on 06-Jan-2022 (Thu)

Thyrotoxicosis The term thyrotoxicosis is retained because hyperthyroidism, i.e. symptoms due to a raised level of circulating thyroid hor- mones, 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 hyperthyroidism, usually occurs in younger women and is frequently associated with eye signs. The syndrome is that of primary thyrotoxicosis (Figure 50.17); 50% of patients have a family history of autoimmune endocrine diseases. The whole of the functioning thyroid tissue is involved, and the hypertrophy and hyperplasia are due to abnormal TSH-RAb that bind to TSH receptor sites and produce a disproportion- ate and prolonged effect.

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 is 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 over- active. 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

A toxic nodule 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 TSH-RAb. TSH secretion is suppressed by the high level of circulating thyroid hormones and the normal thyroid tissue surrounding the nodule is itself suppressed and inactive.

HISTOLOGY

The normal thyroid gland consists of acini lined with flat- tened cuboidal epithelium and filled with homogeneous col- loid (Figure 50.2). In hyperthyroidism (Figure 50.18), there is hyperplasia of acini, which are lined by high columnar epi- thelium. Many of them are empty, and others contain vacuo- lated colloid with a characteristic ‘scalloped’ pattern adjacent to the thyrocytes.

Principles of treatment of thyrotoxicosis

Non-specific measures are rest and sedation and in established thyrotoxicosis should be used only in conjunction with spe- cific measures, i.e. the use of antithyroid drugs, surgery and radioiodine.

ANTITHYROID DRUGS

Those in common use are carbimazole and propylthiouracil. Antithyroid drugs are used to restore the patient to a euthyroid state and to maintain this for a prolonged period in the hope that a permanent remission will occur, i.e. that production of thyroid-stimulating antibodies (TSH-RAb) will diminish or cease. Antithyroid drugs cannot cure a toxic nodule. The overactive thyroid tissue is autonomous and recurrence of the hyperthyroidism is certain when the drug is discontinued.

● Advantages. No surgery and no use of radioactive materials.

● Disadvantages. Treatment is prolonged and the failure rate is at least 50%. The duration of treatment may be tailored to the severity of the toxicity, with milder cases being treated for only 6 months and severe cases for 2 years before stopping therapy.

SURGERY

In diffuse toxic goitre and toxic nodular goitre with over- active internodular tissue, surgery cures by reducing the mass of overactive tissue by reducing the thyroid below a criti- cal mass. After subtotal thyroidectomy the patient should return to a euthyroid state, albeit after a variable period of hypothyroidism. There are however, the long-term risks of recurrence and eventual thyroid failure. In contrast total/ near total thyroidectomy accepts immediate thyroid failure and lifelong thyroxine replacement to eliminate the risk of recurrence and simplify follow-up. Operation may result in a reduction in TSH-RAb. In the autonomous toxic nodule, and in toxic nodular goitre with overactive autonomous toxic nodules, surgery cures by removing all the overactive thyroid tissue; this allows the suppressed normal tissue to function again.

● 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 at least 5% of cases when subtotal thyroidectomy is carried out. There is a risk of permanent hypoparathyroidism and nerve injury. Young women tend to have a poorer cos- metic result from the scar. Every operation carries a risk, but with suitable prepara- tion and an experienced surgeon the mortality is negligible and the morbidity low.

RADIOIODINE

Radioiodine destroys thyroid cells and, as in thyroidectomy, reduces the mass of functioning thyroid tissue to below a crit- ical level.

● Advantages. No surgery and no prolonged drug therapy.

● Disadvantages. Isotope facilities must be available. The patient must be quarantined while radiation levels are high and avoid pregnancy and close physical contact, par- ticularly with children. Eye signs may be aggravated. Choice of therapy 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, how- ever, be modified according to the facilities available and the personality and wishes of the individual patient, business or family commitments and any other coexistent medical or sur- gical condition. Access to post-treatment care and availabil- ity of replacement thyroxine can be important considerations in resource-poor countries. In advising treatment, compliance, influenced by social and intellectual factors, is important; many patients cannot be trusted to take drugs regularly if they feel well, and indefi- nite follow-up, which is essential after radioiodine or subtotal thyroidectomy is a burden for all.

DIFFUSE TOXIC GOITRE

Most patients have an initial course of antithyroid drugs with radioiodine for relapse. Exceptions are those who refuse radi- ation, have large goitres, progressive eye signs or are pregnant.

TOXIC NODULAR GOITRE

Toxic nodular go

...

He holds the record for the 100 metres breaststroke.

他保持着100米蛙泳的记录。

England qualified for the World Cup but got knocked out in the third round. [achieved the necessary standard but lost at the third stage and were then excluded from the competition]

Our team made it to / reached the semi-final but then we were beaten. [won every stage of the competition except the last but one, and so did not enter the final match/event]

Players who disagree with the referee set a bad example to the spectators and to their fans. [people who are present at a sporting event to watch it]

不同意裁判的球员给观众和球迷树立了一个坏榜样。

Player is often necessary, e.g. tennis player, squash player. Some names must be learnt separately, e.g. canoeist, mountaineer, jockey, archer (NOT archerer), gymnast.