Endocrine

Hyperthyroidism: Diagnosis and Management

SUMMARY:

Hyperthyroidism is a form of thyrotoxicosis caused by the excessive production and secretion of thyroid hormones from the thyroid. In iodine-sufficient countries, such as the United States, the majority of cases of hyperthyroidism are due to Graves’ disease, followed by toxic multinodular goiter and solitary toxic adenoma. Diagnosis is made based on symptoms at presentation followed by further imaging and antibody testing. Treatment ranges from antithyroid drugs to reduce hormone secretion, radioactive iodine therapy, and definitive surgery via thyroidectomy.

Clinical Presentation

Hyperthyroidism affects roughly 1.2% of Americans
- Less than half of these cases will have signs and symptoms of overt hyperthyroidism
Increasing prevalence of hyperthyroidism with:
- Older age | Female sex | White race | Family history
Common reported symptoms:
- Palpitations | Fatigue | Tremor | Anxiety | Disturbed sleep | Weight loss (despite increased appetite) | Heat intolerance | Sweating | Polydipsia | Changes in menstruation
Physical exam findings include:
- Tachycardia | Extremity tremor | Weight loss | Tachypnea | Warm and moist skin
Graves’ disease may have additional physical exam findings such as:
- Ophthalmopathy (i.e., Graves’ orbitopathy) occurs in 25% of patients with Graves’ disease | Proptosis | Periorbital edema | Diplopia
- Thyroid dermopathy: Slightly pigmented thickened skin over the pretibial area
- Acropachy: Rare | Clubbing of fingers and toes
Patients with multinodular goiter may additionally present with:
- Globus sensation | Dysphagia | Orthopnea
Older patients are more likely to develop cardiovascular complications such as atrial fibrillation and heart failure
Serious complications of hyperthyroidism include
- Osteoporosis
- Decreased fertility
- Thyrotoxic periodic paralysis (e.g., Triad of acute muscle paralysis | Hypokalemia | Thyrotoxicosis)

Diagnosis

Patients presenting with signs and symptoms of hyperthyroidism should have a TSH checked
- TSH has high sensitivity and specificity for thyroid disorders
If TSH is abnormal, T4 and T3 levels should be checked to distinguish between overt and subclinical hyperthyroidism
- Subclinical hyperthyroidism: Normal T3/T4 levels + Low TSH
- Overt hyperthyroidism: High T3/T4 + Low TSH
TSH may be normal in the case of hyperthyroidism caused by:
- TSH-producing pituitary adenoma
- Thyroid hormone resistance
Patients taking high doses of biotin may also have inaccurate TFT results and should repeat testing 2 days after stopping biotin
- If thyroid function tests (TFTs) suggest hyperthyroidism, then further testing should be obtained to determine etiology and guide treatment
- Thyroid ultrasound + TSH-receptor Antibodies (TRAb, i.e., thyroid-stimulating immunoglobulins or thyroid stimulating antibodies) OR
Radioactive iodine uptake test (RAIU)
- Thyroid US + TRAb
- May be preferred over RAIU due to lower cost and absence of radiation exposure

Graves’ disease: Positive TRAb and doppler US of the thyroid showing increased blood flow with a diffusely enlarged thyroid
Radioactive iodine uptake test
- Graves’ disease: Diffusely increased uptake
- Multinodular goiter: Normal or high uptake with an irregular and asymmetric pattern
- Toxic adenoma: Localized and focal increased uptake with suppression in the remaining thyroid tissue
- Thyroiditis | Drug-induced | Factitious: Diffuse low uptake

Treatment

Symptomatic patients should be started on beta-adrenergic blockade while awaiting improvement in thyroid hormone levels with the below therapies
- Propranolol (Inderal) 10 to 40mg 3 to 4 times per day
- Atenolol (Tenormin) 25 to 100mg 1 to 2 times per day
- Metoprolol (Lopressor) 25 to 50mg 2 to 3 times per day
- Nadolol (Corgard) 40 to 160mg daily
Anti-thyroid drugs (ATD): Propylthiouracil (PTU, Propycil) | Thiamazole (Methimazole)
- Inhibit production of thyroid hormones within the thyroid | 1^st line therapy for hyperthyroidism due to Graves’ disease
- PTU dosing: 50 to 150mg three times daily
- Thiamazole dosing: 10 to 40mg daily
- Thiamazole is preferred in most cases due to its longer duration of action and better side effect profile
- Recommended to titrate to lowest effective dose to maintain TFTs within normal range
- Dosing depends on: Severity of symptoms | Size of thyroid gland
- Check TFTs 4 to 6 weeks after starting therapy | Repeat TFTs every 2 to 3 months afterwards
- Continue maintenance dosing of ATD for ≥ 12 to 18 months
- Cessation of ATD is associated with high rates of relapse within the first 6 months but is uncommon after 4 to 5 years
- Common side effects: Pruritis | Arthralgias | GI distress
- Less common side effects: Agranulocytosis | Hepatotoxicity | Vasculitis
- Agranulocytosis: Generally occurs within 90 days of ATD initiation
- Obtain baseline CBC and CMP prior to starting therapy
Radioactive iodine therapy
- Safe and cost effective
- Can be 1^st line therapy for: Graves’ disease | Toxic multinodular goiter | Toxic adenoma
- Contraindicated in: Pregnancy (or planning to become pregnant | Breastfeeding | Inability to adhere to radiation safety guidelines | Concern for thyroid cancer | Moderate to severe Graves’ orbitopathy
- Radioactive iodine therapy may worsen Graves’ orbitopathy | Give prophylactic steroids for patients with mild Graves’ orbitopathy following treatment
- Some patients might need treatment with an ATD while awaiting radioactive iodine therapy planning | ATD should be stopped 3 to 5 days prior to procedure and restarted 3 to 7 days later until TFTs normalize
- Monitor TFTs 1 to 2 months after radioactive iodine therapy | Repeat every 4 to 6 weeks until patient is euthyroid
- Patients who relapse or have persistent hyperthyroidism after 6 months can repeat therapy
- Side effects: Acute thyroiditis | Worsening of ophthalmopathy
Total thyroidectomy
- Definitive and most successful therapy for Graves’
- Recommended for: Large goiters | Suspected or documented thyroid cancer | Moderate to severe ophthalmopathy | Patients who prefer surgery
- Patients should be treated with an ATD to achieve a euthyroid state prior to surgery
- After surgery patients will need supplemental levothyroxine
- Repeat TFTs after 6 to 8 weeks post surgery
- Complications include: Hypocalcemia (due to hypoparathyroidism)| Recurrent laryngeal nerve injury

Thyroid Storm

Rare disorder of thyrotoxicosis with a high mortality rate requiring inpatient treatment
Can be triggered by: Discontinuation of ATD | Infection
Diagnosis is clinical when patient presents with signs and symptoms of thyroid hormone excess such as:
- Fever | AMS | Diarrhea | Jaundice | Tachycardia | Heart failure | Atrial fibrillation
Burch-Wartofsky Point Scale (BWPS) for Thyrotoxicosis (see Learn More below) can be helpful for diagnosis
Treatment includes:
- High dose anti-thyroid drugs: PTU 500 to 1000mg loading dose + 250mg every four hours | Thiamazole 20mg every 6 hours
- Inorganic iodine: 5 drops of saturated solution of potassium iodide every 6 hours PO
- Cholestyramine (Questran): 4g every 6 hours
- Beta blockers (e.g., Propanolol (Inderal)): For symptom management
- Glucocorticoids: Treat risk of adrenal insufficiency caused by severe thyrotoxicosis
- Acetaminophen (Tylenol) | External cooling: For symptom management

KEY POINTS:

Hyperthyroidism in the US and other iodine-sufficient regions is most commonly due to Graves’ disease, followed by toxic multinodular goiter and solitary toxic adenoma
Diagnosis depends on abnormal thyroid function testing (e.g., Low TSH + Elevated T3/T4) in the setting of signs of and symptoms of hyperthyroidism
Further testing can be obtained to delineate the cause of hyperthyroidism including TRAb + Thyroid ultrasound OR radioactive iodine uptake testing
Treatment options include anti-thyroid drugs, radioactive iodine therapy or thyroidectomy
Thyroid storm is a potentially lethal complication of thyrotoxicosis, often triggered by infection or lack of adherence to ATD therapy, and warrants inpatient treatment