BMH Medical Journal

BMH Med. J. 2020; 7(Suppl): Early Online. Geriatrics & Gerontology Initiative: International Workshop on Care of the Elderly

Keywords: Thyroid, hypothyroidism, hyperthyroidism, subclinical

Introduction

Thyroid disorders are common in elderly [1] and it often goes undiagnosed because of atypical presentations much different from those in the younger population. Even though manifestations of hyperthyroidism and hypothyroidism are very different in younger patients, there are similarities between the two conditions in the elderly. Interpretation of thyroid function tests in older adults is difficult due to age-dependent physiological changes in thyroid function and coexistent chronic illness [2]. Untreated thyroid dysfunction is associated with significant morbidity in the elderly.

Structure and function of thyroid in elderly

The main change occurring in thyroid gland as age advances is reduction in size due to progressive fibrosis and atrophy, and so the thyroid gland may not be palpable in the elderly. Thyroid gland may become more nodular due to neoplastic changes in old age. Increase in auto antibodies is also suggested as a reason for the changes in the gland in the elderly.

The hypothalamo-pituitary thyroid (HPT) axis which regulates thyroid hormone synthesis remains normal in elderly. But there are age related changes in the functions of thyroid hormones. Iodine status of the person is also important in the synthesis of hormones. In the elderly, the iodine status will be low due to decreased dietary intake as well as decreased absorption. This will lead on to decreased secretion of T4. The activity of 5’deiodinase will be reduced as age advances, which in turn decreases the metabolic clearance of T4 thereby compensating for the decreased secretion. Reduction in T3 level is not as pronounced as for T4. The TSH level also will be declined as age advances. With regard to free T3 levels, most studies have demonstrated an age-dependent decline; while free T4 levels remain relatively unchanged and reverse T3 (rT3) levels increase with increasing age. Thyroid binding globulin level decreases with age and, therefore, measurement of free thyroid hormones is more useful in the elderly.

Common disorders of thyroid

Hypothyroidism

Hypothyroidism is the condition which steadily increases with age, and the most common thyroid disorder in patients over 60 years of age. This is predominantly due to a rising incidence of autoimmune thyroiditis (Hashimoto’s). Presence of anti TPO (microsomal) and anti-thyroglobulin antibodies indicates thyroiditis. In patients with thyroiditis there will be an initial stage of hyperthyroidism followed by hypothyroidism. Other causes include drugs like amiodarone, lithium; post-surgical; post radiation ablation etc. Radiation therapy for head and neck malignancy also may contribute to hypothyroidism in elderly.

The common symptoms include fatigue, weakness, constipation, dry skin. Most of these symptoms may usually be attributed to other common problems in older persons, medication side effects or aging itself. Symptoms, such as depression, slowness of mentation and dementia are also seen in older adults with hypothyroidism.

Depression and dementia due to hypothyroidism is reversible with treatment. Gain in weight and cold intolerance may not be present in elderly individuals.

Neurological problems: Cognitive impairment Hypothyroidism in older adults has been associated with neuropsychiatric symptoms like impairment of memory, attention and concentration, language, executive function and perceptual and visuospatial function. Severe hypothyroidism may mimic depression and dementia. Cerebellar dysfunction may also be seen.

Cardiovascular effects: The cardiovascular consequences of hypothyroidism in older adults are thought to be due to a reduction in both stroke volume and heart rate. Other contributing factors include increased risk of atherosclerosis, increased arterial stiffness, endothelial dysfunction and altered coagulation parameters. It is important look for evidence of cardiac ischemia in elderly people with hypothyroidism. When thyroid hormone is replaced, there is chance of increase in metabolic rate leading onto aggravation of ischemic heart disease.

Myxedema Coma: It almost always occurs in the elderly and is usually precipitated by factors that impair respiration, such as drugs (especially sedatives, anesthetics, and antidepressants), pneumonia, congestive heart failure, myocardial infarction, gastrointestinal bleeding, or cerebrovascular diseases. Patients may present with a rapid development of stupor, seizures, or coma along with respiratory depression. Hallmark signs of myxedema coma include localized neurological signs, hypothermia, bradycardia, hyponatremia and hypoglycemia. It is a severe and life-threatening clinical state in older adults with a mortality rate as high as 40%.

Secondary hypothyroidism: It is rare in elderly. This is characterized by decreased free thyroid hormones and an inappropriately decreased TSH levels. If present, this will be associated with deficiency of cortisol and gonodotropin. If cortisol deficiency is suspected cortisol replacement should be done before replacement of thyroid hormones in order to prevent an acute adrenal crisis.

Subclinical hypothyroidism: The T4 and free T3 will be normal with elevated levels of TSH. This is commonly seen in those above 60 years especially in females. Thyroid antibodies also will be seen in sub clinical hypothyroidism. The prevalence of subclinical hypothyroidism increases with age, and ranges from 3 to 16% among individuals aged 60 years and above.

Management: Clues to the possibility of hypothyroidism include a positive family history of thyroid disease, past treatment for hyperthyroidism, or a history of extensive surgery and/or radiotherapy to the neck. A low level of free T4 and T3 along with raised TSH is diagnostic of hypothyroidism. Presence of antibodies may suggest thyroiditis.

The requirement for thyroid replacement in elderly will be less than in young patients. This may be related to factors like declining metabolic clearance, slow progression of underlying thyroid failure, declining body mass, and interactions with other medications. Since increase levels of hormone could precipitate cardiac arrhythmia, angina or cardiac failure, smaller dose should be started. In the elderly, especially patients with known coronary artery disease, the starting dose of levothyroxine is 12.5 μg/d and in those without cardiac problems is 25 μg/d. This dose is increased by 12.5 to 25 μg/d every four weeks until TSH is normalized. In some patients, it may be impossible to achieve full replacement despite optimal antianginal treatment as thyroid hormone increases myocardial oxygen demand, which may induce cardiac arrhythmias, angina pectoris, or myocardial infarction in older patients.

Management of subclinical hypothyroidism in older adults is controversial and guidelines have been published both for and against routine treatment in older adults. Various studies have shown that treatment with levothyroxine in older persons with subclinical hypothyroidism provided no symptomatic benefits. There are a number of studies currently being undertaken to try and pinpoint what TSH levels for older people with an under-active thyroid should be. Current recommendation is levothyroxine replacement therapy in patients with a TSH >10 mIU/L on repeated measurements, definite symptoms or signs associated with thyroid failure, family history of thyroid disease or severe hyperlipidemia not previously diagnosed.

Hyperthyroidism

The prevalence of hyperthyroidism in older adults is estimated to be 1 – 3% in subjects above the age of 60-65 years. The most common etiology is Grave’s disease but nodular toxicosis increases since prevalence of multinodular goiter is on the increase in elderly. Iodine containing drugs like amiodarone, radio contrast agents etc favors thyrotoxicosis. The cardiovascular symptoms and signs predominate in elderly [3] and there is a higher risk of atrial fibrillation [4] There are atypical manifestations as well. Weight loss, lethargy and depression are predominant features sometimes and is termed as “apathetic hyperthyroidism”. The weight loss and loss of appetite may lead onto a suspicion of malignancy.

More common than overt hyperthyroidism in older adults is subclinical hyperthyroidism which is estimated to have a prevalence of 3–8% and is more common in women than men [5]. In a study of the natural history of subclinical hyperthyroidism in female patient ≥ 60 years of age showed that progression to overt hyperthyroidism is infrequent at 1% per year. Ophtalmopathy is not very common in elderly, but when present this will be more severe than that in young people.

In case of nodular goiters, single or multinodular, the toxic nodule secretes more of T3 and will have features of hyperthyroidism. This is termed as “T3 toxicosis”. Increased T3 secretion suppresses TSH and T4 secretion and this situation is mainly seen in elderly.

Atrial fibrillation: Age is associated with an increased risk of developing atrial fibrillation. Atrial fibrillation is estimated to be present in up to 20–35% of older patients with hyperthyroidism. Long-standing low serum TSH concentration in older patients is associated with a 3-fold increased risk of developing atrial fibrillation. However, the degeneration of the sinus node and fibrotic changes in the cardiac conduction system make palpitations less likely. In addition, frequent use of beta-blockers or amiodarone in these patients can mask the arrhythmia.

Cardiovascular mortality: Several studies have found that decreased levels of serum TSH are associated with increased cardiovascular mortality in older adults as they will have widened pulse pressure, exercise intolerance, increased risk for atrial fibrillation and left ventricular hypertrophy. The high cardiac output can lead to worsening of angina or heart failure in the elderly or those with preexisting heart disease.

Osteoporosis: Thyroid hormone acts on osteoblasts and osteoclasts to increase bone turnover, leading to net bone loss. Low bone mineral density and osteoporotic fractures mainly in hip and vertebrae especially in elder women is reported to be common in hyperthyroididsm.

Management: Serum TSH is the first investigation to be done for diagnosis of hyperthyroidism. However, elderly patients who are acutely ill and hospitalized may demonstrate a depressed TSH without actually being hyperthyroid. When the clinical presentation of thyrotoxicosis is not diagnostic of Graves’ disease, a radioactive iodine uptake should be performed to help determine etiology. If thyroid nodule is present, thyroid scan also should be done.

Symptomatic treatment for hyperthyroidism in older adults consists of beta blockers (propranalol 20mg twice daily) which decreases the heart rate and systolic blood pressure. Decision of use of anticoagulation in presence of atrial fibrillation should be individualized taking into consideration other factors also.

Treatment modalities that may be used for the hyperthyroidism include radioactive iodine ablation therapy, antithyroid medications or thyroidectomy.

Radioactive iodine ablation is often used in older adults because of its efficacy, safety and cost-effectiveness. Reversal of hyperthyroidism takes time and so the cardiac problems may need to be managed aggressively until the thyrotoxic state is reversed. 80% of these patients may subsequently develop hypothyroidism and require thyroid hormone replacement therapy. Antecedent treatment with an antithyroid drug and a beta blocker should be considered for all elderly patients or for those with cardiac problems before radioiodine ablation.

Antithyroid drug of choice is methimazole. However, elderly patients may be at greater risk of recurrence of hyperthyroidism after drug therapy and for adverse effects of drugs. The major and serious side effect of the drug is agranulocytosis. The elderly may have a number of co-morbidities like cardiac diseases, hypertension, diabetes mellitus or stroke and the change in thyroid function could also make changes in other systems and they should also be closely monitored.

Surgical management poses an increased risk of morbidity due to comorbidities and so surgical treatment is less preferred. They are reserved for large goiters with obstructive symptoms, or known or suspected malignancy.

A low TSH with a normal free T3 and free T4, suggests the possibility of thyroid autonomy or undiagnosed Graves’ disease particularly in older patients, and is termed subclinical thyrotoxicosis. An isolated low TSH is usually common in older patients.

The benefit of treatment of subclinical thyrotoxicosis, is controversial, but is recommended in the elderly to reduce the risk of atrial fibrillation and bone loss. But most clinicians would like to follow up these patients without treatment, unless they are symptomatic and periodic clinical and biochemical assessment in these patients. Guidelines recommend that patients be treated if TSH is 0.1–0.5 mIU/L and not to treat if TSH is <0.1 mIU/L.

Thyroid Nodules

As age advances, prevalence of thyroid nodules increases reaching 50% by the age of 65 years Thyroid nodules may be benign adenomas, cysts, cancer or inflammation.

Management: The approach to the management of a solitary thyroid nodule in an older adult is the same as that in a younger patient.

Thyroid Malignancy

The prevalence of clinically apparent thyroid cancer in adults aged 50–70 years old is estimated to be 0.1%. Well differentiated papillary thyroid cancer is the most common thyroid cancer in older adults and it presents similar to younger patients. These are slow-growing tumors and majority of patients are asymptomatic or may present with a painless neck mass. Incidence of papillary thyroid cancer is increasing disproportionally in patients older than 45 years.

Follicular thyroid cancer is more common in areas of iodine deficiency with the peak incidence in the sixth decade of life. It commonly presents with an asymptomatic neck mass.

Sporadic forms of medullary thyroid cancer are more common in older patients as compared to familial forms. Many patients present with a palpable neck mass. There may be local or systemic symptoms secondary to metastases. Symptoms of hormone hypersecretion include diarrhea, flushing and bronchospasm.

Anaplastic thyroid cancer is aggressive and has a peak incidence in the seventh decade of life. It often arises within a more differentiated thyroid cancer, and usually presents as a rapidly growing neck mass with metastases at time of diagnosis.

In thyroid cancer, the mortality rates increase after 45 years of age. And a steady decline in survival rates has been reported with increasing age, regardless of the degree of differentiation of the thyroid cancer.

Lymph node metastases and extension outside the gland significantly worsens the prognosis in older adults. Distant metastases are also a worst prognostic sign in older patients with thyroid cancer. This may be related to thyroid cancer being less radioactive iodine-avid in older patients compared to younger patients. Thyroid cancer recurrence rates have also been shown to be influenced by age.

Management: The modalities used for the management of thyroid cancer in older adults are essentially the same as those used in younger patients.

Frequently, the surgical approach for thyroid cancer >1cm is near-total or total thyroidectomy. Thyroid lobectomy alone may be sufficient for tumors <1cm. Central neck dissection should accompany total thyroidectomy in patients with clinically involved central or lateral neck lymph nodes. Age by itself is not a contra-indication to thyroidectomy.

Post-operative radioiodine ablation (RIA) of thyroid remnants is indicated for all patients with known distant metastases, extra thyroidal extension of the tumor regardless of tumor size. Dosimetry-guided RIA therapy may be preferable to the fixed-dose RAI treatment. The TSH-suppressive dose of thyroxine used in younger patients with thyroid cancer should be reduced in elder adults as thyroxine degradation is reduced with age.

Summary

Thyroid gland dysfunction is prevalent in older adults. However, clinical signs and symptoms of thyroid dysfunction may be subtle or absent, making diagnosis more difficult. As thyroid disorders are often amenable to effective treatments that can improve quality of life, a high index of clinical suspicion is warranted. Factors contributing to misinterpretation of thyroid function tests in older adults include age-dependent physiological changes, co-morbidities and drugs used for other conditions. Hyperthyroidism in older adults is usually treated with radioactive iodine ablation and antithyroid medications. Surgery is less preferred. The time to initiate levothyroxine replacement therapy in older adults with hypothyroidism is not determined correctly. However, after assessing the cardiovascular tolerance of a starting dose, the dose should be gradually increased.

Neoplastic disorders of thyroid and hypothyroidism are more common in the elderly, while hyperthyroidism is less common. Early control of hyperthyroidism is needed due to the adverse cardiac outcomes, whereas slow correction of hypothyroidism is desirable in elderly patients. Older patients with thyroid disorders should be offered gradual and careful treatment, and, as always, require lifelong follow-up.

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Thyroid Disorders In The Elderly