Hormonal disturbance- Hyperthyroidism symptoms.

Hyperthyroidism

Hyperthyroidism or thyrotoxicosis consists of the clinical, physiological and biochemical findings resulting from exposure to excessive thyroid hormones.

Epidemiology

Hyperthyroidism occurs predominantly in women (female: male 9:1), with an incidence of approximately 80 per100 000 per year. Graves' disease tends to present in women in the third and fourth decades.

Pathology

Autoimmune disease and thyroid autonomy are the two most common causes of hyperthyroidism . In Graves' disease, excessive release of thyroid hormone is due to presence of IgG thyroid-stimulating antibodies (TSI) that bind to the TSH receptor and mimic the action of TSH. Ophthalmopathy (proptosis, exophthalmos, diplopia) and dermopathy (pretibial myxoedema) are specific to Graves' disease, but the aetiology is less well understood. Antigens in the orbit may cross-react with thyroid-stimulating antibodies leading to an inflammatory reaction, proliferation of fibroblasts and orbital oedema.

Toxic multinodular goitre and toxic solitary adenomas are examples of autonomously functioning thyroid tissue that secretes excessive amounts of thyroid hormone. Mutations in the TSH receptor or in the G-protein pathway are thought to lead to clonal expansion of individual cells and autonomous nodule formation.

Lymphocytic thyroiditis (e.g. in post-partum patients) causes excessive T4 release due to autoimmune destruction of thyroid cells. Choriocarcinoma and hyperemesis gravidarum are uncommon causes of hyperthyroidism. In these conditions, human chorionic gonadotrophin, which has a similar chemical structure to TSH, is present in excessive amounts. The presence of ectopic thyroid tissue is associated with struma ovarii and functioning follicular carcinoma of the thyroid gland. T3 toxicosis due to elevated T3 levels occurs rarely in patients with hyperthyroidism. In this situation, normal serum T4 levels occur despite clinical evidence of hyperthyroidism.

Scope of disease

Hyperthyroidism occurs as a result of excessive thyroid hormone action. The clinical manifestations stem from a general increase in the cellular metabolic process, as well as greater adrenergic activity. Thyrotoxicosis is a systemic disorder and the effect on each system is summarized in . In addition, Graves' disease is associated with a number of other autoimmune disorders . Enlargement of the thyroid gland (usually from a multinodular goitre) can result in compression of adjacent structures such as the trachea and the recurrent laryngeal nerve (hoarseness).

Clinical features

The severity of thyrotoxicosis varies from subclinical (detected only by laboratory testing) to clinically overt. Patient may present with classic symptoms of thyrotoxicosis which may be accompanied by specific symptoms of Graves' disease such as ophthalmopathy and dermopathy.

Symptoms of thyrotoxicosis include nervousness, insomnia, tremors, excessive sweating with heat intolerance and weight loss. On examination, the patient may appear thin with sweaty palms and a fine tremor. The pulse rate may be fast and irregular (atrial fibrillation). The thyroid may be diffusely enlarged (Graves' disease) or nodular (toxic multinodular goitre).

Specific clinical features of Graves' disease include a thyroid bruit, ophthalmopathy (exophthalmos, chemosis, diplopia), pretibial myxoedema and thyroid acropachy (resembles clubbing).

Initial investigations

Thyroid-stimulating hormone and free T4

The simplest initial screening test is the measurement of serum thyroid-stimulating hormone. The diagnosis of hyperthyroidism in patients with suppressed (low) levels of TSH can be confirmed by detection of elevated free T4 levels.

Hyperthyroidism secondary to pituitary adenomas is rare and results in elevated levels of TSH and serum thyroxine.

Further investigations

T3 levels

Measurement of T3 levels is performed when T3 toxicosisis suspected in clinically hyperthyroid patients with suppressed TSH but normal T4 levels.

Thyroid autoantibodies

Measurement of anti-thyroid peroxidase and anti-thyroglobulin antibodies is not essential, but along with anti-TSH receptor antibodies can be used to confirm Graves' disease or autoimmune thyroid disease as the cause, if the diagnosis is not clear.

Ultrasound of the thyroid

High-resolution ultrasound using a high-frequency transducer provides a comprehensive assessment of thyroid structure and can differentiate between diffuse and focal multinodular disease.

Radioactive iodine uptake test

A 131I radioactive iodine uptake scan measures the absorption of circulating iodine by the thyroid gland. The main indication is elucidating the aetiology of hyperthyroidism when the underlying cause is uncertain. Graves' disease is suggested by high uptake evenly across the gland. Patients with autoimmune destructive thyroiditis show low uptake, while those with toxic nodular goitres show uneven uptake or a 'hot' nodule.

Chest X-ray and CT of the neck and chest

Imaging of the size and position of the thyroid is required when there are symptoms suggestive of compression of adjacent structures and to assess the degree of retrosternal extension. A soft tissue mass may be seen on a plain chest film and retrosternal extension confirmed on CT.

Initial management

β-Blockers

β-adrenoceptor blockers such as propranolol and metoprolol are able to provide rapid relief of some thyrotoxic symptoms such as tremor, tachycardia and anxiety. β-blockers do not have any effect on thyroxine levels, oxygen consumption, nor do they reduce goitre size or reverse weight loss.

Most patients with symptomatic hyperthyroidism can initially be treated with β-blockers while awaiting planning surgery, radioactive iodine or pharmacological treatment as the definitive treatment.

Medical management

Antithyroid drugs

Propylthiouracil and methimazole (and its pro-drug carbimazole) are cyclic thiourea derivatives which disrupt the thyroid gland's ability to use iodine. Both agents appear to be equally efficacious, although propylthiouracil may be preferred in thyroid storm because it blocks peripheral conversion of T4 to T3. Methimazole (or carbimazole) ismore convenient for long-term therapy as it can be given once daily, whereas propylthiouracil requires more frequent dosing.

Dosing is guided by TSH and thyroxine levels, which should be monitored at 4-6-weekly intervals in the first6 months. There is no consensus on the length of drug therapy but the initial projected duration is about 1-2 years. Up to 40% of patients with Graves' disease are in remission after this time and may be able to come off the drug treatment. Patients who are unable to stop drug therapyor those in whom remission is not achievable (e.g. toxic nodular goitres) should be offered the options of continuing on drugs, surgery or radioactive iodine.

Both propylthiouracil and methimazole agents can cause nausea, loss of taste and allergic reactions, particularly of the skin. The most serious adverse effect is that of agranulocytosis, which predisposes the patient to serious infections. As the reaction is uncommon and sporadic, there is no consensus on the value of routine blood count monitoring. Patients are, however, advised to consult their medical practitioner if they develop a fever, sore throat or other signs of infection. Those who develop agranulocytosis should not be exposed to any further antithyroid drug and should instead be offered surgery or radioactive iodine treatment.

Radioactive iodine

Radioactive iodine is widely used in the USA as the definitive therapy for patients with Graves' disease and toxic nodular goitres. The optimal dose is not predictable, and some patients who are initially rendered euthyroid will eventually develop hypothyroidism and require thyroxine replacement therapy. Nevertheless, the treatment appears to be safe, with no increased incidence of tumour, leukaemia and birth defects. Patients receiving radioactive iodine have the advantage of being able to discontinue antithyroid medication.

Surgical management

Thyroidectomy

Thyroidectomy is now reserved for patients who have failed or have intolerance to medical therapy, obstructive symptoms, suspicion of malignancy, in pregnant women with thyrotoxicosis and for cosmesis.

Patients should have their thyroid function stabilized with antithyroid drugs prior to surgery and baseline serum calcium is required preoperatively. In an emergency setting, iodine and β-blockers can be given to restore euthyroidism within hours.

The patient is positioned supine with the neck extended. A horizontal skin incision is undertaken and the thyroid gland identified and mobilized. The gland can be very vascular and ligation of many perforating vessels may be required. The recurrent laryngeal nerve and parathyroid glands are identified and preserved. The amount of thyroid tissue removed depends on the underlying aetiology; bilateral subtotal thyroidectomy is performed for toxic multinodular goitres and Graves' disease, and a unilateral thyroidectomy is performed for patients with solitary adenomas. After meticulous haemostasis the skin is closed.

Successful surgery renders the patient immediately euthyroid. With Graves' disease there is a 5% risk of recurrence at 5 years. Exophthalmos regresses in the majority of patients but progressive eye disease can occur in up to 10%. Complications of surgery include bleeding, hypothyroidism (related to extent of surgical excision), transient hypoparathyroidism (hypocalcaemia) and recurrent laryngeal nerve palsy.

Prognosis

The prognosis is related to the underlying cause. Patients who are cured (e.g. subtotal thyroidectomy for toxic adenoma) will have a normal life expectancy. With Graves' disease, approximately 20% become clinically and biochemically euthyroid on β-blockers alone.The course of ophthalmopathy is largely unpredictable and independent of thyroid status and drug treatment. Typically, it worsens over 18 months, followed by stabilization and spontaneous improvement in patients with mild disease.

More by this Author


Comments

No comments yet.

    Sign in or sign up and post using a HubPages Network account.

    0 of 8192 characters used
    Post Comment

    No HTML is allowed in comments, but URLs will be hyperlinked. Comments are not for promoting your articles or other sites.


    Click to Rate This Article
    working