Thyroid dysfunction in older persons.
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Biomedical subjects
Publications and source records attributed to C T Sawin.
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We studied a large population (n = 2575) of unselected ambulatory persons older than 60 years to determine the prevalence of a low serum thyroid-stimulating hormone (TSH) level, ie, of less than 0.1 mU/L using a sensitive assay, a level suggestive of hyperthyroidism in younger adults. One hundred one persons (3.9%) had a low serum TSH level. About half of them (51/101) were taking thyroid hormone. Of the remainder, 44 were not hyperthyroid did not become so during up to 4 years of follow-up. Forty-one of the 44 euthyroid persons had a serum thyroxine level of less than 129 nmol/L; repeated testing showed a serum TSH level of more than 0.1 mU/L in the three euthyroid persons with a serum thyroxine level of more than 129 nmol/L. Only six were hyperthyroid or became so during the follow-up period; all had a serum thyroxine level of more than 129 nmol/L. Routine clinical examination was not a sensitive indicator of hyperthyroidism and did not permit discrimination from euthyroidism. A low value of serum TSH alone, while it had high sensitivity and specificity for hyperthyroidism, had a low positive predictive value (12%) for this diagnosis; addition of the thyroxine assay raised the predictive value fivefold to 67%. A low value of serum TSH is far more common in older persons than is hyperthyroidism. Low values in euthyroid persons are accompanied by a clearly normal serum T4 concentration (less than 129 nmol/L) or by a serum TSH level of more than 0.1 mU/L on repeated testing. We recommend measurement of the serum TSH thyroid concentration, using a sensitive assay, as the initial step in testing any older person for possible hyperthyroidism. Measurement of the serum T4 concentration or the free T4 index on the same sample would be needed only in the approximately 2% with a serum TSH level of less than 0.1 mU/L; alternatively, the TSH assay in these could be repeated at a later time.
The overall prevalence of thyroid hormone use in an unselected population of older adults (n = 2575; average age, 68.6 years) was 6.9% (10.0% in women and 2.3% in men). Eighty-one percent of women taking it were doing so for appropriate indications, eg, hypothyroidism, while 12% were not, eg, for obesity or high serum cholesterol; more men (29%) were taking it inappropriately. Inappropriate use was associated with desiccated thyroid more than with thyroxine. After follow-up averaging 6.9 years, 58% of inappropriate users were still taking it. Underuse also occurred. Thirty-seven percent of those definitely hypothyroid had a clearly elevated serum thyrotropin level (greater than 10 mU/L) despite thyroid therapy. Thyroid therapy is common in the elderly; most is appropriate. When inappropriate use occurs, it is more common in men and more often associated with desiccated thyroid, still commonly used in this age group. In chronic users of thyroid hormone, it is important to review currently appropriate indications and to measure serum thyrotropin levels to assess the adequacy of treatment of primary hypothyroidism.
We studied basal serum prolactin in older (greater than age 50) men (N = 501) and women (N = 384) using younger adults for comparison and excluding those taking medications. Serum prolactin rose slightly with increasing age in men; it fell slightly in women until age 80, when it rose slightly. Men and women were not different except for the higher value in women at age 20 to 29. Serum prolactin did not fall after the menopause, while estrogen treatment had no effect on older women and caused only a slight rise in older men. Thyroid deficiency had only a minimal effect and did not raise the serum prolactin above 25 ng/ml. The prevalence of clearly elevated values (greater than 20 ng/ml) was only 1.3% in women and 0.6% in men above age 50; there is little evidence for a significant prevalence of prolactin-secreting adenomata in older persons. In older persons, prolactin-secreting tumors are uncommon, and neither thyroid failure nor estrogen therapy are good explanations for a clearly elevated serum prolactin.
"Natural" thyroid preparations, a type of bovine desiccated thyroid, are sold without prescription in "health-food" stores or by mail; they may or may not contain thyroid hormone. One such preparation was the cause of erratic thyroid test results in a patient who took it instead of thyroxine. Further study showed that the preparation contained biologically active thyroid hormone and was capable of causing hyperthyroidism. Natural thyroid preparations are biologically active yet unstandardized; because the hormonal content of a natural thyroid product is unknown, its use as a substitute for thyroxine can lead either to relapse of hypothyroidism or to hyperthyroidism.
To determine the utility of laboratory tests for diagnosing thyroid disease in the hospitalized elderly, we measured serum thyroid-stimulating hormone (TSH), thyroxine (T4), free thyroxine index (FT4I), triiodothyronine (T3), and free triiodothyronine index (FT3I) in 125 geriatric inpatients, mostly men, and compared the results to those in elderly ambulatory patients. Hypothyroidism (TSH greater than 10 microU/mL with a low T4 and FT4I or clinical findings) was present in 7.8% (nine of 116) of male inpatients compared to only 0.7% of male ambulatory controls (P less than 0.01). Only a few women were studied but 17% (two of 12) were hypothyroid compared to 2.4% of ambulatory elderly women. Three of the hypothyroid inpatients had no clinical clue to their hypothyroidism. Further, decreased thyroid reserve or subclinical hypothyroidism (TSH greater than 10 microU/mL with a normal T4 and FT4I and no overt clinical findings), a condition which may lead to overt hypothyroidism, was more common in male inpatients (4.3%) than in male ambulatory controls (1.8% [P less than 0.01]). Thus, a clearly elevated serum TSH (greater than 10 microU/mL) was more common in inpatient (12.1%) than in ambulatory (2.4%) elderly men (P less than 0.01). Four inpatients and nine ambulatory controls had an elevated T4 and FT4I, but in only one (0.8%) inpatient and one (0.6%) control was a final diagnosis of hyperthyroidism made; the others had no clinical findings and a normal or low T3 and FT3I.(ABSTRACT TRUNCATED AT 250 WORDS)
The relationship of thyroid antibodies and the serum level of thyrotropin in older adults (over age 60) was studied to determine whether thyroid antibodies were a good clue to thyroid failure in elderly persons. Of those with thyroid failure, evidenced by clearly elevated serum thyrotropin values (more than 10 microU/ml), 67 percent had positive antimicrosomal antibody levels, a prevalence much greater (p less than 0.001) than that among those of comparable age with normal thyroid function (18 percent). Nevertheless, one third (33 percent) had thyroid failure without positive antimicrosomal antibody levels; this was true whether or not a low serum thyroxine value was present. Furthermore, of those with positive antimicrosomal antibody levels, most (68 percent) did not have thyroid failure. Thus, although positive antimicrosomal antibody levels occurred more often in elderly patients with thyroid failure than in those with normal thyroid function, a sizable fraction of those with thyroid failure did not have positive antimicrosomal antibody levels. Hence, measurement of thyroid antimicrosomal antibodies is not a good test of early thyroid failure in older patients; direct demonstration of a clearly elevated serum thyrotropin value is a better approach.
Hypothyroidism is a clinical entity first defined almost 100 years ago; it is caused, for the most part, by an autoimmune disorder or treatment of previous hyperthyroidism and so the vast majority have primary hypothyroidism. While the "textbook picture" does occur, the clinical findings in patients with mild to moderate disease are often nonspecific, particularly in the neonate and in the elderly. Diagnosis of primary hypothyroidism depends on showing that the serum TSH is elevated. Effective treatment, unchanged in principle since the 1890's, is best done with oral L-thyroxine. By using the serum TSH as well as the clinical findings as end-points, one can treat each patient individually.
In an unselected population of elderly (over age 60 years) men and women (the original cohort of the Framingham Study), the prevalence of thyroid deficiency, evidenced by a clearly elevated serum thyrotropin (TSH) level (greater than 10 microU/mL), was 4.4%. Women had thyroid deficiency (5.9%) more often than men (2.3%). Of those with clearly elevated serum TSH levels, only 39% had low serum thyroxine (T4) levels; the remainder had serum T4 levels in the lower half of the normal range. Others (5.9%) had a slightly elevated serum TSH level (5 to 10 microU/mL); their status was not clear, but more (12.7%) had low T4 levels than expected. The level of serum T4 was not a sensitive measure of thyroid deficiency nor was routine examination by a physician, even when the patient's background contained a clue to a possible thyroid problem. An elevated serum TSH level was a sensitive marker of thyroid deficiency in the elderly and was often the only way to detect it. Further studies are needed to determine the relationship of thyroid deficiency to cognitive and cardiovascular function in older persons.
Of 344 relatively healthy persons older than 60 years, 22 (5.9%) had a clearly elevated level of serum thyrotropin (TSH) (greater than 10 muU/mL), a finding more common in women than in men. Ten of the 22 had low values for serum thyroxine (T4) and free T4 (FT4) index, but only one had a low value for serum triiodothyronine (T3) or free T3 (FT3) index. A further 14.4% had a slightly elevated level of serum TSH (greater than 5 less than or equal to 10 muU/mL), but none had low values for serum T4 or FT4 index. Age alone has little effect on the measurements of T4; age is associated with slightly lower T3 levels, but only in men 60 years or older or in women 80 years or older. Longitudinal studies should determine if a slightly elevated serum TSH rises further with age and if there is a causal relationship between a high level of serum TSH and cardiovascular disease.
Large doses of iodide (500 mg three times a day) administered to normal men for 10--12 days caused a rise in basal serum TSH and a concomitant rise in the peak TSH response to TRH. The basal and peak levels of TSH were highly correlated (p less than 0.001). However, the iodide-induced rise in the peak TSH after TRH was poorly correlated with concomitant changes in serum thyroid hormones. Serum T3 wa not lower after iodide and, while serum T4 was somewhat lower, the fall in serum T4 was unexpectedly inversely rather than directly correlated with the rise in the peak TSH response to TRH. Thus, increased TSH secretion after iodide need not always be directly correlated with decreased concentrations of circulating thyroid hormones even when large doses of iodide are used. Clinically, a patient taking iodide may have an increased TSH response in a TRH stimulation test even though there is little or no change in the serum level of T3 or T4.
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Fifty-two percent of patients with chronic heavy intake of ethanol had an abnormally low growth hormone (GH) response to propranolo-glucagon. The effect of ethanol is transient, since the GH response was normal in patients studied 2 wk or more after withdrawal of ethanol. The low GH response was not due to a difference in the levels of glucose or insulin. Ethanol probably suppresses the GH response by acting on the hypothalamus or pituitary gland. Along with previous data suggesting transient ACTH deficiency in chronic alcoholic patients, our findings suggest that these patients may have multiple hypothalamic-pituitary deficiencies.
Riedel's struma with dense fibrous invasion of surrounding muscle and fat was found in a patient who had clinical subacute thyroiditis superimposed on primary hypothyroidism. Riedel's struma may sometimes be an uncommon stage in the more common subacute form of thyroiditis, although in our patient an unusual coincidence of subacute thyroiditis and Riedel's struma is also possible. Of interest in our patient was the development of spontaneous primary hypoparathyroidism; parathyroid function returned to normal concomitant with the spontaneous resolution of the goiter after partial resection. This patient also represents another instance of hyperthyroidism developing in a previously hypothyroid patient.
Ethinyl estradiol (50 micrograms/day) or fluoxymesterone (10 or 20 mg/day), chosen because each is orally active and because fluoxymesterone is probably not converted to an estrogen, were given alone and in combination to adult men over several weeks. Measurements were made of serum FSH, LH, testosterone, and estradiol. The estrogen given alone suppressed serum FSH while the androgen given alone did not; however, the androgen may have enhanced the suppressive effect of the estrogen on the serum FSH. Neither steroid alone changed the serum LH but both together suppressed it. The estrogen alone decreased the serum testosterone, an effect probably mediated by the concomitant fall in serum FSH and a resulting decrease in sensitivity to the constant level of LH; a direct effect of estrogen on the testis seems less likely. The doses of estrogen and androgen used probably had a biologic effect equal to or somewhat above that of endogenously produced estrogen and androgen and thus reflected the maximum physiological effects of the endogenous steroids. Thus, in the chronic physiological control of FSH and LH in adult men, these data indicate that (1) testosterone alone, as an androgen, has little effect on FSH or LH, (2) estradiol (or total estrogen) has a greater suppressive effect on FSH than on LH and by its effect on FSH may indirectly regulate the secretion of testosterone, and (3) testosterone and estradiol together may be involved in the regulation of both FSH and LH.
In nine euthyroid goitrous patients, increasing doses of T4 caused a significant decrease in the PRL response to TRH; the PRL response fell significantly at a dose of T4 of 100 micrograms/day for 1 month (P less than 0.02) and fell further with increasing doses so that at 300 micrograms T4/day, the PRL response was 40% of that in the untreated state. T4 treatment also blunted the PRL response to chlorpromazine (P less than 0.05) in a separate group of euthyroid goitrous patients. In contrast, there was only a small drop of the PRL response to TRH in normal subjects treated with T4 (n = 9) and none at all with T3 (n = 7). These data, together with previously published reports, suggest that thyroid hormone may affect PRL secretion in the presence of thyroid disease (hyperthyroidism, hypothyroidism, or euthyroid goiter), but that physiological amounts of thyroid hormone have little or no modulating effect on PRL secretion in normal persons.