Thyrotoxicosis


  1. Thyrotoxicosis describes a constellation of clinical features arising from elevated circulating levels of thyroid hormone.
  2. The most common causes of thyrotoxicosis are:
    • Graves’ disease
    • Multinodular goitre
    • Autonomously functioning thyroid nodules (toxic adenoma)
    • Thyroiditis.

Clinical Assessment
  1. The most common symptoms of thyrotoxicosis are:
    • Weight loss with a normal or increased appetite
    • Heat intolerance
    • Palpitations
    • Tremor and irritability
  2. Common signs of thyrotoxicosis include:
    • Tachycardia
    • Palmar erythema
    • Lid lag
  3. Not all patients have a palpable goitre, but experienced clinicians can discriminate between:
    • The diffuse soft goitre of Graves’ disease
    • The irregular enlargement of a multinodular goitre
  4. All causes of thyrotoxicosis can cause lid retraction and lid lag due to potentiation of sympathetic innervation of the levator palpebrae muscles.
  5. Only Graves’ disease causes other features of ophthalmopathy, such as:
    • Periorbital edema
    • Conjunctival irritation
    • Exophthalmos
    • Diplopia
  6. Specific features unique to Graves’ disease include:
    • Pretibial myxoedema
    • Thyroid acropachy (a periosteal hypertrophy, indistinguishable from finger clubbing)


Investigations
  1. First-line investigations for thyrotoxicosis include:
    • Serum T3, T4, and TSH measurements.
  2. If abnormal values are found in the initial tests, they should be:
    • Repeated for confirmation due to the likelihood of prolonged medical treatment or destructive therapy.
  3. In most patients with thyrotoxicosis, serum T3 and T4 are both elevated, with T4 usually in the upper part of the reference range. However, T3 is raised (T3 toxicosis) in approximately 5% of cases.
  4. Serum TSH is undetectable in primary thyrotoxicosis, but it can be raised in the very rare syndrome of secondary thyrotoxicosis caused by a TSH-producing pituitary adenoma.
  5. Measurement of TSH receptor antibodies (TRAb), elevated in Graves’ disease, is recommended for confirmation when biochemical thyrotoxicosis is established. Alternatively, radioisotope scanning can be used as a diagnostic approach when TRAb is not available.
  6. Non-specific abnormalities in thyrotoxicosis include:
    • Serum enzymes: raised alanine aminotransferase, γ-glutamyl transferase (GGT), and alkaline phosphatase from liver and bone
    • Raised bilirubin
    • Mild hypercalcaemia
    • Glycosuria: associated diabetes mellitus, ‘lag storage’ glycosuria
  7. An electrocardiogram (ECG) may demonstrate:
    • sinus tachycardia (or)
    • atrial fibrillation.
  8. Radio-iodine uptake tests were used to measure the proportion of isotopes trapped in the whole gland, but they have been largely superseded by 99m-technetium scintigraphy scans. These scans indicate trapping, are quicker to perform with a lower dose of radioactivity, and provide a higher-resolution image.
  9. In cases of low-uptake thyrotoxicosis, the cause is usually a transient thyroiditis.
  10. Factitious thyrotoxicosis can occur when patients consume excessive amounts of a thyroid hormone preparation, most commonly levothyroxine.
  11. The exogenous levothyroxine suppresses pituitary TSH secretion and iodine uptake, resulting in a high T4:T3 ratio (typically 30:1 in conventional thyrotoxicosis) that increases to above 70:1 in factitious thyrotoxicosis.
  12. In factitious thyrotoxicosis, circulating T3 is derived exclusively from the peripheral mono deiodination of T4 and not from thyroid secretion.
  13. The combination of negligible iodine uptake, high T4:T3 ratio, and low or undetectable thyroglobulin is diagnostic for factitious thyrotoxicosis.


Management
  1. Definitive treatment of thyrotoxicosis depends on the underlying cause and may include:
    • Antithyroid drugs
    • Radioactive iodine
    • Surgery
  2. For short-term relief of thyrotoxicosis symptoms, a non-selective β-adrenoceptor antagonist (β-blocker), such as propranolol (160 mg daily), can be used. It alleviates but does not abolish symptoms in most patients within 24–48 hours.
  3. Beta-blockers should not be used for long-term treatment of thyrotoxicosis, but they are extremely useful in the short term, especially while patients are awaiting hospital consultation or following 131I therapy.
  4. Verapamil may be used as an alternative to β-blockers, particularly in patients with asthma. However, it usually only effectively improves tachycardia and has little effect on the other systemic manifestations of thyrotoxicosis.


Atrial fibrillation in thyrotoxicosis
  1. Atrial fibrillation occurs in about 10% of patients with thyrotoxicosis. The incidence is higher in men and increases with age, affecting almost half of all males with thyrotoxicosis over the age of 60.
  2. Subclinical thyrotoxicosis is a risk factor for atrial fibrillation.
  3. Characteristically, the ventricular rate is little influenced by digoxin but responds to the addition of a β-blocker.
  4. Thromboembolic vascular complications are particularly common in thyrotoxic atrial fibrillation, requiring anticoagulation unless contraindicated.
  5. Once thyroid hormone and TSH concentrations have been returned to normal, atrial fibrillation will spontaneously revert to sinus rhythm in about 50% of patients, but cardioversion may be required in the remainder.


Thyrotoxic crisis (Thyroid Storm)
  1. Thyroid storm or thyrotoxic crisis is a rare but life-threatening complication of thyrotoxicosis.
  2. The most prominent signs of thyroid storm include:
    • Fever
    • Agitation
    • Delirium
    • Tachycardia or atrial fibrillation
    • Cardiac failure (more common in older patients)
  3. Thyrotoxic crisis is a medical emergency and has a mortality rate of 10% despite early recognition and treatment.
  4. The most common precipitating factor for thyrotoxic crisis is infection in a patient with previously unrecognized or inadequately treated thyrotoxicosis.
  5. It may also develop in known thyrotoxicosis shortly after thyroidectomy in an ill-prepared patient or within a few days of ^131I therapy, when acute radiation damage may lead to a transient rise in serum thyroid hormone levels.
  6. Urgent specialist endocrine input should be sought in cases of suspected 'thyroid storm' to confirm the diagnosis and provide advice on appropriate treatment.
  7. Initial treatment for thyroid storm includes:
    • Rehydration
    • Administration of propranolol (either orally at 80 mg 4 times daily or intravenously at 1–5 mg 4 times daily)
  8. Glucocorticoids (hydrocortisone 100 mg IV every 8 hours) and iodine to reduce the conversion of T4 to active T3.
  9. Sodium ipodate, a radiographic contrast medium (500 mg per day orally), can restore serum T3 levels to normal in 48–72 hours.
  10. If sodium ipodate is not available, potassium iodide or Lugol's solution are reasonable alternatives.
  11. Oral propylthiouracil (PTU) (200 mg every 4 hours) should be given to inhibit the synthesis of new thyroid hormone.
  12. PTU is preferred to carbimazole (20 mg every 6 hours) as it also inhibits the conversion of T4 to T3.
  13. If the patient is unconscious or uncooperative, PTU and propranolol can be administered by nasogastric tube.
  14. After 10–14 days, the patient can usually be maintained on carbimazole alone.


Hyperthyroidism in old age
  1. Thyrotoxicosis in old age commonly due to multinodular goitre.
  2. Clinical features include:
    • Apathy
    • Anorexia
    • Proximal myopathy
    • Atrial fibrillation
    • Cardiac failure predominate.
  3. Non-thyroidal illness: Thyroid function tests are performed more frequently in older patients, but interpretation may be altered by intercurrent illness.
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