The endocrine history

Past history

A previous history of any endocrine condition must be uncovered. This includes surgery on the neck for a goitre. A partial thyroidectomy or radio-iodine (¹³¹I) treatment in the past can lead to eventual hypothyroidism. The same may apply to radiation of the thyroid for carcinoma. A woman may have been diagnosed with diabetes mellitus after the birth of a large baby. There may be a past history of hypertension, which is occasionally due to an endocrine condition (e.g. phaeochromocytoma, Cushing’s syndrome or Conn’s syndrome). Previous thyroid surgery can be associated with hypoparathyroidism because of surgical damage to the parathyroid glands.

Previous treatment of a patient’s thyroid problems may have included the use of antithyroid drugs, thyroid hormone or radioactive iodine. Surgery on the adrenals or pituitary may have been performed and this may leave the patient with decreased adrenal or pituitary function.

Patients with diabetes mellitus have an important chronic condition (Questions box 10.7, page 316). Treatment may be with diet, insulin or oral hypoglycaemic agents. One must determine how well the patient understands the condition, and whether he or she understands the principles of the diabetic diet and adheres to it. Find out how the blood sugar levels are monitored and whether or not the patient adjusts the insulin dose. Most patients should now be able to monitor their own blood sugar levels at home using a glucometer. There is now good evidence that tight control of blood sugar levels reduces the incidence of diabetic complications. Patients should have records of home blood sugar measurements, and may know the results of tests such as the haemoglobin A1c (a measure of average blood sugar levels) and of tests of renal function and for protein in the urine.

The patient should be aware of the need for care of the feet and eyes to help prevent complications. Most diabetics have regular ophthalmological review, often using retinal photography. There may be a history of laser treatment for proliferative diabetic retinopathy.

Patients with hypopituitarism or hypoadrenalism may be on glucocorticoid (steroid) replacement; the latter also require mineralocorticoid replacement. Details of the patient’s dosage schedule should be obtained.

Social history

Many of these conditions are chronic and their complications serious. How well the patient copes with various problems and the conditions at home and work will have an important effect on the success of treatment.

Family history

There may be a history in the family of thyroid conditions or diabetes mellitus. Occasionally a family history of a multiple endocrine neoplasia (MEN) syndrome may be obtained. These are rare autosomal-dominant conditions. They include pituitary tumours, medullary carcinoma of the thyroid, hyperparathyroidism, phaeochromocytoma and pancreatic islet cell tumours.

The endocrine examination

A formal examination of the whole endocrine system is set out on page 322. Usually there will be some clue from the history and general inspection to indicate what specific endocrine diseases should be pursued.

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

Repeat the assessment while the patient swallows

Decide if a thrill is palpable over the gland, as occurs when the gland is unusually metabolically active as in thyrotoxicosis.

Palpate the cervical lymph nodes (page 228). These may be involved in carcinoma of the thyroid.

Move to the front. Palpate again. Localised swellings may be more easily defined here. Note the position of the trachea, which may be displaced by a retrosternal gland.

Percussion

The upper part of the manubrium can be percussed from one side to the other. A change from resonant to dull indicates a possible retrosternal goitre, but this is not a very reliable sign.

Auscultation

Listen over each lobe for a bruit (a swishing sound coinciding with systole). This is a sign of increased blood supply which may occur in hyperthyroidism, or occasionally from the use of antithyroid drugs. The differential diagnosis also includes a carotid bruit (louder over the carotid itself) or a venous hum (obliterated by gentle pressure over the base of the neck). If there is a goitre, apply mild compression to the lateral lobes and listen again for stridor.

Pemberton’s sign

Ask the patient to lift both arms as high as possible. Wait a few moments, then search the face eagerly for signs of congestion (plethora) and cyanosis. Associated respiratory distress and inspiratory stridor may occur. Look at the neck veins for distension (venous congestion). Ask the patient to take a deep breath in through the mouth and listen for stridor. This is a test for thoracic inlet obstruction due to a retrosternal goitre or any retrosternal mass.³ (Lifting the arms up pulls the thoracic inlet upward so that the goitre occupies more of this inflexible bony opening.)

Examination of the thyroid should be part of every routine physical examination. Causes of a goitre are listed in Table 10.4.

TABLE 10.4 Goitre

Causes of a diffuse goitre (patient often euthyroid) Idiopathic (majority) Puberty or pregnancy Thyroiditis • Hashimoto’s • Subacute (gland usually tender) Simple goitre (iodine deficiency) Goitrogens—iodine excess, drugs (e.g. lithium) Inborn errors of thyroid hormone synthesis—e.g. Pendred’s* syndrome (an autosomal-recessive condition associated with nerve deafness)

Causes of a solitary thyroid nodule Benign: • Dominant nodule in a multinodular goitre • Degeneration or haemorrhage into a colloid cyst or nodule • Follicular adenoma • Simple cyst (rare) Malignant: • Carcinoma—primary or secondary (rare) • Lymphoma (rare)

^* Vaughan Pendred (b. 1869), London physician.

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.

Questions box 10.1

Questions to ask the patient with suspected hyperthyroidism

! denotes symptoms for the possible diagnosis of an urgent or dangerous problem.

1. Have you any history of thyroid problems?

2. Have you a family history of thyrotoxicosis?—There is a familial incidence of Graves disease and associated auto-immune conditions such as vitiligo, Addison’s disease, pernicious anaemia, type 1 diabetes, myasthenia gravis and premature ovarian failure

3. Have you taken amiodarone or thyroxine?

4. Have you had recent exposure to iodine?—Iodinated X-ray contrast materials can precipitate thyrotoxicosis (usually in patients with an existing multinodular goitre)

5. Have you had palpitations?—Thyrotoxicosis can present with atrial fibrillation which may precipitate heart failure

6. Have you noticed insomnia, irritability or hyperactivity?

7. Have you had loss of weight, diarrhoea or increased stool frequency, increased sweating or heat intolerance?

8. Have you had muscle weakness?—Proximal muscle weakness is common and the patient may have noticed difficulty getting out of a chair

9. Have you had eye problems such as double vision, grittiness, redness or pain behind the eyes?

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

Sign	Positive LR	Negative LR
Pulse
≥90/min	4.4	0.2
Skin
Moist and warm	6.7	0.7
Thyroid
Enlarged	2.3	0.1
Eyes
Eyelid retraction	31.5	0.7
Lid lag	17.6	0.8
Neurological
Fine tremor	11.4	0.3

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

General inspection

Look for signs of weight loss, anxiety and the frightened facies of thyrotoxicosis.

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.

Hypothyroidism (myxoedema)

Hypothyroidism (deficiency of thyroid hormone) is due to primary disease of the thyroid or, less commonly, is secondary to pituitary or hypothalamic failure (Table 10.6). Myxoedema implies a more severe form of hypothyroidism. In myxoedema, for unknown reasons, hydrophilic mucopolysaccharides accumulate in the ground substance of tissues including the skin. This results in excessive interstitial fluid, which is relatively immobile, causing skin thickening and a doughy induration.

TABLE 10.6 Thyrotoxicosis and hypothyroidism

TSH = thyroid stimulating hormone. HCG = human chorionic gonadotrophin.

^* Carl von Basedow (1799–1854), German general practitioner, described this in 1840 (Jod = iodine in German).

The symptoms of hypothyroidism are insidious but patients or their relatives may have noticed cold intolerance, muscle pains, oedema, constipation, a hoarse voice, dry skin, memory loss, depression or weight gain (Questions box 10.2).

Examine the patient with suspected hypothyroidism as follows (see Good signs guide 10.3).

GOOD SIGNS GUIDE 10.3 Hypothyroidism

NS = not significant.

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

The face

Inspect the face (Figure 10.8). The skin, but not the sclerae, may appear yellow due to hypercarotenaemia. The skin may be generally thickened, and alopecia may be present, as may vitiligo (an associated autoimmune disease).

Figure 10.8 Myxoedema

Inspect the eyes for periorbital oedema. Loss or thinning of the outer third of the eyebrows can occur in myxoedema but is also common in healthy persons. Look for xanthelasma (due to associated hypercholesterolaemia). Palpate for coolness and dryness of the skin and hair. There may be thinning of the scalp hair.

Look at the tongue for swelling. Ask the patient to speak, and listen for coarse, croaking, slow speech. Bilateral nerve deafness may occur with endemic or congenital hypothyroidism.

The pituitary

Pituitary tumours can present in two ways: as a result of (i) local effects such as headaches, visual field loss and loss of acuity; and (ii) changes in pituitary hormone secretion. These changes include: (i) excess growth hormone, causing acromegaly; (ii) excess adrenocorticotrophic hormone (ACTH), causing Cushing’s syndrome; (iii) excess prolactin, causing galactorrhoea, secondary amenorrhoea or male infertility or deficiency (hypopituitarism), and (iv) excess thyroid stimulating hormone (TSH), causing hyperthyroidism.

The face

Look at the face more closely. Multiple skin wrinkles around the eyes are characteristic of gonadotrophin deficiency. Inspect the forehead carefully for hypophysectomy scars—transfrontal scars will be apparent (Figure 10.9) but not transsphenoidal ones, as this operation is performed through the base of the nose, via an incision under the upper lip.

Figure 10.9 Acromegaly

Examine the eyes (Chapter 13). The visual fields must be assessed for any defects, especially bitemporal hemianopia (an enlarging pituitary tumour may compress the optic chiasm), and the fundi examined for optic atrophy (optic nerve compression from a pituitary tumour). Assess the third, fourth, sixth and first divisions of the fifth cranial nerves, as these may be affected by extrapituitary tumour expansion into the cavernous sinus (Figure 10.10).

Figure 10.10 The cavernous sinus and its relationship with the cranial nerves and pituitary gland

Feel the facial hair over the bearded area in men for normal beard growth (which is lost with gonadotrophin deficiency).

The chest

Go on to the chest. Look for skin pallor and for a decrease in nipple pigmentation. In men, decreased body hair (axillary and chest) may be present. In women, secondary breast atrophy may be found.

The genital region

Loss of pubic hair occurs in both sexes. In men, testicular atrophy may be present. Atrophied testes are characteristically small and firm. The normal-sized testis is about 15–25 mL in volume.

The ankle reflexes

Test for ‘hung-up’ jerks (Figure 10.11). These are an important sign of pituitary hypothyroidism. Occasionally, pituitary hypothyroid patients may be slightly overweight, but the classical myxoedematous appearance is usually absent.

Figure 10.11 Testing ankle jerks (second method— see also page 372)

This method best demonstrates the ‘hung-up’ reflexes of hypothyroidism. Look for rapid dorsiflexion followed by slow plantar flexion after the tendon is tapped.

Acromegaly^k

This is excessive secretion of growth hormone, typically due to an eosinophilic pituitary adenoma.^l Growth hormone stimulates the liver and other tissues to produce somatomedins which in turn promote growth. Growth hormone is also a protein anabolic hormone exerting its effects at the ribosomal level, and it is diabetogenic as it exerts an anti-insulin effect in muscle and increases hepatic glucose release. The disease has a very gradual onset and patients may not have noticed symptoms. Most patients, however, have headache caused by stretching of the dura by the enlarging pituitary tumour.

Gigantism is the result of growth hormone hypersecretion occurring before puberty and fusion of the epiphyses. It results in massive skeletal as well as soft-tissue growth. Acromegaly occurs when the growth plates have fused, so that only soft-tissue and flat-bone enlargement are possible.

Other pituitary syndromes

Cushing’s syndrome can occur as a result of excess pituitary ACTH secretion. Hyperthyroidism can occur as a result of excess pituitary TSH production. Prolactinomas of the pituitary can cause galactorrhoea (production of milk) in both women and men.

The adrenals

ACTH = adrenocorticotrophic hormone.

GOOD SIGNS GUIDE 10.4 Cushing’s syndrome

NS = not significant.

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

Standing

Have the patient undress to the underpants and, if possible, stand up (Figure 10.12). Look from the front, back and sides. Note moon-like facies and central obesity. The limbs appear thin despite sometimes very gross truncal (mostly intra-abdominal rather than subcutaneous fat) obesity.ⁿ This is the characteristic fat distribution that occurs with steroid excess. Bruising may be present (due to loss of perivascular supporting tissue–protein catabolism). Look for excessive pigmentation on the extensor surfaces (because of melanocyte-stimulating-hormone [MSH]-like activity in the ACTH molecule). Ask the patient to squat at this point to test for proximal myopathy, due to mobilisation of muscle tissue or excessive urinary potassium loss. Look at the back for the ‘buffalo hump’, which is due to fat deposition over the interscapular area. Palpate for bony tenderness of the vertebral bodies due to crush fractures from osteoporosis (a steroid anti-vitamin-D effect and increased urinary calcium excretion may be responsible in part for disruption of the bone matrix).

Figure 10.12 Buffalo hump and central obesity in Cushing’s syndrome

From McDonald FS, ed., Mayo Clinic images in internal medicine, with permission. © Mayo Clinic Scientific Press and CRC Press.

Addison’s disease^p

This is adrenocortical hypofunction with reduction in the secretion of glucocorticoids and mineralocorticoids. It is most often due to autoimmune disease of the adrenal glands. Other causes are listed in Table 10.11.

TABLE 10.11 Causes of Addison’s disease

If this disease is suspected, look for cachexia. Then, with the patient undressed, look for pigmentation in the palmar creases (Figure 10.13), elbows, gums and buccal mucosa, genital areas and in scars. This occurs because of compensatory ACTH hypersecretion in primary hypoadrenalism (when there is adrenal disease), as ACTH has melanocyte-stimulating activity. Also inspect for vitiligo (localised hypomelanosis), an autoimmune disease that is commonly associated with autoimmune adrenal failure.

Figure 10.13 Palmar crease pigmentation in Addison’s disease

Take the blood pressure and test for postural hypotension. Remember that the rest of the autoimmune disease cluster may be associated with autoimmune adrenal failure (Table 10.12).

TABLE 10.12 A classification of conditions found in various combinations in autoimmune polyglandular syndromes

Calcium metabolism

Other causes of hypercalcaemia are listed in Table 10.14.

TABLE 10.14 Important causes of hypercalcaemia

The MEN syndromes

The multiple endocrine neoplasias (MENs), types I and II, are autosomal dominant conditions. Hyperparathyroidism can be associated with both. MEN type I (due to a mutation on chromosome 11) is associated with tumours of the parathyroid, pituitary and pancreatic islet cells. MEN type IIA (due to a mutation on chromosome 10 involving the c-ret proto-oncogene) is associated with medullary carcinoma of the thyroid, hyperparathyroidism and phaeochromocytoma. MEN type IIB is characterised by mucosal neuromas (often on the lips and tongue) and medullary carcinoma of the thyroid plus phaeochromocytoma.

Hypoparathyroidism

This results in hypocalcaemia with neuromuscular consequences (tetany) (Questions Box 10.6).

It is usually a postoperative complication after thyroidectomy, but can be idiopathic. Hypocalcaemia can also result from end-organ resistance to parathyroid hormone (pseudohypoparathyroidism) (Table 10.15).

TABLE 10.15 Causes of hypocalcaemia

Look first for Trousseau’s and Chvostek’s signs. Trousseau’s sign is elicited with a blood pressure cuff placed on the arm with the pressure raised above the patient’s systolic pressure. Typical contraction of the hand occurs within 2 minutes when hypocalcaemia has caused neuromuscular irritability. The thumb becomes strongly adducted, and the fingers are extended, except at the metacarpophalangeal joints. The appearance is that of an obstetrician about to remove the placenta manually and is called the main d’accoucheur.

Chvostek’s sign is performed by tapping gently over the facial (seventh) cranial nerve under the ear. The nerve is hyperexcitable in hypocalcaemia and a brisk muscular twitch occurs on the same side of the face.

Next test for hyperreflexia, again due to neuromuscular irritability.

Look at the nails for fragility and monilial infection. Note any dryness of the skin. Go to the face and look for deformity of the teeth. Examine the eyes for cataracts or papilloedema. These signs may all occur in idiopathic hypoparathyroidism, an autoimmune disease. Cataracts may also follow surgically induced hypoparathyroidism.

Pseudohypoparathyroidism

In this disease the patients have tetany (due to hypocalcaemia) as well as typical skeletal abnormalities. These include short stature, a round face, a short neck, thin stocky build and very characteristically short fourth or fifth fingers or toes (due to metacarpal or metatarsal shortening; this can be unilateral or bilateral) (Figure 10.14). Ask the patient to make a fist to demonstrate the characteristic clinical signs.

Figure 10.14 Pseudohypoparathyroidism: (a) feet; (b) hands

From McDonald FS, ed., Mayo Clinic images in internal medicine, with permission. © Mayo Clinic Scientific Press and CRC Press.

Syndromes associated with short stature

These conditions begin in childhood.

General inspection

First measure the height of the patient; in children this should be compared with percentile charts for age and sex. Look for the classical appearance of Turner’s syndrome, Down syndrome, achondroplasia or rickets (Figure 10.15), which may explain the short stature. The height of parents and siblings should be checked as well.

Figure 10.15 Rickets (postrachitic patient)

Look for frontal bossing, proximal myopathy of arms and thighs, and bowing of the ulna, femur and tibia.

Note any evidence of weight loss, including loose skinfolds, which may suggest a nutritional cause (starvation, malabsorption or protein loss). Look for signs of hypopituitarism or hypothyroidism, or steroid excess. Sexual precocity (early onset of secondary sexual characteristics) causes relative tallness at first but short stature later.

Hirsutism

This is excessive hairiness in a woman beyond what is considered normal for her race (Table 10.16). It is caused by androgen (including testosterone) excess. In the examination of such a patient, it is important to decide whether virilisation is also present. Virilisation is the appearance of male secondary sexual characteristics (clitoromegaly, frontal hair recession, male body habitus and deepening of the voice) and indicates that excessive androgen is present.

TABLE 10.16 Causes of hirsutism

Gynaecomastia (Figure 10.16)

This is ‘true’ enlargement of the male breasts.⁵ Careful examination will detect up to 4 cm of palpable breast tissue in 30% of normal young men; this percentage increases with age. These men are unaware of any breast abnormality. Gynaecomastia occurs in up to 50% of adolescent boys, and also in elderly men in whom it is due to falling testosterone levels. Fat deposition (‘false’ enlargement) in obese men can be confused with gynaecomastia.

Figure 10.16 Gynaecomastia

This patient takes spironolactone for heart failure. Note median sternotomy scar (arrow) and defibrillator box (open arrow).

Examine the breasts (page 435) for evidence of localised disease (e.g. malignancy, which is rare), tenderness, which indicates rapid growth, and any discharge from the nipple. Detection of breast tissue in men is best performed with the patient sitting up. Squeeze the breast behind the patient’s nipple between the thumb and forefinger. Try to detect an edge between subcutaneous fat and true breast tissue.

Examine the genitalia now for sexual ambiguity and the testes for absence or a reduced size. Note any loss of secondary sexual characteristics.

Look especially for signs of Klinefelter’s syndrome (47,XXY). These patients are tall, have decreased body hair and characteristically small, firm testes.

Look also for signs of panhypopituitarism or chronic liver disease. Thyrotoxicosis can occasionally be a cause.

Finally, examine the visual fields and fundi for evidence of a pituitary tumour.

Causes of pathological gynaecomastia are summarised in Table 10.17.

TABLE 10.17 Differential diagnosis (causes) of pathological gynaecomastia

Diabetes mellitus^q

Diabetes mellitus is characterised by hyperglycaemia due to an absolute or relative deficiency of insulin. The causes of diabetes are listed in Table 10.18. The disease can present with asymptomatic glycosuria detected on routine physical examination or with symptoms of diabetes (Table 10.1), ranging from polyuria to coma as a result of diabetic ketoacidosis (Questions box 10.7).

TABLE 10.18 Causes of diabetes mellitus

General inspection (Figure 10.17)

Assess for evidence of dehydration because the osmotic diuresis caused by a glucose load in the urine can cause massive fluid loss. Note obesity (non-insulin-dependent diabetics are usually obese) or signs of recent weight loss (this can be evidence of uncontrolled glycosuria).

Figure 10.17 Diabetes mellitus

Lying

1. General inspection

Weight—obesity

Hydration

Endocrine facies

Pigmentation—haemochromatosis, etc

2. Legs

Inspect

• Skin—necrobiosis, hair loss, infection, pigmented scars, atrophy, ulceration, injection sites

• Muscle wasting

Palpate

• Temperature of feet (cold, blue due to ‘small’ or ‘large’ vessel disease)

• Peripheral pulses

Femoral (auscultate)

Popliteal

Posterior tibial

Dorsalis pedis

3. Arms

Inspect

• Injection sites

• Skin lesions

Pulse

4. Eyes

Fundi—cataracts, rubeosis, retinal disease

III nerve palsy, etc

5. Mouth

Monilia

Infection

6. Neck

Carotid arteries—palpate, auscultate

7. Chest

Signs of infection

8. Abdomen

Liver—fat infiltration; rarely haemochromatosis

Neurological assessment

• Femoral nerve mononeuritis

• Peripheral neuropathy

9. Other

Urine analysis—glycosuria, ketones, proteinuria

Blood pressure—lying and standing

Oedema

Look for one of the abnormal endocrine facies (e.g. Cushing’s syndrome or acromegaly) and for pigmentation (e.g. haemochromatosis—bronze diabetes) as these may cause secondary diabetes.

The patient may be comatose due to dehydration, acidosis or plasma hyperosmolality. Kussmaul’s breathing (‘air hunger’) is present in diabetic ketoacidosis due to the acidosis (this occurs because fat metabolism is increased to compensate for the lack of availability of glucose; excess acetyl-coenzyme A is produced, which is converted in the liver to ketone bodies, and two of these are organic acids).

The lower limbs

Unlike most other systematic examinations, assessment of the diabetic can profitably begin with the legs, as many of the major physical signs are found to be here. In particular, vascular and neurological abnormalities in the feet must not be missed.⁶

Inspection

Look at the skin. The skin of the feet and lower legs may be hairless and atrophied due to small-vessel vascular disease and resultant ischaemia (the mechanism is uncertain, but may be related to lipoprotein alterations in the vessel walls).

Note any leg ulcers, particularly on the toes or any area of the feet exposed to pressure (Figure 10.18). These ulcers are due to a combination of ischaemia and peripheral neuropathy (the cause of the neuropathy is unknown, but may be related to small vessel ischaemia and glycosylation of neural proteins).

Figure 10.18 Diabetic (neuropathic) ulcer

From McDonald FS, ed., Mayo Clinic images in internal medicine, with permission. © Mayo Clinic Scientific Press and CRC Press.

Look for superficial skin infection, such as boils, cellulitis and fungal infections. These are more common in diabetics because of a combination of high tissue glucose levels and ischaemia, which provides a favourable environment for the growth of organisms.

Note any pigmented scars (late diabetic dermopathy). There may be small rounded plaques with raised borders lying in a linear fashion over the shins (diabetic dermopathy).

Necrobiosis lipoidica diabeticorum is a reasonably specific skin manifestation of diabetes mellitus, but is rare (fewer than 1% of diabetics) (Figure 10.19). It is found over the shins, where a central yellow scarred area is surrounded by a red margin when the condition is active. These plaques may ulcerate.

Figure 10.19 Necrobiosis lipoidica diabeticorum

From McDonald FS, ed., Mayo Clinic images in internal medicine, with permission. © Mayo Clinic Scientific Press and CRC Press.

Look now at the thighs for insulin injection sites. These may be associated with localised fat atrophy and fat hypertrophy, and may be related to impure insulin use which causes a localised immune reaction (modern genetically engineered insulins have made these rare). Note any quadriceps muscle wasting due to femoral nerve mononeuropathy, which is called (inaccurately) diabetic amyotrophy.

Inspect the knees for the very rare Charcot’s joints (grossly deformed disorganised joints, due to loss of proprioception or pain, or both; this leads to recurrent and unnoticed injury to the joint) (Figure 10.20).

Figure 10.20 Charcot’s joint of left knee

Palpation

Palpate any injection sites for fat atrophy or hypertrophy. Feel all the peripheral pulses and the temperature of the feet, and test the capillary return. Absent peripheral pulses, cold extremities and reduced capillary return are all evidence of peripheral vascular disease.

Neurological examination

Assess formally for peripheral neuropathy, including dorsal column loss (diabetic pseudotabes), and tap the reflexes. Test proximal muscle power (diabetic amyotrophy).

The face

The eyes

Test visual acuity. This may be permanently impaired because of retinal disease or temporarily disturbed because of changes in the shape of the lens associated with hyperglycaemia and water retention. Look for Argyll Robertson pupils^r, which are a rare complication of diabetes.

Using the ophthalmoscope, begin by examining for rubeosis (new blood vessel formation over the iris, which can cause glaucoma) (Figure 10.21). Then note any cataracts, which are related to sorbitol deposition in the lens (when glucose is present in high concentrations in the tissues it is converted to sorbitol by aldose reductase).

Figure 10.21 Rubeosis iridis

Shows new vessels on the anterior surface of the iris. These are secondary to ischaemia (often due to diabetes).

Now examine the retina, where many exciting changes may await the fundoscopist. There are two main types of retinal change in diabetes: non-proliferative and proliferative.

Non-proliferative changes (Figure 10.22) are directly related to ischaemia of blood vessels and include: (i) two types of haemorrhages—dot haemorrhages, which occur in the inner retinal layers, and blot haemorrhages, which are larger and which occur more superficially in the nerve fibre layer; (ii) microaneurysms, which are due to vessel wall damage; and (iii) two types of exudates—hard exudates, which have straight edges, and soft exudates (cottonwool spots), which have a fluffy appearance.

Figure 10.22 Diabetic retinopathy

(a) Soft exudate (arrow) and small haemorrhages.

(b) Microaneurysms (dots), retinal haemorrhages (blots) and hard yellow exudates.

Proliferative changes (Figure 10.23) are changes in blood vessels in response to ischaemia of the retina. They are characterised by new vessel formation, which can lead to vitreal haemorrhage, scar formation and eventually retinal detachment. The detached retina appears as an opalescent sheet that balloons forward into the vitreous. The underlying choroid is visible through the detached retina as a bright red-coloured sheet. Look also for laser scars (small brown or yellow spots), which are secondary to photocoagulation of new vessels by laser therapy.

Figure 10.23 Proliferative diabetic retinopathy

Assess the third, fourth and sixth cranial nerves. In particular examine for a diabetic third nerve palsy from ischaemia, which usually spares the pupil (as infarction of the third nerve affects the inner pupillary fibres more than the outer fibres; in this way it differs from compressive lesions, which have the opposite effect).

Other cranial nerves may be affected sometimes because of cerebrovascular accidents (large vessel atheroma). Rhinocerebral mucormycosis may rarely develop in very poorly controlled diabetic patients, causing periorbital and perinasal swelling and cranial nerve palsies.

The ears

Look in the ears for evidence of infection. The rare malignant otitis externa, usually due to Pseudomonas aeruginosa, causes a mound of granulation tissue in the external canal, and facial nerve palsy in 50% of cases.

The mouth

Look for evidence of Candida infection.

Paget’s^s disease (osteitis deformans)

This disease is characterised by excessive reabsorption of bone by osteoclasts and compensatory disorganised deposition of new bone. It is possibly a disease of viral origin.

The legs

Inspect for anterior bowing of the tibia and lateral bowing of the femur (Figure 10.24). Feel for bony warmth and tenderness. Note any changes of osteoarthritis in the hips and knees, which often coexist with Paget’s disease. Note any localised warm swelling, which may indicate sarcoma.

Figure 10.24 Paget’s disease, showing bowing of the tibia

Examine for evidence of paraplegia, which is uncommon but can occur due to cord compression by bone or vascular shunting in the spinal cord. Cerebellar signs may rarely be present due to platybasia.

Summary

The endocrine system: a suggested method of examination (Figure 10.25)

Inspect the patient for one of the diagnostic facies or body habituses. If the diagnosis is obvious, proceed with the specific examination outlined previously. If not, examine as follows.

Figure 10.25 The endocrine examination

Pick up the hands. Look at the overall size (acromegaly), length of the metacarpals (pseudohypoparathyroidism and pseudopseudohypo-parathyroidism), for abnormalities of the nails (hyperthyroidism and hypothyroidism, and hypoparathyroidism), tremor, palmar erythema and sweating of the palms (hyperthyroidism).

Take the pulse (thyroid disease) and the blood pressure (hypertension in Cushing’s syndrome, or postural hypotension in Addison’s disease). Look for Trousseau’s sign (tetany). Test for proximal muscle weakness (thyroid disease, Cushing’s syndrome).

Go to the axillae. Look for loss of axillary hair (hypopituitarism), or acanthosis nigricans and skin tags (acromegaly).

Examine the eyes (hyperthyroidism) and the fundi (diabetes, acromegaly). Look at the face for hirsutism, or fine-wrinkled hairless skin (panhypopituitarism). Note any skin greasiness, acne or plethora (Cushing’s syndrome).

Look at the mouth for protrusion of the chin and enlargement of the tongue (acromegaly) or buccal pigmentation (Addison’s disease).

Examine the neck for thyroid enlargement. Note any neck webbing (Turner’s syndrome). Palpate for supraclavicular fat pads (Cushing’s syndrome).

Inspect the chest wall for hirsutism or loss of body hair, reduction in breast size in women (panhypopituitarism) or gynaecomastia in men. Look for nipple pigmentation (Addison’s disease).

Examine the abdomen for hirsutism, central fat deposition, purple striae (Cushing’s syndrome) and the external genitalia for virilisation or atrophy. Look at the legs for diabetic changes.

Measure the body weight and height, and examine the urine.