Management of thyroid nodules

B C H Leung 梁知行

HK Pract 2003;25:611-615

Summary

Thyroid function tests, ultrasound and fine needle aspiration cytology (FNAC) should be the first line tests performed in patients with thyroid nodules. Toxic patients should be rendered euthyroid before choosing between drug therapy, radioactive iodine therapy or surgery, depending on the cause. Non-toxic patients should be offered surgery if confirmed or suspected to have malignancy. The rest should be treated conservatively except for obstructive or cosmetic reasons. Figure 2 shows a simplified management plan.

摘要

甲狀腺功能檢查、超聲波檢查和針吸穿刺細胞學檢查（FNAC）是甲狀腺結節的一線檢查方法。 對於毒性甲狀腺結節的病人，應先使用甲狀腺功能降至正常，再根據病因選擇藥物、 放射性碘或手術治療。對於非毒性甲狀腺結節的病人，如果證實或懷疑為惡性， 應進行手術。其餘病人除有堵塞或美容的原因，否則都應採用保守治療。圖 2為一種簡化的治療方案。

Introduction

To different doctors, the thyroid may present as a different problem. Physicians worry about toxicity; surgeons, multinodularity; radiologists, cystic changes or solidity; pathologists, malignancy. At the end of the day, there are really only two problems of concern - hormonal imbalance and nature of the nodules. These two problems can co-exist (e.g. solitary toxic nodules and toxic nodular goitre) and both should be addressed in all thyroid patients.

Prevalence

Thyroid nodules are common - 5% of the adult populations have palpable nodules^1,2 while 25% have impalpable ones detectable only by ultrasound.^3,4 In fact, according to autopsy studies, 50% have nodules,⁵ although most are microscopic and clinically insignificant. Cancer of the thyroid, on the other hand, is not so common, accounting for only 1% of all cancer cases and 0.5% of all cancer deaths.^1,2

History

Local symptoms (mainly concerned with the nature of the nodule)

As for nodules in any other part of the body, rate of onset, site, fluctuation in size, pain, and obstructive symptoms (e.g. dysphagia, dyspnoea and hoarseness of voice) are of major concern.

General symptoms (mainly concerned with hormonal imbalance)

As thyroid hormone affects the metabolic rate of all cells, imbalance can cause widespread effects: metabolic (weight loss despite increase in appetite and sweating), cardiovascular (palpitation), neuromuscular (tremor and muscle weakness), psychiatric (anxiety and insomnia) as well as gastrointestinal (diarrhoea).

Risk factors

Physiological goitre occurs during puberty and pregnancy while different types of cancer tend to occur at different ages (papillary in the 30s, follicular in the 40s and anaplastic in the 70s and 80s).

Both past history and family history of endocrine disturbances, autoimmune diseases, and thyroid cancer are important. Excessive exposure of the neck to radiation should also be noted.

Iodine deficiency is unlikely for anyone born and raised in Hong Kong but should be considered in the immigrant group.

Examination

Movement of the nodule during the act of swallowing confirms it to be a thyroid nodule, while movement during the act of tongue protrusion confirms it to be a thyroglossal cyst.

Local signs

Size, site, fixity, tenderness, hoarseness of voice and lymphadenopathy are important signs.

Toxic signs

Recent weight loss, tachycardia, tremor, hyper-reflexia and eye signs (exopthalmos, lid-lag and lid-retraction) are also important features.

Investigations

Blood tests

Thyroid function tests should be performed in all thyroid patients. Anti-microsomal and anti-thyroglobulin antibodies should be checked in toxic patients to confirm/exclude Graves' disease and Hashimoto's thyroiditis. Anti-thyroglobulin antibodies should not be confused with serum thyroglobulin level, which is only useful in looking for recurrence in cancer patients who have already undergone total thyroidectomy. Where medullary carcinoma is suspected, calcitonin level is diagnostic while other tests should be performed to rule out concomitant endocrine tumours.

Imaging

Ultrasound is now universally accepted as the first line imaging modality.^6-9 It can distinguish, with much certainty, solid from cystic lesions, and has many favourable features, such as detection of non-palpable nodules, estimation of nodule size/goitre volume and guidance of fine needle aspiration cytology (FNAC).¹⁰ The main difficulty is in distinguishing between follicular adenoma and minimally invasive follicular carcinoma. Unfortunately, this is also a difficult area for other modalities.

MRI and CT are probably as good as each other as second line modality in assessing extra-thyroidal invasion as well as the lower extent of retro-sternal extension and/or lymphadenopathy.¹¹

Isotope scan has now mostly been superceded by ultrasound but remains essential in toxic patients with a solitary nodule as distinction between a solitary toxic nodule and a hypo-functioning nodule in a hyperactive background does have a significant bearing on management. Some clinicians also use it to check the functionality of follicular lesions - warm nodules are rarely malignant.¹ It should be emphasised that cold nodules merely mean hypo-functional nodules and are not diagnostic of malignancy, even though malignant nodules do tend to be cold.

Tissue confirmation

FNAC is now the gold standard and is widely used in the management of thyroid nodules.^6-9 It is cheap, minimally invasive and can be done under either palpation or ultrasound guidance. Its use has reduced the number of thyroidectomies by about 50%,¹² and reduces the overall cost of medical care in these patients by 25%.¹ When properly done, FNAC should have a false negative rate of <5% and a false positive rate of about 1%.¹³ Ultrasound guidance dramatically reduces sampling error and significantly improves sensitivity, specificity, as well as overall diagnostic accuracy.^14,15 However, FNAC cannot distinguish between follicular adenoma and follicular carcinoma.¹⁶

Core needle biopsy and trucut biopsy do not have a higher diagnostic accuracy and are more likely to yield insufficient sample.¹⁷ Complications such as haematoma are also more common. Hence, they are seldom used nowadays in thyroid patients.

Routine frozen section has now largely fallen out of favour as it rarely affects intra-operative decision-making in patients with adequate FNAC.^18,19 Unfortunately, where FNAC is weak - in the diagnosis of follicular carcinoma, frozen section cannot provide better diagnostic accuracy. Its use is now limited to patients with suspicious or atypical FNAC findings only.

Management of toxicity

Regardless of the cause of toxicity, patient should first be rendered euthyroid with anti-thyroid drugs (either propyl thiouracil or carbimazole). For patients with tachycardia, propanolol should be added. Thereafter, the management may differ.

Graves' disease

First occurrence should be treated with an 18-months course of anti-thyroid drug at a maintenance dose, followed by a trial period without drug. If toxicity recurs, another course of anti-thyroid drug may be tried although the chance of success diminishes with each recurrence and definitive treatment (surgery or radioactive iodine) should be offered after again rendering the patient euthyroid.

With Graves' disease, the dosage of radioactivity required is low, making radioactive iodine therapy superior to surgery (usually sub-total thyroidectomy). It avoids all possible operative complications (such as general anaesthetics risks, recurrent laryngeal nerve palsy, hypoparathyroidism and scar problems), with the exception of hypothyroidism, but is contra-indicated in children, fertile women who want to be pregnant within a year and patients with huge goitre or severe exopthalmos.

Solitary toxic nodule

Definitive treatment should be offered straight away. Here, radioactive iodine does not hold as much an advantage over surgery as in Graves' disease. Firstly, dosage of radioactivity required depends on the size of the nodule. Secondly, the choice of surgery is a hemi-thyroidectomy, which carries less morbidity than sub-total thyroidectomy. Choice of treatment often depends on individual preference of the patient and the clinician, but in general, surgery is often preferred in younger patients and in those with larger nodules.

Toxic multinodular goitre

Definitive treatment should also be offered straight away. Dosage of radioactivity required is usually much higher and surgery is the preferred option. However, total rather than sub-total thyroidectomy is recommended, as residual nodular tissue is likely to grow and causes problem later due to raised post-operative TSH. The advantage of subtotal thyroidectomy is the avoidance of life long thyroxine replacement, so if the patient requires post-operative thyroxine suppression to prevent future nodular growth, it would rather defeat the purpose of the exercise.

Management of benign nodules

Cysts

Most cysts can be aspirated and any recurrence can often be treated with repeat aspirations. Alternatively, sclerosing therapy by means of injection with ethanol may be performed in small cysts.²⁰ Surgery is advisable if large cysts (>3cm) recur after aspiration as >10% of these lesions harbour cancer.²¹

Multinodular goitre

Most multinodular goitres (MNGs) without a dominant nodule are benign and may be treated conservatively with regular surveillance. Surgery should be offered to patients with obstructive symptoms only, although it may also be considered for cosmetic reasons. Thyroxine suppression therapy is currently under heavy scrutiny in view of possible associated heart and bone complications.^22,23 Radioactive iodine has long been known to reduce goitre size,²⁴ although its use has been mainly restricted to toxic patients in the past. Recent study has shown that it may be superior to thyroxine suppression therapy in non-toxic MNGs²⁵ and is now the routine choice of treatment in some countries like Denmark and the Netherlands.^8,9

Management of malignancy

Nodules confirmed or suspected to be malignant should be offered surgery. Total thyroidectomy is the treatment of choice in most confirmed malignant cases but there is a tendency nowadays to leave the contra-lateral lobe alone in well-differentiated thyroid cancers with a small malignant focus (<1cm).²⁶ In such tumours, total thyroidectomy does not provide better survival rate but does appear to provide a lower recurrence rate.²⁷

Endoscopic thyroid surgery

Figure 1: Three months after "scarless" thyroid lobectomy

Traditional thyroid surgery is an open approach, which leaves an obvious scar in the centre of the neck. As thyroid nodules are more prevalent in young females, this approach is often undesirable, to the point where patients sometimes refuses surgery, despite the possibility of missing malignancy. With the advent of minimally invasive surgery, various techniques have been explored to give a more acceptable cosmetic outcome.

There are many approaches described and can be largely divided into cervical,²⁸ pre-cordial/breast,²⁹ and axillary³⁰ approaches. At Prince of Wales Hospital, we have devised a combination approach (with circumareolar and axillary incisions), which gives a "scarless" outcome at the neck (Figure 1).

Figure 2: Management of thyroid nodules

Key messages

1. Thyroid nodules are very common.
2. Thyroid function tests, ultrasound and fine needle aspiration cytology are first line investigations.
3. Toxic patients should be rendered euthyroid before treatment (drug therapy, radioactive iodine, or surgery depending on the cause).
4. Confirmed or suspected malignancy should be offered surgery.
5. Large benign nodules should also be offered surgery
6. Multinodular goitre without obstructive or cosmetic problems should be treated conservatively.