Hyperthyroidism: Primary, Secondary & Subclinical

• Hyperthyroidism is the overproduction of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland.
• Thyrotoxicosis refers to the effects of excessive thyroid hormones in the body.

Primary vs. Secondary

• Primary hyperthyroidism results from thyroid pathology, causing excessive thyroid hormone production.
• Secondary hyperthyroidism is caused by hypothalamic or pituitary pathology.
• The pituitary gland produces too much thyroid-stimulating hormone, which stimulates the thyroid gland to produce excessive thyroid hormones.

Subclinical Hyperthyroidism

• Thyroid hormones (T3 and T4) are normal
• Thyroid-stimulating hormone (TSH) is suppressed (low).
• Symptoms may be absent or mild.

Specific Conditions

• Graves’ disease is an autoimmune condition where TSH receptor antibodies cause primary hyperthyroidism.
• Toxic multinodular goiter (Plummer’s disease) involves nodules on the thyroid gland that produce excessive thyroid hormones autonomously.
• It is most common in patients over 50 years.
• Exophthalmos (proptosis) is the bulging of the eyes caused by Graves’ disease due to tissue inflammation behind the eyeballs, forcing them forward.
• Pretibial myxoedema is a skin condition specific to Graves’ disease with glycosaminoglycan deposits under the skin on the anterior leg, giving it a discolored, waxy, and oedematous appearance.
• Goitre refers to the neck lump caused by swelling of the thyroid gland.

Causes of Hyperthyroidism ("GIST" Mnemonic)

• G: Graves’ disease
• I: Inflammation (thyroiditis)
• S: Solitary toxic thyroid nodule
• T: Toxic multinodular goitre

Thyroiditis

• Thyroiditis (thyroid gland inflammation) often causes an initial period of hyperthyroidism, followed by hypothyroidism.
• Causes include De Quervain’s, Hashimoto’s, postpartum, and drug-induced thyroiditis.

Universal Presentation of Hyperthyroidism

• Anxiety and irritability
• Sweating and heat intolerance
• Tachycardia
• Weight loss
• Fatigue
• Insomnia
• Frequent loose stools
• Sexual dysfunction
• Brisk reflexes on examination

Graves’ Disease Specific Features

• Diffuse goitre (without nodules)
• Graves’ eye disease, including exophthalmos
• Pretibial myxoedema
• Thyroid acropachy (hand swelling and finger clubbing)

Toxic Multinodular Goitre

• Nodules may be present within a goiter

Solitary Toxic Thyroid Nodule

• Solitary toxic thyroid nodule involves a single abnormal thyroid nodule releasing excessive thyroid hormone.
• The nodules are usually benign adenomas.
• Treatment involves surgical removal of the nodule.

De Quervain’s Thyroiditis

• De Quervain’s thyroiditis (subacute thyroiditis) causes temporary thyroid gland inflammation with three phases:
  • Thyrotoxicosis
  • Hypothyroidism
  • Return to normal
• The initial thyrotoxic phase includes:
  • Excessive thyroid hormones
  • Thyroid swelling and tenderness
  • Flu-like illness (fever, aches, and fatigue)
  • Raised inflammatory markers (CRP and ESR)
• It is a self-limiting condition; treatment includes:
  • NSAIDs for pain and inflammation
  • Beta blockers for hyperthyroidism symptoms
  • Levothyroxine for hypothyroidism symptoms
• <10% remain hypothyroid long-term.

Thyroid Storm

• Thyroid storm (thyrotoxic crisis) is a rare, severe presentation of hyperthyroidism with fever, tachycardia, and delirium.
• It can be life-threatening, requires admission for monitoring, and may need fluid resuscitation, anti-arrhythmic medication, and beta blockers.

Management

• A specialist endocrinologist guides hyperthyroidism treatment.
• Carbimazole is the first-line anti-thyroid drug, typically taken for 12-18 months.
• Once thyroid hormone levels normalize (4-8 weeks), maintenance carbimazole involves titration-block or block and replace.

Carbimazole warnings

• MHRA issued a warning in 2019 about the risk of acute pancreatitis.

Propylthiouracil

• Propylthiouracil is the second-line anti-thyroid drug due to the risk of severe liver reactions.
• Both carbimazole and propylthiouracil can cause agranulocytosis, with a sore throat being a key presenting feature.

Radioactive Iodine Treatment

• Involves drinking a single dose of radioactive iodine.
• The reduction in the number of cells results in a decrease in thyroid hormone production.
• Remission can take 6 months, often resulting in hypothyroidism requiring long-term levothyroxine.
• Specific rules apply, including restrictions on pregnancy and contact with others.

Adjunct Treatments

• Beta blockers (propranolol) block adrenalin-related symptoms
• They are useful in patients with thyroid storm.
• They do not treat the underlying problem.
• Surgery (thyroidectomy) is a definitive option
• Removal of the whole thyroid gland (thyroidectomy), or the toxic nodules, effectively stops the excess thyroid hormone production.
• Patients will be hypothyroid after a thyroidectomy, requiring life-long levothyroxine.