Hyperthyroidism(thyrotoxicosis)

Hypothyroidism

Enlargement of thyroid (goitre or thyroid nodule)

The most common causes are

Graves’ disease

Multinodular goitre

Solitary thyroid adenoma

Iodide-induced

Drugs (amiodarone)

Radiographic contrast media

Iodine prophylaxis programme2

Extrathyroidal source of thyroid hormone Factitious thyrotoxicosis

Struma ovarii

TSH-induced

TSH-secreting pituitary adenoma Choriocarcinoma and

hydatidiform mole

Follicular carcinoma ± metastases

COMMONSymptoms

Weight loss despite normal or increased appetite

Heat intolerance, sweating

Palpitations, tremor

Dyspnoea, fatigue

Irritability, emotional lability

Signs Weight loss

Tremor

Palmar erythema

Sinus tachycardia

Lid retraction, lid lag

Less commonSymptoms

Osteoporosis (fracture, loss of height)

Diarrhoea, steatorrhoea

Angina

Ankle swelling

Anxiety, psychosis

Muscle weakness

Periodic paralysis (predominantly in Chinese)

Pruritus, alopecia

Amenorrhoea/oligomenorrhoea

Infertility, spontaneous abortion

Loss of libido, impotence

SIGNS

Excessive lacrimation

Goitre with bruit

Atrial fibrillation

Systolic hypertension/increased pulse pressure

Cardiac failure

Hyper-reflexia

Ill-sustained clonus

Proximal myopathy

Bulbar myopathy

The first-line investigations are

serum T3, T4 and TSH

In most patients, serum T3 and T4 are both

elevated

Serum TSH is undetectable in primary

thyrotoxicosis, but values can be raised in the

very rare syndrome of secondary thyrotoxicosis

caused by a TSH-producing pituitary adenoma.

When biochemical thyrotoxicosis has been confirmed,

further investigations should be undertaken to

determine the underlying cause, including

Measurement of TSH receptor antibodies (TRAb,

elevated in Graves’ disease)

isotope scanning

Non-specific laboratory abnormalities in

thyrotoxicosis: Serum enzymes: raised alanine aminotransferase, γ-

glutamyl transferase (GGT), and alkaline phosphatasefrom liver and bone

Raised bilirubin

Mild hypercalcaemia

Glycosuria: associated diabetes mellitus, ‘lag storage’ glycosuria

An ECG may demonstrate sinus tachycardia or atrial

fibrillation.

Occasionally, patients induce ‘factitious

thyrotoxicosis’ by consuming excessive amounts of a

thyroid hormone preparation, most often

levothyroxine. The exogenous thyroxine suppresses

pituitary TSH secretion and hence iodine uptake,

serum thyroglobulin and release of endogenous

thyroid hormones. The T4:T3 ratio (typically 30 : 1 in

conventional thyrotoxicosis) is increased to above 70 : 1

because circulating T3 . The combination of negligible

iodine uptake, high T4:T3 ratio and a low or

undetectable thyroglobulin is diagnostic.

Definitive treatment of thyrotoxicosis depends

on the underlying cause and may include

antithyroid drugs, radioactive iodine or surgery.

A non-selective β-adrenoceptor antagonist (β-

blocker), such as propranolol (160 mg daily) or

nadolol (40–80 mg daily), will alleviate but not

abolish symptoms in most patients within 24–48

hours. Beta-blockers should not be used for long-

term treatment of thyrotoxicosis

Graves’ disease can occur at any age but is

unusual before puberty and most commonly

affects women aged 30–50 years

Pathophysiology

The thyrotoxicosis results from the production of

IgG antibodies directed against the TSH receptor

on the thyroid follicular cell, which stimulate

thyroid hormone production and proliferation of

follicular cells, leading to goitre in the majority

of patients. These antibodies are termed

thyroid-stimulating immunoglobulins or TSH

receptor antibodies (TRAb) and can be detected

in the serum of 80–95% of patients with Graves’

disease.

For patients under 40 years of age, most

clinicians adopt the empirical approach of

prescribing a course of carbimazole and

recommending surgery if relapse occurs,

while 131I is employed as first- or second-line

treatment in those aged over 40.

Antithyroid drugs:should be introduced at high doses (carbimazole 40–60 mg daily or propylthiouracil400–600 mg daily). Usually, this results in subjective improvement within 10–14 days and renders the patient clinically and biochemically euthyroid at 3–4 weeks. At this point, the dose can be reduced and titrated to maintain T4 and TSH within their reference range. In most patients, carbimazole is continued at 5–20 mg per day for 12–18 months in the hope that remission will occur. Patients with thyrotoxicosis relapse in at least 50% of cases, usually within 2 years of stopping treatment. Rarely, T4 and TSH levels fluctuate between those of thyrotoxicosis and hypothyroidism at successive review appointments, despite good drug compliance, presumably due to rapidly changing concentrations of TRAb. In these patients, satisfactory control can be achieved by blocking thyroid hormone synthesis with carbimazole 30–40 mg daily and adding levothyroxine100–150 µg daily as replacement therapy

Thyroid surgery:

Patients should be rendered euthyroid with

antithyroid drugs before operation. Potassium

iodide, 60 mg 3 times daily orally, is often added

for 2 weeks before surgery to inhibit thyroid

hormone release and reduce the size and

vascularity of the gland, making surgery

technically easier.

Radioactive iodine:131I is administered orally as a single dose, and is

trapped and organified in the thyroid. Although 131I decays within a few weeks, it has long-lasting inhibitory effects on survival and replication of follicular cells.

This regimen is effective in 75% of patients within 4–12 weeks. During the lag period, symptoms can be controlled by a β-blocker or, in more severe cases, by carbimazole. However, carbimazole reduces the efficacy of 131I therapy because it prevents organification of 131I in the gland, and so should be avoided until 48 hours after radio-iodine administration. If thyrotoxicosis persists after 6 months, a further dose of 131I can be given.

This condition is immunologically mediated but the autoantigen has not been identified. Within the orbit (and the dermis) there is cytokine-mediated proliferation of fibroblasts which secrete hydrophilic glycosaminoglycans. The resulting increase in interstitial fluid content, combined with a chronic inflammatory cell infiltrate, causes marked swelling and ultimately fibrosis of the extraocular muscles and a rise in retrobulbarpressure. The eye is displaced forwards (proptosis, exophthalmos and in severe cases there is optic nerve compression.

The most frequent presenting symptoms are related

to increased exposure of the cornea, resulting from

proptosis and lid retraction. There may be

excessive lacrimation made worse by wind and

bright light, a ‘gritty’ sensation in the eye

Severe inflammatory episodes are treated with

glucocorticoids (e.g. daily oral prednisolone or pulsed IV

methylprednisolone) and sometimes orbital

radiotherapy.Loss of visual acuity is an indication for

urgent surgical decompression of the orbit. In ‘burnt-

out’ disease, surgery to the eyelids and/or ocular

muscles may improve conjunctival exposure, cosmetic

appearance and diplopia.

Atrial fibrillation occurs in about 10% of patients with thyrotoxicosis. The incidence increases with age, so that almost half of all males with thyrotoxicosis over the age of 60 are affected. Moreover, subclinical thyrotoxicosis is a risk factor for atrial fibrillation. Characteristically, the ventricular rate is little influenced by digoxin, but responds to the addition of a β-blocker. Thromboembolic vascular complications are particularly common in thyrotoxicatrial fibrillation so that anticoagulation with warfarin is required, unless contraindicated. Once thyroid hormone and TSH concentrations have been returned to normal, atrial fibrillation will spontaneously revert to sinus rhythm in about 50% of patients, but cardioversion may be required in the remainder.

This is a rare but life-threatening complication of thyrotoxicosis. The most prominent signs are fever, agitation, confusion, tachycardia or atrialfibrillation and, in the older patient, cardiac failure. It is a medical emergency, which has a mortality of 10% despite early recognition and treatment. Thyrotoxic crisis is most commonly precipitated by infection in a patient with previously unrecognised or inadequately treated thyrotoxicosis. It may also develop shortly after subtotal thyroidectomy in an ill-prepared patient or within a few days of 131I therapy, when acute irradiation damage may lead to a transient rise in serum thyroid hormone levels.

Patients should be rehydrated and given propranolol, either orally (80 mg 4 times daily) or intravenously (1–5 mg 4 times daily). Sodium ipodate (500 mg per day orally) will restore serum T3 levels to normal in 48–72 hours. This is a radiographic contrast medium which not only inhibits the release of thyroid hormones, but also reduces the conversion of T4 to T3 and is, therefore, more effective than potassium iodide or Lugol’ssolution.Oral carbimazole 40–60 mg daily should be given to inhibit the synthesis of new thyroid hormone.After 10–14 days the patient can usually be maintained on carbimazole alone.