Disturbance of the fetal thyroid hormone state has long-term consequences for treatment of thyroidal and central congenital hypothyroidism.

BACKGROUND: During T(4) supplementation of patients with thyroidal (primary) congenital hypothyroidism (CH) TSH concentrations are frequently elevated despite free T(4) (FT(4)) concentrations being well within the reference range. To examine the thyroid's regulatory system, we analyzed thyroid function determinants in children with congenital and acquired thyroid disorders and in controls. METHODS: Retrospectively, plasma FT(4), TSH, and T(3) concentrations were analyzed in T(4)-supplemented children aged 0.5-20.0 yr with thyroidal CH, central (secondary or tertiary) CH, or autoimmune thyroid disease and in control children with type 1 diabetes mellitus. RESULTS: When TSH was within the reference range (0.4-4.0 mU/liter), mean FT(4) in thyroidal CH [1.65 ng/dl; 95% confidence interval (CI), 1.62-1.67] was significantly higher than in autoimmune thyroid disease (1.15 ng/dl; 95% CI, 1.11-1.19) and diabetes (1.08 ng/dl; 95% CI, 1.06-1.10). In central CH, when TSH was less than or equal to 0.02 mU/liter, mean FT(4) was 1.27 ng/dl (95% CI, 1.24-1.29). When FT(4) was within the reference range (0.78-1.79 ng/dl), 43% of the TSH measurements in thyroidal CH were more than 4.0 mU/liter, compared with 18% in autoimmune thyroid disease and 0% in type 1 diabetes mellitus; in central CH, 95% of TSH measurements were less than 0.4 mU/liter. CONCLUSIONS: In T(4)-supplemented patients with thyroidal CH, when TSH concentrations are established within the reference range, FT(4) concentrations tend to be elevated, and vice versa. Because this phenomenon could not be observed in acquired thyroidal hypothyroidism, we hypothesize that a pre- and/or perinatal hypothyroid state shifts the setpoint of the thyroid's regulatory system. In central CH, when FT(4) concentrations are established within the reference range, the pituitary secretes only minute amounts of TSH. For monitoring T(4) supplementation, reference ranges for FT(4) and TSH should be adapted to the etiology of hypothyroidism.

[Two neonates with vesicular skin lesions due to incontinentia pigmenti]. / Twee pasgeborenen met blaasjes door incontinentia pigmenti.

In two neonate girls with vesicular skin lesions, incontinentia pigmenti (Bloch-Sulzberger syndrome) was diagnosed. This rare X-linked dominant ectodermal disease can cause abnormalities in several organ systems. Most prominent are the dermatological abnormalities, developing in 4 stages: the vesicular stage, the verrucous stage, the hyperpigmentation phase, and the atrophic phase. In addition to the cutaneous manifestations, many patients have anomalies of nails, hair and teeth. Serious related abnormalities of the eyes (intraocular vasculopathy) and central nervous system (convulsions, mental retardation) may occur. In 1989 the locus for the incontinentia pigmenti mutation was shown to be present on Xq28. Recently it was shown that the causative mutation is located on the NEMO ('NF-kappa B essential modulator') gene. A NEMO knock-out mouse model shows a dermatopathy of a transient nature, resembling the skin lesions in patients with incontinentia pigmenti.

Familial neurofibromatosis type 1 associated with an overgrowth syndrome resembling Weaver syndrome.

The simultaneous occurrence of familial neurofibromatosis type 1 (NF1) and an overgrowth syndrome resembling Weaver syndrome was observed in two related cases (a mother and her son). NF1 was confirmed by molecular genetic analysis showing a large deletion at 17q11.2, encompassing the entire NF1 gene. The other symptoms in the two cases were similar to the features reported in Weaver syndrome. Although the combination of NF1 and an overgrowth syndrome resembling Weaver syndrome in this family may be fortuitous, we favour the hypothesis that the deletion of the entire gene has caused this combined phenotype. Possible pathogenetic mechanisms are discussed. The observation suggests a relation between NF1 with an extraordinarily large gene deletion and a Weaver(-like) syndrome. This warrants investigation for deletions in the 17q11.2 region in Weaver(-like) syndrome patients.

Effects of pre- and postnatal exposure to chlorinated dioxins and furans on human neonatal thyroid hormone concentrations.

Animal studies have shown that dioxins influence plasma thyroid hormone concentrations. To investigate the effect of chlorinated dioxins and furans on thyroid hormone concentrations in humans, we studied 38 healthy breast-fed infants. The study population was divided into two groups according to the dioxin concentrations in milk fat of their mothers. Blood samples were taken at birth and at the ages of 1 and 11 weeks. At birth a tendency to higher total thyroxine (tT4) concentrations was found in the high exposure group. At the ages of 1 and 11 weeks the increase of mean tT4 concentrations and tT4/thyroxine-binding globulin ratios in the high exposure group reached significance as compared to the low exposure group. At birth and 1 week after birth, mean thyrotropin (TSH) concentrations were similar in both groups, but at the age of 11 weeks the mean TSH concentrations were significantly higher in the high exposure group. We postulate that the observed plasma tT4 elevation in infants exposed to dioxins before and after birth is the result of an effect on the thyroid hormone regulatory system.