Thyrotoxicosis (Hyperthyroidism)
Definition and demographics
Thyrotoxicosis refers to a clinical hyper metabolic syndrome caused by high thyroid hormone levels. Hyperthyroidism is more common in women than men. Graves disease commonly presents between the 2nd and 4th decade, toxic nodular goitre increase with age and is more common in regions where there are iodine deficiency is common.
Causes
Graves disease (most common -76%)
multi nodular goitre (14%)
Solitary thyroid adenoma
Rarer causes
Subacute thyroiditis (de Quervain's)
Post partum thyroiditis
Drugs
Very rare causes
Radiographic contrast
Iodine prophylaxis programme
Factitious thyrtoxicosis (where patient takes too much levothyroxine, characterised by raised T4:T3 ratio)
Struma ovarii
TSH secreting pituitary adenoma
Choriocarcinoma and hydatidiform mole
Folicular ± metastases
Pathophysiology
Graves disease: Graves disease is caused by the presence of TSH receptor antibodies (also known as thyroid stimulating immunoglobulin) which binds to TSH receptors stimulating the thyroid cell to synthesise and secrete thyroid hormone.
Solitary thyroid adenoma and multi nodular goitre
This is caused by toxic adenomas which are benign tumours which secrete thyroid hormone. This tends to gradually cause hyperthyroidism, initially sub clinically then overtly.
Thyroiditis
Both painful subacute thyroiditis and post partum thyroiditis cause a transient thyrotoxicosis. Post partum thyroiditis is a autoimmune thyroiditis caused by the lymphocytic infiltration of the thyroid causing thyroid destruction, which causes a transient thyroitoxicosis due to the release of thyroid hormone from the damaged cells. This progresses to hypothyroidism due to depletion of hormone, and may return to normal within 12-18 months in a small number of patients. painful subacute thyroiditis is caused by viruses and may be associated with flu like symptoms, fever, neck pain and neck swelling. Like post partum thryroiditis, this progresses to hypothyroidism although thyroid function will return to normal in most patients.
Clinical history and examination findings
Common symptoms of thyrotoxicosis includes weight loss despite normal or increased appetite, heat intolerance, palpitations, dyspnoea, tremor, sweating, irritability and emotional lability, and fatigue.
Other presentations may include osteoporosis (presenting as a fracture or loss of height), diarrhoea and steatorrhea, angina, ankle swelling, muscle weakness, periodic paralysis, pruritus, alopecia, amenorrhoea/oligmenorrhoea, infertility, spontaneous abortion, loss of libido or impotence, excessive lacrimation, and rarely vomiting, apathy, anorexia, and exacerbation of asthma.
On examination patient may have had some weight loss, may present with a tremor, palmar erythema, sinus tachycaridia and show lid retraction and lid lag. Patients may also present with a palpable goitre which is soft and diffuse in graves' and irregularly enlarged in multi nodular goitre.
Rarer examination findings includes a goitre with bruit (graves only) atrial fibrillation, systolic hypertension, increased pulse pressure, cardiac failure, hyper-reflexia, sustained clonus, proximal myopathy, and bulbar myopathy.
Many eye features such as periorbital swelling and exophalmos, Conjunctival irritation, and dipoplia are only seen in graves disease. Pretibial myxoedema and thyroid acropachy (a periosteal hypertrophy which looks like clubbing) are also only seen in Graves.
Differential diagnosis:
See aetiology, in addition any disease which causes weight loss or primary presenting complaint of the patient such as tiredness and depression.
Investigations:
Primary investigations include serum T3 and T4 and TSH. In primary hyperthyroidism, T3 and T4 tend to be raised and TSH undetectable, although a proportion (5%) of patients may present with raised T3, normal T4 in the upper range and undetectable TSH. Secondary hyperthyroidism caused by a TSH-producing pituitary adenoma is rare.
If abnormality is found, biochemistry should be repeated. Once confirmed further investigations are then performed to determine the cause.
These primarily include:
TSH receptor antibody (TRAb, raised in Graves)- high specificity (low false positive rate) but low sensitivity (high false negative rate).
isotope scanning or 99mtechnetium scintigraphy scan. If patient presents with features of graves disease without features suggesting possible non-graves thyrotoxicosis including recent pregnancy, neck pain, flu like illness, drugs (amiodarone T4) or palpable multi nodular goitre or solitary nodule, graves may be diagnosed without isotope scanning.
Thyroperoxidase antibodies and thyroglobulin levels may also be helpful to determine if the hyperthyroidism has a autoimmune cause.
Graves disease will show diffuse increased isotope uptake, toxic multi nodular goitre will show multiple spots of increased uptake, and a toxic adenoma will show a singular nodule with increased uptake. Iodine uptake is not increased in thryroditis or if excessive levothryroxine is taken.
Additional investigations include ECGs to detect atrial fibrillation or sinus tachycardia and investigations relevant to presenting symptoms. Other tests may be affected because of hyperthyroidism. These include: raised ALT, GGT, ALP, bilirubin, hypercalcaemia, and glycosuria. These tests are not useful in differential diagnoses and should only be investigated further once patient is euthyroid.
Management
Management of hyperthyroidism depends on the cause, and may include drugs, radioactive iodine, or surgery. Non selective B-blockers such as propranolol, and nadolol may be helpful in short term alleviation of certain symptoms. If patient has concurrent atrial fibrillation, treatment may also be needed for this.
Hyperthyroidism should be referred to endocrinologists.
In graves disease, Thionamide drugs tend to be given as a first line treatment. The drugs are given for 12-18 months and leads to a 40-60% long term remission rate. Thyroid function tests are taken 4 weeks after the drug is started then repeated monthly until normal T4 levels are seen. The drug is then titrated down to the minimum dose to maintain a constant T4 level. radioactive iodine treatment or surgery can be considered if drugs fails. Radioactive iodine tends to cause 80% to become hypothyroid, 10% to be euthyroid and the remaining group may require repeated doses. Common side effects include sore throat and radiation thyroiditis. The risk of general anaesthesia, recurrent laryngeal nerve damage, and permanent hypoparathyroidism should be considered in total thyroidectomy.
In multi nodular goitre and thyroid adenomas, drugs can be used for short term control of hyperthyroidism, but this will not lead to remission and more definitive treatment should be used.
Thyroiditis should be treated with symptom relieving drugs only as production of thyroid hormone is not increased.
Thyrotoxic crisis (thyroid storm)
Thyroid storm is a rare but life-threatening complication of hyperthyroidism.
It presents as fever, agitation, confusion, tachycardia or atrial fibrillation and in older patients cardiac failure. Thyrotoxic crises may be precipitated by infections in patients with undiagnosed or under managed hyperthyroidism, or occur after subtotal thyroidectomy and iodine radiation therapy.
Thyrotoxic crises are medical emergencies. Patients should be rehydrated, given broad spectrum antibiotics, propranolol, sodium update to restore serum T3 levels, and carbimazole to inhibit new thyroid hormone synthesis. The patient is then maintained on carbimazole for 10-14 days. Both carbimazole, methimazole and propylthiouracil can cause bone marrow suppression. This is rare, but patients should therefore be warned to come in for a FBC if they experience signs of infection such as fever or sore throat. There have also been reports of propylthiouracil causing a few cases of liver failure.
Mortality rate for thyrotoxic crisis is high (10%) even with early identification and treatment.
Colledge NR, Walker BR, Ralston SH eds. Davidson's principles and practice of medicine, 21st ed. Edinburgh, Churchill livingstone, 2010.
http://www.patient.co.uk/doctor/hyperthyroidism
http://www.patient.co.uk/doctor/hyperthyroidism
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