INSTRUCTION

Look at this patient.

Determine this patient's thyroid status.

SALIENT FEATURES

Patient is fidgety and restless.

Proceed as follows:

History

· Easy irritability, nervousness, insomnia.

· Fatigue.

· Weight loss with increased appetite.

· Frequent defaecation.

· Oligomenorrhoea.

· Dislike for hot weather, heat intolerance, excessiv ,- sweating.

· Palpitations, dyspnoea.

· Family history of thyroid disease.

· Proximal muscle weakness, muscle atrophy, periodic paralysis (particularly in

patients of Oriental extraction).

Examination

Hands:

· While shaking hands with the patient note the wa'm sweaty palms.

· Look for tremor, thyroid acropachy, onycholysis Plummer's nails), vitiligo and

palmar erythema.

· Check pulse (for tachycardia or the irregularly irregular pulse of atrial fibrillation).

Eyes:

· Comment on proptosis (after looking at the eyes t rom behind and above).

· Check for lid lag.

· Check for scars of previous tarsorrhaphy.

Neck:

· Mention previous thyroidectomy scar if present.

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

Chest:

· Gynaecomastia can occur in men due to increased oestrogen production.

· Examine the cardiovascular system: sinus tachycardia, widened pulse pressure,

loud first heart sound, third heart sound, systolic murmur, atrial fibrillation.

Lower limbs:

· Examine the shins for pretibial myxoedema (bilateral pinkish brown dermal

plaques).

· Test for proximal myopathy with hyper-refiexia.

Tell the examiner:

That you would like to check for thyroid-stimulating antibodies, TsAb, which give near

100ok detection rate in Graves' patients.

DIAGNOSIS

This patient has tremor, proptosis and lid lag (lesions) due to autoimmune Graves'

disease (aetiology), and is in fast atrial fibrillation and hyperthyroid (functional

status).

QUESTIONS

How would you confirm the diagnosis in this patient?

Serum thyroxine (T4), serum thyroid-stimulating hormone (TSH) levels and thyroid

autoantibodies.

What are the causes of hyperthyroidism?

· Primary: Graves' disease, toxic nodule, multinodular goitre, Hashimoto's

thyroiditis, iodine-induced, excess thyroid hormone replacement, postpartum

thyroiditis.

· Secondary: pituitary or excess TSH hypersecretion, hydatidiform mole, struma

ovarii, factitious.

What are the components of Graves' disease?

Hyperthyroidism with goitre, eye changes and pretibial myxoedema - they run

independent courses.

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 Meal

2000; 160: 1573-5). Typically, serum concentrations are less than 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 mlU/l or less. Some

less sensitive TSH assays cannot reliably distinguish hyperthyroidism from

euthyroidism. Free T4 and T3 concentrations should 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 suffice and again free T4 and T3 concentrations should be

measured.

What are the causes of isolated TSH suppression?

· Mild (subclinical) hyperthyroidism.

· Recovery from overt hyperthyroidism.

· Non-thyroidal illness (which can cause a low serum free 3,4).

· 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.

What drugs are used in the treatment of thyrotoxicosis?

· Carbimazole.

· Methimazole.

· Propylthiouracil.

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

com-plicated by injury to surrounding structures in the neck in less skilled hands,

and by the risks of anaesthesia. In Graves' disease the indications for surgery

include: a large goitre, the patient's preference, drug non-compliance and 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 in which it is clear that the safety of other persons cannot be

911ar~nteecl

· 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 due to 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.

· 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 preg-nant

women for up to 27 days.

· Patients should be warned that in the first fortnight after administration of therapy

they may experience palpitations or other exacerbations of symptoms, par-ticularly

when not euthyroid before treatment.

· The importance of regular follow-up should be emphasized, as should 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 hours.

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; the prevalence of mild (subclinical)

hyperthyroidism, where serum TSH is less than 0.1 mlU/1 and free T4 and T3 are

normal, is 0.1-6% of the adult population.

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

due to 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 may also be very resistant to treatment. A combination of

potassium perchlorate and carbimazole should be tried; steroids may he etlectlve,

particularly if interleukin-6