Joseph Sack

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.

Clinical Variability of Congenital Adrenal Hyperplasia due to 11β-Hydroxylase Deficiency

Studies in 18 Jewish families from Morocco, Tunis, Turkey and Iran revealed 26 patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. The clinical expression of androgen exces

Umbilical cord cutting triggers hypertriiodothyroninemia and nonshivering thermogenesis in the newborn lamb.

Extract: The present studies in the newborn sheep were undertaken to further clarify the mechanism or mechanisms responsible for the early increases in serum thyroid hormone concentrations in the newborn as well as the significance of these changes to newborn nonshivering thermogenesis. Six groups of animals were studied to determine the influence of neonatal cooling, cord cutting, and the effects of thyrotropin-releasing hormone (TRH) and triiodothyronine (T3) injections.Group I newborns were delivered into room air with immediate cord cutting. Group II animals were delivered into room air and cord cutting was delayed 60 min. Group III animals were delivered into a 39° water bath and maintained for 60 min with the umbilical cord intact; the cord was cut at the time of removal from the water bath. Group IV animals were handled similarly to group III animals except that cord cutting was delayed 60 min after removal from the water bath. Group V and VI newborns were handled similarly to group IV animals except that TRH (group V) or T3 (group IV) was injected at the time of removal from the water bath. Deep rectal temperature and serum free fatty acids (FFA), thyroxfoe (T4), and T3 concentrations were measured in all newborns; FFA was measured as an index of catecholamine release. Serum thyroid-stimulating hormone (TSH) was measured in newborns from groups I and II.The results indicate that the newborn lamb responds to pat turition similarly to the human newborn. There are marked increases in mean serum T3 (50–242 ng/100 ml) and FFA levels (245–744 μEq/liter) during the first 60 min with only a transient fall in body temperature (39.1 ° to 37.4°), indicating effective nonshivering thermogenesis. Serum T4 concentrations do not increase significantly during this time. Warming in the water bath (groups III and IV) prevented the FFA and T3 responses, indicating that parturition per se is not the stimulus to these events. Delayed cord cutting (groups II and IV) produced marked hypothermia (to 35.6 and 34.4°), and the increases in serum FFA and T3 concentrations were not observed until the cord was cut.Mean baseline serum TSH concentrations were 4.7 and 5.3 μU/ml, respectively, in groups I and II animals and increased modestly to peak values at 30–60 min whether or not the umbilical cord was cut. TRH (group VI) did not increase serum T3 levels during the firs 60 min, but a significant 4-hr response (to 336 ng/100 ml) was observed. T3 (group VI) did not stimulate the FFA or thermogenic responses directly, but significantly augmented both responses to cord cutting. In addition, there was a significant correlation between serum FFA or T3 concentrations 60 min after cord cutting and minimal rectal temperature (r = 0.53 and 0.71, respectively; P < 0.005).The present results indicate that in the newborn sheep: (l) umbilical cord cutting, rather than cooling, stimulates FFA release, T3 production, and nonshivering thermogenesis; (2) that the early T3 response is not mediated via TRH and TSH, but probably represents increased peripheral monodeiodination of T4 to T3; and (3) catecholamine and T3 probably both play a significant role in newborn nonshivering thermogenesis.Speculation: The present studies indicate that umbilical cord cutting, rather than cooling, is the stimulus to increased FFA and T3 production and nonshivering thermogenesis in the newborn sheep. The FFA response presumably reflects increased catecholamine secretion. The T3 response probably is due to increased monodeiodination of T4 to T3, and there is preliminary evidence to suggest that this might be mediated by stimulation of tyroxine hydroxylase activity. Thus. increased catecholamine secretion and T3 production, both of which promote nonshivering thermogenesis, might be mediated via adrenergic nervous system stimulation. The mechanism for this stimulation by cord cutting, however, is not yet clear. The present studies also suggest that there are two mechanisms for the thyroidal hyperactivity in response to parturition; an early increase in T3 production due to augmented monodeiodination of T4 to T3; and increased thyroid hormone secretion, mediated by TSH, which more gradually increases serum T4 and T3 concentration during the first 24 hr of extrauterine life.

Reversible male infertility in late onset congenital adrenal hyperplasia

We have studied a male patient who presented with secondary infertility. His eldest daughter suffers from late onset congenital adrenal hyperplasia. Based on his hormonal profile, adrenal and gonadal stimulation tests, semen analyses and testicular biopsy he was diagnosed as suffering from the same disease as his daughter. Steroid treatment yielded improvement in all the parameters mentioned above. Four months later his wife became pregnant and he fathered a child. Suppression of gonadotropin secretion due to overproduction of adrenal androgens would appear to be the reason for the failure of testicular maturation and spermatogenesis in this patient. We conclude: 1) glucocorticoid treatment is indicated in infertile males suffering from nonclassical 21-hydroxylase deficiency; 2) Late onset congenital adrenal hyperplasia should be suspected in any male infertility of unknown origin.

Clinical and genetic heterogeneity of congenital adrenal hypoplasia due to NR0B1 gene mutations.

Introduction  X‐linked adrenal hypoplasia congenita (AHC) is a rare disorder caused by mutations or complete deletion of the NR0B1 gene that encodes the DAX‐1 protein, an orphan member of the nuclear receptor superfamily. AHC is characterized by adrenal insufficiency in infancy and early childhood. Later, hypogonadotropic hypogonadism (HH) manifests as pubertal failure.

Clinical and genetic characteristics of congenital hypothyroidism due to mutations in the thyroid peroxidase (TPO) gene in Israelis

Objectives  Iodide organification defect (IOD) is characterized by a reduced ability of the thyroid gland to retain iodide and results in hypothyroidism. Mutations in the thyroid peroxidase (TPO) gene are a frequent cause of IOD. While TPO mutations have been identified in various populations, none have been reported in Israeli patients with IOD. The objectives of this study were to characterize the molecular basis of IOD in an Israeli Arab‐Muslim population and to analyse the clinical, neurological and imaging data of patients with TPO mutations followed for up to 29 years.

Longitudinal Assessment of Pituitary-Thyroid Axis and Adrenal Function in Preterm Infants Raised by ‘Kangaroo Mother Care’

Objective: To assess whether complete kangaroo mother care (KMC), a skin-to-skin contact intervention, would affect longitudinal/developmental patterns of hormonal change. Method: An open randomized controlled trial was conducted in a large tertiary care hospital, comparing KMC and traditional care for newborn infants weighing less than 2,001 g. Eighty-seven healthy preterm (<37 weeks gestational age) infants from this study provided three blood-spot samples on filter paper: at randomization (postnatal age 1–5 days), 2 weeks later, and at calculated term (41 weeks gestational age). They met a number of additional inclusion criteria including discharge from the hospital within the first postnatal week. The levels of 17α-hydroxy-progesterone (17-OHP), thyroxine-stimulating hormone (TSH) and thyroxine (T4) were assessed by radioimmunoassay. Birth weight (<1,800 or ≧1,800 g) and prenatal maternal corticosteroid treatment were taken into account in the analysis. Interventions: Complete KMC includes early discharge, positioning the infant on the parent’s chest in an upright position, 24 h/day in skin-to-skin contact, and breast-feeding. In the traditional care group, infants were discharged according to routine hospital practice. Results: Levels of 17-OHP and TSH decreased significantly from eligibility to calculated term while T4 levels did not change significantly over time. Most importantly, overall, treatment (KMC) did not interact with the pattern of physiological change. Conclusions: Maturation of the pituitary-thyroid axis and adrenal function is apparently not compromised by KMC, at least in healthy preterm infants.

Somatostatin treatment of congenital chylothorax may induce transient hypothyroidism in newborns

AIM To describe a group of neonates with congenital, non-traumatic chylothorax, one of whom developed transient hypothyroidism following treatment with somatostatin. METHODS The charts of seven infants with congenital chylothorax were reviewed in terms of their clinical presentation, the severity of their disease, the complications they presented and the duration of their hospitalization. Their pituitary-thyroid axis function was monitored in particular. RESULTS The seven infants, all preterm (32-34 wk), suffered from congenital chylothorax and hydrops fetalis diagnosed during the prenatal period. Four were treated by intrauterine drainage, and four had congenital malformations. Hospitalization lasted from 32 to 120 d. Three of the infants suffered from thrombocytopenia, three had chronic lung disease, and one suffered from Gram-negative sepsis. The infant treated with somatostatin initially had normal thyroid function, but later developed primary transient hypothyroidism and was treated with L-thyroxine. The thyroid screening tests for the infants who were not treated with somatostatin were all normal. CONCLUSIONS Repeated doses of somatostatin were effective in reducing chylus production. Administering this treatment earlier should be considered in order to minimize known complications. The only potential side effect observed was primary transient hypothyroidism. Therefore, careful monitoring of the pituitary-thyroid axis is advised.

BREAST MILK THYROXINE AND NOT COW'S MILK MAY MITIGATE AND DELAY THE CLINICAL PICTURE OF NEONATAL HYPOTHYROIDISM

Abstract. Sack, J., Frucht, H., Amado, O., Brish, M. and Lunenfeld, B. (Institute of Endocrinology, the Chaim Sheba Medical Center, Tel Hashomer, Israel). Breast milk thyroxine and not cows milk may mitigate and delay the clinical picture of neonatal hypothyroidism. Acta Paediatr Scand, Suppl. 277: 54, 1979.‐Thyroxine concentration was measured in human milk and Cows milk products by a specific radioimmunoassay. The mean (± S.E.M.) milk T4 concentration during the first 5 days postpartum was 0.7±0.3 µg/dl (n=11). The mean T4 concentration between 6–49 days postpartum rose to 3.1±0.2 µg/dl (n=108), falling after 50 days to a mean of 1.4±0.2 µg/dl (n=39). The mean (± S.E.M.) T3 concentration in breast milk in the first 50 days postpartum was 386±17 ng/dl (n=56). T4 concentration in cows milk products was less than 0.3 µg/dl. Thyroxine concentration in 24 hours breast milk collection ranged from 0.7 to 7.7 µg/dl and the total T4 in this milk ranged from 0.7 to 28 µg/day. These data suggest that milk of human but not bovine origin may provide a significant exogenous source of T4 to the premature infant. This amount of exogenous T4 which is insufficient in preventing the proceeding of neonatal hypothyroidism, may delay the clinical recognition of this disorder. This once again emphasizes the importance of early screening for neonatal hypothyroidism.

Transient Elevation of Triiodothyronine Caused by Triiodothyronine Autoantibody Associated with Acute Epstein-Barr-Virus Infection

A unique 16-year old female patient presented after acute Epstein-Barr virus (EBV) infection with severe primary hypothyroidism. Her thyroid test results were thyrotropin level (TSH) of 198 mU/L (normal, 0.4-4 mU/L), free thyroxine [FT(4)], 2.5 pmol/L (normal, 10-25 pmol/L), total triiodothyronine (TT(3)) > 19.5 nmol/L (normal, 1.3-2.7 nmol/L), and free triiodothyronine (FT(3)), 0.77 pmol/L (normal, 3.3-6.3 pmol/L). She had high titers of thyroglobulin and thyroid peroxidase autoantibodies. In vitro triiodothyronine (T(3))-binding measured by radioimmunoprecipitation was 86% (normal, up to 8.5%) and thyroxine (T(4))-binding 8.2% (normal, 6.4%). Serum immunoglobulin G (IgG) absorption, achieved by protein-G Sepharose beads, decreased TT(3) toward normal. Levothyroxine treatment normalized the low baseline FT(4) and FT(3) values, and suppressed TSH to normal. However, TT(3) remained highly elevated and returned to normal after 20 months, while T(3 )binding gradually decreased. Thus, her severe hypothyroidism was masked by this unusual phenomenon. Thirty-four patients with EBV infection (15 with acute disease and 19 with previous infection) were tested for thyroid hormone levels. EBV antibodies (early antigen immunoglobulin M [IgM] and IgG and anti-Epstein-Barr virus nuclear antigen [EBNA] IgG) were measured by enzyme-linked immunosorbent assay (ELISA). In 15 patients with acute EBV the mean TT(3) level was 2.47 +/- 0.39 nmol/L (5 had TT(3) values above normal) compared to a mean TT(3) of 1.70 +/- 0.53 nmol/L in 19 subjects with previous infection (p < 0.0005; only 1 had a TT(3) result above normal), with no differences in FT(4) and TSH concentrations between the two groups. Acute EBV infection may be associated with transient mild to severe TT(3) elevation as a result of assay interference by anti-T(3) autoantibodies.