Circulating Thyroid Hormone Concentrations Research Articles

Intrathyroidal iodide binding rates and plasma methimazole concentrations in hyperthyroid patients on small doses of carbimazole.

1 The effect of small doses of carbimazole on the binding rate constant of intrathyroidal iodide, plasma methimazole concentrations and circulating thyroid hormone concentrations in five hyperthyroid patients is presented. 2 In all patients there was a marked reduction in iodide binding with carbimazole doses as low as 5 to 10 mg daily. 3 In three patients little further reduction in the observed binding rate occurred with daily doses in excess of 10 mg despite progressive increases in plasma methimazole concentrations. 4 At the end of 4 weeks' treatment with 10 mg carbimazole daily, the reduction in thyroid hormone concentrations and clinical improvement were such as to suggest that this dose may be an effective starting dose in many patients.

Thyroid homeostasis as studied by computer simulation

Physico-chemical factors alone may account for much of the thyroid gland homeostasis and by inference for homeostasis of basal energy metabolism in mammals. Computer simulations indicate that changes of several of the important rate constants for thyroid function have little effect on circulating thyroid hormone concentrations. This was especially true of the rate constants for thyroid hormone release from the thyroid gland and to a lesser extent of the rate constants governing thyroid hormone metabolism and excretion. The rate at which thyroid hormone levels in blood respond to changes was rather slow indicating that transient changes in dietary iodine or in the rate constants governing thyroid function would have little effect. If changes taking place over several days, such as during the initiation of lactation, the parameters of thyroid function change at a corresponding rate.

Rat plasma lipoproteins and apolipoproteins in experimental hypothyroidism.

Hyperlipidemia associated with hypothyroidism is well documented in man and several animal species. The effect of hypothyroidism on apolipoprotein metabolism in the absence of complicating factors such as high cholesterol or fat content in the diet is virtually unknown. Hypothyroidism was therefore induced in male Sprague-Dawley rats by radiothyroidectomy (RTx-treated) or treatment with propylthiouracil (PTU-treated). Both treatments resulted in an over 90% decrease in circulating thyroid hormone concentrations accompanied by a 50-100% increase in plasma cholesterol and a 20-40% reduction in plasma triglyceride concentrations. Plasma apo E and apo B concentrations increased by 100% in the PTU-treated group and 40-50% in the RTx-group. Apo A-I increased 10 and 30% in the RTx- and PTU-treated rats, respectively, while the concentration of apo A-IV was not altered. A large increase in the low-density (LDL) and high-density lipoprotein (HDL) protein was observed and accompanied by a marked reduction of very low density lipoprotein (VLDL) in the hypothyroid rats. The electrophoretic pattern of plasma lipoproteins in the hypothyroid rats was changed by the appearance of a slow pre-beta band shown to be beta-VLDL. A redistribution of apo B occurred within the lipoprotein fractions. Apo B content in the VLDL fraction decreased and a large increase was noted in LDL. The major portion of the apo E and apo A-I increment was recovered in the HDL and to a lesser degree in LDL. An accumulation of apo E-rich larger HDL particles, resembling HDLc in apolipoprotein composition and distinct from the apo A-I-containing species, was observed by column chromatography. The results presented are consistent with the hypothesis that hypothyroidism in the rat may induce an accelerated production of VLDL catabolic remnants, including LDL, but at the same time reduce the rate of removal of these lipoproteins from the circulation.

Thyroid hormone response to thyrotrophin releasing hormone stimulation in subjects from endemic goitre regions of Sarawak, Malaysia.

Summary: Thyroid hormone response to thyro‐trophin releasing hormone stimulation in subjects from endemic goitre regions of Sarawak, Malaysia. G. F. Maberly, C. J. Eastman and J. M. Corcoran, Aust. N.Z. J. Med., 1979, 9, pp. 385–390.In iodine deficient subjects a common finding has been subnormal T4 levels, normal or slightly elevated T3 levels together with normal or elevated TSH levels. A comparative study of circulating thyroid hormone concentrations in 165 severely goitrous (prevalence of 99%) and 122 non‐goitrous control subjects from two regions in Sarawak, Malaysia confirmed serum levels consistent with these findings.There has been some uncertainty whether these altered serum hormone concentrations found in endemic goitrous subjects arise primarily from thyroidal secretion or increased peripheral conversion of T4 to T3 or altered disposal of these hormones. A 20 mg dose of oral TRH was administered to ten goitrous and five non‐goitrous subjects and the serum thyroidal response measured over four hours. The mean maximal increment in TSH in the goitrous (43±2 mU) was almost double that of the non‐goitrous (23±2 mU/) subjects (P<0·02). Despite this the mean maximal increment in T4 in the goitrous (14·2±16·7 nmol/) was less than one quarter of the non‐goitrous group (94±32 nmol/; P <0·02). The mean maximal increment in T3, in the two groups, however, were similar (goitrous, 1·21±0·1 nmol/; non‐goitrous 1·32±0·7 nmol/). Serum thyroid hormone concentrations measured 24 hours following 10 IU parenterally administered bovine TSH to 14 goitrous and seven non‐goitrous subjects gave a similar pattern. TSH suppressed to low levels in both groups. The mean increment in T3 was almost identical in both groups (goitrous, 1·55±0·12 nmol/; non‐goitrous, 1·57±0·12 nmol/). The mean increment in T4 in the goitrous (14±2·10 nmol/) was less than one quarter of the non‐goitrous group (62±14 nmol/; P < 0·05). These findings support evidence, thus far mainly derived from animal studies, that the altered serum thyroid hormone concentrations seen in endemic goitre arise primarily from thyroidal secretion. It is further suggested that the pattern arises from the iodine deficient gland being unable to maintain a normal T4 secretion rather than an adaptation by the thyroid to maintain euthyroidism by increased T3 secretion.

4 Investigation and treatment of hypothyroidism

INVESTIGATION The investigation of patients with suspected hypothyroidism falls naturally into two stages. Preliminary investigation is required to determine the level of thyroid function and confirm, or refute, a clinical diagnosis of thyroid failure, and the use of other diagnostic procedures is required to identify the cause of hypothyroidism in some patients. Tests to Determine the Level of Thyroid Function The laboratory techniques available for assessing the level of thyroid function fall into three groups and the use of each allows different aspects of impaired thyroid function to be defined. The three groups of techniques are: tests of thyroid function; tests of peripheral tissue function; and tests of hypothalamic--pituitary function. The techniques have been reviewed in detail elsewhere (Evered, 1974, 1976). Tests of thyroid function Direct or indirect techniques for measuring circulating thyroid hormone concentrations have been widely available for many years. Serum thyroxine (T4) concentration may be measured by a competitive protein binding assay (Murphy, 1965) or by radioimmunoassay (Mitsuma et al, 1972). These procedures measure total serum T4 concentration, and thus alterations in thyroxine-binding globulin (TBG) capacity (e.g. pregnancy, oral contraceptive therapy, liver disease, etc.) may lead to total hormone concentrations which are at variance with the clinical assessment of the patient. The serum T4 concentration can, however, be corrected for changes in TBG by carrying out a thyroid hormone binding test (e.g. T3 resin uptake, T3 Sephadex uptake), which will estimate residual TBG capacity and may be used to calculate a free thyroxine index (FTI) (Clark and Horn, 1965). The older technique of estimating the protein-bound iodine (PBI) concentration also

The effect of prednisone on serum thyrotropin, thyroxine and triiodothyronine concentrations in hypothyroid patients.

The effect of exogenous prednisone on serum thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) concentrations was investigated in four patients with non-functioning thyroid glands receiving T4 replacement therapy. Orally administered prednisone, in a dose of 20 mg each day for nine days, resulted in a significant decrease in mean serum TSH levels (p less than 0.01) without significant changes in levels of serum T4, T3, and thyroxine binding globulin (TBG). These findings suggest an inhibitory action of relatively low pharmacologic doses of prednisone on TSH release without changes in circulating thyroid hormone concentrations or inhibition of the peripheral conversion of T4 to T3.

Thyroidal and Peripheral Production of Thyroid Hormones

There are two biologically active thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Most T3 is produced extrathyroidally, so that alterations in circulating thyroid hormone concentrations may occur as a result of both thyroidal and extrathyroidal abnormalities. Extrathyroidal T4 conversion to T3 is decreased in patients with different acute and chronic illnesses. When T4 conversion to T3 is impaired and serum T3 concentrations decline, serum concentrations of biologically inactive 3,3',5'-triiodothyronine (reverse T3) increase. In this review, we present current information on thyroidal and extrathyroidal T4 and T3 production in normal subjects and patients with various thyroid diseases and other illnesses, consider the physiologic significance of these changes, and discuss the value and interpretation of various iodothyronine measurements.

Starvation-induced alterations of circulating thyroid hormone concentrations in man

Serum concentrations of triiodothyronine (T3), thyroxine (T4), and TSH were examined in seven men and seven women of normal weight during a 60-hr fast. Similar studies were conducted in two women who received daily for 1 mo before and during a similar fast, 0.4 mg and 0.5 mg of l-thyroxine. The serum concentrations of T3 decreased in each of the untreated normal subjects (sign test of significance, p < 0.001). The mean control concentration of T3 in women was 152 ± 9 ng 100 ml ( X ± SEM); after 24 hr of fasting, 131 ± 31 ng 100 ml ; and at the termination of the fast, 90 ± 15 ng 100 ml . The latter value differed from the control value with a p value of < 0.01. Similar changes of T3 concentration occurred in men (mean basal T = 160 ± 11 ng 100 ml ; mean at termination of fast = 87 ± 16 ng 100 ml ). The range of decrease for T3 in all subjects varied from 24% to 55%. The mean T4 concentration at the beginning of the fast was 6.9 ± 0.9, and at the termination of the fast, 7.5 ± 0.6 ( p = NS). TSH concentrations remained unchanged (Control, 3.8 ± 0.45 μU/ml; at 60 hr, 4.0 ± 0.26 μU/ml, p = NS). Studies in two women who received, before and during a fast, T4, indicate that a decreased peripheral conversion of T4 to T3 is the most likely mechanism responsible for this change.

Circulating thyroid hormone concentrations and posture and venous compression.

Circulating thyroid hormone concentrations and posture and venous compression.

Development of the Hypothalamic-Pituitary-Thyroid Axis in the Neonatal Rat

The hypothalmic content of thyrotropin-releasing hormone (TRH), the pituitary concentration of thyroid-stimulating hormone (TSH), and the serum concentrations of TSH, thyroxine (T4), and triiodothyronine (T3) have been determined at different intervals during the first 50 days following birth in the rat. From a minimum concentration of 1 pg/mug protein at birth, the hypothalamic concentration of TRH increased to a maximum of 5 to 6 pg between 16 and 28 days of age. Serum and pituitary TSH concentrations increased to maximum levels by the end of the first post-natal week; the elevated hormone levels were then maintained to the end of the third post-natal week. Circulating thyroid hormone concentrations were very low at birth. T4 increased rapidly between days 4 and 16 to reach a peak concentration of 6 mug/100 ml, while T3 followed a parallel pattern with a peak concentration of 108 ng/100 ml obtained only at day 28. These data indicate that, in the rat, components of the hypothalamic-pituitary-thyroid axis develop simultaneously during the post-natal period.

Grades of hypothyroidism.

Seventy-nine patients with hypothyroidism and autoimmune thyroid disease were studied, and allotted to one of four categories on the basis of clinical and biochemical features. Firstly, patients with overt hypothyroidism had obvious clinical features of hypothyroidism and abnormal results from routine tests of thyroid function. Secondly, those with mild hypothyroidism, however, had minor and non-specific symptoms, but the routine measurements of circulating thyroid hormone concentration generally lay within the normal range, although they were significantly lower than those seen in subclinical hypothyroidism or in normal subjects. The serum concentration of thyroid-stimulating hormone (TSH) was raised in this group and their symptoms resolve with treatment. Thirdly, patients with subclinical hypothyroidism were asymptomatic, had a raised serum TSH concentration, but all other measurements of thyroid function are indistinguishable from those recorded in people with autoimmune thyroid disease without disturbance of thyroid function and in normal subjects. Lastly, subjects with circulating thyroid antibodies, normal indices of thyroid function, and a normal serum TSH concentration were indistinguishable biochemically from normal subjects. Thus hypothyroidism is a graded phenomenon, the most valuable features for defining the individual grade being the clinical manifestations, the serum TSH concentration, and the presence of circulating antibodies to thyroid tissue.

Grades of hypothyroidism.

Seventy-nine patients with hypothyroidism and autoimmune thyroid disease were studied, and allotted to one of four categories on the basis of clinical and biochemical features. Firstly, patients with overt hypothyroidism had obvious clinical features of hypothyroidism and abnormal results from routine tests of thyroid function. Secondly, those with mild hypothyroidism, however, had minor and non-specific symptoms, but the routine measurements of circulating thyroid hormone concentration generally lay within the normal range, although they were significantly lower than those seen in subclinical hypothyroidism or in normal subjects. The serum concentration of thyroid-stimulating hormone (TSH) was raised in this group and their symptoms resolve with treatment. Thirdly, patients with subclinical hypothyroidism were asymptomatic, had a raised serum TSH concentration, but all other measurements of thyroid function are indistinguishable from those recorded in people with autoimmune thyroid disease without disturbance of thyroid function and in normal subjects. Lastly, subjects with circulating thyroid antibodies, normal indices of thyroid function, and a normal serum TSH concentration were indistinguishable biochemically from normal subjects.Thus hypothyroidism is a graded phenomenon, the most valuable features for defining the individual grade being the clinical manifestations, the serum TSH concentration, and the presence of circulating antibodies to thyroid tissue.

Thyrotrophin radioimmunoassay: another test of thyroid function.

Editorials1 April 1971Thyrotrophin Radioimmunoassay: Another Test of Thyroid FunctionROBERT D. UTIGER, M.D.ROBERT D. UTIGER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-4-627 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe two concepts that secretion of thyrotrophin (TSH) from the pituitary is a major determinant of thyroid secretion and that the circulating thyroid hormone concentration in turn regulates TSH secretion have been well established for many years. An additional hormonal determinant of TSH secretion is the hypothalamic factor, thyrotrophin-releasing hormone (TRH). Nevertheless, only recently, with the application of the highly sensitive and specific radioimmunoassay method to the measurement of TSH in plasma or serum, has it been possible to assess quantitatively the role of TSH in the maintenance of thyroid secretion and the effect of thyroid hormones or other factors...

FURTHER STUDIES ON THE DEVELOPMENT OF THE LATERAL MOTOR COLUMN IN ANURAN LARVAE. I. NORMAL DEVELOPMENT IN RANA TEMPORARIA.

AbstractA study was made of the normal development of the lateral motor column (LMC) in the lumbo‐sacral region of the European grass frog, Rana temporaia. The results were then compared with the development of the LMC in Rana pipiens (Beaudoin, '55), in order to determine if the difference in life cycle between the two species would result in differences in development of the column. The results show that the overall developmental pattern in R. temporaria is no different from that found in other anura. There is a general decrease in the large number of cells present early in the larval period and a concomitant increase in the size of the remaining cells during development through metamorphosis. During metamorphosis, at least 80% of the original population of cells are lost. Immediately following forelimb emergence, nuclear area is at least 52% larger than the nuclear area of cells found at the earliest stage. In both species, the largest decrease in cell number and increase in cell size is at the time the circulating thyroid hormone concentration is at its highest level. Although the pattern of development in the two species is similar, the number and size of the LMC cells differ significantly between the two species during the late larval stages. This difference can be attributed to the difference in life cycle between R. pipiens and R. temporaria.