3.1.3 Clinical assessment of the thyroid patient

Thyroid disorders are common, especially in older people where 10–20% may have structural abnormalities of the thyroid glan and/or thyroid function tests outside the reference range (1). Evaluation of thyroid function, size, and structure is therefore an important part of any complete history and physical examination of a patient.

Deficient or excessive thyroid hormone secretion affects nearly all body systems, and examination of a patient with a proven or suspected thyroid abnormality should include a more general evaluation of the patient. For example, an episode of thyrotoxicosis in an elderly person may provoke atrial fibrillation and impair cardiac function. The abnormality may persist after treatment of the thyrotoxicosis, and supplementary therapy directed against the atrial fibrillation may be needed. In a patient with hypothyroidism, symptoms of arteriosclerotic heart disease may worsen after initiation of treatment. Both the hypothyroidism and the heart disease should be diagnosed to develop an appropriate plan of therapy.

The three key abnormalities of the thyroid gland are: (1) thyrotoxicosis with excessive thyroid hormone effects on the body, (2) hypothyroidism with thyroid hormone deficiency, (3) and goitre with a general or focal abnormal enlargement of the thyroid gland. A less common abnormality is the painful thyroid. Examination of the thyroid patient should lead to a conclusion based on symptoms and signs related to these abnormalities.

The many clinical symptoms and signs of hyper- and hypothyroidism are dealt with in detail in subsequent chapters. However, during the initial assessment symptoms and signs of a clinical condition requiring more than usual observation or even acute therapy should be identified. In a thyrotoxic patient the risk of thyrotoxic crises should be evaluated. The risk of myxoedema coma is very low in a patient with hypothyroidism; the condition certainly should not develop during the period of diagnostic investigations. Some ‘warning’ symptoms and signs in hyper- and hypothyroidism are shown in Box 3.1.3.1. The box also depicts some factors which increase the risk of malignancy in a patient with goitre. Their presence may indicate the need to accelerate further diagnostic evaluation.

Each of the thyroid abnormalities may be caused by a number of diseases with different prognoses, risks, and treatments. Any clinical finding giving suspicion of a thyroid abnormality should be followed by a systematic evaluation of which disease is behind the abnormality (nosological diagnosis). For example, if the patient seems to be thyrotoxic the examination should lead to a provisional conclusion on the disease leading to the thyrotoxicosis. The four most common causes of thyrotoxicosis are Graves’ disease, multinodular toxic goitre, toxic adenoma, and subacute thyroiditis (2). Subsequently the diagnosis should be substantiated by further biochemical tests and often imaging procedures.

Some of the diseases leading to thyroid abnormalities may have other manifestations which should be looked for. A common example is the orbitopathy and (less common) the pretibial myxoedema of Graves’ disease. A rare example is the retroperitoneal fibrosis with ureteral obstruction encountered in some patients with Riedel’s thyroiditis.

The history and clinical examination may be so typical for a specific thyroid disorder that the diagnostic sensitivity and specificity approach 100%. However, the symptoms and signs of hypo- or hyperthyroidism overlap considerably with complaints and abnormalities which are common in other diseases and also in apparently healthy people (e.g. fatigue, weight alterations, nervousness, lack of concentration, constipation). Biochemical testing of thyroid function is therefore central in the evaluation of thyroid patients.

Laboratory tests of thyroid function may be influenced by various clinical circumstances and medication. During the clinical examination, information should be obtained on such circumstances or medication to allow proper interpretation of the tests. One important example is pregnancy (3). Both total and free thyroid hormones in serum vary during normal pregnancy, and pregnancy-induced modulations of the immune system may modify autoimmune thyroid abnormalities.

Transient hypo- or hyperthyroidism as part of autoimmune postpartum thyroiditis are seen in 4–5% of women 3–9 months after delivery. Another example is severe general illness (4) which may be accompanied by various alterations in total and free thyroid hormones and thyroid-stimulating hormone (TSH) in serum even if the thyroid gland is not affected.

Many medications may alter thyroid function tests (5). Some important examples are oestrogens (high thyroxin-binding globulin with high total thyroxine (T₄) and triiodothyronine (T₃)), carbamazepine, and phenytoin (low total and free T₄ and T₃), and amiodarone (high total and free T₄, slightly depressed total and free T₃, and high normal TSH). These are the variations seen in patients without thyroid abnormalities. Amiodarone has high iodine content and is also a frequent cause of thyroid disease.

Excess iodine, whether due to iodine-containing medications, over-the-counter ‘health products’ with iodine, intake of seaweed, or iodine-containing radiocontrast agents, may induce hypo- or hyperthyroidism in susceptible patients. The disease is transient in most cases. In geographical areas with a high basic iodine intake hypothyroidism is the common abnormality induced, while thyrotoxicosis predominates in areas with a low basic iodine intake. This difference in type of abnormality induced by excess iodine reflects the basic difference in the epidemiology of thyroid abnormalities in low and high iodine intake areas. In low iodine intake areas nontoxic and multinodular toxic goitre are the dominating abnormalities, whereas autoimmune diseases with subclinical and clinical hypothyroidism are the most common abnormalities in high iodine intake areas. Hence the history should reveal any excess iodine intake, and additional information on the general iodine intake level in the area where the patient lives will provide clues to the probability of the various thyroid abnormalities (2).

Thyroid diseases cluster in some families and a family history is valuable for risk estimation. Information on more specific genetic defects such as those leading to thyroid hormone resistance syndromes or to alterations of hormone binding proteins in serum is important to avoid diagnostic errors. The presence in a patient of autoimmune disorders such as vitiligo, rheumatoid arthritis, type 1 diabetes, Addison’s disease, and pernicious anaemia considerably enhances the risk for an autoimmune thyroid disorder.

Previous thyroid disease gives a high risk for a current thyroid abnormality. For example, both hyper- and hypothyroidism may be transient if induced by excessive iodine intake (Chapter 3.2.4). However, there may be an underlying subclinical thyroid abnormality (e.g. autonomous thyroid nodules in hyperthyroidism, autoimmune thyroiditis in hypothyroidism). Relapse is therefore common after re-exposure to excess iodine. Spontaneous development of a thyroid function abnormality may also occur.

Patients with postpartum thyroiditis typically harbour an underlying autoimmune thyroiditis. Hence a new episode of thyroiditis is common after the next pregnancy, and the risk for a permanent thyroid hypofunction is considerably increased. If a patient is in remission after previous medication for the hyperthyroidism of Graves’ disease, the risk for relapse is considerable (in the order of 50%). Patients treated with radioiodine or surgery for hyperthyroidism commonly develop immediate or early hypothyroidism. If not, hypothyroidism may develop later, even after decades. Patients who have received external radiation of the neck have an increased risk of hypothyroidism, and if treated with radiation to the neck or exposed to radioactive fallout during childhood a greatly increased risk of malignant and benign thyroid nodules.

The history on tobacco smoking is pertinent because smoking may aggravate the orbitopathy of Graves’ disease (6), and by interacting with iodine deficiency lead to a high frequency of goitre (7).

Inspection and palpation of the anterior region of the neck with the thyroid gland is performed as part of any complete physical examination. In addition, auscultation of the thyroid gland can be used to evaluate blood flow in a goitre, and percussion of the upper part of the sternum to test for the presence of a large retrosternal goitre.

The normal thyroid is situated with the upper poles of the lobes at the level of the cricoid cartilage. The lower poles are 1–2 cm above the sternoclavicular junction in young adults, but the thyroid gland tends to be located more caudally on the neck in elderly patients. The thyroid isthmus transverses the trachea 1–2 cm below the cricoid cartilage. The location varies with the general anatomy of the neck.

The patient is examined sitting or standing with light from a window or a lamp falling obliquely on the anterior of the neck. The chin of the patient is raised moderately. The skin is inspected for scars after thyroid surgery and vascular changes suggesting impaired venous flow or previous radiation of the neck.

The thyroid region should be studied carefully for signs of thyroid enlargement, nodules, and asymmetry (Fig. 3.1.3.1a). The normal thyroid gland is not or is only barely visible in most people. In young women with a slender neck, a high and medially situated normal thyroid gland may give the clinical impression of goitre (‘pseudo-goitre’).

The next step is to inspect the region while the patient is swallowing. If no water for swallowing is available it may be helpful to ask the patient to imagine chewing a piece of lemon. This may induce salivation and facilitate swallowing. The thyroid gland will normally move upwards during swallowing following the trachea (compare the thyroid region before swallowing (Fig. 3.1.3.1b) with the region during swallowing (Fig. 3.1.3.1c)). Small thyroid enlargements and nodules may be identified in this way. Inspection during swallowing is an important part of characterization of a goitre. If the goitre remains fixed to the surroundings and does not move it may be a sign of malignancy (Box 3.1.3.1). If still uncertain, inspect the thyroid region while the patient swallows, with light from various angles and with the neck of the patient more or less extended.

Palpation can be performed while the examiner and the patient are sitting or standing in front of each other or while the examiner is standing behind the sitting patient. The patient should hold the head upright but the neck should not be hyperextended. Palpation involves a superficial and a deep examination of the gland. In addition, thorough palpation for enlarged cervical lymph nodes should be performed. The superficial part of the thyroid is examined by moving the flat fingertips systematically across the thyroid region searching for swellings and nodules (Fig. 3.1.3.1d). When special care is needed the examination may be facilitated by using lubricant (e.g. gel for ultrasound examination). It may also be helpful to ask the patient to swallow while palpating softly over the gland. Nodules and enlarged lobes may be identified when they are moving.

Palpation of the thyroid lobes between the fingers is achieved by displacing the larynx (and thereby the trachea and the thyroid gland) to one side (Fig. 3.1.3.1e) and palpating the thyroid lobe behind the sternocleidomastoid muscle as illustrated in Fig. 3.1.3.1f. Nodules in the deeper parts of the thyroid lobes can be detected in this way.

If goitre or one or more nodules are observed or palpated they should be examined and described with respect to size, hardness, location, mobility, and tenderness. Proper description of location is important as it aids interpretation of the findings of the scintigram (Is this a cold nodule?). Lack of mobility during swallowing is often a sign of malignancy but several other possibilities exist. Fixation could be caused by inflammation surrounding an acute or subacute thyroiditis. Such lesions tend, however, to be painful which is rarely the case with a cancer.

The goitre of patients with active Graves’ disease may have a very high blood flow. The flow can occasionally be heard upon auscultation as a systolic murmur over the gland. When present in the medically treated patient it indicates persistent activity of the disease despite medication and is often accompanied by a ‘high serum T₃ low serum T₄’ pattern. If surgery is planned, pretreatment with iodine for 7–10 days before surgery to reduce blood flow may be considered.

A similar clinical pattern may occasionally be induced if patients with Graves’ disease are grossly overtreated with thyroid-blocking drugs. This is followed by a low serum T₄ and T₃, excessive TSH secretion, and induction of a ‘blocking goitre’ with high blood flow.

A systolic murmur over the thyroid does not always originate in the thyroid gland. Differential diagnostic possibilities are referred sound from the heart in a patient with aortic stenosis or sclerosis and a systolic murmur from an arteriosclerotic carotid artery.

In the typical Graves’ disease patient—a young or middle-aged woman with family history, complaints of nervousness, heat intolerance and palpation, weight loss, high pulse rate, agility, diffuse goitre, and eye signs—the diagnosis based on clinical assessment is nearly 100% reliable. However, both hyper- and hypothyroidism may be difficult to diagnose from clinical findings, especially in elderly people where the diseases may be nearly monosymptomatic with, e.g., slow cerebration in hypothyroidism and weight loss in thyrotoxicosis. Biochemical evaluation of thyroid function is necessary and TSH measurement should be a first-line test in many clinical circumstances.

A special problem is the diagnosis of goitre. Classically goitre is a thyroid gland which is palpable or visible due to focal or general enlargement. Occasionally the goitre is not visible or palpable because the growth and extension of the gland has occurred behind the sternum as a retrosternal goitre.

A visible and/or palpable thyroid gland is not goitre if there is no general or focal enlargement. In young women this may be seen as ‘pseudo-goitre’. Ultrasound examination of the thyroid gland with measurement of volume and identification or exclusion of thyroid nodules is an important supplement to the clinical evaluation of the thyroid gland, and it is most helpful in such patients. The interobserver variability of thyroid volume determinations by ultrasonography is around 10% and the reproducibility of identifying nodules is high.

The size of the thyroid gland of apparently healthy people depends considerably on the iodine intake level of the area where the investigation is performed. Upper normal values of 18 ml for women and 25 ml for men have been suggested (8). However, there is a profound discrepancy between the ‘true’ thyroid volume determined by ultrasound examination and the finding of no goitre or a small goitre by clinical examination. This is illustrated in Fig. 3.1.3.2, which also demonstrates that thyroid volumes several times the upper normal may be present without clinical goitre. Systematic studies of the clinical assessment of goitre have shown that estimation of thyroid size by inspection and palpation is imprecise and large intra- and interobserver variations have been found (10, 11).

Not only the estimation of size by clinical examination but also the evaluation of nodularity of the thyroid gland is difficult. Solitary thyroid nodules identified by palpation are often part of multinodular glands when examined by ultrasonography (in one investigation 50% of cases (12)). Ultrasound examination reveals more patients with thyroid nodules than clinical examination. In a follow-up study of patients who had received neck irradiation as children and therefore had a high risk of later development of thyroid cancer, only approximately 50% of nodules larger than 1.5 cm detected by ultrasonography were identified by palpation (13).

In daily clinical practice the fact that ultrasonography is such a sensitive method for detection of thyroid nodules may cause problems (14). Hence a properly performed clinical investigation for thyroid nodules remains the first-line investigation of the thyroid gland. Clinical investigation is also the primary investigation used for goitre detection. Even if the volume of the thyroid gland is not normal by ultrasound examination this is of limited clinical importance if the function of the gland is normal and if there are no signs and symptoms of goitre.

So the situation differs when considering the necessity to supplement the clinical examination for thyroid function abnormalities on the one hand and for abnormalities of thyroid structure and size on the other. Supplementary investigation of thyroid function using a measurement of serum TSH as the first-line test should be performed relatively freely in many patients with all kinds of complaints of a certain duration, even if the clinical suspicion of thyroid disease is weak. On the other hand, clinical examination of the thyroid gland remains the important first-line evaluation for goitre and thyroid nodules. Sensitive imaging procedures such as ultrasound examination should be reserved for patients with abnormal clinical and/or biochemical findings suggesting thyroid disease, as well as for patients with a special risk of developing thyroid cancer.