Dr Anthony Toft Response Thyroiditis, Thyroid Eye Disease and Thyroxine Dosing
1st June 2010
Endocrinologist Dr Anthony Toft answers GP Dr Pam Browns questions on thyroiditis, thyroid eye disease and thyroxine dosing
1 How common is thyroiditis and what symptoms should alert us to it? How does it affect thyroid tests?
Subacute or de Quervains thyroiditis presents with a flu-like illness associated with pain over the thyroid, often radiating to the ears. Patients also have clinical features of hyperthyroidism caused by release of preformed thyroid hormones from the damaged thyroid follicles.1
So there is biochemical evidence of hyperthyroidism and also an elevated ESR of around 60-80mm/hr. The flu-like symptoms and the pain in the thyroid gland usually settle within 10 to 14 days but the hyperthyroidism may persist for about six weeks. This is followed by a similarly short-lived episode of thyroid failure with a low-serum thyroxine and raised serum TSH, with the damaged thyroid follicles unable to produce hormones.
What is remarkable is that the thyroid architecture and function is restored by three to six months and the patient almost always becomes euthyroid. Treatment of the hyperthyroid phase with antithyroid drugs is of no value and daily slow-release propranolol 160mg is usually adequate.
Simple analgesics will control thyroid discomfort and treatment with steroids is rarely necessary.
Treatment with levothyroxine during the hypothyroid phase is not necessary as the symptoms are usually very mild, if noticed at all. A similar pattern of biochemical disturbance can occur in patients with underlying autoimmune thyroid disease, a condition known as silent thyroiditis or if occurring during the first year after childbirth post-partum thyroiditis.
2 I often see patients who have an elevated TSH but normal T4. How should I be managing them?
The combination of a normal serum T4 and raised serum TSH is known as subclinical hypothyroidism. If measured, serum T3 will also be normal. Repeat the thyroid function tests in two or three months in case the abnormality represents a resolving thyroiditis.2
But if it persists then antibodies to thyroid peroxidase should be measured. If these are positive indicative of underlying autoimmune thyroid disease the patient should be considered to have the mildest form of hypothyroidism.
In the absence of symptoms some would simply recommend annual thyroid function tests until serum TSH is over 10mU/l or symptoms such as tiredness and weight gain develop. But a more pragmatic approach is to recognise that the thyroid failure is likely to become worse and try to nip things in the bud rather than risk loss to follow-up.
Treatment should be started with levothyroxine in a dose sufficient to restore serum TSH to the lower part of its reference range. Levothyroxine in a dose of 75-100g daily will usually be enough.
If there are no thyroid peroxidase antibodies, levothyroxine should not be started unless serum TSH is consistently greater than 10mU/l. A serum TSH of less than 10mU/l in the absence of antithyroid peroxidase antibodies may simply be that patients normal TSH concentration.
3 And what about a normal serum thyroxine, but suppressed serum TSH?
In this situation measure serum T3, which will be elevated in so-called T3-toxicosis, requiring antithyroid therapy.
If the serum T3 concentration is normal and the patient is not taking levothyroxine, the combination is known as endogenous subclinical hyperthyroidism, usually caused by Graves disease in remission or underlying nodular thyroid disease. Refer to a specialist centre where imaging may be needed to define the cause.
Nodular thyroid disease should be treated with iodine-131 or surgery as endogenous subclinical hyperthyroidism due to nodular thyroid disease is now thought to be a risk factor for osteoporosis and atrial fibrillation in contrast to exogenous subclinical hyperthyroidism due to treatment with levothyroxine.
4 How does thyroid eye disease manifest itself and how is it treated?
Most patients presenting with the hyperthyroidism of Graves disease will have some evidence of thyroid eye disease, ranging from lid retraction with excessive lacrimation in bright light to marked exophthalmos with limited eye movements, diplopia and reduced visual acuity.3
The hyperthyroidism of Graves disease and thyroid eye disease are best considered as two separate, organ-specific autoimmune conditions, which frequently coexist. This explains why the eye disease may precede the hyperthyroidism or even occur for the first time years after successful treatment of hyperthyroidism.
The eye disease has its own natural history a period of deterioration, followed by one of stability and ultimately of some improvement. But the ophthalmopathy will worsen if thyroid function is not controlled whether through inadequate or excessive treatment.
The eye changes often persist for two to three years after successful treatment of the hyperthyroidism and although there may be significant improvement there is often residual disease, which can be improved by orbital decompression, strabismus surgery and eyelid surgery.
Of all treatments of the hyperthyroidism of Graves disease, iodine-131 therapy is associated most often with a worsening of the ophthalmopathy. For that reason it is relatively contraindicated in patients with significant eye disease. For these it may be better to use combination therapy with carbimazole and levothyroxine for the best possible control of thyroid function.
But if radioiodine is the chosen therapy, enteric-coated prednisolone 30-40mg daily should be prescribed for six weeks, as this has been shown to prevent deterioration of ophthalmopathy.
5 Patients with hyperthyroidism often ask for advice on drug treatment versus radioiodine therapy. Can you summarise the pros and cons of each?
The three treatments for hyperthyroidism of Graves disease antithyroid drugs, iodine-131 and surgery are effective but none is perfect.4
Iodine-131 will almost certainly cause hypothyroidism, usually within the first year of treatment, as will surgery, given the move towards total rather than subtotal thyroidectomy.
There is no consensus among endocrinologists about the correct dose of thyroid hormone replacement so patients may prefer to opt for long-term treatment with carbimazole. Standard practice is that carbimazole is given for 18 months in those destined to have just one episode of hyperthyroidism lasting a few months.
But theres no reason why carbimazole shouldnt be used for many years in those who do relapse. Any adverse effects such as urticarial rash or agranulocytosis will have occurred within a few weeks of starting the first course.
Iodine-131 treatment for toxic multinodular goitre is the most appropriate choice as hypothyroidism is uncommon. Surgery would be reserved for those with very large goitres and mediastinal compression.
Once hyperthyroidism has developed in a patient with a multinodular goitre, it will not remit and any antithyroid therapy would have to be lifelong.
6 What is the correct dose of thyroxine and is there any rationale for adding in tri-iodothyronine?
The appropriate dose of levothyroxine is that which restores euthyroidism and serum TSH to the lower part of the reference range 0.2-0.5mU/l.
In this case, free thyroxine is likely to be in the upper part of its reference range or even slightly elevated 18-22pmol/l. Most patients will feel well in that circumstance.
But some need a higher dose of levothyroxine to suppress serum TSH and then the serum-free T4 concentration will be elevated at around 24-28pmol/l.
This exogenous subclinical hyperthyroidism is not dangerous as long as serum T3 is unequivocally normal that is, serum total around T3 1.7nmol/l (reference range 1.0-2.2nmol/l).
Even while taking the slightly higher dose of levothyroxine a handful of patients continue to complain that a sense of wellbeing has not been restored. A trial of levothyroxine and tri-iodothyronine is not unreasonable. The dose of levothyroxine should be reduced by 50g daily and tri iodothyronine in a dose of 10g (half a tablet) daily added.
While taking both hormones it is important serum TSH is normal and not suppressed. If the patient is still dissatisfied it should be made clear that the symptoms have nothing to do with thyroid disease or its treatment and perhaps issues at home and in the workplace should be addressed.
There is no place for the use of animal thyroid extract in the treatment of hypothyroidism. Although preparations contain both thyroxine and tri-iodothyronine, the hormone content varies between batches.5
7 How low should we aim to suppress TSH levels following thyroid carcinoma? And are these patients at increased risk of bone loss?
The treatment for papillary and follicular carcinoma of thyroid is usually total thyroidectomy followed by ablative iodine-131 and long-term treatment with levothyroxine in a dose high enough to suppress serum TSH concentrations.
Higher doses of levothyroxine are used compared with those in patients with spontaneous primary hypothyroidism because the growth of differentiated thyroid carcinoma is TSH-dependent.
In the past it has been customary to make sure that serum TSH concentrations are undetectable by using doses of levothyroxine of 125-200g or more daily, depending upon the patients weight.
There is no good evidence that a suppressed serum TSH concentration in the presence of an unequivocally normal serum total tri-iodothyronine is a risk factor for atrial fibrillation or osteoporosis.
But the clinical consensus is that serum TSH concentrations in such patients should be low but detectable at 0.1-0.2mU/l.
8 Should all pregnant woman with hyperthyroidism receive specialist endocrinology management?
In Graves disease the TSH-receptor antibody responsible for the hyperthyroidism crosses the placenta and, if the mother is hyperthyroid, the foetus is too. Good control of maternal thyroid function is therefore important as it will be mirrored in the foetus throughout pregnancy.
All pregnant patients with hyperthyroidism due to Graves disease should be managed in a specialist clinic and reviewed every four to six weeks.6
Autoimmune disease tends to improve during pregnancy, so the dose of antithyroid drug needed to maintain a normal serum TSH concentration is usually in the order of 5-10mg of carbimazole daily or 50-100mg of propylthiouracil daily.
Its customary to stop the antithyroid drug some four weeks before the expected date of delivery when brain growth is at a maximum to avoid any possibility of foetal hypothyroidism. Its unusual for hyperthyroidism to recur before three months post-partum.
Its important to distinguish between recurrent Graves disease for which treatment is necessary and post-partum thyroiditis in which the hyperthyroidism is short-lived followed by an equally transient episode of hypothyroidism, then recovery.
In Graves disease the TSH-receptor antibody is detected in serum and isotope uptake by the thyroid is normal or increased. But in post-partum thyroiditis the TSH-receptor antibody is usually absent and the isotope uptake by the thyroid gland negligible.
9 How does a hyperthyroid womans decision to breast-feed affect treatment?
If antithyroid therapy is required in a patient who is breast-feeding, propylthiouracil is the drug of choice as its excretion in breast milk is one-tenth that of carbimazole. If the dose of carbimazole can be restricted to 15mg daily there will be no significant effect on thyroid function in the infant.
10 And what about hypothyroidism in pregnant women?
Untreated maternal hypothyroidism results in neuropsychological damage to the offspring. Patients with hypothyroidism who become pregnant need to have the dose of levothyroxine increased on average by 50g daily in order to maintain normal serum TSH concentrations.
The advice to patients with established hypothyroidism is that they should increase their dose of levothyroxine by 25g daily as soon as pregnancy is confirmed and make an appointment for thyroid function tests to be measured some two weeks later. The aim is to achieve a free T4 concentration of 16-20pmol/l.
Further measurement of serum free T4 and TSH should be made six weeks later and again in the middle of the second and third trimesters.
The pre-pregnancy dose of levothyroxine can be restored four weeks after delivery by which time the increased concentrations of thyroxine binding globulin will have returned to normal. Its not clear whether this meticulous care is necessary and it may well be that any thyroxine therapy in the hypothyroid mother will allow normal foetal development.
Dr Tony Toft is consultant physician and endocrinologist at the Royal Infirmary of Edinburgh, and a former president of the Royal College of Physicians of Edinburgh and of the British Thyroid Association
Competing interests None declared
Dr Pam Brown is a GP in Swansea
1 American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi. Medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocrine Practice 2006;12:63-102
2 Association for Clinical Biochemistry, British Thyroid Association and British Thyroid Foundation. UK guidelines for the use of thyroid function tests. 2006 http://acb.org.uk/docs/tftguidelinefinal.pdf
3 Perros P, Neoh C, Dickinson J. Thyroid eye disease. BMJ 2009;338:b56O
4 Brent GA. Clinical practice: Graves disease. NEJM 2008;358:2594-605
5 British Thyroid Association executive committee. Armour Thyroid (USP) and combined thyroxine/tri-iodothyronine as thyroid hormone replacement. British Thyroid Association 2007
6 Marx H, Amin P, Lazarus JH. Hyperthyroidism and pregnancy. BMJ 2008;336:663-7