Hypothyroidism
Primary hypothyroidism affects 2–5% of the UK
population. more women than men, and prevalence.
Causes
Primary hypothyroidism
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
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.
Clinical features
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.
Investigations
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
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
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.
