Salicylates and Thyroid Function. I. Depression of Thyroid Function

Austen, Frank K.; Rubini, Milton E.; Meroney, William H.; Wolff, J.

doi:10.1172/jci103703

Cited by 82 publications

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“…Paradoxically, salicylate-induced hypermetabolism is not accompanied by certain of the clinical characteristics of hyperthyroidism and is associated with depressed thyroid function as measured by thyroidal radioiodine uptake and clearance, or the serum protein bound iodine (PBI) concentration. The salicylate level in the serum of such patients is not high enough to interfere with in vitro iodine metabolism in rat thyroid slices, and in acute experiments in rats no depression of the iodide concentrating mechanism can be demonstrated at blood salicylate levels comparable to those attained in the above patients (1). Similar findings had previously been recorded in rats and in man treated with 2,4-dinitrophenol (2)(3)(4).…”

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confidence: 81%

“…However, the production of fever is not required since none of the patients described in the previous paper (1) had temperature elevation. Weight loss, though it can result from treatment with any of these agents and may be associated with a depression in the butanol-extractable iodine of serum (37), appears not to be essential since rats not exhibiting weight loss show similar thyroid depression [ (5) and Table IV], and the salicylate-treated patients described in the previous paper (1) exhibit thyroid inhibition in the absence of weight (40), it is in loss. means of de A theory of action that has been proposed for the literature salicylates is that which emphasizes ortho-phenolic thyroid is e3 substitution and the chelation resulting from in-of cortisone ternal hydrogen bonding (17).…”

Section: Commentsmentioning

confidence: 99%

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Salicylates and Thyroid Function. II. The Effect on the Thyroid-Pituitary Interrelation

Wolff¹,

Austen²

1958

J. Clin. Invest.

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In the preceding paper (1) it was pointed out that the administration of sodium salicylate to man induces a number of changes suggestive of thyrotoxicosis. There is an elevated basal metabolic rate (BMR), negative nitrogen balance, a fall in the cholesterol level of the hypothyroid subject, and an accelerated fractional disappearance rate of labeled thyroxine from the circulation. Paradoxically, salicylate-induced hypermetabolism is not accompanied by certain of the clinical characteristics of hyperthyroidism and is associated with depressed thyroid function as measured by thyroidal radioiodine uptake and clearance, or the serum protein bound iodine (PBI) concentration. The salicylate level in the serum of such patients is not high enough to interfere with in vitro iodine metabolism in rat thyroid slices, and in acute experiments in rats no depression of the iodide concentrating mechanism can be demonstrated at blood salicylate levels comparable to those attained in the above patients (1). Similar findings had previously been recorded in rats and in man treated with 2,4-dinitrophenol (2-4). It was subsequently shown (5) that this thyroid depression produced by 2,4-dinitrophenol probably resulted from inhibition at a pituitary or higher level.The absence of a direct or immediate effect of salicylates on thyroid tissue, despite marked thyroid depression upon more prolonged exposure to the drug, suggested that this effect may also result from a decrease in thyroid stimulation by thyrotropin (TSH). It is the purpose of this report to suggest a locus of salicylate action and to present some observations on the nature of the inhibitory effect. MATERIALS AND METHODSThree euthyroid patients were studied to evaluate the effect of salicylates on the rate of release of radioiodine from the thyroid gland. The technique was similar to that described by Goldsmith, Stanbury, and Brownell (6). Each patient, while fasting, was given approximately 125 microcuries of radioiodine, and 48 hours later was started on 1-methyl-2-mercaptoimidazole, 30 mg. every six hours, to block the reaccumulation of radioiodine. Counts over the thyroid region were measured each morning with a wide angle scintillation counter. Body background was taken as the thigh count, and the logarithm of the counts remaining in the thyroid after correction for body background and physical decay was plotted against time to determine half-life and rate of release of thyroidal I'.

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confidence: 81%

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confidence: 99%

Salicylates and Thyroid Function. II. The Effect on the Thyroid-Pituitary Interrelation

Wolff¹,

Austen²

1958

J. Clin. Invest.

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“…Since sodium salicylate at 6 X 10' M causes a net displacement of about 41% of the Ta-'I and at 6 X 1o-' M displaces about 52% of the T4-'1I (Fig. 3) (20). If salicylates interfere with TBG-T4 and Ta binding one would anticipate a decrease in the total Ta and To and increases in the UFT5 and UFT4.…”

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confidence: 96%

Salicylate-induced increases in free triiodothyronine in human serum

Larsen¹

1972

J. Clin. Invest.

167

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“…All increase in circulating free thyro.vine wonld appear to account for tbe central depression of TSII secretion b\-salicylate which bad been previousK' postulated to occur on the basis of indirect evidence (Wolff and Austen, 1958;Hetzel et al, 1961Hetzel et al, , 1962. More recently direct assay of TSH levels in rats following administration of salicylate has revealed a signifieant depression in TSH (Cood and Hetzel, 1965).…”

Section: The Effect Of Salicylate Nnd Related Dnt^s On Thyroxinementioning

confidence: 94%

“…The meehanism underlying this fall has been extensively investigated with the demonstration of both a central component, produced by a depression in the release of thyrotrophin (TSH) from the pituitary, and a peripheral eomponent {Wolff and Austen, 1958;Hetzel et al, 1961Hetzel et al, , 1962. This finding of a simultaneous depression in both plasma PBI and TSH is contrary to the concept of the negative feedback regulation of the thyroid-pi tuitaiy axis.…”

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confidence: 99%

The Effect of Salicylate and Related Drugs on Thyroxine Binding in Man

Good

Potter

Hetzel

1965

Aust J Exp Biol Med

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Summary. Previons studies have demonstrated a fall in circulating thyroid hormone, measured as plasma protein bonnd iodine (PBI), as well as evidence of a suppression of tbyrotropbin (TSH) from the pituitary following the administration of salicylate to nnrnial human subjects. This assoeiation is contrary to the classical concept of the negative feedback regnlatidn of the thyroidpituitary axis.Using the dialysis procedure of Chri.stensen for tlie determination of free thyroxine, it has been demonstrated in aeiite experiments that the administration to normal subjects of sodium salieylate {5 g.) and sodium y-resoreylate (8 g.) produced an increase in circulating free thyroxine within two hours, in spite of the depression in plasma PBI. The admuiistratinn of sodium p-hydroxybenzoate (5 g.) was witbout effect. Displacement of thyroxine from the thyroxine-binding prealbumin site of the serum proteins separated by paper eleetrophoresis in ammnnhnn carbonate buffer (0-12 M at pH 8-4), was demonstrated following saiicylate and y-f'-'sorcylate in vivo, whereas p-hydroxybenzoate was inactive. Tbns, i» civo, salieylatc and y-resorcylate compete for binding sites on jirealbumin displacing bound tbyroxine into tbe free state.Tbe liyptTmetabolism induced by salicyUite as tbe cause of the depression in tliyroid function may now be excluded since 7-resoreylate is witbout ]netabiilie activity. The depression in TSH release produced by these drugs appears to be correlated with an increase hi free thyroxiiie. It is cdnclnded that the level of circulating free thyroxine ser\es as the regulator of the negative feedback system contralhng thyroid-pituitary interrelations.INTRODUCTION.

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Salicylates and Thyroid Function. I. Depression of Thyroid Function

Cited by 82 publications

References 30 publications

Salicylates and Thyroid Function. II. The Effect on the Thyroid-Pituitary Interrelation

Salicylates and Thyroid Function. II. The Effect on the Thyroid-Pituitary Interrelation

Salicylate-induced increases in free triiodothyronine in human serum

The Effect of Salicylate and Related Drugs on Thyroxine Binding in Man

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