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Describe hypothyroidism and hyperthyroidism with their causes, features and the interpretation of thyroid function tests.

Pathology · 2nd Professional — Para-Clinical

Definition

Hypersensitivity of the endocrine system aside, the pituitary–target organ axes can be summarised by contrasting the effects of hypo- and hyper-function of the thyroid, since these are the commonest endocrine disorders encountered.

Hypothyroidism

Aspect	Details
Causes — primary (95%)	Iodine deficiency (commonest worldwide), hashimoto thyroiditis (commonest where iodine is adequate), iatrogenic (thyroidectomy, radioiodine, antithyroid drugs), drugs (lithium, amiodarone), congenital (dysgenesis, dyshormonogenesis)
Causes — secondary	Pituitary or hypothalamic disease; TSH is low or inappropriately normal
Adults — myxoedema	Fatigue, cold intolerance, weight gain, constipation, hoarse voice, dry coarse skin, hair loss including the outer third of the eyebrows, bradycardia, menorrhagia, depression and slowed cognition; slow-relaxing ankle reflexes; non-pitting periorbital puffiness from glycosaminoglycan deposition
Infants — cretinism	Severe intellectual disability, short stature with delayed bone age, coarse facies, protruding tongue, umbilical hernia, deaf-mutism; the damage is irreversible if treatment is delayed beyond the first weeks
Myxoedema coma	Hypothermia, bradycardia, hypoventilation with CO2 retention, hyponatraemia and coma; precipitated by cold, infection or sedatives; high mortality

Hyperthyroidism

Causes — graves disease (the commonest), toxic multinodular goitre, toxic adenoma, thyroiditis (transient), excess thyroxine, iodine-induced (Jod–Basedow), and rarely a TSH-secreting adenoma or struma ovarii
Features — weight loss with a good appetite, heat intolerance, sweating, palpitations, atrial fibrillation, tremor, anxiety, irritability, diarrhoea, oligomenorrhoea, proximal myopathy, lid lag and lid retraction
Features specific to Graves disease — exophthalmos, ophthalmoplegia, pretibial myxoedema and thyroid acropachy; these do not occur with other causes
Thyroid storm — fever, extreme tachycardia or arrhythmia, agitation, delirium, vomiting and cardiovascular collapse; precipitated by infection, surgery, trauma or radioiodine in an inadequately prepared patient; a medical emergency
Apathetic thyrotoxicosis in the elderly — presenting with weight loss, atrial fibrillation and depression rather than the usual hyperkinetic picture, and easily missed

Interpretation of Thyroid Function Tests

TSH	Free T4	Interpretation
High	Low	Primary hypothyroidism
High	Normal	Subclinical hypothyroidism
Low	High	Primary hyperthyroidism
Low	Normal	Subclinical hyperthyroidism (check T3 for T3-toxicosis)
Low or normal	Low	Secondary (pituitary) hypothyroidism
Normal or slightly abnormal	Low normal	Sick euthyroid syndrome — in acute illness; do not test thyroid function in an acutely ill patient unless there is a specific reason

CLINICAL PEARL

TSH is the most sensitive test because the pituitary responds logarithmically. A small fall in free T4 produces a large rise in TSH, so TSH becomes abnormal before T4 leaves the reference range — which is exactly what "subclinical" disease means. The one situation where TSH misleads is pituitary disease, where the sensor itself is broken.

Applied Aspects

Screen all newborns for congenital hypothyroidism — treatment within the first two weeks entirely prevents cretinism, and this is among the most cost-effective interventions in medicine
Test thyroid function in pregnancy where indicated, using trimester-specific ranges; untreated maternal hypothyroidism impairs fetal neurodevelopment and raises the risk of miscarriage
Amiodarone causes both hypo- and hyperthyroidism, through its iodine load and direct toxicity, and requires monitoring
Antithyroid drugs (carbimazole, propylthiouracil) can cause agranulocytosis — every patient must be told to report a sore throat or fever immediately and stop the drug
Beta-blockers give rapid symptomatic relief in thyrotoxicosis while definitive treatment takes effect
Levothyroxine is started at a low dose in the elderly and in ischaemic heart disease, since correcting hypothyroidism too quickly can precipitate angina or infarction

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