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Home , Colloid nodule, Goitre, Thyroglossal cyst, Thyroid nodule

 CLINICAL PRACTICE lumps and bumps Investigations

BACKGROUND Thyroid nodules are extremely common, with 7% of adults having palpable nodules and up to 50% having nodules visible on . About 5% of thyroid nodules are malignant. Thyroid nodules may occur as isolated, often incidental findings, or may be associated with systemic features of thyrotoxicosis or . They may be solitary or may present as a dominant in a multinodular . Meagan Brennan BMed, FRACGP, DFM, FASBP, OBJECTIVE is a general practitioner and This article presents an outline of the common causes of lumps in the thyroid (solitary and multiple) and provides a breast physician, NSW Breast simple approach to diagnosis and management in the general practice setting. The focus is on the patient presenting Cancer Institute, Westmead with a lump in the thyroid rather than the patient presenting with hyper- or hypo-thyroidism. Hospital, New South Wales. [email protected] DISCUSSION James French The challenge for the general practitioner is to assess the nodule and determine which patients require referral for MBBS, FRACS, is a breast further investigation and management. Referral may be required to exclude or confirm malignancy and is also indicated and endocrine surgeon, NSW for patients who are symptomatic from benign thyroid nodules. Breast Cancer Institute, Westmead Hospital, and Clinical Lecturer, University of Sydney, New South Wales.

A is a ‘discrete lesion within the thyroid Important features in the history gland that is palpably and/or ultrasonographically distinct from the surrounding thyroid parenchyma’.1 Thyroid nodules are more common in women, the elderly, Thyroid nodules are extremely common, with 7% of those with deficiency, and in those with a prior adults having palpable nodules2 and up to 50% of history of exposure to radiation. Most patients with thyroid adults having nodules visible on ultrasound.3 Around nodules do not have any significant symptoms. The absence 5% of thyroid nodules are malignant.4 Thyroid nodules of symptoms however, does not exclude malignancy. may occur as isolated, often incidental findings, Symptoms that are significant if present include: or they may be associated with systemic features • obstruction such as difficulty swallowing (may indicate of thyrotoxicosis or hypothyroidism. They may be impingement of the oesophagus) solitary or may present as a dominant nodule in a • shortness of breath (may indicate impingement of the multinodular goitre. Solitary nodules have a higher ), and likelihood of being malignant although overall the • (uncommonly) hoarseness of the voice which prevalence of cancer is similar between patients suggests recurrent laryngeal nerve compression and with a solitary nodule and patients with multiple therefore the possibility of malignancy. nodules.5 The challenge for the general practitioner is History of duration of symptoms along with rapidity of to assess the nodule and determine which patients change in symptoms, the presence of systemic features of require referral to a surgeon or endocrinologist for hyper- or hypo-thyroidism, and family history of malignancy further investigation and management. Referral may should all be explored. be required to exclude or confirm malignancy and is The following features of the history increase the also indicated for patients who are symptomatic from suspicion of the nodule being malignant: benign thyroid nodules. • extremes of age (<20 or >70 years) • male gender Classification of thyroid nodules • size >4 cm The classification of thyroid nodules is shown in Table 1.6 • rapid growth (may suggest anaplastic carcinoma or While the majority of thyroid nodules are benign, clinical lymphoma) assessment and investigation is essential and is aimed at • family history of: thyroid malignancy or genetic excluding malignancy as a cause. disorders such as syndrome of multiple endocrine

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neoplasia type 2 (MEN2), familial polyposis lump such as a , salivary gland, Table 1. Classification of thyroid nodules6 coli and thyroglossal and skin/subcutaneous lesion Benign • prior exposure to radiation, including (eg. lipoma, sebaceous cyst). The technique for • multinodular goitre radiotherapy to the head and (eg. clinical examination of the thyroid is described • Hashimoto previous treatment of Hodgkin disease in Table 2.7 • simple or haemorrhagic affecting the neck). Enlargement of the thyroid gland may • follicular adenomas Most thyroid nodules are not painful, however be visible as well as palpable (Figure 1a, b). • the presence of pain may give a clue as to the Clinical examination often underestimates the • aetiology of the nodule. Subacute thyroiditis number of nodules compared with ultrasound. may present as painful thyroid nodule (single It is important to determine whether a goitre Malignant or multiple). Haemorrhage into a colloid nodule is present and if it is, to assess whether • papillary carcinoma or cyst can also be very painful. A malignant the gland is generally enlarged or if there is • follicular carcinoma thyroid nodule that is painful may be an localised swelling. If a nodule is palpable, it • hurthle cell carcinoma anaplastic lesion. should be determined if it is a solitary nodule • medullary carcinoma or a dominant nodule of a multinodular goitre • anaplastic carcinoma Clinical examination of the and an attempt should be made to characterise • primary thyroid lymphoma thyroid gland the lump. The most important aspect of clinical • metastatic malignant lesion Clinical examination must first distinguish a examination however, is the detection of the thyroid nodule from other causes of a neck nodule(s) rather than the determination of its benign or malignant status. Signs that may suggest malignancy are: Table 2. Clinical examination of the thyroid gland7 • firm/hard or fixed nodule, ill defined nodule Inspection – look for: margins on • scars – signs of previous surgery or injury • hoarseness/loss of voice • goitre – swelling – look from front and side of neck; localised or diffuse • presence of palpable cervical lymph nodes. • movement with swallowing – ask the patient to swallow a mouthful of water and Clinical examination of a patient with a thyroid observe the neck – a goitre or will rise during swallowing abnormality should include a generalised • prominent veins – may be a sign of retrosternal extension of goitre (thoracic inlet examination looking for signs of hyper- or obstruction) hypo-thyroidism. This includes assessment for Palpation thyroid eye signs. While it is uncommon for • position the patient to present as a nodule, – examine from behind the patient if eye signs are present this would alert the – neck slightly flexed to relax sternomastoid muscles assessing clinician to the likely benign nature of • feel each lobe and the isthmus of the gland the nodule. • determine clinical characteristics of goitre or nodule(s) In addition, assessment for Pemberton – size, shape, consistency, tenderness, mobility sign (described in Table 2, Figure 1c) should • examine cervical lymph nodes be included in the clinical examination. The • re-examine from the front patient is asked to lift both arms as high as – characteristics of nodules possible. Pemberton sign is positive when – position of trachea (may be displaced) signs of congestion (plethora), respiratory Percussion distress, inspiratory stridor and distension • percussion over the manubrium of the neck veins develop. When present, a – dullness may indicate retrosternal goitre – this procedure has been superseded positive Pemberton sign implies thoracic inlet by CT scan obstruction, which may occur when there is Auscultation retrosternal extension of the thyroid gland. • may occur in Graves disease Pemberton sign Investigations • ask the patient to raise arms up as high as possible; wait a few moments All patients with clinical abnormalities in the • signs of congestion occur from retrosternal extension of the thyroid gland thyroid should be investigated with thyroid Generalised clinical examination function tests. Most should also have thyroid • signs of hyper- or hypo-thyroidism ultrasound and fine needle aspiration

532 Reprinted from Australian Family Physician Vol. 36, No. 7, July 2007 Thyroid lumps and bumps CLINICAL PRACTICE

(FNAB). Computerised tomography (CT) and • If TSH is low, then serum T4 and T3 detect other significant nodules that are not magnetic resonance tomography (MRI) scans, should be measured to further investigate palpable.8 The risk of malignancy is the same for as well as thyroid scintigraphy (nuclear medicine . Thyroid stimulating nodules found as incidental impalpable lesions as scanning) are generally used more selectively. receptor (TRAb) is useful for nodules of the same size that are palpable.9 Algorithms for investigation and management to distinguish Graves disease from toxic Therefore it is important to assess each nodule are shown (Figure 2, 3). multinodular goitre. individually on ultrasound, looking for features The situation of a nodule that is associated suspicious of malignancy. While there is no with hyperthyroidism (‘toxic’ nodule) plays an single ultrasound feature that reliably predicts Serum thyroid stimulating hormone (TSH) levels important role in determining how the clinical malignancy, ultrasound features that increase should be measured in every patient presenting lump is managed. In these cases nuclear the risk of a nodule being malignant include: with a clinical abnormality in the thyroid. medicine scan should be performed and FNAB • irregular margins • If TSH is normal, further analysis of thyroid may not be necessary. • presence of microcalcification function tests (TFTs) is often not required. • hypoechogenicity Ultrasound of the thyroid Some endocrinologists recommend also • absence of a halo checking T4 levels on every patient presenting The role of ultrasound in the investigation of the • predominantly solid composition with a clinical abnormality in the thyroid clinically abnormal thyroid gland is increasing and • intranodule vascularity.10 • If TSH is high, free T4 and thyroid it is now recommended as part of the routine As ultrasound alone is limited in its ability to peroxidase antibody (TPOAb) should be investigation of a palpable thyroid nodule.1,6 distinguish benign from malignant nodules, tested. High levels of this antibody suggest Ultrasound allows correlation of the clinical further investigation of palpable nodules with Hashimoto disease, which may occasionally features with the ultrasound appearance, allows FNAB is usually required even when the lesion present with a palpable nodule the nodule to be characterised further, and may has a benign appearance on ultrasound.

A Thyroid nodule(s)

Ultrasound Thyroid function tests Serum calcium

Fine needle aspiration biopsy* Normal Abnormal (FNAB) of nodules palpable or suspicious on ultrasound Any abnormality on TFTs or calcium B requires separate investigation

Benign result Atypical or Malignant result Investigate further suspicious result Consider: • nuclear medicine Symptomatic thyroid scan Obstructive or • investigation C cosmetic for parathyroid symptoms disease

Observation repeat Surgery Surgery (total ) ultrasound +/- FNAB (hemithyroidectomy) 6–12 months** Thyroxine replacement

Figure 2. Initial investigation and management of a thyroid nodule * FNAB may not be required if the TSH is suppressed. These nodules should be investigated with thyroid Figure 1a, b. Patient with a large multinodular goitre scintigraphy and if a ‘hot’ nodule is seen the risk of malignancy is minimal and management (radioactive causing visible swelling in the neck iodine or surgery) may proceed without the need for FNAB Figure 1c. Patient has a positive Pemberton sign with congestion developing when she raises her ** There is no evidence on which to base recommendations for the interval and method of follow up arms above her head This interval is given as a guide only

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Fine needle aspiration biopsy interval for incidental asymptomatic lesions. reported as: Fine needle aspiration biopsy is indicated for Nodules that do not routinely require • insufficient (technically unsatisfactory) nearly all palpable and symptomatic nodules and FNAB are solitary nodules associated with a • benign should be considered in other nodules >1 cm. suppressed TSH (toxic nodules.) These nodules • atypical, or Fine needle aspiration biopsy should also be should be assessed with thyroid scintigraphy. • malignant. performed for smaller nodules (<1 cm) that have If the nodule is hot, the risk of malignancy is The main difficulty is in cases of follicular suspicious clinical or ultrasound features.11,12 minimal and FNAB is therefore usually not neoplasm. It can be impossible to distinguish The management of multiple incidental required. These nodules can then be managed a follicular adenoma (a benign lesion) from a thyroid nodules seen on ultrasound is with radioactive iodine or surgery.6 follicular carcinoma on cytological assessment. controversial. Biopsy of all these nodules is Fine needle aspiration biopsy is a simple and Follicular lesions therefore often require excision neither practical nor necessary. Focus should be useful test but its usefulness is dependent on and full examination of the lesion and its capsule on nodules that show concerning features on obtaining an adequate specimen and having it before a definitive diagnosis can be made. ultrasound and other nodules should probably examined by an experienced cytopathologist. Rates of insufficiency vary from 4–20%.6,13 be monitored with ultrasound. There is no There is no consensus on the classification In more than half of these cases a sufficient consensus however, on the optimal follow up of thyroid cytology. In general, FNAB can be sample will be achieved if the test is repeated.4 Fine needle aspiration biopsy has a sensitivity of 65–98%, specificity 72–100%, positive Observation of nodule(s) predictive value 50–96%, false-negative rate (previous investigations including FNAB benign) 1–11%, and false-positive rate of 0–7%.6 With an overall accuracy of 95%,6 it is a quick, safe, Follow up ultrasound and TSH at 6–12 months* cost effective and reliable investigation in the detection of thyroid malignancy. It will give an atypical result in up to 20% of specimens. Smaller or unchanged Larger Surgical excision of these nodules for full on progress ultrasound on progress ultrasound or histopathological assessment is recommended, and remains asymptomatic more large nodules seen as 30% may be malignant.4 The accuracy of FNAB increases when it is performed under Repeat FNAB Repeat FNAB not ultrasound rather than manual guidance.14,15 Repeat FNAB performed performed Fine needle aspiration biopsy may be seen as an accurate test to determine which nodules should be managed surgically and which may Atypical or Benign Malignant safely be observed.16 Nodules that are benign suspicious on FNAB and show no suspicious features on Options clinical and ultrasound assessment may be observed. Those showing atypical or malignant Dismiss from Surgery Surgery cytology should be surgically removed. Continued further surveillance (hemi (total Nodules returning a nondiagnostic result may observation observation thyroidectomy) thyroidectomy) be assessed with repeat FNAB or observed if there are no suspicious features on clinical and ultrasound assessment (Figure 2). Repeat ultrasound and Thyroxine TSH at 12 months** replacement CT and MRI scan Computerised tomography and MRI scans are Dismiss from ultrasound and specialist not routinely indicated in the assessment of follow up if stable on further review thyroid nodules. They cannot reliably distinguish benign from malignant lesions. The main Figure 3. Follow up of a thyroid nodule indication for these scans is to determine the *  There is no evidence on the optimal interval and method of follow up. Surveillance generally includes presence and extent of retrosternal extension repeat assessment with clinical examination, ultrasound and TSH after a period of time. Some specialists do this review at 6–12 months and others recommend review 2–3 years later and the presence and degree of tracheal ** There is no evidence on which to base recommendations for the interval and method of follow up. compression when obstructive symptoms are This interval is given as a guide present (Figure 4, 5). Computerised tomography

534 Reprinted from Australian Family Physician Vol. 36, No. 7, July 2007 Thyroid lumps and bumps CLINICAL PRACTICE and MRI scans are also useful when malignancy in the routine assessment of patients with Surgery is likely and further information on the extent of thyroid abnormalities to exclude the presence Surgery is indicated when there is/are: disease, such as involvement of regional lymph of coexisting hyperparathyroidism. If this is • malignancy proven on FNAB nodes, is required. present, there may be an option of treating it • possible malignancy (atypical, suspicious surgically at the same time as thyroidectomy findings on FNAB) Serum calcium if the thyroid nodule requires surgical • symptoms of compression from the nodule Measurement of serum calcium is important management. ( or tracheal compression. A sensation of choking alone without imaging Thyroid scintigraphy A evidence of tracheal compression is a ‘soft’ A nuclear medicine scan may not always be indication for surgery) necessary in the initial assessment of a thyroid • hyperthyroidism (this may be treated nodule. There are some clinicians however, who with surgery or with radioactive iodine or recommend it routinely. Scintigraphy alone is medications) unable to reliably distinguish malignant from • patient choice (usually for cosmetic reasons benign nodules. The main clinical indication for when nodules are >3 cm) thyroid scintigraphy is when hyperthyroidism • other indications (eg. when an adequate (suppressed TSH) is present. The management sample cannot be obtained by FNAB on of such a nodule differs to the management of several attempts or when a nodule that B a thyroid nodule that is not hyperfunctioning. has shown benign features on ultrasound A toxic nodule may be treated with radioactive and FNAB has grown during a period of iodine or may be treated surgically (usually with observation). hemithyroidectomy). Thyroid scintigraphy is also Surgical procedures most commonly performed useful to identify ectopic thyroid tissue or occult are: hyperfunctioning tissue and may have a role in • hemithyroidectomy – this is indicated for: the work up of some neoplasms. – a solitary nodule that is ‘hot’ or atypical on FNAB Management of nodules – a dominant nodule in the context of a Thyroid nodules with a benign appearance on multinodular goitre where only one lobe ultrasound and a benign cytology result on is significantly affected FNAB are usually observed (Figure 3). There is – differentiated <1 cm no evidence on the optimal interval and method • total thyroidectomy (Figure 6, 7) – this is Figure 4a, b. CT scan and chest X-ray showing of follow up. Surveillance generally includes indicated for: narrowing and deviation of the trachea due to a massively enlarged right lobe of the thyroid gland. repeat assessment with clinical examination – thyroid malignancy, except small well These images are of the patient shown in Figure 1 and ultrasound after a period of time. Some differentiated cancers specialists do this review at 6–12 months and – hyperthyroidism due to Graves disease others recommend review 2–3 years later. when thyroid eye signs are present or If the lesion has increased in size on review, medical management is unsuccessful or repeat FNAB is recommended. Increase in contraindicated size, however, is not always a sinister sign as – symptoms or signs of compression of the many (89% in one study)17 cytologically benign trachea or oesophagus (Figure 5, 6) nodules increase in size slowly over time. There – multinodular goitre where both lobes are is an increasing trend to repeat the FNAB at significantly affected follow up examination even for lesions that – patient choice for cosmetic reasons are stable on review. Nodules that are benign related to a large goitre. again on repeat FNAB may be dismissed from Other surgical options including removal further specific follow up and specialist review of the nodule only and the operation of unless they become symptomatic. Lesions subtotal thyroidectomy are performed less Figure 5. A coronal reconstruction of a CT scan that are stable on follow up ultrasound but are often as they generally have no advantages demonstrating tracheal deviation to the left as not assessed with repeat FNAB are usually over the operations listed above and rates of well as narrowing, due to recurrent multinodular goitre 15 years following a bilateral subtotal observed for longer before being dismissed complications are similar. These procedures thyroidectomy from follow up. also have additional disadvantages over total

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temporary or permanent [2–3%]) Conflict of interest: none declared. • hypothyroidism is expected and is Acknowledgments permanent following total thyroidectomy. It Thanks to A/Prof Owen Ung (NSW BCI) who provided may also occur temporarily or permanently input on the algorithms, and Dr Greg Heard (NSW BCI) following hemithyroidectomy. who provided editorial input. Thanks also to A/Prof Katherine Samaras (St Vincent’s Hospital) who provided Other treatments clinical comments on specific topics in the article. The NSW Breast Cancer Institute receives funding from Radioactive iodine is indicated for toxic NSW Health. (hyper functioning) nodules and toxic nodular References goitre. It is not recommended if symptoms of 1. Cooper DS, Doherty GM, Haugen BR, et al. Management Figure 6. An intra-operative picture showing compression are present as surgery is usually guidelines for patients with thyroid nodules and differenti- a large multinodular goitre. This patient had ated thyroid cancer. Thyroid 2006;16:1–33. significant tracheal narrowing on chest X-ray and the best treatment in this situation. 2. Mazzaterri EL. Management of a solitary thyroid nodule. N CT examinations (Figure 4) Percutaneous ethanol injection is available Engl J Med 1993;328:553–9. but is not routinely offered. It tends to be 3. Ezzat S, Sarti DA, Cain DR, Braunstein GD. Thyroid inciden- talomas. Prevalence by palpation and ultrasonography. Arch painful. This procedure can be performed under Intern Med 1994;154:1838–40. ultrasound guidance for cystic lesions. It has 4. Mackenzie EJ, Mortimer RH. Thyroid nodules and thyroid been shown to reduce the recurrence rate of cancer. Med J Aust 2004;180:242–7. 5. Frates MC, Benson CB, Doubilet PM, et al. Prevalence cysts following aspiration. It is recommended and distribution of carcinoma in patients with solitary and only for nodules proven to be benign on FNAB multiple thyroid nodules on sonography. J Clini Endocrinol Metab 2006;91:3411–7. and is not recommended for treating nodules 6. American Association of Clinical Endocrinologists and that are solid or toxic. Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of Summary of important points thyroid nodules. Endocr Pract 2006;12:65–102. 7. Talley NJ, O’Connor S. The endocrine system. In: Talley NJ, Figure 7. A large multinodular goitre after excision • Thyroid nodules are common and most O’Connor S, editors. Clinical examination: a guide to physi- do not cause significant symptoms. The cal diagnosis. Sydney: Williams & Wilkins and Associates 1988;243–52. thyroidectomy or hemithyroidectomy, such absence of symptoms however does not 8. Marqusee E, Benson CB, Frates MC, et al. Usefulness of as recurrence of symptoms or development reliably exclude malignancy so careful ultrasonography in the management of nodular thyroid of cancer in the remaining tissue. These assessment of nodules is required. disease. Ann Intern Med 2000;133:696–700. 9. Hagag P, Strauss S, Weiss M. Role of ultrasound guided problems may require re-operation. Re-do • Nodules that are palpable should be fine needle aspiration biopsy in evaluation of non-palpable thyroid surgery is associated with a higher risk assessed with ultrasound. thyroid nodules. Thyroid 1999;8:989–95. 10. Frates MC, Benson CB, Charboneau JW, et al. Management of complications such as recurrent laryngeal • FNAB is the single most useful test in of thyroid nodules detected at US: Society of Radiologists nerve injury and permanent hypocalcaemia the assessment of a thyroid nodule. It in Ultrasound Consensus Conference Statement. Radiology compared to initial surgery.18 is indicated for most nodules that are 2005;237:794–800. 11. Woeber KA. The year in review: the thyroid. Ann Intern Med Thyroid surgery requires meticulous care to palpable or show suspicious features on 1999;131:959–62. avoid damage to surrounding structures but is ultrasound and should be considered for 12. Utiger RD. The multiplicity of thyroid nodules and carcino- now a low risk procedure in experienced hands. nodules >1 cm. The main exception is a mas. N Engl J Med 2005;352:2376–8. 13. Sangalli G, Serio G, Zampatti C, et al. Fine needle aspiration Complications include: nodule in the context of hyperthyroidism, cytology of the thyroid: a comparison of 5469 cytological and • haemorrhage (an uncommon but potentially which should be assessed with thyroid final histological diagnoses. 2006;17:245–50. 14. Danese D, Sciacchitano S, Farsetti A, et al. Diagnostic accu- fatal complication – occurs in <1% of cases) scintigraphy and may go on to definitive racy of conventional versus sonography guided fine needle • voice disturbance or hoarseness due to management without the need for FNAB. aspiration biopsy of thyroid nodules. Thryoid 1998;8:15–21. injury to the recurrent laryngeal nerve (may • A nodule that is not symptomatic and has 15. Hatada T, Okada K, Ishii H, et al. Evaluation of ultrasound guided fine needle aspiration biopsy for thyroid nodules. be temporary or permanent – permanent benign features on ultrasound and FNAB Am J Surg 1998;175:133–6. damage occurs in <1% of cases). Injury may be safely monitored with clinical and 16. Udelsman R. The thyroid nodule. Ann Surg Oncol to the external branch of the superior ultrasound review. If FNAB is repeated 2001;8:89–90. 17. Alexander EK, Hurwitz S, Heering JP, et al. Natural history laryngeal nerve can cause less obvious and is again benign, then the nodule can of benign solid and cystic thyroid nodules. Ann Intern Med voice changes. Patients may complain of be dismissed from further review unless 2003;138:315–8. an inability to project their voice and easy symptoms develop. 18. Ozbas S, Kocak S, Aydintug S. Comparison of the complica- tions of subtotal, near total and total thyroidectomy in fatigueability of their voice • A nodule that is causing compressive the surgical management of multinodular goitre. Endocr J • hypocalcaemia due to damage to the symptoms or yields an atypical, suspicious 2005;52:199–205. parathyroid glands or their blood supply or malignant result on FNAB should be CORRESPONDENCE email: [email protected] (requires calcium supplementation; may be managed surgically.

536 Reprinted from Australian Family Physician Vol. 36, No. 7, July 2007