Endocrine Disorders

Appendix: Hyperthyroidism

Hyperthyroidism has multiple etiologies, manifestations, and potential therapies. In the United States, the prevalence of hyperthyroidism is approximately 1.2% (0.5% overt and 0.7% subclinical). Women are 2 to 10 times more likely than men to develop hyperthyroidism. There is a spectrum of severity of hyperthyroidism from subclinical hyperthyroidism to thyroid storm.

There is a limited amount of literature on the effect of thyroid disease on productivity (absenteeism and presenteeism). One study (Nexo et al.) found patients with hyperthyroidism faced a significantly higher risk of missing work for 3 weeks or longer due to illness compared to healthy controls. They were twice as likely as peers to miss weeks of work due to illness within a year of diagnosis.

A comprehensive history and physical examination must be done and focus on possible signs and symptoms of hyperthyroidism and its impact on various systems. A workability questionnaire on thyroid disease can be found at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483246/.

The LEO evaluation in people with hyperthyroidism needs to focus on possible co-morbidities which can improve with appropriate therapy of the underlying thyroid condition.

Etiologies:

• Graves’ disease
• Toxic multinodular goiter
• Toxic adenoma
• Thyroiditis: subacute thyroiditis (painful inflammation, infection), postpartum thyroiditis, silent thyroiditis
• Excess exogenous thyroid medication
• Exogenous iodine

Hyperthyroidism is more common in people with:

• a family history of thyroid disease
• other auto-immune conditions such as pernicious anemia, type 1 diabetes, primary adrenal insufficiency

Symptoms and Signs

Symptoms of hyperthyroidism can vary from person to person and may include:

• nervousness or irritability
• fatigue or muscle weakness
• heat intolerance
• trouble sleeping
• tremor
• frequent bowel movements or diarrhea
• weight loss mood swings goiter
• cardiac arrhythmia
• exophthalmos due to Graves’ ophthalmopathy that can cause double vision, light sensitivity, and eye pain, dry eyes, and rarely can lead to vision loss
• osteoporosis

Medical Evaluation

All patients with known or suspected hyperthyroidism should undergo a comprehensive history and physical examination, including measurement of pulse rate, blood pressure, respiratory rate, body weight, thyroid size, tenderness, symmetry, and nodularity; pulmonary, cardiac, and neuromuscular function; and presence or absence of peripheral edema, eye signs, or pretibial myxedema. The evaluation of LEOs with hyperthyroidism needs to focus on possible co-morbidities which improve with appropriate therapy of the underlying thyroid condition.

Cardiovascular System

Background: Hyperthyroidism is associated with:

• Cardiac arrhythmias such as sinus tachycardia and atrial fibrillation. Anticoagulation may be necessary in patients in atrial fibrillation.
• Hypertension
• Rarely, high output heart failure
• Cardiovascular disease associated with hyperthyroidism usually resolves when the person becomes euthyroid.

LEO Evaluation

Assess for signs and symptoms above:

• Sinus Arrhythmia (tachycardia) is not generally associated with symptoms or known to degenerate into malignant arrhythmias. Asymptomatic LEOs with sinus node disturbances and no structural heart disease should not be given job restrictions.
• Asymptomatic Atrial Fibrillation or Atrial Flutter in the absence of structural heart disease with appropriate ventricular response (on or off AV nodal blocking drugs – Beta blockers) can be cleared for unrestricted duty. However, if anti-coagulation treatment is recommended by the treating physician or consulting cardiologist, job restrictions should be provided (see Medications chapter). Follow-up is recommended about 4-6 weeks post therapy for the hyperthyroidism since the cardiac arrhythmia may resolve and anticoagulation therapy may not be needed anymore.
• Heart Failure: LEOs with current heart failure should be restricted. This may be short term. Cardiac evaluation may be necessary, especially in the older patient. This should not postpone therapy of the thyrotoxicosis. Since the heart failure may be reversible, LEOs should be re-evaluated after the underlying hyperthyroidism has been treated, in about 4-6 weeks post therapy.
• Hypertension: Stage I (mild): Systolic 140-159 millimeters of mercury (mmHg) or diastolic 90-99 No restrictions. Stage II (moderate): Systolic 160-179 mmHg or diastolic 100-109 mmHg: No restrictions. Stage III (severe): Systolic ≥180 mmHg or diastolic ≥110 mmHg. Re-evaluate 4-6 weeks post therapy.

Vision

Background: If the cause of the hyperthyroidism is Graves’ disease, visual disturbances may be present. Graves’ ophthalmopathy (GO) is an auto immune disease that results in inflammation and a buildup of tissue and fat behind the eye socket, causing the eyeballs to bulge out. Rarely, inflammation is severe enough to compress the optic nerve that leads to the eye, causing vision loss. Other GO symptoms are:

• dry, gritty, and irritated eyes
• proptosis
• diplopia
• light sensitivity
• pressure or pain in the eyes
• corneal abrasions

One study showed that that Graves’ disease patients with eye complications were 7 times more likely than healthy peers to have an extended sick leave from work within a year of diagnosis. In later years, the risk diminished but remained twice as high compared to healthy peers. An association was found between the severity of the exopthalmos and diplopia and occupational disability (more severe diplopia was associated with a higher the chance of occupational disability).

LEO Evaluation

• If diplopia is present, restrictions are necessary.
• Re-evaluation should be done 4-6 weeks post therapy.
• Ophthalmology consultation may be needed.
• Eye protection to avoid corneal abrasions may be needed.
• Criteria found in the Eye and Vision chapter are met.

Neuro-psychological

Background: People with hyperthyroidism have an increased risk of being hospitalized with psychiatric diagnoses and being treated with antipsychotics, antidepressants, and anxiolytics, both before and after the diagnosis of hyperthyroidism. Also, psychiatric morbidity, such as psychosis, anxiety disorders and bipolar disease seems to be over-represented among patients with hyperthyroidism. If symptoms persist after the person is euthyroid, other causes of the mental health issues should be evaluated.

LEO Evaluation (see LEO Mental Health chapter)

• Assess for signs and symptoms of conditions above.
• A formal psychological evaluation may be necessary to determine if the LEO has met DSM-5 criteria for a specific condition such as depression.
• If there are significant signs of anxiety or bipolar disorder, a formal psychological evaluation may be necessary and short-term restrictions may be necessary. Re-evaluate when hyperthyroidism has resolved.

Musculoskeletal

• A resting tremor is sometimes present.
• A fairly rare co-morbidity is periodic thyrotoxic hypokalemic paralysis. Short term restrictions may be necessary until the hyperthyroidism resolves.
• Proximal muscle weakness may also be present.

LEO Evaluation: Assess for symptoms above. If present, short term restrictions may be necessary. Re-evaluate after treatment.

Diagnostic Tests: Hyperthyroidism

Laboratory results:

• Overt Hyperthyroidism: subnormal (usually undetectable) serum thyroid-stimulating hormone (TSH), elevated serum levels of triiodothyronine (T3) and/or free thyroxine (free T4).
• Subclinical hyperthyroidism: low or undetectable serum TSH, normal reference range for both T3 and free T4.
• In mild hyperthyroidism, serum T4 and free T4 can be normal, only serum T3 may be elevated, and serum TSH will be low or undetectable, ‘‘T3-toxicosis’’ and may represent the earliest stages of hyperthyroidism.

Note: Other causes of euthyroid hyperthyroxinemia include those drugs that inhibit T4 to T3 conversion, such as amiodarone or high-dose propranolol, acute psychosis, extreme high altitude, and amphetamine abuse.

Other tests include the Thyroid Stimulating Hormone Receptor Antibody (TRAb). This test is useful for the differential diagnosis of clinically suspected Graves’ disease. If third generation TRAb assays are not readily available, Radioactive iodine uptake (RAIU) is preferred for initial evaluation.

Thyroid Uptakes and Thyroid Scans

Radioactive iodine uptake (RAIU). An iodine-123 or technetium-99m pertechnetate scan should be obtained when the clinical presentation suggests a toxic adenoma (TA) or toxic multinodular goiter (TMNG).

• Graves’ disease: elevated uptake
• TMNG: Normal or high
• Thyroiditis (painless, postpartum, or subacute), factitious (exogenous) ingestion of thyroid hormone or recent excess iodine intake: Low (near zero)

Note: The RAIU may be low after exposure to iodinated contrast in the preceding 1-2 months or with ingestion of a diet unusually rich in iodine such as seaweed soup or kelp. However, RAIU is rarely <1% unless the iodine exposure is reoccurring as during treatment with amiodarone.

Thyroid scans provide an image of the thyroid gland to assess variability in the concentration of the radioisotope within thyroid tissue. A thyroid scan is useful if the clinical presentation suggests a toxic adenoma or toxic multinodular goiter.

• Graves’ disease (GD): Smooth diffuse pattern unless there are co-existent nodules.
• Single toxic adenoma (TA): focal uptake in the adenoma with suppressed uptake in the surrounding thyroid tissue.
• TMNG: multiple areas of focal increased and suppressed uptake.

Treatment of Hyperthyroidism

• Symptomatic therapies include beta blockers for cardiac arrhythmias, eye drops for dry eyes, therapy for osteoporosis, medications for mental health issues such as anxiety.
• Beta-adrenergic blockade is recommended in all patients with symptomatic thyrotoxicosis, especially elderly patients and thyrotoxic patients with resting heart rates in excess of 90 bpm or coexistent cardiovascular disease. These drugs are generally contraindicated in patients with bronchospastic asthma. In patients with quiescent bronchospastic asthma who need heart rate control, or in patients with mild obstructive airway disease or symptomatic Raynaud’s phenomenon, a relative β-1 selective agent can be used cautiously, with careful monitoring of pulmonary status.
• Therapeutic options depend on the etiology of hyperthyroidism, patient age, co-morbidities, and patient preference. Therapeutic options include anti-thyroid medication (PTU or methimazole), radioactive iodine (RAI), and surgery.
• Follow up and monitoring 4-6 weeks after therapy. LEOs who have received RAI often become hypothyroid and need to have levothyroxine replacement therapy.