Overview
Definition:
Graves' disease is an autoimmune disorder characterized by diffuse hyperplasia of the thyroid gland, leading to hyperthyroidism
In adolescents, it is the most common cause of hyperthyroidism, driven by autoantibodies (Thyroid Stimulating Immunoglobulins - TSI) that mimic TSH, stimulating the TSH receptor and increasing thyroid hormone production.
Epidemiology:
Affects approximately 1 in 1000 children and adolescents
More common in girls than boys, with a female-to-male ratio of approximately 4:1
The peak incidence is in adolescence, particularly between ages 11-15 years.
Clinical Significance:
Untreated or inadequately treated hyperthyroidism in adolescents can lead to significant short-term and long-term morbidity, impacting growth, development, cardiac function, bone health, and psychological well-being
Early and accurate diagnosis and management are crucial for optimal outcomes and successful preparation for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Nervousness and anxiety
Tremors, especially of the hands
Increased appetite despite weight loss
Heat intolerance and increased sweating
Fatigue and muscle weakness
Frequent bowel movements
Irritability and difficulty concentrating
Sleep disturbances
For girls: irregular menstrual periods.
Signs:
Tachycardia and palpitations
Goiter, typically diffuse and smooth
Lid lag (Dalrymple's sign) and lid retraction (von Graefe's sign)
Exophthalmos (proptosis) due to retro-orbital edema and lymphocytic infiltration
Stare
Smooth, warm, moist skin
Fine tremor of the outstretched hands
Hyperreflexia
Elevated systolic blood pressure
Sometimes, signs of thyroid acropachy (rare in children) or pretibial myxedema.
Diagnostic Criteria:
Diagnosis is typically made based on a combination of clinical features, thyroid function tests (TFTs), and thyroid autoantibodies
Key findings include elevated free T4 and T3 levels, suppressed TSH, and elevated TSI or TSH receptor antibodies (TRAb)
Ultrasound may show a diffusely enlarged gland with increased vascularity.
Diagnostic Approach
History Taking:
Detailed history of onset and progression of symptoms
Family history of thyroid disease or autoimmune disorders
Review of medications
Assessment of growth and pubertal development
Inquiry about eye symptoms (diplopia, dryness, irritation) and skin changes
Assess for any precipitating factors like infections or significant stress.
Physical Examination:
Complete physical examination, focusing on vital signs (heart rate, blood pressure)
Palpation of the thyroid gland for size, consistency, nodules, and tenderness
Examination of the eyes for proptosis, lid retraction, ophthalmoplegia, and conjunctival injection
Assess for tremor, skin changes, reflexes, and muscle strength.
Investigations:
Thyroid Function Tests (TFTs): Free T4 (FT4), Free T3 (FT3), and Thyroid Stimulating Hormone (TSH)
In Graves' disease, expect elevated FT4 and FT3, with suppressed TSH
Thyroid Stimulating Immunoglobulin (TSI) or TSH Receptor Antibodies (TRAb): Elevated levels confirm autoimmune etiology
Thyroid Ultrasound: To assess gland size, vascularity, and rule out nodules
Radionuclide Thyroid Scan (less commonly used for initial diagnosis): Shows diffuse uptake, can help differentiate from other causes of thyrotoxicosis.
Differential Diagnosis:
Subacute thyroiditis (painful, tender gland, elevated ESR)
Toxic adenoma or multinodular goiter (localized overactivity, often older patients)
Transient hyperthyroidism due to amiodarone or excessive iodine intake
Factitious thyrotoxicosis
McCune-Albright syndrome
Neonatal Graves' disease (in neonates born to mothers with Graves').
Management
Initial Management:
Pharmacological therapy with antithyroid drugs (ATDs) is the first-line treatment
Beta-blockers (e.g., propranolol) are used to control adrenergic symptoms like tremor, tachycardia, and anxiety
Initial dose of propranolol is typically 0.5-1 mg/kg/day divided into 3-4 doses, titrated to clinical response.
Medical Management:
Antithyroid Drugs (ATDs): Propylthiouracil (PTU) and Methimazole (MMI)
MMI is generally preferred due to fewer hepatic side effects and once-daily dosing
Start MMI at 0.25-0.5 mg/kg/day (max 20-30 mg/day) or PTU at 5-10 mg/kg/day (max 150-300 mg/day)
Aim for biochemical euthyroidism within 4-12 weeks
Gradually titrate dose to maintain normal FT4 and FT3 with a detectable but not fully suppressed TSH
Treatment duration is typically 18-24 months, aiming for remission.
Surgical Management:
Thyroidectomy is considered in cases of severe ATD side effects, poor compliance, contraindications to radioactive iodine, large goiters causing compressive symptoms, or when ATD therapy fails to achieve remission after adequate trial
Total thyroidectomy is usually performed.
Supportive Care:
Regular monitoring of TFTs (every 4-6 weeks initially, then every 3-6 months)
Monitoring for side effects of ATDs (rash, fever, arthralgias, hepatitis, agranulocytosis – requiring immediate discontinuation and CBC)
Management of ophthalmopathy: artificial tears, lubricating ointments, elevated head of bed
In rare, severe cases, corticosteroids or orbital radiation may be considered
Nutritional support to compensate for increased metabolism
Psychological support for irritability and mood changes.
Complications
Early Complications:
Thyroid storm: A life-threatening exacerbation of hyperthyroidism characterized by severe fever, tachycardia, altered mental status, and gastrointestinal symptoms
It is a medical emergency requiring immediate intensive management
Agranulocytosis: A rare but serious side effect of ATDs.
Late Complications:
Cardiovascular complications: Atrial fibrillation, cardiomyopathy, heart failure
Osteoporosis: Due to accelerated bone turnover
Ocular complications: Persistent ophthalmopathy leading to vision impairment
Growth retardation if hyperthyroidism is prolonged and uncontrolled
Recurrence of hyperthyroidism after treatment cessation.
Prevention Strategies:
Prompt diagnosis and initiation of appropriate therapy
Strict adherence to ATD regimen and regular follow-up
Careful monitoring for ATD side effects, especially agranulocytosis and hepatitis
Adequate management of ophthalmopathy to prevent vision loss
Patient and family education regarding the disease and treatment.
Prognosis
Factors Affecting Prognosis:
Remission rates vary, with studies reporting 30-60% remission after 18-24 months of ATD therapy
Factors associated with higher remission rates include younger age at diagnosis, smaller thyroid gland size, and lower baseline antibody titers
Relapse is common.
Outcomes:
With appropriate management, most adolescents can achieve biochemical euthyroidism, with symptom resolution and normal growth and development
Long-term outcomes are generally good, but vigilance for relapse and complications is necessary
Surgical management offers a definitive cure but carries risks of hypothyroidism and surgical complications.
Follow Up:
Adolescents treated with ATDs require long-term follow-up, even after achieving remission, due to the risk of relapse
Follow-up involves regular clinical assessments and TFTs
Those who undergo thyroidectomy require lifelong thyroid hormone replacement therapy and regular monitoring
Eye and bone health should also be monitored periodically.
Key Points
Exam Focus:
Graves' disease is autoimmune, TSI mediated, leading to hyperthyroidism in adolescents
First-line therapy is ATDs (MMI preferred) with beta-blockers for symptoms
Monitor for agranulocytosis, hepatitis, and ophthalmopathy
Remission rates are moderate
relapse is common.
Clinical Pearls:
Always suspect Graves' disease in an adolescent with unexplained weight loss, anxiety, or tremor
Titrate beta-blockers to heart rate and symptom control
Educate families about ATD side effects and the importance of compliance
Do not hesitate to consider RAI or surgery for persistent disease or severe side effects.
Common Mistakes:
Delaying diagnosis due to atypical presentations
Underestimating the severity of adrenergic symptoms and not using beta-blockers
Inadequate monitoring of ATD side effects, especially agranulocytosis
Failing to counsel patients and families about remission rates and the possibility of relapse, leading to poor compliance.