3. Subclinical Hypothyroidism

Subclinical Hypothyroidism

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

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.

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.

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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, eg lithium or amiodarone.
  • Other causes include head and neck surgery or radiotherapy.

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:

Recommendations about thyroid screening have been inconsistent. No organisation currently recommends routine screening. The US Preventive Services Task Force[5] 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.

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][7] A 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.

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:
  • TSH ≥10, or clinical features present.[8]
  • Levothyroxine is the drug of choice as it has a long half-life (seven days) and is partially converted to T3 in the body, resulting in a constant physiological level of both T3 and T4 with a single daily dose.
  • Dosing: young start at 50 mcg od.
  • Elderly: start at 12.5 to 25 mcg od.
  • Goals for treatment are a fall in LDL cholesterol, or symptomatic improvement, or TSH normalising to <4.0. Monitor at 6-8 week intervals initially. Once the correct dose has been established, monitoring can be 6-12 monthly.
  • Aim to lower TSH to mid-normal: 1-3 mU/L.
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]

  • Hypercholesterolaemia
  • Coronary artery disease

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 year[10]
  • 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.
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Further reading & references

  • Herrick B; Subclinical hypothyroidism. Am Fam Physician. 2008 Apr 1;77(7):953-5.
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Arem R, Patsch W; Lipoprotein and apolipoprotein levels in subclinical hypothyroidism. Effect of levothyroxine therapy.; Arch Intern Med. 1990 Oct;150(10):2097-100.
  7. Franklyn JA, Daykin J, Betteridge J, et al; Thyroxine replacement therapy and circulating lipid concentrations.; Clin Endocrinol (Oxf). 1993 May;38(5):453-9.
  8. Fatourechi V; Subclinical hypothyroidism: an update for primary care physicians. Mayo Clin Proc. 2009;84(1):65-71.
  9. Mainenti MR, Vigario PS, Teixeira PF, et al; Effect of Levothyroxine Replacement on Exercise Performance in Subclinical Hypothyroidism. J Endocrinol Invest. 2009 Mar 25.
  10. Hueston WJ; Treatment of hypothyroidism.; Am Fam Physician. 2001 Nov 15;64(10):1717-24.
  11. Brent GA; Maternal hypothyroidism: recognition and management.; Thyroid. 1999 Jul;9(7):661-5.
Original Author: Dr Hayley Willacy Current Version:
Last Checked: 20/04/2011 Document ID: 1664  Version: 23 © EMIS

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

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