Hyperthyroidism

Hyperthyroidism

1. Introduction and Overview

Definition:

Hyperthyroidism is a condition characterized by excessive production and secretion of thyroid hormones (T3 and T4), resulting in a hypermetabolic state and multisystem involvement.

Epidemiology:

  • Prevalence: Affects approximately 1-2% of the population globally; more common in women than men (5-10 times higher prevalence).

  • Age: Most commonly presents between 20–40 years.

  • Ethnic Predisposition: Higher incidence in Caucasians and Asians.

Relevance:

Hyperthyroidism leads to significant morbidity due to complications such as atrial fibrillation, osteoporosis, and thyroid storm, which can be life-threatening if untreated.

2. Etiology

Primary Causes:

  1. Graves’ Disease (most common cause):

    • Autoimmune disorder where thyroid-stimulating immunoglobulins (TSI) activate TSH receptors, leading to diffuse thyroid hyperactivity.

  2. Toxic Multinodular Goiter (TMNG):

    • Autonomous functioning thyroid nodules.

  3. Toxic Adenoma:

    • A single hyperfunctioning nodule.

  4. Subacute Thyroiditis:

    • Transient hyperthyroidism due to inflammation and release of stored thyroid hormones.

Secondary Causes:

  1. TSH-Secreting Pituitary Adenoma (rare).

  2. Gestational Hyperthyroidism:

    • Elevated hCG stimulating TSH receptors in early pregnancy.

  3. Iatrogenic Causes:

    • Excessive thyroid hormone replacement therapy or iodine (e.g., amiodarone, contrast agents).

Risk Factors:

  • Family history of thyroid disorders.

  • Female sex.

  • Smoking (strong association with Graves’ ophthalmopathy).

  • Recent viral infections (in thyroiditis).

3. Pathophysiology

Normal Physiology:

Thyroid hormones regulate metabolic processes, cardiovascular function, and thermogenesis. The hypothalamic-pituitary-thyroid (HPT) axis maintains hormone levels via feedback regulation.

Mechanisms of Disease:

  1. Graves’ Disease:

    • Thyroid-stimulating immunoglobulins mimic TSH, causing excess T3/T4 production.

  2. Autonomous Nodules:

    • Loss of TSH regulation leads to unregulated hormone synthesis.

  3. Thyroiditis:

    • Destruction of thyroid follicles releases preformed thyroid hormones, resulting in transient hyperthyroidism.

Key Pathways:

  • Excess T3/T4 leads to increased basal metabolic rate, beta-adrenergic activity, and sympathetic nervous system stimulation.

  • Dysregulation of feedback loops in Graves’ disease and TSH-secreting adenomas.

4. Clinical Features

Symptoms:

  1. General: Weight loss despite increased appetite, heat intolerance, sweating.

  2. Neurological: Tremors, anxiety, irritability, insomnia.

  3. Cardiovascular: Palpitations, tachycardia, atrial fibrillation.

  4. Gastrointestinal: Diarrhea, increased bowel frequency.

  5. Reproductive: Oligomenorrhea, infertility.

Signs:

  1. Thyroid Gland:

    • Diffuse goiter (Graves’), nodular goiter (TMNG), or a palpable single nodule (toxic adenoma).

  2. Eyes:

    • Exophthalmos, lid lag, and stare (Graves’ ophthalmopathy).

  3. Skin:

    • Warm, moist skin; pretibial myxedema (Graves’).

  4. Hands:

    • Fine tremors, onycholysis, palmar erythema.

Stages and Progression:

  • Mild/Moderate: Subtle symptoms with weight loss, tachycardia.

  • Severe: Thyroid storm with fever, severe tachycardia, and altered mental status.

Differentiating Features:

  • Graves’ disease often presents with ophthalmopathy and pretibial myxedema, absent in toxic nodular goiters or thyroiditis.

5. Diagnostic Approach

Clinical Diagnosis:

  • Detailed history and physical examination focusing on symptoms of hyperthyroidism and thyroid examination.

Laboratory Investigations:

  1. Thyroid Function Tests:

    • Suppressed TSH with elevated free T4 and/or T3.

  2. Autoimmune Markers:

    • TSH receptor antibodies (TRAb) in Graves’.

  3. Inflammatory Markers:

    • Elevated ESR in subacute thyroiditis.

Imaging Studies:

  1. Radioactive Iodine Uptake (RAIU) Scan:

    • Increased uptake in Graves’ and toxic nodular goiters.

    • Decreased uptake in thyroiditis.

  2. Ultrasound:

    • Helps detect nodules and differentiate from diffuse enlargement.

Functional Testing:

  • Not commonly required but may include TSH suppression tests for secondary causes.

Diagnostic Criteria:

  • Diagnosis confirmed by clinical presentation, TSH suppression, and elevated thyroid hormones, supported by imaging (RAIU or ultrasound).

6. Management

Medical Management:

  1. Antithyroid Drugs:

    • Thionamides: Methimazole (preferred), propylthiouracil (PTU) during the first trimester of pregnancy or thyroid storm.

    • Mechanism: Inhibit thyroid peroxidase.

    • Side effects: Agranulocytosis, hepatotoxicity.

  2. Beta-Blockers:

    • Propranolol to manage tachycardia and tremors.

  3. Radioactive Iodine (RAI) Therapy:

    • Effective for Graves’ and toxic nodular goiter.

    • Contraindicated in pregnancy and severe ophthalmopathy.

Surgical Management:

  • Thyroidectomy:

    • Indicated in large goiters, suspicion of malignancy, or contraindications to RAI/antithyroid drugs.

    • Pre-operative preparation with antithyroid drugs and beta-blockers.

Adjunctive Therapies:

  • Steroids for severe Graves’ ophthalmopathy.

Emergency Management:

  • Thyroid Storm:

    • ICU care, PTU loading dose, propranolol, iodine (to block hormone release), and corticosteroids.

7. Prognosis

Natural History:

  • Untreated hyperthyroidism may lead to cardiovascular complications (e.g., atrial fibrillation) and osteoporosis.

Outcomes with Treatment:

  • High success rate with RAI and surgery.

  • Graves’ disease has a recurrence risk after antithyroid drugs.

Long-Term Impacts:

  • Risk of hypothyroidism post-treatment (RAI or surgery).

8. Complications

Primary Disease Complications:

  1. Cardiovascular: Atrial fibrillation, heart failure.

  2. Skeletal: Osteoporosis due to increased bone turnover.

  3. Crisis: Thyroid storm.

Therapeutic Complications:

  • Hypothyroidism from RAI or surgery.

  • Agranulocytosis with antithyroid drugs.

9. Prevention

Primary Prevention:

  • No definitive prevention; avoid modifiable risk factors like smoking.

Secondary Prevention:

  • Screening in high-risk populations (e.g., family history, postpartum women).

Tertiary Prevention:

  • Regular follow-up with TSH and free T4 monitoring.

  • Eye protection measures in Graves’ ophthalmopathy.

10. Patient Education

Disease Understanding:

Explain the cause, symptoms, and importance of compliance with treatment.

Self-Monitoring:

  • Report palpitations, weight loss, or worsening symptoms promptly.

Lifestyle Advice:

  • Avoid iodine-rich supplements or medications without medical advice.

When to Seek Help:

  • Symptoms of thyroid storm or agranulocytosis (e.g., fever, sore throat).

11. Recent Research and Advances

  • Biological Therapy: Teprotumumab for Graves’ orbitopathy.

  • Genetic Insights: Novel markers for predicting Graves’ recurrence.

  • Minimally Invasive Techniques: Endoscopic thyroidectomy.

12. Case Studies

Example:

A 35-year-old female presents with weight loss, palpitations, and protruding eyes. Labs confirm suppressed TSH and elevated T3/T4. Diagnosed with Graves’ disease and treated with methimazole and propranolol, with subsequent symptom resolution.

13. References

  1. American Thyroid Association (ATA) Guidelines for Hyperthyroidism and Graves’ Disease (2022).

  2. Harrison’s Principles of Internal Medicine, 21st Edition.

  3. Brunicardi FC, Andersen DK, Billiar TR. Schwartz's Principles of Surgery, 11th Edition.

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