Hypothyroidism

Hypothyroidism is an endocrine disorder in which the thyroid gland fails to produce sufficient thyroid hormones to meet the body’s metabolic demands. Thyroid hormones play a crucial role in regulating metabolism, growth and organ function; therefore, inadequate hormone production affects multiple physiological systems. The condition may develop gradually and often presents with subtle or non-specific symptoms, making early diagnosis challenging. Hypothyroidism is common worldwide and affects individuals of all ages, with higher prevalence among women and older adults.

Causes and Risk Factors

The causes of hypothyroidism are diverse and depend on geography, dietary patterns and underlying health conditions. Globally, iodine deficiency remains the most common cause. Populations with low dietary iodine intake often develop endemic goitre and reduced thyroid hormone synthesis. In regions where iodine intake is sufficient, Hashimoto’s thyroiditis, a chronic autoimmune condition, is the leading cause. In this disorder, immune-mediated destruction of thyroid tissue results in progressive loss of function, often accompanied by the presence of antithyroid antibodies such as thyroid peroxidase and thyroglobulin antibodies.
Other causes include:

• Previous radioactive iodine therapy, typically administered for hyperthyroidism
• Surgical removal of the thyroid gland
• Congenital thyroid disorders
• Disorders of the hypothalamus or pituitary gland leading to secondary or tertiary hypothyroidism
• Certain medications, including lithium and amiodarone
• Transient postpartum thyroiditis, in which women may initially experience hyperthyroidism followed by hypothyroidism

Primary hypothyroidism, involving impaired function of the thyroid gland itself, is considerably more common than central (secondary or tertiary) hypothyroidism caused by inadequate pituitary or hypothalamic stimulation.

Signs and Symptoms

Symptoms of hypothyroidism vary widely and depend on the severity of hormone deficiency. Many individuals experience few or mild symptoms initially, while others develop noticeable physical and mental changes. Common features include fatigue, cold intolerance, constipation, dry skin, weight gain, low mood or depression, slowed heart rate and cognitive slowing. Some individuals develop a goitre due to thyroid enlargement.
Neurological signs such as delayed relaxation of the ankle reflex are characteristic and reflect the degree of hormone deficit. Hashimoto’s thyroiditis may produce a visible goitre due to inflammatory infiltration. In middle-aged women, symptoms may be mistaken for those associated with menopause, leading to delayed diagnosis.
Severe untreated hypothyroidism can progress to myxoedema coma, a rare but life-threatening condition. It typically presents with hypothermia, altered consciousness, hypoventilation, bradycardia and distinctive physical signs such as dry skin and macroglossia. This state often arises in the context of acute illness superimposed on longstanding hypothyroidism.

Hypothyroidism in Pregnancy

Untreated hypothyroidism during pregnancy is associated with infertility, miscarriage and increased perinatal mortality. Thyroid disease affects a small proportion of pregnancies, but even subclinical hypothyroidism may raise the risk of preterm birth. Adequate thyroid hormone levels are essential for normal fetal brain development, particularly in early gestation before the fetal thyroid becomes fully functional. Thyroid hormone replacement is safe in pregnancy, and regular monitoring of thyroid-stimulating hormone levels is recommended to ensure optimal maternal and fetal outcomes.

Hypothyroidism in Children

Congenital hypothyroidism may initially present with normal birth size, but infants may develop symptoms such as hypotonia, poor feeding, constipation, prolonged jaundice, large fontanelles, macroglossia and umbilical hernia. Delayed diagnosis can result in intellectual impairment, reduced muscle tone, strabismus, and delayed motor and speech development. Early detection through newborn screening and prompt treatment with levothyroxine significantly improve long-term outcomes.
In older children and adolescents, signs may include slow growth, fatigue, cold intolerance, dry skin, thickened skin texture, constipation, early weight gain and delayed puberty. A goitre may be present, either diffusely enlarged or nodular.

Diagnosis

Diagnosis is based on laboratory assessment of thyroid function. A raised thyroid-stimulating hormone level with reduced thyroxine indicates primary hypothyroidism, whereas a low thyroid-stimulating hormone level associated with low thyroxine suggests central hypothyroidism. Additional assessment may include measurement of thyroid autoantibodies to identify autoimmune thyroiditis. In many regions, population-wide iodisation of salt has significantly reduced the incidence of iodine deficiency-related hypothyroidism.

Epidemiology

Approximately one billion people worldwide are estimated to be iodine deficient, although not all develop hypothyroidism. In the United States, overt hypothyroidism affects around 0.3–0.4 per cent of the population, while subclinical hypothyroidism is more common, occurring in roughly 4–8 per cent of people. Women are more frequently affected than men, and prevalence increases with age, especially after 60 years. While humans are most commonly affected, hypothyroidism also occurs in animals such as dogs, and more rarely in cats and horses.

Pathophysiology

Thyroid hormones, predominantly thyroxine (T4), are synthesised by the thyroid gland using iodine and the amino acid tyrosine. T4 is converted in peripheral tissues to the biologically active triiodothyronine (T3), which binds to nuclear receptors and regulates gene transcription. T3 also interacts with membrane receptors to influence cell metabolism, angiogenesis and growth. Most circulating thyroid hormones are bound to plasma proteins; only the free fraction is biologically active.
When hormone levels fall, the metabolic rate decreases, affecting cardiovascular, neurological and musculoskeletal systems. Electrocardiographic changes may occur in both overt and subclinical hypothyroidism, including prolonged ventricular repolarisation and predisposition to arrhythmias such as atrial fibrillation.
Primary hypothyroidism results from impaired hormone synthesis, whereas central hypothyroidism reflects reduced stimulation from the pituitary or hypothalamus. Autoimmune thyroid destruction, iodine deficiency, or post-surgical changes may reduce the gland’s capacity to produce T4. In postpartum thyroiditis, a temporary inflammatory process leads to a biphasic pattern of initial hormone excess followed by deficiency.

Management

The cornerstone of treatment is thyroid hormone replacement, usually with levothyroxine. The dosage is tailored to the individual, with adjustments made on the basis of clinical response and normalisation of thyroid-stimulating hormone levels. Treatment is lifelong in most cases. During pregnancy, dosage adjustments are often required due to increased metabolic demands. Although adequate dietary iodine is essential, excessive intake may exacerbate some forms of thyroid dysfunction.