Elevated Free T4 Research Articles

A long-term follow-up study of patients with non-toxic diffuse goitre in Japan.

Although non-toxic diffuse goitre is a common disorder, little is known of the clinical course of patients. We therefore decided to investigate the long-term clinical outcome of patients with non-toxic diffuse goitre. A retrospective study. Of 850 patients with non-toxic diffuse goitre who met our criteria and were seen in our thyroid clinic between 1977 and 1985, 108 who had been followed for from 5 to 14 years (mean 8 years) were entered in this study. All patients fulfilled our criteria having soft diffuse goitres, normal serum TSH and T4 concentrations, and undetectable antithyroglobulin and antithyroid microsomal antibodies. A family history of thyroid disease was obtained and the occurrence of Graves' ophthalmopathy was noted. Serum TSH and T4 concentrations, and antithyroglobulin and antithyroid microsomal antibodies were measured during the follow-up period. Thyroidal radioactive iodine uptake (RAIU), serum free T4 and free T3 concentrations, and TSH binding inhibitory immunoglobulin (TBII) activities were determined in all patients who were subsequently found to have abnormal serum TSH or T4 concentrations or signs of Graves' ophthalmopathy. Thirty-six of the 108 patients (33%) had a family history of autoimmune thyroid disease. Elevated serum T4 or free T4 concentrations and depressed serum TSH concentrations were found in six patients during the follow-up period. Hyperthyroid Graves' disease was diagnosed in four of the six patients, subacute thyroiditis in one, and transient post-partum thyrotoxicosis in one. Hypothyroidism was found in one patient who was diagnosed as having transient post-partum hypothyroidism. Euthyroid Graves' disease was diagnosed in one patient. Furthermore, six of these eight patients had a family history of autoimmune thyroid disease in first-degree relatives. During a prolonged follow-up period of patients with non-toxic diffuse goitre, Graves' disease was found in five of 108 patients (four hyperthyroid Graves' and one euthyroid Graves'), post-partum thyroid dysfunction in two, and subacute thyroiditis in one. Six of these eight patients had a family history of autoimmune thyroid disease in first-degree relatives. Long-term follow-up is necessary for patients with non-toxic diffuse goitre, especially those who have a family history of autoimmune thyroid disease.

Endemic goitre in Senegal--thyroid function etiological factors and treatment with oral iodized oil.

Endemic goitre and its response to orally administered iodized oil has been studied in seven villages 25-30 km south of Velingara, Eastern Casamance, Senegal. In 502 adults aged greater than 15 years goitre prevalence was 62% with 18.2% having goitre grade 2 or 3. Mean free T4 (FT4) was 11.9 +/- 3.5 (SD) pmol/l and iodine deficiency was confirmed by noting median urinary I of 0.079 mumol/l (14.9 mumol I/mol creatinine) with elevated free T3 (FT3)/FT4 ratios. Serum selenium concentrations were normal. The response to 480 mg of oral iodized oil assessed at 6 and 12 months was characterized by a 35.8% increase in FT4, a 25% decrease in FT3 and a 50% decrease in TSH (all p less than 0.01) at 12 months associated with a significant decrease in goitre size measured in 70 persons when compared to 65 controls not receiving iodine. Urinary iodine rose from 0.071 mumol/l to 0.189 mumol/l (p less than 0.01) during this time and no adverse effects on thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) were observed. A variation in goitre prevalence between villages was noted which, in such a small geographical area, suggests that etiological factors in addition to iodine deficiency may be important in goitre pathogenesis. Oral iodized oil administration is an effective treatment for iodine deficiency goitre in the short term.

5 Thyroid emergencies

Thyroid storm is a rapid decompensation of severe hyperthyroidism which can best be described by the three criteria of hyperthermia, tachycardia and altered mental state with severe agitation. There has to be a precipitating factor such as infection, iodine contamination, surgery or even I-131 treatment. Severe hyperthyroidism not fulfilling the criteria of thyroid storm can also be an indication for emergency treatment, particularly in the elderly with heart disease. Suppressed serum TSH and elevated free T4 levels are essential to confirm the diagnosis. When rapidly available, radioiodine uptake of the thyroid can be useful. Therapy aims at rapidly reducing the active circulating hormone pool, hypermetabolic state, tachycardia, and finally hormone synthesis. Thyroid secretion can be blocked by ioipanoic acid or ipodate while hypermetabolic state can be reduced with β-blockers or calcium channel-blockers. Treatment of hyperthyroidism in patients with iodine contamination is a real therapeutic challenge. Myxoedema coma, a complication of severe hypothyroidism, is defined by hypothermia (rectal temperature less than 36°C), bradycardia, slow mentation, precipitating factor such as infection or drug overdose, and increased serum creatine phosphokinase levels. Diagnosis of severe hypothyroidism should be confirmed by serum measurements of TSH and free T4. Treatment consists of general supporting measures including rewarming, correction of serum electrolyte disturbances, and adequate alimentation. Thyroid hormone treatment should initially be aggressive using either 300–400 μg of T4 or 20–40 μg of T3 intravenously. Cortisone therapy may be added. Patients should be under close monitoring as arrhythmias and myocardial infarction are frequent complications of myxoedema coma and/or its treatment with thyroid hormones.

Changes in circulating thyroid hormone levels and systolic time intervals in acute hypothyroidism

We have previously reported that, in thyrotoxic patients treated with carbimazole, serum T4 and T3 levels are the first parameters to return to normal, followed by the systolic time interval (STI, a marker of thyroid function at tissue level) and then the serum TSH. The aim of this study was to compare the rate of change of thyroid hormones, TSH and STI in treated hypothyroid patients after the sudden withdrawal of thyroxine. Serum T4, T3 (free and total) and TSH were measured in 12 patients taking thyroxine for primary hypothyroidism; seven were biochemically euthyroid and five were over-replaced, as defined by an elevated free T4 and a sub-normal TSH. Thyroxine was withdrawn and the measurements repeated three times a week until the STI rose above the euthyroid range (0.26-0.32). After stopping thyroxine, the serum TSH and STI left the normal range, in advance of the free T4 and T3, after 9.5 +/- 0.95 and 12.2 +/- 1.5 days respectively (mean +/- SEM). The TSH was the first parameter to leave the euthyroid range in all subjects except one in whom the serum TSH was fully suppressed (less than 0.05 mU/l) initially. In the euthyroid group the TSH and STI increased rapidly after stopping thyroxine (time to leave euthyroid range 7.4 +/- 0.8 and 9.4 +/- 0.7 days respectively). In contrast, in the over-replaced group serum TSH and STI became elevated after 12.4 +/- 1.0 days (P less than 0.005 vs euthyroid group) and 16.0 +/- 2.7 days (P less than 0.05 vs euthyroid group) respectively. There was no delay in the fall in serum T4 or T3 in the over-replaced group when compared with the euthyroid group. In the evolution of primary hypothyroidism, markers of thyroid function at a tissue level (TSH and STI) become abnormal in advance of thyroid hormones. After stopping thyroxine therapy in treated hypothyroid patients, there is a delayed rise in STI and serum TSH levels in subjects with a subnormal TSH level, as compared with those with a normal TSH on treatment. This suggests mild tissue thyrotoxicosis in these individuals.

A Study of the Serum Concentration of Tumor Necrosis Factor-α in Thyroidal and Nonthyroidal Illnesses*

We have studied serum concentrations of immunoassayable tumor necrosis factor-alpha (TNF alpha) and iodothyronines (T4, T3, and rT3) in normal subjects (n = 16) and patients with nonthyroidal illnesses (NTI; n = 13), hyperthyroidism (n = 10), and hypothyroidism (n = 9). The mean (+/- SEM; femtomoles per mL) serum concentration of TNF alpha was 45 +/- 4.3 in normal subjects, 84 +/- 38 in NTI, 54 +/- 6.0 in hyperthyroidism, and 50 +/- 10 in hypothyroidism; the various values did not differ significantly from one another. Serum TNF alpha was well within the normal range in all NTI patients, except one patient with a brain glioma and infection in whom it was elevated (540 fmol/mL). There was no significant correlation between serum TNF alpha and serum T4, T3, or rT3 levels in NTI patients. Similarly, there was no correlation between serum TNF alpha and serum thyroid hormone (T3 or T4) levels when data in normal subjects were combined with those in NTI patients. The dialyzable fraction of T3 and the free T3 concentration did not correlate with serum TNF alpha levels. However, there was a tendency toward a positive correlation between dialyzable fraction of T4 and the serum concentration of TNF alpha in NTI (r = 0.54; n = 11; 0.05 greater than P less than 0.1). The relationship between these two parameters became more clear when data in normal subjects and NTI patients were combined for statistical analysis (r = 0.59; n = 22; P less than 0.005). The free T4 concentration correlated positively with serum TNF alpha levels whether the data in NTI patients were analyzed alone (r = 0.93; P less than 0.001) or in combination with data from normal subjects (r = 0.85; P less than 0.001). Our data suggest that circulating TNF alpha may contribute to elevated free T4 in NTI. However, it is not a universal or common factor in the pathogenesis of other alterations in serum thyroid hormone levels in NTI (euthyroid sickness syndrome).

A homozygous deletion in the c-erbA beta thyroid hormone receptor gene in a patient with generalized thyroid hormone resistance: isolation and characterization of the mutant receptor.

Different point mutations have been identified in the T3-binding domain of the c-erbA beta thyroid hormone receptor gene that are associated with variant phenotypes of generalized thyroid hormone resistance (GTHR). In most cases of GTHR, heterozygotes are affected; a single mutant allele results in the inhibition of the function of normal thyroid hormone receptors. We report here a novel genetic abnormality, a 3-basepair (bp) deletion in the T3-binding domain of the beta-receptor in a kindred, S, with GTHR. One patient, S1, was the product of a consanguineous union of two heterozygotes and was homozygous for this defect. Heterozygotes from kindred S harbored a CAC deletion at nucleotides 1295-1297, which resulted in the deduced loss of amino acid residue threonine at codon 332, and they displayed elevated free T4 levels and inappropriately normal TSH levels characteristic of other kindreds with GTHR. However, patient S1, who had two mutant alleles, had markedly elevated TSH and free T4 levels and displayed profound abnormalities in brain development and linear growth. A fibroblast c-erbA beta cDNA extending from codon 175 to stop codon 457 was cloned from patient S1, sequenced, and used to create a full-length mutant cDNA. The kindred S mutant receptor was synthesized in vitro and did not bind T3. This mutant receptor did bind with similar avidity as the wild-type human beta-receptor to thyroid hormone response elements of the human TSH beta (-12 to 43 bp) and rat GH (-188 to -160 bp) genes. Kindred S showed the effect in man of heterozygous and homozygous expression of a dominant negative form of c-erbA beta.

Triiodothyronine Antibodies in a Case of Graves' Disease: Long-Term Follow-Up Under Carbimazole

We present a case of 50-year-old man with Graves' disease who had antibodies against triiodothyronine (T3) resulting in inappropriately elevated total T3 (TT3) and free T3 (FT3) concentrations, during an 8-year period of treatment with carbimazole

Influence of dietary lipid and carbohydrate levels and chronic 3,5,3′-triiodo-l-thyronine treatment on thyroid function in immature rainbow trout, Oncorhynchus mykiss

The influence of varying dietary levels of nonprotein energy sources (lipid, L; carbohydrate, C) and 3,5,3'-triiodo-L-thyronine (T3) on thyroid function in immature rainbow trout was studied. Three diets of equivalent available energy content and identical nutrient composition, except for dissimilar concentrations of L and C (diet 1, L = 7%, C = 28.3%; diet 2, L = 13%, C = 14.9%; diet 3, L = 19%, C = 1.5%), were each supplemented with 0, 4, 8, or 12 ppm T3 and fed to satiation to trout at 6.5 +/- 0.5 degrees on a 12-hr photoperiod for 12 weeks. Dietary L and C concentrations did not influence plasma total L-thyroxine (T4) or T3 levels, indices of free T4 or free T3 levels, hepatic T4 5'-monodeiodinase (5'D) activity, capacity or affinity of hepatic nuclear T3 receptors, or thyroid follicle epithelial cell height. T3 treatment elevated total and free T3 levels and decreased 5'D activity (Vmax) in approximate proportion to T3 dose, and without effect on plasma total or free T4 levels or T3 receptor properties. However, thyroid follicle epithelial cell height was depressed at 8 or 12 ppm dietary T3. In trout reverted for 20 days to a T3-free diet from a T3 (12 ppm) diet, plasma total T3 levels fell to 30% of those of control trout (0 ppm T3 throughout). It was concluded that, under our experimental conditions, (i) trout thyroid function was refractory to dietary concentrations of L and C, (ii) the primary response to T3 supplementation was suppressed hepatic 5'D level and T3 production, which was sustained for at least 20 days after T3 treatment ceased, and (iii) despite causing a probable indirect decrease in thyroidal secretion, T3 did not modify the set point of the hypothalamo-hypophyseal-thyroid axis based on plasma total or free T4 levels.

Flavonoid Administration Immediately Displaces Thyroxine (T4) from Serum Transthyretin, Increases Serum Free T4, and Decreases Serum Thyrotropin in the Rat*

Naturally occurring and synthetic plant flavonoids, such as EMD 21388, are potent inhibitors of thyroid hormone 5'-deiodinase (5'-D) in vitro, but not when given in vivo, since they are tightly bound by serum transthyretin (TTR). EMD 21388 also inhibits the binding of T4 to human, dog, and rat serum TTR in vitro and when administered to rats in vivo. In the present studies the administration of EMD 21388 inhibited the binding of T4 to TTR within 3 min, resulting in a decrease in the serum T4 concentration, an increase in the percentage of serum free T4 assessed by equilibrium dialysis, and an increase in the serum total free T4 concentration. Depending upon the dose of EMD 21388 employed, the serum total free T4 concentration was either elevated for at least 60 min or transiently elevated, returning to normal values by 60 min. Although the total serum T3 concentration was decreased and the percent free T3 increased, these changes were modest, and the serum free T3 concentrations remained normal after EMD 21388 administration. The transient elevations of serum free T4 concentrations 10 and 20 min after the administration of 0.3 mumol EMD 21388/100 g BW resulted in a significant decrease in the serum TSH concentration at 60 min. These observations strongly suggest that the serum free T4 concentration and not T4 bound to serum TTR is biologically available to the pituitary to regulate TSH secretion and/or synthesis. The administration of EMD 21388, which rapidly increases the serum free T4, but not the serum free T3, concentration, will now permit studies of the effect(s) of endogenously elevated serum free T4 concentrations, rather than those after the administration of pharmacological quantities of T3 and T4, on various aspects of the biosynthesis and release of pituitary TSH.

Catecholamines and the Thyroid

Low TSH levels are frequently encountered in patients presenting with goiter. We assayed TSH in 599 goitrous patients who were referred to us for scintigraphy and ultrasonography. When TSH levels were low or when a hot nodule was discovered at scintigraphy, free T3, free T4 and sex hormone-binding globulin (SHBG) were also assayed. TSH levels were always low in overt hyperthyroidism with elevated free T3. TSH levels were also low in patients with normal free T3 and free T4 in circumstances leading to mild hyperthyroidism such as hot nodules that suppressed extranodular thyroid tissue uptake, toxic multinodular goiter, De Quervain thyroiditis and some patients on amiodarone treatment. Low TSH levels were also encountered in 29% of the clinically euthyroid patients presenting with a multinodular goiter with normal iodine uptake, no hot area and normal free T3 levels. In diffuse goiter, low TSH and normal free T3 levels were more frequently associated when iodine uptake was low, mainly due to subacute thyroiditis which can be clinically silent. Low TSH levels were rarely observed in patients with "simple" goiter or uninodular goiter without hot areas. SHBG, which was elevated in 94% of the Graves' disease patients tested, was normal in all but two patients with low TSH and normal free T3 levels. This assay appeared to be of little relevance in goiter. In addition to imaging techniques which are usually performed first, TSH should be systematically assayed in goiter, except in cases of solitary cold nodules. When low, the patient is at risk of developing overt hyperthyroidism. Conversely, when an isolated low TSH level is observed, scintigraphy should be performed.

A STRUMA OVARII WITH HYPERTHYROIDISM FOLLOWING RESECTION

A rare case of struma ovarii with hyperthyroidism following surgical removal of the tumor is reported. A 72-year-old female had a multicystic tumor measuring 10×9×5cm in the right ovary, which was accidentally found at laparotomy for perforated duodenal ulcer. Microscopic examination revealed the tumor to be composed solely of a follicular structure resembling thyroid tissue. Immunohistochemically, most follicules contained triiodothyronine (T3), thyroxine (T4), and thyroglobulin. A month after the operation, thyroid function tests revealed elevated serum T4 and free T4 levels. Most cases of struma ovarii occur within ovarian teratomas. It is believed that teratomatous thyroid component has predominantly overgrown the remainder of the components. The apparently high incidence of cervical goiter in the patients with this disease raises the possibility of stimulation of both strumas by a circulating factor, though serum TSH level is suppressed and TSH receptor antibody is negative like in this case.

Low serum TSH with normal total thyroid hormone levels: an indicator of free T4 excess.

We have studied 18 patients with low serum thyrotrophin (TSH) levels accompanied by normal thyroxine (T4) and triiodothyronine (T3) levels in order to clarify whether or not they are thyrotoxic. Serum T4, T3, free T3, free T4 and TSH were estimated three times weekly for 3-4 weeks. Thyroxine binding globulin (TBG) levels were estimated on one occasion only. Thyroid hormone data were expressed as the cumulative probability of having at least one result above the relevant normal range by the nth sample (Pn). For free T4 this probability was 61% by the 10th sample. Free T4 values were confined to the upper half of the normal range or above throughout the study. In contrast, free T3 values were distributed evenly within the normal range (P10 = 12%). For total T4 and total T3, P10 was 34 and 11% respectively. Thus, subjects with subnormal TSH levels but normal T4 and T3 levels have been shown to have elevated serum free T4 levels, an indicator of biochemical hyperthyroidism.

C-Cell Hyperplasia of the Thyroid in a Patient with Goitrous Hypothyroidism and Hashimotoʼs Thyroiditis

A 63-year-old man with a goiter and primary hypothyroidism due to Hashimoto's thyroiditis was found to have hypercalcitonemia and, though hypothyroid, markedly elevated serum total and free T3 levels. The latter findings were attributable to circulating T3 autoantibodies and interference with radioimmunoassay. An infusion of calcium and pentagastrin resulted in abnormal increases in serum calcitonin levels. Because there was no evidence of a nonthyroidal cause for the hypercalcitonemia, the patient had a total thyroidectomy. Pathological examination of the thyroidectomy specimen revealed typical Hashimoto's thyroiditis and extensive C-cell hyperplasia symmetrically distributed throughout the upper and middle thirds of each lobe. The C cells stained strongly with immunoperoxidase stains for calcitonin, chromogranin, and CEA using absorbed polyclonal anti-CEA antibody. Less extensive staining for CEA was obtained using the monoclonal antibodies for CEA, 374/14, 250/183, and 431/31; only a few reactive cells were noted using 431/31. Postoperatively, serum calcitonin levels fell to normal and did not rise with a repeat calcium-pentagastrin infusion test. This patient appears to be the first instance of C-cell hyperplasia associated with Hashimoto's thyroiditis, while elsewhere an association with medullary thyroid carcinoma has been reported. These observations raise questions regarding a possible pathogenetic relationship between Hashimoto's thyroiditis and C-cell neoplasia.

Familial dysalbuminaemic hyperthyroxinaemia and other causes of euthyroid hyperthyroxinaemia.

Clinical and biochemical studies on a family in which 3 members have familial dysalbuminaemic hyperthyroxinaemia (FDH) are presented. They were clinically euthyroid with elevated serum thyroxine (T4) and free T4 indices but normal free T4 by equilibrium dialysis and normal serum triiodothyronine (total and free). All thyroid function tests on the remaining family members were normal. The inheritance is consistent with autosomal dominance. Also presented are data on 4 unrelated patients with FDH and two patients with T4 autoantibodies. The methods for detecting FDH, T4 antibodies and other causes of euthyroid hyperthyroxinaemia are now freely available. Since these anomalies may be more common than previously supposed, clinical awareness of the conditions is necessary to protect patients from the consequences of incorrect diagnosis of thyrotoxicosis.

Factors affecting suppression of endogenous thyrotropin secretion by thyroxine treatment: retrospective analysis in athyreotic and goitrous patients.

Factors affecting TSH suppression by L-T4 administration were retrospectively evaluated in 452 patients: 180 who were athyreotic after total thyroidectomy and remnant radioiodine ablation for differentiated thyroid carcinoma and 272 with nontoxic diffuse or nodular goiter. All patients were considered clinically euthyroid. TSH secretion was assessed by iv TRH stimulation testing. The T4 dose associated with an undetectable basal serum TSH level and no increase in serum TSH after TRH administration (suppressive dose) averaged 2.7 +/- 0.4 (SD) micrograms/kg body weight (BW)/day in athyreotic patients and 2.1 +/- 0.3 micrograms/kg BW/day in goitrous patients (P less than 0.001). The 25th-75th percentile intervals were 2.5-2.9 micrograms/kg BW/day for athyreotic patients and 1.9-2.3 micrograms/kg BW/day for goitrous patients. The suppressive dose of T4 was dependent in both groups on patient age, younger patients needing higher doses than older patients. The duration of treatment also proved to be an important parameter, since in both groups the percentage of patients with suppressed TSH secretion increased if TRH testing was carried out after at least 6 months after the initiation of therapy. Serum total T4, total T3, free T3 (FT3), free T4 (FT4) index, and FT3 index values did not differ in the two groups and were significantly higher (P less than 0.001) than in normal subjects. Mean serum FT4 was significantly higher in athyreotic patients than in goitrous patients with suppressed TSH secretion. Among athyreotic patients with suppressed TSH secretion, 24% had elevated serum FT4 and FT3, and 47% had elevated serum FT4 alone. Of goitrous patients with suppressed TSH secretion, 20% had elevated serum FT4 and FT3, and 27% had elevated serum FT4 alone. On the other hand, 35% of athyreotic patients and 14% of goitrous patients whose TSH secretion was not suppressed had elevated serum FT4. Serum sex hormone-binding globulin concentrations were measured in 3 groups of goitrous women. Values above normal limits were found in 13/26 patients (50%) with high serum FT4 and FT3, in 4/30 patients (13%) with elevated serum FT4 alone, and in 1/25 patients (4%) with normal FT4 and FT3. TSH suppression requires daily doses of T4 between 2.5 and 2.9 micrograms/kg BW in athyreotic patients and between 1.9 and 2.3 micrograms/kg BW in goitrous patients, with appropriate adjustments in relation to the age of the patient; Assessment of the adequacy of treatment should not be carried out before 6 months after the institution of therapy.

Thyroid Function and Histology in Forty-Five Patients with Hyperthyroid Graves' Disease in Clinical Remission More Than Ten Years after Thionamide Drug Treatment

Thyroid function was determined in 45 patients with hyperthyroidism due to Graves' disease who had been diagnosed and treated with thionamide drugs between 1965 and 1971 and had remained clinically euthyroid for greater than 10 yr after discontinuation of therapy. Physical examination revealed that only 2 patients had signs of mild hyperthyroidism; all others were euthyroid. Measurements of serum concentrations of thyroid hormones and TSH revealed elevated free T4 index values and serum T3 in 3 (6.7%), T3 toxicosis in 4 (8.9%), and subclinical hypothyroidism in 2 patients (4.4%). The remaining 36 patients were biochemically euthyroid. TRH tests were performed in these 36 patients, and hyporesponsiveness was found in 3 and hyperresponsiveness in 5 patients. T3 suppression tests were performed in 15 of the 36 patients; 10 were suppressible and 5 were nonsuppressible. All suppressible patients responded to TRH. Large needle biopsies performed in 8 biochemically euthyroid patients and 1 patient with subclinical hypothyroidism revealed chronic lymphocytic thyroiditis in 7 and normal biopsies in 2 patients. Diffuse epithelial hyperplasia was not found in any of the specimens. Antithyroid antibody titers were significantly higher than in 1972 at the time of discontinuation of therapy using the same methods. These results suggest that Graves' disease may evolve into chronic thyroiditis in some patients who are in permanent remission, and some patients in apparent permanent remission have hyperthyroidism and concomitant chronic thyroiditis.

IODINE EXCRETION AND THYROID FUNCTION IN MOTHERS AND THEIR NEWBORNS AFTER USE OF PVP-IODINE IN OBSTETRICS

Screening for hypothyroidism shows that use of PVP-Iodine as desinfectant may cause TSH elevations in the newborns. In order to examine if these elevations are a pathological symptom,we determined TSH,T4,T3 and fT4 and the iodine excretion on days 1,3 and 5 in 23 mothers and their newborns after use of PVP-I.for different periods of time before delivery (7-14o h.mean 25h). Results are shown below (mean values, mother = M, newborn = NB, day = D). Four NB had elevated TSH levels, but T4, T3 and free T4 were normal. Two other NB showed hyperthyroid serum levels on days 3 and 5.None of the mothers had TSH elevations or other impairment of thyroid function. No correlation was found between duration of PVP-I. use and iodine levels, nor between iodine levels of mothers and newborns.Finally, there was no correlation between iodine levels and impairment of newborn thyroid function. We conclude that the newborn thyroid is very sensitive towards iodine excess,but we don't think that these infants need treatment.

Inherited thyroxine excess: a serum abnormality due to an increased affinity for modified albumin.

Further analysis of sera from euthyroid subjects with dominantly-inherited, elevated serum total thyroxine (T4) and free T4 index but with normal free T4 levels was performed as an extension of a previous study (Hennemann et al., 1979a). Scatchard analysis and isoelectric focusing of whole sera and purified serum fractions suggest that this T4 excess is due to increased T4 binding by modified serum albumin. Recognition of this syndrome and appreciation that the free T4 index does not reflect the free T4 levels is important to protect patients from the consequences of an incorrect diagnosis of thyrotoxicosis.

Familial thyroid hormone resistance

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 μg/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.

Elevated serum levels of T3 without metabolic effect in nutritionally deficient rats, attributable to reduced cellular uptake of T3.

Rats receiving a nutritionally deficient diet displayed markedly elevated serum free T3 levels but showed no increase in oxygen consumption. This was associated with greatly reduced ratios of hepatic cellular and nuclear 125I-T3 to serum 125I-T3. Kinetic data supported the conclusion that cellular uptake of T3 was decreased in the nutritionally deficient rats. The lack of metabolic effect, despite the elevated serum T3 levels, is attributable to reduced availability of serum T3 to tissue nuclear receptor sites.