Thyroid Stimulating Hormone Level at Diagnosis as a Predictor of Persistent Subclinical Hypothyroidism in Children with Down Syndrome

Objective

To evaluate subclinical hypothyroidism in a cohort of children with Down syndrome and identify a TSH level at the time of diagnosis to predict persistent hypothyroidism.

Methods

192 children (age <3 years) with Down syndrome, registered in the Genetic Clinic of a referral tertiary care Hospital from 2010 to 2015 were evaluated with thyroid function test at initial visits and subsequently based on standard protocol. Children with subclinical hypothyroidism were evaluated at 3 years of age after discontinuation of thyroxine for 3 months.

Results

47 (24.5%) children had elevated TSH and among them 43 (91.5%) had subclinical hypothyroidism. Among the subclinical hypothyroidism group, 25 (73.5%) had transient hypothyroidism and 9 (26.5%) persistent hypothyroidism. Initial TSH level at the time of diagnosis was higher in persistent hypothyroidism group as compared to transient group (P= 0.003). The best cut-off level for prediction of persistent hypothyroidism for initial TSH level was 11.6 mIU/L.

Conclusion

Subclinical hypothyroidism, especially transient, is the commonest form of thyroid dysfunction in children with Down syndrome. The initial TSH level may help to predict the possibility of persistence of hypothyroidism.

     

Thyroid status of iodine deficient newborn infants living in central region of Turkey: a pilot study

Background

Iodine deficiency (ID) during the fetal and neonatal periods can lead to neonatal hypothyroidism. This study was conducted to evaluate the effect of ID on the thyroid hormone level of newborns living in Turkey.

Methods

Between 1998 and 2013, 71 newborns with a urinary iodine concentration <100 μg/L were recruited into the study. Data on thyroid volume, free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroglobulin (Tg) were collected from all newborns, and on breast milk iodine from their mothers. Infants who were classified as having congenital hypothyroidism (TSH >40 mU/L and fT4 <8.5 pmol/L) were treated with levothyroxine (n=26, T group), while the remaining infants remained untreated (n=45, UT group). Thyroid hormones were subsequently measured 7-14 days later in a sub-sample of both treated and untreated infants.

Results

The average values at the time of admission were as follows [median (min-max)]. fT3: 5.0 (2.8-7.1) pmol/L, fT4: 7.7 (0.13-19.1) pmol/L, TSH: 75 (14-426) mU/L, Tg: 464 (226-1100) ng/mL, urinary iodine concentration (UIC): 30 (0-61) μg/L, breast milk iodine levels: 21 (10-150) μg/L, thyroid ultrasound (USG): 1.10 (0.24-1.95) mL for the T group; and fT3: 5.7 (1.7-12.7) pmol/L, fT4: 16.2 (9.9-33.5) pmol/L, TSH: 5.4 (0.63-41.8) mU/L, Tg: 171 (15-2124) ng/mL, UIC: 39 (0-90) μg/L, breast milk iodine levels: 47 (10-120) μg/L, thyroid USG: 0.75 (0.35-1.72) mL for the UT group. A significant difference was found between groups in respect to fT3, fT4, TSH and Tg levels. No significant difference in thyroid ultrasonography, UIC, and breast milk iodine levels was found between the two groups. The Tg levels of 50 out of 71 patients were measured, 40 (80%) of whom had Tg levels above the normal range (101 ng/mL).

Conclusions

In our country, despite the use of iodized salt, congenital hypothyroidism due to ID remains a problem. The Tg level of newborns can be used as a good indicator of ID.

     

Cord blood thyroid stimulating hormone level — interpretation in light of perinatal factors

Objectives

To study the influence of perinatal factors on cord blood TSH (CB TSH) levels.

Design

Cross-sectional study.

Setting

Tertiary care private hospital.

Methods

CB TSH levels were measured in 952 live-born infants using electrochemiluminescence immunoassay. The effect of perinatal factors on the CB TSH levels was analyzed statistically.

Results

The median CB-TSH was 8.75 microIU/mL (IQR = 6.475–12.82) with 11.5% neonates having values more than 20. CB TSH was significantly raised in first order neonates (P <0.01) and in babies delivered by assisted vaginal delivery and normal delivery (P <0.01). Neonates who had fetal distress or nonprogress of labour had significantly higher CB TSH than those who were delivered by elective caesarean section. Requirement of resuscitation beyond the initial steps and low Apgar scores at 1 minute also resulted in significantly raised CB TSH (both P <0.01). Maternal hypothyroidism, maternal hypertension and neonates’ weight appropriateness for gestation, gestational age and birth weight did not have significant effect.

Conclusions

The incidence of high cord blood TSH (>20 microU/mL) is 11.45%. On multivariate analysis, requirement of resuscitation, mode of delivery and fetal distress as indication for LSCS were significant factors affecting CB TSH values. Hence, these values need to be interpreted in light of perinatal factors.     

Prediction of Transient or Permanent Congenital Hypothyroidism from Initial Thyroid Stimulating Hormone Levels

Objective

To identify factors that discriminate between transient and permanent congenital hypothyroidism.

Methods

Retrospective evaluation of 58 children with congenital hypothyroidism and eutopic thyroid gland. Gender, gestational age, birth weight, TSH and serum thyroxine levels at diagnosis and L-thyroxine dose at 12 and 24 months of age were analyzed.

Results

Median (IQR) initial TSH levels were 73.3 (276.5) μIU/mL in permanent hypothyroidism and 24.24 (52.7) μU/mL in transient hypothyroidism (P =0.0132). The optimum cut-off value of initial TSH to predict transient hypothyroidism was 90 μIU/mL. Mean (SD) L-thyroxine doses at 24 months of age were 2.64 (0.98) μg/kg/day in permanent hypothyroidism and 1.91 (0.65) μg/kg/day in transient hypothyroidism. Requirement of Lthyroxine dose at 24 months of ≤0.94 μg/kg/day had the highest sensitivity (100%) to predict transient hypothyroidism.

Conclusions

L-thyroxine doses at 24 months can predict transient hypothyroidism in patients with eutopic thyroid gland earlier than at 36 months.

     

Thyroid function in children with growth hormone deficiency,either idiopathic or caused by diseases of the central nervous system

Thyroid function was assessed in thirty two patients with growth hormone deficiency (GHD) by clinical examination and by measurement of T₄-levels, free T₄-indices, basal TSH values and TSH responses to TRH (100 g/m²). Sixteen patients (50%) were hypothyroid. In thirteen patients, the endocrine disorders were considered to be of hypothalamic origin. Ten of them showed prolonged responses to TRH and in the other three the responses were exaggerated. In three patients hypothyroidism was due to a primary pituitary disorder. Sixteen patients were euthyroid although three of them showed impaired TSH responses. In the cases with idiopathic hypopituitarism (n=20) there was a high incidence of abnormal births in the children with additional hypothalamic hypothyroidism, but not in the euthyroid patients. It is concluded that in patients with previous breech or vacuum extraction delivery, growth hormone deficiency when combined with hypothalamic hypothyroidism may be due to birth trauma.     

Evaluation of Congenital Hypothyroidism in Fars Province,Iran

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.     

Hypothyroidism in neonates post-iodinated contrast media: a systematic review

Aim: To determine if neonates exposed to iodinated contrast media are at risk of hypothyroidism. Methods: A systematic review was conducted by searching electronic databases (e.g. MEDLINE), contacting experts and scanning reference lists. Studies examining the effects of contrast media on neonatal thyroid function were included. Two reviewers independently screened the literature and assessed the risk of bias, while one reviewer abstracted data. Results: Eleven studies were included; nine studies directly examined the risk of hypothyroidism (n = 182 neonates exposed to contrast media). All were highly affected by bias. In the three studies including term infants, one showed a trend towards increased thyroid‐stimulating hormone (TSH) and decreased free thyroxine (FT4) among exposed groups. Six of 72 (8.3%) term infants exposed were treated for hypothyroidism. In studies of premature infants, there was a trend towards increased TSH (n = 3/7 studies), lower total thyroxine (n = 1), decreased triidothyronine and FT4 (n = 3) and hypothyroidism (n = 5). Twenty of 110 (18.2%) premature infants exposed were treated for hypothyroidism. Conclusion: Hospitalized neonates exposed to iodinated contrast media are at risk for abnormal thyroid function and development of hypothyroidism. Premature infants might be at increased risk. Well‐controlled studies are required to replicate our findings because the included studies were highly affected by bias.     

Does Congenital Hypothyroidism Have Different Etiologies in Iran?

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.     

Normative Data for Thyroid Stimulating Hormone for Screening of Congenital Hypothyroidism

Objective

To generate normative data for thyroid stimulating hormone (TSH) levels in heel prick samples collected from newborns from 24 h to 7 d of age.

Methods

Five regional laboratories were designated as the testing laboratories. Dried blood spots (DBS) from babies (> or?=?34 wk of gestation) were collected by heel prick at least after 24 h and within seven days after birth. TSH estimation was done using time resolved fluoroimmunoassay. Values above 20mIU/L were labelled as presumptive positive. Hour interval specific normative data was categorized at 6 h intervals. Another category placed was division into 24–72 h category, 73–96 h and 99–168 h. Percentile charts were calculated across these specified intervals.

Results

Samples analysed were 104,006 collected cumulatively from the 5 centers. Of the total samples analysed for TSH, 92.8% had values less than 5 mIU/l. When TSH values were interpreted with respect to time, a steady decrease with time was observed. Of the babies' samples, 48,839 were collected between 24 and 48 h, 23,983 between 49 to 72 h and 30,883 were collected after 72 h. The mean TSH concentration demonstrated a steady decline from 24 h to 168 h. It is apparent that 10 mIU/l is the 97.5th percentile value even when corrected for gender, birth weight and age at sampling. Thus 10 mIU/l seems to be the right cutoff beyond which a second sample should be sought.

Conclusions

This is the largest series reported with a broader population mix with representations of both urban (including slums) as well as a rural population. As this study excluded preterm babies, the utility of cut offs generated is not applicable to this subset and also to critically sick neonates. However, this study gives a true representation of the normative values for majority of the newborns born at term with weight appropriate for the gestation.

     

Transient secondary hypothyroidism and thyroxine binding globulin deficiency in leukemic children during polychemotherapy: An effect of L-asparaginase

Recently it has been observed that L-asparaginase causes transient thyroxine binding globulin (TBG) deficiency in adults. In the present study we investigated the influence of L-asparaginase on the pituitary-thyroid axis and on the synthesis of TBG. 14 children with acute lymphoblastic leukemia were treated with a combination of L-asparaginase, vincristine, prednisone and daunomycin for remission induction. Thyroid function was monitored by measuring total T₄, free T₄, total T₃, TSH and TBG with specific radioimmunoassays before, during and after treatment. Within 3 weeks of L-asparaginase therapy total T₄ fell significantly from 10.7±1.6 to 2.9±1.8 g/100 ml, free T₄ from 1.77±0.4 to 0.94±0.35 ng/100 ml, total T₃ from 0.99±0.23 to 0.35±0.2 ng/ml and TBG from 29.4±3.6 to 8.0±3.8 g/ml. Basal TSH values tinuation of L-asparaginase, but following further treatment with other antileukemic agents, all values became normal within 2–4 weeks. In 6 patients with hypothyroid free T₄ values TRH induced TSH release was totally blocked during L-asparaginase therapy. Our data clearly demonstrated that L-asparaginase caused a transient TBG deficiency. Total T₄ and T₃ were in the hypothyroid range because of low TBG concentrations. In addition to TBG deficiency transient, secondary hypothyroidism occurred in approximately 40–50% of all patients treated with L-asparaginase. These alterations were most likely caused by drug induced inhibition of protein synthesis. Under certain circumstances thyroid hormone replacement might be life-saving in severely ill patients suffering from transient, drug induced hypothyroidism.Presented in part at the 19th Meeting of the European Society for Pediatric Endocrinology, August 31–September 3, 1980, Bergamo/Italy     

Evaluation of the pituitary-thyroidal axis in newborns undergoing exchange transfusion

To evaluate whether the hypothyroxinaemia, previously noted in hyperbilirubinaemic newborns immediately after exchange transfusion for Rh or AB0 incompatibility, was due to impairment in the secretion of thyroid stimulating hormone (TSH) by the pituitary, we studied the thyroid hormone response to thyrotropin releasing hormone (TRH) and compared this response to that seen in a control population of healthy neonates. All infants studied responded with a brisk TSH increase; 30 min after TRH injection the mean TSH concentration of the hyperbilirubinaemic patients was 37 U/ml, ten times their basal level, which was not different from the value noted in the control population.No significant change in total thyroxine (T₄), 3,5,3 triiodothyronine (T₃), free thyroxine (FT₄) or 3,3,5 triiodothyronine (rT₃), (FT₄) or (rT₃) was noted after TRH administration in either group of neonates. In addition the effect of exchange transfusion on the thyroid axis of hyperbilirubinaemic newborns was evaluated. Before the exchange transfusion TSH, T₄, rT₃, T₃ and FT₄ levels were higher in the hyperbilirubinaemic newborns than in donor blood; immediately post-exchange transfusion TSH and T₄ concentrations of the hyperbilirubinaemic neonates decreased significantly and remained significantly below pre-exchange values 30h later.Newborns undergoing an exchange transfusion respond appropriately to TRH stimulation and seem to have an intact pituitary-thyroidal axis.Abbreviations T₄ total thyroxine - FT₄ free thyroxine - T₃ (Ru) T₃ resin uptake - T₃ 3,5,3 triiodothyronine - rT₃ 3,3,5triiodothyronine - TSH thyroid stimulating hormone - TRH thyrotropin releasing hormone - RIA radioimmunoassay     

Subclinical Hypothyroidism in Grown-Up Congenital Heart Disease Patients

Subclinical hypothyroidism usually is asymptomatic, but it can be associated with various adverse cardiologic outcomes. With the objective of gaining insight into the role of thyroid-stimulating hormone (TSH) in congenital heart abnormalities, this study measured serum TSH concentrations in different subtypes of grown-up congenital heart disease (GUCHD) patients. Serum TSH (reference range, 0.34–5.6 mIU/L), creatinine, cholesterol, C-reactive protein (CRP), N-terminal proB-type natriuretic peptide (NT-pro-BNP), and 24-h proteinuria were measured in 249 GUCHD patients. Of 24 GUCHD patients (9.6 %) with a TSH level higher than 5.6 mUI/L, nine were cyanotic (37.5 %) and seven (29.1 %) had Down syndrome. The GUCHD patients with serum TSH exceeding 5.6 mIU/L had a significantly higher level of serum NT-pro-BNP (195.1 [0.28; 5,280.3] vs 57.6 [0.00; 929.8]; p = 0.001) and CRP (0.30 [0.06; 1.87] vs 0.16 [0.00; 1.40]; p = 0.011] than those with a TSH level of 5.6 mIU/L or lower. No significant differences were found in serum creatinine, lipids, or 24-h proteinuria between the two groups. The T4 concentrations in the GUCHD patients with TSH exceeding 5.6 mIU/L were within the normal range (0.89 ± 0.23 ng/dL). In the multivariate analysis, cyanosis (odds ratio [OR], 6,399; 95 % confidence interval [CI] 2,296–17,830; p < 0.001), Down syndrome (OR, 6,208; 95 % CI, 1,963–19,636; p = 0.002), and NT-pro-BNP concentrations (OR, 1,001; 95 % CI, 1,000–1,002; p < 0.026) proved to be risk factors for TSH levels higher than 5.6 mIU/L. Because subclinical hypothyroidism entails a cardiovascular risk, the authors postulate that TSH screening should be included in the routine follow-up evaluation of GUCHD patients with cyanosis or Down syndrome.     

Non-autoimmune subclinical and overt hypothyroidism in idiopathic steroid-resistant nephrotic syndrome in children

Objective

To evaluate the frequency of non-autoimmune subclinical and overt hypothyroidism in children with idiopathic steroid-resistant nephrotic syndrome (SRNS).

Methods

This cross-sectional study recruited 30 children (age 1–18 y) with idiopathic SRNS; and 30 healthy controls. Serum T3, T4 and TSH were performed in cases as well as controls. Anti-thyroid peroxidase and anti-thyroglobulin antibody tests were performed in all cases.

Results

Non-autoimmune subclinical or overt hypothyroidism was detected in 10 out of 30 children with idiopathic SRNS; 2 had overt hypothyroidism, while 8 patients had subclinical hypothyroidism. Children with SRNS had a mean (SD) TSH value 4.55 (4.64) mIU/L that was higher as compared to controls (1.88 (1.04) mIU/L) (P<0.01). Focal segmental glomerulosclerosis (FSGS) was the commonest histopathological condition, seen in 13 (43.3%). Children with overt hypothyroidism (2 cases) and grade III subclinical hypothyroidism (1 case) were subsequently started on levothyroxine therapy.

Conclusions

The prevalence of subclinical and overt hypothyroidism seems to be high in idiopathic SRNS, with almost one-third of children having overt or subclinical non-autoimmune hypothyroidism.

     

Neonatal screening for hypothyroidism in Greece

One year's experience in screening for congenital hypothyroidism in Greece is reported. Thyroidstimulating hormone (TSH) determination by a radioimmunoassay on dried blood spots was selected as the screening method. During the first year of screening 75,879 newborn infants were tested from Guthrie blood spots taken on the 5th day of life. Eighteen cases of primary congenital hypothyroidism with serum TSH levels over 100 IU/ml were detected, giving an incidence of 1:4200. One case had already been diagnosed clinically. Replacement treatment was started between the 22nd and the 50th days of life.     

Congenital Hypothyroidism Screening Program in Iran; a Systematic Review and Metaanalysis

Objective:

Unrecognized congenital hypothyroidism (CH) leads to mental retardation. Newborn screening and thyroid therapy started within 2 weeks of age can normalize cognitive development. In this systematic review, the local results of the national CH screening program in different provinces in Iran are reviewed and evaluated.

Methods:

Literature on the CH screening, the national databases including SID, Medlib, Iran Medex, Magiran as well as international databases including PubMed/Medline, ISI Web of Knowledge and web of science, EMBASE, SCOPUS and Google Scholar. Appraisal was guided by a checklist assessing clarity of aims and research questions. The 95% confidence intervals were calculated by I-square models. Meta regression was introduced to explore the heterogeneity between studies.

Findings:

We identified 25 samples including 1425124 neonates in our country. Data were Meta analyzed using random-effects models, and we found a TSH levels of 19633 babies in the first sampling were greater than the cut-off level (TSH ≥5mIU/L). The pooled recall rate was 0.014 (95 % CI: 0.013 – 0.015). According to Meta analysis the overall incidence of CH was 2/1000 (95% CI: .002 – .002). The incidence of CH did not appear to be increasing over time (P=0.08).

Conclusion:

Considering TSH ≥5mIU/L as a cut-off point for recalling neonates and low positive predictive value (14%) of this point shows that more investigation and research is needed for establishing accurate level of TSH as a criterion for recalling patients.     

Newborn screening for congenital hypothyroidism,galactosemia and biotinidase deficiency in Uttar Pradesh,India

Objective

To assess feasibility and recall rates for newborn screening for congenital hypothyroidism, galactosemia and biotinidase deficiency in a predominantly rural and inner city population in and around the City of Lucknow in Uttar Pradesh, India.

Design

Prospective observational study.

Setting

Two tertiary-care and 5 district hospitals in and around Lucknow.

Participants

All babies born in above hospitals during the study period.

Methods

Heel prick samples were collected after 24 hours of life. Dried blood spot TSH, total galactose and biotinidase were assayed by immunofluorometry. Age related cut-offs were applied for recall for TSH. For galactosemia and biotinidase deficiency, manufacturer-suggested recall cut-offs used initially were modified after analysis of initial data.

Main outcome measure

Recall rate for hypothyroidism, galactosemia and biotinidase deficiency.

Results

Screening was carried out for 13426 newborns, 73% of all deliveries. Eighty-five percent of those recalled for confirmatory sampling responded. Using fixed TSH cut off of 20 mIU/L yielded high recall rate of 1.39%, which decreased to 0.84% with use of age-related cut-offs. Mean TSH was higher in males, and in low birth weight and vaginally delivered babies. Eleven babies had congenital hypothyroidism. Recall rates with modified cut-offs for galactosemia and biotinidase deficiency were 0.32% and 0.16%, respectively.

Conclusion

An outreach program for newborn screening can be successfully carried out in similar socio-cultural settings in India. For hypothyroidism, the high recall rate due to early discharge was addressed by age-related cut-offs.     

Growth response to growth hormone therapy following craniospinal irradiation

Nineteen (12 male, 7 female) children, who have received craniospinal irradiation for the treatment of a brain tumour distant from the hypothalamic-pituitary axis, resulting in growth hormone (GH) deficiency (CS-PRGHD), have been treated with GH. Eight have completed growth. Comparison has been made with the growth of seven untreated children, whose heights and growth rates at presentation were normal despite GH deficiency secondary to irradiation. GH produced a significant increase in growth velocity over the first 3 years' treatment in CS-PRGHD patients with a mean first year increment of 3 cm/year. Patients, treated to completion of growth, showed a significant increase in leg length standard deviation (SD) score (SDS+0.2) compared to that of the untreated (SDS–0.9) (P<0.05). Stitting height SD scores decreased irrespective of GH therapy (by -1.7 for the treated and -2.2 for the untreated). The onset of puberty in the irradiated patients occurred at a mean bone age of 10.7 years in males and 9.9 years in females. This limited the time available for GH therapy. These factors resulted in a decrease in standing height SDS of 0.9 at completion of GH therapy in CS-PRGHD, but a decrease of 1.7 in those not treated with GH. Thus GH therapy failed to induce catch-up growth in irradiated patients, but it did prevent further loss of adult stature, with a mean final height SD score of -3.4 in CS-PRGHD patients.Abbreviations GH growth hormone - CS-PRGHD post craniospinal irradiation growth hormone deficiency - change in - SDS standard deviation score - ALL acute lymphatic leukaemia - IGHD isolated growth hormone deficiency - C-PRGHD post cranial irradiation growth hormone deficiency - FSH follicle stimulating hormone - LH luteinising hormone - BA bone age - TSH thyroid stimulating hormone - CA chronological age     

Thyroid dysfunction and developmental anomalies in first degree relatives of children with thyroid dysgenesis

Background

Familial clustering in patients with permanent congenital hypothyroidism (CH) caused by thyroid dysgenesis (TD) has been reported in developed countries. There is no information on familial TD from developing countries.

Methods

A total of 312 first degree relatives belonging to 80 families of children with TD (group 1) and 40 families of age-matched normal children (group 2) were screened by thyroid ultrasonography, serum total thyroxine (T4) and thyroid stimulating hormone (TSH).

Results

Thyroid scintigraphy revealed agenesis in 78.7% of the patients, ectopic gland in 15%, and hypoplasia in 6.2%. The mean thyroid volumes were similar in parents and siblings of both groups. Eight (10.6%) mothers in group 1 were identified to have thyroid hypoplasia as compared with none in group 2 (P=0.03). Serum TSH was significantly higher in group 1 than in group 2 (P=0.004). Sixteen (7.8%) subjects (6 mothers, 5 fathers, and 5 siblings) in group 1 were found to have subclinical hypothyroidism as compared to none in group 2 (P<0.05). Four families were identified to have thyroid developmental anomalies and abnormal thyroid functions accounting for 5% of cases of familial TD in our cohort.

Conclusion

Thyroid developmental anomalies and thyroid function abnormalities are more frequent in first degree relatives of children with TD as compared with a control population. These findings suggest that possibly there is a genetic component of TD in Indian patients.

     

Circulating thyroid antibodies and thyroid function studies in children and adolescents with insulin-dependent diabetes mellitus

Significant high titres (1400–125,600) of circulating thoroid microsomal antibodies (MCHA) were found in the sera of 5 out of 59 non-ketoacidotic, insulin-dependent diabetic (IDDM) patients (mean age 14.5 years). Among these five patients (four females, one male), all of whom were over 11 years, two also had thyroglobulin antibodies. Increased thyrotropin (TSH) response to TRH was found in 3/5 MCHA positive patients and in 3/54 without circulating MCHA. Serum thyroxine (T₄) and free T₄ (FT₄) average values were significantly lower (P<0.01 and P<0.001) in diabetics (7.1±1.8g/dl and 10.2±3.1 pg/ml, x±SD) as compared to normal sex and age matched controls (8.9±1.9 g/dl and 12.2±2.2 pg/ml, respectively). T₄ and FT₄ values were inversely related to the duration of the disease. Subnormal T₄ values were found in six (five females and one male) patients, four of whom had subnormal FT₄ values. No patient had low triiodothyronine (T₃) and high reverse T₃ (rT₃) values, i.e. none displayed the biochemical pattern of the low T₃ syndrome described with ketoacidotic status. This indicates also a satisfactory compensation of IDDM in all the patients. At the time of study no patient (including also those with circulating MCHA and TGHA and with TSH hyper-response to TRH) showed either thyroid size enlargement or clinical features of thyroid dysfunction including impaired growth and bone age retardation.Abbreviations MCHA thyroid microsomal antibodies - IDDM insulin-dependent diabetes mellitus - TSH thyrotropin - T₄ serum thyroxine - FT₄ free T₄ - T₃ triiodo thyronine - FT₃ free T₃ - rT₃ reverse T₃ - TGHA thyroglobulin antibodies - TRH thyrotrophin releasing hormone     

Relation of thyroid hormone levels with fluid-resistant shock among preterm septicemic neonates

Objective

To compare thyroid hormone levels between septicemic preterm neonates with and without shock.

Methods

Preterm septicemic infants with shock constituted Group A (n=36) and those without shock constituted Group B, with groups matched (1:1) for gestation and postnatal age. Those with maternal thyroid disorders, thyrotropic medication and life expectancy <12 hours were excluded. We compared serum tri-iodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) between the groups by univariate and multivariate (adjusting for SNAPPE-II) analysis.

Results

Median (IQR) TSH was significantly lower in Group A [1.39 (0.83,3.48)] vs Group B [5.1 (2.32,7.19)] mmol/dL (P<0.001). Serum T3 and T4 were also lower in Group A (P<0.001). On multivariate analysis, none of these measures were independently associated with septic shock.

Conclusions

Thyroid hormone levels do not independently predict presence of shock among septic preterms.