Hypothyroidism
د. حسين محمد جمعةاختصاصي الامراض الباطنة
البورد العربي
كلية طب الموصل
2010
"Hypothyroidism is a common condition that presents with non-specific symptoms across a wide age range. It is often an incidental finding on routine blood tests.
In most patients, management involves monitoring thyroid function and appropriate replacement with thyroxine.
Hypothyroidism is common, insidious, and difficult to diagnose, particularly in elderly people and in post-partum women.
Mild thyroid failure (subclinical hypothyroidism) is a common finding in the normal population.
Screening in primary care detects only a few cases of overt hypothyroidism. Screening should be limited to perimenopausal women or those presenting to their GP with non-specific symptoms.
Surveillance for hypothyroidism is required following radio iodine therapy or thyroidectomy for hyperthyroidism
The diagnosis of hypothyroidism must be confirmed by measuring serum thyroid stimulating hormone and serum free thyroxine.
Once recognised, hypothyroidism is treatable with thyroxine. Referral to a specialist is required only in rare circumstances, such as suspected hypopituitarism.
Patients with subclinical hypothyroidism (raised serum thyroid stimulating hormone and normal free serum thyroxine) have an increased risk of progression to overt hypothyroidism, particularly if they are positive for thyroid antibodies.
Clinical tip
The target of thyroxine replacement is to maintain a serum thyroid stimulating hormone within the normal range. Thyroid function tests should be checked no earlier than six to eight weeks after each change in thyroxine dose to allow the thyroid function tests to stabilise.
Primary hypothyroidism
Is most often caused by chronic autoimmune thyroiditis. Iatrogenic causes include treatments with destructive effects on thyroid tissue. Among patients undergoing treatment for hyperthyroidism, interventions such as radioiodine therapy and surgery are associated with an increased risk of subsequent subclinical or overt hypothyroidism.Patients previously treated with radical radiotherapy for head and neck cancers are also at increased risk of primary hypothyroidism. Mantle radiotherapy for Hodgkin's disease was associated with an actuarial risk of clinical and subclinical hypothyroidism of 47% at 27 years post-treatment. Hypothyroidism is the most common consequence of direct thyroid irradiation Drug causes include amiodarone and lithium.
Secondary hypothyroidism
occurs when damage to the pituitary or hypothalamus results in insufficient serum thyroid stimulating hormone production.Non-thyroidal illness (formerly known as sick euthyroid syndrome) manifests in severe illness with low levels of free thyroxine and free tri-iodothyronine. The serum thyroid stimulating hormone may be normal or inappropriately low. Thyroid hormone levels return to normal after the illness resolves.
Congenital hypothyroidism affects 1 in 4000 live births. If untreated within the first four weeks, it causes irreversible mental retardation. Before the advent of neonatal screening in the developed world, the average intelligence quotient of children with congenital hypothyroidism was 76. Less than 5% of newborns with hypothyroidism are diagnosed clinically because there are often few clinical features. The intelligence quotient in later life has been shown to be inversely related to the age at diagnosis. Worldwide, iodine deficiency is the most common cause of congenital hypothyroidism.
To avoid delay in diagnosis, neonates in the UK are screened using the Guthrie heel prick test in the first week of life. But remember: don't automatically assume that every infant that presents to you has been Guthrie tested, especially if they have recently immigrated to the UK.
Hypothyroidism affects 9.3% of women and 1.3% of men in the UK.
A longitudinal 20 year follow up study in a UK population showed an annual incidence of clinical hypothyroidism of 40 per 10 000 women and 6 per 10 000 me The incidence of hypothyroidism can be higher in areas with high iodine intake than in areas with normal or low iodine intakeThe incidence of hypothyroidism is higher in people with Down's syndrome, Turner's syndrome, and autoimmune conditions - especially type 1 diabetes and coeliac disease.
Amiodarone contains a large amount of iodine (75 mg in each 200 mg tablet) and can induce thyroid dysfunction. Clinical hypothyroidism can occur in up to 20% of patients on long term amiodarone.
Lithium is associated with clinical hypothyroidism in up to 15% of patients.
In a population-based study of over 30 000 subjects with no previous history of thyroid dysfunction, the prevalence of overt and subclinical hypothyroidism among women who were current smokers was significantly lower than for never-smokers
How do I diagnose it?
History
The symptoms of hypothyroidism develop insidiously:
Lethargy
Mental slowing
Depression
Cold intolerance
Weight gain
Dry skin
Coarsening of hair
Constipation
Paraesthesia
Heavy or irregular menstrual periods
Examination
Look for:Coarse facies
Dry, pale, or yellowish skin
Hair thinning
Loss of outer third of eyebrow
Voice hoarseness
Goitre
Bradycardia
Slow-relaxing deep tendon reflexes
Myxoedema (non-pitting oedema).
Investigations
If you suspect the diagnosis, check serum thyroid stimulating hormone and serum free thyroxine.
Elevated serum thyroid stimulating hormone is diagnostic of hypothyroidism. Sensitivity of thyroid stimulating hormone in unselected ambulant populations is 89% to 95% and specificity is 90% to 96% for clinical (overt) hypothyroidism
Decreased serum free thyroxine confirms clinical hypothyroidism
Serum free thyroxine is normal in subclinical hypothyroidism
The next investigation is testing for thyroid antibodies.
The presence of antithyroid peroxidase antibodies indicates increased risk of later progression to clinical hypothyroidismWomen with type 1 diabetes who are trying to conceive. The presence of thyroid antibodies in this group carries a threefold increase in the risk of developing post-partum thyroiditis.
Hypothyroidism may affect the results of other blood tests that you may have requested, for example:
Full blood count may show a mild macrocytosis or a normochromic normocytic anaemia
Hypothyroidism is a secondary cause of dyslipidaemia.
Note: Clinical hypothyroidism is a potentially reversible cause of dyslipidaemia. It causes elevated levels of total and LDL (low density lipoprotein) cholesterol due to reduced uptake of LDL cholesterol by its receptor on the surface of liver cells. A retrospective follow up study in the Netherlands looked at 1509 consecutive patients referred with severe dyslipidaemia (total cholesterol >6.5 mmol/l and/or high density lipoprotein (HDL) cholesterol level <0.9 mmol/l and/or triglyceride level >2.3 mmol/l).
The observed prevalence of clinical hypothyroidism in this group was 0.7%; double that of their general population (0.3%). After the hypothyroid patients were treated with levothyroxine, a statistically significant reduction in total cholesterol and LDL cholesterol levels was shown only for those patients with pre-treatment TSH levels greater than 10.0 mU/l.
Note: consider Addison's disease in patients presenting with symptoms suggestive of hypothyroidism-like fatigue.
How should I treat it?
Clinical hypothyroidismTreatment is aimed at eliminating the symptoms of hypothyroidism and maintaining a serum thyroid stimulating hormone within the reference range.
Benefits of thyroxine in clinical hypothyroidism
Although there are no randomised controlled trials comparing thyroxine with placebo, the consensus is that treatment is beneficial in people with clinical hypothyroidism. It is considered unethical to undertake a placebo controlled trial
Side effects of thyroxine
Hyperthyroidism can be induced by over replacement with thyroxine
Bone mass: 13 randomised controlled trials found that long term thyroxine significantly reduced bone mass in postmenopausal women (average age 61.2 years) compared with controls after 9.9 years. It showed no significant difference in bone mass between premenopausal women on thyroxine and controls
Fracture rate: one longitudinal observational study involving 1180 people followed up over an average of 8.6 years showed no significant increase in fracture rate between people receiving thyroxine and controls.
Atrial fibrillation: in one observational study of people older than 60 taking thyroxine, a low serum thyroid stimulating hormone level (subclinical hyperthyroidism) was associated with a fourfold increased risk of atrial fibrillation (diagnosed by ECG) compared with controls
Drug interactions with thyroxine
Patients on warfarin may need careful monitoring and adjustment of their warfarin dose when their thyroxine dose is altered. Thyroxine can enhance the anticoagulant effect of warfarinThyroxine may increase the metabolism of propranolol
Anticonvulsants and rifampicin increase hepatic metabolism of thyroxine and may increase thyroxine replacement requirements
Dose of thyroxine in hypothyroidism
In elderly people and those with coronary heart disease: 25 to 50 µg daily. Increase dose cautiously by 25 µg, checking thyroid stimulating hormone and serum free thyroxine at six to eight weekly intervals. Once clinically euthyroid, wait six to eight weeks before rechecking thyroid stimulating hormone..In younger patients: 50 to 100 µg daily.
Learning bite
Thyroxine is usually given as levothyroxine.
Recheck thyroid stimulating hormone and serum free thyroxine six weeks after each change in thyroxine dose.
There is no evidence that adding tri-iodothyronine to thyroxine therapy is of value in patients who remain symptomatic despite reaching a serum thyroid stimulating hormone within the reference range.
• Hypothyroidism: diagnosis and treatment
• Subclinical hypothyroidism
• Not all patients with subclinical hypothyroidism need thyroxine therapy. People who test negative for thyroid antibodies can be followed up with annual thyroid function tests (thyroid stimulating hormone and serum free thyroxine) on the basis that their annual risk of developing clinical hypothyroidism is just 2% per year.
Benefits of thyroxine in subclinical hypothyroidism
Several randomised controlled trials have evaluated thyroxine treatment in people with subclinical hypothyroidism.The evidence of benefit is less clear than for clinical hypothyroidism.
Side effects of thyroxine in subclinical hypothyroidism
Two randomised controlled trials reported side effects with thyroxine.One trial found worse anxiety scores in patients treated with thyroxine, compared with patients treated with placebo
The second trial reported that 11% of people on thyroxine withdrew because of complications (worsening angina or atrial fibrillation)
To which patients with subclinical hypothyroidism should I give thyroxine?
Confirm the diagnosis by repeating the serum thyroid stimulating hormone three months later to exclude a thyroiditis or non-thyroidal illness. If antithyroid antibodies are not present and the serum thyroid stimulating hormone level is only mildly elevated (<10 mU/l) then treatment can be deferred.These patients have an annual conversion rate to clinical hypothyroidism of just 2% (Patients testing positive for antibodies with an elevated serum thyroid stimulating hormone have a 4% annual risk of developing clinical hypothyroidism.)
Annual thyroid function tests are sufficient to follow up these patients.
Thyroxine therapy should be started when the serum thyroid stimulating hormone rises to 10 mU/l.
Pregnancy
Clinical hypothyroidism in pregnancyThyroxine is safe to use in pregnancy and while breast feeding.
Subclinical hypothyroidism in pregnancy
Women with subclinical hypothyroidism who are trying to get pregnant should be treated with thyroxine. Untreated hypothyroidism in pregnancy is associated with an increased risk of fetal loss, stillbirth, and premature labour
The aim is to normalise women's serum thyroid stimulating hormone before pregnancy, even in mild thyroid failure
The daily dose of thyroxine may need to increase by 25 to 50 µg during pregnancy
This dose increase must happen within the first 12 weeks of the pregnancy. Do not delay until the antenatal booking consultation
Type 1 diabetes and pregnancy
Women with type 1 diabetes should have their thyroid function and thyroid peroxidase antibody status established before conception, at antenatal booking, and six to eight weeks after giving birth.Post-partum thyroiditis develops in up to 25% of women with type 1 diabetes
Women with type 1 diabetes are three times more likely to develop post-partum thyroid dysfunction than women without type 1 diabetes
Hypothyroidism can usually be treated by GPs, and referral to a specialist is necessary only in the following circumstances:
• Patients with pituitary or hypothalamic disease (secondary hypothyroidism). These patients will need to have the extent of their hypopituitarism assessed before starting thyroxine
• Children younger than 16
• Post-partum or pregnant women
• Patients with type 1 diabetes
• Patients taking long term amiodarone or lithium therapy
• Patients with suspected adrenal insufficiency.
Follow up
Annual check of serum thyroid stimulating hormone and free serum thyroxinePregnant women with hypothyroidism should have their serum thyroid stimulating hormone measured in each trimester. Many will need an increased dose of thyroxine during pregnancy, but should return to their pre-pregnancy dose immediately after delivery. Check serum thyroid stimulating hormone six to eight weeks post-partum
All patients on amiodarone and lithium therapy should have their thyroid function checked before treatment and annually while on treatment
What's the outlook?
Most patients will need life long thyroxine replacement.
What do patients want to know?
Does hypothyroidism affect my life expectancy?
There are no data to suggest long term thyroxine therapy is associated with increased morbidity or mortality.
Is it safe to take thyroid hormones during pregnancy and breast feeding?
Yes. Thyroxine replacement therapy is safe in these circumstances. Thyroxine dose requirements may increase during pregnancy and you may need to increase your dose soon after conception.
Will thyroxine affect my angina?
Thyroxine may aggravate angina in people with ischaemic heart disease, and therefore thyroxine should be started at low dose.I have been treated with thyroxine. Why do I still have symptoms of hypothyroidism despite achieving a serum thyroid stimulating hormone within the reference range?
Overtreatment with thyroxine (subclinical hyperthyroidism) is associated with harmful side effects. If symptoms persist despite a normal level of thyroid stimulating hormone an alternative explanation for the symptoms should be sought.
There is no evidence that adding tri-iodothyronine to thyroxine therapy improves symptoms or quality of life.
GMS contract
Hypothyroidism is in the quality and outcomes framework of the general medical services contract. Points are awarded for practices achieving targets:2 points for producing a register of patients with hypothyroidism
Up to 6 points for the percentage of patients (up to 90%) with hypothyroidism with thyroid function results recorded within the previous 15 months
Thyroid antibodies are useful for screening patients at increased risk of post-partum thyroiditis. This includes women with a previous history of post-partum thyroiditis and people with type 1 diabetes.
Thyroxine should be given to normalise serum thyroid stimulating hormone if a woman with subclinical hypothyroidism thinking about becoming pregnant
Three randomised controlled trials found no effect of thyroxine on dry skin, cold intolerance, constipation, health related quality of life, or cognitive function in subclinical hypothyroidism. One small randomised controlled trial, involving 20 patients, did find that thyroxine significantly improved left ventricular function at six months compared with placebo.
