THERAPY OF PRIMARY HYPOTHYROIDISM WITH L‐TRIIODOTHYRONINE: DISCORDANT CARDIAC AND PITUITARY RESPONSES
Abstract
SUMMARY: Cardiac systolic time intervals were studied in ten patients with primary hypo‐thyroidism before and during therapy with increasing doses of oral L‐triiodo‐thyronine (L‐T3). Therapy was increased sequentially from 10, 20, 25 to 50 μg of L‐T3 daily on a monthly basis. On L‐T3, 20 to 25 μg/day, cardiac systolic time intervals and other peripheral responses to thyroid hormone including serum cholesterol concentration, serum creatine phosphokinase (CPK) activity, and basal metabolic rate had normalized. However, serum thyrotrophin (TSH) levels and peak TSH responses to thyrotrophin‐releasing hormone (TRH) remained elevated on these doses of L‐T3. As the dose of L‐T3 was increased from 20 to 50 μg/day, mean basal serum TSH levels decreased from 55 to 16 μu/ml, and the peak TSH response to TRH decreased from 243 to 58 μu/ml (P < 0.001) while systolic time intervals did not decrease further. Changing to L‐thyroxine (L‐T4) therapy at this point resulted in further suppression of TSH secretion, without significantly altering systolic time intervals or the other peripheral responses to thyroid hormone. These data suggest (a) that some biological responses to thyroid hormone were normalized on lower doses of L‐T3 than were required to normalize TSH secretion, and (b) that higher doses of L‐T3 or substituting L‐T4 therapy could suppress TSH secretion further without altering the other peripheral responses to thyroid hormone.
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Compared with normal individuals with similar TSH levels, LT4-treated patients exhibit a slightly lower basal metabolic rate.
“exhibit a slightly lower basal metabolic rate (BMR) (15,17,18)”
From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [18]
In 10 hypothyroid patients treated with increasing LT3 doses, 20-25 mcg/day normalized cardiac systolic time intervals and serum creatine phosphokinase activity but not BMR, total cholesterol, or serum TSH; increasing to 50 mcg/day decreased mean basal serum TSH from 55 to 16 μU/mL and brought all parameters within normal reference range except total cholesterol, which remained above 200 mg/dL.
“On LT3, 20–25 mcg/day, cardiac systolic time intervals and serum creatine phosphokinase activity had normalized, but BMR, total cholesterol concentration, and serum TSH levels had not. As the dose of LT3 was increased to 50 mcg/day, mean basal serum TSH levels decreased from 55 to 16 μU/mL, bringing all parameters to within normal reference range, except for total cholesterol that remained above 2”
From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [18]
Only 50 mcg/day LT3 normalized the 24-hour-integrated serum concentration of T3, and no adverse drug reactions were reported.
“Notably, only 50 mcg/day LT3 normalized the 24-hour-integrated serum concentration of T3; no ADRs were reported (18).”
From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [18]
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Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928 · see citing works
“It has previously been suggested that LT4 therapy provides a signal of greater magnitude to the thyrotrophs than LT3 because T3 is provided not only by the circulating levels but also from intrapituitary conversion of T4 to T3 (370).”
Self-citationPrimary hypothyroidism and quality of life
Hegedüs, L., Bianco, A. C., Jonklaas, J., Pearce, S. H., Weetman, A. P., & Perros, P. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00625-8 · Cited by 144 · see citing works
Optimal thyroid hormone replacement
Jonklaas, J. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab031 · Cited by 89 · see citing works
Individualized Therapy for Hypothyroidism: Is T4 Enough for Everyone?
Ettleson, M. D., & Bianco, A. C. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa430 · Cited by 75 · see citing works
Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism
Idrees, T., Palmer, S., Maciel, R. M. B., & Bianco, A. C. (2020) · Thyroid® · doi:10.1089/thy.2020.0153 · Cited by 58 · see citing works
Serum thyrotropin and triiodothyronine levels in levothyroxine-treated patients
Ettleson, M. D., Prieto, W. H., Russo, P. S. T., de Sa, J., Wan, W., Laiteerapong, N., Maciel, R. M. B., & Bianco, A. C. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac725 · Cited by 25 · see citing works
- Authors
- RIDGWAY, E. C., COOPER, D. S., WALKER, H., DANIELS, G. H., CHIN, W. W., MYERS, G., & MALOOF, F.
- Affiliations
- Harvard University (US)
- Corresponding author
- RIDGWAY, E. C.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 1980-11
- Volume
- 13
- Issue
- 5
- Pages
- 479-488
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2127692335
- Cited by
- 30
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 3 · 2014: 1
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Philosophical Society
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- primary hypothyroidism, triiodothyronine, levothyroxine, thyroid hormone replacement, thyrotropin secretion, thyrotropin-releasing hormone stimulation, serum cholesterol, creatine kinase, basal metabolic rate, TSH suppression
- MeSH terms
- Adult, Aged, Cholesterol, Female, Heart, Humans, Hypothyroidism, Male, Middle Aged, Pituitary Gland, Systole, Thyrotropin, Thyroxine, Triiodothyronine
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