Thyroid Disorders

Introduction

The thyroid gland secretes 3 main hormones

• Thyroxine (T₄)
• Tri-iodothyronine (T₃)
• Calcitonin - involved in the control of plasma calcium

* Thyroid-stimulating hormone (TSH; thyrotrophin)

The majority of the secreted hormone is T₄.

• This is converted into the (three- to five-fold) more active species, T₃, in a tissue-specific manner.
• Both hormones are critically important for normal growth and development and for controlling energy metabolism.

Hypothyroidism

In hypothyroidism, there is a deficiency in T₄ and consequently, an elevation in TSH.

• Hypothyroidism occurs more commonly in females (~80% of cases), and the incidence increases with age.
• Both iodine deficiency and excess can cause hypothyroidism; however, global deficiency is largely being addressed by mandatory salt iodization programs in many countries.
• Therefore, in developed nations, the most common cause of hypothyroidism is Hashimoto's disease, an autoimmune condition in which a patient's own antibodies attack the thyroid gland.

The goals of treatment are to resolve symptoms, normalize TSH within the reference range and avoid over-treatment.

• Even when patients have no symptoms (such as in subclinical hypothyroidism), treatment may be advised to reduce the risk of long-term complications.
• Patients should be counseled that symptom resolution may lag behind biochemical treatment changes for several weeks to months.

Levothyroxine (T₄) is usually the drug of choice for hypothyroidism, except in myxoedema coma, where T₃ may be used in the first instance.

• A consistent preparation (i.e. the same formulation and manufacturer) is preferred to minimize variability from refill to refill.
• Levothyroxine should be taken with water consistently at least 30-60 minutes before breakfast or at bedtime (at least 3-4 hours after the last meal) for consistent absorption.
• Do not administer within 4 hours of calcium- or iron-containing products.

Hyperthyroidism

Hyperthyroidism is defined as the thyroid gland's production of excessive amounts of thyroid hormones. Thyrotoxicosis refers to the clinical syndrome associated with prolonged exposure to elevated levels of thyroid hormone.

• Free T₄ is high and TSH is low, and symptoms are nearly opposite of those seen in hypothyroidism.

The most common cause of hyperthyroidism is Graves' disease, which primarily affects females aged 30-50 years.

• Graves' disease is an autoimmune disorder resulting from the production of an abnormal immunoglobulin G. This antibody occupies the TSH receptor on the thyroid follicular cell, causing cell division and continuously stimulating thyroid hormone secretion.
• Other causes include toxic nodular goitre and drug-induced thyrotoxicosis.

Three forms of therapy are available: antithyroid drugs, radioactive iodine and surgery. There is no universal agreement on the specific indications for each therapy, and none is ideal, as all are associated with both short- and long-term sequelae.

• Symptom control: With any option, the patient should be treated with beta-blockers first for symptom control (to reduce palpitations, tremors, and tachycardia).
• Euthyroid requirement: Neither surgery nor radioactive iodine should be administered until the patient has been rendered euthyroid due to the risk of inducing a life-threatening thyroid crisis (thyroid storm).

Antithyroid drugs may be used temporarily to control hyperthyroidism prior to definitive therapy with radioiodine or surgery, or they may be prescribed for 12 to 24 months to attain remission.

• In recent years, long-term antithyroid drug therapy has become increasingly popular.
• This avoids permanent hypothyroidism and is supported by studies demonstrating long-term safety and higher remission rates with extended use.
• Conversely, radioactive iodine has become less popular due to its association with worsening thyroid eye disease and patient fears regarding radiation exposure.

Anti-thyroid medications, e.g. propylthiouracil, carbimazole, methimazole

• Carbimazole is a prodrug completely metabolized to methimazole, though the carbimazole dose required to yield an equivalent dose of methimazole is approximately 40% higher.
• When substituting, carbimazole 1 mg is considered equivalent to propylthiouracil 10 mg but the dose may need adjusting according to response.
• The most common adverse effect of antithyroid treatment is rash and arthropathy (5%) and less commonly agranulocytosis, hepatitis, aplastic anaemia and lupus-like syndromes. Overall, serious effects such as these occur in approximately 0.3% of patients treated. These side effects usually occur during the first 6 weeks of treatment, but this is not invariable.
• Cross-sensitivity between carbimazole and propylthiouracil is around 10%, and the patient can often be safely changed to the alternative agent unless they experience a severe reaction.
• All three antihyroid drugs have possible teratogenic effects, but teratogenic effects are more severe with methimazole and carbimazole compared with propylthiouracil. Therefore, propylthiouracil is preferred during the first trimester of pregnancy. After 16 weeks, guidelines recommend switching back to carbimazole/methimazole to mitigate the risk of propylthiouracil-induced hepatotoxicity, though patients may occasionally continue propylthiouracil if switching is contraindicated or risks destabilizing hormone levels.

Radioactive iodine (¹³¹I)

• Antithyroid drugs must be withdrawn 1 week prior to radioiodine is given and should not be restarted for at least 3 days afterwards (otherwise the isotope will not be trapped by the thyroid).
• Because the ablative effect of radioiodine usually commences within 2-3 months, many patients with mild or moderate disease will not need to restart their drug treatments, although close monitoring is required.
• Patients with severe thyrotoxicosis should restart their antithyroid drugs on day 3. Treatment is then withdrawn periodically to assess the effects of the radioiodine.
• Depending on the dose given, 24-90% of patients will develop hypothyroidism over their lifetime.
• Absolutely contraindicated during pregnancy and lactation.

Surgery (Thyroidectomy or hemithyroidectomy)

• Surgery may be considered for patients with severe hyperthyroidism and an obstructive goitre, or for pregnant women who cannot tolerate antithyroid drugs (since radioactive iodine is strictly contraindicated in pregnancy).
• Patients scheduled for surgery should first be rendered biochemically euthyroid whenever possible. If surgery must be performed semi-urgently, it requires rapid patient preparation with a combination of antithyroid drugs and β-blockers, and iodide given as Lugol's solution.
• Following surgery, 6-75% of patients will develop hypothyroidism over their lifetime, depending on the amount of remnant tissue left behind.

Summary

As pharmacists, we must actively identify causative medications that have the potential to induce hypothyroidism, hyperthyroidism or goiter.

• A primary example is amiodarone, a potent antiarrhythmic that can cause both hypothyroidism and hyperthyroidism.

External Links

• CPG Management of Thyroid Disorders, 2019
  
• Continuous methimazole therapy and its effect on the cure rate of hyperthyroidism using radioactive iodine: an evaluation by a randomized trial, 2006
  
• Gastrointestinal Malabsorption of Thyroxine, 2018