Management of nodular thyroid disease

Thyroid nodules are found in 5% of middle aged women and are commoner in women than in men. A nodule raises concerns about malignant disease, but thyroid cancer is rare, accounting for about 1000 new cases in England and Wales each year. The main aim of management is to identify the small proportion of patients with thyroid cancer who require treatment and avoid unnecessary testing and treatment for the majority.

Nodules are more likely to be malignant in men, particularly men aged over 70.¹ A history of neck irradiation, rapid tumour growth, or a family history of thyroid cancer increases risk. Physical signs associated with increased risk include firm, non-tender nodules, local lymphadenopathy, and recurrent laryngeal nerve palsy in the absence of previous surgery. The incidence of cancer in those with clinical features strongly suggestive of malignancy is high,² but most patients do not have these features.

Solitary nodules are more common than multinodular goitres clinically, and solitary nodules used to be considered more likely to harbour malignant disease. This view was questionable, however, as half of patients with clinically apparent solitary nodules turn out to have multinodular goitres at surgery.³ A recent study shows that the incidence of cancer is similar in those with clinically apparent solitary and multiple nodules.¹ In those with true solitary nodules confirmed at operation the risk of cancer is the same as in those with multinodular goitres.³

The only biochemical test routinely performed is a thyroid function test. Most patients are euthyroid, but overt thyroid dysfunction effectively rules out malignancy. Calcitonin is measured in screening families for medullary cell carcinoma. A recent study of patients with thyroid nodules reported a surprisingly high number with raised serum calcitonin concentrations who at surgery were shown to have sporadic medullary cell carcinoma.⁴ Further studies, however, are needed before routine serum calcitonin measurement is accepted in the evaluation of thyroid nodules.

Radionuclides (iodine-123 or technetium pertechnate) classify nodule function on their ability to trap iodine. A malignant nodule should appear as a “cold,” non-functioning area, a benign nodule as “warm” or “hot.” Since, however, most nodules are cold and generally benign, and warm or hot nodules can be malignant,⁵many centres have abandoned radionuclide scanning. Ultrasound techniques classify nodules as solid or cystic in the belief that solid lesions might be malignant and cystic lesions benign. But, again, recent studies suggest that the risk of carcinoma is in fact similar, or higher, in cystic nodules.⁶ Most “cystic” lesions are partly solid, and purely cystic lesions are rare. Thus neither radionuclide scans nor ultrasound reliably distinguish benign from malignant disease.

Trials of thyroid hormone (thyroxine) suppression are given assuming that dependency on serum thyroid stimulating hormone is different in benign and malignant disease. Benign tumours might shrink, malignant tumours would not. Follow up of benign nodules over 10 years suggests that most remain the same, shrink, or disappear.⁷A prospective study in iodine sufficient areas showed that nodules shrink in a significant proportion of those who do not receive thyroxine.^8. Thyroid stimulating hormone suppression treatment may lead to hyperthyroidism and reduced bone density and is a risk factor for atrial fibrillation. Trials of thyroxine suppression do not seem to be indicated.

Fine needle aspiration cytology is safe, simple, and quick (results are available within an hour). Pistol handle syringe holders or disposable plastic 10 ml syringe and 25 gauge needles are used. Each nodule is aspirated as there is a significant risk of malignancy in non-dominant, palpable thyroid nodules.¹ About 4% of aspirates are malignant, generally papillary cell carcinoma, and over 60% are benign.⁹

Fine needle aspiration cytology has three limitations. Firstly, about 20% of samples are initially unsatisfactory, although repeat sampling increases the likelihood of obtaining adequate samples. Partly cystic or cystic lesions account for 20% of thyroid nodules and often yield insufficient cells for diagnosis. Neither the size of the cyst or the colour of the aspirate is discriminatory. The cyst should be aspirated to dryness but generally recurs. If it does recur surgery should be considered.⁶ Secondly, follicular adenomas cannot be distinguished from carcinomas; 15% will be malignant. Cellular follicular lesions are also difficult to classify. Large bore needle biopsy is no more accurate and is associated with more side effects. Follicular lesions must be regarded as suspicious and management is controversial. Age, clinical features, and discussion with the patient will influence the decision on surgery. Many centres, however, suggest surgical excision of all indeterminate follicular lesions to make a definitive histological diagnosis. Finally, although most nodules are labelled as benign a major concern is the number of false negatives—missed carcinomas. Follow up of those labelled as benign on previous fine needle aspiration cytology showed 1% to be malignant.¹⁰,¹¹ Routine follow up fine needle aspiration cytology is not indicated, and clinical assessment at 12 months, with discharge of those without worrying clinical features, is reasonable.

The optimum diagnostic strategy for the euthyroid patient with nodular thyroid disease is still a matter for debate.¹² There is agreement, however, that fine needle aspiration cytology and a first line test of thyroid function are cornerstones of investigation.