5. Grave's disease and thyrotoxicosis; inflammatory diseases of the thyroid gland

Graves disease, thyrotoxicosis and inflammatory thyroid disease

DEFINITIONS

• Thyrotoxicosis is the clinical state caused by excess circulating thyroid hormone from any source.
• Hyperthyroidism specifically means increased synthesis and secretion by the thyroid gland.
• Graves disease is an autoimmune cause of hyperthyroidism due to stimulating antibodies against the TSH receptor.
• Thyroiditis causes release of preformed hormone from damaged follicles and is often a transient thyrotoxic phase rather than increased synthesis.

AETIOLOGY AND MECHANISMS

• Graves disease is associated with genetic susceptibility, female sex, smoking and other autoimmune conditions.
• TSH-receptor antibodies stimulate follicular cells, causing diffuse goitre and excess T3/T4; orbital fibroblast activation produces thyroid eye disease.
• Other causes of thyrotoxicosis include toxic adenoma, toxic multinodular goitre, exogenous thyroid hormone, amiodarone-related disease and thyroiditis.
• Inflammation may be painful subacute granulomatous (often post-viral), painless/silent, postpartum or chronic autoimmune (Hashimoto).
• Acute suppurative thyroiditis is uncommon and bacterial.

CLINICAL FEATURES

• Thyrotoxicosis produces weight loss despite appetite, heat intolerance, sweating, tremor, palpitations, anxiety, insomnia, proximal myopathy, frequent stools and menstrual disturbance.
• Examination may reveal tachycardia, atrial fibrillation, warm moist skin, fine tremor, brisk reflexes and goitre.
• Graves-specific signs include diffuse vascular goitre, lid retraction, proptosis, diplopia and pretibial dermopathy.
• Thyroid storm is severe decompensated thyrotoxicosis with fever, marked tachycardia, agitation/delirium, vomiting/diarrhoea, heart failure or hepatic dysfunction.
• Subacute thyroiditis typically causes a tender thyroid, fever and pain radiating to jaw/ear; Hashimoto often presents with painless goitre and hypothyroidism.

INVESTIGATIONS AND DIFFERENTIATION

• Measure TSH, free T4 and T3.
• In primary hyperthyroidism, TSH is suppressed and free hormones are raised; T3-predominant disease may occur.
• TSH-receptor antibodies support Graves disease.
• ESR/CRP may be raised in painful subacute thyroiditis.
• Ultrasound with Doppler may show diffuse hypervascularity in Graves and heterogeneous echotexture in thyroiditis.
• Radioiodine uptake is increased diffusely in Graves, focal in toxic adenoma, patchy in multinodular disease and low in thyroiditis or exogenous hormone use.
• ECG evaluates tachyarrhythmia; assess full blood count and liver function before antithyroid drugs.

DIFFERENTIAL DIAGNOSIS

• Anxiety disorders, sepsis, stimulant use, pheochromocytoma, medication effects and other causes of weight loss/tachycardia may mimic thyrotoxicosis.
• Distinguish hormone overproduction from hormone leakage using uptake studies, antibodies and clinical context.

MANAGEMENT OF GRAVES DISEASE

• Beta-blockers control adrenergic symptoms when appropriate.
• Antithyroid drugs (usually carbimazole/methimazole; propylthiouracil in selected situations such as first trimester pregnancy or thyroid storm) inhibit hormone synthesis.
• Counsel patients to stop the drug and seek urgent assessment for fever or sore throat because of possible agranulocytosis; jaundice or dark urine requires evaluation for hepatic injury.