Thyroid Hormone Indices Research Articles

Optimal daily levothyroxine dose in primary hypothyroidism. Its relation to pretreatment thyroid hormone indexes

Optimal daily levothyroxine dose in primary hypothyroidism. Its relation to pretreatment thyroid hormone indexes

Unique Alterations of Thyroid Hormone Indices in the Acquired Immunodeficiency Syndrome (AIDS)

To determine alterations in serum thyroid hormone indices in patients with human immunodeficiency virus (HIV) infection. Prospective, single-blind study. Large metropolitan hospital where 20% of all patients with the acquired immunodeficiency syndrome (AIDS) in Los Angeles are treated. Twenty-six inpatients with bronchoscopy-proven Pneumocystis carinii pneumonia and AIDS. Outpatients included 10 persons seropositive for HIV, 10 with AIDS-related complex, and 10 with AIDS. There were 19 survivors and 7 nonsurvivors of P. carinii infection. Serum triiodothyronine (T3) values generally remained normal until hospitalization, with nonsurvivors having lower values than survivors (0.56 +/- 0.1 nmol/L compared with 1.3 +/- 0.1 nmol/L, P less than 0.002, respectively). Reverse triiodothyronine (rT3) levels were low in persons with AIDS-related complex (0.21 +/- 0.02 nmol/L, P less than 0.001) and in AIDS outpatients (0.17 +/- 0.02 nmol/L, P less than 0.001). Normalization of rT3 occurred after patients were hospitalized (0.28 +/- 0.01 nmol/L). Serum thyroxine-binding globulin values rose with progression of HIV infection (seropositive, 369.7 +/- 18.1 nmol/L, P less than 0.005; AIDS-related complex, 419.1 +/- 37.0 nmol/L, P less than 0.005; AIDS, 423.3 +/- 31.9 nmol/L, P less than 0.005; survivors, 476.3 +/- 24.6 nmol/L, P less than 0.001), whereas nonsurvivors had normal values. All values are compared with normal values (T3, 2.3 +/- 0.04 nmol/L; rT3, 0.28 +/- 0.01 nmol/L; thyroxine-binding globulin, 288.2 +/- 6.9 nmol/L). Infection with HIV produces unique alterations in thyroid function. A progressive decline in rT3 and elevation in thyroxine-binding globulin accompany advancing HIV infection. The persistence of a normal T3 despite progression of HIV infection may contribute to weight loss. A low serum T3 on admission correlates with mortality.

Thyroid hormone indices in adult healthy subjects: no influence of aging.

Controversy exists regarding the influence of aging on thyroid hormone metabolism. Several investigators report lowering of T3 and/or a rise in reverse T3 (rT3) in elderly subjects. Others suggest that these thyroid hormone alterations were secondary to associated disorders rather than old age, and questioned the "healthy" status of the subjects studied in the earlier reports. Therefore, to assess the possible effect of aging we studied T3 resin uptake, T4, free T4, T3, and rT3 concentrations in 152 euthyroid healthy adult subjects. These subjects were selected carefully and were therefore devoid of any illness, acute or chronic, and were not treated with any medications at the time of study. No significant alterations were noted in any of the thyroid hormone concentrations in subjects divided into groups according to age. Nor was there a significant difference in these parameters between men and women of any individual age group or for all ages combined. Therefore, old age per se may not influence thyroid hormone metabolism and hence may not induce changes in serum thyroid hormone concentrations. The changes in thyroid hormones noted previously in elderly subjects may be a reflection of concurrent disorders and not old age.

Electrophysiologic effects of desethylamiodarone, an active metabolite of amiodarone: Comparison with amiodarone during chronic administration in rabbits

During acute superfusion studies by means of the standard microelectrode technique, we previously showed that both amiodarone and its major metabolite, desethylamiodarone, had a modest effect on the lengthening of the action potential duration (APD) at high drug concentrations and produced a rate-dependent block of the sodium channel in cardiac muscle. In this study the comparative electrophysiologic effects of the two compounds in rabbits treated chronically with these compounds were determined with particular reference to repolarization and sinus node automaticity. The changes were correlated with those in serum and tissue drug levels and in thyroid hormone indices. After 1 week neither compound had a significant effect on atrial or sinus nodal potentials; after 3 weeks, amiodarone increased the atrial APD at 90% repolarization time by 10.5% ( p < 0.05) and the effective refractory period (ERP) by 6.7% ( p < 0.05). The corresponding figures for desethylamiodarone were 13% (NS) and 18% (NS). The sinus cycle length was increased 12% (NS) by amiodarone and 27.9% ( p < 0.05) after the metabolite. In animals treated for 6 weeks, amiodarone increased the ventricular APD at 90% repolarization by 58.8% ( p < 0.001) and desethylamiodarone by 42.0% the corresponding figures for the ERP were 63.4% ( p < 0.01) and 47.4% ( p < 0.01), respectively. At the stimulation frequency used, neither compound exerted a significant effect on V max. Both amiodarone and desethylamiodarone significantly decreased serum triiodothyronine and increased reverse triiodothyronine levels but had no effect on thyroxine. Neither the electrophysiologic effects nor those in thyroid hormone indices could be related systematically to the serum or tissue levels of amiodarone or desethylamiodarone. The data indicate the after chronic drug administration, desethylamiodarone exerts electrophysiologic effects, the magnitude and latency of onset of which were comparable to those of the parent compound. The metabolite has significant electrophysiologic effects that are likely to be additive to those of the parent compound during chronic administration.

Pituitary-thyroid axis in critical illness.

Severe nonthyroidal illness has been claimed to cause secondary hypothyroidism. We reevaluated this concept measuring serum free T4 and free T3 by an ultrafiltration method and serum TSH by an ultrasensitive technique (detection limit, and serum TSH by an ultrasensitive technique (detection limit, 0.05 mU/L). Forty-five critically ill patients suffering from hepatic coma (n = 10), terminal cancer (n = 9), stroke (n = 8), and respiratory insufficiency not treated (n = 7) and treated (n = 11) with dopamine were studied. The mortality rate was 80%. No patients received glucocorticoids, and only patients in the last group received dopamine. Serum total as well as free thyroid hormone index values were grossly reduced in the majority of the patients. The 34 patients not receiving dopamine in general had normal values of serum free T4 (32 of 34) and free T3 (31 of 34), measurable TSH (33 of 34), and detectable TSH responses to iv TRH (33 of 34). In contrast, the dopamine-treated patients had reduced serum free T4 and TSH levels compared to normal subjects (P less than 0.05), as well as reduced TSH responses to TRH (P less than 0.01). Serum free T4 and free T3 were below the normal range in 3 patients and 1 patient, respectively, and serum TSH was below the detection limit in 2 patients. We conclude that critically ill patients with nonthyroidal illness not receiving dopamine have normal pituitary-thyroid function, whereas dopamine induces some degree of secondary hypothyroidism.

Amiodarone, thyroid hormone indexes, and altered thyroid function: Long-term serial effects in patients with cardiac arrhythmias

Amiodarone, a drug that has electrophysiologic actions resembling those of hypothyroidism, increases serum levels of T4 and reverse T3 (rT3) and decreases T3. The drug's long-term effects on thyroid function are poorly defined. Serial thyroid hormone indexes in 76 patients given amiodarone for 6 to 32 months (mean +/- standard deviation 16 +/- 7) for arrhythmias were determined serially. Over this period, 68 patients (89%) remained euthyroid; hypothyroidism developed in 6 (8%) and hyperthyroidism developed in 2 (3%). In patients who remained euthyroid, thyroid hormone alterations attained steady-state values at 3 months: T4 increased 42% (p less than 0.01), rT3 increased 172% (p less than 0.01) and T3 decreased 16% (p less than 0.05), without significant effect on thyroid stimulating hormone. For the euthyroid patients, the 90% tolerance limits (95% confidence) over the follow-up period for T4 was 5 to 19 micrograms/dl (normal 4 to 12), for T3 36 to 163 ng/dl (normal 60 to 160), for rT3 22 to 131 ng/dl (normal 15 to 50) and for thyroid stimulating hormone 0 to 14 microU/ml (normal 1 to 6). The changes in hormone indexes in hyperthyroid or hypothyroid patients were unrelated to the cumulative dose or duration of drug therapy. The most reliable diagnostic indexes for amiodarone-induced altered thyroid state were: thyroid stimulating hormone level over 20 microU for hypothyroidism and T4 over 20 ng/dl or high T3 over 200 ng/dl for hyperthyroidism. All levels were within the 90% tolerance limits derived for these hormones from patients remaining euthyroid on amiodarone long-term.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid hormone abnormalities at diagnosis of insulin-dependent diabetes mellitus in children

Comprehensive evaluation of thyroid hormone indices was performed in 58 children with insulin-dependent diabetes mellitus (IDDM) at the time of diagnosis and prior to insulin therapy. Two patients were found to have primary hypothyroidism, with markedly elevated TSH and very low T4, free T4, T3, and reverse T3 concentrations. The remaining 56 patients had the transient alterations in thyroid hormone indices that are characteristic of "euthyroid sick" or "low T3" syndrome. Mean TSH and reverse T3 values were significantly higher and the mean T3, T4, and free T4 levels were significantly lower than those observed in the control population. Ten of the diabetic patients had elevated TSH concentrations and normal or low free T4 values; eight had normal TSH levels and low T4 and free T4 values. The remainder of the group had thyroid indices compatible with abnormal peripheral metabolism of thyroid hormones. Elevated titers of antimicrosomal antibodies were found in 16% of the children with IDDM. We conclude that abnormal peripheral metabolism and altered hypothalamic-pituitary function are responsible for the transient changes in thyroid hormone indices in patients with untreated IDDM. The most reliable indicators of concomitant primary hypothyroidism in untreated IDDM are markedly elevated TSH and low reverse T3 values.

Serum Thyroid Hormone Indexes in Patients With Primary Hyperparathyroidism

Serum total reverse triiodothyronine (rT3) levels are normal in patients with renal diseases with and without renal insufficiency but elevated in nonrenal nonthyroidal illnesses. To evaluate the role of secondary hyperparathyroidism of renal diseases in this difference, serum thyroid hormone levels were studied in 27 patients with primary hyperparathyroidism (PHP) and normal renal function. In PHP, total T3 levels were reduced (118 +/- 6 ng/dL, normal: 147 +/- 3 ng/dL) and correlated with PTH levels. Serum rT3 levels were also decreased (27 +/- 3 ng/dL, normal: 34 +/- 2 ng/dL). Values for serum total thyroxine (T4), T3 uptake ratio, free T4 index, and thyrotrophin were not altered. Serum rT3 levels were increased (63 +/- 13 ng/dL) in patients with hypercalcemia due to malignant neoplasms who had low T3 levels, undetectable PTH and normal renal function. Thus, PTH excess may be the factor responsible for the failure of rT3 levels to increase in PHP and secondary hyperparathyroidism.

Serum thyroid hormone indexes in patients with primary hyperparathyroidism

Serum thyroid hormone indexes in patients with primary hyperparathyroidism

Free thyroid hormone estimates related to measurements of total serum thyroid hormone levels and free thyroid hormone indices.

Free thyroid hormone estimates related to measurements of total serum thyroid hormone levels and free thyroid hormone indices.

Dynamics of serum thyrotropin and thyroid hormone changes in fasting.

This study was designed to address the question of whether decreased hypothalamic TRH secretion was responsible for the transient decline in serum TSH levels characteristic of the early phase of fasting in man. Changes in serum TSH, total T4 (TT4), free T4 (FT4), and total T3 (TT3)/TT4 and total rT3(TrT3)/TT4 ratio values together with plasma TRH levels were evaluated before, during, and after a constant 48-h infusion of either TRH (75 ng/min), or saline, initiated at 10 h into a 6-day fast, in groups of six ambulating, mildly obese female subjects. On the first day of the fast, no change in serum TSH levels was seen with saline infusion relative to control, whereas mean TSH levels rose 2 1/2-fold with TRH infusion. On the second day of the fast, serum TSH levels simultaneously declined in both the saline- (43%, P less than 0.005) and TRH- (52%, P less than 0.005)-infused groups relative to the previous day. On the third day of the fast, after stopping the infusions, mean serum TSH levels fell below control in both the saline- and TRH-treated groups, but subsequently returned to prefasting levels. A distinct circadian pattern of TSH release was present throughout the study. Plasma TRH values were unaffected by fasting in the saline-infused group, but rose 2 1/2-fold in the TRH-infused group. The sequence of changes in the serum thyroid hormone indices were similar for the two groups: a rapid rise in FT4 was followed by a gradual fall in TT3/TT4 ratios during the first 24 h of fast, which was followed by a rise in TrT3/TT4 ratios after 48 h of fast. This study in fasting, mildly obese females suggests that: 1) The transient suppression of serum TSH during early fasting is not TRH mediated. 2) Fasting does not alter plasma TRH levels. 3) A temporal sequence of changes in serum thyroid hormone indices occurs in fasting, this being an initial rise in FT4 (10 h) followed by a fall in both serum TT3/TT4 (12-14 h) and TSH (30-36 h) and finally by a rise in TrT3/TT4 levels (48 h). This sequence of events suggests that the initial inhibition of serum TSH levels in early fasting results from the acute elevation in FT4 levels, and that the reestablishment of normal serum TSH levels with continued fasting is associated with declining serum TT3 levels.

Free thyroid hormone index, thyroid hormone/thyroxin-binding globulin ratio, triiodothyronine uptake, and thyroxin-binding globulin compared for diagnostic value regarding thyroid function.

The thyroid hormone/thyroxin-binding globulin (TBG) ratio and the free thyroid hormone index (FTI) were compared in 372 subjects classified according to age, sex, and biochemical and clinical findings. Age-related variations in thyroid function tests were investigated, as was the relationship between triiodothyronine uptake and TBG. Men, but not women, showed significant age-dependent changes in concentrations of thyroid hormones. FTI was as good as the thyroid hormone/TBG ratio in hyperthyroidism and was a better index of thyroid status in pregnancy, TBG deficiency, and hypothyroidism. In addition, the triiodothyronine uptake correlated extremely well with TBG (r = -0.95, p less than 0.001) and was very efficient in detecting decreased and significantly increased concentrations of TBG. I conclude that FTI is a better discriminator of functional status of the thyroid over a wider range of TBG values than is the thyroid hormone/TBG ratio. Further, the triiodothyronine uptake test produced diagnostic information equivalent to that of TBG estimation and thus should not be replaced in routine use.

Relationship of altered thyroid hormone indices to survival in nonthyroidal illnesses.

SUMMARYAlthough alterations of serum thyroid hormone indices are frequent in nonthyroidal illnesses, their relationship to survival is poorly defined. Consequently, the prevalence and prognostic relevance of alterations in thyroidal indices were evaluated prospectively in 195 patients requiring intensive medical therapy and in 75 critically ill patients with serum total T4 (TT4) levels below 3 μg/dl. In the 195 patients, serum total T3 (TT3) and TT4 levels were reduced in 69% and 43% respectively. Decreased TT4 levels had the highest correlation with mortality (P &lt; 0·001) and correctly predicted outcome in 70% of patients. Other thyroidal indices, which were significantly different between survivors and nonsurvivors, correlated with TT4 and did not contribute independently to prediction accuracy when assessed by discriminant function analysis.In seventy‐five patients with TT4 levels below 3 μg/dl, the nadir TT4 level appeared a median of 9 days (range 1–28) after hospital admission. The nonsurvivors lived a median of 6 days (range 0–42) and the survivors were discharged a median of 20 days (range 4–55) after the TT4 nadir. Only an increased free fraction of T4 (FFT4) was found to correlate significantly with mortality and contribute to prediction accuracy.An inhibition of serum T4 binding to carrier proteins could account for both the decreased serum TT4 and the increased FFT4 values. Serum TT4 and/or FFT4 levels may be useful in assessing the severity and predicting the clinical outcome of acute critical nonthyroidal illnesses.

Thyroid function in patients with nephrotic syndrome and normal renal function.

Alterations of thyroid hormone indices have been described in patients with nephrotic syndrome. However, the majority of these patients also had either diabetes mellitus or significant renal failure,

Free thyroxine, thyroxine/TBG ratio and other in vitro tests of thyroid function evaluated by discriminant analysis.

T4, T3, TSH, FT4 (Corning method), TBG, T3U and a diversity of free thyroid hormone indices were determined in serum from 72 reference persons and 337 patients with either thyroid diseases, TBG abnormalities, non-thyroid illnesses, or medications known to affect the results of thyroid function tests. Ninety-six per cent were 20 years or older. None of the laboratory parameters showed significant age or sex dependence, whereas systemic illness and medications frequently influenced test results. Thus the mean values of all patient groups differed significantly from those of the reference group in two or more laboratory tests, and significantly from those of the reference group in two or more laboratory tests, and significant differences were detected in 73% of the total number of 209 paired comparisons of test results between reference and patient groups. As a single parameter, free thyroxine index was found to be a marginally more efficient thyroid function discriminator than FT4, which again was more efficient than the T4/TBG ratio. However, non of these parameters were included in the combinations of laboratory tests identified as optimum by discriminant analysis. The overall optimum test combination was T4, TSH and T3U, which had an efficiency for correct thyroid function reclassification better than 98% in the total material. T3 replaced TSH in distinguishing between hyperthyroidism and euthyroidism.

Optimum laboratory test combinations for thyroid function studies, selected by discriminant analysis.

In 430 patients with a variety of thyroid disorders, linear discriminant analysis was used to select laboratory test combinations giving optimum diagnostic efficiency in thyroid function studies. Unexpectedly, TSH was found valuable in the diagnosis of hyperthyroidism and T3 in hypothyroidism. These test combinations were found optimal for the separation of euthyroidism/hyperthyroidism: T3, TSH and T4; euthyroidism/hypothyroidism: Combined free thyroid hormone index (FTI) and TSH; and hyperthyroidism/euthyroidism/hypothyroidism: T3, TSH, T4, FTI and T3U. The latter test combination had a total efficiency of 94%. Cholesterol, achilles reflex time, PBI and radioiodine uptake measurement contributed little to the discrimination.

A new combined thyroid hormone index based on thyroxine, triiodothyronine and resin uptake.

A new thyroid hormone index, based on measurements of thyroxine (T4), triiodothyronine (T3) and resin uptake (RT3U), is proposed. In contrast to previous thyroid hormone indices, it incorporates both T3 and T4 measurements. This combined thyroid hormone index appears to have superior predictive value in terms of clinical correlation with thyroid disease.

Serum thyrotropin response to thyrotropin-releasing hormone and free thyroid hormone indices in patients with familial thyroxine-binding globulin deficiency.

The response in serum thyrotropin (TSH) to synthetic thyrotropin-releasing hormone (TRH) as well as serum free thyroxine index (FT4I) and free triiodothyronine index (FT3I) was investigated in six patients with familial thyroxine-binding-globulin (TBG) deficiency. The total serum thyroxine (T4) and triiodothyronine (T3) concentrations were significantly decreased, compared with those of normal subjects (3.4 +/- 0.9 microgram/dl, mean +/- SD. vs. 9.0 +/- 1.5 microgram/dl, p less than 0.01 and 87 +/- 27 ng/dl vs. 153 +/- 37 ng/dl, p less than 0.01, respectively). FT4I was lower than the normal range in all but one (5.3 +/- 1.5 vs. 8.9 +/- 1.6, p less than 0.01), whereas FT3I was all in the normal range and of no significant difference from the normal control (132 +/- 22 vs. 148 +/- 25). Serum TSH concentrations in TBG deficiency were all in the normal range (1.0-4.2 muU/ml) and the maximum TSH increments following TRH 500 microgram iv were 8.9 +/- 2.0 muU/ml and of no significant difference from the normal control (10.2 +/- 4.5 muU/ml). These results indicate that the euthyroid state in familial TBG deficiency is more clearly defined by TRH-test and the normal response to TRH in familial TBG deficiency is presumably under the control of the serum free T3 level rather than the serum free T4 level.

Thyrotoxicosis during pregnancy.

The diagnosis of thyrotoxicosis during pregnancy is difficult on clinical grounds only. The determination of free thyroid hormones or free thyroid hormone indices is important and is possibly supplemented by the TRH stimulation test. Thyrotoxicosis during pregnancy should always be treated actively. The authors recommend subtotal thyroidectomy if there are indications for surgical therapy (nodular goitre or large diffuse goitre). Otherwise treatment with thyrostatic agents is used. After operation during pregnancy, substitution with thyroid hormones should be given throughout the pregnancy in order to avoid deterious effects of possible maternal hypothyroidism. Antithyroid treatment should be continued till after delivery. Beta-receptor blockers are used only as adjuncts but are not recommended as the sole therapy.