Presenting symptoms (Table 10.1)

Hormones control so many aspects of body function that the manifestations of endocrine disease are protean. Symptoms can include changes in body weight, appetite, bowel habit, hair distribution, pigmentation, sweating, height and menstruation, galactorrhoea (unexpected breast-milk production—in men and women), as well as polydipsia, polyuria, lethargy, headaches and loss of libido and erectile dysfunction. Many of these symptoms have other causes as well and must be carefully evaluated. On the other hand, the patient may know which endocrine organ or group of endocrine organs has been causing a problem. In particular, there may be a history of a thyroid condition or diabetes mellitus. A list of common symptoms associated with various endocrine diseases is presented in Table 10.1. In this section some of the important symptoms associated with endocrine disease will be discussed.

TABLE 10.1 Endocrine history

Changes in appetite and weight

An increased appetite associated with weight loss classically occurs in thyrotoxicosis or uncontrolled diabetes mellitus. An increased appetite with weight gain may occur in Cushing’s syndrome, hypoglycaemia or in hypothalamic disease. A loss of appetite with weight loss can occur with adrenal insufficiency but is also seen in anorexia nervosa and with gastrointestinal disease (particularly malignancy). A loss of appetite with weight gain can occur in hypothyroidism.

Changes in bowel habit

Diarrhoea and an increase in the frequency of bowel movements are associated with hyperthyroidism and adrenal insufficiency, while constipation may occur in hypothyroidism and hypercalcaemia.

Changes in sweating

Increased sweating is characteristic of hyperthyroidism, phaeochromocytoma, hypoglycaemia and acromegaly, but may also occur in anxiety states and at the menopause (page 411).

Changes in hair distribution

Hirsutism refers to an increased growth of body hair in women. The clinical evaluation and differential diagnosis are presented on page 315. The absence of facial hair in a man suggests hypogonadism, while temporal recession of the scalp hair in women occurs with androgen excess. The decrease in adrenal androgen production that occurs as a result of hypogonadism, hypopituitarism or adrenal insufficiency can cause loss of axillary and pubic hair in both sexes.

Lethargy

This common symptom can be due to a number of different diseases. Patients with hypothyroidism, Addison’s disease and diabetes mellitus can present with this problem. Anaemia, connective tissue diseases, chronic infection (e.g. HIV, infective endocarditis), drugs (e.g. sedatives, diuretics causing electrolyte disturbances), chronic liver disease, renal failure and occult malignancy may also result in lethargy. Importantly, depression is a common cause of this symptom (page 411).

Changes in the skin and nails

The skin becomes coarse, pale and dry in hypothyroidism, and dry and scaly in hypoparathyroidism. Flushing of the skin of the face and neck occurs in the carcinoid syndrome (due to the release of vasoactive peptides from the tumour). Soft-tissue overgrowth occurs in acromegaly and skin tags may appear in the axillae. These are called molluscum fibrinosum. Acanthosis nigricans can also occur in acromegaly and in insulin-resistant states including Cushing’s syndrome and polycystic ovarian syndrome. Xanthelasma can be present in patients with diabetes or hypothyroidism.

Onycholysis occurs in Graves’ disease and Cushing’s syndrome is associated with spontaneous ecchymoses, thin skin and purple striae.

Changes in pigmentation

Increased pigmentation may be reported in primary adrenal insufficiency, Cushing’s syndrome or acromegaly. Decreased pigmentation occurs in hypopituitarism. Localised depigmentation is characteristic of vitiligo, which may be associated with certain endocrine diseases such as Hashimoto’s^a disease with hypothyroidism and Addison’s disease with adrenal insufficiency as well as other auto-immune conditions.

Changes in stature

Tallness may occur in children for constitutional reasons (tall parents) or, rarely, may reflect growth hormone excess (leading to gigantism), gonadotrophin deficiency, Klinefelter’s syndrome^b, Marfan’s syndrome or generalised lipodystrophy. Short stature can also result from endocrine disease, as discussed on page 313.

Erectile dysfunction (impotence)

A persistent inability to attain or sustain penile erections may occasionally be due to primary hypogonadism or to secondary hypogonadism due to hyperprolactinaemia or hypopituitarism. More often, it is related to emotional disorders. Vascular disease, autonomic neuropathy (e.g. in diabetes mellitus or alcoholism), spinal cord disease or testicular atrophy can also cause this problem.

Galactorrhoea

Hyperprolactinaemia (usually the result of pituitary adenoma) can cause galactorrhoea in up to 80% of women and 30% of men. Galactorrhoea in men occurs from a normal-appearing male breast.

Menstruation

Failure to menstruate is termed amenorrhoea.

Primary amenorrhoea is defined as a failure to start menstruating by 17 years of age. True primary amenorrhoea may result from ovarian failure (e.g. X chromosomal abnormalities such as Turner’s syndrome) or from pituitary or hypothalamic disease (e.g. tumour, trauma or idiopathic disease). Excess androgen production or systemic disease (e.g. malabsorption, chronic renal failure, obesity) can also result in primary amenorrhoea.

Apparent primary amenorrhoea can also occur if menstrual flow cannot escape: for example, if there is an imperforate hymen.

Secondary amenorrhoea is defined as the cessation of menstruation for 6 months or more. Pregnancy and menopause are common causes. The polycystic ovarian syndrome, hyperprolactinaemia, virilising syndromes or hypothalamic or pituitary disease can also result in this problem, as can use of the contraceptive pill or psychiatric disease.

Polyuria

Polyuria is defined as a urine volume of more than 3 litres/day. Patients who report urinary frequency may find it difficult to tell if large volumes of urine are being passed. Causes include diabetes mellitus (due to excessive filtration of glucose, a poorly resorbed solute); diabetes insipidus (due to inadequate renal water conservation from a central deficiency of antidiuretic hormone, or a lack of renal responsiveness to this hormone); primary polydipsia, where a patient drinks excessive water (due to psychogenic or hypothalamic disease or drugs such as chlorpromazine or thioridazine); hypercalcaemia; and tubulointerstitial or cystic renal disease.

The thyroid

The thyroid gland^c

Examination anatomy

Even when it is not enlarged, the thyroid (Figure 10.2) is the largest

Figure 10.2 The anatomy of the thyroid

Figure 10.1 The endocrine glands

endocrine gland. Enlargement is common, occurring in 10% of women and 2% of men and more commonly in iodine-deficient parts of the world. The normal gland lies anterior to the larynx and trachea and below the laryngeal prominence of the thyroid cartilage. It consists of a narrow isthmus in the middle line (anterior to the second to fourth tracheal rings and 1.5 cm in size), and two larger lateral lobes each about 4 cm long. Although the position of the larynx varies, the thyroid gland is almost always about 4 cm below the larynx.

Inspection

The normal thyroid may be just visible below the cricoid cartilage in a thin young person (Table 10.2).^1,2. Usually only the isthmus is visible as a diffuse central swelling. Enlargement of the gland, called a goitre (Latin guttur, ‘throat’), should be apparent on inspection (see Good signs guide 10.1), especially if the patient extends the neck. Look at the front and sides of the neck and decide whether there is localised or general swelling of the gland. In normal people the line between the cricoid cartilage and the suprasternal notch should be straight. An outward bulge suggests the presence of a goitre (Figure 10.3). Remember that 80% of people with a goitre are biochemically euthyroid, 10% are hypothyroid and 10% are hyperthyroid.

TABLE 10.2 Causes of neck swellings

Midline Goitre (moves up on swallowing) Thyroglossal cyst (moves on poking out the tongue with the jaw stationary) Submental lymph nodes

Lateral

Lymph nodes^*

Salivary glands (e.g. stone, tumour)

• Submandibular gland

• Parotid gland (lower pole)

Skin: sebaceous cyst or lipoma

Lymphatics: cystic hygroma (translucent)

Carotid artery: aneurysm or rarely tumour (pulsatile)

Pharynx: pharyngeal pouch, or brachial arch remnant (brachial cyst)

Parathyroid gland (very rare)

^* Aulus Celsus (page 297), the Roman medical writer who was active early in the 1st century AD, was the first to publish work distinguishing a goitre from cervical lymphadenopathy.

GOOD SIGNS GUIDE 10.1 Detection of a goitre (compared with ultrasound findings)

Sign	Positive LR	Negative LR*
No goitre on inspection or palpation	0.4	—
Goitre palpated and visible only on neck extension	NS	—
Goitre palpated and visible with neck in normal position	26.3	—

NAS = not significant.

^* No values available.

From McGee S, Evidence-based physical diagnosis, 2nd edn. St Louis: Saunders, 2007.

Figure 10.3 The thyroid and goitre

Adapted from McGee S, Evidence-based physical diagnosis, 2nd edition, St Louis, Saunders, 2007.

The temptation to begin touching a swelling as soon as it has been detected should be resisted until a glass of water has been procured. The patient takes sips from this repeatedly so that swallowing is possible without discomfort. Ask the patient to swallow, and watch the neck swelling carefully. Only a goitre or a thyroglossal cyst, because of attachment to the larynx, will rise during swallowing. The thyroid and trachea rise about 2 cm as the patient swallows; they pause for half a second and then descend. Some non-thyroid masses may rise slightly during swallowing but move up less than the trachea and fall again without pausing. A thyroid gland fixed by neoplastic infiltration may not rise on swallowing, but this is rare. Swallowing also allows the shape of the gland to be seen better.

It should be noted whether an inferior border is visible as the gland rises. The thyroglossal cyst is a midline mass that can present at any age. It is an embryological remnant of the thyroglossal duct. Characteristically it rises when the patient protrudes the tongue.

Inspect the skin of the neck for scars. A thyroidectomy scar forms a ring around the base of the neck in the position of a high necklace. Also look for prominent veins. Dilated veins over the upper part of the chest wall, often accompanied by filling of the external jugular vein, suggest retrosternal extension of the goitre (thoracic inlet obstruction). Rarely, redness of the skin over the gland occurs in cases of suppurative thyroiditis.

Palpation

Palpation is best begun from behind (Figure 10.4) but warn the patient. Both hands are placed with the pulps of the fingers over the gland. The patient’s neck should be slightly flexed so as to relax the sternomastoid muscles. Feel systematically both lobes of the gland and its isthmus.

Figure 10.4 Palpating the thyroid from behind while the patient swallows sips of water

Consider the following:

• Size: only an approximate estimation is possible (Figure 10.5). Feel particularly carefully for a lower border, because its absence suggests retrosternal extension.

• Shape: note whether the gland is uniformly enlarged or irregular and whether the isthmus is affected. If a nodule that feels distinct from the remaining thyroid tissue is palpable, determine its location, size, consistency, tenderness and mobility. Also decide whether the whole gland feels nodular (multinodular goitre).

• Consistency: may vary in different parts of the gland. Soft is normal; the gland is often firm in simple goitre and typically rubbery hard in Hashimoto’s thyroiditis. A stony, hard node suggests carcinoma (Table 10.3), calcification in a cyst, fibrosis or Riedel’s thyroiditis.

• Tenderness: a feature of thyroiditis (subacute or rarely suppurative), or less often of a bleed into a cyst or carcinoma.

• Mobility: carcinoma may tether the gland.

Figure 10.5 Goitre: (a) large; (b) massive

TABLE 10.3 Differential diagnosis of thyroid nodules

1 Carcinoma (5% of palpable nodules)—fixed to surrounding tissues, palpable lymph nodes, vocal cord paralysis, hard, larger than 4 cm (most are, however, smaller than this)

2 Adenoma—mobile, no local associated features

3 Big nodule in a multinodular goitre—palpable multinodular goitre

Hyperthyroidism (thyrotoxicosis)

This is a disease caused by excessive concentrations of thyroid hormones. The cause is usually overproduction by the gland but may sometimes be due to accidental or deliberate use of thyroid hormone (thyroxine) tablets; thyrotoxicosis factitia. Thyroxine is sometimes taken by patients as a way of losing weight. The cause may be apparent in these cases if a careful history is taken (Questions box 10.1). The anti-arrhythmic drug amiodarone which contains large quantities of iodine can cause thyrotoxicosis in up to 12% of patients in low-iodine-intake areas.

Many of the clinical features of thyrotoxicosis are characterised by signs of sympathetic nervous system overactivity such as tremor, tachycardia and sweating. The explanation is not entirely clear. Catecholamine secretion is usually normal in hyperthyroidism; however, thyroid hormone potentiates the effects of catecholamines, possibly by increasing the number of adrenergic receptors in the tissues.

The commonest cause of thyrotoxicosis in young people is Graves’ disease,^d an autoimmune disease where circulating immunoglobulins stimulate thyroid stimulating hormone (TSH) receptors on the surface of the thyroid follicular cells.

Examine a suspected case of thyrotoxicosis as follows (see Good signs guide 10.2).

GOOD SIGNS GUIDE 10.2 Thyrotoxicosis

From McGee S, Evidence-based physical diagnosis, 2nd edn. St Louis: Saunders, 2007.

The hands

Ask the patient to put out his or her arms and look for a fine tremor (due to sympathetic overactivity). Laying a sheet of paper over the patient’s fingers may more clearly demonstrate this tremor, to the amazement of less-experienced colleagues.

Look at the nails for onycholysis (Plummer’s^e nails) (Figure 10.6). Onycholysis (where there is separation of the nail from its bed) is said to occur particularly on the ring finger, but can occur on all the fingernails, and is apparently due to sympathetic overactivity. Inspect now for thyroid acropathy (acropathy is another term for clubbing), seen rarely in Graves’ disease but not with other causes of thyrotoxicosis.

Figure 10.6 Onycholysis (Plummer’s nails)

Inspect for palmar erythema and feel the palms for warmth and sweatiness (sympathetic overactivity).

Take the pulse. Note the presence of sinus tachycardia (sympathetic overdrive) or atrial fibrillation (due to a shortened refractory period of atrial cells related to sympathetic drive and hormone-induced changes). The pulse may also have a collapsing character due to a high cardiac output.

Test for proximal myopathy and tap the arm reflexes for abnormal briskness, especially in the relaxation phase.

The eyes

Examine the eyes for exophthalmos, which is protrusion of the eyeball from the orbit (Figure 10.7, Table 10.5). This may be very obvious, but if not, look carefully at the sclerae, which in exophthalmos are not covered by the lower eyelid. Next look from behind over the patient’s forehead for exophthalmos, where the eye will be visible anterior to the superior orbital margin. Now examine for the complications of proptosis, which include: (i) chemosis (oedema of the conjunctiva and injection of the sclera, particularly over the insertion of the lateral rectus); (ii) conjunctivitis; (iii) corneal ulceration (due to inability to close the eyelids); (iv) optic atrophy (rare and possibly due to optic nerve stretching); and (v) ophthalmoplegia (the inferior rectus muscle power tends to be lost first, and later convergence is weakened).

Figure 10.7 Thyrotoxicosis: thyroid stare and exophthalmos

TABLE 10.5 Causes of exophthalmos

Bilateral Graves’ disease

Unilateral

Tumours of the orbit: e.g. dermoid, optic nerve glioma, neurofibroma, granuloma

Cavernous sinus thrombosis

Graves’ disease

Pseudotumours of the orbit

The mechanism of exophthalmos is uncertain. It occurs only in Graves’ disease. It may precede the onset of thyrotoxicosis, or may persist after the patient has become euthyroid. It is characterised by an inflammatory infiltrate of the orbital contents, but not of the globe itself. The orbital muscles are particularly affected, and an increase in their size accounts for most of the increased volume of the orbital contents and therefore for protrusion of the globe. It is probably due to an autoimmune abnormality.

Next examine for the components of thyroid ophthalmopathy, which are related to sympathetic overactivity and are not specific for Graves’ disease. Look for the thyroid stare (a frightened expression) and lid retraction (Dalrymple’s sign^f), where there is sclera visible above the iris. Test for lid lag (von Graefe’s sign^g) by asking the patient to follow your finger as it descends at a moderate rate from the upper to the lower part of the visual field. Descent of the upper lid lags behind descent of the eyeball.

If ptosis is present, one should rule out myasthenia gravis, which can be associated with autoimmune disease.

The neck

Examine for thyroid enlargement, which is usually detectable (60%–90% of patients). In Graves’ disease the gland is classically diffusely enlarged and is smooth and firm. An associated thrill is usually present but this finding is not specific for thyrotoxicosis caused by Graves’ disease. Absence of thyroid enlargement makes Graves’ disease unlikely, but does not exclude it. Possible thyroid abnormalities in patients who are thyrotoxic but do not have Graves’ disease include a toxic multinodular goitre, a solitary nodule (toxic adenoma), and painless, postpartum or subacute (de Quervain’s^h) thyroiditis. In de Quervain’s thyroiditis there is typically a moderately enlarged firm and tender gland. Thyrotoxicosis may occur without any goitre, particularly in elderly patients. Alternatively, in hyperthyroidism due to a rare abnormality of trophoblastic tissue (a hydatidiform mole or choriocarcinoma of the testis or uterus), or excessive thyroid hormone replacement, the thyroid gland will not usually be palpable.

If a thyroidectomy scar is present, assess for hypoparathyroidism (Chvostek’sⁱ or Trousseau’s^j signs; page 311). These signs are most often present in the first few days after operation.

The arms

Ask the patient to raise the arms above the head and so test for proximal myopathy.

The chest

Gynaecomastia (page 315) occurs occasionally. Examine the heart for systolic flow murmurs (due to increased cardiac output) and signs of congestive cardiac failure, which may be precipitated by thyrotoxicosis in older people.

The legs

Look first for pretibial myxoedema. This takes the form of bilateral firm, elevated dermal nodules and plaques, which can be pink, brown or skin-coloured. They are caused by mucopolysaccharide accumulation. Despite the name, this occurs only in Graves’ disease and not in hypothyroidism. Test now for proximal myopathy and hyperreflexia in the legs which is present in only about a quarter of cases.