Endocrine
Lec: 4
Dr.Mohammed Alhamdany
Graves’ ophthalmopathy
This condition is immunologically mediated but the autoantigen has not been
identified.
Pathophysiology:
There is cytokine-mediated proliferation of fibroblasts which secrete
hydrophilic glycosaminoglycans. The resulting increase in interstitial fluid
content, combined with a chronic inflammatory cell infiltrate, causes marked
swelling and ultimately fibrosis of the extraocular muscles and a rise in
retrobulbar pressure. The eye is displaced forwards (proptosis, exophthalmos)
and in severe cases there is optic nerve compression.
Clinical feature:
It is helpful to distinguish patients with active inflammation from those in
whom the inflammation has ‘burnt out’. The sign of active inflammation
include:
1- periorbital oedema.
2- conjunctival inflammation.
3- changing orbital signs.
Eye disease is detectable in up to 50% of thyrotoxic patients at presentation, but
active ocular inflammation may occur before or after thyrotoxic episodes. It is
more common in cigarette smokers and is exacerbated by poor control of
thyroid function, especially hypothyroidism.
The symptoms include:
1- There may be excessive lacrimation made worse by wind and bright light.
2- A ‘gritty’ sensation in the eye.
3- Pain due to conjunctivitis or corneal ulceration.
4- There may be reduction of visual acuity and/or visual fields as a consequence
of corneal edema or optic nerve compression. Other signs of optic nerve
compression include reduced colour vision and a relative afferent pupillary
defect, if the extraocular muscles are involved diplopia results.
Treatment:
1- The majority of patients require no treatment.
2- Smoking cessation.
3- Methylcellulose eye drops and gel reduce gritty discomfort of dry eyes.
4- Tinted glasses reduce the excessive lacrimation triggered by sun or wind.
5- In patients with mild Graves’ ophthalmopathy, oral selenium (100 μg twice
daily for 6 months) improves quality of life, reduces ocular involvement and
slows progression of disease; the benefits persisted 6 months following
cessation of therapy.
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6- More severe inflammatory episodes are treated with glucocorticoids (e.g.
daily oral prednisolone or pulsed IV methylprednisolone).
7- Sometimes orbital radiotherapy.
8- Immunosuppressant therapies, such as ciclosporin, in combination with
glucocorticoids.
9- Loss of visual acuity is an indication for urgent surgical decompression of the
orbit. In ‘burnt-out’ disease, surgery to the eyelids and/or ocular muscles may
improve conjunctival exposure, cosmetic appearance and diplopia.
Pretibial myxoedema
This infiltrative dermopathy occurs in fewer than 10% of patients with Graves’
disease and has similar pathological features as occur in the orbit. It takes the
form of raised pink-coloured or purplish plaques on the anterior aspect of the
leg, and may be itchy and the skin may have a ‘peau d’orange’ appearance,
rarely the face and arms are affected. Treatment is rarely required, but in severe
cases topical glucocorticoids may be helpful.
Hashimoto’s thyroiditis
Pathophysiology:
Hashimoto’s thyroiditis is characterized 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
rare.
Pathologically the disease of two types; the first called ‘Hashimoto’s thyroiditis’
for patients with positive antithyroid peroxidase autoantibodies and a firm goitre
who may or may not be hypothyroid, and the second called ‘spontaneous
atrophic hypothyroidism’ for hypothyroid patients without a goitre in whom
TSH receptor-blocking antibodies may be more important than antiperoxidase
antibodies.
Hashimoto’s thyroiditis increases in incidence with age and affects
approximately 3.5 per 1000 women.
Clinical feature and investigation: Many present with a small or moderately
sized diffuse goiter, 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.
Treatment: Levothyroxine therapy is indicated as treatment for
hypothyroidism, and also to shrink an associated goiter.
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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, and rarely caused by drug like interferon-α and lithium.
Clinical feature: 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, 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.
Investigation: 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. Low-titer 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.
Treatment: 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. levothyroxine can be prescribed
temporarily in the hypothyroid phase.
Post-partum thyroiditis
Pathophysiology: The maternal immune response, which is modified during
pregnancy to allow survival of the fetus, is enhanced after delivery and may
unmask previously unrecognized subclinical autoimmune thyroid disease.
Surveys have shown that transient biochemical disturbances of thyroid function
occur in 5–10% of women within 6 months of delivery. Those affected are
likely to have anti-thyroid peroxidase antibodies in the serum in early
pregnancy.
Clinical feature and investigation: Symptoms of thyroid dysfunction are rare.
However, symptomatic thyrotoxicosis presenting for the first time within 12
months of childbirth is likely to be due to post-partum thyroiditis and the
diagnosis is confirmed by a negligible radio-isotope uptake. The thyroid
function test show feature of primary hyperthyroidism at beginning than show
feature of primary hypothyroidism, than retune back to the normal.
Treatment: same as painless subacute thyroiditis.
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Prognosis:
Postpartum thyroiditis tends to recur after subsequent pregnancies, and
eventually patients progress over a period of years to permanent
hypothyroidism.
Simple and multinodular goitre
These terms describe diffuse or multinodular enlargement of the thyroidThese
terms describe diffuse or multinodular enlargement of the thyroid.
Simple diffuse goiter
This form of goitre usually presents between the ages of 15 and 25 years, often
during pregnancy, there is a tight sensation in the neck, particularly when
swallowing. The goitre is soft and symmetrical, and the thyroid enlarged to two
or three times normal. There is no tenderness, lymphadenopathy or overlying
bruit. All thyroid investigations are normal and need no treatment.
Prognosis:
The goitre usually regresses. In some, however, the unknown stimulus to
thyroid enlargement persists and, as a result of recurrent episodes of hyperplasia
and involution during the following 10–20 years, the gland becomes
multinodular with areas of autonomous function.
Multinodular goitre
Natural history:
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Clinical features and investigations
Multinodular goitre is usually diagnosed in patients presenting with
thyrotoxicosis, a large goitre with or without tracheal compression, or sudden
painful swelling caused by haemorrhage into a nodule or cyst. The goitre is
nodular or lobulated on palpation and may extend retrosternally. Very large
goitres may cause mediastinal compression with stridor, dysphagia and
obstruction of the superior vena cava. Hoarseness due to recurrent laryngeal
nerve palsy can occur, but is far more suggestive of thyroid carcinoma.
The diagnosis can be confirmed by ultrasonography and/or thyroid scintigraphy.
In patients with large goiters, a flow-volume loop is a good screening test for
significant tracheal compression, and confirm by a CT or MRI of the thoracic
inlet. Nodules should be evaluated for the possibility of thyroid neoplasia.
Management
If the goitre is small: no treatment is necessary but annual thyroid function
testing should be arranged, as the natural history is progression to a toxic
multinodular goitre.
For euthyroid patients: Thyroid surgery is indicated for large goiters which
cause mediastinal compression or which are cosmetically unattractive. 131I can
result in a significant reduction in thyroid size and may be of value in elderly
patients. Levothyroxine therapy is of no benefit in shrinking multinodular
goitres in iodine-sufficient countries and may simply aggravate any associated
thyrotoxicosis.
For thyrotoxicosis patients: treatment is usually with 131I, In thyrotoxic
patients with a large goitre, thyroid surgery may be indicated. Long-term
treatment with antithyroid drugs is not usually employed, as relapse is
invariable after drug withdrawal.
For Asymptomatic patients with subclinical thyrotoxicosis: are increasingly
being treated with 131I on the grounds that a suppressed TSH is a risk factor for
atrial fibrillation and, particularly in post-menopausal women, osteoporosis.
With best regard
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