Subclinical Hyperthyroidism
I recently saw a 97-year-old woman in consultation who had fallen in the assisted living facility where she was residing. She said she had tripped over the wheels of her walker but had no prior dizziness, shortness of breath, or chest pain. She was taken to the emergency department with a chief symptom of upper back pain. Because no imaging tests showed any fractures, her pain was thought to be musculoskeletal in nature. An initial electrocardiogram (ECG) revealed sinus tachycardia with a first-degree atrioventricular block and a right bundle branch block; however, she had no prior ECGs for us to use for comparison. Her cardiac troponin level was within normal limits. The results of a urinalysis were abnormal, showing an elevated white blood cell count. A diagnosis of urinary tract infection was made, and she was empirically started on antibiotic therapy.
The patient remained tachycardic and required use of beta blockers to control her heart rate. Her medical history included macular degeneration, cataracts, fibromyalgia, arthritis, and hypothyroidism treated with levothyroxine 88 µg daily. She was previously taking 75 µg of this medication, but her primary care physician increased the dosage after she reported feeling tired. The results of a full laboratory work-up were all within normal limits, except for a low sodium serum concentration of 131 mEq/L (normal, 136-142 mEq/L), which her family said was normal for her, and a low serum thyroid-stimulating hormone (TSH) level of 0.32 mIU/L (normal, 0.4-4.2 mIU/L). The result of the patient’s Free T4 test, which measures the free, unbound thyroxine levels in the bloodstream, was normal at 1.2 ng/dL.
While no mention was made of her thyroid status in the medical record, I made a diagnosis of subclinical hyperthyroidism and suggested that her dose of thyroid hormone replacement therapy be reduced. At this time, she remains tachycardic without treatment on beta blockers. I do not have anything else to report about her status, but I thought it would be a good time to review the all-too-common problem of subclinical hyperthyroidism with you.
Subclinical hyperthyroidism refers to low levels of TSH in the setting of normal levels of circulating thyroid hormone. The condition was identified as a clinical entity only after a second-generation TSH assay was developed. Prior to this medical advancement, normal TSH values were reported as
<5 mIU/L, and there was no way to distinguish normal levels of TSH from low or suppressed levels because of a technical limitation with the assay available at that time.
After development of the second-generation assay, we were for the first time able to identify persons with low or suppressed levels of TSH, attributable to either a low production of TSH endogenously or because excessive doses of thyroid hormone replacement were administered to manage their hypothyroidism. It was then recognized that there were in fact clinical consequences to having low levels of TSH, even in the setting of normal levels of circulating thyroid hormone.
Subclinical hyperthyroidism has been associated with cardiovascular mortality and all-cause mortality in some studies,1 although not in all. Shorter systolic time intervals, atrial fibrillation, and osteopenia have been associated as well. Clearly, if patients are already receiving thyroid hormone replacement for primary failure of their thyroid gland and their TSH levels are suppressed, the protocol is to reduce their dose of thyroid hormone, wait 4 to 6 weeks until a new steady state is reached, recheck their TSH levels, and continue to adjust the dosage as appropriate.
Epidemiological data suggest, however, that this problem also affects between 4% and 7% of persons older than 60 years of age who are not on thyroid hormone therapy. Most agree that treatment in these cases should be initiated if there are clearly associated symptoms, such as worsening cardiovascular function or cardiac arrhythmias, excessive muscle wasting, anorexia, depression, or significant osteoporosis. Atrial fibrillation has been described in 10% of these patients.2 Studies have reported that 47% to 61% of those with this disorder will have normal serum TSH levels upon retesting within 1 year without any intervention, and 1.5% to 13% will develop hyperthyroidism. It remains unclear exactly when to treat subclinical hyperthyroidism in the absence of the aforementioned symptoms because therapy has the potential for toxicity and expense, and in some patients, the problem may resolve on its own. For this reason, treatment is best considered on an individualized basis with careful follow-up. It is important to remember that hyperthyroidism often presents in a nonspecific and/or atypical manner in elders and may lead to a decline in functional capacity before or without more classic signs or symptoms of hyperthyroidism. If identified, treatment of subclinical hyperthyroidism may improve bone mineral density and atrial fibrillation. If treatment is decided upon, ablation therapy with iodine-131 is the preferred method.3
References
1. Parle JH, Sheppard MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet. 2001;358(9285):861-865.
2. Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med. 1994;331(19):1249-1252.
3. Toft AD. Clinical practice. Subclinical hyperthyroidism. N Engl J Med. 2001;345(7):512-516.