Mean T4 Research Articles

The Hypothalamic-Pituitary-Thyroid Negative Feedback Control Axis in Children with Treated Congenital Hypothyroidism

Measurements of serum concentrations of free T4, T3, TSH, and thyroglobulin (Tg) were conducted in 42 infants (2–9 months of age) detected and treated through the Northwest Newborn Regional Screening Program and 63 children and adolescents (1–18 yr of age) with congenital hypothyroidism (CH) detected and managed in the Northern California Kaiser Permanente Medical Care Program. Normal feedback control axis data were developed by Quest Diagnostics, Inc. - Nichols Institute Diagnostics and Loma Linda University, from free T4 and TSH measurements in 589 healthy subjects, 2 months to 54 yr of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Twenty-four of the 42 CH infants and 57 of the 63 CH children manifested serum TSH concentrations appropriate for the measured free T4 level. In the remaining 18 infants and 6 children, serum free T4 values were increased 0.2–1.4 ng/dL (2.6–18.0 pmol/L) for the prevailing TSH level, suggesting a state of mild to moderate pituitary-thyroid hormone resistance. In the treated children, the mean T3 concentration was lower (by 32%, 102 vs. 150 ng/dL; 1.57 vs. 2.31 nmol/L) than in normal children, in agreement with earlier data in hypothyroid adults treated with exogenous T4. Serum Tg concentrations were normal or elevated in 90% of the 19 children with ectopic glands and 93% of 27 children with eutopic glands in whom measurements were available. There was a positive correlation between serum TSH and Tg concentrations (P < 0.001), suggesting significant endogenous thyroid hormone production in these children. Our results suggest that the majority of infants and children with CH have a normal hypothalamic-pituitary-thyroid negative feedback control axis during treatment and that the measurement of serum TSH is a useful marker complementing the free T4 measurement in the management of children with CH. A minority have variable pituitary-thyroid hormone resistance, with relatively elevated serum TSH levels for their prevailing serum free T4 concentration. The prevalence of resistance is greater (43%) in young infants (<1 yr of age) than in older children (10%), indicating that, in most children, the resistance improves with age.

The hypothalamic-pituitary-thyroid negative feedback control axis in children with treated congenital hypothyroidism.

Measurements of serum concentrations of free T4, T3, TSH, and thyroglobulin (Tg) were conducted in 42 infants (2-9 months of age) detected and treated through the Northwest Newborn Regional Screening Program and 63 children and adolescents (1-18 yr of age) with congenital hypothyroidism (CH) detected and managed in the Northern California Kaiser Permanente Medical Care Program. Normal feedback control axis data were developed by Quest Diagnostics, Inc. - Nichols Institute Diagnostics and Loma Linda University, from free T4 and TSH measurements in 589 healthy subjects, 2 months to 54 yr of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Twenty-four of the 42 CH infants and 57 of the 63 CH children manifested serum TSH concentrations appropriate for the measured free T4 level. In the remaining 18 infants and 6 children, serum free T4 values were increased 0.2-1.4 ng/dL (2.6-18.0 pmol/L) for the prevailing TSH level, suggesting a state of mild to moderate pituitary-thyroid hormone resistance. In the treated children, the mean T3 concentration was lower (by 32%, 102 vs. 150 ng/dL; 1.57 vs. 2.31 nmol/L) than in normal children, in agreement with earlier data in hypothyroid adults treated with exogenous T4. Serum Tg concentrations were normal or elevated in 90% of the 19 children with ectopic glands and 93% of 27 children with eutopic glands in whom measurements were available. There was a positive correlation between serum TSH and Tg concentrations (P < 0.001), suggesting significant endogenous thyroid hormone production in these children. Our results suggest that the majority of infants and children with CH have a normal hypothalamic-pituitary-thyroid negative feedback control axis during treatment and that the measurement of serum TSH is a useful marker complementing the free T4 measurement in the management of children with CH. A minority have variable pituitary-thyroid hormone resistance, with relatively elevated serum TSH levels for their prevailing serum free T4 concentration. The prevalence of resistance is greater (43%) in young infants (< 1 yr of age) than in older children (10%), indicating that, in most children, the resistance improves with age.

Monitoring iodine following consumption of iodized salt in Tehrani inhabitants.

As the production, distribution and consumption of iodized salt has increased in recent years, this study was carried out to assess iodine status in Tehran in 1996. 1146 families comprising 5140 subjects in the twenty districts of Tehran city from all age groups were randomly selected. Thyroid size was examined by palpation and graded according to the WHO classification. In 163 families selected randomly, thyroid size was determined by ultrasonography and urinary iodine was measured by digestion method. Serum T4, T3 and TSH (IRMA) concentrations were also assayed by kits. Percentage of grades 1 & 2 goiter were 44 & 44% in females and 49 & 33% in males respectively. Median urinary iodine was 17.5 micrograms/dl. Mean serum T4, T3 and TSH were 8.41 +/- 1.4 micrograms/dl, 170 +/- 37 ng/dl and 1.4 +/- 0.8 mu/ml, respectively. In 118 children aged 6-10 years median urinary iodine was 17.5 micrograms/dl. Thyroid volume in children was 4.3 +/- 1.9 ml. No correlation was established between the thyroid volume and goiter grade. This study points to the adequacy of iodine intake in the majority of families residing in Tehran.

Impact of lead exposure on pituitary-thyroid axis in humans.

Thyroid function tests (serum levels of thyroxine-T4, triiodothyronine-T3 and thyroid stimulating hormone-TSH) were performed in fifty-eight men (mean age: 31.7 +/- 10.6 years; mean duration of lead exposure: 156.9 +/- 122.7 months). These subjects were exposed to lead either as petrol pump workers or automobile mechanics. The mean whole blood lead (Pb-B) levels were 2.49 +/- 0.45 micromole/l (51.90 +/- 9.40 microg/dl) in the lead exposed workers and were approximately 5 times higher than in the control (n = 35) subjects. No significant alteration was seen in their mean T3 and T4 levels as compared with the controls. Interestingly, T3 was significantly lower with the longer (210 months) exposure time in comparison with the group having shorter (29 months) exposure duration. The mean TSH levels were significantly (p < 0.01) higher in workers exposed in comparison with the control group. This rise in TSH was independent of exposure time, but it was definitely associated with the Pb-B levels. The increase being more pronounced with mean Pb-B levels of 2.66 +/- 0.2 micromole/l (55.4 +/- 4.25 microg/dl) when compared with the group having mean levels of 1.51 +/- 0.30 micromole/l (31.5 +/- 6.20 microg/dl). The rise is TSH associated with Pb-B levels was only statistical valid, however, the levels fall within the normal laboratory range. We thus conclude that the Pb-B levels of > or = 2.4 micromole/l (50 microg/dl) could enhance the pituitary release of TSH without having any significant alterations in the circulating levels of T3 and T4.

Maternal thyroid function in multiple pregnancy: the variable thyrotropic activity of human chorionic gonadotropin.

The present study was undertaken to evaluate thyroid function and thyrotropic action of hCG in multiple pregnancy. We examined serum samples from 9 multiple pregnant women (3 triplets and 6 twins) and 27 singleton pregnant women as control subjects. Serum hCG levels in multiple pregnancy were higher than those in singleton pregnancy in the second and third trimesters (P < 0.01). The mean free T3 and T4 concentrations in multiple pregnancy did not differ from those in singleton pregnancy in each trimester. Serum hCG levels showed a statistically significant positive correlation with free T3 and T4 levels in singleton pregnancy (P < 0.001). However, these correlations were not observed in multiple pregnancy. Thyroid stimulation activity (TSA) determined by cAMP accumulation in FRTL-5 cells in multiple pregnancy sera was significantly higher than that in singleton pregnancy in the first trimester (P < 0.05), but did not differ in the second and third trimesters. Moreover, TSA did not show any correlation with serum hCG levels in multiple pregnancy in contrast with the results in normal pregnancy. A bioactivity/immunoreactivity ratio of hCG in multiple pregnancy was lower than in singleton pregnancy in the second and third trimesters. The discrepancy between immunoreactivity and thyrotropic activity of hCG may be caused by the variable thyrotropic potency of heterogeneous hCG molecules in multiple pregnancy.

Circulating iodide concentrations during and after pregnancy.

Early, indirect studies suggested that an important aspect of thyroid economy during pregnancy was a decline in plasma or serum inorganic iodide (PII) concentrations, but there is little information concerning circulating iodide concentrations as assessed by direct measurement. The present study was undertaken to determine the relationship between gestation and serum iodide concentrations as assessed by direct measurement of PII. PII concentrations, urinary iodide levels, and other parameters of thyroid economy were measured during the first, second, and third trimesters and after delivery in 16 women. Mean serum T4 concentrations were significantly higher in all 3 trimesters than those after delivery. Serum free T4 index concentrations were significantly higher in the first trimester than during later periods of gestation or after delivery, but serum TSH concentrations were not depressed in the first trimester. Serum thyroglobulin concentrations were similar during pregnancy and after delivery. There was wide variability in PII and urinary iodide concentrations during and after pregnancy, but there was no trend for PII concentrations to be depressed during pregnancy. Pregnancy, at least in iodine-sufficient regions, does not have an important influence on circulating concentrations of iodide.

Differences in thyroid function between bipolar manic and mixed states

High rates of thyroid axis abnormalities have been reported in most studies of patients with rapid-cycling bipolar disorder. Mixed states share similarities with rapid-cycling, including close temporal occurrence of manic and depressive symptoms, predominance in women, poor outcome, and less robust response to lithium compared with pure mania; however, thyroid axis abnormalities have not been well studied in mixed mania. To test the hypothesis that mixed states are associated with a higher prevalence of hypothyroidism than pure mania, immunoreactive triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) concentrations were determined from serum obtained at the time of admission in 37 consecutive patients with DSM-III-R bipolar disorder, manic or mixed. The mean TSH concentration was significantly higher, and the mean T4 concentration was significantly lower in patients with mixed mania compared with pure mania. There were no significant differences in T3 concentration or in previous lithium exposure. These findings suggest thyroid axis dysfunction is more common in bipolar mixed than in bipolar manic patients.

Thyroid function in very low birth weight infants.

The purpose of this study was to test the hypothesis that low circulating thyroxine concentrations characteristic of very low birth weight (VLBW) neonates (< 1500 g) are the result of decreased protein binding of thyroid hormones and to elucidate the mechanism(s) responsible and possible significance thereof. Cross-sectional comparison of thyroid related measurements in cord blood specimens from VLBW infants and from full term infants. Longitudinal comparison in cord and 2- and 4-week blood specimens from VLBW infants. Cord blood specimens were analysed from 47 VLBW and 45 full term infants weighing > or = 2500 g. Repeat analyses in venous bloods from 32 of the VLBW infants were analysed at 2 weeks of age and again at 4 weeks in 23. The first cohort of patients was studied in 1994 and comprised 28 VLBW and 24 full term infants (Cohort A). The studies were repeated in 1995-96 in 19 VLBW infants and 21 full term infants (Cohort B). T4, free T4 (FT4), T3, thyroxine binding globulin (TBG), and TSH were measured in cord blood and 2- and 4-week venous specimens from VLBW infants and in cord blood specimens of full term infants. Molar ratios of T4/TBG were calculated. (1) Cord blood TBG, T4 and T3 concentrations of VLBW infants were each 60% of those of term infants. TBG concentrations were 397 +/- 111 vs 680 +/- 172 nmol/l (P < 0.0005). T4 concentrations were 76 +/- 22 vs 139 +/- 26 nmol/l (P < 0.0005). FT4 concentrations were in the normal adult range in both neonatal groups. T4/TBG ratios did not differ between the neonatal groups but were significantly less than that of adults (P < 0.001). (2) TSH concentrations in VLBW infants at 2 and 4 weeks were less than 50% of cord blood values. At 2 weeks, TBG concentrations of VLBW infants were unchanged from cord blood concentrations but mean T4 concentration fell by 18% and T4/TBG ratios by 21% (P < 0.005). Mean FT4 rose by 78% (P < 0.02). The changes in mean T4 and FT4 were due largely to FT4 concentrations of 37-113 pmol/l and T4 concentrations of 13-48 nmol/l in 5 infants. These infants also had lower T4/TBG ratios and were smaller and more ill than the remainder of the cohort. The changes disappeared by 4 weeks in 3 of the 4 infants tested. Cord T4/TBG ratios are the same in very low birth weight and term infants and are significantly lower than in adult blood. These are more than compensated for in term infants by a 236% increase in thyroxine binding globulin concentrations. The lower thyroxine binding globulin concentrations in very low birth weight infants explain their much lower T4 concentrations. Cord FT4 concentrations of full term and very low birth weight infants are in the normal adult range. T4 concentrations are further depressed and free T4 concentrations elevated in the most ill very low birth weight infants at 2 weeks of age in a manner analogous to that of the 'sick euthyroid syndrome'.

Topical iodine-containing antiseptics and subclinical hypothyroidism in preterm infants

The influence of topical iodine-containing antiseptics on thyroid function test results of premature infants was determined in two separate studies. Thyroxine and thyrotropin levels were measured on blood-spotted filter paper. Samples were obtained from 128 premature infants on their tenth day of life; the infants were treated in two neonatal intensive care units. Both units used similar treatment protocols; however, one routinely used topical iodinated antiseptic agents (n = 73), whereas the other used chlorhexidine-containing antiseptics (n = 55). There was no difference in the mean T4 levels between the two groups. The mean thyrotropin levels were elevated in preterm babies exposed to iodine (15.4 vs 7.8 mIU/L, p < 0.01). Among the iodine-exposed infants, elevated thyrotropin levels (> 30 mIU/L) were found in 13.7% of infants, compared with none in the chlorhexidine-treated group (p < 0.01). We then studied an additional 46 premature infants who were treated in one neonatal intensive care unit. Iodine-containing solutions were used in 24 infants and chlorhexidine was used in 22 infants. T4 and thyrotropin levels were measured weekly during the first 28 days, one every 2 weeks until the age of 60 days, and at the age of 90 days. Among iodine-exposed infants, 20.8% had thyrotropin values > 30 mIU/L, whereas none of the infants in the chlorhexidine group had elevated thyrotropin values (p < 0.05). The elevated thyrotropin levels correlated positively with the area of disinfection. Elevated urine iodine levels were present reflecting an abnormally high iodine absorption. This study suggests that iodine absorption from topical iodine-containing antiseptics may cause disturbances in thyroid function test results in premature infants. We recommend that caution be exercised in the use of iodine-containing antiseptics in premature infants.

Anemia in infants with congenital hypothyroidism diagnosed by neonatal screening

Although anemia is a common finding in adult hypothyroid patients, there are no studies on anemia in hypothyroid infants. The aim of this study, therefore, was to review the hematologic status during the first year of life in 50 infants with congenital hypothyroidism detected through the regional neonatal screening program. The mean age at diagnosis was 23.7±6.5 days and treatment was initially begun with a mean L-thyroxine dose of 6.8±1.3 μg/kg/day. Clinical and haematological assessments were performed at diagnosis, 3, 6 and 12 months of age. The patients were devided in 2 groups based on whether T4 serum concentration at diagnosis was < 3 μg/dl (Group A) or ≥3 μg/dl (Group B). Data for hemoglobin (Hb), hematocrit (Ht), red cells count (RCC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), serum iron and ferritin were expressed as Standard Deviation Score (SDS). Although at diagnosis the mean value of Hb-SDS, Ht-SDS and RCC-SDS were in the low-normal range in both groups, at 3 months of age the values in Group A (Hb −1.9±0.79; Ht −2.34±1.02; RCC −1.56±1.25) were significantly lower than in Group B (Hb −1.14±0.78, p<0.005; Ht −1.59±0.94, p<0.05; RCC −0.55±1.32, p<0.02). A rise of the Hb, Ht and RCC values was observed in both groups from 6 to 12 months. The mean values of MCV-SDS and MCH-SDS were in the normal range at diagnosis in both groups, decrease progressively at 3 and 6 months and returned to normal at 12 months of age; no differences were found between the 2 groups at any time. Mean Hb levels at 3 months of age were correlated with mean serum T4 at diagnosis (r=0.30, p<0.05). The present results indicate that anemia is a frequent finding in infants with congenital hypothyroidism and is depended on the degree of neonatal hypothyroidism and imply that hypothyroidism during development may produce persisting changes even after thyroid replacement has begun.

Pituitary-thyroid axis in short- and long-term experimental diabetes mellitus.

Short-term experimental diabetes mellitus (DM) produces a significant decrease in serum thyroid hormones, a decreased or normal serum thyroid-stimulating hormone (TSH) and a reduction in hepatic and renal T4-5'-deiodination. However, little is known about the effects of chronic diabetes mellitus on the pituitary-thyroid axis function. We evaluated the changes induced by very short-term (6 days), short-term (15 days) and chronic (6 months) streptozotocin-induced diabetes mellitus in 3-month old female Dutch-Miranda rat serum T4, serum TSH and T4-5'-deiodinase activity in the thyroid and pituitary glands. Serum hormones were determined by specific radioimmunoassays. Iodothyronine-5'-deiodinase activities were assayed in the thyroid and pituitary microsomal fractions using 2 microM T4 as substrate. Mean serum T4 was significantly decreased from 3.3 to 2.0 micrograms/dl 6 days after diabetes mellitus induction, and from 2.2 to 1.5 micrograms/dl after 15 days of DM, with no significant changes in serum TSH, indicating a decreased pituitary TSH responsiveness to the diminished suppression by T4, even though pituitary T4-5'-deiodinase activity was unchanged. Thyroid T4-5'-deiodinase was unchanged after 6 days of diabetes mellitus, but was significantly increased from 20.6 to 37.0 pmol T3/mg protein after 15 days. Six months after diabetes mellitus induction, both serum T4 and thyroid T4-5'-deiodinase returned to normal ranges and serum TSH was unchanged, although pituitary T4-5'-deiodinase was now significantly decreased from 2.7 to 1.7 pmol T3/mg protein. These findings indicate that some kind of adaptation to chronic insulinopenia may occur at the thyroid level, but this does not seem to be true for the pituitary.

Anemia in infants with congenital hypothyroidism diagnosed by neonatal screening.

Although anemia is a common finding in adult hypothyroid patients, there are no studies on anemia in hypothyroid infants. The aim of this study, therefore, was to review the hematologic status during the first year of life in 50 infants with congenital hypothyroidism detected through the regional neonatal screening program. The mean age at diagnosis was 23.7 +/- 6.5 days and treatment was initially begun with a mean L-thyroxine dose of 6.8 +/- 1.3 micrograms/kg/day. Clinical and haematological assessments were performed at diagnosis, 3, 6 and 12 months of age. The patients were divided in 2 groups based on whether T4 serum concentration at diagnosis was < 3 micrograms/dl (Group A) or > or = 3 micrograms/dl (Group B). Data for hemoglobin (Hb), hematocrit (Ht), red cells count (RCC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), serum iron and ferritin were expressed as Standard Deviation Score (SDS). Although at diagnosis the mean value of Hb-SDS, Ht-SDS and RCC-SDS were in the low-normal range in both groups, at 3 months of age the values in Group A (Hb -1.9 +/- 0.79; Ht -2.34 +/- 1.02; RCC -1.56 +/- 1.25) were significantly lower than in Group B (Hb -1.14 +/- 0.78, p < 0.005; Ht -1.59 +/- 0.94, p < 0.05; RCC -0.55 +/- 1.32, p < 0.02). A rise of the Hb, Ht and RCC values was observed in both groups from 6 to 12 months. The mean values of MCV-SDS and MCH-SDS were in the normal range at diagnosis in both groups, decrease progressively at 3 and 6 months and returned to normal at 12 months of age; no differences were found between the 2 groups at any time. Mean Hb levels at 3 months of age were correlated with mean serum T4 at diagnosis (r = 0.30, p < 0.05). The present results indicate that anemia is a frequent finding in infants with congenital hypothyroidism and is depended on the degree of neonatal hypothyroidism and imply that hypothyroidism during development may produce persisting changes even after thyroid replacement has begun.

Concentrations of thyroid hormones and iodothyronine binding proteins in serum of the koala (Phascolarctos cinereus).

To examine circulating total and free thyroid hormone (T3 and T4) concentrations, determine serum iodothyronine binding characteristics and estimate thyroid stimulating hormone (TSH) activity in sera of coastal and inland koalas. A prospective study. Koala serum T3 and T4 were measured by radioimmunoassay. T4 binding parameters were determined by radioligand binding and electrophoresis. Koala TSH values were determined by bioassay. Mean total T4 concentrations were 3.2 +/- 2.1 nM although values were significantly higher in inland-dwelling females in comparison to coastal-dwelling males. Free T4 was 3.3 +/- 2.1 pM. Total and free T3 were 0.4 +/- 0.2 nM and 1.4 +/- 0.9 pM respectively, although these values were at the lower end of the assay detection limit and should be viewed with reservation. Electrophoresis of [125I]-T4-labelled serum revealed only two proteins of electrophoretic mobility similar to human transthyretin (TTR) and albumin. Scatchard analysis of T4 binding to serum gave a curvilinear plot, which could be resolved into two binding sites with affinities identical to that of TTR and albumin but both of low concentration. The bioactivity of the TSH present in the sera was measured using a cell line (JP09) transfected with the human TSH receptor. The mean level of stimulation found in the sera corresponded to a bovine TSH activity of less than 10 mU/L. These results suggest that the serum concentrations of free and total thyroid hormones in koalas are low compared to other marsupials and very low compared to eutherian mammals. The mechanism of maintenance of euthyroidism in this species remains to be determined.

Management of Thyroxine Therapy During Pregnancy

To review the management of thyroxine (T4) therapy in pregnant patients with hypothyroidism. The results of pertinent published studies are summarized, and practical recommendations are presented. The conditions for which T4 therapy is administered during pregnancy are the same as those in nonpregnant patients: hypothyroidism, thyrotropin or thyroid-stimulating hormone (TSH) control after surgical treatment of thyroid cancer, and, in selected patients, suppression treatment for postsurgical thyroid remnants, thyroid nodules, or goiter. Untreated hypothyroidism during pregnancy can potentially cause adverse effects in both mother and fetus. Up to 75% of T4-treated women with hypothyroidism require higher doses of T4 during pregnancy than before or after conception, to maintain serum TSH levels in the normal range. Otherwise, in a substantial percentage of these women, subnormal serum free T4 levels, TSH elevations >20 microIU/L, or both will develop. The mean T4 dose needed to correct hypothyroidism during pregnancy is about 150 microg/day, but individual dose requirements vary widely. The increment in T4 dose needed to normalize an increased TSH level in women taking T4 can be estimated from the serum TSH concentration during pregnancy. Increased TSH levels can appear as early as 4 to 8 weeks of gestation or as late as the third trimester. Although the optimal schedule is uncertain, assessing the TSH once each trimester seems reasonable. After pregnancy, the T4 dose should be reduced to the preconception level, and postpartum reassessment should be done at 6 to 12 weeks.

Effects of iodine deficiency on insulin‐like growth factor‐I, insulin‐like growth factor‐binding protein‐3 levels and height attainment in malnourished children

The expression and synthesis of IGF-I and IGFBP-3 have been shown to be regulated by hormones and nutrition. We study the effects of malnutrition and iodine deficiency on these growth factors and the height attainment of a group of children. We measured serum IGF-I and IGFBP-3 levels in a group of Malaysian aborigine children from three jungle settlements; Sinderut and Pos Lanai are known for iodine deficiency and endemic goitre, and Gombak is an iodine replete area with better socioeconomic status. A total of 246 children were studied, 188 in the age group 4-10 years and 88 in the age group 11-15 years. All children were assessed anthropometrically and height standard deviation score (SDS) were calculated using the CDC Anthropometric Software package. Malnutrition was confirmed clinically and according to the WHO definition of malnutrition. IGF-I and IGFBP-3 were determined by radioimmunoassay, and T4 and TSH by immunoradiometric assay. Based on the height SDS, Sinderut and Pos Lanai children were significantly more malnourished and stunted than the Gombak children P = 0.0001). T4 levels were significantly lower (P = 0.0001) amongst the 4-10-years old Sinderut (81 +/- 2 nmol/l) than in Pos Lanai (101 +/- 3 nmol/l) or Gombak (123 +/- 3 nmol/l) children. Similar findings were also seen in the older children; mean T4 levels of those from Sinderut and Pos Lanai (83 +/- 3 and 88 +/- 4 nmol/l respectively), were low (P = 0.0001) compared to Gombak (118 +/- 3 nmol/l). Conversely, TSH levels in both age groups of Sinderut children were significantly elevated (P = 0.0001) (3.5 +/- 0.2 and 3.9 +/- 0.3 mU/l respectively) compared to age-matched groups from Pos Lanal (2.1 +/- 0.1 and 2.2 +/- 0.2 mU/l respectively) and Gombak (1.5 +/- 0.1 and 1.5 +/- 0.2 mU/l respectively). IGF-I and IGFBP-3 correlated significantly with the height SDS of the children, In both the 4-10 (r = 0.400, P = 0.0001 and r = 0.365, P = 0.0001 respectively) and 11-15 years age groups (r = 0.324, P = 0.002 and r = 0.533, P = 0.0001 respectively). Correlation between IGFBP-3 and T4 levels was more significant in the younger children (r = 0.412, P = 0.0001). Association between IGF-I and T4 levels was significant only in the 4-10 years age group (r = 0.237, P = 0.001). Varying duration and degree of exposure to malnutrition and iodine deficiency resulted in different mean levels of T4, TSH, IGF-I and IGFBP-3 in the three areas. The strong positive associations between IGF-I and IGFBP-3 levels and height SDS suggest that these biochemical measurements are indeed useful indicators of growth and nutritional status in children. The significant correlations between T4 and IGFBP-3 and IGF-1 suggests the importance of thyroid hormones in regulating the synthesis of these growth factors. The age-related increase of these growth factors even amongst malnourished, iodine deficient children implies that age-matched reference ranges are essential for proper evaluation of laboratory results.

SCREENING THYROXINE LEVEL AND DEVELOPMENTAL OUTCOME IN VERY LOW BIRTHWEIGHT(VLBW) INFANTS. 546

Studies estimate that marked hypothyroxinemia (thyroxine [T4] <6.5μg/dl) is present in 25% of all prematures and 50% of babies born at <30 weeks gestation. The effects of hypothyroxinemia on neonatal status and developmental outcome in VLBW infants are unknown. We hypothesized that the T4 obtained as part of the routine newborn screen would correlate with developmental outcome scores in VLBW infants. We retrospectively collected the T4 screen for 185 infants with BW <1250 gm admitted to the NICU from 1/1/88 to 12/31/89. The mean T4 was 5.9±3.4 μg/dl; the mean BW was 980±180 gm. Correlation analyses were completed to evaluate the relationship of screening T4 with neonatal risk factors and with the Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores at 7, 12 and 24 months. Pearson Correlation Coefficients:Table ↑ Screening T4 correlated with ↑ Apgar scores, ↑ birth weight, ↑ gestational age and inversely with days hospitalized. There was no relationship with days of mechanical ventilation or oxygen. Screening T4 correlated with the 7 month MDI, but did not show a significant correlation with 7 month PDI, nor with developmental outcome scores at 12 or 24 months. We conclude that T4 screen correlates with parameters of neonatal illness severity in VLBW infants. These preliminary data suggest that although screening T4 may impact on Bayley MDI at 7 months, the effects of T4 level on developmental outcome diminish by 12 to 24 months of age. In summary, neonatal hypothyroxinemia is a measure of illness severity in VLBW infants and appears to affect developmental performance at 7 months of age.

Effect of treatment of hyperthyroidism on renal function in cats

Objective To determine whether increases in BUN and serum creatinine (SCr) concentrations, which have been reported to develop after surgical bilateral thyroidectomy in hyperthyroid cats, also develop after treatment of hyperthyroidism with radioactive iodine and methimazole. Design Prospective, clinical trial. Animals 58 hyperthyroid cats. Procedure Urine specific gravity, SCr, BUN, and serum thyroxine (T4) concentrations were determined before and 30 and 90 days after treatment of hyperthyroidism with radioactive iodine, methimazole, or surgical bilateral thyroidectomy. Results Mean SCr and BUN concentrations determined 30 and 90 days after treatment were significantly higher than those measured before treatment. Mean SCr, BUN, and T4 concentrations were not different among groups before treatment or 30 and 90 days after treatment. Clinical Implications Reduction of serum T4 concentrations after treatment of hyperthyroidism may result in azotemia in older cats with chronic renal disease. Treating azotemic hyperthyroid cats with methimazole until it can be determined whether correction of the hyperthyroid state will exacerbate the azotemia may be prudent. (J Am Vet Med Assoc 1996;208:875–878)

Neonatal Screening for Congenital Hypothyroidism in Riyadh: Analysis of Six Years' Experience

The regional screening program for congenital hypothyroidism (CH) in Riyadh Province was started as a pilot study in December 1988. By September 1990, the program covered all deliveries at the Ministry of Health (MOH) and King Saud University hospitals. The program utilizes cord serum thyroid-stimulating hormone (TSH) with a low recall rate of 0.1%. The average cost per specimen was SR 12 (US$ 3.20). Among 283,647 infants screened, 83 infants were confirmed to have CH (incidence 1:3417). In 17 infants, however, the diagnosis was not confirmed due to difficulties in recall. Eleven infants with cord serum TSH of more than 100 mU/L proved to be clinically and biochemically euthyroid at recall. Three of these were secondary to maternal proplthiouracil (PTU) therapy. The female to male ratio was 1.5:1. The majority of infants lacked clinical symptoms and signs of hypothyroidism. Thyroid scans showed the most common etiology to be thyroid ectopy (50%), followed by dyshormonogenesis (26%) and athyrosis (24%). Although there was no significant difference in the mean cord T4 values among the different groups, the mean T4 value at recall in the athyrotic group was significantly (P <0.001) lower than the cord results (14.8 versus 62.7) and that is of recall for the ectopic and dyshormonogenesis groups (14.8 versus 47.0 and 51.3 respectively0. There was bo significant difference in the mean TSH among the different groups in the cord and recall samples. Skeletal maturation was more delayed in the athyrotic group. The mean age at the time of recall was 16.4 days (range 4 to 64), and the mean age at the start of therapy was 17.8 days (range 5-64).

Anomalies du fonctionnement thyroidies chez les enfants tris oniques 21

To assess whether adding liothyronine (LT3) to levothyroxine (LT4) monotherapy normalizes serum thyrotropin (TSH) and thyroxine (T4) concentrations in children with congenital hypothyroidism and central resistance to thyroid hormone.We retrospectively studied 12 patients with congenital hypothyroidism and central resistance to thyroid hormone (6 treated with LT3+LT4 combined therapy and 6 treated with LT4 monotherapy). In patients receiving combined therapy, we compared serum concentrations of TSH, T4, and triiodothyronine before and after addition of LT3. We used repeated measures analysis to compare thyroid function in participants receiving combined therapy vs monotherapy, while accounting for age and intrasubject correlation.In patients receiving combined therapy, the addition of LT3 was associated with normalization of mean TSH (9.2 vs 4.5 mIU/L, P = .002), a lower proportion of TSH values greater than 10 mIU/L (35% vs 8%, P = .03), and a decrease in mean serum T4 by 23 ± 9% (P < .001). Compared with patients receiving LT4 monotherapy, patients receiving combined therapy had lower mean TSH (8.5 ± 0.9 vs 4.3 ± 0.4, P < .001), lower odds of TSH elevation greater than 10 mIU/L (OR 0.20, 95% CI 0.10-0.41, P < .001), and lower odds of T4 elevation (OR 0.21, 95% CI 0.04-1.09, P = .06). LT3 treatment did not increase serum T3 levels significantly.The addition of LT3 to LT4 monotherapy facilitates normalization of both serum TSH and T4 in patients with congenital hypothyroidism and central resistance to thyroid hormone. Larger prospective studies are needed to confirm these findings and to determine the effect of combined therapy on neurodevelopmental outcomes.

832 Acute radiation-induced thyroiditis—A prospective study

Purpose We prospectively studied acute radiation-induced thyroid dysfunction by performing thyroid function tests. Materials and methods The subjects were 28 patients who underwent neck irradiation incidentally including the thyroid for various malignancies. The total dose absorbed by the thyroid was 4500–5000 cGy. Thyroid function tests included serum thyroid stimulating hormone (TSH), free triiodothyronine (T3), and free thyroxine (T4). These data were obtained before irradiation, at 40 Gy irradiation, and 3 and 6 months thereafter. Results Mean TSH levels were 1.57,0.66, 1.34, and 6.23 μU/ml at preirradiation, 40 Gy irradiation, and 3 and 6 months after irradiation, respectively. The decrease in TSH levels at 40 Gy was significant (P = 0.0001, Wilcoxon signed-rank test). TSH levels significantly increased thereafter until 6 months (40 Gy vs 3 months:P = 0.001,3 months vs 6 months:P = 0.028). Mean T4 levels increased from 1.13 to 1.21 ng/ml during 40 Gy irradiation (P = 0.02). Conclusion The elevation of T4 and decrease in TSH observed at the time of irradiation was attributed to acute thyroid follicular cell destruction by irradiation.