Related Articles

Objective

In Iran thyroid-stimulating hormone (TSH) based neonatal screening program is included in health care services from 2005 for detection of patients with primary congenital hypothyroidism (CH). This study was performed for a critical evaluation of the screening program primary congenital hypothyroidism in Fars province, Iran.

Methods

From November 2006 to September 2007, TSH serum concentrations of 63031 newborns, 3 to 5 days old born in Fars province, were measured by heel prick. The newborns with TSH ≥5mIU/L were recalled for measurement of serumT4 and TSH in venous blood samples

Findings

Of 127 recalled subjects, 43 were confirmed to be hypothyroid, showing a prevalence of 1:1465 with F:M ratio of 1.05:1. The most common clinical and radiological findings were prolonged jaundice (73%), large anterior fontanel (56%), wide posterior fontanel (55%), absence of distal femoral epiphysis (20%), and umbilical hernia (11%). Scintigraphy of the thyroid with 99mTC revealed eutopia (67.4%), hypoplasia (23.3%), agenesis (4.7%) and ectopia (2.3%).

Conclusion

It is concluded that a cut off value of TSH≥5mIU/L overestimates recalling the number of patients with CH. The most common cause of congenital hypothyroidism is not dysgenesis of the gland and perhaps dyshormonogenesis in Iran is more common than what is reported in other countries.

Background:

Considering the role of maternal thyroid stimulating hormone (TSH) receptor blocking antibody (TRAb) in the etiology of congenital hypothyroidism (CH), this study aimed to determine TRAb among patients with CH in Isfahan, Iran.

Methods:

In this case–control study, patients with CH and their mothers were compared with a group of healthy neonates and their mothers. Venous blood samples were obtained for measurement of TRAb using enzyme-linked immunosorbent assay (ELISA) method among mothers and their neonates. TSH of mothers was also determined.

Results:

The case group consisted of 65 patients with CH and their mothers; controls were 148 healthy neonates and their mothers. The prevalence of positive TRAb in patients with CH and their mothers was higher than in the control group (81.5% vs. 1.3% in mothers and 80% vs. 0% in neonates, respectively, P<0.05). The relationship between the TRAb and occurrence of CH was significant (P<0.05), whereas the corresponding figure was not significant for TRAb and the level of maternal and neonatal TSH in case and control groups (P>0.05).

Conclusion:

It seems that autoimmunity has an important role in the etiology of CH. Further studies are necessary to determine other autoantibodies in CH patients.

Background:

Considering the high prevalence of congenital hypothyroidism (CH) in Isfahan and its different etiologies in comparison with other countries, the high rate of parental consanguinity, and the role of NIS gene in permanent CH due to dyshormonogenesis, the aim of this study was to investigate the G395R mutation of the NIS gene in patients with permanent CH due to dyshormonogenesis

Methods:

In this case–control study, patients diagnosed with permanent CH due to dyshormonogenesis during CH screening program were selected. Venous blood sample was obtained to determine the G395R mutations of NIS gene using polymerase chain reaction (PCR) sequencing method.

Results:

In this study, 35 CH patients with permanent CH due to dyshormonogenesis and 35 neonates with normal screening results as a control group were studied. We did not find any changes of the mentioned mutation of NIS gene in the patients’ group.

Conclusion:

Considering the findings of the current study, it seems that further studies with larger sample size and with consideration of other gene mutations such as pendrin and thyroglobulin are needed for more accurate conclusion.

Objective

To determine the prevalence of congenital hypothyroidism (CH), permanent and transient CH.

Methods

From November 2006 to September 2007, 63031 newborns were screened by measuring serum TSH obtained by heel prick. The neonates who had a TSH≥5mU/L were recalled for measurement of serum T4, thyroid stimulating hormone (TSH) and TSH receptor blocking antibodies (TRBAb) in venous samples. In 43 primarily diagnosed as cases of CH, treatment was discontinued at age 2–3 years for 4 weeks and T4 and TSH were measured again. Permanent or transient CH was determined from the results of these tests and radiologic evaluation.

Findings

The incidence of congenital hypothyroidism was found to be 1:1465 with a female to male ratio of 1.19:1. The most common clinical findings were prolonged jaundice (73%), large anterior fontanel (56%) and wide posterior fontanel (55%). In 43 patients with CH, prevalence of permanent and transient form of the disorder was 53.6% and 46.4% respectively. Permanent CH was associated with higher initial TSH level than transient hypothyroidism (P<0.001). The most common etiology of permanent CH was dyshormonogenesis (57%). TRBAb was found in 6.8% of the total 43 cases.

Conclusion

Congenital hypothyroidism in Iran may have different etiologies. Due to higher rate of transient CH than other similar researches, it is reasonable to follow these patients for a longer period to rule out the possibility of permanent hypothyroidism.

This article explores the basic development and pathophysiology of the thyroid gland. New factors in the normal development of the thyroid in the neonate are mentioned. The incidence of congenital hypothyroidism continues to increase. We describe congenital hypothyroidism, its possible etiologies, treatment and outcomes. We explore hypothyroxinanemia in pre−term neonates and the risk/benefit of prophylactic thyroid hormone replacement. We discuss the late rise of thyrotropin (TSH) in ill infants and those with very low birth weight. Ill infants or those born premature should have their thyroid function tests routinely monitored. On the occasion of borderline thyroid function test results, TRH testing can be useful in identifying those infants with either persistent or transient hypothyroidism. TRH testing is also helpful in identifying those patients with secondary hypothyroidism. With the early identification and prompt and proper treatment, neonates with congenital hypothyroidism, transient or persistent, should have positive long−term outcomes.

Conflict of interest:None declared.

Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first four years of treatment in 418 children with congenital hypothyroidism, identified by neonatal screening, were examined in relation to paired measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836), triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to severity of hypothyroidism at diagnosis. Mean values for thyroxine and free thyroxine, and to a lesser extent free triiodothyronine, were consistently lower in samples with TSH concentrations over 7 mU/l and this was the case in patients with either severe or less severe hypothyroidism. Raised TSH concentrations were also associated with lower mean doses of thyroxine (micrograms/kg/day) but here the mean doses of thyroxine in children with severe hypothyroidism were higher than in the children with less severe hypothyroidism. The mean dose of thyroxine associated with low/normal TSH values was highest in the first 6 months and fell progressively. Thyroxine dose was significantly related to thyroxine and free thyroxine concentrations but not to triiodothyronine and free triiodothyronine and the latter appeared to be of limited value as measures of plasma thyroid hormone status during treatment.

Objective

Congenital hypothyroidism is characterized by inadequate thyroid hormone production in newborn infants. Many infants with CH have co-occurring congenital malformations. This is an investigation on the frequency and types of congenital anomalies in infants with congenital hypothyroidism born from May 2006-2010 in Hamadan, west province of Iran.

Methods

The Iranian neonatal screening program for congenital hypothyroidism was initiated in May 2005. This prospective descriptive study was conducted in infants diagnosed with congenital hypothyroidism being followed up in Pediatric Endocrinology Clinic of Besat Hospital, a tertiary care centre in Hamadan. Cases included all infants with congenital hypothyroidism diagnosed through newborn screening program or detected clinically. Anomalies were identified by clinical examination, echocardiography, and X-ray of the hip during the infant’s first year of life.

Results

A total of 150 infants with biochemically confirmed primary congenital hypothyroidism (72 females and 78 males) were recruited during the period between May 2006-2010. Overall, 30 (20%) infants had associated congenital anomalies. The most common type of anomaly was Down syndrome. Seven infants (3.1%) had congenital cardiac anomalies such as: ASD (n=3), VSD (n=2), PS (n =1), PDA (n=1). Three children (2.6%) had developmental dysplasia of the hip (n=3).

Conclusion

The overall frequency of Down syndrome, cardiac malformation and other birth defect was high in infants with CH. This reinforces the need to examine all infants with congenital hypothyroidism for the presence of associated congenital anomalies.

Objective: Congenital hypothyroidism (CH) increases the prevalence of kidney and urogenital malformations. There are limited studies considering different aspects of kidney function in well-controlled CH patients. We evaluated some features of kidney function in euthyroid children with CH who have been receiving thyroxine hormone since early life.

Methods: This cross-sectional study was conducted in Isfahan, Iran, on 74 children aged 2-15 years old (36 CH patients and 38 healthy children). Inclusion criteria for CH patients were euthyroidism at the time of the survey and initiation of replacement therapy during the early neonatal period. Kidney ultrasound evaluation was performed in all participants. Serum biochemistry included urea, creatinine, sodium (Na), potassium (K), magnesium, calcium, and cystatin C levels. Urine electrolytes, fraction excretion (FE) of electrolytes and microalbumin, and glomerular filtration rate (GFR) were also determined.

Results: The male/female ratio was 0.8/1 and 1.5/1 in the patient and control groups, respectively. Mean age and height did not differ significantly between the two groups. Ultrasound evaluation of the kidney revealed that the anteroposterior diameter of the right kidney was significantly higher in CH patients as compared to healthy subjects. No significant difference was observed between GFRs in patients with CH and healthy children. The mean values for FENa and FEK were significantly higher in the patient group.

Conclusions: Increased FENa and FEK may be a manifestation of impaired tubular maturation in CH. More longitudinal studies are needed to evaluate kidney function in CH patients.

Conflict of interest:None declared.

BACKGROUND:

To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran.

METHODS:

During a 4-year period (2003 to 2007), 55 children (33 male and 22 female) diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this cross-sectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III) crite-ria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR).

RESULTS:

The mean age of participates was 10.4 years (range 6-19 years) and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55) of survivors (10 male, 1 female) met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004). Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was positively correlated with serum triglycerides (0.543, p ≤ 0.001), systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively), insulin levels (0.914, p < 0.001) and blood sugar (0.398, p = 003).

CONCLUSIONS:

The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors.

Objective

Thyroid hormone is necessary for normal development of the auditory system. The aim of this study was to investigate the rate of hearing impairment in congenitally hypothyroid (CH) patients, and its relation with factors such as CH severity and age at starting treatment, during CH screening program in Isfahan.

Methods

Hearing acuity was assessed in two groups of children with (94 patients aged 4 months – 3 years) and without CH (450), between 2000-2006. Otoacostic emission (OAE) was performed by a two step method. After two tests without OAE signals bilaterally, they were referred for auditory brainstem response (ABR) test. Subjects with both OAE and ABR abnormal test results were considered to have hearing problem. Obtained data was compared in case and control group and also CH patients with and without hearing impairment.

Findings

Three (3.2%) of patients and 1 of control group (0.2%) were diagnosed with sensorineural hearing loss. The rate of hearing loss was not different significantly in two studied groups (P>0.05). There was no difference between age of starting treatment and first T4 and TSH level in CH patients with and without hearing loss (P>0.05). CH neonates with hearing impairment had thyroid dyshormonogenesis according to the follow up results.

Conclusion

The rate of hearing loss was low among our studied CH patients. It may be due to proper management of CH patients. In view of the fact that all CH neonates were dyshormonogentic and considering the relation between certain gene mutations and hearing impairment in CH patients, further studies with larger sample size, with regard to different etiologies of CH should be investigated to indicate the possible gene mutations related to hearing loss in CH.

Although hemangioendothelioma (HHE) is a commonly encountered hepatic tumor during infancy, HHE−related hypothyroidism is rare. We present a patient who developed HHE−related hypothyroidism during the neonatal period and showed marked improvement in hypothyroidism by regression of HHE. A 28−day−old boy with TSH level of 77 mIU/mL on neonatal screening and diagnosed as congenital hypothyroidism was started on L−thyroxine (L−T4) (11 μg/kg/day) therapy on the 21th day of life. On physical examination, the liver was palpable 5 cm below the right costal margin, and the thyroid gland was nonpalpable. Thyroid ultrasonography was normal. Although L−T4 dose was increased to 15 μg/kg/day, TSH was not suppressed and free T3 level remained low. HHE in both lobes of the liver was detected by abdominal ultrasonography and magnetic resonance imaging. Treatment was started with prednisolone 2 mg/kg/day and alpha−interferon 3 million U/m2/3 times per week. Thyroid dysfunction was thought to be due to type 3 iodothyronine deiodinase activity expressed by HHE. L−T4 therapy was changed to Bitiron® tablet, which includes both T4 and T3, and euthyroidism was attained within 1 month. Thyroid hormone requirement was reduced and treatment was discontinued after regression of the HHE. At the most recent visit, the patient was 21 months old and off treatment. His growth and neurological development were normal for age and he was euthyroid. HHE should be considered in cases with severe hypothyroidism resistant to high−dose thyroid hormone replacement. The treatment of HHE in combination with T4 and T3 therapy results in euthyroidism.

Conflict of interest:None declared.

Background

Female prisoners are at risk of acquiring sexually transmitted infections (STIs). There has been no previous study regarding the epidemiological status of STIs among female prisoners in Isfahan, central Iran.

Objectives

The aim of this study was to investigate the prevalence and risk factors of the aforementioned infections among women incarcerated in the central prison, Isfahan, to determine appropriate prevention measures.

Patients and Methods

In a cross-sectional study, all of the 163 women incarcerated in the central prison, Isfahan in 2009, were voluntarily enrolled by the census method. After completing a checklist consisting of demographic, social, and risk factors, a 5ml blood sample was taken from each individual. The sera were analyzed for markers of the hepatitis B virus (HBV; HBsAg, HBsAb, HBcAb), hepatitis C virus (HCV; HCV antibodies), human immunodeficiency virus (HIV; HIV antibodies), and syphilis (RPR). Confirmatory tests were performed on HCV antibody-positive cases.

Results

The mean age of the participants in the study was 34.54 ± 11.2 years old, 94.3% of these women were Iranian, and many of them had only a primary level of education. The prevalence of HBsAg, HBcAb, HBsAb, and HCV antibodies were; 1.2%, 7.4%, 12.9% and 7.4% respectively. No positive RPR or HIV antibodies were detected.

Conclusions

A significant relationship was seen between the HCV antibody, drug injection and illegal sex in the women, and also between HBc-Ab and drug injection. Regular screening, educational programs, and facilitation of access to suitable treatment care should be widely implemented in the prison population. Testing for immunity against HBV should be considered on admission, and afterwards vaccination of all prisoners and an appropriate preventative approach should be applied.

Background:

This study aimed to establish a comprehensive screening and referral system for chronic non-communicable diseases (CNCD) in the routine primary health care, and to determine the prevalence of diabetes, pre-diabetes, metabolic syndrome, and dyslipidemia in adult population invited by public announcement to the Health clinics in Isfahan, Iran.

Methods:

This survey was conducted from March 2010, and the current paper presents data obtained until November 2011. To provide health services for prevention and control of CNCDs, with priority of type2 diabetes mellitus, Health clinics were established in different parts of Isfahan city with a population of approximately 2,100,000 in Iran. The general populations aged 30 years and above were invited to the Health clinics by public announcement.

Results:

A total of 198972 participants were screened. The mean age of participants was 47.8 years (48.5 men, 47.3 women), with a range of 1 to 95 years old and standard deviation of 12.3 years (12.7 men, 12.1 women). Overall, 22% of participants had impaired fasting glucose, 25% had hypercholesterolemia, 31% had hypertriglyceridemia, and 20% had metabolic syndrome.

Conclusion:

The high prevalence of dysglycemia and diabetes in our survey may serve as confirmatory evidence about the importance of mass screening and early diagnosis of CNCDs′ risk factors. Our model of establishing Health clinics, as a comprehensive referral system in the routine primary health care can be adopted by Middle Eastern countries, where CNCDs notably diabetes are an emerging health problem.

Accepted 30 January 1997


OBJECTIVE—To evaluate the efficiency of the screening programme for congenital hypothyroidism in Scotland and to determine the outcome in the cohort of children with positive testing for thyroid stimulating hormone (TSH).
DESIGN—Establishment of comprehensive database for all Scottish infants with high TSH, detected on Guthrie screening.
SUBJECTS—344 infants born between August 1979 and December 1993 with TSH greater than 40 mU/l on initial Guthrie, or 15-40 mU/l on repeat Guthrie.
MAIN OUTCOME MEASURES—Ages at time of: (a) Guthrie collection, (b) notification of positive result by laboratory, and (c) start of treatment; audit of late diagnosis/missed cases; categorisation of positive cases into definite and probable congenital hypothyroidism, transient TSH elevation, and uncertain status; educational status of children with definite and probable congenital hypothyroidism.
RESULTS—344 positive cases were categorised as having definite (224) and probable (11) congenital hypothyroidism, transient TSH elevation (88), and status uncertain (21). The overall incidence of definite/probable congenital hypothyroidism was 1 in 4400 live births. For the definite/probable groups median age of Guthrie collection was consistently between 6 and 7 days from 1983 onwards but for the whole cohort was later than 10 days in 10.5%. Median age of notification fell from 14days in 1980 to 11 days in 1993. Median age of starting treatment ranged between 11 and 15 days from 1983 onwards. Treatment was delayed in four cases, three due to failed or late Guthrie card submission. Of 149 children with definite/probable congenital hypothyroidism who were of school age, educational status was ascertained in 139 (93%). Only two children (1.4%) were attending special school, one of whom was known to have mild hypothyroidism. Sixteen children (11.5%) were receiving extra help in mainstream education compared with 18% of control children in the Scottish very low birth weight study.
CONCLUSION—The current screening programme is working well, but efficiency could be increased by earlier and more reliable Guthrie collection. A substantial proportion of children picked up on the screening programme have a transient rise in TSH rather than true congenital hypothyroidism. The incidence of special education and learning support in Scottish children with congenital hypothyroidism appears to be no different to that of the general population.



OBJECTIVES--To assess whether early treatment of congenital hypothyroidism fully prevents intellectual impairment. DESIGN--A national register of children with congenital hypothyroidism who were compared with unaffected children from the same school classes and matched for age, sex, social class, and first language. SETTING--First three years (1982-4) of a neonatal screening programme in England, Wales, and Northern Ireland. SUBJECTS--361 children with congenital hypothyroidism given early treatment and 315 control children. MAIN OUTCOME MEASURES--Intelligence quotient (IQ) measured at school entry at 5 years of age with the Wechsler preschool and primary scale of intelligence. RESULTS--There was a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with a threshold at 42.8 nmol/l (95% confidence interval 35.2 to 47.1 nmol/l). Hypothyroid children with thyroxine values below 42.8 nmol/l had a mean IQ 10.3 points (6.9 to 13.7 points) lower than those with higher values and than controls. None of the measures of quality of treatment (age at start of treatment (range 1-173 days), average thyroxine dose (12-76 micrograms in the first year), average thyroxine concentration during treatment (79-234 nmol/l in the first year), and thyroxine concentration less than 103 nmol/l at least once during the first year) influenced IQ at age 5. CONCLUSIONS--Despite early treatment in congenital hypothyroidism the disease severity has a threshold effect on brain development, probably determined prenatally. The 55% of infants with more severe disease continue to show clinically significant intellectual impairment; infants with milder disease show no such impairment. The findings predict that 10% of early treated infants with severe hypothyroidism, compared with around 40% of those who presented with symptoms in the period before screening began, are likely to require special education.

BACKGROUND:

The aim of this study was to compare the usefulness of ultrasonography and scintigraphy in diagnosing the etiology of primary congenital hypothyroidism (CH).

METHODS:

The newborns that were examined by both thyroid scintigraphy and ultrasonography during CH screening program in Isfahan were included in this study. The ultrasonographic findings were compared with the scintigraphic findings and the sensitivity and specificity of the ultrasonography was determined.

RESULTS:

During this study, 102 CH newborns were studied. According to the ultrasonographic results, 61.8%, 26.5%, 2.9% and 8.8% of them had normal thyroid gland, agenesia, ectopia and hypoplasia, respectively, and according to scintigraphic results, 55.9%, 35.3% and 8.8% of them had normal thyroid gland, agenesia and ectopia, respectively. Ultrasound detected sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratio were 77%, 92%, 89%, 84%, 9.6 and 0.25, respectively. The sensitivity and specificity of ultrasonography compared with thyroid scintigraphy in diagnosis of thyroid gland ectopia was 33% and 100%, respectively.

CONCLUSIONS:

Though thyroid ultrasonography failed to diagnose 67% of ectopic cases and nonfunctioning thyroid gland, it had the ability to determine the anatomy of thyroid gland. So, considering some limitations of scintigraphy, we concluded that ultrasonography is a relatively appropriate imaging tool for diagnosing CH etiologies, especially in the initial phase of CH screening.

Background

The use of neonatal screening for cystic fibrosis is widely debated in the United Kingdom and elsewhere, but the evidence available to inform policy is limited. This paper explores the cost-effectiveness of adding screening for cystic fibrosis to an existing routine neonatal screening programme for congenital hypothyroidism and phenylketonuria, under alternative scenarios and assumptions.

Methods

The study is based on a decision model comparing screening to no screening in terms of a number of outcome measures, including diagnosis of cystic fibrosis, life-time treatment costs, life years and QALYs gained. The setting is a hypothetical UK health region without an existing neonatal screening programme for cystic fibrosis.

Results

Under initial assumptions, neonatal screening (using an immunoreactive trypsin/DNA two stage screening protocol) costs £5,387 per infant diagnosed, or £1.83 per infant screened (1998 costs). Neonatal screening for cystic fibrosis produces an incremental cost-effectiveness of £6,864 per QALY gained, in our base case scenario (an assumed benefit of a 6 month delay in the emergence of symptoms). A difference of 11 months or more in the emergence of symptoms (and mean survival) means neonatal screening is both less costly and produces better outcomes than no screening.

Conclusion

Neonatal screening is expensive as a method of diagnosis. Neonatal screening may be a cost-effective intervention if the hypothesised delays in the onset of symptoms are confirmed. Implementing both antenatal and neonatal screening would undermine potential economic benefits, since a reduction in the birth incidence of cystic fibrosis would reduce the cost-effectiveness of neonatal screening.

Objectives:

Hepatitis C virus (HCV) is the major cause of post-transfusion hepatitis infection (PTH). Patients with thalassemia major are at high risk of hepatitis C due to the blood transfusion from donors infected by HCV. The aim of this study was to detect the prevalence of anti-HCV antibodies and risk factors in multitransfused thalassemic patients in Isfahan-Iran to establish more preventive strategies.

Methods:

This study was conducted to assess the patients with beta-thalassemia in Isfahan hospitals during 1996-2011 for HCV infection. A structured interview questionnaire was developed by the trained researcher to collect the demographic and risk factors. Statistical analysis was done by Chi-square test, Mann-Withney and multiple logistic regressions using SPSS software, version 15.

Results:

466 patients with major thalassemia participated in this study. The mean age of patients was 17.46 ± 8.3. Two hundred and seventy (58.3%) and 193 (41.7%) of participants were male and female, respectively. The prevalence of HCV was estimated 8% among thalassemia patients. History of surgery, history of dental procedure, number of units transfused per month, number of transfusion per month and duration of transfusion had significant association with HCV seropositivity in univariate analysis. There were no statistical significant risk factors for HCV seropositivity in multiple logistic regression models.

Conclusions:

Our findings revealed that blood transfusion was the main risk factors for HCV infection among beta-thalassemic patients. Therefore, more blood donor screening programs and effective screening techniques are needed to prevent transmission of HCV infection among beta-thalassemic patients.

Background

Thyroid hormone treatment in children with congenital hypothyroidism can prevent intellectual disability. Guidelines recommend that children diagnosed with congenital hypothyroidism through newborn screening remain on treatment to at least 3 years of age, after which a trial off therapy can determine which children have transient hypothyroidism. The purpose of this study was to describe the rate at which children with congenital hypothyroidism in the United States discontinue thyroid hormone treatment in early childhood.

Methods

Retrospective analysis of the 2002-2006 MarketScan® Commercial Claims and Encounters research databases and the 2001-2005 MarketScan Multi-State Medicaid databases. Children were classified as having congenital hypothyroidism based on billing codes and having filled a prescription for thyroid hormone treatment. Kaplan-Meier curve analysis was used to determine discontinuation rates.

Results

There were a total of 412 Medicaid-enrolled children and 292 privately-insured children with presumed congenital hypothyroidism included in this study. The overall birth prevalence of congenital hypothyroidism across both datasets was about 1 per 2,300. By 36 months, the percentage who had discontinued thyroid replacement treatment was 38% (95% Confidence Interval: 32%-44%). Medicaid-enrolled children had a more rapid decline in the first 24 months of treatment compared to those with private insurance (P = 0.02).

Conclusions

More than one-third of children treated for congenital hypothyroidism discontinued treatment within 36 months, which is inconsistent with current guidelines. It is not known how many of these children required continued treatment or experience adverse effects from discontinuation. These findings emphasize the critical need for follow-up systems to monitor the outcome of newborn screening.

Dyshormonogenesis is an uncommon cause of congenital hypothyroidism. The most common abnormality is absent or insufficient thyroid peroxidase enzyme. Maternal intake of antithyroid drug can also lead to elevated thyroid stimulating hormone (TSH) in a neonate, albeit the scenario is temporary. We report one such interesting case where a clinically euthyroid neonate borne to a mother on antithyroid drug presents on 12th day of life with reports of elevated TSH and increased tracer uptake in 99mTc thyroid scan. Disproportionately high TSH in comparison to low maternal antithyroid drug dosage and further elevation of TSH after stopping mother's antithyroid drugs ruled out maternal antithyroid drug-induced congenital hypothyroidism in the baby. Early institution of therapy in these patients can prevent mental retardation and other features of hypothyroidism.

Radioactive iodine (RAI) is used effectively in the treatment of hyperthyroidism and thyroid cancer, but it is contraindicated during pregnancy. RAI treatment during pregnancy can lead to fetal hypothyroidism, mental retardation and increased malignancy risk in the infant. Pregnancy tests must be performed before treatment in all women of reproductive age. However, at times, RAI is being used before ruling out pregnancy.

We herein present a male newborn infant with congenital hypothyroidism whose mother was given a three-week course of methimazole therapy for her multiple hyperactive nodules and subsequently received 20 mCi RAI during the 12th week of her pregnancy. The patient was referred to our neonatology unit at age two weeks when his thyrotropin (TSH) level was reported to be high in the neonatal screening test. Physical examination was normal. Laboratory investigations revealed hypothyroidism (free triiodothyronine 1.55 pg/mL, free thyroxine 2.9 pg/mL, TSH 452 mU/L, thyroglobulin 20.1 ng/mL). The thyroid gland could not be visualized by ultrasonography. L-thyroxine treatment was initiated.

Conflict of interest:None declared.

All the Italian Centres in charge of screening, diagnosis, and follow-up of infants with congenital hypothyroidism participate in the Italian National Registry of affected infants, which performs the nationwide surveillance of the disease. It was established in 1987 as a program of the Health Ministry and is coordinated by the Istituto Superiore di Sanità. The early diagnosis performed by the nationwide newborn screening programme, the prompt treatment and the appropriate clinical management of the patients carried out by the Follow-up Centres, and the surveillance of the disease performed by the National Register of infants with congenital hypothyroidism are the components of an integrated approach to the disease which has been successfully established in our country.

The aim of the Register is to monitor efficiency and effectiveness of neonatal screening, to provide disease surveillance and to allow identification of possible aetiological risk factors for the disease. During the past twenty years the active and continuous collaboration between the Register and the Italian Screening and Follow up Centres for Congenital Hypothyroidism allowed to perform a standardization of screening procedures and considerable improvements in the time at starting treatment and in the dose of therapy. Furthermore, the large amount and the high quality of information collected in the Register provided a unique opportunity for research into the disease. This because data collected in the Register are highly representative as referred to the entire Italian population with congenital hypothyroidism. The results derived from the epidemiological studies performed in these years, by using the Register database, contributed to deepen the knowledge of congenital hypothyroidism, to start identifying the most important risk factors for the disease, and to orient molecular studies aimed at identifying new genes involved in the aetiology of this condition.

The occurrence of neurological symptoms and developmental delay in patients affected by congenital hypothyroidism (CH) has been attributed to the lack of thyroid hormone in the developing CNS. Accordingly, after the introduction of neonatal screening programs for CH, which allowed early and adequate treatment, an almost normal outcome for most CH patients could be achieved. However, a few patients did not reach this favorable outcome despite early and adequate treatment. Here we describe five patients with variable degrees of CH who suffered from choreoathetosis, muscular hypotonia, and pulmonary problems, an association of symptoms that had not been described before this study. Since this clinical picture matched the phenotype of mice targeted for deletion of the transcription factor gene Nkx2-1, we investigated the human NKX2-1 gene in these five patients. We found heterozygous loss of function mutations in each of these five patients, e.g., one complete gene deletion, one missense mutation (G2626T), and three nonsense mutations (2595insGG, C2519A, C1302A). Therefore, the unfavorable outcome in patients with CH, especially those with choreoathetosis and pulmonary symptoms, can be explained by mutations in the NKX2-1 gene rather than by hypothyroidism. Moreover, the association of symptoms in the patients with NKX2-1 mutations points to an important role of human NKX2-1 in the development and function of thyroid, basal ganglia, and lung, as already described for rodents.

Background. For unknown reasons, the prevalence of thyroid autoimmune disorders is higher in patients with Down's syndrome than in the general population. The present case strongly supports a recent evaluation of propagating screening for thyroid disease in this group of patients to assure early diagnosis of hypothyroidism. Methods. In a 25-year-old man diagnosed with Down's syndrome, clinical manifestations of hypothyroidism were lacking, but profound biochemical abnormalities were found with particularly high levels of thyroid stimulating hormone (TSH). Antigenic properties of TSH were characterized using a panel of anti-TSH antibodies. Results. Technical problems not infrequently associated with TSH measurements are convincingly ruled out. Antigenic characterization of the patient's circulating TSH revealed circulating forms of TSH different from pituitary TSH which closely resembled TSH recombinant human hormone. Conclusions. It appears counterintuitive that the bioactivity of TSH decreases in the hypothyroid state as higher bioactivity of TSH is anticipated in hypothyroidism promoted by an increased hypothalamic TRH drive. In contrast, diminished negative thyroid hormone feedback will enhance posttranslational glycosylation of TSH subunits and increase sialylation of the carbohydrate side chains. Both exert a negative effect on TSH bioactivity, only compensated by the very high levels of the hormone as in the present case.

All patients identified in the neonatal screening programme for congenital hypothyroidism in Northern Ireland between 1983 and 1993 were reviewed. 131 infants were recalled because of TSH elevation of whom 85 proved to have true permanent congenital hypothyroidism, while 44 had transient TSH elevation and 2 cases died before the diagnosis could be confirmed. TSH elevation at presentation was milder in the transient group and these infants were more likely to be unwell and/or suffering from congenital malformation.