Is Graves' disease a form of hyperthyroidism or hypothyroidism?

Graves' Disease is a Form of Hyperthyroidism

Graves' disease is definitively a form of hyperthyroidism characterized by overactivity of the thyroid gland, resulting in overproduction of thyroid hormones and increased metabolic rate. 1

Pathophysiology and Classification

Graves' disease is an autoimmune disorder and represents the most common cause of hyperthyroidism in iodine-sufficient areas. The key mechanism involves:

• Autoantibodies (TSH receptor antibodies or TRAb) that bind to and stimulate the thyroid hormone receptor, causing unregulated thyroid hormone production 1, 2
• Thyroid hypertrophy and overactivity resulting in excessive thyroid hormone secretion 3
• Accounts for approximately 95% of hyperthyroidism cases in pregnancy 1

Clinical Manifestations

The clinical presentation of Graves' disease reflects its hyperthyroid state:

• Systemic symptoms: Tremors, nervousness, insomnia, excessive sweating, heat intolerance, tachycardia, hypertension, and goiter 1
• Ophthalmopathy: Occurs in approximately 50% of patients, with symptoms including eyelid lag or retraction 1, 4
• Dermal manifestations: Including localized and pretibial myxedema 1

Diagnostic Confirmation

The diagnosis of Graves' disease as a hyperthyroid condition is confirmed by:

1. Thyroid function tests:

   • Low or suppressed TSH (<0.45 mIU/L) 1
   • Elevated Free T4 and/or Free T3 levels 1
   • Some patients have normal FT4 but elevated FT3 (T3 toxicosis occurs in ~8-16% of hyperthyroid cases) 1

2. Antibody testing:

   • Positive TSH receptor antibodies (TRAb) - the hallmark of Graves' disease 1, 3
   • May also have thyroid peroxidase antibodies (TPOAb) 1

Treatment Options

The FDA-approved treatments for Graves' disease further confirm its classification as hyperthyroidism:

1. Antithyroid medications:

   • Methimazole is indicated "in patients with Graves' disease with hyperthyroidism" 5
   • Propylthiouracil can be used, particularly in the first trimester of pregnancy 6
   • These medications work by inhibiting thyroid hormone synthesis 7, 3

2. Beta-blockers (e.g., propranolol) are used to control hyperthyroid symptoms 1, 7

3. Definitive treatments:

   • Radioactive iodine ablation (RAIU)
   • Thyroidectomy (total or partial) 7, 3

Complications of Untreated Disease

The consequences of untreated Graves' disease further confirm its hyperthyroid nature:

• Thyroid storm - a life-threatening hyperthyroid emergency 1
• In pregnancy: increased risk of severe preeclampsia, preterm delivery, heart failure, and possibly miscarriage 1
• Long-term cardiovascular complications related to persistent hyperthyroidism 1

Common Pitfalls to Avoid

1. Confusing Graves' disease with other thyroid disorders:

   • Unlike Hashimoto's thyroiditis (which typically causes hypothyroidism), Graves' disease causes hyperthyroidism
   • However, patients treated for Graves' disease may develop hypothyroidism as a result of treatment 3

2. Missing extrathyroidal manifestations:

   • Graves' ophthalmopathy can sometimes occur even when thyroid function is controlled 4
   • The presence of ophthalmopathy can influence treatment decisions 2

3. Inadequate monitoring:

   • Patients with subclinical hyperthyroidism should be retested within 3 months (TSH 0.1-0.45 mIU/L) or within 4 weeks for TSH <0.1 mIU/L 1

In conclusion, Graves' disease is unequivocally a form of hyperthyroidism, as evidenced by its pathophysiology, clinical presentation, diagnostic findings, and treatment approaches.