Graves disease | Medical Science Optional Notes for UPSC PDF Download

Epidemiology of Graves' Disease

• Incidence:
  • Approximately 30 cases per 100,000 people per year.
• Sex Distribution:
  • More common in females but exhibits a higher frequency in males.
  • Male-to-female ratio is approximately 1:8.
• Typical Age Range:
  • Predominantly affects individuals within the age range of 20-40 years.
• High Iodine Intake:
  • Increased risk associated with elevated iodine intake.
• Autoimmune Nature:
  • Primarily a B and T lymphocyte-mediated autoimmune disorder.
• Genetic Predisposition:
  • About 50% of patients with Graves' disease have a family history of autoimmune disorders.
  • Examples include type 1 diabetes mellitus, Hashimoto's disease, pernicious anemia, and myasthenia gravis.
• Triggers:
  • May be triggered by factors such as surgery or trauma to the thyroid gland.
  • Severe psychological stress is also considered a potential trigger.

Pathophysiology

of Graves' Disease

• TSH-Receptor Stimulating IgG Immunoglobulin (TRAb):
  • TRAb, a type II hypersensitivity reaction, stimulates the TSH receptor.
  • Results in increased thyroid function and growth, leading to hyperthyroidism and a diffuse goiter.
• Effect on Orbital Fibroblasts:
  • TRAb also activates orbital fibroblasts.
  • Induces fibroblast proliferation, synthesis of hyaluronic acid, and the differentiation of fibroblasts into adipocytes.
  • Leads to ophthalmopathy with exophthalmos (protruding eyeballs).
• Impact on Dermal Fibroblasts:
  • TRAb affects dermal fibroblasts.
  • Promotes the deposition of glycosaminoglycans in connective tissue.
  • Results in pretibial myxedema, a condition characterized by thickened, swollen skin on the lower legs.

Clinical feature of Graves' Disease

• Hyperthyroidism Symptoms:
  • General manifestations include heat intolerance, excessive sweating (moist, warm skin), weight loss despite increased appetite, hyperdefecation (increased bowel movements), weakness, fatigue, and hyperreflexia.
• Triad of Graves' Disease:
  • Hyperthyroidism symptoms encompass a triad specific to Graves' disease.
• Ophthalmic Involvement (Graves' Ophthalmopathy):
  • Presents with lid lag, lid retraction ("staring look"), and Graves' ophthalmopathy.
  • Graves' ophthalmopathy involves orbital manifestations such as exophthalmos (protruding eyeballs).
• Goiter:
  • Characterized by a diffuse, smooth, nontender goiter.
  • Often accompanied by an audible bruit at the superior poles.
  • Similar findings can be observed in subacute thyroiditis, toxic adenoma, and toxic multinodular goiter.
• Cardiovascular Manifestations:
  • Tachycardia is a consistent feature in almost all cases of hyperthyroidism.
  • Palpitations, irregular pulse (attributed to atrial fibrillation/ectopic beats), hypertension with a widened pulse pressure.
  • Elderly patients may present with features of cardiac failure, including pedal edema and dyspnea on exertion.
• Musculoskeletal Effects:
  • Fine tremor of the outstretched fingers.
  • Myopathy leading to muscle weakness, especially in patients older than 40.
  • Osteopathy-related complications such as osteoporosis and fractures, particularly in the elderly.
• Endocrinological Changes:
  • Oligo/amenorrhea and anovulatory infertility.
  • Gynecomastia, decreased libido, and erectile dysfunction.
• Neuropsychiatric Symptoms:
  • Anxiety, agitation, emotional instability, and insomnia are common neuropsychiatric manifestations.

Triad of Graves disease

• Diffuse Goiter:
  • Characterized by a smooth, uniformly enlarged thyroid gland.
  • Possible auscultation of a bruit at the superior poles of the lobes.
• Ophthalmopathy:
  • Presents with exophthalmos (protruding eyeballs), ocular motility disturbances, and lid retraction.
  • Additionally involves conjunctival conditions.
• Dermopathy (Pretibial Myxedema):
  • Manifests as non-pitting edema and firm plaques.
  • Typically observed on the anterior/lateral aspects of both legs.

Diagnosis of Graves' Disease

• Clinical Examination:
  • Graves' disease diagnosis is often evident during clinical examination.
• Initial Testing:
  • The best initial test involves assessing TSH (thyroid-stimulating hormone) and T3/T4 levels.
  • Detection of an undetectable TSH and elevated T3/T4 suggests hyperthyroidism.
• Thyroid Antibodies Measurement:
  • Measure specific thyroid antibodies, including TRAbs (thyroid receptor-stimulating antibodies), which are specific to Graves' disease.
  • Additionally, assess anti-TPO (anti-thyroid peroxidase) and anti-Tg (anti-thyroglobulin) antibodies, which are nonspecific markers.
• Thyroid Scintigraphy:
  • Conduct thyroid scintigraphy if TRAbs levels are low, aiming to establish a diagnosis.
  • This diagnostic procedure reveals a diffuse uptake of radioactive iodine (123I).
  • Note that thyroid scintigraphy is contraindicated during pregnancy.
• Thyroid Ultrasound (with Color Doppler):
  • Perform thyroid ultrasound, especially in pregnant women with low TRAbs levels.
  • The ultrasound reveals an enlarged, hypervascular thyroid, aiding in the diagnostic process.

Treatment of Graves' Disease

• Beta-Blockers:
  • Utilize beta-blockers for the rapid control of hyperthyroidism symptoms.
• Antithyroid Drugs:
  • Common medications include methimazole and propylthiouracil.
  • The goal is to achieve a euthyroid state.
  • In cases with a small goiter and mild hyperthyroidism, antithyroid drugs alone may lead to remission in approximately 50% of cases.
  • Once remission is achieved, a gradual tapering and discontinuation of the drugs may be undertaken.
• Radioactive Iodine Ablation:
  • Considered first-line therapy for nonpregnant patients with small goiters.
  • Second-line therapy for patients experiencing a relapse after prolonged antithyroid drug therapy.
• Surgery:
  • Near-total thyroidectomy is rarely performed in Graves' disease.

Complications of Therapy

• Permanent Hypothyroidism:
  • Following radioactive iodine ablation or surgery, there is a risk of permanent hypothyroidism.
  • Individuals may require lifelong thyroid replacement therapy.
• Graves Ophthalmopathy Complications:
  • New-onset or exacerbation of Graves' ophthalmopathy may occur after radioactive iodine ablation.

Acute Meningitis

Differential Diagnosis

• HSV Encephalitis: Presents with focal seizures and focal neurological deficits.
• Rocky Mountain Spotted Fever (RMSF): Characterized by a distinctive rash.
• Ehrlichioses: Exhibits a characteristic rash.
• Subdural and Epidural Empyema and Brain Abscess: Conditions involving purulent collections around or within the brain.
• Subarachnoid Hemorrhage (SAH): Hemorrhage within the subarachnoid space.
• Medication-Induced Hypersensitivity Meningitis: Meningitis triggered by a hypersensitive reaction to medications.
• Chemical Meningitis: Results from the release of tumor contents into the cerebrospinal fluid (CSF), as seen in cystic glioma or craniopharyngioma, epidermoid, or dermoid cyst.
• Carcinomatous or Lymphomatous Meningitis: Meningitis associated with cancerous or lymphomatous conditions.
• Meningitis Associated with Inflammatory Disorders: Inflammatory disorders such as sarcoidosis, systemic lupus erythematosus (SLE), and Behcet's syndrome may cause meningitis.
• Uveomeningitic Syndromes (Vogt-Koyanagi-Harada Syndrome): Syndromes involving both uveitis and meningitis.

Clinical Manifestations

• Fever with Rash (Petechial or Purpuric)
• Vomiting
• Irritability
• Headache
• Neck Stiffness
• Photophobia
• Decreased Level of Consciousness
• Seizures
• Focal Neurological Deficits

Signs of meningism 

Kernig Sign

• Assessment Methods:
  • The Kernig sign can be evaluated through two methods.
• First Method:
  • Passively elevate the extended leg at the hip joint.
  • If pain is present, reflex flexion of the knee occurs.
• Alternative Method:
  • Assess the Kernig sign by flexing the hip and knee to a 90° angle.
  • Subsequent extension of the leg induces stretching of the nerve roots or meninges.
  • This stretching can lead to pain and muscle guarding against extension.

Brudzinski Sign

When the neck is passively flexed, an automatic reflex response is observed as the hips spontaneously flex. This reflex action serves to alleviate the painful strain on the meninges.

Diagnosis Criteria for Meningitis

[Intext Question]

Management of Meningitis

• Medical Emergency:
  • Immediate initiation of empirical antimicrobial therapy is crucial and should begin within 60 minutes of suspicion.
• Antimicrobial Therapy:
  • Administer a third or fourth generation cephalosporin (Ceftriaxone/Cefepime).
  • Include Acyclovir in the treatment plan.
  • Consider Doxycycline as part of the antimicrobial regimen.
  • Administer Dexamethasone (10 mg intravenously) 15-20 minutes before the first antimicrobial dose, repeating the same dose every 6 hours for 4 days.
• Special Considerations:
  • In specific populations, consider additional coverage:
  • Add Ampicillin for Listeria monocytogenes coverage in individuals <3 months, those >55, or those with suspected impaired cell-mediated immunity (e.g., chronic illness, organ transplantation, pregnancy, malignancy, or immunosuppressive therapy).
  • Add metronidazole to cover gram-negative anaerobes in patients with otitis, sinusitis, or mastoiditis.
• Hospital-Acquired Infections and Neurosurgical Patients:
  • In hospital-acquired infections and neurosurgical patients, augment the regimen with vancomycin plus Ceftazidime or meropenem to cover Pseudomonas aeruginosa.

 Specific therapy

 Management of Elevated Intracranial Pressure (ICP)

• Head Elevation: Raise the patient's head to an angle of 30-45 degrees.
• Intubation: Consider endotracheal intubation for airway protection and control.
• Hyperventilation: Initiate controlled hyperventilation to achieve a PaCO2 level of 25-30 mmHg.
• Mannitol Administration: Administer mannitol as part of the treatment strategy.

These measures aim to reduce intracranial pressure and mitigate the risk of complications associated with elevated ICP.