Graves’ disease

Published on 02/04/2015 by admin

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Last modified 22/04/2025

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136 Graves’ disease

Instruction

Look at this patient.

Determine this patient’s thyroid status.

Salient features

• Patient is fidgety and restless.

Examination

Proceed as follows: Hands:

• While shaking hands with the patient note the warm sweaty palms.

• Look for tremor, thyroid acropachy (Fig. 136.1; a hypermetabolic state leading to axial bone destruction; do not confuse it with clubbing, which is usually painless), onycholysis (Plummer’s nails), vitiligo and palmar erythema.

• Check pulse for tachycardia or the irregularly irregular pulse of atrial fibrillation.

Fig. 136.1 Rare thyroid acropachy.

(With permission of Kronenberg et al. 2008.)

• Comment on proptosis (after looking at the eyes from behind and above)

• Check for lid lag

• Check for scars of previous tarsorraphy.

• Mention previous thyroidectomy scar if present

• Examine the neck for goitre and auscultate over the gland.

• Gynaecomastia can occur in men as a result of increased oestrogen production.

• Examine the cardiovascular system: sinus tachycardia, widened pulse pressure, loud first heart sound, third heart sound, systolic murmur, atrial fibrillation.

• Examine the shins for pretibial myxoedema (bilateral pinkish, brown dermal plaques; see Fig. 139.1).

• Test for proximal myopathy with hyper-reflexia.

Tell the examiner:

• that you would like to check for thyroid-stimulating antibodies (TsAb): near 100% detection rate in patients with Graves’ disease.

Diagnosis

This patient has tremor, proptosis and lid lag (lesions) caused by autoimmune Graves’ disease (aetiology), and is in fast atrial fibrillation and hyperthyroid (functional status).

Advanced-level questions

What happens to radioactive iodine uptake in Graves’ disease?

Radioactive iodine uptake increases in Graves’ disease.

Which is the best laboratory test to diagnose hyperthyroidism?

Serum TSH measurement is the single most reliable test to diagnose all common forms of hyperthyroidism, particularly in an outpatient setting (Arch Intern Med 2000;160:1573–5). Typically serum concentrations are <0.1 mIU/l in Graves’ disease, toxic adenoma, nodular goitre, subacute and lymphocytic (silent, postpartum) thyroiditis, iodine-induced hyperthyroidism and exogenous thyroid hormone excess. To diagnose hyperthyroidism accurately, TSH assay sensitivity, the lowest reliably measured TSH concentration, must be ≤0.02 mIU/l. Some less-sensitive TSH assays cannot reliably distinguish hyperthyroidism from euthyroidism. Free T₄ and triiodothyronine (T₃) concentrations should also be measured when less-sensitive TSH assays are utilized. In rare types of TSH-mediated hyperthyroidism (pituitary adenomas and selective pituitary resistance to thyroid hormone), serum TSH alone will not be suffice and again free T₄ and T₃ concentrations should be measured.

Remember: Although serum TSH is the best initial diagnostic test, it is useless in assessing response to therapy as it remains suppressed until after patient becomes euthyroid. Clinical assessment and free plasma T₄ is used to monitor response to therapy.

What are the causes of isolated thyroid-stimulating hormone suppression?

• Mild (subclinical) hyperthyroidism

• Recovery from overt hyperthyroidism

• Non-thyroidal illness (which can cause a low serum free T₄)

• Pregnancy during the first trimester

• Medications such as dopamine and glucocorticoids.

Mention a few causes of hyperthyroidism with reduced iodine uptake

• Thyroiditis

• Malignancy of thyroid

• Struma ovarii (ovarian tumour).

What drugs are used in the treatment of thyrotoxicosis?

• Carbimazole

• Methimazole

• Propylthiouracil.

Note: Antithyroid drug therapy is the preferred first-line therapy outside the USA, and methimazole or carbimazole are favoured over propylthiouracil because of their simple once-a-day dosing and higher adherence.

What are the disadvantages of antithyroid drugs?

• High rates of relapse once treatment is discontinued

• Occasionally complicated by troublesome hypersensitivity reaction and very rarely by life-threatening agranulocytosis and hepatitis.

What are the advantages and disadvantages of radioactive iodine compared with partial thyroidectomy for thyrotoxicosis?

Both radioactive iodine therapy and surgical thyroidectomy are extremely effective and usually result in permanent cure. Patients will require lifelong thyroxine replacement. Thyroid surgery is expensive, inconvenient and occasionally complicated by injury to surrounding structures in the neck in less skilled hands; it is also complicated by the general risks of anaesthesia. In Graves’ disease, the indications for surgery include:

• a large goitre

• patient preference

• drug non-compliance

• disease relapse when radioiodine is not available.

Radioactive iodine, although safe, may not be acceptable to patients who are sensitive to the calamities of Chernobyl and Hiroshima.

What are the contraindications to radioiodine therapy?

• Breastfeeding and pregnancy

• Situations where it is clear that the safety of other persons cannot be guaranteed

• Patients who are incontinent who are unwilling to have a urinary catheter

• Allergy to iodine.

What are the indications for radioiodine therapy in hyperthyroidism?

• Hyperthyroidism in Graves’ disease with moderate goitre (40–50 g), with no significant eye signs and first presentation

• Toxic multinodular goitre in older persons complicated by heart failure or atrial fibrillation

• Toxic adenoma, usually with mild hyperthyroidism

• Ophthalmopathy with thyroid dysfunction with stable eye disease (note radioiodine treatment may exacerbate eye changes in Graves’ disease and is not recommended in severe Graves’ opthalmopathy)

• Ablation therapy in those with severe manifestations such as heart failure, atrial fibrillation or psychosis.

What advice would you give to patients who are administered radioiodine?

• Depending on the dose, they should avoid journeys on public transport, stay off work, avoid places of entertainment or close contact with other people for up to 12 days and avoid non-essential close personal contact with children and pregnant women for up to 27 days.

• Patients should be warned that in the first 14 days after administration of therapy they may experience palpitations or other exacerbations of symptoms, particularly when not euthyroid before treatment.

• The importance of regular follow-up should be emphasized and the need to report the recurrence of thyrotoxic symptoms or the development of hypothyroidism.

• Patients should be informed that atrial fibrillation often reverts to normal rhythm and that digitalis may then be discontinued.

• Patients should be reminded to avoid pregnancy for 4 months after radioiodine therapy.

Is there an increased frequency of cancer in patients with Graves’ disease?

There is little evidence to suggest an increased frequency of thyroid cancer in patients with Graves’ disease.

Does thyrotoxicosis affect the bone?

Yes, chronic thyrotoxicosis is associated with osteoporosis.

If a patient with thyrotoxicosis develops muscle weakness following oral carbohydrate or intravenous dextrose, which condition comes to mind?

Hypokalaemic periodic paralysis, which occurs particularly in Asian men. These attacks may last for 7–72 h.

What is the effect of iodine on thyroid status?

It may cause transient hypothyroidism (Wolff–Chaikoff effect) or hyperthyroidism (Jod–Basedow phenomenon).

What is the prevalence of hyperthyroidism?

The prevalence is 0.2% in the adult population. Mild (subclinical) hyperthyroidism (serum TSH <0.1 mIU/l, free T₄ and T₃ normal) has a prevalence of 0.1–6% of the adult population.

What is the role of monitoring thyroid-stimulating antibody in these patients?

Titres for TsAb progressively decreases over 18 months after surgery or an antithyroid drug, and ultimately disappears in most patients (Eur J Endocrinol 2008; 158:69–75).

After radioiodine ablation, TsAb levels actually increase during the first year and are less likely to disappear: over a 5-year follow-up, only 60% of patients achieed undetectable levels.

This last observation underscores the importance of TsAb monitoring in pregnant women previously treated with radioiodine, who may still harbour TsAb even though they are hypothyroid.

What do you know about the pathogenesis of Graves’ opthalmopathy?

It is postulated that the TSH receptor is a target of autoimmunity within the orbit and that its recognition by a circulating TSH-like factor explains the link between hyperthyroidism and Graves’ ophthalmopathy. A failure of T cells to tolerate the receptor allows autoimmunity to develop against it. The antibodies formed, in turn, stimulate the TSH receptor on thyroid follicular epithelial cells, leading to their proliferation and increased production of T₃ and T₄. The antibodies also recognize the TSH receptor on fibroblasts in the orbit and, together with the secreted interferon-γ and tumour necrosis factor, initiate the tissue changes typically occurring in Graves’ ophthalmopathy (N Engl J Med 2010;362:726–38).

What is thyroid pathology in Graves’ disease?

It is characterized by a non-homogeneous lymphocytic infiltration with an absence of follicular destruction.

What do you know about amiodarone-induced hyperthyroidism?

Amiodarone, which contains 37% iodine, can induce hyperthyroidism; this disorder is more common in iodine-deficient areas (Ann Intern Med 1984;101:28–34) and in patients with nodular goitres and thyroid autoantibodies.

There are two mechanisms by which amiodarone may cause hyperthyroidism: thyroid destruction through an iodine-associated increase in circulating interleukin-6 (J Clin Endocrinol Metab 1994;78:423–7) or an increase in thyroid hormone synthesis. Amiodarone-induced hyperthyroidism sometimes responds to thionamide antithyroid drugs, but it may be very resistant to treatment. A combination of potassium perchlorate and carbimazole should be tried; steroids may be effective, particularly if interleukin-6 concentrations are high, which suggests a destructive thyroiditis. In resistant disease, total thyroidectomy should be considered (Lancet 1997;349:339–43).

Which drug would you prefer in the management of a pregnant woman with thyrotoxicosis?

Propylthiouracil is preferred in the USA for pregnant hyperthyroid women because methimazole may have teratogenic effects.

Robert James Graves (1796–1853) was a Dublin physician who described this condition. In 1835, he described three patients and wrote of one patient, ‘It was now observed that the eyes assumed a singular appearance for the eyeballs were apparently enlarged, so that when she slept or tried to shut her eyes her lids were incapable of closing, when the eyes were open, the white sclerotic could be seen, to a breadth of several lines all around the cornea’ (Graves R. London Med Surg J 1835;7:516). Graves’ disease is also termed Basedow’s or Parry’s disease.

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