10 Endocrine disease

Endocrinology concerns the synthesis, secretion and action of hormones. These are chemical messengers released from endocrine glands that coordinate the activities of many different cells. Endocrine disease, therefore, has a wide range of manifestations in many organs.

MAJOR ENDOCRINE FUNCTIONS AND ANATOMY

Although some endocrine glands (e.g. the parathyroids and pancreas) respond directly to metabolic signals, most are controlled by hormones released from the pituitary gland. Anterior pituitary hormone secretion is controlled in turn by substances produced in the hypothalamus and released into portal blood which flows down the pituitary stalk. Posterior pituitary hormones are synthesised in the hypothalamus and transported down nerve axons to be released from the posterior pituitary. Hormone release in the hypothalamus and pituitary is regulated by numerous nervous, metabolic, physical or hormonal stimuli, in particular feedback control by hormones produced by target glands (thyroid, adrenal cortex and gonads). These integrated endocrine systems are called ‘axes’ (Figs 10.1, 10.2).

Fig. 10.1 The principal endocrine ‘axes’ and glands. Parathyroid glands, adrenal zona glomerulosa and endocrine pancreas are not controlled by the pituitary. Italics show negative regulation. (GnRH = gonadotrophin-releasing hormone. For other abbreviations see text.)

Fig. 10.2 The principal endocrine glands.

The classical model of endocrine function involves hormones which are synthesised in endocrine glands and are released into the circulation, acting at sites distant from those of secretion. However, most major organs also secrete hormones or contribute to the metabolism and activation of prohormones; many hormones act on adjacent cells (paracrine system, e.g. neurotransmitters) or even back on the cell of origin (autocrine system); and the sensitivity of target tissues is regulated in a tissue-specific fashion. Some hormones (e.g. insulin, adrenaline (epinephrine)) act on specific cell surface receptors. Other hormones (e.g. steroids, triiodothyronine, vitamin D) bind to specific intracellular receptors, which in turn bind to response elements on DNA to regulate gene transcription.

CLINICAL EXAMINATION IN ENDOCRINE DISEASE

Pathology arising within an endocrine gland is often called ‘primary’ disease (e.g. primary hypothyroidism in Hashimoto’s thyroiditis), while abnormal stimulation of the gland is often called ‘secondary’ disease (e.g. secondary hypothyroidism in patients with thyroid-stimulating hormone (TSH) deficiency).

PRESENTING PROBLEMS IN ENDOCRINE DISEASE

Patients with endocrine disease present in many ways, to many different specialists, reflecting the diverse effects of hormone deficiency and excess. Presenting symptoms are often non-specific and long-standing (Box 10.1). In many patients, endocrine disease is asymptomatic and detected by routine biochemical testing. The most common classical presentations are of thyroid disease, reproductive disorders and hypercalcaemia. In addition, endocrine diseases are often part of the differential diagnosis of other disorders, including electrolyte abnormalities, hypertension, obesity and osteoporosis. Although diseases of the adrenal glands, hypothalamus and pituitary are relatively rare, their diagnosis often relies on astute clinical observation in a patient with non-specific complaints, so it is important that clinicians are familiar with their key features.

10.1 MOST COMMON PRESENTING SYMPTOMS OF ENDOCRINE DISEASE

Symptom	Most likely disorder(s)
Lethargy/depression	Hypothyroidism, DM, Cushing’s syndrome, hyperparathyroidism, hypogonadism, adrenal insufficiency
Weight gain	Hypothyroidism, Cushing’s
Weight loss	Thyrotoxicosis, adrenal insufficiency, DM
Proptosis	Graves’ disease
Thyroid nodule	Solitary thyroid nodule, dominant nodule in multinodular goitre
Polyuria/polydipsia	DM, diabetes insipidus, hyperparathyroidism, Conn’s syndrome
Coarse features	Acromegaly, hypothyroidism
Galactorrhoea	Hyperprolactinaemia
Ureteric colic	Hyperparathyroidism
Paraesthesiae/tetany	Hypoparathyroidism
Muscle weakness (usually proximal)	Thyrotoxicosis, Cushing’s, hypokalaemia (e.g. Conn’s), hyperparathyroidism, hypogonadism
Heat intolerance	Thyrotoxicosis, menopause
Thyroid swelling	Simple goitre, Graves’ disease, Hashimoto’s thyroiditis
Palpitations	Thyrotoxicosis, phaeochromocytoma
Hirsutism	Idiopathic, PCOS, congenital adrenal hyperplasia, Cushing’s
Amenorrhoea/oligomenorrhoea	Menopause, PCOS, hyperprolactinaemia, thyrotoxicosis, premature ovarian failure, Cushing’s
Pain over thyroid	Haemorrhage into nodule, de Quervain’s thyroiditis
Loss of libido	Male hypogonadism
Headache	Acromegaly, pituitary tumour, phaeochromocytoma
Visual dysfunction	Pituitary tumour

(DM = diabetes mellitus; PCOS = polycystic ovarian syndrome)

THE THYROID GLAND

Diseases of the thyroid affect 5% of the population, predominantly females. The thyroid axis is involved in the regulation of cellular differentiation and metabolism in virtually all nucleated cells, so that disorders of thyroid function have diverse manifestations. Follicular epithelial cells synthesise thyroid hormones by incorporating iodine into the amino acid, tyrosine. The thyroid secretes predominantly thyroxine (T₄) and only a small amount of triiodothyronine (T₃), the more active hormone; ∼85% of T₃ in blood is produced from peripheral conversion of T₄. They both circulate in plasma almost entirely (>99%) bound to transport proteins, mainly thyroxine-binding globulin (TBG). The unbound hormones diffuse into tissues and exert diverse metabolic actions. The advantage of measuring free over total hormone is that the former is not influenced by changes in TBG concentrations; in pregnancy, for example, TBG levels are increased and total T₃/T₄ may be raised, but free thyroid hormone levels are normal.

Production of T₃ and T₄ in the thyroid is stimulated by thyroid-stimulating hormone (TSH), a glycoprotein released from the thyrotroph cells of the anterior pituitary in response to the hypothalamic tripeptide, thyrotrophin-releasing hormone (TRH). There is a negative feedback of thyroid hormones on the hypothalamus and pituitary such that in thyrotoxicosis, when plasma concentrations of T₃ and T₄ are raised, TSH secretion is suppressed. Conversely, in primary hypothyroidism low T₃ and T₄ are associated with high circulating TSH levels. TSH is, therefore, regarded as the most useful investigation of thyroid function. However, TSH may take several weeks to ‘catch up’ with T₄/T₃ levels, e.g. after prolonged suppression of TSH in thyrotoxicosis is relieved by antithyroid therapy. Common patterns of abnormal thyroid function tests (TFTs) are shown in Box 10.2.

10.2 PATTERNS OF THYROID FUNCTION TEST (TFT) RESULTS

PRESENTING PROBLEMS

THYROTOXICOSIS

• Approximately 75% of cases are due to Graves’ disease, 15% to multinodular goitre and 5% to toxic adenoma.

• Less common causes include transient thyroiditis (de Quervain’s, post-partum), iodide-induced (drugs, supplementation), factitious and TSH-secreting pituitary tumour.

Clinical assessment

Manifestations of thyrotoxicosis are shown in Box 10.3. The most common symptoms are:

• Weight loss with a normal appetite.

10.3 CLINICAL FEATURES OF THYROTOXICOSIS

	Symptoms	Signs
General	Weight loss (normal appetite), heat intolerance, fatigue, apathy¹, osteoporosis	Weight loss, goitre with bruit², lymphadenopathy³
GI	Hyperdefecation, diarrhoea, steatorrhoea, anorexia¹, vomiting³
Cardio-respiratory	Palpitations, dyspnoea on exertion, angina, ankle swelling, asthma exacerbation³	Sinus tachycardia, atrial fibrillation, systolic hypertension, cardiac failure
Neuromuscular	Anxiety, irritability, emotional lability, psychosis, tremor, weakness	Tremor, hyper-reflexia, ill-sustained clonus, proximal/bulbar¹ myopathy
Dermatological	Sweating, pruritus, alopecia	Palmar erythema, pretibial myxoedema², thyroid acropachy², onycholysis³, pigmentation³, vitiligo²
Reproductive	Oligo-/amenorrhoea, infertility, ↓libido, impotence	Gynaecomastia
Ocular	Grittiness, red eyes, excessive lacrimation, diplopia², loss of acuity²	Lid retraction, lid lag, chemosis², exophthalmos², periorbital oedema², corneal ulceration², ophthalmoplegia², papilloedema²

Italics indicate common features.

1 Particularly in elderly patients.

2 Graves’ disease only.

3 Rare.

All causes of thyrotoxicosis can cause lid retraction and lid lag, but only Graves’ disease causes other ocular features (see Box 10.3).

Investigations

Figure 10.3 summarises the approach to establishing the diagnosis.

Fig. 10.3 Establishing the differential diagnosis in thyrotoxicosis. Scintigraphy is not necessary in most cases of drug-induced thyrotoxicosis.

TFTs: T₃ and T₄ are elevated in most patients, but T₄ is normal and T₃ raised (T₃ toxicosis) in 5%. In primary thyrotoxicosis, serum TSH is undetectable (<0.05 mU/l).

Antibodies: TSH receptor antibodies (TRAb) are elevated in 80–95% of patients with Graves’ disease. Other thyroid antibodies are unhelpful, as they are present in the healthy population.

Imaging: ^99mTechnetium scintigraphy scans indicate trapping of isotope in the gland (see Fig. 10.3). Iodine can also be used but yields lower resolution images.

• In Graves’ disease there is diffuse uptake.

• In multinodular goitre, there is low, patchy uptake within the nodules.

• A hot spot is seen in toxic adenoma, with no uptake in the dormant gland tissue.

• In low-uptake thyrotoxicosis, the cause is usually a transient thyroiditis, although rarely patients may induce ‘factitious thyrotoxicosis’ by consuming thyroxine.

Definitive treatment of thyrotoxicosis depends on the underlying cause (see pp. 343–346) and may include antithyroid drugs, radioactive iodine or surgery. A non-selective β-blocker (propranolol 160 mg daily) will alleviate symptoms within 24–48 hrs.

Atrial fibrillation (AF) in thyrotoxicosis: AF is present in ∼10% of all patients with thyrotoxicosis (more in the elderly). Subclinical thyrotoxicosis is also a risk factor for AF. Ventricular rate responds better to β-blockade than digoxin. Thromboembolic complications are particularly common so anticoagulation with warfarin is indicated. Once the patient is biochemically euthyroid, AF reverts to sinus rhythm spontaneously in ∼50% of patients.

Thyrotoxic crisis (‘thyroid storm’): This is a medical emergency with a mortality of 10%. The most prominent signs are fever, agitation, confusion, tachycardia or AF, and cardiac failure. It is precipitated by infection in patients with unrecognised thyrotoxicosis and may develop after subtotal thyroidectomy or ¹³¹I therapy.

Patients should be rehydrated and given broad-spectrum antibiotics.

• Propranolol is rapidly effective orally (80 mg 6-hourly) or intravenously (1–5 mg 6-hourly).

• Sodium ipodate (500 mg daily orally) restores serum T₃ levels to normal in 48–72 hrs by inhibiting release of hormones and conversion of T₄ to T₃.

• Oral carbimazole 40–60 mg daily inhibits the synthesis of new hormones. In the unconscious patient, carbimazole can be administered rectally. After 10–14 days, maintenance with carbimazole alone is possible.

HYPOTHYROIDISM

The prevalence of primary hypothyroidism is 1 in 100, with a female : male ratio of 6 : 1.

• Autoimmune disease (Hashimoto’s thyroiditis) and thyroid failure following ¹³¹I or surgical treatment of thyrotoxicosis account for >90% of cases where the population is not iodine-deficient.

• Less common causes include secondary hypothyroidism, transient thyroiditis, amiodarone-induced and dyshormonogenesis.

Clinical assessment

Clinical features depend on the duration and severity of the hypothyroidism. The classical clinical features listed in Box 10.4 occur when deficiency develops insidiously over months/years.

10.4 CLINICAL FEATURES OF HYPOTHYROIDISM

	Symptoms	Signs
General	Weight gain, cold intolerance, fatigue, somnolence, hoarseness	Weight gain, hoarseness, goitre, macrocytosis, anaemia
GI	Constipation	Ileus^, ascites^
Cardio-respiratory		Bradycardia, hypertension, pericardial/pleural effusions^*
Neuromuscular	Carpal tunnel syndrome, muscle stiffness, deafness, depression, psychosis^*	Delayed relaxation of reflexes, cerebellar ataxia^, myotonia^
Dermatological	Dry skin, dry hair, alopecia	Myxoedema, purplish lips, malar flush, vitiligo, erythema ab igne
Reproductive	Menorrhagia, infertility, galactorrhoea^, impotence^
Ocular		Periorbital oedema, loss of lateral eyebrows

Italics indicate common features.

* Rare.

Solitary nodule

• Simple cyst

• Colloid nodule

• Primary thyroid cancer (see Box 10.7 below)

• Follicular adenoma

• Metastasis

Multinodular goitre

¹ May shrink with thyroxine therapy.

² Usually tender.

Diffuse goitre: In the absence of thyrotoxicosis or hypothyroidism, a diffuse goitre rarely needs further investigation unless it is very large, causing cosmetic symptoms or compression. Absence of autoantibodies in a younger patient suggests a simple goitre. Thyroxine therapy may help to shrink the goitre.

Solitary thyroid nodule: It is important to determine whether the nodule is benign or malignant. Cervical lymphadenopathy increases the likelihood of malignancy, as does a solitary nodule presenting in the elderly. Rarely, a metastasis from renal, breast or lung carcinoma presents as a painful, rapidly growing solitary nodule.

TFTs should be measured in all patients with a solitary nodule. Undetectable TSH is suggestive of an autonomously functioning benign follicular adenoma, which can only be confirmed by thyroid isotope scanning. For euthyroid patients, fine needle aspiration (FNA) of the nodule is undertaken. Aspiration may be therapeutic if the swelling is a cyst. Cytological examination will differentiate benign (80%) from suspicious nodules (20%), of which 25–50% are confirmed as cancer at surgery. The advantage of FNA over isotope scanning is that a higher proportion of patients avoid surgery. However, FNA cannot differentiate between follicular adenoma and carcinoma, and 10–20% of specimens are inadequate.

Solitary nodules with either inconclusive or malignant cytology are treated by surgical excision. Benign lesions are sometimes excised but the majority of patients can be reassured.

Multinodular goitre: The clinical diagnosis is confirmed using ^99mTc scintigraphy or USS. Sometimes one nodule is larger than others (dominant); if ‘cold’ on isotope scanning, it is investigated as a solitary nodule since there is a risk of malignancy.

AUTOIMMUNE THYROID DISEASE

GRAVES’ DISEASE

The most common manifestation is thyrotoxicosis with or without a diffuse goitre. Clinical features are described in Box 10.3. Graves’ disease also causes ophthalmopathy and rarely pretibial myxoedema. These features can occur in the absence of thyroid dysfunction. Graves’ disease most commonly affects women aged 30–50 yrs.

Management

Symptoms respond to β-blockade but definitive treatment requires control of thyroid hormone secretion. The different options are compared in Box 10.6. For patients <40 yrs old many centres prescribe a course of carbimazole and recommend surgery if relapse occurs, while ¹³¹I is employed as first- or second-line treatment in older patients. It is unclear whether ¹³¹I increases the incidence of some malignancies; the association may be with Graves’ disease rather than its therapy. In many centres, however, ¹³¹I is used more extensively, even in young patients.

10.6 COMPARISON OF TREATMENTS FOR THE THYROTOXICOSIS OF GRAVES’ DISEASE

Antithyroid drugs: The most commonly used are carbimazole and propylthiouracil. These drugs reduce thyroid hormone synthesis by inhibiting tyrosine iodination. Antithyroid drugs are introduced at high doses (carbimazole 40–60 mg daily, propylthiouracil 400–600 mg daily). There is subjective improvement within 2 wks and the patient is biochemically euthyroid at 4 wks, when the dose can be reduced. The maintenance dose is determined by measurement of T₄ and TSH. Carbimazole is continued for 12–18 mths in the hope that permanent remission will occur. Unfortunately, thyrotoxicosis recurs in at least 50% within 2 yrs of stopping treatment. Adverse effects of antithyroid drugs include rash and idiosyncratic but reversible agranulocytosis.

Subtotal thyroidectomy: Patients must be rendered euthyroid before operation. Potassium iodide, 60 mg 8-hourly orally, is given for 2 wks before surgery to inhibit thyroid hormone release and reduce the size and vascularity of the gland, making surgery technically easier. Complications are uncommon (see Box 10.6). One year post-surgery, 80% of patients are euthyroid, 15% are hypothyroid and 5% remain thyrotoxic. Hypothyroidism within 6 mths of operation may be temporary. Long-term follow-up is necessary, as the late development of hypothyroidism and recurrence of thyrotoxicosis are well recognised.

Radioactive iodine: ¹³¹I is administered as a single dose (185–370 MBq, 5–10 mCi) and is trapped and organified in the thyroid. It is effective in 75% of patients within 4–12 wks. Symptoms can initially be controlled by β-blockade or with carbimazole. However, carbimazole reduces the efficacy of ¹³¹I therapy and should be avoided until 48 hrs after radio-iodine administration. If thyrotoxicosis persists after 12–24 wks, a further dose of ¹³¹I should be employed. The majority of patients eventually develop hypothyroidism, necessitating long-term follow-up.

Thyrotoxicosis in pregnancy

TFTs must be interpreted with caution in pregnancy. Thyroid-binding globulin, and hence total T₄/T₃ levels, are increased and TSH normal ranges are lower; a fully suppressed TSH with elevated free hormone levels indicates thyrotoxicosis. The thyrotoxicosis is almost always caused by Graves’ disease. Maternal thyroid hormones, TRAb and antithyroid drugs can all cross the placenta.

Treatment with propylthiouracil is preferred, as carbimazole is rarely associated with the childhood skin defect, aplasia cutis. The smallest dose of propylthiouracil (<150 mg/day) is used that maintains maternal TFTs within their normal ranges, thereby minimising fetal hypothyroidism and goitre. TRAb levels in the third trimester predict the likelihood of neonatal thyrotoxicosis; if they are not elevated, antithyroid drugs can be discontinued 4 wks before delivery to avoid fetal hypothyroidism at the time of maximum brain development. • During breastfeeding, propylthiouracil is used, as it is minimally excreted in the milk.

Graves’ ophthalmopathy

Within the orbit, there is immune-mediated fibroblast proliferation, increased interstitial fluid and a chronic inflammatory cell infiltrate. This causes swelling and ultimately fibrosis of the extraocular muscles and a rise in retrobulbar pressure. The eye is displaced forwards (proptosis, exophthalmos) with optic nerve compression in severe cases.

Ophthalmopathy is typically episodic. It is detectable in ∼50% of thyrotoxic patients at presentation, more commonly smokers, but may occur long before or after thyrotoxic episodes (exophthalmic Graves’ disease). Presenting symptoms are related to increased corneal exposure due to proptosis and lid retraction:

• Excessive lacrimation worsened by wind and sun.

• ‘Gritty’ sensations.

• Pain due to corneal ulceration.

• Reduced visual acuity/fields or colour vision due to optic nerve compression.

• Diplopia resulting from extraocular muscle involvement.

Most patients require no treatment. Methylcellulose eye drops are used for dry eyes and sunglasses reduce the excessive lacrimation. Severe inflammatory episodes are treated with glucocorticoids (prednisolone 60 mg daily) and sometimes orbital irradiation. Loss of visual acuity requires urgent surgical decompression of the orbit. Surgery to ocular muscles may improve diplopia.

HASHIMOTO’S THYROIDITIS

Hashimoto’s thyroiditis increases in incidence with age. It is characterised by destructive lymphoid infiltration leading to a varying degree of fibrosis and thus a varying degree of thyroid enlargement. There is a slightly increased risk of thyroid lymphoma. The term ‘Hashimoto’s thyroiditis’ has been reserved for patients with thyroid peroxidase autoantibodies and a goitre (with or without hypothyroidism), whilst ‘spontaneous atrophic hypothyroidism’ has been used in hypothyroid patients without a goitre with TSH receptor-blocking antibodies. However, these syndromes are both variants of Hashimoto’s.

• At presentation, a small or moderately sized firm diffuse goitre may be palpable.

• 25% of patients are hypothyroid and the remainder are at risk of developing overt hypothyroidism in future years.

• Thyroid peroxidase antibodies are present in >90%.

• Thyroxine therapy is given.

TRANSIENT THYROIDITIS

SUBACUTE (DE QUERVAIN’S) THYROIDITIS

Subacute thyroiditis is a virus-induced (e.g. Coxsackie, mumps) transient inflammation of the thyroid usually affecting 20–40-yr-old females.

• There is classically pain around the thyroid radiating to the jaw and ears, which is worsened by swallowing and coughing. The thyroid is enlarged and tender. Painless transient thyroiditis also occurs.

• Systemic upset is common.

• Inflammation in the thyroid causes release of colloid and stored hormones, and damages follicular cells. As a result, T₄/T₃ levels are raised for 4–6 wks until depletion of colloid. A period of hypothyroidism follows, during which follicular cells recover, restoring thyroid function within 4–6 mths. In the thyrotoxic phase, iodine uptake and technetium trapping are low due to follicular cell damage and TSH suppression.

• Pain and systemic upset respond to NSAIDs. Occasionally, prednisolone 40 mg daily for 3–4 wks is required. Mild thyrotoxicosis is treated with propranolol.

• Monitoring of thyroid function is required so that thyroxine can be prescribed temporarily in the hypothyroid phase.

POST-PARTUM THYROIDITIS

The maternal immune response is enhanced after delivery and may unmask subclinical autoimmune thyroid disease. Transient asymptomatic disturbances of thyroid function occur in 5–10% of women post-partum. However, symptomatic thyrotoxicosis presenting within 6 mths of childbirth is likely to be due to post-partum thyroiditis and the diagnosis is confirmed by negligible radioisotope uptake. The clinical course is similar to painless subacute thyroiditis. Post-partum thyroiditis can recur after subsequent pregnancies and may progress to hypothyroidism.

IODINE-ASSOCIATED THYROID DISEASE

IODINE DEFICIENCY

In mountainous areas (e.g. Andes, Himalayas), dietary iodine deficiency causes thyroid enlargement (endemic goitre) affecting >10% of the population. Most patients are euthyroid and have normal or raised TSH levels.

IODINE-INDUCED DYSFUNCTION

Chronic excess of iodine inhibits thyroid hormone release; this is the basis for its utility in treatment of thyroid storm and prior to subtotal thyroidectomy. Transient thyrotoxicosis may be precipitated in iodine deficiency following prophylactic iodinisation programmes. In individuals who have underlying thyroid disease predisposing to thyrotoxicosis (e.g. multinodular goitre or Graves’ disease), thyrotoxicosis can be induced by iodine administration (e.g. radiocontrast media).

AMIODARONE

The anti-arrhythmic agent amiodarone contains large amounts of iodine. Amiodarone also has a cytotoxic effect on thyroid follicular cells and inhibits T₄ to T₃ conversion. Around 20% of patients develop hypothyroidism or thyrotoxicosis. TSH provides the best indicator of thyroid function.

Thyrotoxicosis has been classified as:

• Type I (stimulatory effect of iodine in underlying thyroid disease). • Type II (transient thyrotoxicosis due to cytotoxic thyroiditis).

In hypothyroid patients, thyroxine can be given while amiodarone is continued. Treatment of thyrotoxicosis, however, is difficult. Excess iodine renders the gland resistant to radio-iodine. Antithyroid drugs may be effective in patients with type I thyrotoxicosis, but not in type II. If the cardiac state allows, amiodarone should be discontinued. Prior to amiodarone therapy, thyroid function should be measured and avoided if TSH is suppressed. Thyroid function should be monitored regularly.

SIMPLE AND MULTINODULAR GOITRE

SIMPLE DIFFUSE GOITRE

This presents in 15–25-yr-olds, often during pregnancy. The goitre is visible, soft and symmetrical and the thyroid is 2–3 times its normal size. There is no tenderness, lymphadenopathy or bruit, and TFTs are normal. The goitre may may regress without treatment or may progress to multinodular goitre.

MULTINODULAR GOITRE

Occasionally, simple goitres become multinodular over 10–20 yrs. These nodules grow at varying rates and secrete thyroid hormone ‘autonomously’, thereby suppressing TSH-dependent growth and function in the remaining gland. Ultimately, complete TSH suppression occurs in ∼25% of cases, with T₄/T₃ levels often within the normal range (subclinical thyrotoxicosis) but sometimes elevated (toxic multinodular goitre). The nodules may represent multiple adenomas or focal hyperplasia.

Management

Small goitre: Annual review is required, as progression to toxic multinodular goitre can occur.

Large goitre: Partial thyroidectomy is indicated in cases of mediastinal compression or for cosmesis. ¹³¹I is used in the elderly to reduce thyroid size but recurrence is common after 10–20 yrs.

Toxic multinodular goitre: ¹³¹I is used; hypothyroidism is less common than in Graves’ disease. Partial thyroidectomy may be required for a large goitre. Antithyroid drugs are not usually used, as drug withdrawal invariably leads to relapse.

Subclinical thyrotoxicosis: This is increasingly being treated with ¹³¹I, as a suppressed TSH is a risk factor for AF and osteoporosis.

THYROID NEOPLASIA

Patients with thyroid tumours usually present with a solitary nodule (p. 341). Most are benign and a few (toxic adenomas) secrete excess thyroid hormones. Primary thyroid malignancy is rare (<1% of all carcinomas). As shown in Box 10.7, it can be classified according to the cell type of origin. With the exception of medullary carcinoma, thyroid cancer is more common in females.

10.7 MALIGNANT THYROID TUMOURS