Measurement of serum TSH is generally considered the best screening test for thyroid disease. Increased values indicate hypothyroidism. The test is both sensitive and specific.
However, its sensitivity causes a dilemma, as some patients are found to have elevated TSH levels, but have normal free thyroxine hormone levels, and may also be asymptomatic.
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Epidemiology
It is common in older people. One study found 7% of women and 3% of men aged 60-89 years had TSH level greater than twice the upper level of the "normal" range.
Aetiology
Causes are the same as those of overt thyroid disease.
- The main cause is chronic autoimmune thyroiditis - Hashimoto's disease.
- Treatment of hyperthyroidism - most commonly after radioactive iodine treatment.
Hypothyroidism can occur in 5-25% of patients treated with surgery or antithyroid drugs.1,2 - Less common causes are medications, e.g. lithium or amiodarone.
- Other causes include head and neck surgery or radiotherapy.
Clinical features
The term subclinical may be inaccurate as some of the patients have symptoms.
In the elderly a diagnosis of hypothyroidism may be delayed by wrongly attributing the symptoms of, for example, fatigue and constipation to ageing.
Clinical manifestations can be explained by assuming that a T4 level of 6-7 mcg/dL, although inside the normal range, may represent a significant decrease from a previous normal of 10 mcg/dL, and is low for this particular patient.
In one study, symptoms in 33 patients with subclinical hypothyroidism were compared with euthyroid patients in the same clinic.3
Dry skin, cold intolerance and easy fatiguability were significantly more common in the patients with raised TSH levels. The symptoms improved after treatment with thyroxine.
Another study showed that in 69 female patients with subclinical hypothyroidism, the clinical index of signs and symptoms was more abnormal in those with higher TSH levels. Even when they had normal serum thyroxine levels.4
Common clinical features include:
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Investigations
Recommendations about thyroid screening have been inconsistent. No organisation currently recommends routine screening. The US Preventive Services Task Force5 has recommended that asymptomatic adults should not be screened because of the insubstantial evidence of benefit.
Other authors disagree and the practical approach may be to measure TSH in those patients who have persistent, nonspecific complaints - women in particular, and the elderly.
Borderline results may need to be repeated at a consistent time of day, with consistent fasting status.
Associated diseases
It is important as a risk factor for cardiovascular disease.
Patients with full hypothyroidism have serum levels of triglycerides, total cholesterol and low density lipoprotein (LDL) cholesterol that are elevated. The same changes exist in subclinical hypothyroidism, but are less marked and less consistent.
Some studies have shown a decrease in LDL and total cholesterol levels after treatment with l-thyroxine, although others have refuted this.3,6,7A sensitive measure of myocardial contractility, the ratio of pre-ejection period to left ventricular ejection time, has also been shown to improve in patients with subclinical hypothyroidism, treated with l-thyroxine, compared with those on placebo.
Management
The main point here is should we treat, and if so, when?
If the elevation of TSH level is large and it has been so for a long period of time, antithyroid antibodies will also have been present. This situation carries a greater likelihood of progression to overt hypothyroidism and therefore a greater potential benefit from treatment.
Indications for treatment:
Contra-indications to treatment are osteoporosis and fracture risk. |
Recent research has shown that submaximal cardiopulmonary exercise performance improves after six months of TSH normalisation and this improvement can help enhance the ability to carry out daily life activities.9
Complications
- Hypercholesterolaemia
- Coronary artery disease
Prognosis
Risk of progression to overt hypothyroidism can be ranked according to serum TSH level:
- TSH 6-10 mU/L: no risk for future hypothyroidism
- TSH greater than 10mU/L: 1-20% risk of progression per year10
Pregnancy
- During the first trimester thyroxine is supplied exclusively by the mother. Fetal production begins at 10-12 weeks' gestation. Thyroxine is important for fetal neural development throughout pregnancy, but particularly so in the first trimester. Maternal hypothyroidism has been associated with mental retardation in their euthyroid children, and with increased fetal loss.11
- Pregnant women with goitre, high antithyroid antibody titre, family history of thyroid disease or symptoms suggestive of hypothyroidism, should be screened early in pregnancy, or preferably prior to conception, and treated.
Document references
- Franklyn JA, Daykin J, Drolc Z, et al; Long-term follow-up of treatment of thyrotoxicosis by three different methods.; Clin Endocrinol (Oxf). 1991 Jan;34(1):71-6. [abstract]
- Tamai H, Kasagi K, Takaichi Y, et al; Development of spontaneous hypothyroidism in patients with Graves' disease treated with antithyroidal drugs: clinical, immunological, and histological findings in 26 patients.; J Clin Endocrinol Metab. 1989 Jul;69(1):49-53. [abstract]
- Cooper DS, Halpern R, Wood LC, et al; L-Thyroxine therapy in subclinical hypothyroidism. A double-blind, placebo-controlled trial.; Ann Intern Med. 1984 Jul;101(1):18-24. [abstract]
- Staub JJ, Althaus BU, Engler H, et al; Spectrum of subclinical and overt hypothyroidism: effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues.; Am J Med. 1992 Jun;92(6):631-42. [abstract]
- U.S. Preventive Task Force. Guide to Clinical preventive services: report of the U.S. Preventive Services Task Force.; 2d Ed. Baltimore,Md,: Williams and Wilkins, 1996.
- Arem R, Patsch W; Lipoprotein and apolipoprotein levels in subclinical hypothyroidism. Effect of levothyroxine therapy.; Arch Intern Med. 1990 Oct;150(10):2097-100. [abstract]
- Franklyn JA, Daykin J, Betteridge J, et al; Thyroxine replacement therapy and circulating lipid concentrations.; Clin Endocrinol (Oxf). 1993 May;38(5):453-9. [abstract]
- Fatourechi V; Subclinical hypothyroidism: an update for primary care physicians. Mayo Clin Proc. 2009;84(1):65-71. [abstract]
- Mainenti MR, Vigario PS, Teixeira PF, et al; Effect of Levothyroxine Replacement on Exercise Performance in Subclinical Hypothyroidism. J Endocrinol Invest. 2009 Mar 25. [abstract]
- Hueston WJ; Treatment of hypothyroidism.; Am Fam Physician. 2001 Nov 15;64(10):1717-24. [abstract]
- Brent GA; Maternal hypothyroidism: recognition and management.; Thyroid. 1999 Jul;9(7):661-5. [abstract]
Internet and further reading
- Herrick B; Subclinical hypothyroidism. Am Fam Physician. 2008 Apr 1;77(7):953-5.
Acknowledgements
EMIS is grateful to Dr Hayley Willacy for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2011.Document ID: 1664
Document Version: 23
Document Reference: bgp2296
Last Updated: 3 Mar 2010