Changes of circulating thyroxine, triiodothyronine and reverse triiodothyronine after radiographic contrast agents.

Thyroid function was studied for 42 days in 58 patients, 28 of whome had euthyroid goiter, after urography (diatrizoic acid), cholangiography (ioglycamic acid), and cholecystography (Naiopanoate). After urography and cholangiography short-lived increases of the serum thyroxine occurred in a few patients, but the mean thyroxine and triiodothyronine concentration did not change. By contrast, 7 days after oral cholecystography serum thyroxine had risen consistently by 22% with a concomittant rise of the free thyroxine, while triiodothyronine declined by 15%. The thyroxine metabolite 3,3',5'-triiodo-1-thyronine (reverse T3) rose by 50% and serum thyrotropin concentration doubled. After 42 days thryoxine and triiodothyronine had returned to baseline, and none of the 58 patients developed clinical hyperthyroidism. In patients with severe myxoedema kept on a constant replacement dose with 1-thyroxine NA-iopanoate produced similar changes with the exception of the rise of the serum thyroxine. The primary event after Na-iopanoate seems to be a fall of the serum triiodothyronine, which in turn augments thyrotropin and indirectly thyroxine secretion. the marked and sometimes sustained rose of serum thyroxine after cholecystography may lead to the erroneous diagnosis of hyperthyroidism.     

Effect of long-term amiodarone therapy on thyroid hormone levels and thyroid function

Both hyperthyroidism and hypothyroidism have been noted to occur in some patients treated with amiodarone for cardiac arrhythmias. To determine the frequency of the development of thyroidal abnormalities in patients receiving amiodarone, 45 euthyroid patients were prospectively evaluated. Serum samples were obtained for measurement of thyroxine, thyrotropin, triiodothyronine, and triiodothyronine resin uptake prior to initiation of amiodarone treatment and serially over a 12- to 27-month period during which amiodarone was administered. The patients were divided into four subgroups as follows: Group I (n = 22) had elevated thyroxine levels, Group IIA (n = 13) had normal thyroxine levels and normal thyrotropin levels, Group IIB (n = 7) had normal thyroxine levels and elevated thyrotropin levels, and Group III (n = 3) had subnormal thyroxine levels. Demographic factors (such as route of administration, cardiac diagnosis, sex of the patient, or indication for amiodarone therapy) and amiodarone levels had no significant effect on the thyroid hormone parameters. However, Group I patients were statistically older than the patients in the other groups. Linear regression analysis revealed a negative correlation for thyroxine levels and a positive correlation with thyrotropin levels with age for the whole group. The various groups were not statistically affected by duration of therapy, but a positive trend existed for increasing thyroxine levels. Although virtually all patients showed changes in their thyroid hormone levels, chemical hyperthyroidism (elevated thyroxine and triiodothyronine levels without symptoms) developed in only two patients (4 percent), and clinical hyperthyroidism (elevated thyroxine and triiodothyronine levels with symptoms) developed in no patients. Four patients (9 percent) became biochemically and clinically hypothyroid. Thus, amiodarone frequently influences thyroid hormonal parameters, but less commonly causes a change in actual thyroid function. However, hyperthyroidism and hypothyroidism do occur in a significant number of patients.     

Thyrotropin secretion during oral glucose tolerance test in acromegalic patients and control subjects

It has been suggested that acute hyperglycemia stimulates somatostatin release from the hypothalamus, thus causing inhibition of growth hormone and thyrotropin secretion. Abnormal growth hormone secretory pattern to glucose load is characteristic of acromegaly, and it might reflect alterations in somatostatin release. We evaluated the sensitivity of serum thyrotropin response to presumed somatostatin inhibition during oral glucose tolerance test in 29 patients with active acromegaly, in 13 patients with inactive disease, and in 19 control persons suspected of impaired glucose tolerance. Both the acromegalic patients and the control subjects were euthyroid. Serum insulin, growth hormone, thyrotropin, free triiodthyronine, free thyroxine, and glucose were collected before and 30, 60, 90, and 120 min after the ingestion of 75 g glucose. While the free triiodthyronine and free thyroxine values did not change during the glucose test, the thyrotropin levels progressively and significantly declined in all groups. The basal to nadir thyrotropin ratio was higher in active acromegaly than in inactive disease and in control subjects (p<0.01), suggesting that the glucose load inhibited thyrotropin stronger in active acromegalic patients. These data suggest that there is a possible strong somatostatin response to glucose load in acromegalic patients, which inhibits thyrotropin secretion. These data do not support the concept of decreased somatostatin drive in acromegaly.     

Thyroid test abnormalities in traumatic brain injury: correlation with neurologic impairment and sympathetic nervous system activation

Acute illness is well known to affect thyroid function, but there are few studies correlating the severity of the underlying medical problem with indexes of thyroid function and little is known about its cause. Traumatically brain-injured patients were selected because they were a relatively homogeneous, previously healthy group with a condition whose severity was readily quantifiable. In 66 such patients, the relationships between changes in thyroid function tests (thyroxine, free thyroxine, triiodothyronine, reverse triiodothyronine, and thyrotropin levels), catecholamine and cortisol concentrations measured on admission and again four days after the accident, and neurologic function assessed by the Glasgow Coma Score (GCS) were studied. Triiodothyronine and thyroxine levels fell significantly within 24 hours of injury. Four days after the accident, patients with the greatest neurologic dysfunction had the lowest triiodothyronine and thyroxine levels; significant correlations were present between the Day 4 GCS and concomitant thyroxine (r = 0.47, p less than 0.0001), free thyroxine (r = 0.32, p less than 0.02), and triiodothyronine (r = 0.50, p less than 0.0001) levels. Reverse triiodothyronine values remained unchanged throughout the study even in the most severely affected patients; the rise in thyrotropin levels was not significant (1.2 +/- 0.2 to 1.7 +/- 0.3 microU/ml, p = NS). Patients who died or remained vegetative had thyroxine and triiodothyronine levels 30 percent to 50 percent lower than those who had a good recovery (p less than 0.05). Highly significant correlations were present between Day 4 thyroxine and triiodothyronine levels and admission and Day 4 norepinephrine and epinephrine concentrations. There was no association between admission or concomitant cortisol levels and thyroid function on Day 4; treatment with high-dose dexamethasone did not influence these indexes. Thus, patients with traumatic brain injury exhibit a gradient of thyroid dysfunction that occurs promptly, is dependent upon the degree of neurologic impairment, and reflects ultimate outcome. The significant association with catecholamine levels suggests a role for sympathetic nervous system activation in its causation, independent of a generalized stress response, since there is no correlation of thyroid test abnormality with the degree of adrenocortical secretion.     

Thyrotoxicosis caused by weight-reducing herbal medicines

The weight-reducing herbal medicines "Dream Shape" and "Ever Youth" became available in Japan in 2000. Herein, we describe 12 patients who developed thyrotoxicosis after taking them. The thyroid hormone content of 1 capsule or tablet of herbal medicine, measured following Pronase digestion and ethanol extraction, was approximately 1 mug of triiodothyronine and 3 to 4 mug of thyroxine. Two of us took 10 capsules or tablets of Dream Shape or Ever Youth, and changes in thyroid hormone levels were observed during the first 24 hours. Serum free triiodothyronine levels began to rise 2 hours after ingestion and reached peak levels at 4 to 8 hours; changes in free thyroxine and thyrotropin levels were small during the first 24 hours. Similar herbal medicines may have been distributed to other countries via the Internet. Resultant factitious thyrotoxicosis can create diagnostic and therapeutic confusion, particularly in patients with thyroid disease.     

Subclinical Thyroid Disease

Subclinical thyroid disease, a term applied to patients with no or minimal thyroid-related symptoms with abnormal laboratory values, is diagnosed more frequently with the use of thyroid-stimulating hormone (TSH) screening and newer high-sensitivity assays. These are laboratory diagnoses, with subclinical hypothyroidism defined as an elevated TSH with a normal free thyroxine and triiodothyronine concentration, and subclinical hyperthyroidism as a subnormal TSH with normal free thyroxine and triiodothyronine levels. Although studies defining which patients require treatment are few, decisions should be individualized based upon laboratory values and symptoms. This article reviews the etiologies, diagnoses, treatments and indications, and monitoring of patients with subclinical thyroid disease.     

Pituitary hyperthyroidism. Case report and review of the literature

A 58 year old woman with an enlarged sella turcica was found to have hyperthyroidism with a supranormal concentration of serum thyrotropin. Transsphenoidal microsurgery resulted in the removal of a chromophobe adenoma comprised mainly of thyrotropes. Postoperatively, serum thyrotropin, thyroxine and triiodothyronine levels fell within normal limits, and the patient maintained normal thyroid and pituitary function.     

Risk factors for thyroid abnormalities after neck irradiation for childhood cancer

Thyroid evaluations were performed in 95 patients who received radiotherapy to the neck region for childhood cancer five to 34 years earlier. Fifty-six patients (61 percent) had at least one abnormality of serum free thyroxine index, serum thyroid-stimulating hormone (thyrotropin), or thyroid palpation. Seven had subnormal free thyroxine index and 40 had elevated thyrotropin concentrations. Thyroidal radiation doses of 3,000 or more rads and lymphangiography independently increased the risk (p ≤ 0.01) of an elevated serum thyrotropin concentration (present in 11 percent of patients with neither risk factor, 50 percent of those who underwent lymphangiography and received less than 3,000 rads, 46 percent of those who had 3,000 or more rads and no lymphangiography, and 76 percent of those with both), but duration of follow-up did not. Twenty-six patients had thyroid nodules and six others had diffuse thyroid enlargement. The frequency of palpable abnormalities increased with the follow-up time after radiation (30 percent of patients followed up less than 10 years had abnormalities versus 43 percent of those followed up 10 or more years, p = 0.03), but was not related to the serum thyrotropin level, radiation dose, or lymphanglography. Among 10 patients who had surgery for nodules, three had localized papillary thyroid carcinomas.     

Hyperthyroxinemia in patients treated with high-dose propranolol

Six patients with hyperthyroxinemia (five men and one woman) were evaluated for possible hyperthyroidism. All were taking large daily doses of propranolol—480 ± 155 (± SE) mg—for treatment of angina pectoris. The patients had no clinical evidence of hyperthy-roidism, although three had small goiters. Further evaluation of the patients revealed elevated serum free thyroxine levels and/or free thyroxine index, low-normal serum triiodothyronine levels, and elevated serum reverse triiodothyronine levels in all six. The thyroid-stimulating hormone response to thyrotropin-releasing hormone was normal in two patients, subnormal in three patients, and absent in one patient. One patient was restudied while receiving low-dose propranolol (80 mg a day), with normalization of all thyroid functional parameters. The data suggest that the abnormalities seen in patients taking high doses of propranolol were due to drug-induced blockade of iodothyronine deiodination. Signs and symptoms of hyperthy-roidism are lacking in patients taking large doses of propranolol. If such a patient is discovered to have an elevated serum thyroxine level, a more complete evaluation of thyroid function is necessary before the diagnosis of thyrotoxicosis can be made. The thyrotropin-releasing hormone test may be of particular value in this circumstance.     

Thyroid gland volume and thyroid function during and after acute hepatitis infection

Thyroid function, the occurrence of goiter, and ultrasonically determined thyroid gland volume were investigated in 23 consecutive nonalcoholic patients with acute viral hepatitis during and six months after recovery, and compared with data obtained from 23 matched controls. Seven patients had clinically detectable goiter during disease, but only one after recovery (P less than 0.05). Median thyroid volume was 28 mL (range 15 to 42 mL) compared with 18 mL (range 12 to 27 mL) after recovery (P less than 0.001), and 17 mL (range 11 to 24 mL) in the controls (P less than 0.001). During acute hepatitis, serum levels of thyroxine, thyroxine binding globulin, and free thyroxine index were significantly increased while triiodothyronine and thyrotropin levels were unaltered and triiodothyronine resin uptake and free triiodothyronine index levels were decreased. After recovery all thyroid variables were normalized. In conclusion, acute liver disease was associated with a marked increase in thyroid volume, but the study did not clarify the mechanism underlying thyroid enlargement.     

SERUM TRIIODOTHYRONINE CONCENTRATION IN THE DIAGNOSIS OF HYPERTHYROIDISM

The serum triiodothyronine concentration is superior to the serum thyroxine concentration, the resin uptake test and the free thyroxine index in the diagnosis of hyperthyroidism. Over a 14 month period fifty-five patients attending an endocrine clinic with suspected thyrotoxicosis of all degrees of severity had blood taken on initial attendance and the serum was stored for routine thyroid function tests and triiodothyronine estimation. The patients were followed up and forty-six proved to be toxic and seven to be euthyroid; two could not be classified. Analysis of the initial serum showed that the serum triiodothyronine concentration was superior to the serum thyroxine concentration, the resin uptake test and the free thyroxine index in predicting the clinical outcome.     

Appropriate Replacement Dose of Thyroxine in Primary Hypothyroidism

ABSTRACT An ultrasensitive thyrotropin (TSH) assay was used to determine how many of 65 patients with primary hypothyroidism on thyroxine (T₄) replacement therapy had suppressed serum TSH. In 13 patients (20%) TSH levels ≤0.1 mlU/l were found, indicating an overdose of thyroxine. After correction of the dose, 48 patients had normal TSH values. Their mean dose of thyroxine was 119 μg/24 hours, and the appropriate replacement dose tended to decline with advancing age. The serum level of thyroid hormones during replacement therapy with thyroxine very imperfectly reflected serum TSH values. It is concluded that overdose of thyroxine is common when suppressed serum TSH is used as an end point. Biochemical follow-up of replacement therapy with thyroxine in primary hypothyroidism therefore requires the use of an ultrasensitive TSH assay in order to detect such suppression. Serum levels of thyroxine or triiodothyronine (T₃) during thyroxine therapy are poor indicators of pituitary TSH secretion and are therefore not useful as parameters of adequate thyroxine dosage.     

Angiotensin-converting enzyme activity. A potential marker of tissue hypothyroidism in critical illness

We measured serum angiotensin-converting enzyme (ACE) activity radiometrically as a possible indicator of reduced thyroid function in 57 euthyroid controls, 27 patients in a noncardiac intensive care unit (13 with medical and 14 with surgical disorders), and 29 patients having coronary artery bypass grafting. In the last group, blood was obtained preoperatively and one day and one month after surgery (group 1; n = 18) or preoperatively and six hours and one day after surgery (group 2; n = 11). Patients in group 1 had significant reductions in levels of serum thyroxine (T4), triiodothyronine (T3), and thyrotropin response to protirelin one day postoperatively. The ACE activity fell significantly. Patients in group 2 had low levels of T4, T3, thyrotropin, and ACE six hours postoperatively. All these levels remained low the next day, and free T4 and free T3 levels were also reduced; the reverse T3 level became elevated. Changes in ACE significantly paralleled changes in T3. The 27 patients without coronary artery bypass grafting also had significant reductions in serum T4, T3, and ACE levels. Dilution studies and dialysis of serum with low ACE activity failed to demonstrate an inhibitor to explain the reduced enzyme function.     

Hyperthyroxinemia in patients receiving thyroid replacement therapy

Eleven patients, with a history of hypothyroidism, who had hyperthyroxinemia and an elevated free thyroxine index but normal serum triiodothyronine concentrations on levothyroxine replacement underwent levothyroxine dose reduction at three-month intervals until the free thyroxine index fell into the normal range. All were clinically euthyroid throughout. Normalization of the thyrotropin response to thyrotropin-releasing hormone occurred concomitantly, indicating correction of subtle hyperthyroidism. The mean thyroxine dose decreased from 161 micrograms/d (2.06 micrograms/kg) to 120 micrograms/d (1.51 micrograms/kg). The resting heart rate fell in eight of 11 patients (P less than .02). The left ventricular ejection fraction decreased in eight of 11 patients, although the decrease was not statistically significant. Considering the sensitivity of pituitary, cardiac, and bone tissue to even a small excess of thyroxine over time, hyperthyroxinemia associated with an elevated free thyroxine index should be corrected even in patients taking levothyroxine replacement who are clinically euthyroid and whose serum triiodothyronine concentrations are within normal limits.     

Serum-free thyroxine and thyrotropin concentrations in euthyroid patients with decompensated congestive heart failure

We realized a prospective study of 106 consecutive patients hospitalized in an Internal Medicine Service with decompensated CHF. Between the 95 patients with normal serum-free thyroxine and thyrotropin concentrations, patients older than 70 years had a significant higher serum free thyroxine concentration (13.1+/-2.6 vs. 10.1+/-1.5 pmol/l, p=0.006) and a lower, but not significant, serum thyrotropin concentration (1.3+/-1.2 vs. 1.7+/-1.1 mU/l, p=0.11). No correlation was found between the functional class, the echocardiographic ejection fraction or the in-hospital stay and the serum free thyroxine and thyrotropin concentrations. The sex, the presence of systolic dysfunction, diastolic dysfunction, atrial fibrillation or comorbidity did not determine significant differences in the serum-free thyroxine and thyrotropin concentrations.     

Cost-effectiveness of thyroid function tests

The cost-effectiveness of thyroid function tests (serum thyroxine concentration, triiodothyronine [T3]-resin uptake, free thyroxine index, serum T3, and serum thyrotropin concentration) was assessed in 135 ambulatory patients suspected of hypothyroidism or hyperthyroidism who did not have a history of thyroid disease requiring medication or thyroid surgery within the preceding two years. Of patients with five or more signs and symptoms compatible with thyroid dysfunction, 50.0% had biochemical abnormalities substantiating hypothyroidism or hyperthyroidism, while only 1.5% of patients with fewer than two signs and symptoms had either disease. The cost of thyroid function tests was twice as much per patient evaluated by residents as for those evaluated by faculty physicians. These results suggest that interventions to reduce the number and type of tests in patients without multiple signs and symptoms of thyroid disease could improve the cost-effective use of these tests.     

Involvement of circulating interleukin-6 and its receptor in the development of euthyroid sick syndrome in patients with acute myocardial infarction

OBJECTIVE: In patients with acute myocardial infarction (AMI), low triiodothyronine (T(3)) levels with normal or subnormal levels of thyrotropin (TSH), the euthyroid sick syndrome (ESS), have been reported, however, the mechanism of altered thyroid hormone metabolism is unknown. Recent reports have shown that interleukin-6 (IL-6) plays a key role in the pathogenesis of AMI and ESS. This preliminary study investigates the relationship between thyroid states and plasma levels of IL-6, the soluble IL-6 receptor (sIL-6R), and the soluble transducing 130kDa glycoprotein (sgp130) in AMI. DESIGN AND METHODS: We measured the concentration of TSH, free T(3) (FT(3)), free thyroxine (FT(4)), IL-6, sIL-6R and sgp130 in plasma from 24 patients with AMI and 20 normal controls. RESULTS: All 24 AMI patients showed significantly lower concentrations of FT(3) with normal or subnormal levels of TSH, and higher concentrations of IL-6 and sIL-6R than controls. IL-6 level was correlated with creatine phosphokinase (CPK) and FT(3) levels but not with FT(4 )or TSH levels in patients with AMI. The time course of IL-6 and FT(3 )concentration seemed to be closely linked. sIL-6R level was correlated with CPK and sgp130 levels, but not with FT(3), FT(4) or TSH levels. FT(4 )level was correlated with sgp130 level. CONCLUSION: Patients with AMI develop ESS through activation of IL-6 and its receptor system.     

Euthyroid familial hyperthyroxinemia due to abnormal thyroid hormone-binding protein

A family is described in which three members had an elevated total serum thyroxine level and free thyroxine index. Each affected subject was clinically euthyroid and had a normal pulse wave arrival time (QKd), serum triiodothyronine and free thyroxine levels, and a normal serum thyroxine-binding globulin (TBG) concentration. Electrophoresis of their serum with 125I-labeled thyroxine revealed increased thyroxine binding in the albumin region. In addition, this abnormal protein, like thyroxine-binding globulin, bound 125I-labeled triiodothyronine and 125I-labeled reverse triiodothyronine. However, electrophoresis of serum treated by sialidase (neuraminidase) digestion suggested that this abnormal protein is not an anomalous form of thyroxine-binding globulin "buried" in the albumin area. These cases of euthyroid familial hyperthyroxinemia due to an abnormal thyroid hormone-binding protein show that an elevated serum thyroxine level or free thyroxine index is not always sufficient to confirm the presence of thyrotoxicosis.     

Classification of asymptomatic autoimmune thyroiditis by thyrotropin-releasing hormone loading

Thyrotropin-releasing hormone loading was performed on 91 patients with asymptomatic autoimmune thyroiditis. Four women had no response to this loading test and had high levels in serum total and free thyroxine (TT4, FT4) and in serum total and free triiodothyronine (TT3, FT3). These patients might be classified as subclinical hyperthyroidism (Group G). Twenty-four patients had normal levels of both basal and peak thyrotropin after loading and were classified as Group I. There were no significant differences between 45 controls (Group C) and Group I patients in serum thyroid hormone levels. Patients with normal basal and high peak levels of thyrotropin were included in Group II. The number of patients in this group was 53. The mean levels of basal and peak thyrotropin were 4.8 microU/ml and 39.6 microU/ml, respectively, and were significantly higher than in Group C and Group I (P less than 0.005). In 10 patients classified as Group III with high levels of both basal and peak thyrotropin, serum concentrations of TT4, FT4 and FT3 were significantly lower than in the other groups (P less than 0.025); however, significant differences in TT3 could not be seen among them. Serum cholesterol levels gradually increased from Group C to Group III. There were significant differences between Group C and Group II (P less than 0.05).     

Propranolol-induced hyperthyroxinemia

A patient on a regimen of 400 mg/day of propranolol hydrochloride was observed to have elevated thyroxine (T4) and free T4 levels with a normal thyrotropin response to protirelin. This led us to study the prevalence of hyperthyroxinemia in 14 consecutively treated patients with hypertension on daily doses of propranolol of 320 mg or more. Four of 14 patients had elevated serum T4 levels. As a group, the patients on propranolol therapy had higher serum T4 levels, free T4 indices, and triiodothyronine levels than did healthy controls. The use of high-dosage propranolol may be associated with euthyroid hyperthyroxinemia and be a source of diagnostic confusion. All patients receiving therapy with high-dosage propranolol should undergo protirelin testing before one can conclude that their elevated thyroid hormone levels are due to hyperthyroidism.