Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies
Abstract
OBJECTIVE: The significance of mild hypercholesterolaemia in subclinical hypothyroidism and whether there is beneficial reduction after thyroxine replacement, remain controversial. We aimed to describe the association between hypercholesterolaemia and subclinical hypothyroidism, and to quantify the effect of thyroid substitution therapy by an analysis of previously published intervention studies. DATA SOURCES: Intervention studies cited in the Medline database from January 1976 until January 1995, with index terms cholesterol, hypercholesterolaemia, hyperlipidaemia, thyrotrophin (TSH), hypothyroidism, thyroid and human. A total of 148 studies were reviewed. DATA EXTRACTION: We recorded the year of publication, study design, number of patients enrolled, mean age, duration of thyroid substitution, normal range of TSH levels, TSH levels pre and post-substitution treatment and total cholesterol in plasma before and after treatment. DATA ANALYSIS: (1) Qualitative description of studies on the relationship between hypercholesterolaemia and hypothyroidism, both subclinical and clinical. (2) Precision weighted pooled estimates of the effect of thyroid substitution therapy on the plasma levels of total cholesterol, in patients with subclinical and overt hypothyroidism. RESULTS: Subclinical hypothyroidism was two to three times more frequent in people with an elevated total plasma cholesterol. In addition, the total plasma cholesterol levels were slightly elevated in patients with subclinical dysfunction of the thyroid. Thyroid substitution therapy in patients with subclinical hypothyroidism, restoring the TSH levels to normal, decreased total cholesterol by 0.4 mmol/l (95% confidence interval (Cl) 0.2-0.6 mmol/l) independently of the initial plasma level. The effect of thyroid substitution therapy on HDL-cholesterol in patients with subclinical hypothyroidism was not consistent. The effect of thyroid substitution in patients with overt hypothyroidism was highly dependent on the pretreatment levels of total cholesterol. In these patients substitution therapy decreased total cholesterol by 1.2 mmol/l (95% Cl 0.9-1.5 mmol/l) when the plasma levels were elevated up to 8 mmol/l, and by 3.4 mmol/l (95% Cl 3.0-3.7) when plasma levels were higher than 8 mmol/l. The high density lipoprotein (HDL)-cholesterol level decreased and amounted to 0.16 mmol/l (95% Cl 0.07-0.24). CONCLUSIONS: Thyroid substitution treatment in patients with hypercholesterolaemia and subclinical hypothyroidism decreases total plasma cholesterol by 0.4 mmol/l, but plasma levels remain elevated in most patients. Further treatment with dietary restriction and cholesterol synthesis inhibitors should then be considered.
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If an association exists, subclinical hypothyroidism likely contributes to a small increase in serum low-density lipoprotein cholesterol ranging between 3 and 15 mg/dl (0.1 to 0.4 mmol/l).
“Thus, an association, if present, is likely to be weak, with SCH contributing to a small increase in serum LDL-C, ranging between 3 and 15 mg/dl (0.1 to 0.4 mmol/l) (42).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [42]
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Fadeyev, V. V., Sytch, J. P., Kalashnikov, V., Rojtman, A., Al, S., & Mel'nichenko, G. A. (2006) · Endocrine Practice · doi:10.4158/ep.12.1.5 · Cited by 31 · see citing works
Effect Of Levothyroxine Treatment On Qt Dispersion In Patients With Subclinical Hypothyroidism
Unal, O., Ertürk, E., Özkan, H., Kiyici, S. K., Güçlü, M., Ersoy, C., Yener, F., & İmamoğlu, Ş. (2007) · Endocrine Practice · doi:10.4158/ep.13.7.711 · Cited by 31 · see citing works
Correlation Between Subclinical Hypothyroidism and Dyslipidemia
Haghi, A. R., Solhjoo, M., & Tavakoli, M. H. (2017) · Iranian journal of pathology · doi:10.30699/ijp.2017.24867 · Cited by 31 · see citing works
“the effects of thyroxine therapy on lipid profiles in patients with SCH (19, 20).”
BackgroundGluvic, Z. M., Sudar-Milovanovic, E. M., Tica, J., Jovanović, A., Zafirovic, S. S., Tomašević, R., & Isenović, E. R. (2015) · International Journal of Endocrinology · doi:10.1155/2015/147070 · Cited by 30 · see citing works
“The degree of improvement in lipid levels after biochemical euthyroidism is achieved with LT4 therapy and depends on the severity and duration of the thyroid dysfunction as well as the degree of hypercholesterolemia before the treatment [12, 24, 47].”
BackgroundRole of Thyroid Disease in the Development of Statin-Induced Myopathy
Rush, J., Danzi, S. E., & Klein, I. L. (2006) · The Endocrinologist · doi:10.1097/01.ten.0000240960.40281.2b · Cited by 28 · see citing works
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Association of Thyroid-stimulating Hormone and Cardiovascular Risk Factors
Sun, X., Sun, Y., Li, W., Chen, C.-Y., Chiu, Y.-H., Chien, H.-Y., & Wang, Y. (2015) · Internal Medicine · doi:10.2169/internalmedicine.54.4514 · Cited by 29 · see citing works
“Numerous studies have demonstrated the serum TSH levels to positively correlate with atherogenic lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apoB, Lp(a) levels, nonhigh-density lipoprotein cholesterol (non-HDL-C) and the LDL-C/HDL-C (L/H) ratio (1,…”
BackgroundSubclinical thyroid disease in patients with Parkinson's disease
Tandeter, H. B., Levy, A., Gutman, G., & Shvartzman, P. (2001) · Archives of Gerontology and Geriatrics · doi:10.1016/s0167-4943(01)00196-0 · Cited by 25 · see citing works
“, 1999) [thyroid substitution therapy may decrease total cholesterol (Tanis et al., 1996)]; impaired muscle energy metabolism (Monzani et al.”
BackgroundEnfermedad tiroidea subclínica en la población anciana sana institucionalizada
Ayala, C., León, M. V. C., Rodríguez-Hernández, J. R., Silva, H., Pereira, J. L. S., & García‐Luna, P. P. (2001) · Medicina Clínica · doi:10.1016/s0025-7753(01)72169-0 · Cited by 25 · see citing works
Sarkar, D., Chakraborty, A., Saha, A., & Chandra, A. K. (2018) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2017-0204 · Cited by 24 · see citing works
Plasma viscosity, an early cardiovascular risk factor in women with subclinical hypothyroidism.
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Evaluation of effects of prenatal exposure to the cyanide and thiocyanate in wistar rats
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Cost Effectiveness of Screening for Subclinical Hypothyroidism in the Elderly
Bona, M., Santini, F., Rivolta, G., Grossi, E., & Grilli, R. (1998) · PharmacoEconomics (Auckland) · doi:10.2165/00019053-199814020-00009 · Cited by 11 · see citing works
“to be approximately 6% on the basis of published meta-analysis of data from available studies.[21] Table I.”
BackgroundMethodInfluentialSubclinical hypothyroidism and the risk of hypercholesterolemia
Jayasingh, I., & Puthuran, P. (2016) · Journal of Family Medicine and Primary Care · doi:10.4103/2249-4863.201177 · Cited by 23 · see citing works
“There is an absolute need for large studies designed to assess the risk of developing overt hypothyroidism and subsequent cardiovascular health risks among patients with SCH.[5] Journal of Family Medicine and Primary Care 815 October-December 2016 : Volume 5 : Issue 4 The measurement of antithyroid peroxidase (TPO) an…”
BackgroundInfluentialEinfeldt, M. N., Olsen, A. S., Kristensen, S. L., Khalid, U., Faber, J. O., Torp-Pedersen, C. T., Gislason, G., & Selmer, C. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01604 · Cited by 23 · see citing works
Disfunções mínimas da tiróide: hipotiroidismo subclínico e hipertiroidismo subclínico
Romaldini, J. H., Sgarbi, J. A., & Farah, C. S. (2004) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302004000100016 · Cited by 22 · see citing works
Effect of levothyroxine replacement therapy on coagulation and fibrinolysis in severe hypothyroidism
Chadarevian, R., Jublanc, C., Bruckert, E., Giral, P., Ankri, A., Leenhardt, L., Chapman, J., & Turpin, G. (2005) · Journal of Endocrinological Investigation · doi:10.1007/bf03347217 · Cited by 22 · see citing works
- Authors
- Tanis, B. C., Westendorp, R. G. J., & Smelt, A. H. M.
- Affiliations
- Leiden University Medical Center (NL)
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 1996-06
- Volume
- 44
- Issue
- 6
- Pages
- 643-649
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2078996989
- Cited by
- 177
- References
- 0
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 5 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 8 · 2014: 6 · 2013: 5 · 2012: 2
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (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 › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- subclinical hypothyroidism, hypercholesterolemia, thyroid hormone replacement, thyroxine, total cholesterol, HDL cholesterol, thyroid-stimulating hormone, overt hypothyroidism, serum lipids, meta-analysis of intervention studies, dose-response relationship, cardiovascular risk, dyslipidemia, thyroid function tests, lipoprotein cholesterol, triglycerides
- MeSH terms
- Adult, Female, Humans, Hypercholesterolemia, Hypothyroidism, Cholesterol, HDL, Thyrotropin, Thyroxine
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