Lec .4 Dr. Nihad Abdallah Al-jeboori /Subspecialty Endocrinology &Diabetes
Hashimoto’s thyroiditis
Hashimoto’s thyroiditis is characterised by destructive lymphoid infiltration
of the thyroid, ultimately leading to a varying degree of fibrosis and thyroid
enlargement. There is an increased risk of thyroid lymphoma, although this
is exceedingly rare. Some authorities reserve the term ‘Hashimoto’s
thyroiditis’ for the condition of patients with positive antithyroid peroxidase
autoantibodies and a firm goitre who may or may not be hypothyroid, and
use the term ‘spontaneous atrophic hypothyroidism’ for the condition of
hypothyroid patients without a goitre in whom TSH receptor-blocking
antibodies may be more important than antithyroid peroxidase antibodies.
However, these syndromes can both be considered as variants of the same
underlying disease process.
Hashimoto’s thyroiditis increases in incidence with age and affects
approximately 3.5 per 1000 women and 0.8 per 1000 men each year. Many
present with a small or moderately sized diffuse goitre, which is
characteristically firm or rubbery in consistency. Around 25% of patients are
hypothyroid at presentation. In the remainder, serum T4 is normal and TSH
normal or raised, but these patients are at risk of developing overt
hypothyroidism in future years. Antithyroid peroxidase antibodies are
present in the serum in more than 90% of patients with Hashimoto’s
thyroiditis. In those under the age of 20 years, antinuclear factor (ANF) may
also be positive.
Levothyroxine therapy is indicated as treatment for hypothyroidism and also
to shrink an associated goiter. In this context, the dose of levothyroxine
should be sufficient to suppress serum TSH to low but detectable levels.
Transient thyroiditis
Subacute (de Quervain’s) thyroiditis
In its classical painful form, subacute thyroiditis is a transient inflammation
of the thyroid gland occurring after infection with Coxsackie, mumps or
adenoviruses. There is pain in the region of the thyroid that may radiate to
the angle of the jaw and the ears, and is made worse by swallowing,
Lec .4 Dr. Nihad Abdallah Al-jeboori /Subspecialty Endocrinology &Diabetes
coughing and movement of the neck. The thyroid is usually palpably
enlarged and tender.
Systemic upset is common. Affected patients are usually females aged 20–
40 years. Painless transient thyroiditis can also occur after viral infection and
in patients with underlying autoimmune disease. The condition can also be
precipitated by drugs, including interferon-α and lithium.
Irrespective of the clinical presentation, inflammation in the thyroid gland
occurs and is associated with release of colloid and stored thyroid hormones,
but also with damage to follicular cells and impaired synthesis of new
thyroid hormones. As a result, T4 and T3 levels are raised for 4–6 weeks
until the pre-formed colloid is depleted. Thereafter, there is usually a period
of hypothyroidism of variable severity before the follicular cells recover and
normal thyroid function is restored within 4–6 months (Fig. 18.9). In the
thyrotoxic phase, the iodine uptake is low because the damaged follicular
cells are unable to trap iodine and because TSH secretion is suppressed.
Low-titre thyroid autoantibodies appear transiently in the serum, and the
erythrocyte sedimentation rate (ESR) is usually raised. High-titre
autoantibodies suggest an underlying autoimmune pathology and greater risk
of recurrence and ultimate progression to hypothyroidism.
The pain and systemic upset usually respond to simple measures such as
non-steroidal anti-inflammatory drugs (NSAIDs). Occasionally, however, it
may be necessary to prescribe prednisolone 40 mg daily for 3–4 weeks. The
thyrotoxicosis is mild and treatment with a β-blocker is usually adequate.
Antithyroid drugs are of no benefit because thyroid hormone synthesis is
impaired rather than enhanced. Careful monitoring of thyroid function and
symptoms is required so that levothyroxine can be prescribed temporarily in
the hypothyroid phase. Care must be taken to identify patients presenting
with hypothyroidism who are in the later stages of a transient thyroiditis,
since they are unlikely to require life-long levothyroxine therapy (see Fig.
18.6).
Post-partum thyroiditis
Lec .4 Dr. Nihad Abdallah Al-jeboori /Subspecialty Endocrinology &Diabetes
In Lec. No.2 Graves disease
Iodine-associated thyroid disease
Iodine deficiency
Iodine is an essential micronutrient and is a key component of T4 and T3.
The World Health Organisation (WHO) recommends a daily intake of iodine
of 150 μg/day for adult men and women; higher levels are recommended for
pregnant women (p. 1279).
Dietary sources of iodine include seafood, dairy products, eggs and grains.
Dietary iodine deficiency is a major worldwide public health issue, with an
estimated one-third of the world population living in areas of iodine
insufficiency. Iodine deficiency is particularly common in Central Africa,
South-east Asia and the Western Pacific. It is associated with the
development of thyroid nodules and goitre (endemic goitre); the reduced
substrate available for thyroid hormone production increases thyroid activity
to maximize iodine uptake and recycling, and this acts as a potent stimulus
for enlargement of the thyroid and nodule formation. Most affected patients
are euthyroid with normal or raised TSH levels, although hypothyroidism
can occur with severe iodine deficiency.
Suspected iodine deficiency can be assessed by measuring iodine in urine
(either a 24-hour collection or a spot sample). Endemic goitre can be treated
by iodine supplementation, and a reduction in nodule and goitre size can be
seen, particularly if it is commenced in childhood. Iodine deficiency is not
associated with an increased risk of Graves’ disease or thyroid cancer, but
the high prevalence of nodular autonomy does result in an increased risk of
thyrotoxicosis and this risk may be further increased by iodine
supplementation. Conversely, iodine supplementation may also increase the
prevalence of subclinical hypothyroidism and autoimmune hypothyroidism.
These complex effects of iodine supplementation are further discussed
below.
In pregnancy, iodine deficiency is associated with impaired brain
development, and severe deficiency can cause cretinism. Worldwide, iodine
Lec .4 Dr. Nihad Abdallah Al-jeboori /Subspecialty Endocrinology &Diabetes
deficiency is the most common cause of preventable impaired cognitive
development in children (p. 1279). The WHO and other international
organisations have made reversal of iodine deficiency a priority and have
helped organise national supplementation programmes. These have mainly
involved the iodisation of table salt, but have also included schemes to
administer oral or intramuscular iodised oil to at-risk populations and the
addition of iodine to wells supplying water to local communities. These
schemes have been extremely effective in reducing the prevalence of iodine
deficiency, but lower consumption of table salt has actually led to an
increase in iodine deficiency in some developed countries like Australia and
New Zealand.
Iodine-induced thyroid dysfunction
Iodine has complex effects on thyroid function. Very high concentrations of
iodine inhibit thyroid hormone synthesis and release (known as the Wolff–
Chaikoff effect) and this forms the rationale for iodine treatment in thyroid
crisis and prior to thyroid surgery for thyrotoxicosis . This is an
autoregulatory response to protect the body from the sudden release of large
amounts of thyroid hormone in response to the ingestion of a substantial
load of iodine. This effect only lasts for about 10 days, after which it is
followed by an ‘escape phenomenon’: essentially, the return to normal
organification of iodine and thyroid peroxidase action . Therefore, if iodine
is given to prepare an individual with Graves’ disease for surgery, the
operation must happen within 10–14 days; otherwise, a significant relapse of
the thyrotoxicosis could occur.
Iodine deficiency and underlying thyroid disease can both moderate the
effects of iodine on thyroid function. In iodine deficient parts of the world,
transient thyrotoxicosis may be precipitated by prophylactic iodinisation
programmes. In iodine-sufficient areas, thyrotoxicosis can be precipitated by
iodine-containing radiographic contrast medium or expectorants in
individuals who have underlying thyroid disease predisposing to
thyrotoxicosis, such as multinodular goitre or Graves’ disease in remission.
Induction of thyrotoxicosis by iodine is called the Jod–Basedow effect.
Chronic excess iodine administration can also result in hypothyroidism; this
Lec .4 Dr. Nihad Abdallah Al-jeboori /Subspecialty Endocrinology &Diabetes
is, in effect, a failure to escape from the Wolff–Chaikoff effect and usually
occurs in the context of prior insult to the thyroid by, for example,
autoimmune disease, thyroiditis, lithium, antithyroid drugs or surgery.
Amiodarone
The anti-arrhythmic agent amiodarone has a structure that is analogous to
that of T4 and contains huge amounts of iodine; a 200 mg dose contains 75
mg iodine. Amiodarone also has a cytotoxic effect on thyroid follicular cells
and inhibits conversion of T4 to T3 (increasing the ratio of T4:T3). Most
patients receiving amiodarone have normal thyroid function but up to 20%
develop hypothyroidism or thyrotoxicosis, and so thyroid function should be
monitored regularly. TSH provides the best indicator of thyroid function.
The thyrotoxicosis can be classified as either:
• type I: iodine-induced excess thyroid hormone synthesis in patients with an
underlying thyroid disorder, such as nodular goitre or latent Graves’ disease
(an example of the Jod–Basedow effect).
• type II: thyroiditis due to a direct cytotoxic effect of amiodarone
administration.
These patterns can overlap and may be difficult to distinguish clinically, as
iodine uptake is low in both. There is no widely accepted management
algorithm, although the iodine excess renders the gland resistant to 131I.
Antithyroid drugs may be effective in patients with the type I form but are
ineffective in type II thyrotoxicosis. Prednisolone is beneficial in the type II
form.
A pragmatic approach is to commence combination therapy with an
antithyroid drug and glucocorticoid in patients with significant
thyrotoxicosis. A rapid response (within 1–2 weeks) usually indicates a type
II picture and permits withdrawal of the antithyroid therapy; a slower
response suggests a type I picture, in which case antithyroid drugs may be
continued and prednisolone withdrawn. Potassium perchlorate can also be
used to inhibit iodine trapping in the thyroid. If the cardiac state allows,
Lec .4 Dr. Nihad Abdallah Al-jeboori /Subspecialty Endocrinology &Diabetes
amiodarone should be discontinued, but it has a long half-life (50–60 days)
and so its effects are long-lasting.
To minimise the risk of type I thyrotoxicosis, thyroid function should be
measured in all patients prior to commencement of amiodarone therapy, and
amiodarone should be avoided if TSH is suppressed.
Hypothyroidism should be treated with levothyroxine, which can be given
while amiodarone is continued.