Hyperthyroidism (Thyrotoxicosis)

Thyrotoxicosis: the clinical, physiological, and biochemical state arising when the tissues are exposed to excess thyroid hormone — with symptoms

Hyperthyroidism: refers specifically to conditions in which overactivity of the thyroid gland leads to thyrotoxicosis — no symptoms

Aetiology

Graves disease

• Accounts for 85% of cases

• Higher incidence in females - 10:1

• Usually presents between 20-40 years

• Interacting susceptibility genes plus environmental factors

• Increased incidence in family members
• Sisters and children of women with Graves' have a 5-8% risk of developing autoimmune thyroid disease (Graves' or autoimmune hypothyroidism)

• Susceptibility associated with certain HLA haplotypes

• Polymorphisms in immune regulation associated genes e.g. CTLA-4, PTPN-22 have also been linked to Graves' disease

• There is an association with other autoimmune diseases

Other causes of thyrotoxicosis associated with hyperthyroidism

• Hashitoxicosis - transient hyperthyroidism caused by inflammation associated with Hashimoto's thyroiditis, patient will then develop hypothyroidism

• Thyrotropinoma - TSH secreting pituitary adenoma (very rare)

• Thyroid cancer - only very rarely cause thyrotoxicosis

• Choriocarcinoma - trophoblast tumour secreting hCG

• Toxic solitary nodule

• Toxic multinodular goitre

Causes of thyrotoxicosis not associated with hyperthyroidism

• Subacute (de Quervain's) thyroiditis

• Post-partum thyroiditis

• Drug-induced thyroiditis (e.g. amiodarone)

• Over-treatment with levothyroxine

• Thyrotoxicosis factitia

• Metastatic thyroid carcinoma

• Struma ovarii (teratoma containing thyroid tissue)

Pathophysiology

Graves disease

• Involves auto-antibodies to TSH receptor (TRAb/TSHrAb), thyroid peroxisomes and thyroglobulin

• The anti-TSH receptor antibodies stimulate the thyroid resulting in increased function

• Some antibodies can inhibit function - may explain paradoxical episodes of hypofunction which can occur

Clinical presentation

General symptoms

• Weight loss despite increased appetite

• Frequent, loose bowel movements

• Sweating and heat intolerance

• Goitre - diffuse in Graves, goitre with firm nodules if toxic multinodular goitre

General signs

• Thyroid bruit - associated only with large goitres
• Reflective of hypervascularity of thyroid
• Auscultate over the thyroid

Systemic review

• Double vision

• Graves ophthalmopathy (see below)

• Increased pulse rate

• Palpitations, AF

• Rarely cardiac failure

• Fine tremor of the outstretched fingers

• Muscle weakness, especially in thighs and upper arms

• Increased nervousness and excessively emotional

• Sleep disturbance

• Depression

• Insomnia

• Hair change (thin, brittle hair)

• Rapid fingernail growth

• Menstrual cycle changes, including lighter bleeding and less frequent periods

Specific signs of Graves' disease

• Pretibial myxoedema (also occasionally seen in Hashimoto's thyroiditis)

• Thyroid arcropachy - thickening of the extremities manifested by digital clubbing, soft tissue swelling of the hands and feet, and periosteal new bone formation

• Graves eye disease
• Autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, erythema, conjunctivitis, and bulging eyes (exophthalmos)
• Occurs in ~20% of Graves' patients
• Results from autoimmune inflammation of the extra-ocular muscles as orbital fat and connective tissue TSH receptors
• Association with smoking (smoking cessation very important)
• Presentation can precede diagnosis of Graves'
• Can be unilateral
• Most disese is mild but can be severe and sight-threatening

• Diffuse goitre

Investigations

Thyroid hormones

• TSH low

• Free T3/T4 high

• TSH high

• Free T4 and T3 high (or 'normal')

Thyroid autoantibodies in Graves' diseasae

• Anti-TPO antibody - 70-80%

• Anti-thyroglobulin antibody - 30-50%

• TSH receptor antibody (stimulating) - 70-100%

Scintiscan

• Used in patients who are antibody negative to look for toxic nodular disease

Management

Antityhroid Drugs

• Propylthiouracil (PTU) — safe in 1st trimester pregnancy
• starting dose 300-600 mg/day, max dose 2.000 mg/day

• Methimazole (1st line except 1st trimester pregnancy)
• Start dose 20-40 mg/day

β-blockers — symptoms reliever

• Propanolol 10-20 mg/6 hr/PO

• Dosage can be increased until symptoms controlled

• Generally 80-320 mg/day

Radioiodine

• 1st choice treatment for relapsed Graves' disease and nodular thyroid disease

• High risk of hypothyroidism when used in Graves' disease (1:2)

Thyroidectomy

• Useful when radioiodine is contraindicated e.g. pregnancy

• Will leave a scar

• Surgical/anaethetic risks:
• Recurrent laryngeal nerve palsy
• Hypothyroidism
• Hypoparathyroidism

Complications

Thyroid storm

• Rapid deterioration of hyperthyroidism with
• Hyperpyrexia >40 C
• Severe tachycardia, atrial fibrillation, hypotension, or shock
• Agitation, Delirium, Psychosis, Seizures, Coma
• Nausea and vomiting, Diarrhea, Abdominal pain, Jaundice (severe cases)

• Precipitatin Factors
• Infection (most common trigger)
• Surgery (especially thyroid or non-thyroid surgery)
• Trauma
• Acute myocardial infarction
• Diabetic ketoacidosis
• Parturition
• Sudden withdrawal of antithyroid drugs
• Iodine load (contrast media, amiodarone)

• Diagnostic Scoring
• Burch–Wartofsky Point Scale (BWPS)

• Propylthiouracil (PTU) 500-1000mg loading dose, then 250-500mg PO QID

• β-blockers → propranolol PO 60-80mg QID

• Potassium iodide

• IV Hydrocortisone 100mg/8 hours

• IV fluids +/- inotropes

• Treat precipitating cause e.g. MI, infection, PE