THYROTOXICOSIS

THYROTOXICOSIS

• Thyrotoxicosis- the state of thyroid hormone excess
• Hyperthyroidism- thyroid hormone excess due to excessive thyroid function.
• Etiology
• Primary hypothyroidism
• Graves' disease
• Toxic multinodular goiter
• Toxic adenoma
• Functioning thyroid carcinoma metastases
• Activating mutation of the TSH receptor
• Activating mutation of G_sα (McCune-Albright syndrome)
• Struma ovarii
• Drugs: iodine excess (Jod-Basedow phenomenon)
• Thyrotoxicosis without hyperthyroidism
• Subacute thyroiditis
• Silent thyroiditis
• Other causes of thyroid destruction: amiodarone, radiation, infarction of adenoma
• Ingestion of excess thyroid hormone (thyrotoxicosis factitia) or thyroid tissue
• Secondary hypothyroidism
• TSH-secreting pituitary adenoma
• Thyroid hormone resistance syndrome: occasional patients may have features of thyrotoxicosis
• Chorionic gonadotropin-secreting tumors^a
• Gestational thyrotoxicosis^a 
• Clinical features
• Symptoms- (in descending order of frequency)
• Hyperactivity, irritability, dysphoria
• Heat intolerance and sweating
• Palpitations
• Fatigue and weakness
• Weight loss with increased appetite
• Diarrhea
• Polyuria
• Oligomenorrhea, loss of libido
• Signs- (in descending order of frequency)
• Tachycardia; atrial fibrillation in the elderly
• FineTremor
• Goiter
• Warm, moist skin
• Muscle weakness, proximal myopathy
• Lid retraction or lag
• Gynecomastia
• Common neurologic manifestations include hyperreflexia, muscle wasting, and proximal myopathy without fasciculation
• most common cardiovascular manifestation is sinus tachycardia. high cardiac output produces a bounding pulse, widened pulse pressure, and an aortic systolic murmur and can lead to worsening of angina or heart failure
• Gastrointestinal transit time is decreased, leading to increased stool frequency
• Graves' disease is associated with specific eye signs that comprise Graves' ophthalmopathy This condition is also called thyroid-associated ophthalmopathy
• NO SPECS" scheme is an acronym derived from the following eye changes:

0 = No signs or symptoms

1 = Only signs (lid retraction or lag), no symptoms

2 = Soft tissue involvement (periorbital edema)

3 = Proptosis (>22 mm)

4 = Extraocular muscle involvement (diplopia)

5 = Corneal involvement

6 = Sight loss

• Thyroid dermopathy- most frequent over the anterior and lateral aspects of the lower leg (hence the term pretibial myxedema), The typical lesion is a noninflamed, indurated plaque with a deep pink or purple color and an "orange-skin" appearance
• Thyroid acropachy refers to a form of clubbing found in <1% of patients with Graves' disease (Fig. 335-7C ). It is so strongly associated with thyroid dermopathy
• Lab investigations (see flow-chart)

• Treatment
• Medical treatment (anti-thyroid drugs)
• Thionamides- (inhibit Thyroid Peroxidase- TPO)
• Drugs-
• Propylthiouracil (inhibits peripheral conversion of T₄ g T₃)
• Carbimazole
• Methimazole (active metabolite of carbimazole)
• Titration regimen-
• The starting dose of antithyroid drugs can be gradually reduced as thyrotoxicosis improves.
• Initial dose- propylthiouracil- 100–200 mg every 6–8 h; carbimazole or methimazole- 10–20 mg every 8 or 12 h
• Maintenance dose- propylthiouracil- 50–100 mg/d; carbimazole or methimazole- 2.5–10 mg/d.
• Remission by 18–24 months.
• Thyroid function tests and clinical manifestations reviewed 3–4 weeks after starting treatment, and the dose is titrated based on unbound T₄ levels.
• Block-replace regimen
• high doses combined with levothyroxine supplementation to avoid drug-induced hypothyroidism
• remission by 6 months.
• A/E
• Rash, urticaria, fever, and arthralgia
• Hepatitis
• SLE-like syndrome
• Agranulocytosis (<1%)
• Propanolol- 20-40 mg QID
• Radioiodine therapy
• ¹³¹I dosage- ranges between 185 MBq (5 mCi) to 555 MBq (15 mCi)
• Indicated as initial Rx or relapses
• Risk of Thyrotoxic crisis- prevented by 1 month prior Rx with antithyroid drugs
• Absolute contraindications- Pregnancy and breast feeding
• Surgical treatment
• Subtotal or near-total thyroidectomy
• Thyroid storm
• Thyroid storm, a.k.a Thyrotoxic crisis-
• Clinical features-
• life-threatening exacerbation of hyperthyroidism
• fever
• delirium, seizures, coma
• vomiting, diarrhea and jaundice
• mortality due to ¹cardiac failure, ²arrhythmia or ³hyperthermia
• Precipitating factors-
• Acute illness (e.g., stroke, infection, trauma, diabetic ketoacidosis)
• Surgery (esp. on the thyroid)
• Radioiodine treatment of a patient with partially treated or untreated hyperthyroidism
• Treatment-
• Intensive monitoring and supportive care
• Identification and treatment of the precipitating cause
• Antithyroid treatment-
• Propylthiouracil (600 mg loading dose and 200–300 mg every 6 h oral/ per rectum.
• 1 hour after the first dose of propylthiouracil, stable iodide is given to block thyroid hormone synthesis via the Wolff-Chaikoff effect (the delay allows the antithyroid drug to prevent the excess iodine from being incorporated into new hormone. [saturated solution of potassium iodide (5 drops SSKI every 6 h), or ipodate or iopanoic acid (0.5 mg every 12 h) oral]
• Propranolol - to reduce tachycardia and other adrenergic manifestations (40–60 mg orally every 4 h; or 2 mg intravenously every 4 h).
• Glucocorticoids (e.g., dexamethasone, 2 mg every 6 h)
• Antibiotics if infection is present
• Cooling, O₂, and i.v. fluids