Multinodular goitre

Nodular thyroid swelling which may be associated with hyperthyroidism, and is not auto-immune in origin. The diagnosis is usually made clinically, though an ultrasound scan and thyroid function testing are often performed as part of the assessment.

Any suspicious characteristics

Any patients in whom a solitary nodule, suspicious or dominant nodule within the gland, or with palpable lymph nodes requires urgent ultrasound guided aspiration.

Pregnancy and fertility plans should be discussed with all patients

It is standard practise to use propylthiouracil rather than carbimazole in thyrotoxic patients who may be or are planning pregnancy, due to small but real concerns regarding teratogenicity from carbimazole. Treatment may frequently be stopped by the second trimester as the disease often spontaneously improves until the post partum period. Monitoring should continue throughout pregnancy and breastfeeding, and carbimazole substituted for propylthiouracil if required during the second trimester (since organogenesis is complete, and the risk of liver failure from propyl thiouracil outweighs the risks of carbimazole during this stage of the pregnancy). 

Patients with uncontrolled thyrotoxicosis should be advised to avoid pregnancy until biochemical control is achieved due to the risk of miscarriage. Treatment during pregnancy requires close monitoring typically every six weeks.

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.


Medical treatment for thyrotoxicosis

All patients with severe thyrotoxicosis should be considered for immediate medical treatment before long term decisions are taken.

All patients must receive written and verbal warnings about possible side effects of drug therapy.

Exact treatment depends on the severity of thyrotoxicosis. Doses as low as 5-10mg carbimazole may be appropriate in asymptomatic patients with mild biochemical disease.  With more severe disease, a typical starting dose is 40mg carbimazole daily. 

All patients should receive instructions as to the timing of dose reduction and firm arrangements made for serial monitoring. Appropriate dose reduction will depend on symptom control, and on the rapidity of the fall in free thyroxine levels in the early stages, as TSH does not tend to respond as quickly to treatment. Typical monitoring intervals are every six weeks, with dose reduction from 40mg, to 20mg, 15mg, 10mg and then to maintenance therapy of 5mg. 

Long term treatment should be monitored with serum TSH, aiming for a level within the normal range with complete resolution of all symptoms.

Long term medical treatment may be appropriate in some cases

Some patients with toxic nodular goitres may choose long term medical therapy. Patients need to be warned that this treatment will be lifelong as hyperthyroidism secondary to multinodular goitres does not tend to remit. Antithyroid drugs are thus usually used short term prior to radioactive iodine therapy.  

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. 

Radioactive iodine should be offered to all patients

Radioactive iodine is the treatment of choice for most patients. It will prevent future growth and reduce the size of most goitres by up to 50% and so is particularly suitable for modest sized goitres. Radioactive iodine is also the treatment of choice for toxic nodular goitres which will otherwise require life long anti-thyroid drugs. The dose should be determined in line with local results by the responsible ARSAC officer. Typical doses for a multinodular goitre would be 800MBq, or 400MBq for a small toxic adenoma.

However, it is usual to start medical treatment at presentation in patients with severe thyrotoxicosis in order to allow them to make an informed decision regarding long term management. Written information should be given to all patients on the different treatments available, and they should be warned specifically about standard radiation safety precautions, the possibility of transient thyroid swelling, the need for long term monitoring and possibile thyroxine requirements.

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 treatment

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

Subsequent hypothyroidism should be treated conventionally.

Subsequent recurrence of hyperthyroidism may occur, though this is unusual, and should be treated with a repeat application of radioactive iodine.

Surgery should be discussed with all patients

With very large goitres, where cosmetic symptoms are severe or where there are definite obstructive symptoms, surgery is the standard treatment, although tracheal deviation or narrowing are not absolute contraindications to radioactive iodine.

Patients should be warned that surgery cannot prevent future re-growth or hyperthyroidism in all cases.

Long term follow up

Most patients with multinodular goitres will receive radioactive iodine treatment and so require annual thyroid stimulating hormone (TSH) measurement to monitor thyroxine replacement only.

Patients who have not required treatment should also have their TSH monitored on an annual basis. Permanent suppression of their TSH should prompt a review of whether radioactive iodine or other treatments are now indicated. Long term low TSH is associated with osteoporosis and atrial fibrillation. Consider bone densitometry scanning in such cases. 

Asymptomatic and euthyroid multinodular goitres

Asymptomatic goitres of any size may not necessarily require treatment. Increasing size, TSH suppression, frank thyrotoxicosis, osteoporosis, or atrial fibrillation should all inform the decision whether treatment is indicated in an individual case.