Management of Thyroid Disorders

Describe the physiology of the thyroid (1)

Thyroid gland is situated in the neck. Responsible for the synthesis of tri-iodothyronine (T3), tetra-iodothyronine (T4, additional iodine bound), calcitonin (involved in Ca and bone metabolism)

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Describe the physiology of the thyroid (2)

5'-deiodinase converts T4 to T3 (conversion takes place in the body's cells/tissues, periphery, mainly liver)

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Describe features of the thyroid hormones (1)

Dietary iodine (binds to tyrosine residues, essential for adequate production of thyroid hormones). Only T3 and T4 are proper thyroid hormones. 90% T4 released, 10% T3 released. Majority of T3 (80-90%) is produced by peripheral conversion of T4

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Describe features of the thyroid hormones (2)

Metabolic activity of thyroid hormone is determined by the amount of fT3 and fT4 (T4 is highly protein bound in plasma, 99.95%, 0.05% free). 99.5% of circulating T3 is bound (0.5% free). T3 is produced by the peripheral deiodination of T4

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Describe features of the thyroid hormones (3)

T3 is more potent than T4. Thyroid hormones help with metabolism

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Describe the functions of T3 and T4

Increase basal metabolic rate - increase body temperature, increase HR, brain matures (in children), growth is promoted (in children). Activation of NS leads to improved concentration and faster reflexes

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Outline thyroid regulation (1)

Hypothalamus secretes TRH which stimulates the release of TSH from the anterior pituitary gland. This stimulates the thyroid gland to secrete thyroid hormones

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Outline thyroid regulation (2)

T3 sends back a negative feedback loop to hypothalamus and anterior pituitary to inhibit the release of TRH and TSH (negative feedback)

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How do you investigate thyroid disease?

Measure TSH levels

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What is the normal range of TSH?

0.5 - 5 micro-units/mL

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What does a suppressed TSH level indicate?

Hyperthyroidism (high level of thyroid hormones, inhibits the release of TSH via negative feedback loop)

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What does an elevated TSH level indicate?

Hypothyroidism (negative relationship between T4 and TSH concentrations). Low thyroid hormone levels, unable to inhibit release of TSH via negative feedback loop

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If the TSH levels are abnormal, which test is requested?

Test free T4

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What does an elevated T4 level indicate?

Hyperthyroidism (high thyroid hormone levels)

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What does a suppressed T4 level indicate?

Hypothyroidism (low thyroid hormone levels)

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What is euthyroidism?

Normal TSH and normal free T4/3

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What is hyperthyroidism (in terms of TSH and T4/3 levels)?

Suppressed TSH, raised T4/3

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What is hypothyroidism (in terms of TSH and T4/3 levels)?

Elevated TSH, low T4/3

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What is hypopituitarism (in terms of TSH and T4/3 levels)?

Low levels of TSH, low levels of T4/3 (pituitary unable to release TSH, thyroid unable to release thyroid hormones, insufficient feedback loop)

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What are the effects of a TSH secreting tumour (in terms of TSH and T4/3 levels)?

High TSH levels, high T4/3 levels

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Describe features of hyperthyroidism (1)

Thyrotoxicosis. 4x more common in women than men. Causes - Graves' disease (auto-immune condition, IgG auto antibodies bind to TSH receptors and increase T4/3 levels)

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Describe features of hyperthyroidism (2)

Multinodulat goitre (enlargement of gland), autonomously functioning nodules. TSH-oma (rare), drugs (less common)

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What are the typical clinical features of hyperthyroidism?

Feeling hot/sweaty constantly (fever/hyperpyrexia), tremor, palpitation/tachyarrhythmias, neck swelling, muscle weakness, secondary amenorrhea/lighter periods, weight loss, diarrhoea/nausea/vomiting/abdominal pain, prominent eyes, HTN (hypo if in HF)

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How do patients with hyperthyroidism feel?

Underweight, always hungry, tired, sweaty, anxious, experience palpitations, experience mood changes

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What are the appropriate treatment options for hyperthyroidism?

Thioamide drugs (carbimazole, propylthiouracil), block and replace regimen. For symptomatic relief - beta blockers (propranolol, IV labetalol). Radioiodine. Surgery

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What is the mechanism of action for carbimazole?

Suppression of the synthesis of thyroid hormones. Inhibits thyroid peroxidase (TPO) and decreases incorporation of iodide into tyrosine molecules. Inhibits coupling of monoiodinated and di-iodinated residues to form T3 and T4

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What are the side effects of carbimazole? (1)

Nausea, headache, arthralgia (joint pain), mild GI disturbance, skin rashes, pruitis. Blood and lymphatic system disorders. Bone marrow suppression (neutropenia, eosinophilia, leucopenia, agranulocytosis (can be fatal))

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What are the side effects of carbimazole? (2)

Rare cases of panctyopenia/alplastic anaemia and isolated thrombocytopenia have also been reported. Very rare causes of haemolytic anaemia

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What are the patient counselling points for carbimazole? (1)

Report symptoms and signs suggestive of infection (especially sore throat). Warn about the onset of bruising or bleeding, mouth ulcers, fever and malaise. If patient experiences any of the symptoms they should be instructed to stop the drug

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What are the patient counselling points for carbimazole? (2)

Seek medical advice immediately. WBCC should be performed immediately (particularly where there is any clinical evidence of infection)

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What is the mechanism of action for propylthiouracil?

Suppression of the synthesis of thyroid hormones. Inhibits TPO and decreases incorporation of iodide into tyrosine molecules. Inhibits coupling of mono-iodinated and di-iodinated residues to form T3/4. Also inhibits peripheral conversion of T4/3

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What are the side effects of propylthiouracil? (1)

Alopecia, arthralgia (joint pain), arthritic, fever, encephalopathy, gastrointestinal disturbances, haemorrhage & headache. Severe hepatic reactions reported - discontinue if significant liver-enzyme abnormalities develop

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What are the side effects of propylthiouracil? (2)

Bone marrow suppression - neutropenia, leucopenia, thrombocytopenia, agranulocytosis (can be fatal)

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What is the 'block and replace' regimen? (1)

Block (high doses of anti-thyroid drugs e.g. carbimazole 40-60 mg/day). Replace (T4 - levothyroxine treatment, doses vary 25-300 micrograms/day)

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What is the 'block and replace' regimen? (2)

Thought to be advantageous in terms of permanent remission of hyperthyroidism (not demonstrated in meta-analysis, high pill burden, higher doses anti-thyroid drugs confer a greater risk of agranulocytosis). Single treatment of carbimazole preferred

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What is the 'block and replace' regimen? (3)

Treatment for a few months, check TSH and T4/3 levels then discontinue use. Once euthyroid, 50% chance of going back to being hyperthyroid, 50% chance of remaining euthyroid

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What is a thyroid storm?

Severe form of thyrotoxicosis (with end organ compromise). Often occurs very suddenly. Can occur in men/women of any age, most common in adolescent/young adult women. Mortality of 80-90% if untreated, 20% with early recognition/management

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What are the causes of a thyroid storm?

Thyroid (or other) surgery, trauma, infection, acute iodine load, radiodine, untreated chronic thyrotoxicosis (very rare)

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What is the treatment for a thyroid storm? (1)

Drugs given at higher doses and more frequently. Beta blockers - labetalol (acts on alpha/beta receptors) IV infusion 10-200 mg/hr for symptomatic relief of palpitations, tachycardia, tremulousness, anxiety, heat intolerance

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What is the treatment for a thyroid storm? (2)

(Beta blockers block peripheral effects of excessive thyroid hormone, hyperthyroidism associated with increased number of beta-adrenergic receptors). Anti-thyroid drugs (carbimazole 20-30 mg PO/NG BD or propylthiouracil 200-300 mg NG QDS)

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What is the treatment for a thyroid storm? (3)

PTU has theoretical advantage over carbimazole as it blockers peripheral conversion of T4 and T3. But carbimazole has a longer duration of action an dis used with other drugs (e.g. radioiodine contrast agents) which reduces peripheral conversion

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What is the treatment for a thyroid storm? (4)

Corticosteroids - IV hydrocortisone 100 mg TDS (reduces T4 and T3 conversion and helps underlying autoimmune process in Graves' disease

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What is hypothyroidism?

Myxoedema - low thyroid hormone levels

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What are the causes of hypothyroidism? (1)

Auto-immune (Hashimoto's thyroiditis, increased levels of anti TPO antibody, destroys thyroid tissue), low dietary intake, congenital, hypothalamic disorder, surgery, drug-induced

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What are the causes of hypothyroidism? (2)

(Thyroid regulation - low levels of T4/3, more TSH secreted for compensation)

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What are the clinical features of hypothyroidism?

Hypothermia, decreased metabolic rate (weight gain, decreased bowel transit, constipation), dry skin, puffy face, hair loss, raised cholesterol

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How do patients with hypothyroidism feel?

Overweight, tired/sleepy, cold, mood changes

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What is the treatment for hypothyroidism? (1)

Reversal of metabolic derangements and relief of clinical symptoms - achieved by constant daily dose of levothyroxine (T4) tablets. Can be take up to 2 months to become euthyroid. Dose range 25-300 micrograms/day

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What is the treatment for hypothyroidism? (2)

S/E well tolerated, symptoms of thyrotoxicosis. Patient counselling - absorption decreased by food/caffeine, take on an empty stomach 30 mins before food or other medication (could take first thing in the morning), or 2 hours after food

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Which drugs induce thyroid disorders?

Lithium and amiodarone

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How does lithium induce thyroid disorders? (1)

Lithium is mainly used for treatment of BPAD, 5-15% patients develop over hypothyroidism. Evidence of sub-clinical hypothyroidism (raised TSH, normal T4)

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How does lithium induce thyroid disorders? (2)

Mechanism for lithium - direct inhibitory actions of lithium on thyroid function have been observed, reduction of iodine concentrating capacity, lithium may inhibit secretion of thyroid hormones by stabilising follicular cell microtubule system

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Describe features of amiodarone (1)

Class III anti-rhythmic agent. Half life of 50 days. 37% of molecular mass derived from iodine. Structural similarities with thyroid hormones. At normal doses, patients consume 6-12 mg/day of iodine but recommended intake is 0.15-0.30 mg/day

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Describe features of amiodarone (2)

(leads to deranged thyroid function tests)

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Describe features of amiodarone induced thyrotoxicosis (1)

Occurs in 2-12% of patients on long-term therapy. Unpredictable/severe onset, presents at any point during treatment. If patient has pre-existing thyroid disorder (AIT caused by excess iodine build up)

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Describe features of amiodarone induced thyrotoxicosis (2)

If patient has no pre-existing thyroid disorder (AIT caused by thyroid gland damage and an increase in circulating thyroid)

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Describe features of amiodarone induced hypothyroidism (1)

Range from 6% in countries with high iodine intake to 13% in countries with low dietary iodine intake. More common in women. Iodine uptake into thyroid gland is inhibited leading to reduced hormone production. Reduced intracellular T4/3 conversion

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Describe features of amiodarone induced hypothyroidism (2)

Reduced T4 cellular uptake

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Management of Thyroid Disorders

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