Permanent and transient congenital hypothyroidism in preterm infants

Aim: Transient fluctuations in thyroid function are well recognized in preterm infants. We wanted to assess TSH variation in babies with transient and permanent congenital hypothyroidism (CHT). Methods: Whole bloodspot TSH data in preterm infants (<35 weeks; 2005–2010) were assessed, and infants with bloodspot TSH values >6 mU/L identified. Permanent CHT was defined as a requirement for thyroxine beyond 3 years of age. Results: A first TSH sample was obtained from 5518 infants (median gestational age, 32 w; range, 22–35), with a second sample obtained from 5134 infants (median gestational age, 32 w; range, 22–35). Five infants had raised TSH concentrations on both occasions. Three of the five infants had a serum TSH >80 mU/L on second screen but two came off thyroxine beyond 3 years of age. All preterm babies with permanent or transient hypothyroidism were detected by the first TSH cut‐off of 6 mU/L. Only one infant with a birth weight <1500 g remains on thyroxine treatment beyond 2 years of age. Conclusions: The incidence of permanent CHT in preterm infants is similar to term infants. Profound abnormalities of thyroid function can occur in preterm babies with transient hypothyroidism but both categories of hypothyroidism can be detected by a ‘once‐only’ TSH screening strategy with a relatively low cut‐off.     

Pituitary-thyroid responsiveness to thyrotropin-releasing hormone in preterm and small-for-gestational age newborns.

A dose of 40 microgram TRH was injected intravenously in 12 preterm (PT) and 15 small-for-gestational age (SGA) babies (with advanced gestational ages) between 5 and 167 hours after birth. Serum-thyrotropin (TSH) was measured prior to and 30 and 180 min after TRH; serum-thyroxine (T4) and serum-triiodothyronine (T3) were measured prior to and 180 min after TRH. The percentage increase in serum-TSH in PT and SGA babies was comparable to that of fullterm newborns. The serum-TSH 30 min after TRH in SGA newborns was significantly correlated to basal TSH values, such a correlation could not be shown in the preterms. One SGA and four PT babies had a repeat TRH-test performed later in infancy: In all but one PT with a gestational age of 27 weeks the TSH rise was lower than in the neonatal period. The thyroid hormone responses after TRH were similar in the two groups of babies. The percentage increase above basal levels were: Median serum-T3 increase about 46% and median serum-T4 increase about 14%. It is concluded that in low-birth-weight newborn babies the pituitary TSH response to exogenous TRH was like that detected in fullterm newborns and more pronounced that later in infancy. The effect of endogenous TSH as measured by thyroid hormone increases was of the same magnitude as observed in fullterms and in adults.     

PITUITARY-THYROID RESPONSIVENESS TO THYROTROPIN-RELEASING HORMONE IN PRETERM AND SMALL-FOR-GESTATIONAL AGE NEWBORNS

Abstract. A dose of 40 μg TRH was injected intravenously in 12 preterm (PT) and 15 small-for-gestational age (SGA) babies (with advanced gestational ages) between 5 and 167 hours after birth. Serum-thyrotropin (TSH) was measured prior to and 30 and 180 min after TRH; serum-thyroxine (T₄) and serum-triiodothyronine (T₃) were measured prior to and 180 min after TRH. The percentage increase in serum-TSH in PT and SGA babies was comparable to that of fullterm newborns. The serum-TSH 30 min after TRH in SGA newborns was significantly correlated to basal TSH values, such a correlation could not be shown in the preterms. One SGA and four PT babies had a repeat TRH-test performed later in infancy: In all but one PT with a gestational age of 27 weeks the TSH rise was lower than in the neonatal period. The thyroid hormone responses after TRH were similar in the two groups of babies. The percentage increase above basal levels were: Median serum-T₃ increase about 46% and median serum-T₄ increase about 14%. It is concluded that in low-birth-weight newborn babies the pituitary TSH response to exogenous TRH was like that detected in fullterm newborns and more pronounced than later in infancy. The effect of endogenous TSH as measured by thyroid hormone increases was of the same magnitude as observed in fullterms and in adults.     

Longitudinal study on thyroid function in patients with thalassemia major

Primary hypothyroidism is one of the most frequent complications observed in patients suffering from thalassemia. We investigated thyroid function in a group of patients attending the Pediatric Department of Cardarelli Hospital in order to determine in how many patients thyroid function worsened during a 12 year-period of follow up. PATIENTS AND MEASUREMENTS: Fifty patients with beta-thalassemia major (27 females and 23 males), mean age 25.7+/-1.4 years, were re-evaluated according to the criteria of Faglia et al. Thyroid dysfunction was defined as follows: overt hypothyroidism (low FT4 and increased TSH levels >10 microU/ml); compensated hypothyroidism (normal FT4, TSH 5-10 microU/ml, and abnormal TRH test); subclinical hypothyroidism (normal FT4, basal TSH 0-5 microU/ml, abnormal TRH test). Correlation with hematological, biochemical and growth parameters was evaluated. RESULTS: Ten out of 50 patients evaluated in a previous study had moved to other centers, and four patients had died from cardiac problems. Thus, 36 patients completed a 12 year-period of follow-up. In 25% of the patients the degree of thyroid dysfunction worsened with different degrees of severity. The prevalence of overt hypothyroidism had risen to 13.9% from 8.4%. No cases of secondary hypothyroidism were observed, and anti-thyroglobulin and anti-thyroperoxidase (TPO) antibody titers were negative in all patients. Five (28%) out of 17 patients with normal thyroid function previously (one female, four male) showed an exaggerated TSH response to a TRH test, with normal serum levels of FT4, and they were classified as having subclinical hypothyroidism; while another patient died of cardiac complications. Four out of twelve patients with previous subclinical hypothyroidism showed worsening with a different degree of severity: two females changed to compensated hypothyroidism, and two males to overt hypothyroidism. Furthermore, two out of six patients with compensated hypothyroidism and one out of four patients with overt hypothyroidism died of cardiac failure. In all patients there was no correlation between serum ferritin levels, blood transfusion, pretransfusion Hb levels and worsening of thyroid function. Echographic data showed features of dishomogeneity of the parenchyma with different degrees of severity in accordance with the criteria of Sostre and Reyes. The highest score was observed in all patients with overt and compensated hypothyroidism. CONCLUSIONS: A slow worsening of thyroid function was observed in 25% of the studied patients and only two of them developed overt hypothyroidism. The echographic pattern seems to be strongly predictive of thyroid dysfunction.     

SERUM LEVELS OF THYROTROPIN, THYROXINE AND TRIIODOTHYRONINE IN FULLTERM, SMALL-FOR-GESTATIONAL AGE AND PRETERM NEWBORN BABIES

Abstract. Simultaneous serum concentrations of TSH, total thyroxine (T₄) and triiodothyronine (T₃) were determined in 93 fullterm (FT), 37 small-for-gestational age (SGA) and 38 preterm (PT) babies with a postnatal age from 2 to 144 hours. In addition, TSH, T₄ and T₃ concentrations were measured in cord sera from 27 FT, 4 SGA and 5 PT babies and in venous blood from 20 mothers at delivery. Cord blood concentrations of TSH were higher and T₄ and T₃ concentrations were lower than seen in the mothers. Serum concentrations of TSH were high during the first day of life followed by a decline. There was no statistically significant difference between serum TSH concentrations of the three groups of newborns. On the 5th day of life no elevated serum TSH values were found in any of the groups (TSH<5mU/l). Serum concentrations of thyroid hormones increased after birth and reached maximum levels within 24 hours in all groups. The relative increases above cord level were of the same magnitude in the newborns: Two times for serum T₄ and six times for serum T₃. The thyroid hormone concentrations in blood samples from FT babies decreased from the second day of life, whereas in low birth weight newborns the decreases were more variable. The serum levels of T₄ and T₃ were significantly different in the three groups of newborns, the highest values were seen in FT and the lowest values in PT babies. In contrast, the ratios between molar serum concentrations of T₄ and T₃ were found to be highest in PT, lower in SGA and lowest in FT babies, approaching maternal values during the first week of life. The data are discussed with regard to hormone secretion, thyroxine-binding capacity and peripheral T₄ to T₃ conversion in the three groups of newborns. It is concluded that from day 5 after birth serum TSH determinations, alone or in combination with serum T₄, seem to be the method of choice in screening for congenital hypothyroidism.     

Changes in thyroid function after bone marrow transplant in young patients

BACKGROUND: Changes in thyroid function among young patients who received bone marrow transplantation (BMT) were evaluated. METHODS: The study included 91 patients (50 males) who underwent BMT from 1985 to 1995 at the age of 0.6-21 years. Sixty patients had neoplastic disease such as leukemia or lymphoma, and the remainder had non-neoplastic diseases. Preconditioning regimen for BMT included 12 Gy of fractionated-total body irradiation (TBI) for patients with neoplastic disease and 3-8 Gy of irradiation for the remaining patients, in addition to chemotherapy. Evaluation of thyroid function was performed by serial assessment of basal serum FT4, FT3, TSH concentrations as well as by TRH test. RESULTS: No patient had overt hypothyroidism or elevated basal TSH concentrations (>10 mU/L). However, 6 (7%) of patients experienced exaggerated peak TSH response to TRH stimulation several years after BMT. In 33 patients whose thyroid status was evaluated before, within 3 months, and 1 year after BMT, serum FT3 concentrations as well as peak TSH response to TRH stimulation significantly decreased immediately after BMT (<3 months) and normalized within 1 year. However, serum FT4 concentrations did not change significantly. One patient developed primary hypothyroidism and another developed follicular adenoma of the thyroid 5 and 12 years after BMT, respectively. CONCLUSION: Short-term changes in thyroid function after BMT can indicate euthyroid sick syndrome rather than tertiary hypothyroidism. It must be noted that overt hypothyroidism may occur several years after BMT, hence long-term follow-up of thyroid function is warranted.     

Identification and characterization of two groups of congenital hypothyroid infants: implications for newborn screening

A retrospective analysis of 400 newborns diagnosed with congenital primary hypothyroidism between 1983 and 1987 was conducted. Two distinct groups of cases were identified and characterized based on their newborn screening TSH value. The two groups are separated at a TSH concentration of 50 mU/1 of serum by a normal probability plot. This finding is in agreement with the 1993 recommendation from the American Academy of Pediatrics that infants with a low T4 level and a TSH concentration greater than 40 mU/1 be considered to have primary hypothyroidism until proven otherwise. The group of infants with TSH less than 50 mU/1 have a higher proportion of males and low birthweight infants. For this group, T4 increases with increasing TSH. We find that screening TSH, T4, and birthweight are predictive of follow-up serum TSH level for the cases with TSH > 50 mU/1 but not for cases with TSH < 50 mU/1. An optimal rule for selecting screening cutoff levels is presented based on only T4, TSH and their interaction. Adjustments for sex, birthweight or age at which sample was taken did not aid in distinguishing cases from controls for newborns whose age of sample is 2 days or greater.     

Thyrotropin and prolactin response to thyrotropin-releasing hormone in healthy and asphyxiated full-term neonates

To evaluate the effect of perinatal asphyxia on the pituitary response to thyrotropin-releasing hormone (TRH) in full-term newborn infants, serum thyrotropin (TSH) and prolactin (PRL) levels were measured before and 30 and 180 min after i.v. administration of 40 micrograms TRH. Birth weight, gestational and postnatal age were similar in the healthy (group NA) and in the asphyxiated (group A) babies. Hormone levels were determined by radioimmunoassay using commercial kits. It was demonstrated that the basal TSH level was slightly higher and the basal PRL level significantly (p less than 0.05) higher in group A than in group NA. In response to TRH administration in group A a marked increase in PRL occurred from 6781 +/- 887 to 11 072 +/- 1318 and 9636 +/- 1024 mU/l at 0, 30 and 180 min, respectively. A similar response was seen in group NA; the values, however, remained significantly lower during the TRH-test. The respective PRL values at 0, 30 and 180 min were 4672 +/- 411, 7945 +/- 343 (p less than 0.05) and 5963 +/- 372 mU/l (p less than 0.05). TRH administration also resulted in a significant elevation of the serum TSH level from 6.20 +/- 1.30 to 49.02 +/- 7.25 (p less than 0.01) and 18.72 +/- 6.35 mU/l (p less than 0.05) in group A, and from 3.90 +/- 0.57 to 24.01 +/- 3.81 (p less than 0.01) mU/l in group NA, but in group NA the 180 min TSH value of 6.07 +/- 1.25 mU/l did not differ statistically from the basal level (p greater than 0.1). It is concluded that the pituitary PRL and TSH reserves are maintained in full-term newborn infants recovering from perinatal asphyxia whose biochemical findings are indicative of subclinical hypothyroidism.     

Genetic Analysis in Children with Transient Thyroid Dysfunction or Subclinical Hypothyroidism Detected on Neonatal Screening

About 30% of children with elevated TSH levels during neonatal screening have a transient form of disorder. On the other hand, it has been reported that subclinical hypothyroidism persists in late childhood in about 30% of children found to be false-positive during neonatal screening. The aim of this study was to determine whether transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening are influenced by genetic background. The TSH receptor (TSHR), thyroid peroxidase (TPO) and dual oxidase 2 (DUOX2) genes, for which it has been reported that heterozygous defects cause neonatal transient thyroid dysfunction, were analyzed. Nine children with transient thyroid dysfunction or subclinical hypothyroidism detected during neonatal screening were studied. One child was heterozygous for a TSHR gene mutation (R450H), and another child was heterozygous for a TPO gene mutation (P883S). No children with mutation of the DUOX2 gene were identified. Genetic background may contribute to development of transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening.     

THYROTROPIN RESPONSE TO THYROTROPIN-RELEASING HORMONE IN FULLTERM, EUTHYROID AND HYPOTHYROID NEWBORNS

Abstract. The serum concentration of thyrotropin (TSH) and the TSH response following thyrotropin-releasing hormone (TRH) were studied in 16 euthyroid babies from 16 to 172 hours after birth and in 2 primary hypothyroid babies, 3 and 28 days of age. Serum-TSH was measured before an intravenous injection of 40 μug TRH and after 30 and 180 min. In the euthyroid babies increased basal levels of TSH were seen shortly after birth, followed by a pronounced decline. The extent of TSH increase after TRH could be correlated with the basal levels, and the relative increase was comparable to that which occurs in adults. In the hypothyroid babies very high basal levels of serum-TSH were seen, 125 and 400 μ/ml respectively, with no further increase following TRH stimulation. It was concluded that in euthyroid fullterm newborn, the relative response of serum-TSH to TRH was equal to that of adults, in spite of elevated thyroid hormone concentrations. In the hypothyroid newborn very high levels of serum-TSH were seen and a supplementary TRH-test seems without diagnostic value in congenital hypothyroidism.     

Turner综合征患儿的甲状腺自身抗体的初步观察

目的　观察Turner综合征(TS)患儿甲状腺自身抗体 (TAA)的阳性率及其对患儿甲状腺功能的影响。方法　采用放射免疫方法及化学发光法对 24例经临床检查和染色体分析确诊的TS患儿血抗甲状腺球蛋白抗体(TgAb)、抗甲状腺过氧化酶抗体(TPOAb)及甲状腺功能进行检测。超过正常值(TgAb<30%、TPOAb<20% )者为TAA阳性。对TAA阳性和TAA阴性患儿的年龄、骨龄及甲状腺功能等进行了分析。结果　24例TS患儿中有 7例(29% )为TAA阳性, 17例为阴性。两组患儿年龄、骨龄差异均无统计学意义。TAA阳性者中 3例为亚临床甲状腺功能低下, 2例为甲状腺功能低下,而TAA阴性患儿只有 4例表现为亚临床甲状腺功能低下,两组差异有统计学意义(P<0.05)。结论　TS患儿的TAA阳性率约为 29%,TAA阳性的TS患儿甲状腺功能异常的例数远多于TAA阴性的TS患儿。     

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.

     

Thyroid function in children with Down's syndrome]

The aim of the present study was to evaluate thyroid function in 45 Down's syndrome patients in order to verify the hypothesis of an increased risk of thyroid disorders associated with trisomy 21. A patient with subclinical hypothyroidism (TSH 16.6 microU/ml; T4 6.4 micrograms/dl) was diagnosed in a group of 28 subjects with Down's syndrome studied at a mean age of 6 years and 5 months using T3, T4, FT3, FT4, TSH assays and clinical examination. T4 and TSH values were also measured in 10 of these children at the neonatal screening. One infant presented transient neonatal hyperthyrotropinemia but later became euthyroid. The analysis of thyroid hormone values at the neonatal screening of other 17 subjects with Down's syndrome did not reveal other cases with thyroid function disorders. The results of this study highlight that altered thyroid functions are evident in children with trisomy 21 associated with heart anomalies. A careful clinico-endocrinological follow-up of patients with Down's syndrome is recommended in order to ensure an early diagnosis of thyroid function disorders and/or autoimmune diseases which might complicate the evolution of trisomy and negatively affect outcome.     

Thyroid dysfunction and high thyroid stimulating hormone levels in children with Down's syndrome

In order to delineate the spectrum of thyroid abnormalities in children with Down's syndrome (DS), first visit height data (SDS) and serum TSH, T4 and antiperoxidase antibodies concentrations were retrospectively evaluated in 137 children (71 girls) with DS (0.04-16 years). RESULTS: Congenital hypothyroidism was detected in 2.9% of patients. Thyroid disease occurred in 9%: four hyperthyroidism and eight hypothyroidism. Overt thyroid disease was always related to thyroid autoimmunity. The remaining 121 patients had normal T4 levels but increased mean TSH compared with controls (4.7 +/- 2.8 vs 2.3 +/- 1.3 mU/l). According to TSH levels, they were divided into two groups: G1 (n = 68) with normal TSH (<5 mU/l), and G2 (n = 53) with high TSH (> 5 mU/l). T4 levels were significantly lower in G2 (p < 0.01 vs G1 and controls). Height SDS was not different. CONCLUSIONS: Thyroid disorders are frequent in children with DS. Subtle thyroid abnormalities found in patients with DS with no evidence of clinical dysfunction need further investigation to demonstrate whether there is a need for therapeutic intervention.     

Thyroid dysfunction in antiretroviral treated children

BACKGROUND: A high rate of thyroid disorders has been described in HIV-infected adults treated with highly active antiretroviral therapy (HAART), but data on children are lacking. We aimed to assess thyroid function in pediatric patients. METHODS: Fifty-two HIV-infected children receiving HAART were assessed for signs of thyroid dysfunction and serum concentrations of thyrotropin (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroglobulin (TG), reverse triiodothyronine (rT3), anti-TG and antimicrosomal (anti-TSM) antibodies. RESULTS: Eighteen (35%) children showed thyroid abnormalities: isolated low FT4 value in 16; subclinical hypothyroidism in 1; and symptomatic hypothyroidism in 1.Children with low FT4 values as compared with the 34 children without thyroid dysfunction were similar for stage of disease, number of patients with undetectable HIV-RNA, FT3, TSH, TG, rT3, anti-TSM and anti-TG values, whereas they had shorter duration of HAART exposure (P = 0.019) and lower CD4 cell percentage (P = 0.035). The thyrotropin-releasing hormone (TRH) test was normal in all children with low FT4 values. Among children with low FT4, FT4 concentrations correlated positively with CD4 cell percentage (P < 0.05) and duration of HAART exposure (P < 0.05).The case with subclinical hypothyroidism had high basal TSH (7.3 microunits/ml), normal TSH response to TRH test and normal FT4, FT3, TG, rT3, anti-TG and anti-TSM antibodies.The case with symptomatic hypothyroidism had low FT4 (6.6 pg/ml) and high TSH (44 microunits/ml), TG (55 ng/ml), anti-TG (666 IU/ml) and anti-TSM (123 IU/ml). CONCLUSION: Thyroid abnormalities occur frequently in HAART-treated children even in the absence of clinical symptoms. These data suggest a need of regular thyroid function monitoring.     

Retrospective Analysis of Infants Designated as Positive on Mass-Screening for Congenital Hypothyroidism at Kagoshima University

Mass-screening for congenital hypothyroidism has identified cases of mild hypothyroidism, transient hypothyroidism, and transient hyperthyrotropinemia as well as typical hypothyroidism. In this paper, we examine the clinical data of the cases found positive in the screening test at our hospital. From 1989 to 1999 there were 72 patients with positive screening tests who started levothyroxine sodium (l-T4; Thyradin-S) as supplement therapy. At the age of 3 to 4 yr the patients were re-evaluated to determine whether treatment should be continued. Thyroid scintigraphies were done at the same time. We divided these cases into 4 groups. Those in group 1A started l-T4 in early infancy without a TRH test because of obvious clinical evidence of hypothyroidism, and treatment was continued after re-evaluation (n=37). Those in group 1B also started treatment in early infancy without a TRH test, but treatment was discontinued after re-evaluation (n=20). Patients in group 2A started l-T4 after evaluation by a TRH test and treatment was continued after re-evaluation (n=14), while those in group 2B started treatment after a TRH test, but after re-evaluation, treatment was discontinued (n=1). In group 2A, only a low dose of l-T4 was needed, and a slightly elevated TSH and slightly decreased free T4 (FT4) were observed after the drug washout period. However, these patients had an exaggerated response to the TRH test at re-evaluation. These findings indicate that this group, forming not a small part of whole screening-positive subjects, had mild hypothyroidism. Such patients require careful follow-up and repeated evaluation to determine whether treatment should be continued.     

Brain TRH levels during development of the rat, in neonatal hypothyroidism and after caloric deprivation

The effect of neonatal hypothyroidism and neonatal caloric deprivation on brain TRH levels and serum and pituitary TSH levels has been determined in rats on the following postnatal days: 1, 5, 10, 15, 25, 40 and 60. After neonatal hypothyroidism, there was a slight reduction in brain TRH content although TRH concentration in the brain increased. Serum TSH was elevated at birth, suggesting that the feedback of thyroid hormones on the pituitary gland acts in rat fetuses. After neonatal caloric deprivation, a decrease in brain TRH content was observed along with a decrease in circulating TSH levels, however, there was no change in brain TRH concentration.     

Plasma thyroid hormones and prolactin in premature infants and their mothers after prenatal treatment with thyrotropin-releasing hormone.

We assayed TSH, triiodothyronine, free thyroxine, and prolactin (PRL) in plasma of women and infants participating in a trial of prenatal thyrotropin-releasing hormone (TRH) treatment for prevention of newborn lung disease. Women in labor at 26-34 wk of gestation received 400 micrograms of TRH i.v. every 8 h (one to four doses) plus 12 mg betamethasone (one or two doses); controls received saline plus betamethasone. Mean cord concentrations in control infants were TSH 9.7 mU/L, triiodothyronine 0.6 nmol/L (40.2 ng/dL), free thyroxine 14.4 pmol/L (1.13 ng/dL), and PRL 67.6 micrograms/L. TRH increased maternal plasma TSH by 100% at 2-4 h after treatment and decreased levels by 28-34% at 5-36 h. In cord blood of treated infants delivered at 2-6 h, TSH, triiodothyronine, and PRL were all increased about 2-fold versus control, and free thyroxine was increased 19%; the response was similar after one, two, three, or four doses of TRH. In treated infants delivered at 13-36 h, cord TSH and triiodothyronine levels were decreased 62 and 54%, respectively, and all thyroid hormones were lower after birth at 2 h of age versus control. We conclude that prenatal TRH administration increases thyroid hormones and PRL in preterm fetuses to levels similar to those normally occurring at term. Pituitary-thyroid function is transiently suppressed after treatment to a greater extent in fetus than mother, and infants born during the early phase of suppression do not have the normal postnatal surge in thyroid hormones.     

Borderline congenital hypothyroidism in the neonatal period

One of the most important etiological factors causing prolonged jaundice in the neonatal period is congenital hypothyroidism. Some infants may have abnormal thyroid function test results rather than overt congenital hypothyroidism. Although serum TSH levels are accepted as diagnostic when >20 microIU/l, TSH values higher than 7 microIU/ml cause a hypometabolic condition. In this study, we evaluated infants who had prolonged jaundice for hypothyroidism. A hundred and ten infants suffering from prolonged jaundice were admitted to our clinic during the study period. Among them, 61 infants had normal thyroid function results. Six patients had overt primary hypothyroidism. TRH stimulation test was administered to the 43 patients with mildly elevated TSH levels of between 5 and 20 microIU/ml. Peak TSH values were above 35 microIU/ml in seven patients, and these were considered as having an exaggerated response (borderline hypothyroidism). During the neonatal period, prolonged jaundice is a valuable diagnostic clue for hypothyroidism. In addition, the TRH stimulation test can be a diagnostic tool in evaluating infants with mildly abnormal thyroid function test results.