Hypothyroid Individuals Research Articles

Reversible abnormalities of myocardial relaxation in hypothyroidism.

Fifteen selected hypothyroid patients without symptoms or signs of cardiovascular disease and an equal number of matched control subjects underwent simultaneous recording of electrocardiogram and phono-, apex-, and echocardiography to assess dynamic systolic and diastolic left ventricular function. Both the systolic preejection period and the isovolumic relaxation period were significantly increased in the hypothyroid group. However, whereas the rate of myocardial contraction, assessed from the echocardiograph of the left ventricular posterior wall, was identical in patients and control subjects, the diastolic thinning rate of the muscle was markedly slowed in the hypothyroid individuals. The abnormalities demonstrated were in the main completely reversed after 3 months of T4 therapy. These results demonstrate a relatively selective and readily reversible disturbance of the rate of myocardial relaxation in hypothyroidism, suggesting an intrinsic abnormality of cardiac muscle. This allows an intriguing parallel to be drawn with the delayed relaxation phase of voluntary muscle contraction, long recognized as a direct measure of tissue thyroid function in hypothyroidism. The abnormality of diastolic function we have described is of similar character to that found in patients with other cardiomyopathies and which has been shown to be a major cause of disturbance of global cardiac action.

Methodische und klinische Evaluation einer neuen enzymimmunologischen Methode zur Bestimmung des Thyroxin bindenden Globulins (TBG) und des T4/TBG-Quotienten: Eine multizentrische Studie

A heterogeneous enzyme immunoassay for the determination of thyroxine binding globulin (TBG) was developed and assessed in clinical trials in 12 laboratories. The assay is based on the competition principle and employs plastic tubes coated with goat anti-TBG. CV's between 1.4-8.9% for intra-assay precision and 2.9-8.6% for inter-assay precision were found over the concentration range of 4-40 mg/l TBG. In comparative studies using highly purified TBG as standard, values with Enzymun-Test TBG were found to be on average 30% lower than those obtained by various TBG-RIAs. A broad-base study, to determine reference values, was carried out on a group of control persons 18 to 50 years old without previous history of thyroid disease. This study revealed a median of 14.33 mg/l TBG, with 95% of all values between 9.6 and 18.5 mg/l TBG. The median in women of 14.5 mg/l TBG was significantly higher than in men (13.4 mg/l TBG). TBG values in hyperthyroid patients were within the reference range while those in hypothyroid individuals were elevated. Highly elevated TBG values were seen in women receiving oestrogen (median: 22.2 mg/l TBG) and in pregnant women (median: 28.5 mg/l TBG). The T4/TBG ratios made it possible to distinguish between euthyroid, hyperthyroid and hypothyroic subjects (median: 4.9, 11.3 and 1.0, respectively). These ratios were significantly lower in pregnant women (median: 3.1) than in the control persons.

The behavior of the triiodothyronine/thyroxine (T3/T4) ratio in normal individuals, and its implications for the regulation of euthyroidism.

In order to examine the significance of differences in the triiodothyronine/thyroxine (T3/T4) ratio in the control of euthyroidism in a normal population, we measured the serum T3, T4 and FT4 index (FT4I) in 121 healthy men and 68 women. The correlation between T3 and T4 was poor (r = 0.24), suggesting that most of the natural variation in T3 among normal individuals occurs independently of the T4 level. There was, however, a strong inverse correlation (r = 0.59, p less than 0.001) between T3/T4 ratio and FT4I. This correlation reflected a constancy in mean T3 at different levels of T4 such that the T3 changed by only 0.35 nmol/l (22%) throughout the range of normal T4. Furthermore, the T3/T4 ratios of 48 hypothyroid individuals with subnormal T4 represented a simple extension of the relationship found in the healthy individuals, indicating that the rise in T3/T4 classically associated with falling T4 in primary hypothyroidism is merely part of a continuous process of change which begins in euthyroidism. It is proposed that the relationship between T3 and T4 is finely controlled in healthy individuals in such a way that differences in hormone activity due to the wide range of serum T4 among normals may be buffered by systematic adjustment of the T3/T4 ratio. Those with the highest T4 appear to maintain euthyroidism with a minimal T3/T4 ratio. The remainder, with T4 levels towards the lower limit of normal, are subject to a progressive increase in the T3 fraction and may depend on it to remain euthyroid.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum α-fetoprotein-A Biochemical Indicator of Prenatal Hypothyroidism

Serum alpha-fetoprotein (AFP) was analysed at 10-30 days of age in infants with positive TSH screening tests for congenital hypothyroidism. These levels were significantly higher in infants with true positive screening tests than in those with false positive tests; 27 of 43 infants with congenital hypothyroidism had serum AFP levels above the age-related reference range. The postnatal rate of elimination of AFP from serum did not differ in hypothyroid and euthyroid infants, indicating that the difference in serum AFP was due to more extensive synthesis in hypothyroid individuals. The level of serum AFP was inversely correlated with the roentgenological skeletal maturation index. It is postulated that increased serum AFP is caused by prenatal hypothyroidism and that analysis of serum AFP is a valuable tool to identify those infants with congenital hypothyroidism who are at risk of neuropsychological sequelae.

3,5-Diiodotyrosine excretion in human urine in individuals of differing thyroidal status.

The urinary excretion of 3,5-diiodotyrosine was determined in euthyroid, hypothyroid and hyperthyroid individuals using a sensitive gas chromatographic mass spectrometric assay. This involved a multi-step extraction of the amino acid from urine (mean efficiency 28 +/- 5.7%) then conversion to the N,O-diheptafluorobutyryl methyl ester. The fragmentation of the derivative is discussed. Although the mean excretions in the two pathological states were significantly different from that of euthyroid individuals (P less than 0.01 in both instances) there was considerable overlap with the normal range.

Fasting decreases thyrotropin responsiveness to thyrotropin-releasing hormone: a potential cause of misinterpretation of thyroid function tests in the critically ill.

We have previously reported that caloric deprivation inhibits peripheral T4 metabolism and blunts the TSH response to TRH in euthyroid obese subjects. To determine whether these phenomena also occur in hypothyroid subjects, T4, T3, rT3, and the TSH response to TRH were measured initially and after a 60-h fast in seven hypothyroid patients. Short term fasting caused a 29% decrement in the maximum serum TSH increment and a 32% decrement in the integrated TSH response to TRH (P less than 0.01). In two subjects with mild hypothyroidism, basal TSH as well as the TSH response to TRH were reduced to levels within the normal range. Specifically, basal TSH values decreased from 7.6 to 3.5 microU/ml and from 11 to 4.1 microU/ml. In the seven subjects, mean serum T3 decreased significantly from 88 to 60 ng/dl, (P less than 0.05) and rT3, initially undetectable in six of seven subjects, rose to detectable or low normal values in four of seven subjects, serum T4 remained at 2.7 micrograms/dl during both study periods. We conclude that 1) fasting induces changes in both peripheral thyroid hormone metabolism and the hypothalamic-pituitary axis in hypothyroid individuals which are qualitatively similar to those that occur in euthyroid subjects; and 2) in certain hypothyroid subjects, fasting alone can decrease basal TSH values to within the normal range. If these data can be extrapolated to critically ill subjects whose caloric intake may be diminished, they suggest that basal TSH concentrations in moderately and severely hypothyroid critically ill subjects will accurately reflect the biochemically hypothyroid state. However, mild degrees of hypothyroidism in critically ill subjects might be overlooked due to the lowering effect of fasting or poor caloric intake alone on basal TSH concentrations.

SERUM α‐FETOPROTEIN—A BIOCHEMICAL INDICATOR OF PRENATAL HYPOTHYROIDISM

Serum alpha-fetoprotein (AFP) was analysed at 10-30 days of age in infants with positive TSH screening tests for congenital hypothyroidism. These levels were significantly higher in infants with true positive screening tests than in those with false positive tests; 27 of 43 infants with congenital hypothyroidism had serum AFP levels above the age-related reference range. The postnatal rate of elimination of AFP from serum did not differ in hypothyroid and euthyroid infants, indicating that the difference in serum AFP was due to more extensive synthesis in hypothyroid individuals. The level of serum AFP was inversely correlated with the roentgenological skeletal maturation index. It is postulated that increased serum AFP is caused by prenatal hypothyroidism and that analysis of serum AFP is a valuable tool to identify those infants with congenital hypothyroidism who are at risk of neuropsychological sequelae.

Status of the red cell Na,K-pump in hyper- and hypothyroidism

To investigate the status of the sodium-potassium pump in cells of human subjects with abnormal thyroid function, we measured the number of pump units as well as the cation transport activity of the pump in erythrocytes from 23 hyperthyroid and 7 hypothyroid patients. It was found that the number of Na +-K +-ATPase units in erythrocytes (as measured by ouabain binding) was significantly reduced in hyperthyroidism (mean 36% below controls, p < 0.001). The rate of rubidium uptake by the same cells was also reduced, but to a smaller extent (mean 9%, p < 0.02). These changes were reversible with control of the hyperthyroidism. Hypothyroid individuals showed changes in erythrocyte Na +-K + pump which were in the opposite direction to those seen in hyperthyroidism. It is concluded that thyroid hormone exerts a marked negative influence on the number of Na +-K + pump units in one easily available human cell type. The direction of the effect suggests a complex relationship between thyroid hormone and the level of the Na,K-ATPase in any one tissue. Whatever the cellular mechanism responsible for the effects observed in the red cell, these changes should provide a measure of thyroid hormone action at a cellular level and this may prove useful in the study of thyroid hormone physiology in man.

Thyroid hormone levels after acute L-thyroxine loading in hypothyroidism.

While extrathyroidal conversion of T4 to T3 sustains circulating T3 blood levels in patients receiving maintenance doses of L-T4, the serum T3 rise after the acute administration of large doses of L-T4 may involve an additional mechanism, T3 contamination in L-T4 preparations. L-T4 (1000 micrograms; Synthroid) was given orally to four noncompliant hypothyroid individuals (mean T4, 1.0 micrograms/dl; mean T3, 28 ng/dl). Continuously withdrawn blood sampling revealed a mean rise in serum T4 to 7.7 micrograms/dl at 4 h and a parallel rapid mean rise in serum T3 to 66 ng/dl (136% over baseline) at 4 h. RIA analysis of the experimental batches of Synthroid revealed 0.7-0.9% T3 contamination. Oral administration of 5 or 10 micrograms Cytomel (T3; corresponding to 0.5% and 1% T3 contamination in 1000 micrograms Synthroid) to two of the hypothyroid subjects at a later date resulted in T3 serum elevations 12% and 68% as great as post 1000 micrograms L-T4. To eliminate basal hormone changes between these experiments, a third subject received 7.5 micrograms Cytomel on day 1 (corresponding to the measured T3 contamination in 1000 micrograms Synthroid), followed by 1000 micrograms Synthroid on day 2. Resulting peak T3 levels were identical. In summary, hypothyroid individuals rapidly absorb acute L-T4 loads, with parallel increases in T4 and T3 blood levels. The major source of this T3 elevation is the contaminant in L-T4 preparations. This degree of T3 contamination becomes clinically significant in acute large dose T4 regimens and results in euthyroid levels of T3.

Metabolic Clearance and Production Rates of 3,3′,5′- Triiodothyronine in Hyperthyroid, Euthyroid, and Hypothyroid Subjects*

To further elucidate the peripheral metabolism of rT3 and to determine if rT3 production rates vary directly with thyroid function, we measured the disappearance of [125I]rT3 in thyrotoxic and hypothyroid subjects as well as in athyreotic patients maintained eumetabolic on exogenous T4. Kinetic parameters were determined by noncompartmental analysis, and serum concentrations of rT3 and T4 were determined by specific RIAs. In six hyperthyroid, seven euthyroid, and six hypothyroid subjects, the MCRs were 190.7 +/- 15.7, 111.7 +/- 13.2, and 71.8 +/- 7.0 liters/day kg, respectively (mean +/- SE). Production rates (PR) for these same groups were 271.3 +/- 40.5, 51.7 +/- 9.1, and 4.3 +/- 0.6 micrograms/day/70 kg. The observed differences in MCR and PR among the three study groups were highly significant (P less than 0.002). These data indicate that in comparison to euthyroid subjects, rT3 PR and MCR are increased in thyrotoxic and decreased in hypothyroid individuals.

Improved diagnosis and management of hyper- and hypothyroidism by timing the arterial sounds.

"Sphygmo-Recording," a non-invasive method for timing the arterial pulse wave contour provides an objective measure of responses to medication in patients with hyper- and hypothyroidism. The QKd interval, i.e., the interval from the onset of the QRS complex (Q) to the onset of the Korotkoff sounds (K) at the brachial artery when the sphygmomanometer cuff is at diastolic pressure (d) is the QKd interval. QKd is normally 205 +/- 12 msec. In the hyperthyroidism the QKd interval may be shortened to 110 msec. In hypothyroidism the QKd interval may be prolonged to 320 msec. Changes in QKd parallel changes in clinical status and serum total T4 and T3, measured by radioimmunoassay. QKd can be used as an objective guide to antithyroid therapy in hyperthyroidism and replacement therapy with thyroid hormone in hypothyroid individuals.

Effect of TRH on serum arginine vasopressin in euthyroid and hypothyroid subjects.

To test the effect of thyrotropin-releasing hormone (TRH) on serum arginine vasopressin (AVP) in euthyroid and hypothyroid individuals, 500 mug of TRH was administered to four euthyroid subjects and three patients with primary hypothyroidism. Serum AVP was significantly depressed below basal levels from 30 to 60 min in the euthyroid and hypothyroid subjects after administering the releasing agent. The basal serum AVP in the hypothyroid subjects (3.1 +/- 1.1 muU/ml) was not significantly greater than the basal serum AVP in the euthyroid subjects (2.8 +/- 1.2 muU/ml). The maximal incremental depression in serum AVP after TRH in the hypothyroid subjects (1.4 +/- 0.7 muU/ml) was similar to the depression observed in the euthyroid subjects (1.8 +/- 0.9 muU/ml). These data suggest that TRH may have a physiologic role in modulation of AVP release in man.

Effect of iodine upon the TRH induced release of TSH in euthyroid, hypothyroid and hyperthyroid individuals.

The effects of prolonged administration of iodide upon the serum concentrations of thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) and their response to thyrotropin releasing hormone (TRH, 400 mug i.v.) have been studied in euthyroid (n = 9) subjects, and in hypothyroid (n = 4) patients. Administration of iodide (25 mg daily for two weeks) increased in healthy subjects the basal concentrations of TSH and the release of TSH in response to TRH (p less than 0.05-0.01). Serum concentrations of T4 and T3 were reduced (T4, 6.5 +/- 0.2 mug/100 ml to 5.9 +/- 0.3 mug/100 ml; T3, 159 +/- 8.3 ng/100 ml to 145 +/- 7.3 ng/100 ml) in parallel. Responses of T4 but not of T3 to TRH were also reduced after iodide. Two out of four hypothyroid patients also showed an increased response of TSH to TRH. Changes in serum T4 and T3 were due to their low basal concentration not measureable in this group. No response of TSH, T4 or T3 to TRH was observed in hyperthyroid patients either before or after iodide treatment (708 mg daily for one week), in spite of a fall in serum T4 (25%) and T3 (50%) upon iodide administration. These observations demonstrate that small changes in serum T4 and T3 are easily monitored by the thyrotrophs in the normal or in the hypothyroid range. Conversely a reduced sensitivity of the anterior pituitary upon the administration of TRH is found in hyperthyroid patients, since even large reductions in serum T4 and T3 do not facilitate an increased response of TSH to TRH in this group.

Infiltrative Ophthalmopathy and Primary Hypothyroidism

Case Studies1 August 1967Infiltrative Ophthalmopathy and Primary HypothyroidismROBERT A. FOX, M.D., THEODORE B. SCHWARTZ, M.D., F.A.C.P.ROBERT A. FOX, M.D.Search for more papers by this author, THEODORE B. SCHWARTZ, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-67-2-377 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptExophthalmos and associated eye changes are classically linked with hyperthyroidism in the form of Graves' disease, and the ophthalmopathy may persist or progress in severity even though the euthyroid state is restored or hypothyroidism supervenes. In recent years it has become evident that infiltrative ophthalmopathy may occur in euthyroid individuals in whom there is no evidence of prior hyperthyroidism (1-4). This report is presented primarily to draw attention to the fact that infiltrative ophthalmopathy may also appear in hypothyroid individuals without a previous history of hyperthyroidism.CASE REPORTPatient B. T. (PSLH 795904) is a 40-year-old white housewife who was...

Determination of the thyroxine iodine content of serum contaminated by organic iodines. A method based on gel filtration.

A new method employing Sephadex G-25 gel filtration for the separation of various iodinated radiographic contrast agents from thyroxine (T4) in serum is described. Since T4 is split from serum binding proteins on the alkaline gel columns, no prehandling or extractions of serum are required. The contaminating iodinated substances are eluted from the columns with Tris-HCl, and T4 is only later eluted with a 2N NH4OH eluent. PBI and serum T4 iodine content (T4IC) determinations in 60 euthyroid, 16 hyper thyroid and 8 hypothyroid individuals were as follows: euthyroid—PBI 6.9 ± 1.2 (sd), T4IC 6.2 ± 1.3 μg/100 ml; hyperthyroid—PBI 16.2 ±3.7, T4IC 13.7 ±2.8 μg/100 ml; hypothyroid —PBI 3.0 ±0.7, T4IC 2.5 ±0.8 μg/100 ml. Results of T4IC determinations on serum obtained from several patients before and shortly after x-ray studies employing the administration of Hypaque, Pantopaque, Cholografin and Telepaque have shown statistically identical results (p > 0.2), attesting to the effective separation of these iodinated contaminants from T4 by this method. In addition, preliminary experiments in which Gastrografin, Dionosil, Lipiodol and Ethiodal have been added to serum in vitro have demonstrated the effective separation of these agents from T4. The method is simple, rapid, and the recoveries are sufficiently high and reproducible to obviate the need of an 131I-T4 tracer to correct for recovery.

The thyroid and reproductive performance in the adult male guinea pig.

Experiments on the relationship between the thyroid and reproduction in male mammals have been numerous; nevertheless, much uncertainty exists with respect to reproductive performance in hyper-and hypothyroid individuals. Degeneration of the germinal epithelium or decreased spermatogenesis is reported to follow the administration of thyroid substance to rats (Monterosso, 1912; Smelser, 1939a; Cunningham, King and Kessell, 1941). Elsewhere it is reported that spermatogenesis is unaffected (Cameron and Carmichael, 1920; Courrier, 1921; Doderlein, 1928; Cohen, 1935; Richter, 1944) or that any harmful action is transitory (Belawenetz, 1942). Spermatogenic activity and epithelial proliferation in the seminal vesicles are reported to have been stimulated by feeding mice synthetic thyroprotein (Maqsood and Reineke, 1950). The administration of thyroxine stimulated spermatogenesis and improved the semen quality in young rabbits and rams (Maqsood, 1951). An increased reactivity of the testes of the mouse to pituitary gonadotrophins is reported following treatment with thyroxine (Meites and Chandrashaker, 1948),