Primary hypothyroidism affects 2–5% of the UK population. more women than men, and prevalence.
This is most commonly caused by disease, characterised by the presence of thyroid antibodies, lymphocytic infiltration, fibrosis and atrophy, or enlargement of the gland with goitre (Hashimoto’s thyroiditis) (Figure 13.1a).
Pregnancy can lead to transient or permanent hypothyroidism after delivery, and can be misdiagnosed as postnatal depression (post-partum thyroiditis). In developing countries, iodine deficiency is a preventable cause of neonatal hypothyroidism, which causes severe mental retardation (cretinism). A rare genetic defect in thyroid hormone synthesis can cause hypothyroidism in infancy (familial thyroid dyshormonogenesis).
Drugs causing hypothyroidism include amiodarone and lithium. Iatrogenic hypothyroidism is caused by intentional treatment of thyroid disease (e.g. surgery, RAI), or inadvertent damage from radiation to the head and neck area.
Secondary hypothyroidism is much less common than primary hypothyroidism and is caused by TSH deficiency resulting from hypothalamic–pituitary disease. Secondary hypothyroidism is characterised by low fT4 with non-elevated TSH, and should prompt full investigation of the pituitary gland.
The classic features of hypothyroidism are weight gain, cold intolerance, fatigue, constipation, bradycardia, with thickening of the skin and puffiness around the eyes (myxoedema) (Figure 13.1b). More commonly, hypothyroidism develops with subtle symptoms and is often diagnosed incidentally during routine blood tests. Symptoms of hypothyroidism can be similar to depression or chronic fatigue, which is experienced by up to 40% of the population.
Hypothyroidism in special situations
Myxoedema coma (Figure 13.1c) is a rare medical emergency with a high mortality requiring treatment in a high dependency setting (Chapter 41). Children with hypothyroidism can present with poor growth and development or delayed puberty, while young women may present with reproductive symptoms alone, such as menstrual disturbance or reduced fertility.
The hallmark of primary hypothyroidism is a low fT4 with elevated TSH. Most laboratories in the UK use TSH alone to diagnose hypothyroidism. This is sufficient to diagnose primary hypothyroidism, but fT4 must be measured as well as TSH when secondary hypothyroidism is suspected. Autoimmune hypothyroidism is confirmed by measuring thyroid antibodies. TPO antibodies are usually strongly positive in Hashimoto’s thyroiditis.
Treatment consists of thyroxine replacement, given at a dosage sufficient to improve symptoms and normalise thyroid function (Figure 13.1d). A typical starting dose is 50–100 µg/day. Elderly patients or those with ischaemic heart disease may be started on 25 µg/day. A persistently elevated TSH suggests under-replacement, poor compliance or malabsorption (e.g. from coeliac disease or concurrent medication such as iron, calcium or proton pump inhibitors) (Figure 13.1e). Asuppressed or undetectable TSHsuggests over-replacement, leading to increased risk of AF and osteoporosis. The use of T3 (liothyronine) and dessicated thyroid extract (‘armour thyroid’) as alternatives to thyroxine is not recommended routinely. Patients who remain symptomatic despite normalisation of thyroid function should be investigated for non-thyroid pathology.
In patients with secondary hypothyroidism, fT4 should be replaced to the upper part of the normal range because TSH cannot be relied upon as a measure of optimal replacement. Dosage should not be mistakenly reduced on the basis of a suppressed TSH level.
Subclinical hypothyroidism refers to a normal fT4 with elevated TSH (Figure 13.1f). If patients are asymptomatic, treatment may not be needed; thyroid function spontaneously reverts to normal during repeat testing in 10–15% of patients. Guidelines recommend starting thyroxine if TSH is >10 mIU/L even if patients are asymptomatic, because of the high likelihood of progression to frank hypothyroidism. Treatment should also be considered at lower levels of TSH elevation (TSH 5–10 mIU/L) in women planning pregnancy, on a trial basis in symptomatic patients and in patients with significant dyslipidaemia. Patients with positive thyroid antibodies should have an annual TFT to ensure they do not progress to overt hypothyroidism.
Hypothyroidism and pregnancy
The fetal thyroid gland only develops after 10–12 weeks’ gestation, hence the fetus is reliant on maternal thyroxine before this time. Thyroid replacement should be optimised before conception and/or in early pregnancy. A high TSH in the first trimester can have an adverse effect on infant IQ, so thyroxine dosage is empirically increased by 25–50 µg in early pregnancy. Autoimmune hypothyroidism slightly increases the risk of recurrent miscarriage, as well as maternal and neonatal problems. Patients with previous hyperthyroidism who have undergone RAI or thyroidectomy should be monitored closely because of the risk of placental antibody transfer (Chapter 12). Maternal hypothyroxinaemia describes fT4 in the low normal range with normal TSH, which results from subtle iodine deficiency; women planning pregnancy should have a diet rich in iodine (seafood and dairy products). There is currently no evidence that screening for hypothyroidism in all pregnancies is useful. All babies born in the UK are screened for congenital hypothyroidism during the heel-prick test on days 6–8.
Polyglandular autoimmune disease
Patients with autoimmune hypothyroidism commonly have other primary gland deficiencies. In children, the presence of mucocutaneous candidiasis together with two or more autoimmune deficiencies suggests the presence of autoimmune polyendocrinopathy syndrome type 1 (APS-1). APS-1 is an autosomal recessive disorder caused by a mutation in the AIRE gene. In adults, the association of hypothyroidism with Addison’s disease, with or without type 1 diabetes, suggests autoimmune opathy syndrome type 2 (APS-2), previously nown as Schmidt’s syndrome.