Hyperthyroidism

• Background

  Definitions

  Thyrotoxicosis refers to high thyroid hormone levels due to ↑secretion (hyperthyroidism) or ↑release of stored hormones (thyroiditis).

  Causes

  • Graves' disease (70%): autoimmune TSHR-Ab activates TSH receptor in thyroid gland (IgG) and orbital pre-adipocytes (IgM). Aka diffuse toxic goitre. Usually young women.
  • Toxic multinodular goitre (20%). Usually older patients.
  • Solitary toxic nodule/adenoma (5%).
  • Causes of mixed thyroid disease: subacute granulomatous thyroiditis (aka de Quervain's), subacute lymphocytic thyroiditis (aka painless/silent), post-partum thyroiditis, amiodarone.

• Signs and symptoms

  Symptoms

  • Systemic: hot, thirsty, weight loss.
  • GI: diarrhoea, vomiting
  • Motor: tremor, proximal weakness.
  • Psychological: anxiety, irritable, labile emotions.
  • Reproductive: ↓menstruation, infertility
  • Dermatological: hair loss, itch.
  • Graves ophthalmopathy (30%): diplopia and blurring (from reduced eye movement), gritty, sore eyes, and tears, dryness, or photophobia.

  Compression by goitre can lead to:

  • Dysphagia
  • SOB ± stridor.
  • Hoarseness

  Signs

  General:

  • Palmar erythema.
  • CV: ↑HR, AF.
  • Eyes: lid retraction (hyperthyroid stare) and lid lag.
  • Fine tremor.
  • Thyroid bruit.
  • Goitre or lumps. Absence may suggest levothyroxine ingestion.

  Graves:

  • Diffuse, non-tender, firm goiter.
  • Graves ophthalmopathy (30%): proptosis (aka exophthalmos). May exacerbate lid retraction appearance.
  • Pretibial myxoedema (rare): purple/red discolouration and non-pitting oedema above the lateral malleolus. Thyroid dermopathy can also occur in other sites.
  • Thyroid acropachy (rare): clubbing, bony finger growths.

• Investigations

  Bloods:

  • Screen with TSH (↓) and confirm with T4 (↑). In secondary (pituitary) hyperthyroidism, both ↑.
  • Check T3 alongside T4. Usually normal, but can be raised in rare cases of T3 toxicosis.
  • Graves: ↑TSHR-Ab, ↑TPO-Ab.

  Imaging:

  • Thyroid US if nodules suspected. FNA may be needed, especially for solitary nodules, which are more likely to be malignant than multiple nodules.
  • Technetium radioactive thyroid scan if TSHR-Ab negative: distinguishes Graves (high uptake) from subacute lymphocytic or granulomatous thyroiditis (low uptake).

• Management

  Antithyroid treatment

  Radioactive iodine

  • 1st line in adults with severe Graves or toxic nodule(s).
  • Unsuitable if: pregnancy or attempting pregnancy (male or female), thyroid eye disease, malignancy/compression suspected.

  Antithyroid drugs

  1st line in adults with milder Graves, all kids with Graves or toxic nodule, or whenever radioactive iodine is unsuitable.

  Antithyroid thioamide drugs – carbimazole (1st line) or propylthiouracil – are used to suppress function, with treatment duration 12-18 months. 2 approaches:

  • 'Block and replace': completely suppress function with a thioamide and give levothyroxine to replace T4.
  • Alternatively, 'dose titration' involves only a thioamide. Practically harder and requires more monitoring. Avoid in thyroid eye disease, as it may exacerbate the condition by causing hypothyroidism.
  • Both have similar outcomes: 50% remission.

  In pregnancy and breastfeeding:

  • The lowest effective dose of a thioamide should be used i.e. not block and replace.
  • Propylthiouracil is safer for the fetus so is preferred.

  Surgical thyroidectomy

  Indicated if suspected malignancy, compressing goitre, or other treatments contraindicated.

  Adjuncts

  • β-blocker for symptom control as many symptoms are sympathetic-mediated.
  • Smoking cessation improves eye disease.
  • Eyelid surgery sometimes needed for eye disease.

• Thioamides

  Drugs

  • Carbimazole
  • Propylthiouracil

  Mechanism

  • Act as preferential substrates for thyroid peroxidase (TPO), preventing iodination of tyrosine residues on thyroglobulin and thus reducing T3 and T4 synthesis.
  • Several weeks to take effect.

  Side effects

  • Agranulocytosis (1/500) → sore throat, ulcers, fever → stop treatment. If it happens, it is usually in the first 8 weeks.
  • Commoner but less serious: rash, myalgia, headache, nausea.

  Choice of drug

  • Carbimazole is 1st line as propylthiouracil carries a small risk of severe liver injury.
  • NICE only recommend propylthiouracil in (a) pregnancy, (b) thyrotoxic storm, and (c) if there are minor reactions to carbimazole and other treatment options (radioiodine, surgery) are declined.
  • However, both drugs have similar mechanisms and in many contexts e.g. agranulocytosis, there will be no benefit of switching from one to the other.

• Complications

  Acute:

  • Thyroid storm.

  Chronic:

  • Cardiovascular: AF, angina, HF.
  • Osteoporosis
  • Gynecomastia

• Thyroid storm

  Aka hyperthyroid crisis, thyrotoxic storm.

  Pathophysiology

  • Severe, acute manifestation of hyperthyroidism.
  • Illness or surgery are often triggers.

  Signs and symptoms

  • Fever
  • CV: ↑HR, AF, HF.
  • Diarrhoea, vomiting, acute abdomen.
  • Confusion and coma.

  Management

  Standard hyperthyroid treatment – β-blocker and thioamide (propylthiouracil 1st line) – plus:

  • Iodine compounds to block T4 and T3 release. Give 1 hour after thioamide as otherwise it may increase thyroid hormone synthesis.
  • Glucocorticoids (hydrocortisone or dexamethasone) to reduce T4 to T3 conversion.
  • Bile acid sequestrants (e.g. cholestyramine) to prevent T4 and T3 reabsorption in the gut.