23rd May 2025

Hypothyroidism

Hypothyroidism is a condition where the thyroid gland is underactive, leading to T3 and T4 deficiencies. The commonest cause is autoimmune thyroid diseases.

Causes of hypothyroidism can be classified as thyroid-related or central, and are summarised in table 5 below.

Table 5: Hypothyroidism causes

Hypothyroidism may also be classified as primary, secondary, or tertiary:     

• Primary hypothyroidism: failure in thyroid hormone production due to disease targeting thyroid gland itself, e.g., Hashimoto’s thyroiditis, postpartum thyroiditis, subacute thyroiditis, iatrogenic, gland dysplasia, and Riedel’s thyroiditis.
• Secondary hyperthyroidism: occurs due to deficiency of TSH which occurs with pituitary disorders.
• Tertiary hyperthyroidism: occurs due to hypothalamic disorders causing  Thyroid Releasing Hormone (TRH) deficiency and subsequently thyroid hormone deficiency.

Clinical picture in hypothyroidism disorders:

• Cardiovascular:
  • ↓ HR
  • Myxoedematous heart disease (bradycardia, dilated cardiomyopathy, dyspnoea)
  • ↓ Cardiac output (CO)
• Neuromuscular and psychiatric signs:
  • Impaired cognition
  • Somnolence
  • Depression
  • Hyporeflexia
  • Woltman sign (delayed relaxation of deep tendon)
  • Myopathy (proximal muscle weakness with increased creatinine kinase levels)
  • Entrapment syndrome (e.g., carpal tunnel syndrome)
  • Myxoedema (localised muscle contraction induced by light muscle percussion)
• Reproductive:
  • Abnormal menstrual cycle (either amenorrhoea or menorrhagia)
  • Galactorrhoea
  • Decreased libido, erectile dysfunction, delayed ejaculation, and infertility
• Metabolic and dermatological signs:
  • Cold intolerance
  • Weight gain
  • Fatigue
  • Cold dry skin
  • Decreased sweating.
  • Pretibial oedema
  • Coarse hair with loss especially of the outer 1/3 of eyebrows
• Gastrointestinal:
  • Constipation
• Other manifestations:
  • Deep hoarse voice

Hashimoto’s disease

• Hashimoto’s’ thyroiditis (also known as chronic autoimmune of atrophic thyroiditis) is the commonest form of hypothyroidism in non-iodine deficient areas. Its peak incidence is mainly between 30–50-year-olds with female predominance. 
• It is an autoimmune disease associated with HLA-DR5 genotype. Cytotoxic T cells attack the follicular cells of the gland and associated with unregulated production of autoantibodies against thyroid peroxidase (TPO), and thyroglobulin(Tg).  As a result, the gland is destroyed and hypofunction results. 

Clinical picture

• It can be either subclinical (75%) or with overt clinical picture of hypothyroidism (20%) (see full description above). It is of insidious onset slowly progressing over months to years. 
• In the early stage, patients occasionally may have painless goitre especially which tends to be rubbery and of symmetrical enlargement. Hashitoxicosis (5%) sometimes present with transient hyperthyroidism picture. Upon later stage (end-stage gland extensive fibrosis), the gland tends to be of normal size as seen in  atrophic thyroiditis. Hypothyroidism picture is predominant. Patients have increased risk to other autoimmune conditions as T1DM, SLE, Grave’s disease, Addison disease, other HLA-associated conditions, or non-Hodgkin lymphoma.  

Investigations

• TFTs: within the early-stage transient hyperthyroidism picture occurs then progress to hypothyroid picture of high TSH and low levels of T3 and T4.
• Thyroid antibodies: may be positive for anti-TPO (>90%) also known as thyroid microsomal antibodies, and anti-Tg (20-25%).
• Other blood tests can show macrocytic anaemia and hypercholesterolemia.
• Thyroid biopsy: It is characterised with extensive infiltration of the thyroid parenchyma by lymphocytes and plasma cells. Germinal centres are formed as a result. Occasionally done in case of malignancy suspicion.

Prognosis and management

• The long-term prognosis of the chronic type is good because it can be easily corrected with T4 replacement. Local manifestations due to goitre size are not common. However, in case of rapidly enlarging goitre and pain, further investigation may be required. A short course of prednisolone may prove helpful. 
• The mainstay of management for hypothyroidism is oral thyroxine replacement.
• Levothyroxine has a long half-life which enables the patient to take 2 doses at once if a dose is omitted. Normal metabolic state should be restored gradually to avoid precipitating cardiac arrhythmias. Fasting ingestion of levothyroxine in the morning or the evening is recommended, as concurrent ingestion of calcium, iron, food, and other medications may impair its absorption. NICE guidelines advise the following:
  • For adults <65 with primary hypothyroidism and no cardiovascular disease history, start levothyroxine at a dosage of 1.6 mcg/kg of body weight per day (rounded to the nearest 25 mcg).
  • Adults ≥ 65 and patients with cardiovascular history, start levothyroxine at a dose of 25 to 50 mcg/ day with titration by 25 mcg at 4-week intervals until normal metabolic state and TSH level is reached.
  • In antenatal and perinatal period: Patients who become pregnant and on replacement therapy, recommendation to increase levothyroxine by 25 mcg. Dose requirements can increase by 25-50% in pregnancy due to increased thyroid-binding globulin (TBG), to avoid impaired cognitive function in offspring.

Subclinical hypothyroidism

This condition refers to a clinical picture of raised TSH in the presence of normal free thyroid hormone concentrations in an asymptomatic patient. It is most commonly caused by chronic autoimmune thyroiditis. It occurs more commonly in postmenopausal women. 

Clinical picture and investigations

• Many patients will be asymptomatic, and subclinical hypothyroidism will be picked up on blood tests done for other reasons.
• Some patients may have mild nonspecific symptoms such as tiredness or weight gain. It can progress to overt hypothyroidism with a rate 2-5% per annum. There is increased incidence of cardiovascular risk which is greater if <65 years old. 
• As mentioned above, TSH will be raised but thyroid hormones are within normal. Patients who show +ve anti-TPO antibodies (TPOABs) are more likely to develop overt hypothyroidism. Thus, monitoring for TSH is required for them for 6-12 months. If TPOAbs are -ve, then TSH monitoring is advised every 3-5 years.

Management

There is some controversy with regards to treatment of subclinical hypothyroidism. Some authorities prefer to start treatment before progression to overt hypothyroidism. NICE guidelines suggest:

• Measuring TPOAbs for adults with TSH above the reference range.  
• Considering treatment with levothyroxine for adults when TSH is ≥ 10mIU/L on 2 separate occasions of 3 months apart. 
• 6-month trial of levothyroxine for adults <65 with TSH findings above reference range but below 10mIU/L on 2 separate occasions (3-months apart) and symptoms of hypothyroidism. NICE advises to re-adjust dose accordingly if symptoms do not improve. If TSH falls below 10mIU/L, then levothyroxine is advised to stop but monitoring continues.

In case of subclinical hypothyroidism due to non-thyroidal illness or transient thyroiditis from which the patient is recovering, it is advised not to start treatment on the basis of a single raised TSH level with negative TPOAbs.

Congenital hypothyroidism

• Congenital hypothyroidism refers to the deficiency of thyroid hormone from birth. It is the commonest neonatal endocrine disorder. It occurs in about 1 in 4000 live births in the UK, with predominance in females. Most of the cases are familial and inherited as autosomal recessive conditions. Errors in the formation or migration of the thyroid tissue can result in thyroid aplasia, dysplasia, or ectopy (primary hypothyroidism). It occurs due to an error in thyroid metabolism, enzyme, or iodine deficiency. If TSH deficiency is present, this can cause secondary or central hypothyroidism. Both of these types cause permanent hypothyroidism. 
• Transient congenital hypothyroidism can be due to maternal ingestion of antithyroid drugs or maternal TPOAbs or iodine deficiency.

Clinical picture

Clinical features are subtle, so making the diagnosis at birth may be challenging. Later infants show the following symptoms:

• coarse facies, macroglossia, and hoarse cry
• the posterior fontanelle remains open, and closure of the anterior fontanelle is delayed
• umbilical hernia
• cold or mottled skin
• hypotonia and hypothermia
• anaemia or prolonged jaundice may be present
• poor feeding  and constipation
• presence of a palpable goitre

If not detected early and treated, profound intellectual disabilities may develop. If delayed treatment is delivered, neurological problems such as spasticity, gait abnormalities, dysarthria or behavioural issues can result.

Investigations

Due to severe complications resulting from delayed treatment of congenital hypothyroidism, in the UK filter paper blood spot TSH measurement is used for screening. The test is done at least 48 hours after birth (within 2-8 days) to avoid false positive results.

• High TSH is diagnostic for primary hypothyroidism. 
  • Confirmatory examinations within 2 weeks should be done. Serum TSH and free T4 are measured. Again, high TSH and low T4 indicates the diagnosis of primary hypothyroidism.
• Low or normal TSH occurs in secondary hypothyroidism.
• Caution with preterm infants and acutely ill infants should be considered as there is delayed TSH rise. This requires a routine second screening test.

Management

The mainstay of treatment is with thyroxine replacement, which should start as soon as possible within the first 18 days of life. The aim is to increase serum free T4 levels to normal as rapidly as possible. This is because a delay in the restoration of normal T4 levels within a week may result in long-term cognitive function impairment . . Regular monitoring of TSH and T4 levels as well as growth measurement and bone age assessment are required until growth is completed.

Myxoedema coma

• Myxoedema describes the clinical syndrome that develops as a result of severe hypothyroidism. This term is also applied to cases with deposition of mucinous substances in the subcutaneous tissue causing skin thickening. 
• Myxoedema coma is a life-threatening condition,  with decreased levels of consciousness, which may result in coma,  and hypothermia. It occurs due to longstanding undiagnosed hypothyroidism. It occurs most commonly in the elderly.

Causes

• Most commonly occurs as a complication of chronic autoimmune thyroiditis. 
• It also occurs post-thyroidectomy or post-radioactive iodine therapy for hyperthyroidism. 
• Rarely may happen due to medication such as lithium and amiodarone.
• May be triggered by cold exposure,  trauma , infection, cerebrovascular accident, heart failure, or due to CNS depressants administration.
• The long-standing reduced metabolic rate and decreased oxygen consumption due to hypothyroidism affects all body systems resulting in the decreased conscious level and hypothermia.

Clinical picture and prognosis

Features suggestive of a precipitating cause may be present, along with a history of hypothyroidism or thyroidectomy (note that the hypothyroidism may be undiagnosed, but patients will be symptomatic). Precipitating factor features can be present.  Associated with these features are the following:

• depressed conscious level – may be comatose.
• hypothermia (core temperature < 35oc)
• bradycardia or various degrees of heart block.
• hypoventilation with hypoxia and hypercapnia
• other pathologies related to hypothyroidism e.g., heart failure, cyanosis.
• hyporeflexia

This condition has a mortality rate >50%. With immediate recognition of the condition and management, the mortality rate can reach 25%. Death occurs due to respiratory failure, sepsis, and GI bleeding.

Investigations

Assessment of thyroid function is  required alongside investigations for detecting precipitating factors and possible complications. TFTs (taken prior to commencing treatment) usually show increased TSH in primary hypothyroidism and decreased in secondary causes. T3 and T4 are reduced. Investigations for cause and complications may include:

• FBC, urea and electrolytes (U&Es) (deranged due to decreased renal perfusion)
• Hyponatraemia (Na < 130 mmol/l) due to low serum osmolarity.
• Hypoglycaemia is common (due to sepsis, decreased oral intake or adrenal insufficiency).
• ECG: can show sinus bradycardia, stages of heart block, QT interval prolonged or non-specific changes in ST segment or T waves. 
• CXR: might show signs of infection or heart failure (HF).
• Random cortisol level (taken prior to commencing treatment).

Management

This includes treatment of the precipitating factors, hypothyroidism state and treatment of complications. If myxoedema coma is suspected, management should not be delayed pending investigation results.

• Precipitating factors management can be treatment of infection through the acknowledged sepsis 6 management whilst identifying the source of infection.
• Thyroid hormone replacement: There is controversy regarding regimen to follow. An example of a regimen is as follows: 
  • T4 300-500 mcg IV or NG as a starting dose 
  • Followed by 50-100mcg daily until the patient is tolerating oral formulations .
  • If no improvement in 24-48h, T3 10mcg IV 8 hourly or 25mcg IV 8-hourly can be added to the previous replacement. 
  • T3 acts more quickly but may worsen ischemic heart disease.
• Management of complications:
  • Supportive management entails managing hypothermia is managed via passive external rewarming. Aim for slow rise in core temperature of 0.5oC/h. Warm humidified O2 via face mask or mechanical ventilation if needed. IV fluids with caution due to potential risk of left ventricular HF. Cardiac monitoring for possible arrhythmias occurrence. Patient will need ITU admission if comatose.
  • Correction or hypotension, hyponatraemia, and hypoglycaemia.
  • If concurrent hypoadrenalism/adrenal insufficiency, steroid replacement should also be given (this should be given prior to thyroxine replacement, as thyroxine replacement may precipitate ventricular fibrillation in adrenal crisis).