Hyperthyroidism: Special
Circumstances
Hyperthyroidism and pregnancy
Hyperemesis gravidarum
Pregnancy affects thyroid status in
numerous ways (Figure 12.1a). TSH has a similar molecular structure to β human
chorionic gonadotrophin (β-HCG), therefore the hyperemesis of pregnancy (which
is characterised by raised β-HCG) can be associated with mild biochemical
hyperthyroidism. This usually resolves spontaneously in the second trimester of
pregnancy.
Graves’ disease in pregnancy
Patients with Graves’ disease
require observation during pregnancy every 4–6 weeks, because of the increased
risk of maternal complications as well as reduced fetal growth (Figure 12.1b).
Pregnancy usually has a beneficial effect on autoimmune disease, including
Graves’ disease, such that the dose of anti-thyroid medication can usually be
reduced or even stopped. Propylthiouracil (PTU) is preferred to carbimazole in
the first trimester because congenital malformations (notably choanal atresia
and aplasia cutis) have not been described with PTU. Carbimazole is preferred
during the second and third trimesters, because of the increased risk of
PTU-associated hepatitis later in pregnancy. Placental transfer of TSH receptor
stimulating antibodies can affect the fetus so additional scans are performed
during pregnancy to ensure there is no evidence of tachycardia, goitre or
growth restriction, which are signs of fetal hyperthyroidism.
Patients with Graves’ disease who
have had previous surgery or RAI require fetal monitoring during pregnancy. In
this situation, although the mother has had her thyroid removed or ablated,
there is still a risk of placental antibody transfer to the fetus and neonatal
thyrotoxicosis. Signs of this include irritability and failure to thrive during
the first 3 weeks of life.
Breastfeeding is safe on
anti-thyroid medication, as long as doses are not excessive. Hyperthyroidism
often becomes worse after delivery, because the immunosuppressive effect of
pregnancy is removed, demanding an appropriate dosage increase in thionamide
therapy.
Subclinical hyperthyroidism
Subclinical hyperthyroidism refers
to a suppressed TSH with normal fT4 and fT3, often in the upper part of the
normal range. Subclinical hyperthyroidism suggests a degree of autonomous
thyroid hormone production. This is often due to the presence of nodular
thyroid disease. Patients may not be symptomatic, but are at risk of the same
long-term complications as frank hyperthyroidism (notably AF and osteoporosis),
especially if the TSH is completely unmeasurable. Treatment is indicated to
control symptoms, and can also be considered on a case-by-case basis in
asymptomatic patients, dependent on comorbidities (e.g. AF) and extent of TSH
suppression. Surveillance alone, until the development of frank hyperthyroidism,
is an alternative.
Elevated fT4 with unsuppressed
TSH
Thyroid results are usually easy to
interpret. A high fT4 with a suppressed TSH is the norm in hyperthyroidism. It
is unusual in clinical practice to
see a high fT4 with non-suppressed TSH. In this situation it is important to
consider assay interference, TSHoma and thyroid hormone resistance (Figure
12.1c).
Assay interference
If the thyroid results do not fit
with the clinical presentation, blood should be sent to another laboratory for confirmation
by another method. Equilibrium dialysis is the most accurate way to measure
fT4, and eliminates the possibility of interfering antibodies affecting the
result. Antibodies to TSH (heterophile antibodies) can make the TSH look
falsely high or low, and these can be detected. Familial dysalbuminaemic
hyperthyroxinaemia (FDH) should also be considered in the context of high fT4
and normal TSH. FDH leads to falsely elevated T4 due to an abnormal albumin,
which has a higher affinity for thyroxine than TBG.
TSHoma and thyroid hormone
resistance
If the high fT4 and non-suppressed
TSH is not due to assay interference, the differential diagnosis lies between
TSHoma and thyroid hormone resistance.
TSHoma
TSHoma is a rare TSH-secreting
pituitary tumour, which drives fT3 and fT4 production from the thyroid.
Patients present with symptoms of hyperthyroidism, or mass effect from the
pituitary tumour if it is a macroadenoma. If MRI confirms a pituitary tumour,
trans-sphenoidal surgery is indicated, although somatostatin analogues are also
effective in achieving biochemical control.
Thyroid hormone resistance
Thyroid hormone resistance causes
high fT3/fT4 and non-suppressed TSH due to reduced end-organ unresponsiveness
to thyroxine. This is caused by an inactivating mutation in the thyroid hormone
receptor β (TR-β) gene. This condition is autosomal dominant and there
is usually a family history of unusual thyroid function results. There may be
variable sensitivity to thyroid hormones in different tissues. A diagnosis of
thyroid hormone resistance can be confirmed by genetic testing.
Distinuishing TSHoma from
thyroid hormone resistance
SHBG is produced by the liver, and
is elevated in hyperthyroid states. In TSHoma, patients are truly hyperthyroid
and therefore typically have high SHBG levels, while thyroid hormone resistance
is associated with low or normal SHBG. TRH injection (the TRH test) typically
leads to a flat TSH response in TSHoma, with an exaggerated rise seen in
thyroid hormone resistance. Patients with TSHoma will usually also display a
raised α-subunit, have evidence of a pituitary tumour on MRI 11 onine PET) and normalise thyroid function in
esponse to somatostatin analogues.
