSH > or =20 mU/l were recalled. CH was confirmed in neonates (aged > or =7 days) with serum TSH >10 mU/l and T4 <84 nmol/l. Cases were followed up until September 2003. Dysgenesis was detected by thyroid imaging. In eutopic cases, serum TSH and T4 measurements following levothyroxine discontinuation (2-3 years of age) confirmed dyshormonogenesis and transient CH. Of 35,067 neonates, 373 (1.06%) were recalled and 25 (1:1,403 births) had permanent CH (six had transient CH and four remain unknown). Dysgenesis was detected in 18 (1:1,948 births) and dyshormonogenesis in seven (1:5,010 births) infants. Parental consanguinity was present in 10 (55.6%) dysgenetic, three (42.9%) dyshormonogenetic, and overall 6,648 (28.6%) of 23,227 screened infants. Odds ratio (95%CI(OR)) of consanguinity in permanent CH and dysgenesis was 2.75 (1.17-6.47) and 3.74 (1.33-10.52), respectively. The high prevalence of parental consanguinity in infants with permanent CH warrants genetic assessment.

Congenital hypothyroidism in Iran

Objective : Following elimination of iodine deficiency in Iran, the program of screening for congenital hypothyroidism (CH) was established in 1998. The descriptive findings of the study are reported here.Methods : From February 1998 to June 2001, cord blood spot samples from 8 hospitals and a rural birth center in Tehran and Damavand were collected and tested for TSH measurement using a two-site IRMA method. TSH values ≥ 20 μU/mL were recalled. The diagnosis of CH was confirmed using age adjusted reference values for serum TSH and T4 levels.Results : Of 20107 screened neonates, 256 had cord TSH values ≥ 20 μU/mL (recall rate: 1.3%) and 22 showed hypothyroidism (1:914 live births). History of maternal ingestion of drugs and dietary goitrogens were negative and minimal, respectively. 15 out of 21 CH neonates had parental consanguinity. The odds ratio of CH occurrence in blood-related to non-related marriages was 6.9 (Cl=1.82-25.87). Thyroid dysgenesis occurred in 10 neonates; 1: 2011 births. Urinary iodine excretion was between 12–22 (n=3) and 40–42.5 (n=5) μg/dL tn 10 eutopic neonates (2 not assessed).Conclusion: Parental consanguinity and iodine excess could be the causative factors for the high incidence of CH.

An interim report of the pilot study of screening for congenital hypothyroidism in Tehran and Damavand using cord blood spot samples.

Following elimination of iodine deficiency in Iran [1], a pilot study to determine congenital hypothyroidism (CH) incidence was started in February 1998. Seven hospitals from NEWS and Centre of Tehran and the only general hospital and a rural birth centre in Damavand, covering the majority of births in the latter, were prepared for the collection of cord dried blood spot samples on filter papers. Specimens were collected immediately after birth and transported by a trained motorcyclist in Tehran or ambulances in Damavand in Ziplock bags to the Endocrine Research Centre (ERC) laboratory and tested within 7 days of collection. Thyroid-stimulating hormone (TSH) levels of whole blood elutes were measured using a two-site IRMA method (RAW/6/003 Project, International Atomic Energy Agency) and patients with levels of ‡20 lU/ml were recalled by telephone calls or home visits. On recall, neonatal venous TSH and T4 (IRMA and RIA, respectively; Orion Diagnostica, Fenzia, Finland) levels were measured for confirmation of CH diagnosis, followed by the measurement of maternal and neonatal urinary iodine concentrations (Sandell-Kolthoff digestion method). Normal ranges for serum TSH, T4 and urinary iodine concentrations between 1 and 4 weeks of age were 1.7–9.1 lU/ml, 8.2–17.1 lg/dl [5] and 15– 22 lg/dl, respectively [6]. Iodine excretion >5 lg/dl was considered to be non-iodine deficient [3]. Between 7 and 14 days of life, venous TSH >10 lU/ml and T4<6.5 lg/dl or TSH >30 lU/ml alone were considered to be cases of CH [4]. Serum thyroglobulin measurement was followed by 99mTC thyroid scanning (and thyroid ultrasonography for no-uptake scanning) in CH neonates. Some of the findings of the program are shown in Table 1. Twenty-two (1:914 live births) newborns with CH were detected who were all mature (‡37 weeks’ gestation). Of 10 dysgenetic cases (45% of CH neonates), 1 had agenesis, 4 had ectopia, and 5 had hypoplasia of the thyroid. Eutopic thyroid gland was present in 10 neonates (7 neonates with goitre) of whom 3 were non-iodine deficient or normal (range 12–22 lg/dl) and 5 increased (range 40–42.5 lg/dl) urinary iodine concentrations (2 neonates were not assessed). The median age for starting L-T4 replacement therapy was 8.5 (range 4–46) days. The odds ratio of CH occurrence in bloodrelated compared with non-related marriages was 6.9 (95%CIOR 1.82–25.87). The high prevalence of CH, dysgenesis and bloodrelated marriages in Tehran and Damavand, probably reflecting similar patterns in other regions of Iran, warrant a national screening program. Parental consanguinity may be a causative factor for the high CH incidence. By continuing our program, dyshormonogenesis is expected to be present in more than 10–15% of CH cases reported elsewhere [2]. Iodine excess may be another less probable causative factor, because in our mature eutopic neonates the increased iodine excretions were not large [2]. Damavand (a Primary Health Care [PHC] model) showed better birth-coverage than Tehran (non-PHC). Unless the program is legislated, the total coverage of all neonates is unattainable, especially in large cities. Eur J Pediatr (2003) 162: 202–203 DOI 10.1007/s00431-002-1150-2

Transient congenital hypothyroidism in an iodine-replete area is not related to parental consanguinity, mode of delivery, goitrogens, iodine exposure, or thyrotropin receptor autoantibodies.

Objective: To assess transient congenital hypothyroidism (TCH) etiologies in two Iranian cities. Materials and methods: Cord dried blood spot samples were collected from neonates in Tehran and Damavand. Serum TSH and T4 were measured in those with cord TSH ≥20 mlU/l. Normal serum values at 2–3 weeks of age confirmed transient hyperthyrotropinemia (THT), while persistently abnormal levels revealed congenital hypothyroidism (CH). Normal serum TSH and T4 4–6 weeks after levothyroxine replacement therapy discontinuation at 2–3 yr of age differentiatedTCH from persistent CH. Results: Among 50,409 screened newborns, 9 (1:5601 births) were diagnosed as TCH and compared to 88 full-term neonates (≥37 weeks’ gestation) with THT and 45 normal (cord TSH<20 mIU/l) neonates. At a median age of 11 days, median (range) serum TSH values in TCH, THT, and normal neonates were 36.8 (13–130), 3.6 (0.1–13.3), and 2.9 (0.7–8.0) mIU/l (p<0.0001) and serum T4 values were 97 (36–168), 142 (74–232), and 160 (79–228 nmol/l), respectively (p=0.002). Urinary iodine concentration (UIC) >220 μg/l was observed in 5 (55.6%) of TCH neonates. The occurrence of TCH was not associated with gender, parental consanguinity, mode of delivery, pre- or post-natal consumption of goitrogens and/or thyroid affecting medications, TSH receptor autoantibodies, or neonatal UIC. Conclusions: Elevated UIC was the most frequent finding in newborns with TCH but the distribution of excessive UIC was not significantly different among TCH, THT, and normal neonates. Since no other etiologies were found in TCH neonates without elevated UIC values, evaluation of other environmental and/or genetic factors is warranted.

Prevalence of goiter among schoolchildren from Gorgan, Iran, a decade after national iodine supplementation: Association with age, gender, and thyroperoxidase antibodies

Background: One decade after universal salt iodization in Iran, goiter prevalence, urinary iodine concentration (UIC) and thyroperoxidase antibody (TPOAb) values were assessed among schoolchildren in Gorgan, Iran. Methods: From 2003–2004, 500 girls and 900 boys aged 7–11 yr were evaluated for goiter by palpation. UIC was measured in 183 randomly-selected goitrous children. Serum TSH, T4, and TPOAb were measured in 53 goitrous and 30 non-goitrous children with adequate UIC. Results: Goiter was detected in 370 (26.4%) children. Goiter was present in 31 % of girls and 17% of boys age 9 (p<0.012); 37% of girls and 20% of boys age 10 (p<0.003); and 52% of girls and 19% of boys age 11 (p<0.0001). Median (range) UIC for all goitrous children sampled was 190 (20–600) μg/I; 220 (30–590) in boys and 170 (20–600) in girls (p=0.001). Eight point seven percent of goitrous children and 22% of goitrous girls aged 10–11 had UIC<100 μg/I, while 47% of the goitrous children had UIC≥200 μg/ I. TPOAb was present in 52.8% of goitrous children and 10% of non-goitrous children (p=0.0001 ). TPOAb was present in 53.9% of 10–11 and 22.7% of 7–9 yr old goitrous and non-goitrous children (p=0.003) with adequate UIC. Median (range) TSH was 2.9 (0.3–10.9) mIU/I in TPO-positive and 1.8 (0.5–4.1) in TPO-negative children (p=0.001). Conclusions: Gorgan, Iran, is an iodine-sufficient area and almost half of schoolchildren have more than adequate UIC. TPOAb is associated with endemic goiter. Despite sufficient UIC overall, some school-aged girls remain at risk of iodine deficiency.

Seasonal variation of neonatal transient hyperthyrotropinemia in Tehran province, 1998-2005.

Seasonal aggregation and the monthly rate of neonatal transient hyperthyrotropinemia (THT) were assessed. From November 1998 to April 2005, neonates of gestational age ≥37 wks, birth weight 2500–4000 g, birth length 45–55 cm, and 1st min Apgar score >3, who had thyrotropin (TSH) ≥20 mU/L in their cord dried-blood specimen, but without congenital hypothyroidism, were enrolled in the study. The recall rate equals the rate of THT occurrence in this study. Of 47,945 neonates, 555 had THT (recall rate: 1.2%). The aggregated seasonal recall rate (recall for further assessment to rule out congenital hypothyroidism) was significantly higher in winter (January, February, and March) than the other seasons (p < .0001). Winter had higher recall rate in each year as compared to other seasons, but the overall rate of recalls decreased in 2001 and 2002. Excluding the first 6 months (due to erratic variations), the remaining 72 months revealed a relatively sinusoidal pattern in monthly recall rates; indeed, there was an initial 11-month high recall rates (1.7%), followed by a 33-month decrease (0.7%), a 19-month increase (1.9%), and a final 9-month decrease (0.8%). The recall rate of each of these time intervals was significantly different from that of the next time interval (p < .0001). The monthly recall rates were best fitted to cubic curve estimation and then autoregressive integrated moving average (ARIMA) (0, 1, 1) models. THT occurs significantly more in winter than in other seasons, and this suggests a possible role for time-varying factor(s) contributing to its seasonal preponderance. (Author correspondence: E-mail: arash_ordookhani@yahoo.com)