A Textbook of Clinical Pharmacology and Therapeutics

SPECIALSITUATIONS 295

fertility. It is contraindicated during pregnancy because it dam-
ages the fetus, causing congenital hypothyroidism and conse-
quent mental retardation. Patients are usually treated as
outpatients during the first ten days of the menstrual cycle and
after a negative pregnancy test. Pregnancy should be avoided
for at least four months and a woman should not breast-feed
for at least two months after treatment. High-dose^131 I is used
to treat patients with well-differentiated thyroid carcinoma to
ablate residual tumour after surgery. Thyroxineis stopped at
least one month before treatment to allow TSH levels to
increase, thereby stimulating uptake of the isotope by the
gland. Patients are isolated in hospital for several days initially
after dosing, to protect potential contacts.

SPECIAL SITUATIONS

GRAVES’ OPHTHALMOPATHY

Eye signs usually occur within 18 months of the onset of
Graves’ disease and commonly resolve over one to two years,
irrespective of the state of the thyroid. Over-aggressive treat-
ment of hyperthyroidism in patients with eye signs must be
avoided because of a strong clinical impression that iatrogenic
hypothyroidism can exacerbate eye disease. Peri-orbital
oedema can be reduced by sleeping with the head of the bed
elevated. Simple moisturizing eye drops (e.g. hypromellose)
may be useful. Tarsoroplasty is indicated to prevent corneal
abrasion in severe cases. Radiotherapy is used in moderate
Graves’ ophthalmopathy, provided that this is not threatening
vision. Severe and distressing exophthalmos warrants a trial
ofprednisolone. Urgent surgical decompression of the orbit is
required if medical treatment is not successful and visual acu-
ity deteriorates due to optic nerve compression.

THYROID CRISIS

Thyroid crisis is a severe, abrupt exacerbation of hyperthy-
roidism with hyperpyrexia, tachycardia, vomiting, dehydration
and shock. It can arise post-operatively, following radioiodine
therapy or with intercurrent infection. Rarely, it arises spontan-
eously in a previously undiagnosed or untreated patient.
Mortality is high. Urgent treatment comprises:

• β-adrenoceptor antagonists;


• intravenous saline;


• cooling;


• propylthiouracil;


• Lugol’s iodine;


• glucocorticoids;


• fast atrial fibrillation can be especially difficult to treat: DC
  cardioversion may be needed.
  Aspirin must be avoided, because salicylate displaces
  bound T 4 and T 3 and also because of its uncoupling effect on
  oxidative phosphorylation, which renders the metabolic state
  even more severe.

PREGNANCY AND BREAST-FEEDING

Radioactive iodine is absolutely contraindicated in pregnancy

and surgery should be avoided if possible. T 4 and T 3 do not

cross the placenta adequately and, if a fetus is hypothyroid,

this results in congenital hypothyroidism with mental retard-

ation caused by maldevelopment of the central nervous sys-

tem. Antithyroid drugs (carbimazoleandpropylthiouracil)

cross the placenta and enter breast milk, and management of

hyperthyroidism during pregnancy requires specialist expert-

ise. Overtreatment with antithyroid drugs must be avoided.

Blocking doses of antithyroid drugs with added T 4 must never

be used in pregnancy, as the antithyroid drugs cross the pla-

centa but T 4 does not, leading inevitably to a severely

hypothyroid infant. Propylthiouracilmay be somewhat less

likely than carbimazoleto produce effects in the infant, since

it is more highly protein bound and is ionized at pH 7.4. This

reduces its passage across the placenta and into milk. Minimal

effective doses of propylthiouracilshould be used during

pregnancy and breast-feeding.

DRUG-INDUCED THYROID DYSFUNCTION

Other drugs are known to cause thyroid hypofunction. Iodinated

radio-contrast dyes can cause transient hyperthyroidism.

Amiodarone, interferons and interleukins can cause hypo- or

hyperthyroidism. Lithiumand several of the novel kinase

inhibitors (imatinib,sorafenib,sunitinib, see Chapter 48) can

cause hypothyroidism and/or goitre. The patient should be

assessed for the need for continuing the implicated drug and the

degree of thyroid dysfunction evaluated. If drug therapy has to

be continued, antithyroid or replacement thyroxine therapy with

careful monitoring of the thyroid axis is the standard treatment.

Case history

A 19-year-old Chinese woman develops secondary amenor-

rhoea followed by symptoms of palpitations, nervousness,

heat intolerance and sweating. There is a strong family his-

tory of autoimmune disease. On examination, she appears

anxious and sweaty, her pulse is 120 beats per minute regu-

lar and there is a smooth goitre with a soft bruit. There is

tremor of the outstretched fingers and lid lag is present.

A pregnancy test is positive and you send blood to the labora-

tory for standard investigations, including T 3 and T 4.

Comment

This young woman has the clinical picture of Graves’ dis-

ease, which is common in this ethnic group. Management

is complicated by the fact that she is probably pregnant,

and specialist input will be essential. Treatment with a

β-adrenoreceptor antagonist and a low dose of an anti-

thyroid drug (propylthiouracil is preferred as it crosses the

placenta poorly) should be considered. Radioactive iodine

is absolutely contraindicated in pregnancy and a high dose

of antithyroid drug should be avoided because of the risk

of causing congenital hypothyroidism, and consequent

mental retardation, in the baby.