Thyroid disease: challenges in Primary care

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Requests for thyroid tests are increasing, although in many cases clinical need is not evident.

If thyroid dysfunction is suspected, measuring TSH alone is recommended as the first step. Test T4 only when TSH is abnormal.

Ultrasound should be considered for patients with thyroid dysfunction and goitre (enlarged thyroid) or palpable thyroid nodules, but NOT if the only abnormality is hypothyroidism or elevated antithyroid antibodies.

Repeat TSH testing within 12 months is generally not recommended if TSH is normal.

Fatigue alone should not be the basis of thyroid testing. Instead, take a detailed clinical history and perform a targeted physical examination before requesting tests or treatment.

Identifying thyroid disease in general practice

Thyroid disease can be broadly categorised as:

thyroid dysfunction (hypothyroidism, hyperthyroidism,) or

structural disease (goitre, nodules and cancer).

Hypothyroidism (high TSH, low T4) is the most common disorder of thyroid function, with a prevalence ranging from 0.5% to 5% for overt and subclinical cases, respectively.

Hyperthyroidism (low TSH, high free T4/T3) is less common than hypothyroidism, with a prevalence of around 0.5%–1.0%.

When to suspect thyroid dysfunction

Hypothyroidism

Signs and symptoms of hypothyroidism may vary depending on patient characteristics and the severity of dysfunction.

Classic symptoms include fatigue, weight gain, cold intolerance, arthralgia, constipation, menorrhagia, irregular menstrual cycles, and dry skin and hair.

Physical signs include coarse skin and hair, bradycardia and goitre but these may be absent in mild hypothyroidism.

Many of the signs and symptoms are not specific to hypothyroidism: around 20%–25% of people with normal TSH report one or two of these symptoms. Laboratory tests are required to establish a diagnosis of hypothyroidism.

Hypothyroidism can be classified as overt, subclinical or secondary (central).

Overt hypothyroidism (high TSH, low free T4) is usually symptomatic and readily diagnosed, although there are exceptions.
Subclinical hypothyroidism (elevated TSH, normal free T4) is more common than overt hypothyroidism, but less frequently detected clinically as many patients have vague symptoms.
Secondary (or central) hypothyroidism is caused by disorders of the pituitary gland or hypothalamus and is characterised by decreased TSH and a disproportionately low concentration of free T4.

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Hyperthyroidism

Classic symptoms for hyperthyroidism include weight loss, heat intolerance, palpitations, breathlessness, anxiety, diarrhoea, menstrual disturbances, tremor and proximal muscle weakness.

Physical signs include tremor, tachycardia, ophthalmopathy (if due to Graves disease), goitre and difficulty rising from a squatting position. However some patients (especially in older age groups), may present with ‘apathetic hyperthyroidism’ and lack many of the classical features.

Overt hyperthyroidism is characterised by increased free T4 and free T3 and low TSH. It is most commonly caused by Graves disease, or toxic nodular goitre.
Subclinical hyperthyroidism is characterised by suppressed TSH and normal free T3/T4 in patients with or without symptoms of hyperthyroidism. Mild subclinical hyperthyroidism (with low but detectable TSH levels) may be caused by autonomous thyroid nodules but may also be found in healthy individuals.

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Thyroid function tests

These include tests for thyroid stimulating hormone (TSH), free thyroxine (T4) and free triiodothyronine (T3).

Thyroid ultrasounds may be used to assess clinically detected, visible or palpable thyroid nodules or goitre.

Thyroid nuclear scans are primarily useful in differentiating the causes of hyperthyroidism and assessing the function of thyroid nodules, but may also be used to differentiate probable causes of hyperthyroidism even when nodules are not present.

Antithyroid antibody tests:

Positive antibody tests indicate the following conditions:

TSH receptor antibodies (TRAb): Graves disease
Thyroid peroxidase antibodies (TPOAb): Hashimoto disease
Thyroglobulin antibody (TgAb): Hashimoto disease. This test may also be part of thyroid cancer follow-up when interpreting the results of thyroglobulin levels.

Antibody testing is not recommended when TSH is in the normal reference range.

Optimizing the use of thyroid testing and imaging

Screening for thyroid dysfunction is not recommended in asymptomatic patients unless there is a clinical suspicion of thyroid dysfunction or the patient is in a high-risk group (such as patients with autoimmune disease or type 1 diabetes).

Measuring TSH is recommended as the first-line test for possible thyroid dysfunction.1 If TSH is in the reference range, additional tests (T3, T4 and thyroid antibodies) are generally not required except in patients with pituitary disease (in which case TSH is unreliable).

When should T3 also be tested?

Serum T3 should only be tested when TSH is less than 0.1 mIU/L (milli-international units per litre). If TSH is low but free T4 is normal, elevated T3 may indicate early Graves disease or ‘T3 toxicosis’ caused by an autonomously functioning thyroid nodule.

Physiologic factors influencing TSH values

Several factors can alter the normal range of TSH values, and should be considered when making a clinical decision.

First, unexplained intra-individual variation may occur in healthy individuals, as well as those with subclinical hypothyroidism. These changes do not necessarily indicate a change in thyroid function or status.
Second, the normal range for TSH values tend to increase with age, such that the upper limit (97.5th percentile) of normal values ranges from 3.5 mIU/L for 20–29-year-olds to 7.5 mIU/L for 80+ year-olds.
Third, TSH values follow a circadian rhythm, with peak values from midnight to 4 am and a nadir from midday to 6 pm. This variation can account for differences of 1-2 mIU/L in healthy individuals as well as those with subclinical hypothyroidism.

Finally, low TSH values are common in the first trimester of pregnancy, but often normalise in the second and third trimesters.

Management and Medicines

The goals of treatment for hypothyroidism are normalisation of TSH levels and relief of symptoms.

For patients with diagnosed overt hypothyroidism recommended first-line treatment is thyroid hormone replacement at an initial dose of levothyroxine 50–100 micrograms /day, or 25 micrograms/day for frail or elderly patients.

Current recommendations are that patients should have TSH and T4 retested 6–8 weeks after initiating levothyroxine to determine if a change in dosage is required.

Most guidelines recommend treatment in subclinical hypothyroidism cases (< 10 mIU/L) only for patients who are younger than 65, symptomatic or have other clear indications, such as cardiovascular disease.

For hyperthyroidism, choice of treatment depends on the patient’s age, symptoms, comorbidities and the underlying cause of illness.

Most symptomatic patients, regardless of the cause of their condition, benefit from beta blockers to manage their adrenergic symptoms.

Graves disease can be treated with antithyroid medicines (thionamides, which inhibit thyroid peroxidase), radioactive iodine or surgery.

After prescribing antithyroid medicine, refer patient to an endocrinologist.

Radioactive iodine or thyroidectomy are the primary treatment options for toxic nodular goitre.

Patients with milder subclinical hyperthyroidism often stabilise without treatment, so careful monitoring and repeat testing may be all that is required.

Treatment should also be considered for symptomatic elderly patients, patients with underlying cardiovascular disease, and those with symptoms suggestive of hyperthyroidism or associated comorbidities.

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