Thyroid Disorders and Treatments

Hypothyroidism

• Hyposecretion of thyroid hormone
• Treated with thyroid hormone replacement therapy
• Two thyroid hormone preparations:
  • Levothyroxine sodium (thyroxin, T4)
  • Liothyronine sodium (T3)

Hyperthyroidism

• Hypersecretion of thyroid hormone
• Treated with:
  • Antithyroid drugs
  • Irradiation
  • Surgical removal of the overactive tissue

Levothyroxine and Liothyronine

• Levothyroxine is the drug of choice for thyroid hormone replacement in patients with hypothyroidism
• Both Levothyroxine and Liothyronine are adequately absorbed following oral administration.
• Levothyroxine has a longer half-life than Liothyronine (one week vs two days)
• Adverse effects:
  • Elderly patients and those with ischemic heart disease may experience angina or myocardial infarction if a high initial dose is given
  • Excess thyroid hormone can lead to thyrotoxicosis

Thioamide drugs

• Include:
  • Carbimazole
  • Methimazole
  • Propylthiouracil (PTU)
• Propylthiouracil is the drug of choice during pregnancy and lactation
• Used in patients with Graves' disease to control symptoms before surgery or RAI treatment
• Pharmacokinetics:
  • Administered orally
  • Carbimazole is hydrolyzed into methimazole
• Adverse effects:
  • Cross the placenta and are secreted in breast milk
  • Can cause:
    • Hypothyroidism
    • Goiter enlargement
    • Agranulocytosis (rare)

β-Adrenoceptor Antagonists

• Example: Propranolol
• Used to reduce cardiovascular stimulation associated with hyperthyroidism
• Also used in thyroid storm

Iodide salts

• Examples:
  • Potassium iodide tablets and solutions
  • Saturated solution of potassium iodide
  • Lugol solution
• Immediate reducing effect on the release of thyroid hormones
• Used for short-term therapy:
  • Preparing patients for surgery
  • Inhibiting the release of thyroid hormone after RAI treatment
• Effect:
  • Inhibit thyroid hormone formation
  • Reduce iodide trapping
  • Reduce gland vascularity
• Maximum effect occurs after 10-15 days, then diminishes due to loss of inhibitory effect on thyroid.

Radioactive Iodine (RAI)

• Colorless and tasteless solution of sodium iodide I-131
• Mechanism: absorbed from the gut and concentrated by the thyroid gland, emits β-particles that destroy thyroid tissue
• Definitive treatment for:
  • Relapsed Graves' disease
  • Toxic multinodular goiter
  • Toxic solitary nodule
• Contraindication: Pregnancy and lactation
• Well absorbed orally, given as a single dose.
• Half-life: 8 days
• Maximum effect takes several weeks, with peak effect around two months.

Bone Disorders

• Osteoporosis: gradual reduction in bone mass, leading to fractures after minimal trauma
• Osteomalacia: abnormal mineralization of new bone matrix
• Rickets: osteomalacia in children
• Common causes of osteomalacia:
  • Vitamin D deficiency
  • Abnormal vitamin D metabolism
  • Phosphate deficiency
  • Osteoblast dysfunction

Drugs Affecting Calcium and Bone

• Bisphosphonates Inhibit bone resorption by osteoclasts
• Examples:
  • Alendronate
  • Pamidronate
  • Risedronate
  • Tiludronate
  • Ibandronate
  • Zoledronic acid
• Uses:
  • Management of Paget disease of bone
  • Hypercalcemia
  • Osteolytic bone lesions of metastatic cancer
  • Reduced risk of developing breast cancer
• Effects:
  • Inhibit bone resorption
  • Reduce tumor burden in bone
  • Decrease bone pain
  • Reduce risk of fractures in patients with bone metastases.

Estrogen and Raloxifene

• Estrogen:
  • reduces the formation and activation of osteoclasts, slowing bone loss
• Raloxifene:
  • Increases bone density in postmenopausal women
  • Decreases vertebral fractures in women with osteoporosis

Denosumab

• Inactivates gene transcription required for osteoclast survival and function
• Administered subcutaneously every 6 months
• Used to treat osteoporosis

Calcitonin

• Poorly absorbed from the gut, must be administered parenterally or by nasal inhalation
• Products:
  • Salmon calcitonin
  • Recombinant human calcitonin
• Salmon calcitonin is 50 to 100 times more potent than human calcitonin
• Clinical uses:
  • Treats osteoporosis, Paget disease of bone, and hypercalcemia.

Teriparatide

• Recombinant form of human PTH
• Used to treat osteoporosis

Strontium ranelate

• Treatment option for the prevention of osteoporosis
• Decreases osteoclastic activity and reduces bone resorption

Fluoride

• Sodium fluoride:
  • Used to prevent tooth decay and dental caries
  • Replaces the hydroxyl group in calcium phosphate salts to form fluorapatite, which is more resistant to erosion

Pharmacological Treatment of Anemia

• Iron deficiency anemia (IDA)
• Anemia of inflammation and chronic disease (AI/ACD)