Low Serum Free Thyroxine Index in Ambulating Elderly Is due to a Resetting of the Threshold of Thyrotropin Feedback Suppression*
Abstract
Subnormal free T4 index (FT4I) values (less than 80) with inappropriately normal serum TSH concentrations that could not be attributed to illness or drugs were found in 2.5% of ambulating elderly clinic patients. Six such individuals (three men and three women, aged 68.8 +/- 4.8 yr) were selected for their persistent thyroid test abnormalities and were sex and age matched to six subjects (67.7 +/- 4.9 yr) with normal FT4I (greater than 90) and TSH levels. The former also had low serum total T4 (TT4) and rT3 (TrT3) concentrations, but total T3 (TT3) and basal TSH values were normal and did not differ between the groups. Responses of ACTH, LH, FSH, TSH, and PRL to stimulation with CRH, GnRH, and TRH showed no differences between the two groups, indicating that the normal TSH concentration, inappropriate for the low FT4I level, is not due to generalized hypothalamic or pituitary dysfunction. Administration of 3 g iopanoic acid (IOP) daily for 3 days produced significant increases in the TT4 and TrT3 concentrations to the same degree in both groups. Also, in both groups the IOP-induced suppression of T4 to T3 conversion in the pituitary gland provoked similar increases in basal TSH (280 +/- 47% and 288 +/- 33%) and TSH secretion in response to TRH (173 +/- 7% and 156 +/- 13%). These results indicate that the low FT4I is not the consequence of reduced pituitary TSH reserve. In addition, evidence for normal thyroid gland reserve and the secretion of TSH of normal biological activity was obtained by comparing the acute iodothyronine responses to TRH-induced TSH release in both groups. It is concluded that the normal serum TSH concentration, inappropriate for the low FT4I value in some elderly subjects, is due to an apparent resetting of the thyroid hormone feedback regulation threshold of TSH secretion. It may, in turn, be the result of enhanced pituitary conversion of T4 to T3 or increased T4 uptake by the thyrotrophs.
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Some otherwise healthy older persons may have low serum TSH levels, low-normal serum levels of free T4 and total T3, and no evidence of thyroid or pituitary disease, suggesting an altered set point of the pituitary-thyroid axis.
“Finally, some otherwise healthy older persons may have low serum TSH levels, low-normal serum levels of free T 4 and total T 3 , and no evidence of thyroid or pituitary disease, suggesting an altered set point of the pituitary-thyroid axis (368,369).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [368]
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References 25 · Cited by 51
- Authors
- LEWIS, G. F., ALESSI, C. A., IMPERIAL, J. G., & REFETOFF, S.
- Affiliations
- University of Chicago (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1991-10
- Volume
- 73
- Issue
- 4
- Pages
- 843-849
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2120035731
- Cited by
- 51
- References
- 25
- Citations by year
- 2024: 2 · 2022: 2 · 2021: 1 · 2019: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 5 · 2012: 4
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 15070)
- National Center for Research Resources (RR-00055)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- free thyroxine index, older adults, TSH secretion, iopanoic acid, T4 to T3 conversion, reverse T3, TRH stimulation, thyroid function
- MeSH terms
- Adrenocorticotropic Hormone, Aged, Aged, 80 and over, Aging, Corticotropin-Releasing Hormone, Feedback, Female, Follicle Stimulating Hormone, Humans, Iopanoic Acid, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Middle Aged, Prolactin, Thyroid Gland, Thyrotropin, Thyrotropin-Releasing Hormone, Thyroxine, Triiodothyronine
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