Transient Hypothyroxinemia Research Articles

Euthyroid Low Thyroxine (T4) and Triiodothyronine (T3) States in Prematures and Sick Neonates

This article reviews the ontogenesis of thyroid system function in the human fetus and newborn and characterizes thyroid function in the premature infant. Thyroid function disorders associated with neonatal adaptation and illness also are reviewed; these include transient hypothyroxinemia, transient primary hypothyroidism, and the syndrome of nonthyroidal illness.

Isolated ACTH Deficiency Associated with Transient Thyrotoxicosis and Hyperprolactinemia.

A 43-year-old woman with isolated ACTH deficiency in association with transient thyrotoxicosis is reported. The initial evaluation revealed that plasma ACTH and cortisol did not respond to corticotropin-releasing hormone (CRH) in the presence of hyperthyroxinemia and hyperprolactinemia. During the replacement therapy with dexamethasone, she developed transient hypothyroxinemia with persistent hyperprolactinemia. Although thyroid open biopsy did not show any evidence of autoimmune thyroiditis or subacute thyroiditis, the data appear to provide other evidence of a possible relationship between acute adrenal insufficiency and transient thyroid dysfunction.

Thyrotropin measured by the immunoradiometric assay in low birth weight infants.

In 37 infants, the blood levels of TSH were determined by the immunoradiometric assay (IRMA) and the relation between TSH and thyroid hormone was evaluated. The ranges of gestational age (weeks) and birth weight (g) of infants were 28-42 and 982-3,650, respectively. The birth weights of 19 infants were below 2,500 g. The free T4 levels in the low birth weight (LBW) infants were lower than those of the normal infants and significantly correlated to the birth weight (r = 0.64, P less than 0.01) and gestational age (r = 0.58, P less than 0.01). In addition, free T4 levels were significantly correlated to the levels of total T4 (r = 0.66, P less than 0.01). The concentrations of TSH measured by IRMA method were significantly correlated to those of free T4 (r = 0.51, P less than 0.01). From these data, we consider that the transient hypothyroxinemia observed frequently in LBW infants might be a physiological reaction regulated by hypothalamus and that thyroid hormone treatment should be avoided.

Thyroid function in fullterm and preterm newborns

The development of the hypothalamic-pituitary-thyroid system in the fetus occurs through three phases: thyroid pituitary embryogenesis, maturation of hypothalamus, maturation of thyroid system, neuroendocrine control and T4 tissue deiodination. Defects in early phases I and II lead to permanent disorders whereas abnormalities in phase III result in transient functional immaturities especially in preterms. Cord serum TSH, T4 and T3 were estimated in 450 newborns (390 full term>36 wk gestation and 60 preterms 3 kg and <2 kg rather than in all intermediate groups. No significant differences in these hormones were evident amongst the AGA and SGA infants above and below 36 weeks gestation. Transient hypothyroxinemia, and hyper-thyrotropinemia, transient primary hypothyroidism and low T3 syndromes are some of the transient abnormalities of thyroid function and are more commonly encountered in preterms.

447 THE EFFECT OF POST-NATAL AGE ON THE RESPONSE OF THE PITUTITARY-THYROID AXIS TO THYROTROPIN RELEASING HORMONE

Transient hypothyroxinemia is a common problem in the preterm infant. The response of the pituitary-thyroid (P-T) axis to exogenous thyrotropin releasing hormone (TRH) infusion has been used to confirm the euthyroid state of these preterm infants. The purpose of this study was to define the effect of post-natal age on the response of the P-T to TRH infusion. Eight preterm infants with RDS (Group I) and 10 preterm infants without RDS (Group II) received 20 mcg/kg TRH IV on days 3 and 14 of life. The mean birth weights, gestational age and Apgar scores were similar in both groups. The pattern of the serum thyroid stimulating hormone (TSH) response to TRH was similar in both groups on both days. In each group, the mean serum TSH level prior to TRH infusion was similar at day 3 and day 14. The mean serum TSH level was significantly elevated by 30 minutes (m) and declining by 180 m. At 30 and 180 m, the mean serum TSH level was significantly higher at day 3 compared to day 14. Compared to pre-infusion of TRH values, the mean serum thyroxine (T4) and triiodothyronine T3) levels were significantly increased on day 3 at 180 m in both groups. There were no other significant differences in mean serum T4 and T3 levels in either group at any other time.Conclusions: 1) In the preterm infant with or without RDS, the serum TSH response following infusion of TRH is significantly different at day 3 compared to day 14 of life; 2) the thyroid gland response is similar at 3 and 14 days.

SERUM THYROXINE (T4), FREE T4 (FT4) AND TSH IN PREMATURE INFANTS LESS THAN 1000 GRAMS DURING THE FIRST THREE MONTHS OF LIFE

The incidence of transient hypothyroidism in very low birth weight infants has not been delineated. We studied 22 premature infants <1000 grams and <30 weeks gestation. Eight infants died within four days and their data excluded.The nadir of T4 and FT4 and the peak TSH levels occurred at 2 weeks. Eight of 10 babies had T4's <6μg/dl and 7 had FT4's <0.8ng/dl (below accepted normal values). No TSH value was >20μU/ml. The FT4's were lower than anticipated. These data are compatible with transient hypothyroxinemia. However, it is possible that these babies had transient hypothyroidism with a blunted TSH response secondary to immaturity of the hypothalamo-pituitary-thyroid axis.

Frequency of transient hypothyroxinaemia in low birthweight infants. Potential pitfall for neonatal screening programmes.

Thyroid function was studied in 54 low birthweight infants during a 3-week period. Each infant was placed in one of three groups. Group 1 (n = 21), infants who were well and appropriately grown fro gestational age; group 2 (n = 23), infants who were appropriately grown but who had hyaline membrane disease; group 3 (n = 10), infants who were small-for-gestational-age. In group 1, 5 (24%) infants had at least one serum thyroxine value less than 3.0 micrograms/100 ml (39 nmol/l). There were 8 (35%) infants in group 2 who had similarly low serum thyroxine values as did 5 (50%) of the 10 infants in group 3. Serum thyrotropin levels and serum binding of the thyroid hormones, as measured by a T3-charcoal uptake test, were normal in all infants. In all instances but 2, serum thyroxine values were at least 4.0 micrograms/100 ml (51 nmol/l) by the end of the 3-week period. There is thus a high incidence of transient 'hypothyroxinaemia' in low birthweight infants, particularly if such infants have hyaline membrane disease or are small-for-gestational-age. These findings must be considered when interpreting results of screening programmes for congenital hypothyroidism and they lend further support to the use of a combination of serum thyroxine and thyrotropin determinations for optimum screening of such infants.