Download Hyperthyroid

HYPERTHYROIDISM
Gretchen Berland, M.D.
WEEK 18
Learning Objectives:
1. To know the most common causes of hyperthyroidism
2. To know the laboratory tests used to diagnose hyperthyroidism
3. To be aware of the approach to diagnosis and management of subclinical
hyperthyroidism
CASE ONE
Ms. Shaki is a 38-year-old healthy high school drama teacher who presents to your
clinic reporting that she “just hasn’t been feeling right.” Over the past six months
she reports “feeling tired most of the time” and has lost 15 pounds despite an
increased appetite. She also describes some heat intolerance as well as increased
perspiration and reports that her skin “feels really smooth.” Her past medical and
surgical history is unremarkable, and she reports no personal or family history of
thyroid disease. She takes no medications, does not use alcohol or tobacco, and has
monthly menstrual periods. On exam, her resting heart rate is 100, her blood
pressure is 122/64. Her thyroid feels enlarged, but is non-tender. The rest of her
physical exam is unremarkable.
Questions:
1. What might Ms. Shaki have?
In this patient, hyperthyroidism should be suspected given the constellation of
symptoms and the physical exam findings. Hyperthyroidism is the clinical
expression of a group of disorders that produce an excess of circulating thyroid
hormones including free thyroxine (FT4) and/or triiodothyronine (T3). The most
common causes of hyperthyroidism include Graves’ disease, followed by toxic
multinodular goiter, and solitary functioning nodules (see Table 1, Lancet paper).
Autoimmune postpartum and subacute thyroiditis, tumors that secrete thyrotropin,
and drug-induced thyroid dysfunction are also important causes.
Graves’ disease is an autoimmune disorder characterized by antibodies in the
circulation that are directed against the thyrotropin receptor. It accounts for
about 85% of the cases of hyperthyroidism in patients younger than age 40. In
most patients with Graves’, the typical symptoms of hyperthyroidism are present.
Symptoms include heat intolerance, weight loss, weakness, palpitations,
oligomenorrhea and anxiety. Signs include brisk tendon reflexes, fine tremor,
proximal weakness, stare and eyelid lag.
Toxic multinodular goiter accounts for most cases of hyperthyroidism in middleaged and elderly persons. The condition is often associated with a long-standing
simple goiter. Cardiac abnormalities may be present including sinus tachycardia,
atrial fibrillation and exacerbation of coronary artery disease or heart failure.
Lid lag may be noted on occasion but exopthalmos does not occur. In the elderly,
hyperthyroidism may present only as weight loss and apathy, so a high index of
suspicion is needed to make the diagnosis.
2. What tests would you like to order?
The serum TSH is the best initial diagnostic test, as a TSH level higher than
0.1 uU/ml excludes overt clinical hyperthyroidism.
If the serum TSH is lower than 0.1 uU/ml, plasma free T4 and T3 should be
measured. If the serum TSH is low, and free T4 and T3 are high, the diagnosis of
hyperthyroidism is confirmed, and a 24-hour thyroid radioiodine uptake scan can
be ordered to differentiate Grave’ hyperthyroidism from other causes (see p. 461,
Lancet article).
According to Cooper, the 24-hour radioactive iodine uptake (RAI) is a measure of
the iodine avidity of the thyroid gland. Uptake will be increased in patients with
Graves’ disease, toxic multinodular goiter and toxic adenoma. Uptake will be
low in patients with thyroiditis, exogenous hormone intake, extraglandular
hormone production and iodide exposure. The radioactive iodine scan is very
helpful in distinguishing mild Graves’ disease from painless or postpartum
thyroiditis.
CASE ONE CONTINUED:
The laboratory results for Ms. Shaki indicate she has overt hyperthyroidism, her
TSH is less than 0.1 uU/ml and her free T4 and T3 are markedly elevated. A 24-hour
RAI is elevated. You call her to discuss her results.
3. What do you tell her?
The clinical symptoms and laboratory findings indicate that Ms. Shaki has
Graves’ disease. Some forms of hyperthyroidism are transient and require only
symptomatic therapy (subacute or postpartum thyroiditis). The three methods
available for definitive therapy include: anti-thyroid drugs (thionamides),
radioiodine, and subtotal thyroidectomy (see Table 2, Lancet paper). The
selection of therapy depends on many factors. In the US, RAI therapy is the
treatment of choice for most patients, but cannot be used in pregnancy. Betaadrenergic antagonists are used to relieve symptoms of hyperthyroidism,
including tremor, palpitations, and anxiety. During treatment, patients are
followed by clinical evaluation and measurement of T4 (TSH maybe misleading
as it may remain low for weeks to months even though the patient is euthyroid and
T4 is normal). Thyroid function should be assessed every 4-6 weeks for the first
4-6 months. All patients with Graves’ disease require lifelong follow-up for
recurrent hyperthyroidism or development of hypothyroidism.
CASE TWO:
Ms. Fraser is a 74-year-old woman with coronary artery disease, s/p CABG in 2001,
hyperlipidemia, and osteoporosis. She reports she is feeling fine, and other than
occasionally feeling “tired”, reports no specific complaints. She denies chest pain,
dyspnea at rest or with exertion, and has had no recent change in weight. Her
medicine list includes aspirin, atenolol, atorvastatin, and alendronate weekly. Her
thyroid gland is non-tender on exam, and you think it is somewhat enlarged. Thyroid
function tests indicate a TSH concentration lower than 0.1 uU/ml but free T4 and T3
are within the reference ranges. An ultrasound reveals a multinodular goiter.
4. What do you want to do?
Figure 2 on page 241 of the JAMA paper outlines the approach to the diagnosis
and management of subclinical hyperthyroidism.
Subclinical hyperthyroidism is defined as a decrease in serum TSH concentration
below the reference range with normal serum free T4 and T3 concentrations.
Subclinical thyroid disease is a diagnosis based on laboratory evaluation,
patients often do not present with any clinical signs or symptoms suggestive of
thyroid dysfunction.
According to Col et al, management of patients with thyroid dysfunction remains
controversial because the body of scientific evidence needed to guide clinical
decision-making is limited. Because untreated subclinical hyperthyroidism with
suppressed serum TSH carries the potential risk of atrial fibrillation,
cardiovascular mortality and osteoporosis, the balance is shifted towards
treatment in older patients.
References:
1. Cooper DS. Hyperthyroidism. Lancet. 2003; 362:459-467.
2. Col, NF, Surks, MI, Daniels, GH. Subclinical thyroid disease. JAMA. 2004;291:
239-243.