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.)
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.
PRESENTING PROBLEMS
THYROTOXICOSIS
Clinical assessment
Manifestations of thyrotoxicosis are shown in Box 10.3. The most common symptoms are:
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.
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.
Management
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.
HYPOTHYROIDISM
The prevalence of primary hypothyroidism is 1 in 100, with a female : male ratio of 6 : 1.
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.
Investigations
Management
Most patients require life-long thyroxine therapy. A replacement regimen is:
Thyroxine has a half-life of 7 days, and so 6 wks should pass before repeating TFTs following a dose change. Patients feel better within 2–3 wks; resolution of skin and hair texture and effusions may take 3–6 mths.
The long-term correct dose of thyroxine restores TSH to within the reference range. This usually requires a T4 level in the upper normal range because the more active T3 is derived exclusively from peripheral conversion of T4 without the usual contribution from thyroid secretion. Some physicians advocate combined T4/T3 replacement but this approach remains controversial. TFTs should be checked every 1–2 yrs once the dose of thyroxine is stabilised.
Thyroxine requirements may increase with co-administration of other drugs (e.g. phenytoin, ferrous sulphate, rifampicin) and during pregnancy. In non-compliance, if thyroxine is taken just prior to clinic, the anomalous combination of a high T4 and high TSH may result. Around 40% of patients with angina cannot tolerate full replacement thyroxine despite the use of β-blockers. Exacerbation of myocardial ischaemia, infarction and sudden death are well-recognised complications. In known ischaemic heart disease, thyroxine should be introduced at low dose and increased under specialist supervision. Coronary intervention may be required to allow full replacement dosage. Most pregnant women with primary hypothyroidism require a ∼50 μg increase in thyroxine dose. This is due to increased TBG. Inadequate maternal T4 therapy may be associated with impaired cognitive development in offspring.
Myxoedema coma: This is a rare presentation of hypothyroidism in which there is depressed consciousness, usually in an elderly patient who appears myxoedematous. Body temperature may be low, convulsions are not uncommon, and CSF pressure and protein content are raised. The mortality rate is 50% and survival depends upon early recognition and treatment.
Myxoedema coma is a medical emergency and treatment must begin before biochemical confirmation of the diagnosis. Triiodothyronine is given as an i.v. bolus of 20 μg followed by 20 μg 8-hourly until there is sustained clinical improvement. After 48–72 hrs, oral thyroxine (50 μg daily) may be substituted. Unless the patient has primary hypothyroidism, the thyroid failure should be assumed to be secondary to hypothalamic or pituitary disease and treatment given with hydrocortisone 100 mg 8-hourly, pending TFT and cortisol results. Other measures include slow rewarming, cautious i.v. fluids, broad-spectrum antibiotics and high-flow oxygen with or without assisted ventilation.
ASYMPTOMATIC ABNORMAL THYROID FUNCTION TEST RESULTS
Subclinical thyrotoxicosis: TSH is undetectable, while T3/T4 is in the upper normal range. This condition is usually found in older patients with multinodular goitre. There is an increased risk of AF and osteoporosis; hence the consensus view is that such patients require therapy (usually 131I). Otherwise, annual follow-up is required, as overt thyrotoxicosis occurs in 5% annually.
Subclinical hypothyroidism: TSH is raised, while T3/T4 is in the lower normal range. Progression to overt thyroid failure is highest in those with antithyroid peroxidase antibodies or TSH >10 mU/l. This group should be treated with thyroxine to normalise TSH.
Non-thyroidal illness (‘sick euthyroidism’): TSH is low, T4 raised and T3 normal or low. Other patterns are also seen. During illness, there is decreased conversion of T4 to T3 and alterations in affinity to binding proteins. TSH may be low as a result of the illness itself or drug treatments (e.g. corticosteroids). During convalescence, TSH may increase to levels found in primary hypothyroidism. TFTs should therefore not be checked during an acute illness in the absence of clear signs of thyroid disease. If an abnormal result is found, tests should be repeated after recovery.
THYROID ENLARGEMENT
Palpable thyroid enlargement affects 5% of the population but a minority seek medical attention. Multinodular goitres and solitary nodules sometimes present with acute painful enlargement due to haemorrhage into a nodule. There are several causes of thyroid enlargement (Box 10.5). Whereas diffuse and multinodular goitre are invariably benign, there is a 1 : 20 chance of malignancy in a solitary lesion. TFTs should always be performed.
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.
Graves’ thyrotoxicosis
IgG antibodies are directed against the TSH receptors on follicular cells, stimulating hormone production and goitre formation. These TSH receptor antibodies (TRAb) can be detected in 80–95% of patients. The natural history of the disease follows one of three patterns:
There is an association of Graves’ disease with HLA-B8, DR3 and DR2. Smoking is weakly associated with Graves’ thyrotoxicosis, but strongly linked with the development of ophthalmopathy.
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.
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.
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:
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.
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.
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:
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.
Clinical features and investigations
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.
TOXIC ADENOMA
The presence of a toxic solitary nodule is the cause of <5% of cases of thyrotoxicosis. The nodule is a follicular adenoma, usually >3 cm, which secretes excess thyroid hormones. The remaining gland atrophies following TSH suppression. Most patients are female and >40 yrs old.
DIFFERENTIATED CARCINOMA
Papillary carcinoma: The most common thyroid malignancy. It may be multifocal and spread is to regional lymph nodes.
Follicular carcinoma: A single encapsulated lesion. Cervical lymph nodes spread is rare. Metastases are blood-borne and are found in bone, lungs and brain.
Management
ANAPLASTIC CARCINOMA AND LYMPHOMA
These two conditions are difficult to distinguish clinically. Patients are usually elderly women with rapidly enlarging, hard and symmetrical goitre over 2–3 mths.
MEDULLARY CARCINOMA
This tumour arises from the parafollicular C cells of the thyroid. The tumour may secrete calcitonin, 5-HT (serotonin) and adrenocorticotrophic hormone (ACTH). As a consequence, carcinoid syndrome and Cushing’s syndrome may occur.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
