Adequacy of thyroid hormone replacement in a general population
Abstract
BACKGROUND: Suboptimal thyroid hormone replacement may carry harmful health consequences. AIMS: Our objectives were to determine the prevalence and factors associated with inadequate replacement in patients receiving treatment with levothyroxine. DESIGN: Retrospective general practice audit. METHODS: We identified levothyroxine users through electronic searches of primary care records in all 11 practices within a county borough. The adequacy of thyroid hormone replacement was determined from the current serum, serum thyrotropin (TSH) as: (i) adequate replacement (normal TSH; 0.4-4.0 mU/l); (ii) over replacement (low TSH; <0.4 mU/l); and (iii) under replacement (high TSH; >4.0 mU/l). RESULTS: Out of a registered patient population of 58 567, we identified 1037 patients who were first included in the hypothyroidism disease register between January 2004 and December 2009 (mean age 62.4 ± 15.9 years; female 85.9%, male 14.1%). Inadequate replacement was seen in 385 patients (37.2%), comprising 205 patients (19.8%) with over replacement and 180 patients (17.4%) with under replacement. Step-wise logistic regression showed that the factors associated with under replacement were male gender [odds ratio (OR) 2.85, confidence interval (CI) 1.86-4.38; P < 0.001 and younger age (OR 0.88, CI 0.80-0.98; P = 0.02 per 10 year increase in age) while longer duration of treatment was associated with over-treatment (OR 1.06, CI 1.01-1.10). A thyroid function test was performed in the preceding 12 months in 914 patients (88.1%) and appropriate dose adjustments had been made in 81.0% (312/385) of patients with abnormal results. CONCLUSION: Despite frequent monitoring and dose adjustment activities, inadequate thyroid hormone replacement remained a problem in over a third of levothyroxine users in this population.
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Nine studies over nearly 30 years across five different countries show that only 50%-70% of patients prescribed levothyroxine maintain serum TSH within reference range.
“nine studies over nearly 30 years across five different countries show that only 50% -70% of patients prescribed levothyroxine maintain serum TSH within reference range. 20,30 -34”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [34]
Levothyroxine has a narrow therapeutic index, and both under-treatment (TSH above reference range) and over-treatment (TSH below reference range) are common, with cross-sectional studies consistently showing that 30%-50% of patients on levothyroxine have TSH values outside of the laboratory reference range.
“Levothyroxine has a narrow therapeutic index, however, and both under -treatment (TSH above the reference range) and over -treatment (TSH below the reference range) are common, with cross -sectional studies consistently showing that 30% -50% of patients on levothyroxine have TSH values outside of the laboratory reference range. 20,30 -34,65”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [34]
The larger risk of fracture in women than men may be related to differences in body size and pharmacokinetics between the sexes.
“This may be related to differences in body size and pharmacokinetics between the sexes.14 28 61”
From Levothyroxine dose and risk of fractures in older adults: nested case-control study (2011) · cites this paper as [61]
More than 30% to 50% of LT4-treated patients are estimated to be either undertreated or overtreated.
“Unfortunately, more than 30% to 50% of LT4-treated patients are estimated to be either undertreated or overtreated (45–47).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [45]
The proportion of annual TSH measures outside the recommended optimal range is largely in line with previous relevant reports.
“which is largely in line with previous relevant reports.44”
From Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study (2019) · cites this paper as [44]
Around 30% of patients fail to stably achieve the recommended serum TSH level (0.4-4.0 mIU/L) with a standard body-weight-based starting LT4 dose (typically 1.5-1.7 μg/kg/day in patients with residual endogenous thyroid function).
“around 30% of patients fail to stably achieve the recommended serum level of thyroid-stimulating hormone (TSH; between 0.4 and 4.0 mIU/L, according to the American Thyroid Association guidelines) with a standard, body-weight-based starting dose of LT4 (typically 1.5 to 1.7 µg/kg/day in patients with residual endogenous thyroid function, such as those with auto-immune thyroiditis) [ 2 , 10 – 12 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [10]
Cites
Hollowell, J. G., Staehling, N. W., Flanders, W. D., Hannon, W. H., Gunter, E. W., Spencer, C. A., & Braverman, L. E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.2.489 · Cited by 4,279 · see citing works
The Colorado Thyroid Disease Prevalence Study
Canaris, G. J., Manowitz, N. R., Mayor, G., & Ridgway, E. C. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.4.526 · Cited by 2,824 · see citing works
The Clinical Significance of Subclinical Thyroid Dysfunction
Biondi, B., & Cooper, D. S. (2008) · Endocrine Reviews · doi:10.1210/er.2006-0043 · Cited by 1,418 · see citing works
Low Serum Thyrotropin Concentrations as a Risk Factor for Atrial Fibrillation in Older Persons
Sawin, C. T., Geller, A., Wolf, P. A., Belanger, A. J., Baker, E., Bacharach, P., Wilson, P., Benjamin, E. J., & D'Agostino, R. B. (1994) · New England Journal of Medicine · doi:10.1056/nejm199411103311901 · Cited by 1,259 · cited 2× · see citing works
“Uncorrected hypothyroidism is associated with adverse effects on body weight,5 lipid profile6 and blood pressure7 while thyroid hormone excess has been shown to increase the risks of atrial fibrillation,8,9 osteoporosis10,11 and fractures.9 In a cohort of older adults including patients taking levothyroxine, Sawin et…”
BackgroundInfluentialAdvances in Male Contraception
Page, S. T., Amory, J. K., & Bremner, W. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0041 · Cited by 1,134 · see citing works
Duntas, L. H. (2002) · Thyroid · doi:10.1089/10507250252949405 · Cited by 725 · see citing works
Treatment adherence in chronic disease
Dunbar‐Jacob, J. M., & Mortimer-Stephens, M. (2001) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(01)00457-7 · Cited by 440 · see citing works
Flynn, R. W., Bonellie, S. R., Jung, R. T., MacDonald, T. M., Morris, A. D., & Leese, G. P. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1625 · Cited by 415 · see citing works
Neurocognitive Aspects of Hypothyroidism
Dugbartey, A. T. (1998) · Archives of Internal Medicine · doi:10.1001/archinte.158.13.1413 · Cited by 252 · see citing works
Long-term L-thyroxine therapy is associated with decreased hip bone density in premenopausal women.
Paul, T. L., Kerrigan, J., Kelly, A., Braverman, L., & Baran, D. (1988) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.1988.03720210027023 · Cited by 241 · see citing works
Somwaru, L. L., Arnold, A. M., Joshi, N., Fried, L. P., & Cappola, A. R. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1696 · Cited by 239 · see citing works
Thyroid dysfunction in patients with diabetes: clinical implications and screening strategies
Kadiyala, R. U., Peter, R., & Okosieme, O. E. (2010) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2010.02376.x · Cited by 224 · see citing works
Self-citationAccelerated Bone Loss in Hypothyroid Patients Overtreated with L-Thyroxine
Stall, G. M., Harris, S., Sokoll, L. J., & Dawson-Hughes, B. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-113-4-265 · Cited by 203 · see citing works
Management of hypothyroidism in adults
Vaidya, B., & Pearce, S. H. S. (2008) · BMJ · doi:10.1136/bmj.a801 · Cited by 178 · see citing works
Fommei, E., & Iervasi, G. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.5.1996 · Cited by 172 · see citing works
(1993) · Europe PMC (PubMed Central) · Cited by 167 · see citing works
Bolk, N., Visser, T. J., Kalsbeek, A., van Domburg, R. T., & Berghout, A. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02681.x · Cited by 96 · see citing works
Diez, J. J. (2002) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/57.5.m315 · Cited by 91 · see citing works
PSA testing in general practice
Little, B., Ho, K., Gormley, G., et al. (2003) · Prostate Cancer and Prostatic Diseases · doi:10.1038/sj.pcan.4500646 · Cited by 65 · see citing works
Morris, J. C. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03536.x · Cited by 59 · see citing works
Once weekly thyroxine treatment as a strategy to treat non-compliance
Rangan, S., Tahrani, A. A., Macleod, A. F., & Moulik, P. K. (2007) · Postgraduate Medical Journal · doi:10.1136/pgmj.2007.060244 · Cited by 42 · see citing works
(1995) · Europe PMC (PubMed Central) · Cited by 32 · see citing works
Baron, D. N. (1956) · The Lancet · doi:10.1016/s0140-6736(56)92080-3 · Cited by 31 · see citing works
Is annual surveillance of all treated hypothyroid patients necessary?
Viswanath, A., Avenell, A., Philip, S., Acharya, S., Maclennan, G., Dalziel, K., Pereira, O., Copland, S. A., Bevan, J., & Abraham, P. (2007) · BMC Endocrine Disorders · doi:10.1186/1472-6823-7-4 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
2013 ETA Guideline: Management of Subclinical Hypothyroidism
Pearce, S. H. S., Brabant, G., Duntas, L. H., Monzani, F., Peeters, R. P., Razvi, S., & Wemeau, J.-L. (2013) · European Thyroid Journal · doi:10.1159/000356507 · Cited by 877 · see citing works
Thyroid hormones and cardiovascular disease
Jabbar, A., Pingitore, A., Pearce, S. H. S., Zaman, A., Iervasi, G., & Razvi, S. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.174 · Cited by 729 · see citing works
Treatment with thyroid hormone
Biondi, B., & Wartofsky, L. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1083 · Cited by 259 · see citing works
Levothyroxine dose and risk of fractures in older adults: nested case-control study
Turner, M. R., Camacho, X., Fischer, H. D., Austin, P. C., Anderson, G. M., Rochon, P. A., & Lipscombe, L. L. (2011) · BMJ · doi:10.1136/bmj.d2238 · Cited by 152 · see citing works
Thayakaran, R., Adderley, N. J., Sainsbury, C., Torlinska, B., Boelaert, K., Šumilo, D., Price, M., Thomas, G. N., Toulis, K. A., & Nirantharakumar, K. (2019) · BMJ · doi:10.1136/bmj.l4892 · Cited by 138 · 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
Thyroxine replacement: a clinical endocrinologist’s viewpoint
Eligar, V, Taylor, P., Okosieme, O., Leese, G., & Dayan, C. (2016) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1177/0004563216642255 · Cited by 72 · see citing works
Self-citationLevothyroxine: conventional and novel drug delivery formulations.
Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63 · see citing works
Guglielmi, R., Grimaldi, F., Negro, R., Frasoldati, A., Misischi, I., Graziano, F., Cipri, C., Guastamacchia, E., Triggiani, V., & Papini, E. (2018) · Endocrine, Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530318666180125155348 · Cited by 57 · see citing works
Caron, P., Grunenwald, S., Persani, L., Borson-Chazot, F., Leroy, R., & Duntas, L. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09691-9 · Cited by 53 · see citing works
Vigário, P. D. S., Vaisman, F., Coeli, C. M., Ward, L., Graf, H., Carvalho, G., Júnior, R. M., & Vaisman, M. (2013) · Endocrine · doi:10.1007/s12020-013-9886-1 · Cited by 54 · see citing works
Brancato, D., Scorsone, A., Saura, G., Ferrara, L., Di Noto, A., Aiello, V., Fleres, M., & Provenzano, V. (2014) · Endocrine Practice · doi:10.4158/ep13418.or · Cited by 44 · see citing works
Ahluwalia, R., Baldeweg, S. E., Boelaert, K., Chatterjee, K., Dayan, C., Okosieme, O., Priestley, J., Taylor, P., Vaidya, B., Zammitt, N., et al. (2023) · Clinical Endocrinology · doi:10.1111/cen.14935 · Cited by 34 · see citing works
“67 34, 65 Long ‐ term treatment is associated with well ‐ established risks 1.0 – 2.8; p = .049) compared to those taking levothyroxine alone, that was most marked in patients with more than a year of liothyronine exposure.”
BackgroundResultInfluentialSelf-citationDew, R., King, K., Okosieme, O. E., Pearce, S. H., Donovan, G., Taylor, P. N., Hickey, J., Dayan, C. M., Leese, G., Razvi, S., et al. (2018) · BMJ Open · doi:10.1136/bmjopen-2017-019970 · Cited by 31 · see citing works
Self-citationLevothyroxine sodium pentahydrate tablets – formulation considerations
Kaur, N., & Suryanarayanan, R. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2021.08.006 · Cited by 19 · see citing works
The use of levothyroxine absorption tests in clinical practice
Caron, P., & Declèves, X. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad132 · Cited by 18 · see citing works
Oteri, V., Volpe, S., Lopes, M., Sceusa, G., Tumminia, A., Belfiore, A., Frasca, F., & Gullo, D. (2024) · Endocrine · doi:10.1007/s12020-024-04016-7 · Cited by 9 · see citing works
- Authors
- Okosieme, O. E., Belludi, G., Spittle, K., Kadiyala, R., & Richards, J.
- Affiliations
- Prince Charles Hospital (GB)
- ORCID
- Okosieme, O. E.
- Venue
- QJM
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-11-24
- Volume
- 104
- Issue
- 5
- Pages
- 395-401
- ISSN
- 0033-5622 (ISSN-L)
- 1460-2725
- 1460-2393
- OpenAlex
- W2099111117
- Cited by
- 96
- References
- 24
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 7 · 2021: 11 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 1 · 2014: 5 · 2013: 9 · 2012: 1
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- QJM (publishedVersion)
- PubMed (publishedVersion)
- 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 › Thyroid Cancer Diagnosis and Treatment
- Keywords
- levothyroxine, hypothyroidism, serum thyrotropin, overtreatment, undertreatment, dose adjustment, thyroid function monitoring, primary care, risk factors
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Child, Dose-Response Relationship, Drug, Epidemiologic Methods, Female, Humans, Hypothyroidism, Male, Middle Aged, Sex Factors, Thyroid Function Tests, Thyrotropin, Thyroxine, Hormone Replacement Therapy
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