3'-monoiodothyronine sulfate and Triac sulfate are thyroid hormone metabolites in developing sheep.

We used novel 3'-monoiodothyronine sulfate (3'-T1S) and 3,3',5-triiodothyroacetic acid sulfate (TriacS) RIAs to characterize sulfation pathways in fetal thyroid hormone metabolism. 3'-T1S and TriacS levels were measured in serum samples obtained from fetal (n = 21, 94-145 d gestational age), newborn (NB, n = 5), and adult sheep (AD, n = 5) as well as from fetuses after total thyroidectomy (Tx), or sham-operated twin fetuses controls, conducted at gestational age 110-113 d (n = 5). Peak levels (expressed as ng/dL) of both 3'-T1S and TriacS occurred at 130 d gestation. These levels in fetuses were higher than those in NB and AD. In Tx fetuses, there was a significant decrease in the mean serum level of 3'-T1S, but not TriacS. The decrease in 3'-T1S in Tx is similar to that observed for thyroxine sulfate (T4S) and 3,3',5'-triiodothyronine sulfate (rT3S), whereas TriacS levels were not altered in the hypothyroid state, similarly to 3,3',5-triiodothyronine sulfate (T3S). These data demonstrate that 3'-T1S and TriacS are normal thyroid hormone metabolites in ovine serum and that TriacS is likely derived from T3S or from the same precursor(s) as T3S.

Fetal-to-maternal transfer of thyroid hormone metabolites in late gestation in sheep.

3,3'-Diiodothyronine sulfate (T2S) derived from T3 of fetal origin is transferred to the maternal circulation and contributes significantly to the maternal urinary pool. The present study quantitatively assesses the fetal to maternal transfer of T4 metabolites compared with those of T3. Labeled T4 or T3 was infused intravenously to four singleton fetuses in utero in each group at gestational age 138 +/- 3 d. Maternal and fetal serum and maternal urine samples were collected hourly for 4 h and at 24 h (serum) or in pooled 4-24 h samples (urine). Radioactive metabolites were identified by HPLC and by specific antibody in serum and urine extracts and expressed as percentage infusion dose per liter. The results demonstrate a rapid clearance of labeled T3 from fetal serum (disappearance T(1/2) of 0.7 h versus 2.4 h for T4 in the first 4 h). The metabolites found in fetal serum after labeled T3 infusion were T2S > T3 > T3S; in maternal urine, T2S > unconjugated iodothyronines (UI) > T3S > unknown metabolite (UM). After labeled T4 infusion, the metabolites in fetal serum were rT3 > T3 > T2S > T4S in the first 4 h, and rT3 = T3 = T4S = T2S > T3S at 24 h; in maternal urine we found T2S > UM > UI > T4S > T3S in the first 4 h and UM > T2S > UI in 4-24 h pooled sample. In conclusion, the conversion of T3 to T2S followed by fetal to maternal transfer of T2S and other iodothyronines appears to contribute importantly to maintaining low fetal T3 levels in late gestation.

Managing a pediatric hospitalist practice requires team approach.

Establishing and maintaining a productive hospitalist program relies on the forging of multiple partnerships involving pediatric hospitalists, community practitioners, and administrative organizations including hospitals and multiple practice groups. When these professional relationships are successful, everyone in the relationship benefits, especially the children and families who deserve the best medical practices that can be offered. Establishing these relationships within defined communities ultimately improves pediatric outcomes.

Adrenal and thyroid axis function in preterm ventilated baboons.

Cortisol and thyroid hormones are critical to normal fetal development and neonatal transition, and baseline values and stimulation tests are abnormal after preterm birth. To evaluate cortisol and thyroxine (T4) responses that are not influenced by uncontrolled antenatal events associated with human preterm labor, we measured cortisol and T4 after standard-dose adrenocorticotropin (ACTH) and corticotropin-releasing hormone (CRH) stimulation tests, as well as high-dose CRH and thyrotropin-releasing hormone stimulation tests in baboons that were delivered for 3 separate protocols at 125 days of gestation (term is 186 days). The animals were surfactant treated and ventilated for up to 14 days. Some fetuses were exposed to fetal or maternal betamethasone, and some newborns were treated with 10 microg/kg T4 for 9 days after birth. Baseline cortisol levels were in a stress range of 30-60 microg/dl by day 5. Cortisol did not increase consistently until day 11 in response to a high CRH dose or ACTH. T4 treatment for 9 days after birth suppressed the cortisol responses and subsequent baseline T4 levels. The hypothalamic-pituitary-adrenal (HPA) axis was unresponsive to standard dose stimulation tests until 11 days of age in preterm baboons, indicating HPA immaturity.