Hypothyroidism

Results from any disorder that results in insufficient secretion of thyroid hormones from the thyroid gland

Aetiology

Congenital hypothyroidism

• Absent or under-developed thyroid gland

• Dyshormogenesis - genetic defects in the synthesis of thyroid hormones, resulting in hypothyroidism with goitre

• Iodine deficiency during pregnancy

• Maternal transmission of antithyroid drugs

Aquired hypothyroidism

• Hashimoto's thyroiditis (chronic lymphocytic thyroiditis)
• Most common cause of hypothyroidism in iodine-sufficient regions
• Affects middle aged women (45-60 years)
• Associated with family history of autoimmune thyroiditis or other autoimmune diseases
• Associated with HLA - DR3 and DR5

• Iodine deficiency - most common cause worldwide, particularly in iodine-deficient regions

• Iatrogenic e.g. post-ablative therapy (e.g. radioiodine, surgery)

• Others: atrophic thyroiditis (autoimmune), de Quervain's thyroiditis and post-partum thyroiditis

• Pituitary disorders (e.g. pituitary adenoma) resulting in TSH deficiency

• Hypothalamic disorders resulting in TRH deficiency

Pathophysiology

Hasimoto's thyroiditis

• Gradual failure of throid function due to autoimmune destruction of thyroid tissue

• Characterised by anti-thyroglobulin and anti-peroxidase antibodies which, when bound, cause antibody dependent cell mediated cytotoxicity

• CD 8+ cells may mediate destruction of thyroid epithelium

• Cytokine mediated cell death
• 𝛾 interferon from T cell activation recruits macrophages that may damage thyroid follicles

• May be preceded by transient hyperthyroidism (Hashitoxicosis)

• Prominent lymphoid infiltrate - lymphocytes, plasma cells and reactive follicles with germinal centres

• Thyroid follicles atrophy

• Follicular cells have abundant eosinophilic cytoplasm (Hurthle cells)

• May see progressive fibrosis within the gland

Clinical presentation

Symptoms related to decreased metabolic rate

• Tiredness/malaise

• Weight gain, despite decreased appetite

• Cold intolerance

• Decreased sweating

• Coarse, sparse hair, brittle nails and cold, dry skin

• Constipation

• Bradycardia - slow pulse

• Hypothyroid myopathy - myalgia, stiffness, cramps

• Delayed relaxation of deep tendon reflexes

• Hyperlipideamia - xanthlasma

• Hypercarotenaemia

Symptoms related to generalised myxoedema

• Myxoedema refers to the accumulation of mucopolysaccharide in subcutanous tissues

• Doughy skin texture, puffy appearance

• Myxoedematous heart disease - dilated cardiomyopathy, brachycardia, dyspnoea, pericardial effusion, worsening of heart failure

• Periorbital oedema (hypothyroidism only) and pretibial myxoedema (also seen in Graves' disease)

• Entrapment syndromes e.g. carpal tunnel syndrome

• Peripheral neuropathy

• Macroglossia

• Deep hoarse voice

• Myxoedema coma

Symptoms related to hyperprolactinaemia

• Hyperprolactinaemia - increased TRH causes increased PRL secretion

• Menorrhagia

• Later oligo or amenorrhoea

Further symptoms

• Goitre (in Hashimoto thyroiditis) or atrophic thyroid (in atrophic thyroiditis)

• Impaired cognition, depression

• Vitiligo may be present

• Obstructive sleep apnoea - macroglossia or the presence of a goitre can inhibit breathing during sleep

Congenital hypothyroisim

• Cretinism - dwarfism and limited mental functioning due to deficiency of thyroid hormones

Investigations

Primary hypothyroidism

• TSH high

• Free T4 and T3 low

• Macrocytosis (↑ MCV)

• ↑ creatinine kinase

• ↑ LDL cholesterol

• Hyponatraemia
• ↓ renal tubular water loss

• Hyperprolactinaemia

• Anti-TPO antibody - 95%

• Anti-thyroglobulin - 60%

• TSH receptor antibody (blocking) - 10-20%

Secondary hypothyroidism

• TSH low (or 'normal')

• Free T4 and T3 low

Management

• Normal metabolic rate should be restored gradually as rapid restoration of metabolic rate may precipitate cardiac arrhythmias

Primary hypothyroidism

• Younger patients: start levothyroxine at 50-100 µg daily and gradually increase

• In the elderly with a history of IHD: start levothyroxine at 25-50 µg daily, adjusted every 4 weeks according to response

• Check TSH 2 months after any dose change

• Once stabilised within the normal range, TSH should be checked every 12-18 months

Secondary hypothyroidism

• Titrate dose of levothyroxine to the tT4 level - should be higher end of normal (TSH unreleable due to low TSH production)

Complications

Myxoedema Coma — Hypothyroid Crisis

• Typically affects elderly women with long standing but frequently unrecognised or untreated hypothyroidism

• Mortality up to 60% despite early diagnosis and treatment

• Triggered by infection (pneumonia, UTI), acute trauma, myocardial infarction

• Altered mental status (confusion → stupor → coma)

• Hypothermia (core temp often <35°C)

• Non-pitting edema (myxedema)

• Cardiovascular: Bradycardia, hypotension, shock

• ECG: bradycardia, low voltage complexes, varying degrees of heart block, T wave inversion, prolongation of the QT interval

• ABGs: type 2 respiratory failure (hypoxia, hypercarbia, respiratory acidosis)

• Co-existing adrenal failure present in 10% of patients

• Airway and Breathing
• Oxygen therapy or mechanical ventilation if hypoventilating

• Thyroid Hormone Replacement
• IV Levothyroxine (T4) loading dose
(e.g., 5–8 mcg/kg IV then 50–100 mcg/day)
• May combine IV Liothyronine (T3) in severe or non-responsive cases

• Glucocorticoids
• Hydrocortisone 50–100 mg IV every 6–8 hours
• Given before thyroid hormone to prevent adrenal crisis

• Supportive Care
• Passive rewarming (avoid aggressive warming → vasodilation collapse)
• Correct hypoglycemia (IV dextrose)
• Manage hyponatremia carefully
• Treat hypotension (fluids + vasopressors if needed)
• Treat underlying cause (antibiotics if infection suspected)

• Monitor continuously
• Cardiac rhythm, electrolytes, ABG, urine output, mental status

Long-term complications of autoimmune hypothyroidism

• Increases risk of developing other auto-immune diseases

• Increased risk of developing B-cell NHL in the affected gland