triiodothyronine--reverse and Goiter

The aim of the present study was to compare the effects of iopanoic acid (IOP) or a saturated solution of potassium iodide (SSKI) administration to patients with toxic diffuse goiters (TDG).. Patients with TDG are treated with thionamides and high doses of iodine preoperatively. In this study, two types of preoperative drug regimens were used: propylthiouracil or methimazole plus SSKI for 10-15 days (n=8) or IOP for 7 days (n=6).. Serum thyroid hormones (total and free thyroxine (T(4)), total tri-iodothyronine (T(3)) and reverse T(3) (rT(3)), were evaluated after 7 days of either SSKI or IOP treatment, and after 10-15 days of SSKI administration. During thyroidectomy, samples of thyroid gland were obtained to evaluate thyroperoxidase and thyroid H(2)O(2)-generating activities.. Serum total T(3) was significantly decreased after 7 days of either treatment, and serum rT(3) was significantly increased in IOP-treated patients. Serum total and free T(4) were unaffected by 7 days of IOP treatment, but decreased after 7 days of SSKI treatment, although significantly diminished levels were only reached after a further 3-8 days of SSKI administration. During both drug regimens, serum TSH remained low (SSKI: 0.159+/-0.122; IOP: 0.400+/-0.109 microU/ml). Thyroperoxidase activity was significantly lower in thyroid samples from patients treated with SSKI for 10-15 days than in the thyroid glands from IOP-treated patients. However, thyroid H(2)O(2) generation was inhibited in samples from patients treated with either IOP or SSKI.. We show herein that IOP treatment can be effective in the management of hyperthyroidism and that this drug inhibits thyroid NADPH oxidase activity, just as previously described for SSKI, probably due to its iodine content.

Topics: Adolescent; Adult; Calcium; Enzyme Inhibitors; Female; Goiter; Humans; Hydrogen Peroxide; Iodide Peroxidase; Iopanoic Acid; Male; NADP; NADPH Oxidases; Potassium Iodide; Thyroid Gland; Thyroidectomy; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

We studied the effect of suppressive therapy with graded doses of thyroxine (T4) on serum levels of T4, 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine [rT3] in patients with diffuse, nontoxic goiter. For comparison and in order to elucidate the degree of suppression of the pituitary thyroid axis by T3 the effect of suppressive therapy with T3 was studied in the same type of patients. We found that T4 in serum rose significantly to a constant level during T4 treatment (0.10, 0.15 and 0.20 mg/day). Dose-related rises in T4 were only seen after 3 months of treatment. T3 and rT3 only changed minimally. The T4/T3 ratio rose to a constant level during the initial 3 months of treatment. T3/rT3 ratio remained unchanged. No dose-related differences in T4/T3 and T3/rT3 ratio were observed. Treatment with T3 in doses of 0.06 mg per day caused a significant but slow fall in T4 and rT3 to hypothroid levels while T3 only rose slightly. The T4/T3 ratio dropped significantly during T3 therapy.

Topics: Adult; Aged; Female; Goiter; Humans; Male; Middle Aged; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Congenital defects in thyroglobulin (Tg) synthesis in animals have proven to be useful models for the study of Tg synthesis and regulation. Defects in Tg synthesis have been well described in Afrikander cattle, Australia Merino sheep, and goats in The Netherlands. This report describes a study of goiter in a nondomesticated bovine species, bongo antelope (Tragelaphus eurycerus), an African bovid. Three animals housed at the National Zoological Park, Washington, D.C. were studied; two had visible goiters, and a third bongo had microscopic evidence of goiter. Tg extracted from thyroid glands or thyroid colloid from these animals had a high mol wt component that was greater than 220K daltons and differed in apparent mol wt from 19S Tg from domestic cattle. Thyroid extracts also had thyroid albumin; albumin was more than half the total protein in colloid extract. The animals with goiter were euthyroid according to their circulating levels of thyroid hormones.

Topics: Animals; Antelopes; Artiodactyla; Chromatography, Gel; Cytochromes; Female; Goiter; Iodine; Male; Pedigree; Thyroglobulin; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

We assessed changes in serum total tri-iodothyronine (TT3), total thyroxine (TT4), free thyroxine (FT4), reverse tri-iodothyronine (rT3), thyroid stimulating hormone (TSH), and serum thyroglobulin (hTg) levels in 20 patients with toxic diffuse goiter who received subtotal thyroidectomy after metabolic control with antithyroid drugs and 22 patients with non-toxic solitary nodular goiter who received lobectomy only. In the first 2 days postoperatively the toxic diffuse goiter group had approximately a 50% decrease in the mean serum TT3 concentration, and a 28% decrease in the mean serum TT4 concentration. In the same period, the non-toxic nodular goiter group had approximately a 30% decrease in mean serum TT3 concentration, and a 15% decrease in mean serum TT4 concentration. The toxic diffuse goiter group and the non-toxic nodular goiter group each had transient elevations of the mean serum rT3 concentration, amounting to 34% and 48% respectively. Neither group had any change in the mean serum FT4 level, while both showed a several-fold elevation of serum hTg. At the 6th week postoperatively in both groups, the mean serum TT3 level had returned to the preoperative value, the mean serum TT4, rT3 and hTg levels were significantly lower than preoperative values, and the mean serum FT4 level remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Female; Goiter; Humans; Male; Middle Aged; Thyroglobulin; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Antibodies; Female; Goiter; Humans; Male; Microsomes; Middle Aged; Recurrence; Risk; Thyroglobulin; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Aminotriazole, a goitrogen, in addition to its known inhibitory effects on the thyroid, demonstrated a unique effect on peripheral deiodination of thyroxine (T4). In contrast to the well-known peripheral effects of goitrogens such as propylthiouracil in inhibiting 5'-deiodinase activity, i.e., to effect a decrease in T4 to triiodothyronine (T3) conversion, aminotriazole had no effect on the 5'-deiodinative pathway. Rather, this goitrogen appeared to stimulate the alternative pathway, viz. T4 5-deiodination, resulting in an increased reverse triiodothyronine (rT3) serum concentration. This was shown in comparisons of serum T4, T3 and rT3 concentrations and serum T3/T4 and rT3/T4 ratios between rats treated with aminotriazole and T4, and rats treated with T4 alone. The finding that aminotriazole may specifically enhance T4 5-deiodination, independently of T4 5'-deiodination, is novel, as this has not been observed in the case of other goitrogens. It is of interest that this goitrogen is devoid of sulphur, which is a prominent constituent of thiourylene compounds which have been noted to affect 5'-deiodination. The potentiating effect of aminotriazole on 5-deiodination of T4 was not attributable to dietary factors.

Topics: Amitrole; Animals; Goiter; Iodine; Male; Rats; Rats, Inbred Strains; Thyroxine; Triazoles; Triiodothyronine; Triiodothyronine, Reverse

Amiodarone, an iodine-containing drug used frequently in the treatment of cardiac arrhythmias and angina pectoris, has many effects on thyroid hormone metabolism, including decreasing the production of triiodothyronine (T3) and decreasing the clearance of thyroxine and reverse T3. These effects result in elevated serum thyroxine and reverse T3 concentrations and decreased serum T3 concentrations. In addition, iodine-induced hyperthyroidism or hypothyroidism may occur in patients chronically treated with amiodarone. This study is a retrospective analysis of the incidence of thyroid dysfunction in Lucca and Pisa, West Tuscany, Italy, and in Worcester, Massachusetts. Hyperthyroidism was a more frequent (9.6%) complication of amiodarone therapy in West Tuscany, where iodine intake is moderately low; hypothyroidism was more frequent (22%) in Worcester, where iodine intake is sufficient. In patients receiving chronic amiodarone therapy, clinically suspected hyperthyroidism is best confirmed by showing elevations in serum T3 or free T3 concentrations; hypothyroidism is best diagnosed by showing an elevated serum thyrotrophin concentration. Thyroid function should be carefully monitored in patients receiving amiodarone chronically, especially if they have goiter or Hashimoto's thyroiditis.

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Goiter; Heart Diseases; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Italy; Long-Term Care; Male; Massachusetts; Middle Aged; Retrospective Studies; Thyroglobulin; Thyroid Diseases; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The secretion rates of T4, T3, and rT3 were studied in experiments of short duration by a new method based on determinations of the hormone difference across the thyroid combined with simultaneous electromagnetic thyroid blood flowmetry during surgery in 70 euthyroid patients. The secretion rate of T3 was similar in normal thyroid tissue and nodular goitre, but those of T4 and rT3 were lower in nodular goitre and solitary adenoma (P less than 0.05). In 61 patients with normal thyroid tissue or nodular goitre the secretion rates during surgery (mean +/- SEM) were for T4 222 +/- 28 nmol/day, for T3 27.4 +/- 3.1 nmol/day, and for rT3 3.5 +/- 0.5 nmol/day. In relation to the individual T4 secretion rate, the secretion rate of T3 was 12.5 +/- 3.0% and that of rT3 1.2 +/- 0.9%. In these short-term experiments we found a secretion rate for T4 during operation about 50% greater than in earlier long-term kinetic studies, but which tallied with a recent report using a 4-compartment model. For T3 and rT3 it was 2-3 times greater than earlier estimates. The secretion was estimated to be 50% of the total production rate for T3 and 6% for rT3. If proportional adjustment were performed to yield a T4 secretion of about 130 nmol/day. T3 and rT3 secretion rates would still be greater than earlier reported.

Topics: Adenoma; Adult; Aged; Carcinoma; Electromagnetic Phenomena; Female; Goiter; Goiter, Nodular; Humans; Hyperparathyroidism; Intraoperative Period; Male; Middle Aged; Rheology; Surgical Procedures, Operative; Thyroid Gland; Thyroid Neoplasms; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Morphological and functional properties of dispersed cells of human adenomatous goiter and those of the thyroid tissue adjacent to and distant from the nodular lesion (normal control) were investigated. In the presence of TSH, reconstructive arrangement of adenomatous goiter cells into a three-dimensional follicular structure occurred in a similar manner to that of normal controls. An addition of thyrotropin (TSH) to culture resulted in the secretion of thyroid hormones in control cells, but adenomatous goiter cells showed no response to TSH. It was found that the ratio of rT3, T3, the ratio of an inactive to an active form, was about three times higher in adenomatous goiter than in normal control. These findings suggested that conversion from T4 to rT3 is increased in adenomatous goiter.

Topics: Adenoma; Cells, Cultured; Goiter; Humans; Thyroid Hormones; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Without firm diagnosis a 16-year old boy was submitted to subtotal thyroidectomy because of a diffuse goitre and emotional instability. No definite improvement was obtained in the alleged toxic symptoms and the goitre recurred. During subsequent years increased serum concentrations of thyroid hormones have repeatedly been observed in the absence of clear-cut hyperthyroid symptoms. Judging from clinical examination and a normal basal metabolic rate the patient, now 35 years old, was euthyroid at the present study. Basal serum-TSH concentration was normal to slightly elevated; it was definitely abnormal in relation to the high serum concentration of free T4. Serum T4, T3 and rT3 concentrations were also abnormally high in the face of normal levels of TBG and prealbumin. Agarose gel electrophoresis revealed normal binding pattern for T4. After 200 micrograms of TRH intravenously there was an abnormally high rise of serum TSH. Concentrations of prolactin and glycopeptide-hormone alpha subunit as well as the pituitary-gonadal and adrenocortical functions were normal. Sella turcica was seemingly normal. During oral administration of T3, 160 micrograms daily for 5 days, the circulating T4, free T4 and rT3 concentrations decreased and the response to TRH was suppressed to that found in normal, untreated individuals. However, no clinical response to the drug was seen and the metabolic rate was unchanged. The patient had poor performance at school but acceptable performance at routine manual work. He had defective colour vision, a refractory anomaly, neurogenic auditory damage but no skeletal abnormalities. Laboratory investigation revealed features characteristic of partial thyroid hormone resistance in the pituitary and the peripheral tissues.

Topics: Adult; Body Temperature; Goiter; Heart Rate; Humans; Male; Metabolic Clearance Rate; Pituitary Gland; Prolactin; Recurrence; Thyroid Function Tests; Thyroid Hormones; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Eight patients with thyroid hormone resistance were found in four generations of a kindred containing 19 members. Results of studies in this family are consistent with an autosomal dominant mode of inheritance for this disorder. The affected family members were clinically euthyroid but all had goiters and markedly increased serum thyroid hormone levels: thyroxine (T4) = 21.1 +/- 2.1 microgram/dl; triiodothyronine (T3) = 323 +/- 60 ng/dl; free T4 = 5.4 +/- 0.9 ng/dl; and free T3 = 1,134 +/- 356 pg/dl (mean +/- SD). Serum thyrotropin (TSH) levels were normal or slightly elevated in six patients and responded normally to the administration of thyrotropin-releasing hormone (TRH) and L-triiodothyronine. Two patients who had previously undergone subtotal thyroidectomy had elevated baseline serum TSH levels and exaggerated TSH responses to the administration of TRH suggesting subclinical hypothyroidism despite elevated total and free thyroid hormone levels. The absence of thyrotoxicosis and normal serum TSH levels despite elevated serum free T3 and T4 levels in the untreated members of this family are consistent with resistance of pituitary and peripheral tissues to the actions of thyroid hormones. In addition, the absence of hypothyroidism and normal responsiveness of serum TSH to TRH and L-triiodothyronine administration in untreated family members suggest that the thyroid has compensated for the hormone resistance by increased secretory activity under the control of pituitary TSH secretion.

Topics: Adolescent; Adult; Child; Chromosome Aberrations; Chromosome Disorders; Female; Genes, Dominant; Goiter; Humans; Infant; Male; Middle Aged; Pedigree; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Animals; Binding, Competitive; Blood; Child; Goiter; Humans; Immunoglobulins; In Vitro Techniques; Male; Protein Binding; Rabbits; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum reverse T3, T3, T4, and TSH concentrations were measured in children with goitre of grade II and III, and in controls of the same age. The average rT3 level was decreased in both goitrous groups and the difference between them was significant. The rT3/T4 ratio in each group changed in a similar way. It seems that in goitre not only the T3 secretion of the thyroid gland is increased but also the deiodination of T4 to T3 increases against rT3, or the degradation and metabolic clearance of T3 and rT3 change.

Topics: Child; Goiter; Humans; Iodine; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The thyroid function of patients with three different types of organification defect was studied. All patients were characterized by a high thyroidal 131I uptake and a positive perchlorate discharge. Patients with Pendred's syndrome who had goitre and congenital nerve deafness were mostly euthyroid with normal circulating thyroid hormone levels. Only two of them had compensated euthyroidism with elevated total T3, high basal TSH and delayed return to basal value with TRH. The patients who were euthyroid with large goitres and normal hearing had elevated total T3 and an exaggerated TSH response to TRH. The thyroid function of these two groups of patients contrasted with that of goitrous cretins, who were clinically hypothyroid with low circulating total T4, increased T3 and decreased rT3 levels. The data suggest that in patients with intrathyroidal iodine deficiency secondary to organification defect, there is preferential T3 production in an effort to maintain euthyroid state, and this is further substantiated in the case of gross thyroid insufficiency either by enhanced peripheral conversion of T4 to T3, or reduced metabolic clearance of T3 and increased clearance of rT3, resulting in elevated T3 and decreased rT3 levels.

Topics: Adolescent; Adult; Congenital Hypothyroidism; Deafness; Female; Goiter; Humans; Iodine; Male; Pedigree; Syndrome; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Child; Goiter; Humans; Triiodothyronine; Triiodothyronine, Reverse