Thyroid nodule

Any individual mass palpable within the thyroid gland. Nodules are typically benign, may be hyperfunctioning, and may occur within a multinodular goitre, but always require assessment for possible malignancy. Diagnosis is usually clinical but assessment should always include serum hormone testing, and may require uptake scanning or ultrasound guided fine needle aspiration.

Suspicious features

Any patient with a solitary palpable nodule greater than 1cm in diameter, or any nodule with suspicious characteristics arising within a multinodular goitre, or any nodule with associated lymph nodes, will require urgent an ultrasound scan. The radiological characteristics taken with the level of clinical suspicious will then determine whether ultrasound guided aspiration is required according to international guidelines. Clinically guided fine needle aspirations of thyroid nodules are now rarely performed, and only if ultrasound is unavailable to help define whether aspiration is indicated at all, and which area of the lesion to aspirate.

Patients with thyrotoxicosis and an isolated nodule

These patients are unlikely to have malignancy and are more likely to have a toxic follicular adenoma. However, their nodule should still be assessed clinically and with ultrasound if indicated in the usual way. Similarly if the nodule has any suspicious features it will still require ultrasound guided fine needle aspiration performed.

If aspiration is not necessary, treatment is usually with radioactive iodine. If the nodule is shrinking at three months, no further assessment is indicated. If the patient declines or is unsuitable for radioactive iodine, surgery to resect the nodule or medical therapy with antithyroid drugs to control the thyrotoxicosis should be discussed in the usual way.

Common side effects of antithyroid drugs

Agranulocytosis is an uncommon but important side effect of all anti-thyroid drugs. Patients should receive written and verbal warnings to discontinue the drug until they have had a blood count checked if they develop a severe sore throat or mouth ulcers.

Mild neutropaenia <1.5x10*9 is commonly observed in people with Graves disease, some racial groups and with anti-thyroid drugs.

Neutrophil count 1-1.5 - continue drug but institute close monitoring of blood count. 

Neutrophil count <1 - stop antithyroid drug and monitor blood count daily.

Neutrophil count <1 with suspected sepsis or in the unwell patient - stop antithyroid drug and arrange urgent admission. Treat as for neutropaenic sepsis, remembering that pseudomonas is a common infective organism in this group. Monitor blood count every 12 hours initially and take haematological advice. Bone marrow biopsy may be helpful to determine response. Granulocyte-colony stimulating factor (GCSF) should be considered after haematology review of the patient's response to drug cessation. DO NOT RECHALLENGE THE PATIENT WITH AN ALTERNATIVE ANTI-THYROID DRUG.

Rash is common and usually controlled by antihistamines. Alternatively switch to alternative anti-thyroid drug.

Arthralgia and arthritis are uncommon with carbimazole but more common with PTU. Stop the drug. Check antibody screen including ANCA for drug induced lupus and discuss wtih rheumatologist. 

Mild abnormalities of liver function are common with thyrotoxicosis and do not require treatment. Mild transaminitis (<1.6x upper limit of normal) is also common after 3 months therapy with PTU and does not require treatment or monitoring unless baseline liver function was abnormal.

Allergic hepatitis with submassive necrosis occurs in 0.1-0.2% of patients receiving PTU. Stop PTU and involve a hepatologist immediately if this is suspected.

Carbimazole is not associated with this condition, but may cause a cholestatic picture of abnormal liver function. Stop the drug and inform hepatology if this is suspected, though complete resolution is normal on drug withdrawal. 

Patients with hypothyroidism and an isolated nodule

These patients should be assessed and the nodules aspirated if indicated. Thyroxine treatment should also be instituted and the nodule re-assessed at three months.

Fine needle aspiration results

Non diagnostic results on fine needle aspiration

Non diagnostic aspirations should be repeated on at least two further occasions three months apart, according to British Thyroid Association guidelines.

If results are non diagnostic on two occasions, consider surgery to establish a diagnosis. 

Benign results on fine needle aspiration

A clearly benign result indicating thyroiditis may not need to be repeated. A result classified as Thy2 according to the Royal College of Physicians criteria indicates benign nodular disease, but should be repeated after 3-6 months.

Many patients may then be discharged, or treated with radioactive iodine if there is thyrotoxicosis or the nodule has arisen within a multinodular goitre which merits treatment in its own right.

This aims to shrink the nodules and treat the hyperthyroidism.

Follicular cells on fine needle aspiration

Any follicular cells are difficult to differentiate between benign and malignant disease. Those classified Thy 3a have atypical features, though Thy3f are more likely to represent a follicular cancer. Any Thy3 results must be referred for discussion at a thyroid multidisciplinary team for consideration of hemithyroidectomy, though in some cases a repeat aspiration of a low risk Thy3a lesion will be acceptable.

If histology confirms the lesion to be a follicular adenoma then the patient can be discharged. If histology reveals a follicular carcinoma, completion thyroidectomy and radioactive iodine are required.

Results of fine needle aspiration suggestive, or diagnostic, of malignancy

Results diagnostic of malignancy (Thy5) require immediate referral to a thyroid multidisciplinary team for consideration of total thyroidectomy, followed by radioactive iodine if appropriate according to national thyroid cancer guidelines.

Results suggestive of but not diagnostic of malignancy (Thy4) should be repeated to establish a diagnosis, and also referred to a multidisciplinary team.

Pregnancy and fertility plans should be discussed with all patients

Nodules should be assessed and treated conventionally in pregnant patients, though surgery should be deferred to the second trimester in most cases.

Radioactive iodine treatment

This is the treatment of choice for most patients with thyrotoxicosis secondary to nodular disease, or euthyroid multinodular goitres causing early compressive symptoms. Radioactive iodine will prevent future growth and reduce the size of most goitres and solid nodules by up to 50%. Radioactive iodine is also the treatment of choice for hyperthyroidism due to nodular disease, which will otherwise require life long anti-thyroid drugs.

Radioactive iodine is contraindicated in pregnant or breast feeding individuals. Women should be advised to avoid conception for six months and men should avoid fathering children for four months following radioactive iodine treatment.

Post radioactive iodine monitoring and hypothyroidism

Thyroid function should be assessed at least every three months for the first year after radioactive iodine, and then annually thereafter for emerging hypothyroidism.

All patients should be warned that monitoring is required and that hypothyroidism develops in up to 70% of patients. Subsequent hypothyroidism should be treated conventionally.

Inadequate control of thyrotoxicosis by six months should prompt consideration of a repeat application of radioactive iodine.

Nodules should be shrinking within three months.

New growth or change in the characteristics of a nodule despite previous radioactive iodine should prompt reassessment as for a new nodule.

Thyroid surgery

Surgery should be discussed in all cases. Patients with a hyperfunctioning nodule who are unsuitable for, or decline, radioactive iodine may be offered a hemithyroidectomy. Thyroidectomy may also be considered for multinodular goitres, especially those causing compressive symptoms. Surgery is also appropriate after more than two non-diagnostic fine needle aspirations to establish a diagnosis, or after a Thy3, Thy4 or Thy5 aspiration result according to national guidelines and MDT discussion.