Clinical features

Goitre is a visible or palpable enlargement of the thyroid (Fig. 20.4). The swelling appears in the lower part of the neck and retains the shape of the normal gland (thyreos – Greek for shield). The swelling characteristically moves upwards on swallowing because of the gland’s attachment to the trachea. Patients may have a dry mouth, and when asking them to swallow, water should be provided.

Fig. 20.4 Massive goitre.

‘Physiological’ enlargement

Transient enlargement may occur during puberty or pregnancy.

Aetiology

This common disease occurs endemically in areas of iodine deficiency, but can be sporadic or a reaction to drugs. It occurs much more commonly in females. In the past, lack of iodine in the diet was a common cause of thyroid enlargement, but ‘endemic goitres’ in populations where iodine was deficient are now rare because table salt is iodized.

Pathology

In iodine deficiency, the gland initially enlarges diffusely as the follicles fill with colloid. Later, multiple nodules develop, some of which contain abundant colloid; others show degenerative changes, with the formation of cysts, areas of old and new haemorrhage, and even calcification. The goitre varies greatly in size, from little more than normal to weighing several hundred grams. The whole gland may be involved, or the changes may be confined to one lobe.

Clinical features

Most multinodular goitres are asymptomatic. Others cause tracheal compression and dyspnoea, particularly when they extend behind the sternum (retrosternal goitre). Oesophageal compression can cause dysphagia. Very rarely, bleeding into a nodule may cause pain and rapid enlargement and, for retrosternal goitre, respiratory distress. The thyroid is visibly enlarged and multiple nodules are usually palpable. Sometimes only one nodule is palpable, giving the erroneous impression of a solitary nodule.

Investigations

In the case of retrosternal goitre, plain films of the thoracic inlet may reveal tracheal deviation (Fig. 20.5A) and CT may show tracheal compression (Fig. 20.5B) The presence of stridor indicates compromise of the tracheal lumen. T₃, T₄ and TSH are usually normal and that being the case isotope scans are not indicated.

Fig. 20.5 Retrosternal goitre images showing marked tracheal deviation.

A Plain X-ray. B CT.

Management

The administration of thyroxine rarely prevents further gland enlargement via the negative feedback loop. Large goitres and those causing symptoms of compression require total or subtotal thyroidectomy. Some patients request surgery for cosmetic reasons. Patients usually choose total thyroidectomy with lifelong replacement therapy in preference to the high chance of recurrence and the need for reoperation with subtotal thyroidectomy.

Subacute thyroiditis (de Quervain’s disease)

This rare condition is associated with an influenza-like illness, during which there is painful diffuse swelling of the gland. Thyroid antibodies may appear in the serum. The disease may be due to a viral infection and usually resolves spontaneously.

Autoimmune thyroiditis (Hashimoto’s disease)

Riedel’s thyroiditis

In this very rare condition the thyroid is replaced by dense fibrous tissue, resulting in a firm painless swelling and tracheal compression. The cause is unknown. Surgery is reliably difficult but decompression of the trachea may be required.

Pathophysiology

This condition accounts for 75% of cases. It is an autoimmune disease in which TSH receptors in the thyroid are stimulated by circulating thyroid receptor antibodies (TRAbs). The gland is uniformly hyperactive, very vascular and usually symmetrically enlarged. Histologically, there is marked epithelial proliferation, with papillary projections into follicles devoid of colloid. TRAbs can cross the placental barrier, so that neonatal thyrotoxicosis can occur.

Clinical features

The patient is usually a young female (male:female ratio 1:8) and the condition can be familial. The thyroid is usually moderately and diffusely enlarged and soft, and because of its vascularity a bruit may be audible. High circulating levels of T₃ and T₄ increase the basal metabolic rate and potentiate the actions of the sympathetic nervous system.

Other features

Exophthalmos is usual but not invariable (Fig. 20.7). Ophthalmoplegia, pretibial myxoedema, proximal muscle myopathy and finger clubbing are sometimes present. Menstrual irregularity and infertility can occur.

Fig. 20.7 Thyroid-associated ophthalmopathy.

(Courtesy of Prof Michael Sheppard, University of Birmingham Medical School.)

Diagnosis

The diagnosis is usually obvious clinically, although in patients with anxiety, distinction from neurosis can be difficult. Raised T₃ and T₄ levels, coupled with low TSH levels, are confirmatory. The TSH response to intravenous injection of TRH is absent owing to atrophy of the TSH-producing cells of the pituitary.

Management

Pathophysiology

A toxic multinodular goitre is responsible for thyrotoxicosis in about 25% of patients. There is usually a long-standing non-toxic goitre in which one or more nodules become hyperactive and begin to hyperfunction independently of TSH levels. A single hyperfunctioning adenoma is a rare cause of thyrotoxicosis (1–2% of patients). The adenoma secretes thyroid hormones autonomously; TSH secretion and the remainder of the gland are suppressed.

Clinical features

Toxic multinodular goitre is more common in older women, and cardiac complications such as arrhythmias are particularly frequent. Eye signs are rare in these patients.

Diagnosis

In a toxic multinodular goitre, the isotope scan demonstrates one or more areas of increased uptake. In toxic adenoma, the nodule is ‘hot’ and the remainder of the gland is ‘cold’.

Management

Treatment consists of removal of the hyperfunctioning glandular tissue by total thyroidectomy (multinodular goitre) or lobectomy (toxic adenoma), or if surgery is contraindicated, radioiodine.

Clinical features

This tumour is most prevalent before the age of 40 years and presents as a slow-growing solitary thyroid swelling. Enlarged lymph nodes are palpable in one-third of patients and may be the only finding in some patients with a microscopic primary (the so-called ‘lateral aberrant thyroid’). Distant metastases are rare. In thyroid glands resected for non-malignant causes, microscopic papillary carcinoma is discovered as an incidental finding in up to 20%. Histologically, complex papillary folds lined by several layers of cuboidal cells project into what appear to be cystic spaces.

Management

The disease is commonly multifocal, so bilateral total lobectomy is commonly indicated. Microscopic disease (< 1cm and unifocal) and tumours with favourable histology and < 2cm in size may be treated by single lobectomy alone. Involved lymph nodes, usually identified by preoperative ultrasound scanning, are removed according to selective anatomical compartments, but routine radical neck dissection is unnecessary. Thyroid replacement therapy (T₃, 20 μg 6–8-hourly, or thyroxine 150 μg/day) is given with the intention of suppressing TSH. Widespread metastases are rare but may be amenable to radioactive iodine therapy. For this reason an isotope scan should be performed postoperatively to identify any iodine uptake in the neck or elsewhere. The disease has an excellent prognosis, with 10-year survival rates approaching 90%.

Clinical features

This disease typically presents as a solitary thyroid nodule in patients aged 30–50 years. Lymph node metastases are much less common than haematogenous spread, with deposits in the lungs, bone or liver (Fig. 20.8). Histologically, malignant cells are arranged in solid masses with rudimentary acini. Vascular and capsular invasion characterize this neoplasm and distinguish it from a benign follicular adenoma.

Fig. 20.8 Metastatic follicular cancer.

A Primary tumour. B Bony metastases (arrowed).

Management

Treatment consists of total thyroidectomy with preservation of the parathyroids. If a postoperative radioisotope scan (challenge scan) reveals increased uptake in the skeleton or neck, therapeutic doses of radioiodine are given. Prior to challenge scanning the short half-life hormone T3 should be given and once all treatment is completed T₄ is administered to suppress TSH secretion. Plasma thyroglobulin levels should be undetectable after surgery and radioiodine therapy. Subsequent detection of thyroglobulin indicates recurrent disease. The disease is more aggressive than papillary carcinoma and the 10-year survival rate is 75%.

Clinical features

These rapidly growing, highly malignant tumours tend to occur in older patients. Local invasion may involve the recurrent laryngeal nerve(s) and cause hoarseness, the trachea causing dyspnoea and stridor, and the oesophagus causing dysphagia. Invasion of the cervical sympathetic nerves may cause Horner’s syndrome (contraction of the pupil, enophthalmos, narrowing of the palpebral fissure and loss of sweating on the face and neck). Pulmonary metastases are common.

Management

Resection is rarely appropriate but surgery can relieve tracheal compression. External beam radiotherapy may be of value but chemotherapy seldom is.

Clinical features

This tumour arises from the parafollicular C cells. There is hard enlargement of one or both thyroid lobes, and in 50% of patients the cervical lymph nodes are involved. The tumour may occur sporadically or as part of an inherited multiple endocrine neoplasia (MEN) syndrome type II (Sipple’s syndrome). Calcitonin levels are elevated, and can be used to monitor progress and screen relatives. The gene causing the inherited form of this tumour is the Ret proto-oncogene, and the finding of a mutation allows the diagnosis to be made at any age. Prophylactic thyroidectomy for affected children is recommended at different ages depending on the specific mutation and level of risk associated with that mutation. This varies from age 1 for the 918 mutation through to age 5 for the commonest 634 mutation and in some good prognosis families may be delayed to age 13.

Management

Treatment consists of total thyroidectomy and, if the calcitonin level is raised, dissection of the lymph nodes in the central compartment of the neck (levels 6 and 7). Medullary carcinoma in MEN IIb syndrome (918 mutation) is particularly aggressive, and those affected rarely live beyond 30–40 years of age. Other forms, e.g. pure inherited medullary thyroid cancer occurring without other endocrine tumours, can be very indolent. Preoperative CT of the neck and mediastinum is advised and the exclusion of a phaeochromocytoma before neck surgery is mandatory.

Technique

The gland is exposed through a transverse skin-crease incision placed 2–3 cm above the sternal notch. The deep cervical fascia is divided longitudinally in the midline and the strap muscles are separated. Each lobe is mobilized by dividing the vessels supplying the superior pole, the middle and inferior thyroid veins, and the inferior thyroid artery. It is quick, easy and safe to do this using for example the harmonic scalpel in place of liagatures or clips. The recurrent laryngeal nerves should be identified, so that they can be protected from injury. Generally nothing less than a total lobectomy should be performed, to avoid the need for reoperation on that side. Care is taken to preserve the parathyroid glands. Haemostasis must be meticulous and drains are rarely necessary. The layers of the neck are reconstituted with continuous absorbable sutures and the skin with a subcuticular suture. Minimally invasive thyroidectomy is being explored in the minority of very small goiters.

Complications

Patient information

A forewarned patient is much less aggrieved than one who learns about previously unmentioned complications on the first postoperative day. Full informed consent should be obtained by the surgeon who will carry out the procedure and should describe the potential complications with their own complication rates and information on how these compare with national averages. Explanations should be given in simple language and should be full and honest. Written advice may better inform the patient who may have accessed the Internet which may not provide accurate and appropriate information.

Hypercalcaemia and hypocalcaemia

Hypercalcaemia is a common biochemical abnormality and may be due to many causes other than excess PTH secretion (Table 20.1). Similarly, hypocalcaemia may be due to causes other than parathyroid removal or damage (Table 20.2).

Table 20.1 Causes of hypercalcaemia

Pathophysiology

Functioning pituitary adenomas may result from over-stimulation by hypothalamic factors. Initially small and confined within the gland (microadenomas), they grow slowly and can ultimately expand the sella turcica. Eccentric enlargement is common. Upward extension of the adenoma may stretch the diaphragm or herniate through it, to compress the optic chiasma and cause visual defects. It is therefore important that pituitary adenomas are detected before they enlarge the fossa or extend above it. CT with contrast enhancement and MRI (Fig. 20.12) are used to image the tumour. Three endocrine syndromes caused by anterior pituitary disorders have surgical relevance.

Fig. 20.12 MRI scan showing a pituitary tumour (arrow).

Pathophysiology

The neurohypophysis is part of a secretory and storage unit that includes the nerve cells of the supraoptic and paraventricular hypothalamic nuclei (Fig. 20.14). Fibres pass from these nuclei via the hypothalamo-hypophysial tract to the median eminence of the hypothalamus and posterior pituitary. The nerve cells secrete arginine vasopressin (antidiuretic hormone, ADH) and oxytocin, both of which pass down the nerve fibres to be stored in vesicles in the pituitary. The close anatomical relationship of the anterior and posterior pituitary has functional significance in that oxytocin release during lactation is paralleled by increased TSH and prolactin production, and the posterior pituitary may influence prolactin secretion by dopamine release.

Fig. 20.14 The neurohypophysial system.

Clinical features

Cushing’s syndrome occurs most frequently in young women. The most striking feature is truncal obesity, a ‘buffalo hump’ (due to redistribution of water and fat) and ‘mooning’ of the face (Fig. 20.20). Cushing’s original description was a ‘tomato head, potato body and four matches as limbs’. As a result of protein loss, the skin becomes thin, with purple striae, dusky cyanosis and visible dermal vessels. Proximal muscle weakness is prominent. Other features include increased capillary fragility, purpura, osteoporosis, acne, loss of libido, hirsutism, diabetes, hypertension and amenorrhoea. The clinical signs develop insidiously over years and sometimes are only fully appreciated when the patients and their family review old photographs. In some cases, the disease runs a fulminant course, particularly when due to an adrenal carcinoma or ectopic ACTH secretion. Electrolyte disturbances, cachexia, pigmentation, severe diabetes and psychosis are common in these patients.

Fig. 20.20 Features of Cushing’s syndrome.

A Moon face and puffy eyes. B Papery skin with striae and a propensity to bruising, muscle wasting of limbs and centripetal obesity.

(Courtesy of Prof Michael Sheppard, University of Birmingham Medical School.)

Investigations

Before proceeding to adrenalectomy, the surgeon must be convinced that:

Fig. 20.21 The principle of the dexamethasone test in differentiating between adrenal and pituitary causes of excess cortisol secretion.

Fig. 20.22 CT of an adrenal tumour (arrow).

Management

Primary hyperaldosteronism (Conn’s syndrome)

This is usually due to a benign adenoma and is most common in young or middle-aged women. The adenoma is small, single, canary yellow on bisection and composed of cells of the glomerulosa type. Only rarely is the syndrome due to bilateral adrenal hyperplasia or multiple microadenomas. The high circulating levels of aldosterone suppress renin secretion – a helpful biochemical diagnostic observation.

Secondary hyperaldosteronism

Hyperaldosteronism is most commonly secondary to excessive renin secretion (and stimulation of the zona glomerulosa by angiotensin) in chronic liver, renal or cardiac disease.

Pathophysiology

This syndrome is due to one of a number of genetically determined enzyme defects that impair cortisol synthesis. The resultant increase in pituitary ACTH production causes adrenal hyperplasia and inappropriate adrenal androgen secretion.

Clinical features

The effects depend on the patient’s sex and age. Female infants show enlargement of the clitoris and varying fusion of the labial folds. Later, other signs of virilism appear, leading to precocious heterosexual puberty. Young boys have precocious isosexual puberty. In both sexes, growth is at first rapid, but the epiphyses fuse early so that the final height is stunted. Excess muscle growth produces an ‘infant Hercules’ appearance. Milder forms of the disease may affect older girls and cause hirsutism and acne.

Management

The patient is given cortisol for replacement purposes and to suppress ACTH production. Surgical correction of the genital abnormality may be needed. Rarely, virilism is due to an adrenal tumour, which is usually large and malignant.

Pathophysiology

The adrenal medulla is not essential for life. There are other collections of chromaffin cells in paraganglia in the retroperitoneum, mediastinum and neck that release noradrenaline (norepinephrine). The normal adrenal medulla secretes catecholamines in the ratio 80% adrenaline to 20% noradrenaline. It also secretes the noradrenaline precursor, dopamine. Small amounts of catecholamines are excreted in the urine in free and conjugated form. Larger amounts are excreted as metnoradrenaline and 3-methoxy-4-hydroxymandelic acid (VMA).

Pathology

Phaeochromocytomas are tumours either of the adrenal medulla (80%) that secrete large amounts of adrenaline (epinephrine) and noradrenaline (norepinephrine), or of the extra-adrenal paraganglionic tissue (20%) that secrete only noradrenaline. Virtually all (99%) arise within the abdomen, 10% are multiple and 10% are malignant. Benign tumours are usually chocolate-brown and highly vascular. Associated conditions are neurofibromatosis, medullary carcinoma of the thyroid (as part of MEN type II), duodenal ulcer and renal artery stenosis. If it presents in pregnancy, phaeochromocytoma can be mistaken for hypertension of pregnancy and may cause maternal and fetal mortality. Genetic testing for predisposition syndromes such as SDHB, C and D should be done in all patients under 50.

Clinical features

The median age for presentation of phaeochromocytomas is 40 years. Excess noradrenaline secretion causes hypertension; adrenaline excess has metabolic effects (e.g. diabetes and thyrotoxicosis). Paroxysmal hypertension is a very characteristic symptom; due to the sudden release of catecholamines. It may be precipitated by abdominal pressure, exercise stress or postural change. During a paroxysm the blood pressure may rise to 200/100 mmHg and there is headache, palpitation, sweating, extreme anxiety, chest and abdominal pain. Pallor, dilated pupils and tachycardia are prominent features. In some patients, persistent and severe hypertension develops at the age of 30–40 years, often in association with severe retinopathy, which can cause optic atrophy and blindness. Glycosuria is common. The skin may be mottled, with tingling of the extremities. Extra-adrenal phaeochromocytomas are also associated with persistent hypertension. On rare occasions, the tumour is in the bladder, and micturition may precipitate a syncopal attack. A few patients present with predominantly metabolic effects, such as those found in thyrotoxicosis. Occasionally, a phaeochromocytoma may cause sudden and unexplained death after trauma or during surgery, owing to severe hypertension causing a cerebrovascular accident or by precipitating a fatal arrhythmia.

Investigations

All young hypertensive patients (age < 40 years) should be screened for a catecholamine-secreting tumour. Twenty-four hour or overnight collections of urine should be analysed for metadrenaline and normetadrenaline levels. A CT or MRI may show the tumour. It may also be demonstrated by scintigraphy after giving radio-iodine-labelled metaiodobenzylguanidine (MIBG), a catecholamine precursor taken up by sites of synthesis (Fig. 20.23).

Fig. 20.23 Extra-adrenal phaeochromocytoma.

A MIBI scan. B CT scan.

Management

Surgical removal of the tumour is the treatment of choice. The use of α- and β-blocking drugs has greatly reduced the risk of hypertensive crisis, tachycardia and arrhythmias during induction of anaesthesia or tumour handling. The patient should come to operation with blood pressure and pulse rate controlled. Adrenergic blockade also allows restoration of blood volume, so that sudden hypotension after removal of the tumour is unusual. To achieve blockade, an α-adrenergic receptor blocker such as phenoxybenzamine or doxazosin should be used, with incremental dose escalation according to response A typical starting dose for doxazocin would be 1 mg 12-hourly, building up to 6 or 8 mg a day until hypertension is controlled and postural symptoms occur.

Once and only once α-blockade has been established, unopposed β effects, such as tachycardia, may become evident and are treated with a β-blocker such as propranolol. β-blockade should not be instituted first, as this may allow unopposed α-agonist effects, which may make hypertension worse and precipitate heart failure.

Peroperatively, short-acting α- and β-blocking agents and sodium nitroprusside (which acts directly on vessels independent of adrenergic receptors and gives additional control of hypertension) should be available.

Ganglioneuromas

These are benign, firm, well-encapsulated tumours of ganglion cells. They grow slowly, may become large and can cause diarrhoea. Surgical excision gives excellent results.

Neuroblastomas

These are highly malignant tumours arising from sympathetic nervous tissue. They are one of the most common malignant tumours of infancy and childhood, and metastasize widely. About 75% secrete catecholamines. Treatment by radical excision, radiotherapy and chemotherapy offers the only hope of cure, although spontaneous regression has been reported.

Indications

Indications for adrenalectomy include adrenal adenomas producing Cushing’s syndrome, Conn’s syndrome or excess catecholamines (phaeochromocytoma). Bilateral adrenalectomy may be needed for bilateral tumours, nodular hyperplasia producing Conn’s or Cushing’s syndrome, and if pituitary surgery fails to cure Cushing’s disease.

Technique

The approach of choice is laparoscopically by the transperitoneal or posterior route. The exception to this is the known or suspected adrenal malignancy. If an open approach is required then the anterior transperitoneal route requires a large incision, inevitably causes ileus, and has a high incidence of wound and respiratory complications (especially in patients with Cushing’s syndrome).

Large tumours which may be malignant are best approached through a flank incision, after removing a rib to allow access; if possible, the diaphragm, pleura and peritoneum are left intact.

The open posterior approach through the bed of the 11th or 12th rib is technically more difficult, but has low morbidity and patients return to normal activity more quickly. If the pleura is breached in the course of adrenalectomy, it can be repaired on closing the wound, ensuring that the lung is fully inflated. There is no need for pleural or wound drains.

Adrenalectomy, however, is best carried out using minimally invasive techniques. The usual route is anteriorly, beneath the costal margins, transperitoneally with reflection of liver on the right and spleen, pancreas and colon on the left. The adrenal vein can often be divided early in laparoscopic surgery which, in phaeochromocytomas, prevents catecholamines from circulating, thereby reducing blood pressure swings following manipulation of the tumour. It is occasionally necessary to convert to an open procedure if bleeding is encountered or there are other technical or access problems. The posterior extra peritoneal approach is gaining popularity.

Replacement therapy

Corticosteroid replacement is needed for life after bilateral total adrenalectomy, but may not be needed permanently after unilateral adrenalectomy. Replacement is best achieved by a combination of oral hydrocortisone (30 mg daily in divided doses) and the mineralocorticoid fludrocortisone acetate (0.1 mg daily). If both adrenals are removed or the remaining adrenal is non-functional, the operation must be covered by commencing steroid replacement at the time of surgery. Adequacy of replacement is assessed by serum levels and response to the dexamethasone test.

Doses of hydrocortisone are given intravenously until the patient can take oral steroid. It cannot be overemphasized that blood pressure is the best early guide to adequacy of therapy. If hypotension occurs, 100 mg hydrocortisone is given immediately by intravenous injection, followed by 100 mg every 6–8 hours All adrenalectomized patients must be warned to increase the dose of steroid if stress or infection occurs. Failure to anticipate the need for added steroid may precipitate an ‘adrenal crisis’, with acute hypotension and collapse. Such patients should carry a ‘steroid card’ giving details of dosage and possible complications, and should be able to recognize the symptoms of adrenal insufficiency (i.e. loss of appetite, nausea, cramps, muscle pains and malaise). If such symptoms occur, the patient should take an extra two tablets of hydrocortisone and seek urgent medical help.

Patient information

Although adrenal cortical function is vital for life, patients are unlikely to have heard of the adrenal glands. Adrenal tumours occur at a rate of about 1 per million population per annum, so patients may not have an awareness of cortisone or adrenaline. It is necessary to discuss the technicalities of surgery and the approach to be used, and to forewarn patients that a laparoscopic procedure may have to be converted to an open one. Complications should be minimal, but it is essential to mention blood loss and common complications as well as ones which though rare have a major impact on quality of life.

One of the most important features to describe will be any requirement for steroid replacement therapy (necessary after bilateral adrenalectomy, unilateral adrenalectomy

for an adenoma producing Cushing’s syndrome, and after pituitary surgery) and the need for dosage increase at times of stress (e.g. other surgery) or intercurrent illness (e.g. pneumonia).

MEN type I

This is characterized by hyperplasia and/or adenomas of the parathyroid, pancreatic islets and anterior pituitary. There may also be non-functioning tumours of the thyroid, pituitary, adrenal cortex and soft tissues (lipomas), and functioning carcinoid tumours of the gut or lungs. The earliest biochemical sign in affected individuals is usually hypercalcaemia from hyperparathyroidism or hyperprolactinaemia from an asymptomatic pituitary tumour. Families are often uncovered when an index patient presents dramatically with small bowel perforation or bleeding due to the Zollinger–Ellison syndrome, or with hypoglycaemia due to an insulinoma of the pancreas. Family members should be screened by measurement of fasting serum calcium and other hormonal markers such as prolactin. Mutations in the MENIN gene on chromosome 11 can be detected. A bracelet may be worn to alert medical attendants to the condition. Treatment is directed at the dominant clinical or biochemical feature. For example, pancreatic endocrine tumours are localized by endoscopic ultrasonography or CT and removed as necessary. Hypercalcaemia is treated by parathyroid surgery, where either all diseased glands are excised, followed by calcium replacement therapy, or by subtotal (three and half glands) parathyroidectomy, when replacement therapy can be avoided, but recurrence of the remnant to a hyperfunctioning state at some later date is inevitable.

MEN type II

This is characterized by medullary carcinoma of the thyroid, phaeochromocytoma and parathyroid hyperplasia. Genetic diagnosis, based on a mutation in Ret proto-oncogene chromosome 10, obviates the need for biochemical testing in family members. Unlike in MEN I, there is advantage in prophylactic surgery with affected individuals undergoing total thyroidectomy at an age dictated by the mutation identified and the level of risk associated with that mutation. Kindred members not showing the mutation can be dismissed from follow-up and can be reassured that they will not pass on the genetic abnormality to their offspring. Phaeochromocytomas are diagnosed by annual screening using urinary and or plasma metadrenaline and normetadrenaline levels, and localized by CT and MIBG scanning. Surgical treatment of the phaeochromocytoma must take precedence over the thyroid and parathyroid disease, as anaesthesia and surgery in patients with undiagnosed or untreated phaeochromocytoma can be life-threatening.