Thyroid Disease in Aging

Abstract

Thyroid disease is common in older adults. Increasing numbers of older persons will present to physicians for care in the United States as the U.S. and world populations age. It is expected that by the year 2030 that 19–20% of the U.S. population will be over 65-years old and by 2040 that 25% of the U.S. population will be over 65-years old. It is important for clinicians to be familiar with thyroid disease in this population because of its impact on the patient’s functional and cognitive state. Thyroid disease often presents in older adults with nonspecific presentations such as falls, weakness, or cognitive impairment. Thyroid abnormalities may also be detected with routine testing.

Case Study

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An 85-year-old woman lived in her community for 50 years, continuing to live in her home after her husband passed away. Her family noticed that she was more forgetful, had an unsteady gait, and was falling. Her family took her to her physician who indicated she was just getting older, which was causing her weakness, falls, and confusion. Her family moved her out of her home into an assisted living facility as she continued to worsen cognitively and functionally. Finally she was so weak and confused she could not live in assisted living. Her family brought her to live with them, anticipating nursing home placement. They also brought her for a Geriatric Assessment Clinic evaluation. That afternoon in clinic she was weak, had an unsteady gait, and scored poorly on the Mini Mental State Examination, with a score in the dementia range. Evaluation included checking a thyroid stimulating hormone (TSH) level, which came back quite elevated at 92 uIU/ml, reference range 0.34–5.60. The patient’s diagnosis was then hypothyroidism. Due to her advanced age with cardiac risk, her levothyroxine replacement was started low at 25 mcg orally daily, increasing the dose periodically until a daily dose of 100 mcg was reached. Her TSH was then in normal 0.34 – 5.60 range. The patient returned to Geriatric Assessment Clinic for follow up and her strength was improved, her gait stable, and her Mini Mental State Exam score was in the normal range. The patient had a remarkable improvement in gait and cognition. The patient and her family were very pleased. At that time she did not need nursing home placement.

The lesson: anytime an older person presents with confusion, falls, gait instability, weakness, weight change, or unexpected behavioral change, check thyroid function.

Hypothyroidism

Hypothyroidism can be present in up to 5% of older people, while subclinical hypothyroidism can be present in up to 15% of people 65-years old or older. TSH tends to increase a little with increasing age, with the 97.5^th percentile of TSH distribution of 6.3–7.5 mIU/L in adults 80 and older.¹ With older age, thyroxine (T4) secretion decreases, but this is balanced by decrease in T4 clearance, so T4 levels are unchanged. Triiodothyronine (T3) levels also remain unchanged until a slight decrease can occur with extreme old age.

Hypothyroidism can present with slowly progressive weakness, falls, cognitive impairment, gait disturbance, dry skin. Hypothyroidism among the elderly is often due to Hashimoto’s Disease/autoimmune thyroiditis. Elevated TSH serum values are required to diagnose hypothyroidism in older people. For older adults abnormal laboratory values should be repeated to confirm accuracy of the result. Subclinical hypothyroidism may present with TSH > 4.5 mIU/L and normal free T4, and is defined by lab values despite absence of clinical symptoms. Often, treating the older adult with hypothyroidism with levothyroxine replacement is not started until TSH is 10 or greater. TSH may change during an acute illness, then increase during the recovery from illness. Nonthyroid illness syndrome may cause abnormal thyroid function test results. Thyroid function tests that are difficult to interpret may require endocrinology consultation. Diagnosis of hypothyroidism requires persistent increase of TSH and low T4. A low or normal TSH with low free T4 suggests secondary hypothyroidism associated with hypopituitarism.

Replacement with levothyroxine for older people should start low, 25 mcg/day or 50 mcg/day, especially for those with coronary artery disease. For those with severe cardiac disease one may wish to start replacement at 12.5 mcg/day.¹ More frequent smaller adjustments of levothyroxine may be required in older adults.² Doses may be increased every four to six weeks until TSH normalizes. Levothyroxine combined with triiodothyronine is not recommended for the elderly due to cardiovascular risk. Older adults are at higher risk of myxedema coma or severe hypothyroidism. Most cases of myxedema coma occur in elderly patients. This should be considered when accompanied by hypothermia and bradycardia. Thyroid hormone replacement requirements may be lower in older people due to decreased clearance.

Central hypothyroidism from pituitary or hypothalamic failure is rare.³

We should remember that poor compliance is the most common cause for persistent elevation of TSH despite the patient being prescribed adequate thyroid replacement.⁴

Hyperthyroidism

Hyperthyroidism occurs in up to 2.3% of older people, with 15.25% of cases of thyrotoxicosis being in people 60-years old or older. The majority of hyperthyroidism in the U.S. is due to Graves Disease. Toxic multinodular goiter and autonomously functioning adenomas also occur. Hyperthyroidism in older people can present atypically with weight loss, tachycardia, skin changes, tremor, goiter, ophthalmopathy, atrial fibrillation, heart failure, and weakness. Low TSH combined with elevated T4 or T3 helps make the diagnosis. T3 toxicosis with elevated T3 but normal T4 is seen in some hyperthyroid patients. T4 toxicosis with low TSH, high T4, and normal T3 is also seen.

Graves Disease ophthalmopathy may be present.⁵ Graves Disease and Hashimoto’s Thyroiditis are often associated with antithyroid autoantibodies. Thyrotropin receptor antibodies, usually activating TRAb, are associated with Graves Disease. These antibodies are both highly sensitive and highly specific. Anti thyroid peroxidase antibodies, (anti TPO antibodies), are associated with Hashimoto’s Thyroiditis. TPO antibodies are present in the vast majority of patients with Hashimoto’s and are highly sensitive.

Amiodarone, a cardiac antiarrhythmic medication, contains a significant amount of iodine, and is stored in the body in fat, liver, lung, and myocardium, with a half life of about 50 days. An estimated 2% of patients taking amiodarone develop amiodarone-associated thyrotoxicosis.⁶

Apathetic thyrotoxicosis is almost exclusively seen in older people, presenting with depression, lethargy, inactivity, anorexia, weight loss, constipation, and weakness.

Up to 30% of older people with atrial fibrillation may have hyperthyroidism. Subclinical hyperthyroidism presents with a low TSH with normal T4 and T3, with or without signs or symptoms of typical hyperthyroidism. Prevalence increases with increasing age, up to 10% in the very old. Subclinical hyperthyroidism is associated with atrial fibrillation and accelerated bone mineral loss with increased fracture risk.

Treatment of hyperthyroidism in older people and endocrine consultation is recommended due to increased risk of atrial fibrillation, congestive heart failure, osteoporosis, and increased mortality risk. Radioactive iodine (RAI) supervised by an endocrinologist is the treatment for most older people with Graves Disease or toxic nodular thyroid disease. Medications methimazole or propylthiouracil (PTU) are also used. Beta blockers can help with tachycardia, tremor, and anxiety. Some older patient’s disabilities preventing safe RAI hospital treatment may need methimazole or PTU long term. Most RAI treatment for hyperthyroidism is done as an outpatient. Surgery is another option if RAI or long-term anti-thyroid drugs are not feasible. After RAI, patients should be checked with TSH for development of hypothyroidism or persistent/recurrent hyperthyroidism.

Nodular Thyroid Disease

Thyroid nodules are common in older adults in that 90% of women 70-years old or older and 60% of men 80-years old and older have thyroid nodules. Most are detected on imaging ordered for other reasons. Nonpalpable nodules are as likely to be cancerous as palpable nodules. Thyroid cancer is found in 4–6.5% of nodules, more in people 60-years old and older, and more in men. In older adults papillary and follicular carcinomas are more aggressive. Thyroid lymphomas are more common, and anaplastic thyroid carcinomas are much more common among older people. Constant stimulation of the thyroid to release thyroid hormones may cause the gland to enlarge to become a goiter.⁷ The presence of multinodular goiter increases with increasing age. Those with multinodular goiter can develop iodine induced thyrotoxicosis after radiocontrast or with amiodarone.

The 2017 USPSTF guidelines recommend against screening generally for thyroid cancer. Screening for thyroid cancer is indicated for history of head and neck irradiation, Multiple Endocrine Neoplasia Type 2, family history of thyroid cancer, or high risk characteristics on imaging.

Indications for diagnostic thyroid ultrasound include cervical lymphadenopathy, thyroid nodules or multinodular goiter, selection of thyroid nodule for biopsy, guidance for fine needle aspiration (FNA), evaluation of nodule characteristics, nodules discovered on other imaging. Ultrasound is the most sensitive test for thyroid nodules, often rated by Thyroid Imaging Reporting and Data System (TIRAD), a five-point scoring system for thyroid nodules on ultrasound, developed by the American College of Radiology.⁸ For older adults with nodules or goiter, ultrasound and thyroid function testing should be done. Autonomously functioning thyroid nodules are rarely malignant; cancer workup generally does not need to be done for a thyroid nodule with RAI uptake on a radionuclide thyroid scan, with a normal TSH. Generally, FNA is required to exclude malignancy in a nodule. Usually only thyroid nodules greater than 1 cm need evaluation for malignancy. After RAI is administered for high-risk thyroid cancers, or surgery is performed, levothyroxine suppression may be done to reduce recurrence, but osteoporosis and cardiac effects are possible. Beta blockers and bone mineral strengthening agents may be helpful. Please review the American Thyroid Association clinical practice guidelines for management and monitoring of thyroid malignancies.⁹