A thyroid technetium scan (Figure 49.2) shows an enlarged thyroid with generally increased tracer uptake in a patchy distribution consistent with a multinodular goitre.

Figure 49.2

Q.4

What treatment should be started? How might the treatments for the thyroid and heart problems interact? What are the risks of the thyroid treatments and how should the patient be counselled?

The patient is treated with carbimazole 20 mg bd and propranolol 20 mg bd. Warfarin is started and titrated to an INR of 2–2.5. She is seen with thyroid function tests initially at 3-weekly intervals to check that the thyroid hormone levels are falling and to allow reduction of the carbimazole dose.

After 3 weeks, she reports the resolution of most of her symptoms, particularly reduced anxiety. Her heart rate is 60 and irregularly irregular consistent with atrial fibrillation. Blood tests are as follows:

Investigation 49.2 Summary of results

Q.5

What do these blood tests indicate?

The dose of carbimazole was reduced to 15 mg bd and 3 weeks later to 15 mg daily.

Six weeks later her free T4, free T3 and TSH are all normal although she remains in atrial fibrillation.

Q.6

What are the options now? What are their relative risks and benefits.

Her subsequent clinical course is described in her notes as follows (Figure 49.3):

Figure 49.3

Answers

A.1 This is consistent with atrial fibrillation (AF). Although AF can occur in otherwise healthy individuals, there is often an underlying cause including ischaemic heart disease, myocardial disease such as a cardiomyopathy, or mitral valve disease. Non-cardiac causes include thyrotoxicosis. Thyrotoxicosis is suggested here by the physical finding of a goitre.

Important historical features to suggest thyrotoxicosis include heat intolerance or excessive symptoms of feeling hot even when others are feeling cool, weight loss often with maintained or increased appetite, tremor, proximal muscle weakness, sweating, sleep disturbance, palpitations, diarrhoea, anxiety and sleep disturbance. It is important to recognize that older people may have fewer symptoms than the young but are more likely to present with cardiac features such as arrythmias, angina pectoris and, when very severe, cardiac failure. All patients with new AF should have thyroid hormone levels checked. Thyroid disease tends to run in families, particularly when there is a history of autoimmune disease. Autoimmune thyroid disease is more common in women.

It is important to ask about the recent use of iodine either as a dietary supplement such as kelp tablets or given as a component of some radiocontrast media. Some medications such as amiodarone and some cough mixtures contain large amounts of iodine which may precipitate thyrotoxicosis – the ‘Jodbasedow effect’.

A.2 Thyrotoxicosis is associated with a fine finger tremor, tachycardia, sometimes with arrhythmia which is most often atrial fibrillation, proximal muscle weakness, evident by an inability to stand from a squatting position or abduct the arms above the horizontal, and a thyroid stare accompanied by lid retraction (where the sclera is apparent above the iris on normal forward gaze) and lid lag (where the upper lid does not follow the eye down on rapid downward gaze exposing the sclera above the iris).

In addition, there may be signs of Graves’ disease including exophthalmos, proptosis or forward protrusion of the eye due to inflammatory infiltration of the muscles and other tissues behind the eye. The sclera is often apparent below the limbus on norma forward vision in this situation. The degree of eye proptosis can be measured with a portable bedside device known as an exophthalmometer.

An infiltrative skin lesion known as Graves’ dermopathy may be present, but this is far less common than thyroid or eye involvement. Graves’ dermopathy is also known as pretibial myxoedema with plaques and nodules developing over the shins. Finger clubbing, also known as thyroid acropachy, may also occur in Graves’ disease.

Many patients with thyrotoxicosis have a goitre (enlarged thyroid) which may be diffusely enlarged in Graves’ disease or have a single nodule in thyrotoxicosis due to a toxic nodule. Alternatively, a multinodular gland may be palpable.

A.3 An electrocardiogram should be obtained to confirm the clinical finding of atrial fibrillation. Measurement of serum free thyroxine (fT4), free triodothyronine (fT3) and thyroid-stimulating hormone (TSH) is necessary to confirm thyrotoxicosis. Primary thyrotoxicosis would be expected to be associated with elevated free T4 and/or free T3 and suppression of pituitary sourced TSH by negative feedback.

A thyroid radioisotope (technetium or I-123) scan will assist in differential diagnosis. In this case thyroid uptake of tracer, which is treated like normal iodine by the thyroid iodine uptake mechanism, would be expected to be increased in a pattern consistent with multiple nodular hyperactivity although there may also be nodules with reduced uptake.

Check for TSH receptor antibodies. These are antibodies that stimulate the TSH receptor and lead to excessive TSH-independent thyroid hormone hypersecretion and the thyroid gland growth pathognomic of Graves’ disease.

A.4 Treatments for primary hyperthyroidism include antithyroid drugs which inhibit thyroid hormone synthesis, thyroid destructive therapy such as radioactive iodine or surgery. Often, antithyroid drugs, from the thionamide class (e.g. carbimazole or propylthiouracil) are used to achieve a euthyroid state. Permanent destructive thyroid therapy can be used once the patient has stabilized.

AF and other tachyarrythmias can be treated with beta blockade. Beta blockade also controls many other thyrotoxic features such as tremor and anxiety which represent excessive activity of the sympathetic nervous system. For this reason, non-selective beta blockers, usually propranolol, are the drugs of choice.

AF entails a significant risk of embolization with a substantial risk of stroke which can be reduced by anticoagulation with warfarin. Doses required to produce therapeutic anticoagulation are generally smaller in thyrotoxicosis as thyroid hormone increases the clearance of vitamin-K dependent clotting factors.

It is necessary to counsel her about the risks of thioamide drugs. Agranulocytosis is a rare but serious complication. She should present promptly if she develops sore throat and fever! More common side-effects include skin rash or nausea. Hepatitis occurs rarely.

A.5 These tests reveal a mild persistent elevation of T3 consistent with persistent thyrotoxicosis but substantial resolution of the hyperthyroxinaemia. The TSH is suppressed by negative feedback from high T4 and T3 levels. This suppressive effect may persist for several months, even after T4 and T3 levels are normalized.

Mild neutropenia is often seen in thyrotoxicosis and does not necessarily signify an idiosyncratic effect of thionamides.

A.6 Options include ongoing antithyroid drugs, radioactive iodine or surgery. Patient preference plays a role in therapy selection and there is marked variation in approaches and acceptance of therapies internationally.

If a permanent thyroid destructive treatment is used, radioiodine is preferred, as treatment has minimal immediate risk. Radioiodine given as I-131 is a beta particle emitter that destroys functioning thyroid tissue after uptake by the sodium-iodine symporter. The mean time to euthyroidism is approximately 8 weeks. Therapy can be given as an outpatient. The half-life of I-131 is approximately 6 days and some precautions are advised to minimize unnecessary radiation exposure to others. No long-term side-effects such as tumours have been observed in treated patients. However, some cases of progression of thyroid eye disease have been described.

Surgery involves subtotal thyroidectomy and risks damaging neighbouring structures such as the recurrent laryngeal nerve leading to hoarseness and the parathyroids leading to hypoparathyroidism, as well as the usual risks of surgery and general anaesthesia. It’s useful for those with very large goitres although a reduction in thyroid size is usual after radioiodine.

Issues to Consider

• Which causes of thyrotoxicosis do not lead to reduced uptake of radiotracer?

• What are the different types of thyroid cancer?

• What is a symporter?

• What is a thyroid storm? How is it managed?

Further Information

www http://www.thyroidmanager.org/. Website covering management of thyroid disease in many sections. Available also via the Endotext website (http://www.endotext.org/)

www http://www.endocrineweb.com. A US based patient centred site but with a lot of well written articles on a whole range of endocrine disorders