Hyperthyroidism
Thyrotoxicosis
The term thyrotoxicosis is retained because
hyperthyroidism, i.e. symptoms due to a raised level of circulating thyroid
hormones,
is not responsible for all manifestations of the disease.
Clinical
types are:
•
diffuse toxic goitre (Graves’ disease);
•
toxic nodular goitre;
•
toxic nodule;
•
hyperthyroidism due to rarer causes.
Diffuse
toxic goitre
Graves’ disease — a diffuse vascular goitre appearing at the same time
as the hyperthyroidism, usually in the younger woman and frequently associated
with eye signs. The syndrome is that of primary thyrotoxicosis (Fig.
44.23). The
whole of the functioning thyroid tissue is involved, and the hypertrophy and
hyperplasia are due to abnormal thyroid-stimulating antibodies (TsAb).
Toxic
nodular goitre
A simple nodular goitre is present for a long
time before the hyperthyroidism,
usually in the middle-aged
or elderly and very
infrequently associated with eye signs. The syndrome is that of secondary thyrotoxicosis.
In
many cases of toxic nodular goitre, the nodules are inactive, and it is the internodular thyroid tissue that is overactive. However, in some toxic nodular goitres, one or more nodules are overactive and
here the hyperthyroidism is due to autonomous thyroid tissue as in a toxic
adenoma.
Toxic
nodule
This is a solitary overactive nodule, which may be part of a generalised nodularity or a true toxic adenoma. It is autonomous and its hypertrophy and hyperplasia are not due to TsAb. Because TSH secretion is suppressed by the high level of circulating thyroid hormones, the normal thyroid tissue surrounding the nodule is itself suppressed and inactive.
Histology
The normal thyroid gland (Fig.
44.24) consists
of acini lined by flattened cuboidal epithelium and filled with homogeneous
colloid. In hyperthyroidism (Fig. 44.25) there is hyperplasia of
acini, which are
lined by high
columnar epithelium. Many of
them are empty and others contain vacuolated colloid.
Clinical
features
The symptoms are:
•
tiredness;
•
emotional lability;
•
heat intolerance;
•
weight loss;
•
excessive appetite;
•
palpitations.
The
signs of thyrotoxicosis are:
•
tachycardia;
•
hot, moist palms;
•
exophthalmos;
•
lid lag/retraction;
•
agitation;
•
thyroid goitre and bruit.
Thyrotoxicosis is eight times commoner in
females than in males. It may occur at any age. The most significant symptoms
are loss of weight in spite of a good appetite, a recent preference for cold,
and palpitations.
The most
significant signs are the excitability of the patient, the presence of a goitre,
exophthalmos, and tachycardia or cardiac arrhythmia.
The
goitre in primary thyrotoxicosis is diffuse and vascular, it may be large or
small, firm or soft, and a thrill and a bruit may be present. The onset is
abrupt, but remissions and exacerbations are not infrequent. Hyperthyroidism
is usually more severe
than in secondary
thyrotoxicosis but cardiac failure is rare. Manifestations of thyrotoxicosis not
due to hyperthyroidism per Se, e.g. orbital proptosis, ophthalmoplegia and
pretibial myxoedema, may occur in primary thyrotoxicosis.
In
secondary thyrotoxicosis the goitre is nodular. The onset is insidious and may
present with cardiac failure or atrial fibrillation. It is characteristic that
the hyperthyroidism is not severe. Eye signs other than lid lag and lid spasm
(due to hyperthyroidism) are very rare.
Cardiac
rhythm. A fast heart rate, which persists during sleep, is characteristic.
Cardiac arrhythmias are superimposed on the sinus tachycardia as the disease
progresses, and they are commoner in older patients with thyrotoxicosis because
of the prevalence of coincidental heart disease. Stages of development of
thyrotoxic arrhythmias are:
•
multiple extrasystoles;
•
paroxysmal atrial tachycardia;
•
paroxysmal atrial fibrillation;
•
persistent atrial fibrillation, not responsive to digoxin.
Eye
signs. Some degree of exophthalmos is common (Fig.
44.23). It may be unilateral.
True exophthalmos is a proptosis of the eye, caused by infiltration of the
retrobulbar tissues with fluid and round cells, with a varying degree of
retraction or spasm of the upper eyelid. (Lid spasm occurs because the levator
palpebrae superioris muscle is partly innervated by sympathetic fibres.) This
results in widening of the palpebral
Spasm
and retraction usually disappear when the hyperthyroidism is controlled. They
may be improved by 3-adrenergic blocking drugs, e.g. guanethidine eye drops.
Oedema of the eyelids, conjunctival injection and chemosis are aggravated by
compression of the ophthalmic veins (Fig. 44.26). Weakness of the extraocular
muscles, particularly the elevators (inferior oblique), results in diplopia. In
severe cases, papilloedema and corneal ulceration occur. When severe and
progressive, it is known as malignant exophthalmos (Fig.
44.27) and the eye
may be destroyed. Graves’ ophthalmopathy is an autoimmune disease in which
there are antibody-mediated effects on the ocular muscles.
Exophthalmos
tends to improve with time. Sleeping propped up and lateral tarsorrhaphy will
help to protect the eye but will not prevent progression. Hypothyroidism
increases proptosis by a few millimetres and should be avoided.
Improvement
has been reported with massive doses of prednisone. Intraorbital injection of
steroids is dangerous because of the venous congestion, and total thyroid
ablation has not proved effective. When the eye is in danger, orbital decompression
may be required (see Dysthyroid exophthalmos).
Diagnosis
of thyrotoxicosis
Most cases are readily diagnosed clinically.
Difficulty is most likely to arise in the differentiation of mild
hyperthyroidism from an anxiety state when a goitre is present. In these cases,
the thyroid status is determined by the diagnostic tests described earlier. A
TRH test is rarely indicated.
T3
thyrotoxicosis is diagnosed by estimating the free T3. It should be suspected if
the clinical picture is suggestive but routine tests of thyroid function are
within the normal range. A thyroid scan is essential in the diagnosis of an
autonomous toxic nodule.
Thyrotoxicosis
should always be considered in:
•
children with a growth spurt, behaviour problems or myopathy;
•
tachycardia or arrhythmia in the elderly;
•
unexplained diarrhoea;
•
loss of weight.
Principles
of treatment of thyrotoxicosis
Nonspecific measures are rest and sedation and,
in established thyrotoxicosis, should be used only in conjunction with
specific measures —
the use of
antithyroid drugs, surgery and radioiodine.
Antithyroid
drugs
Those in common use are carbimazole and
propylthiouracil. Beta-adrenergic blockers, such as propranolol and nadolol,
Advantages
No surgery and no use of radioactive materials.
Disadvantages
•
Treatment is prolonged and
the failure rate after a course of 1.5—2 years
is at least 50 per
cent. Recently there has been
a trend towards the
use of shorter courses (6
months) of these
drugs.
•
It is impossible to predict which patient is likely to go
into a remission. [Attempts have been made to predict which patients might
relapse after a 6-month course of antithyroid drugs on the basis of human
leucocyte antigen (HLA) status and the presence of TsAb production.]
•
Some goitres enlarge and become
very vascular during treatment —even
if thyroxine is given at the same time. This is probably due to TsAb stimulation
during the prolonged
course of treatment and not a direct
effect of the drug.
•
Very rarely, there is a dangerous drug reaction, e.g. agranulocytosis or
aplastic anaemia. In the event of agranulocytosis, the patient should be
instructed to discontinue treatment, if a sore throat develops, until the white
cell count has been checked.
Initially,
10 mg of carbimazole4 is given three or four times a day, and there
is a latent interval of 7—14 days before any clinical improvement is apparent.
It is most important to maintain a high concentration of the drug throughout the
24 hours by spacing the doses at 8- or 6-hourly intervals. When the patient
becomes euthyroid, a maintenance dose of 5 mg two or three times a day is
given for another 12—18 months. If tri-iodothyronine (20 jig
up to four times
daily) or thyroxine (0.1 mg daily) is given in conjunction with anti-thyroid
drugs, there is less danger of producing iatrogenic thyroid insufficiency or an
increase in the size of the goitre (‘block and replacement treatment’).
Surgery
In diffuse toxic goitre and toxic nodular
goitre with overactive internodular tissue, surgery cures by reducing the mass
of overactive tissue. Cure is probable if the thyroid tissue can be reduced
below a critical mass. This may result in a reduction of TsAb or it may be that
circulating TsAb, however
Advantages
The goitre is removed, the cure is rapid and
the cure rate is high if surgery has been adequate.
Disadvantages
•Recurrence of thyrotoxicosis occurs in approximately 5 per cent of
cases.
•
Every operation carries a morbidity but with suitable preparation and an
experienced surgeon the mortality is negligible.
•
Postoperative thyroid insufficiency occurs in 20—45 per cent of cases.
•
Long-term follow-up is highly desirable as the few patients who develop
recurrence may do so at any time in the future. In addition, although it is
usually apparent within a year or two, thyroid failure may also he a late
development.
•Parathvroid insufficiency: this should he permanent in less than 0.5 per
cent.
Radioiodine
Radioiodine5 destroys thyroid cells
and, as in thyroidectomy, reduces the mass of functioning thyroid tissue to
below a critical level.
Advantages
No surgery and no prolonged drug therapy.
Disadvantages
•
Isotope facilities must be available.
•
There is a high and progressive incidence of thyroid insufficiency which
may reach 75—80 per cent after 10 years. This is due to sublethal damage to
those cells not actually destroyed by the initial treatment and this eventually
causes failure of cellular reproduction.
•
Indefinite follow-up is essential.
There
is no convincing evidence that radioiodine has been responsible for genetic
damage, leukaemia, damage to the foetus if given inadvertently in early
pregnancy, or carcinoma in the adult. In some clinics, radioiodine is given to
almost all patients over the age of 25, i.e. when development is complete.
Follow-up requirements are reduced if a total ablative dose of radioiodine is
administered followed by routine replacement treatment with thyroxine. In the
UK, reluctance to prescribe radioiodine under the age of 45 has faded. The dose
of radioiodine varies between 300 and 600 MBq. Response is slow, but a
substantial improvement is to he expected in 8—12 weeks. Accurate dosage is
difficult and, should there be no clinical improvement after 12 weeks, a further
dose is given. Two or more doses are necessary in 20—3 0 per cent of cases.
Choice
of therapeutic agent
Each case must be considered individually.
Below are listed guiding principles on the most satisfactory treatment for a particular
toxic goitre at a particular age; these
must however be
modified according to the facilities available and the personality, intelligence and wishes of the individual patient, business
or family commitments and any other coexistent medical or surgical condition.
Diffuse
toxic goitre
Over 45: radioiodine. Under 45: surgery for the
large goitre, antithyroid drugs for the small goitre. As mentioned above,
radioiodine is being increasingly used in younger patients, particularly when their families are complete.
Large
goitres are uncomfortable and remission with antithyroid drugs is less likely
than in the small goitre.
Toxic
nodular goitre
Surgery. Toxic nodular goitre does not respond
as well or as rapidly to radioiodine or antithyroid drugs as does a diffuse
toxic goitre, and the goitre itself is often large and uncomfortable and
enlarges still further with antithyroid drugs.
Toxic
nodule
Surgery or radioiodine. Resection is easy,
certain and without morbidity. Radioiodine is a good alternative over the age of
45 because the suppressed thyroid tissue does not take up iodine and there is
thus no risk of delayed thyroid insufficiency.
Recurrent
thyrotoxicosis after surgery
In general radioiodine, but antithyroid drugs
may be used in young women intending to have children. Further surgery has no
place.
Failure
of previous
treatment with antithyroid drugs or radioiodine. Surgery or thyroid ablation
with 123I
unintelligent patients cannot be trusted to
take drugs regularly if they feel well, and are unlikely to attend follow-up clinics
indefinitely, which is essential after radioiodine or surgical therapy.
Special
problems in treatment
Pregnancy. Radioiodine is absolutely
contraindicated because of the risk to the foetus. The danger of surgery is
miscarriage; and that of anti-thyroid drugs is of inducing thyroid insufficiency
in the mother, and because both TSH and antithyroid drugs cross the placenta, of
the baby being born goitrous (Fig. 44.29) and hypothyroid. The risk of either
surgery in the second trimester, in competent hands, or careful administration
of antithyroid drugs, is very small and the choice is exactly as in the
uncomplicated case.
Postpartum
hyperthyroidism. Pregnancy may lead to an exacerbation of a variety of
autoimmune diseases in the postpartum period. Postpartum hyperthyroidism may
be a problem in a patient previously diagnosed with hyperthyroidism or may
occur in a patient without any previous history of thyroid disease.
Children.
Radioiodine is contraindicated because of the theoretical risk of inducing
thyroid carcinoma. There is an increased risk of recurrence after thyroidectomy
because thyroid cells are highly active in the young. Children and adolescents
should he treated with antithyroid drugs until the late teens, failing which
total or near-total thyroidectomy by an expert surgeon should be undertaken.
The
thyrocardiac. This is a patient with severe cardiac damage due wholly or partly
to hyperthyroidism. The patient is usually middle aged or elderly with secondary
thyrotoxicosis and the hyperthyroidism is not very severe. The cardiac
condition is far more significant than the hyperthyroidism, but this must be
rapidly controlled to prevent further cardiac damage. Betablockade (propranolol)
can assist rapid control of cardiac effects.
Radioiodine
is the treatment of choice together with antithyroid drugs started either before
or after and continued until the radioiodine has had an effect (usually 6
weeks).
High
titres of thyroid antibodies. Their presence indicates lymphatic infiltration of
the goitre, i.e. a diffuse or focal thyroiditis, and a liability to spontaneous
remission.
These
patients are best treated conservatively but if medical treatment fails,
definitive treatment by operation or radioiodine is not contra-indicated.
Steroids may help to reduce pain and swelling.
Proptosis
of recent onset. There is a conventional view that to terminate thyrotoxicosis
abruptly by thyroidectomy or radioiodine when proptosis is recent may induce
malignant exophthalmos. Whilst there is no real proof of this it
is reasonable
to treat these patients with anti-thyroid drugs until the proptosis has been
static for 6 months
Hyperthyroidism
due to other causes
Thyrotoxicosis factitia. (Usually seen in
health ‘cranks’ or those given thyroid extract as ‘a tonic’.)
Hyperthyroidism may he induced by taking thyroxine, but only if the dosage
exceeds the normal requirements of 0.15—0.25 mg a day. Doses below the normal
requirements simply suppress normal hormone production by the thyroid.
Jod-Basedow
thyrotoxicosis. (Jod =
German for iodine
+ Basedow.
In European countries diffuse toxic goitre is often called Basedow’s disease.)
Large doses of iodide given to a hyperplastic endemic goitre which
In
sub acute or acute forms of autoimmune thyroiditis or of de Quervain’s
thyroiditis (see later), mild hyperthyroidism may
occur in the
early stages due to liberation of thyroid hormones from damaged tissue.
A
large mass of secondary carcinoma will rarely produce sufficient hormone to
induce mild hyperthyroidism.
Neonatal
thyrotoxicosis occurs in
babies horn
to hyperthyroid
mothers or to
euthyroid mothers who
have had
thyrotoxicosis. High TsAb titres are present in both mother
and child because
TsAb can cross the placental barrier. The hyperthyroidism gradually subsides
after 3—4 weeks’ time as the TsAb titres fall in the baby’s serum.
Surgery
for thyrotoxicosis
Preoperative
preparation (Fig. 44.30)
Traditional preparation aims to make the
patient euthyroid or near euthyroid at operation. The
thyroid state is
determined by
clinical
assessment, i.e.
by improvement in
previous symptoms and
by objective
signs such as
gain in weight and lowering of the pulse rate, and by serial estimations of the
thyroid profile.
Preparation
is as an
out-patient and only
rarely is admission
to hospital
necessary on account of
severe symptoms
at presentation or failure to control
the
hyperthyroidism. Failure
to control with antithyroid drugs is unusual but may be
due to uneven dosage,
i.e. not taking
the drug at 6- or
8-hourly
intervals.
Carbimazole
30—40 mg a day is the drug of choice for preparation. When euthyroid — after 8—12 weeks
— the
dose may be reduced
to 5 mg
8-hourly and the addition
of thyroxine may
facilitate maintenance of the
euthyroid state. The last dose of carbimazole may he given
on the evening before
surgery. Iodides6
are not
used alone because, if the patient needs preoperative treatment, a more effective drug
An
alternative method of preparation that appears to be safe is to abolish the
clinical manifestations of the toxic state, using beta-blocking drugs. This
results in very rapid control and operation may be arranged within a week or
two. The appropriate
drugs are propranolol 40 mg three times daily or, preferably, the longer acting nadolol 160 mg once
daily. Clinical
response to beta-blockade is rapid and the patient may be reassessed within
days: if clinically euthyroid, an operation date may be arranged; if not, the
dose of beta-blocker is increased with early reassessment. Quite often larger
doses are necessary.
Beta-blockers
act on the target organs and not on the gland itself. Propranolol inhibits the peripheral conversion
of 14 to
The
addition of iodine for 10 days before operation gives an additional measure of safety in case the early morning dose
of beta-blocker on the day of operation is mistakenly omitted (Plummer).
Propranolol
or nadolol control symptoms very rapidly and have additional value in combination with carbimazole
in the immediate treatment of patients with very severe hyperthyroidism.
Subtotal
thyroidectomy
Preoperative investigations to be carried out
and recorded are:
•
thyroid function tests;
•
indirect laryngoscopy —
it is
a matter for local protocols whether
this is routine. The outcome should have little impact on the operation because
every recurrent laryngeal nerve must be routinely and obsessionally preserved;
•
thyroid antibodies;
•
serum calcium estimation;
•
an isotope scan before preoperative preparation is necessary in patients
with toxic nodular goitre if total thyroidectomy is not planned. The surgeon
should know which nodules, if any, are autonomous and active in order to ensure
their resection. A scan is of no value in diffuse toxic goitre when uptake, for
practical purposes, is uniform. The diagnosis of a single toxic nodule can only
be made by demonstrating that the nodule is active and the remaining thyroid
tissue suppressed.
The
extent of the resection depends on the size of the gland, the age of the
patient, the experience of the surgeon,
Technique.
General anaesthesia is administered through an endotracheal tube and good muscle
relaxation obtained. The patient is supine on the operating table with the table
tilted 15degree at
the head end to reduce venous engorgement. A sandbag is placed transversely
under the shoulders and the neck extended (with care particularly in the
elderly) to make the thyroid gland more prominent. A skin crease incision is
made midway between the notch of the thyroid cartilage and the suprasternal
notch. Flaps of skin, subcutaneous tissue and platysma are raised upwards to the
superior thyroid
notch and downwards to
the suprasternal notch. The deep cervical fascia is divided in the midline
between the sternothyroid muscles down to the plane of the thyroid capsule. The
muscles are not divided as a routine but may be if greater exposure is required.
The sternothyroid muscle is mobilised off the thyroid lobes. In 30 per cent of
patients, middle thyroid veins passing directly into the internal jugular vein
require ligation and division. The main blood supply is the superior thyroid
artery which must be ligated securely. The lobe is then free to rotate out of
its bed. The
inferior thyroid arteries are not routinely ligated to preserve parathyroid
blood supply. The recurrent
Postoperative
complications
Haemorrhage. A tension haematoma deep to the
cervical fascia (Fig. 44.33) is usually due to slipping
(If
a ligature on
the superior thyroid artery: occasionally haemorrhage from a thyroid remnant or
a thyroid vein may he responsible. It may, on rare occasions, be necessary to re
open the wound in
the ward to
relieve tension before taking the patient to theatre to evacuate the haematoma
and to tie off a bleeding vessel.
A
small subcutaneous haematoma or collection of serum
may form under the skin flaps and should he evacuated or aspirated in
the following 72 hours. This should not be confused with the potentially
life-threatening deep tension haematoma.
Respiratory
obstruction. This is very rarely due to collapse or kinking of the trachea. Most
cases are due to laryngeal oedema. The most important cause of laryngeal oedema
is a tension haematoma. However, trauma to the larynx by anaesthetic intubation and surgical manipulation is an important
contributory factors —
particularly if
the goitre is very vascular —
and may cause
laryngeal oedema without
If
releasing the tension haematoma does not immediately relieve airway
obstruction, the trachea should he intubated at once. An endotracheal tube can
he left in place for several days; steroids are given to reduce oedema and a
tracheostomy is rarely necessary. Intubation in the presence of laryngeal oedema
may be very difficult and should be carried out by an experienced anaesthetist;
repeated unsuccessful attempts may increase obstruction and cause serious
cerebral anoxia (Wade). In an emergency, it
is far safer for
the inexperienced surgeon to perform a needle tracheostomy as a temporary
measure; a Medicut 12G needle (diameter 2.3 mm) is highly satisfactory.
Recurrent
laryngeal nerve
paralysis may
be unilateral or bilateral, transient or permanent (Chapter 43). Transient paralysis occurs in about 3 per cent of
nerves at risk and recovers in 3 weeks to 3 months. Permanent paralysis is
extremely rare if the nerve has been identified at operation.
Thyroid
insufficiency. This usually occurs within 2 years, but it is sometimes delayed for 5 years or more. It is often insidious
and difficult to recognise. The incidence is considerably higher than used to he
thought and figures of 20—45 per cent have been reported after operations on
diffuse toxic goitres and toxic nodular goitres with internodular hyperplasia.
It represents a change in the autoimmune response from stimulation to
destruction of thyroid cells. There is, however, a definite relationship between
the estimated weight of the thyroid remnant and the development of thyroid
failure after subtotal thyroidectomy for Graves’ disease. Thyroid
insufficiency is rare after surgery for a toxic adenoma because there is no
autoimmune disease present.
Parathyroid
insufficiency is due to removal of parathyroid glands, or infarction through
damage to the parathyroid end-artery; often both factors occur together.
Vascular injury is probably far more important than inadvertent removal. The
incidence of this condition should be less than 0.5 per cent and most cases
present dramatically 2—5 days after operation, but very rarely the onset is
delayed for 2—3 weeks or a patient with marked hypocalcaemia is asymptomatic.
Thyrotoxic
crisis (storm) is an acute exacerbation of hyperthyroidism. It occurs if a
thyrotoxic patient has been inadequately prepared for thyroidectomy, and is now
extremely rare. Very rarely, a thyrotoxic patient presents in a crisis amid this
may follow an unrelated operation. Symptomatic and supportive treatment is for
dehydration, hyperpyrexia and restlessness. This requires the administration of
intravenous fluids, cooling the patient with ice packs, administration of
oxygen, diuretics for cardiac failure, digoxin for uncontrolled atrial
fibrillation, sedation and intravenous hydrocortisone. Specific treatment is
by carbimazole 10—20 mg 6-hourly, Lugol’s iodine 10 drops 8-hourly by mouth
or sodium iodide 1 g intravenously (i.v.). Propranolol 40 mg 6-hourly orally
will block adverse beta-adrenergic effects. This agent may be given by careful
intravenous administration (1—2 mg) under precise electrocardiographic
control.
Wound
infection. A subcutaneous or deep cervical abscess should he drained.
Hypertrophic
or keloid scar is more likely to form if the incision overlies the sternum.
Intradermal injections (If
corticosteroid
should he given at once and repeated monthly if necessary.
Stitch
granuloma. This may occur with or without sinus formation and is seen after the
use of nonabsorbable suture material. Absorbable ligatures and sutures must be
used throughout thyroid surgery. Some surgeons use a subcuticular absorbable
skin suture rather than the traditional skin clips or staples. Skin staples
should be removed in less than 48 hours.
Postoperative
care
Indirect laryngoscopy has been advised as a
routine before leaving hospital. Alternatively, it may he avoided when the voice is normal and the cough
occlusive.
After
operation, stability in terms of thyroid function takes time. It is important
that biochemical (subclinical) thyroid failure should not he aim indication for
treatment during the first year as the majority of patients with early
subclinical failure, which is common, ultimately regains normality. Even when
there are clinical features of failure, thyroxine should he withheld if possible
during the first 6 months. Most patients who develop thyroid failure do so
within the first 2 years, but there is a continiuing incidence thereafter.
Recurrent thyrotoxicosis may occur at any time after operation. Follow-up should
therefore he for life.
Once
a stable situation has been achieved, follow-up after thyroid surgery may be
carried out by an automated computer-activated system. Such systems in Scotland
and Wales have been shown to be extremely cost-effective and dramatically reduce
the number of patient attendances at the thyroid clinic.
The
incidences quoted for thyroid failure (20—45 per cent) and recurrent
thyrotoxicosis (5 per cent) after subtotal thyroidectomy for Graves’
disease refer to UK experience arid may be different elsewhere in the world. In
iceland, for example, an area of high dietary iodine intake, the incidence of
thyroid failure is much lower amid that of recurrent toxicity much higher
than in the UK.