Free Thyroxine Concentrations in Sera of Individuals with Familial Dysalbuminemic Hyperthyroxinemia: A Comparison of Three Methods of Measurement.

Euthyroid individuals with familial dysalbuminemic hyperthyroxinemia (FDH) have often falsely elevated serum free thyroxine (fT4) concentrations determined by different automated immunoassays. We measured serum fT4 using direct dialysis coupled with tandem mass spectrometry (fT4 DDMS) in individuals with the common gene mutation ( R218H) from 14 FDH families and compared them with results obtained by direct immunometric assay (fT4 DIMM) and free thyroxine index (fT4I). While all 14 individuals with FDH had elevated total serum T4, the fT4 measured by DIMM was elevated in 12, by fT4I in 5, and by DDMS in 1.

Reduced Sensitivity to Thyroid Hormone as a Transgenerational Epigenetic Marker Transmitted Along the Human Male Line.

Evidence for transgenerational epigenetic inheritance in humans is still controversial, given the requirement to demonstrate persistence of the phenotype across three generations. A previous study showed that exposure of human and mouse embryos to high maternal thyroid hormone (TH) concentrations not only affects the newborns but also subsequently reduces thyrotroph sensitivity to TH during adult life. The current investigation set out to determine if this epigenetic effect is transmitted by humans not exposed to high TH levels to their offspring.

Homozygous Mutation in Human Serum Albumin and Its Implication on Thyroid Tests.

An individual with familial dysalbuminemic hyperthyroxinemia (FDH) due to a homozygous mutation (c.653G>A, p.R218H) in the human serum albumin (HSA) gene is reported.

Diagnostic Dilemma in Discordant Thyroid Function Tests Due to Thyroid Hormone Autoantibodies.

Objective: Assay interference could be the cause of abnormal thyroid function tests. Early recognition prevents inappropriate patient management. The objective of this report is to present a case with discordant thyroid function tests in different thyroid assay platforms due to thyroid autoantibodies.

A TSHβ Variant with Impaired Immunoreactivity but Intact Biological Activity and Its Clinical Implications.

Background: Thyrotropin (TSH) deficiency caused by TSHβ gene mutations is a rare form of congenital central hypothyroidism. Nine different TSHβ gene mutations have been reported, all with clinical manifestations. The aim was to identify the genetic cause of undetectable TSH levels in two siblings with clinical euthyroidism.

A novel, ultrarapid parathyroid hormone assay to distinguish parathyroid from nonparathyroid tissue.

Background: Frozen section is the gold standard for distinguishing parathyroid tissue from lymph nodes, thyroid nodules, or fat during parathyroidectomy and thyroidectomy. Although a very accurate procedure, it can be time-consuming and costly. We hypothesize that the extremely high concentrations of parathyroid hormone (PTH) in parathyroid tissue allow for modification of a standard PTH assay that would distinguish parathyroid from nonparathyroid tissue in substantially less time than frozen section or any currently available PTH assay.

Twenty-four-hour profiles of acylated and total ghrelin: relationship with glucose levels and impact of time of day and sleep.

Context: The acylation of ghrelin is essential for its stimulatory effects on GH release and appetite. Most of the physiology of ghrelin has been defined based on the assay of total ghrelin (TG), which mainly reflects levels of unacylated ghrelin. Whether levels of acylated ghrelin (AG) are influenced by circadian time and sleep and impact glucose regulation under physiologic conditions is not known.

Autosomal dominant resistance to thyrotropin as a distinct entity in five multigenerational kindreds: clinical characterization and exclusion of candidate loci.

Context: Resistance to TSH (RTSH) is an inherited disorder of variable hyposensitivity to TSH. The metabolic consequences can range from euthyroid hyperthyrotropinemia to severe congenital hypothyroidism with thyroid hypoplasia. Although subclinical and mild hypothyroidism fitting the RTSH phenotype is common in the population, the role of genetic factors is far from being understood.

Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-beta gene: phenotypic variability and founder effect.

Isolated TSH deficiency is a rare cause of congenital hypothyroidism. We here report four children from two consanguineous Turkish families with isolated TSH deficiency. Affected children who were screened at newborn age had an unremarkable TSH result and a low serum TSH level at diagnosis.

Familial dysalbuminemic hyperthyroxinemia in a Swiss family caused by a mutant albumin (R218P) shows an apparent discrepancy between serum concentration and affinity for thyroxine.

Familial dysalbuminemic hyperthyroxinemia (FDH), is the most common cause of inherited increase in serum total T4 (TT4) in the Caucasian population. It is caused by a mutation (R218H) in the human serum albumin (HSA) gene, resulting in 10-fold higher affinity for T4 and, in heterozygous affected subjects, a TT4 level 2-fold higher than that in subjects expressing the wild-type HSA only. We now report FDH in a Swiss family, caused by HSA R218P, previously reported in subjects of Japanese origin.

Congenital central isolated hypothyroidism caused by a homozygous mutation in the TSH-beta subunit gene.

We report a Belgian girl born in 1983 with isolated thyrotropin (TSH) deficiency. Hypothyroidism without goiter was diagnosed at the age of 2 months, with extremely low total thyroxine (T4) at 0.3 microg/dL (4 nmol/L; N[normal]: 5.

Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect.

We report the abnormal albumin in members of a Thai family that presented with high serum total T3 but not T4 when measured by radioimmunoassay. In contrast, total T3 values were very low when measured by ELISA and chemiluminescence. The subjects have no goiter, and clinically euthyroid.

Induction of oral tolerance in human autoimmune thyroid disease.

Our laboratory has reported suppression of experimental autoimmune thyroiditis in mice by oral feeding with antigen. Based on these data, we considered it possible that oral feeding of animal thyroglobulin (TG) might induce tolerance to antigen in human autoimmune thyroid disease (AITD). Thirteen patients receiving thyroid hormone replacement with synthetic thyroxine (T4) (five patients with Graves' disease, treated with radioiodine 4 to 11 years ago and eight patients with Hashimoto's thyroiditis) were randomly assigned to a test group (switched to replacement with desiccated thyroid from porcine thyroids) and a control group (maintained on synthetic T4).

Monoclonal antibodies to rat calcitonin: their use in antigenic mapping and immunohistochemistry.

A library of monoclonal antibodies (mAbs) to rat calcitonin (rCT) was raised from several fusions. Antibodies were screened by enzyme-linked immunosorbent assay with solid phase rCT. Affinities for rCT ranged from 10(9)-10(11) M(-1).

Thyroid function tests and characterization of thyroxine-binding globulin in the carbohydrate-deficient glycoprotein syndrome type I.

Carbohydrate-deficient glycoprotein (CDG) syndrome is a newly recognized hereditary disorder that presents with psychomotor retardation, cerebellar ataxia, peripheral sensorimotor neuropathy, and, variably, skeletal abnormalities, lipodystrophy, and retinitis pigmentosa. These abnormalities appear to be produced by a defect that causes reduced carbohydrate content in glycoproteins. We studied seven patients with CDG type I belonging to five unrelated families.

Does thyroidectomy, radioactive iodine therapy, or antithyroid drug treatment alter reactivity of patients' T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases?

The effect of treatment on thyroid antibody production and T cell reactivity to thyroid antigens was studied in 15 patients with Graves' disease (GD) before and after thyroidectomy, 19 patients with GD before and after radioactive iodine (RAI) therapy, and 9 patients maintained euthyroid on antithyroid drugs (ATD). Twenty subjects matched for age and sex without known thyroid disease served as controls. In GD patients, the responses of peripheral blood mononuclear cells (PBMC) and TSH receptor (TSHR)-specific T cell lines to recombinant human TSHR extracellular domain, thyroglobulin, and TSHR peptides were examined on the day of surgery or RAI therapy (day 0) and also 6-8 weeks and 3-6 months thereafter.

Preliminary studies on the immediate phase-shifting effects of light and exercise on the human circadian clock.

The aim of the present research was to determine the magnitude and direction of immediate phase shifts of human rhythms following a single exposure to a 3-hr pulse of bright light or physical activity. The pulse of light or activity was presented under "constant-routine" conditions, and measurements of the resultant phase shifts were performed under the same constant-routine conditions on the first day following pulse presentation. Four overt rhythms that are strongly dependent on circadian timing--namely, the rhythms of plasma cortisol, plasma thyroid-stimulating hormone (TSH), plasma melatonin, and body temperature--were monitored.

Differential elimination of radioiodine from single- and double-stranded 125I-DNA.

[125I]Iododeoxyuridyl residues in heat-denatured I-DNA underwent deiodination in solutions of sodium bisulfite. In 0.5 M bisulfite containing 1 M trimethylamine, 92% of the iodine was released from denatured DNA in 2.

Site-specific incorporation of [125I]iododeoxyuridine into DNA.

A procedure for the incorporation of [125I]IdU into specific sites in DNA is described. The approach depends upon attachment of radioiododeoxyuridine to a controlled pore glass support which is then used for automated synthesis of an oligomer. The resulting oligomer, containing a terminal 3'[125I]iododeoxyuridine, is used as a primer during DNA synthesis catalyzed by the Taq polymerase employing thermal cycling.

Neonatal detection of generalized resistance to thyroid hormone.

Generalized resistance to thyroid hormone (GRTH) is an inherited disease that is usually suspected when elevated serum thyroid hormone levels are associated with nonsuppressed thyrotropin. Often these test results are obtained because of short stature, decreased intelligence, and/or hyperactivity with learning disability noted in childhood and adolescence, or because of goiter in adulthood. We detected GRTH at birth by analysis of blood obtained during routine neonatal screening.

Anterior pituitary: triiodothyronine and/or dexamethasone induced changes in protein formation in thyroidectomized and/or adrenalectomized rats.

Protein formation in the anterior pituitary was investigated in vitro in thyroidectomized (TX) and/or adrenalectomited (AX) rats treated with a single dose of 100 micrograms/100 g of 3,5,3'-triiodothyronine (T3) and/or with a single dose of 10 micrograms/100 g of dexamethazone (DEX) 12 h before sacrifice. Male Wistar rats of a specific pathogen free colony 6 weeks after TX and/or AX receiving 1% calcium chloride and/or saline after surgery were used in the experiments. Non-pooled anterior pituitaries (in acellular condition) complemented with all essential amino acids, CPK, creatine phosphate in a HEPES buffer containing potassium acetate, magnesium acetate and dithiothreitol, were incubated with 35S-methionine at 28 degrees C for 10 or 40 min.

Translational control of insulin biosynthesis. Evidence for regulation of elongation, initiation and signal-recognition-particle-mediated translational arrest by glucose.

The biosynthesis of insulin in the islets of Langerhans is strongly controlled at the translational level by glucose. We have used a variety of experimental approaches in efforts to dissect the mechanisms underlying the stimulatory effect of glucose. To assess its effects on rates of peptide-chain elongation, isolated rat islets were labelled with [3H]leucine at different glucose concentrations in the presence or absence of low concentrations of cycloheximide.

Direct application of radioiodinated aminoacyl tRNA for radiolabeling nascent proteins.

A two-step procedure to incorporate 125I-iodotyrosine into protein synthesized in a reticulocyte lysate is described. In the first step, the iodination of tyrosyl tRNA was catalyzed by a solid-state glycouril compound. More than one-third of 200 microCi of radioiodine became bound to 70 micrograms of aminoacyl tRNA after 15 min at 0 degrees C.

Elevated serum thyroglobulin level in congenital thyroxine-binding globulin deficiency.

Serum thyroglobulin (TG) is normally under TSH control. Serum TG levels are elevated during increased thyroid gland stimulation and suppressed by exogenous thyroid hormone. High serum TG levels are also found with thyroid gland damage and in patients with differentiated thyroid neoplasms.