Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Common thyroid disorders in the elderly CPT Thomas Francis MC, USA & COL Leonard Wartofsky MC, USA To cite this article: CPT Thomas Francis MC, USA & COL Leonard Wartofsky MC, USA (1992) Common thyroid disorders in the elderly, Postgraduate Medicine, 92:3, 225-236, DOI: 10.1080/00325481.1992.11701452 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701452
Published online: 17 May 2016.
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-®CME credit article
Common thyroid disorders in the elderly
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CPT Thomas Francis, MC, USA
COL Leonard Wartofsky, MC, USA
Preview Diagnosing a thyroid disorder in an elderly patient can be a challenge: Onset is insidious, symptoms and signs are often masked by those of other diseases, and commonly taken medications confound the results of thyroid function tests. Treatment may be complicated by underlying heart disease or osteoporosis. In this article, the authors undertake the task of demystifying the perplexities of accurate diagnosis and rational management of thyroid disease in the elderly.
Although primary care physicians are aware that thyroid disease and abnormalities on thyroid function tests are common in the elderly, the presence of hyperthyroidism or hypothyroidism may be overlooked because "classic" symptoms and signs typically seen in younger patients are absent. Furthermore, common geriatric illnesses (eg, Parkinson's and Alzheimer's disease, depression, psychosis, renal failure) may mask symptoms that might otherwise spur evaluation of the thyroid gland. Because the onset of thyroid disease is often insidious, it is possible that neither patient nor clinician will recognize a "change" other than that attributable to normal aging. Even when thyroid function tests are obtained, results can be misleading because of the effects of malnutrition, medications, and protein-binding abnormalities that accompany
various acute and chronic diseases. Although newer free thyroxine (T4), free triiodothyronine (T3), and supersensitive thyrotropin (thyroid-stimulating hormone [TSH]) assays facilitate specific diagnosis in patients with systemic illness, interpretation of thyroid function tests may still be difficult because of thyroidbinding protein perturbations and otherwise altered thyroid hormone economy (euthyroid sick syndrome). Drugs such as amiodarone hydrochloride (Cordarone) and iodinated radiographic contrast agents, which are often used in elderly patients, provide additional challenge to the accurate clinical interpretation of thyroid function tests. Also, the decision to treat goiter, thyroid nodules, or carcinoma with suppressive doses of synthetic T 4 is of especial concern in elderly patients with underlying cardiac disease or osteoporosis,
both of which could be worsened by T 4 therapy.
Thyroid function tests By secreting TSH, the pituitary gland maintains tight homeostatic feedback control of thyroid T 4 synthesis and release. Thereleased T 4 is immediately bound to binding proteins in the serum, and less than 0.01% remains free. However, T 4 is bioinactive in relation to T 3 and is converted to T 3 by an activating pathway (mediated by 5'-monodeiodinase), predominantly in peripheral tissues (liver, kidney, muscle). Reduced activity of this deiodinase in multiple clinical situations often causes perturbations in both total and free T 4 and T 3 levels. Eighty percent of circulating T 3 is derived from T 4 in peripheral tissues, and only 20% is directly secreted from the thyroid. T 3 is also tightly bound by binding proteins, and binding alterations that affect total T 4 concentrations also affect serum T 3 levels. Consequently, direct measurement of free (rather than total) T 4 or T 3 represents a more precise estimate of thyroid status. With the recent availability of supersensitive TSH assays (and assuming normal pituitary function), clinicians can more readily determine the thyroid status of a patient: A sup-
continued
VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE • THYROID DI80RDIIRS
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Low T 3 concentrations in the elderty may be due to the increased prevalence of disease processes and use of certain medications.
Table 1. Variations in results of thyroid function tests in the elderly
Unchanged RT3 U
rT3 1evel T4 concentration TBG level Increased Serum iodide levels TSH levels Thyroid antibody levels TRH stimulation of TSH (women only) Decreased Iodine trapping by thyrocytes T3 concentration T4-T3 production TRH stimulation of TSH (men only) Diminished TSH response to dropping T4 RAIU
RAIU, radioactive iodine uptake; T3 , triiodothyronine; T4, thyroxine; RT3U, resin T3 uptake (thyroid hormone-binding ratio); rT3 , reverse T3 ; TBG, thyroxinebinding globulin; TRH, thyrotropinreleasing hormone; TSH, thyrotropin (thyroid-stimulating hormone).
pressed TSH level signifies hyperthyroidism, whereas an elevated level signifies hypothyroidism. There are only a few instances in which a normal TSH concentration could be misleading. Glu-
226
cocorticoids and dopamine hydrochloride (Dopastat, lntropin), which are often used in intensive care units, suppress TSH production and give artificially low values even when a patient is actually hypothyroid. When a patient has a history of disease, previous surgery, or irradiation of the pituitary, the validity of using TSH levels to document thyroid status becomes questionable. Although TSH levels are the most sensitive indicators of hypothyroidism or hyperthyroidism, total and/ or free T 4 and T 3 concentrations are often measured to help gauge the magnitude of hyperthyroid or hypothyroid function; knowledge of the free T 4 level is also useful to follow the clinical course of (I) patients taking antithyroid drugs, (2) those who have had ablation of the thyroid gland with iodine 131 (1 3 '1) treatment, and (3) those receiving replacement or suppressive T 4 therapy. Because many clinicians still rely on these and other parameters to assess thyroid function, this article reviews their use in elderly populations.
Tests in the elderly Typical alterations of thyroid function seen in the elderly (table 1) have been well described
and reviewed. '·3 An age-related decrease in iodine trapping by thyrocytes may be expressed as a slight decrease in 24-hour radioactive iodine uptake (RAIU). TSH levels tend to be higher in the elderly, especially in women, and one study4 correlated this rise with increasing prevalence of thyroid antibodies, implying that TSH levels correlate with autoimmune disease rather than age per se. Stimulation testing with synthetic thyrotropin-releasing hormone (TRH) (protirelin [Thypinone, Relefact TRH]) may disclose gender differences, with men showing a slightly decreased and women a slightly enhanced response, again possibly related to differences in autoimmune disease. Depending on the population studied, T 3 concentrations tend to be lower in the elderly. It has been theorized that this is due to the increased prevalence of disease processes and use of medications that inhibit 5'-monodeiodinase, which, as mentioned, converts T 4 to T 3• Such conditions include malnutrition, diabetes, hepatic or renal disease, and a wide variety of acute and chronic illnesses associated with the euthyroid sick syndrome. 5 Inhibition of5'-monodeiodinase also results in reduced dear-
THYROID DtSO-.RS • VOL 92/NO 3/SEPTEMBER 1. 1992/POSTGRAOUATE MEDICINE
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Studies show that hyperthyroidism is about seven times more prevalent in the elderly than in younger age-groups.
Table 2. Results of thyroid function tests in the elderly compared with those in patients with euthyroid sick syndrome
Patient group
Ta
rT3
Elderly
.!.
H
Low-T4 ETS
.!.
High-T4 ETS
.!.
TSH
TRH stimulation
Free T4
RT3 U
T4
Total
Free T4 index
H
H
H
H
H
H
i
HJ.
HJ.
.!.
.!.
i
.!.
i
H
H
i
i
Hi
i
ETS, euthyroid sick syndrome; T3 , triiodothyronine; T4 , thyroxine; RT3 U, resin T3 uptake; rT3 , reverse T3 ; TRH, thyrotropin-releasing hormone; TSH, thyrotropin (thyroid-stimulating hormone).
ance of reverse T 3 (rT3); hence, serum rT 3 levels are usually elevated in patients with euthyroid sick syndrome but should be normal in a healthy elderly population. Distinguishing laboratory results from those of the euthyroid sick syndrome is especially relevant here in view of the greater frequency of illnesses in the elderly. Misinterpretation of laboratory data to suggest either hypothyroidism or hyperthyroidism could lead to inappropriate management. Characteristic findings in cases of euthyroid sick syndrome include the following: a low T 3 level, a high rT3 level, a low to normal T 4 level, and an increased resin T 3 uptake (RT3U). The RT3U is often elevated as a con-
sequence of decreased T 4 protein binding due to circulating inhibitors ofT4 binding, with an associated high-normal free T 4 index and free T 4 level. This should not be mistaken for hyperthyroidism, because the TSH level is usually measurable. TRH stimulation may be blunted and, in more seriously ill patients with low total and free T 4 concentrations, TSH production may be decreased. Although rare as a cause for a low TSH level, secondary hypothyroidism should be considered. A normal result on the TRH stimulation test excludes this, as does measurement of the rT3 level, which is high in cases of euthyroid sick syndrome but low in any hypothyroid state. Summarized in table 2 are
VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE • T1IYROID
some of the key similarities and differences seen between the thyroid function tests of the elderly and those of patients with two common subtypes of the euthyroid sick syndrome.
Hyperthyroidism According to various studies, the prevalence of hyperthyroidism in the elderly is between 0.5% and 2.3%. 3 This is roughly seven times higher than in younger age-groups. 6 SYMP'IDMS AND SIGNs-As
noted, manifestations of hyperthyroidism that are common in younger patients are often absent in the elderly (table 3). Decreased energy, fatigue, and heat intolerance are reported only half as often. Anorexia and weight loss
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Most geriatric hyperthyroidism is caused by either Graves' disease or autonomous toxic nodular disease of the thyroid gland.
Table 3. Signs and symptoms of hyperthyroidism in the elderly
Less common Nervousness and irritability Heat intolerance Muscle weakness Polyphagia and hyperdefecation Tachycardia Goiter Ophthalmopathy More common Tremor Malaise Muscle wasting Anorexia Atrial fibrillation and/or atrioventricular block Angina and/or congestive heart failure
are common, whereas polyphagia and hyperdefecation are rare. Nervous complaints (eg, irritability) occur less often, and muscle weakness is often absent. Toxic multinodular goiter causes about 50% of hyperthyroidism in the elderly but does not result in autoimmune ophthalmopathy, which explains the decreased incidence of eye symptoms. Lahey coined the term "apathetic hyperthyroidism" in 1931, when he observed that elderly patients were presenting with nothing more than lethargy and that up
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to 30% lacked physical findings of goiter and tachycardia. 7 However, symptoms of cardiovascular disturbance, including atrial fibrillation, angina, and congestive heart failure, frequently herald the existence of underlying hyperthyroidism. CAUSES-Most geriatric hyperthyroidism is caused by either Graves' disease or autonomous toxic nodular disease of the thyroid gland. Autonomous nodular disease can present as either a solitary autonomously functioning thyroid nodule (AFTN) or as multinodular goiter. In either case, the autonomous thyroid tissue may or may not be producing quantities of thyroid hormone sufficient to cause thyrotoxicosis. When the tissue is hyperfunctioning, the nodule is designated as "toxic" and the goiter is designated as "toxic multinodular goiter" (Plummer's disease). Generally, AFTNs and Plummer's disease progress slowly to thyrotoxicosis and patients require therapy only if they have nodules that are producing hyperthyroidism or are growing large enough to cause obstructive symptoms. AFTNs usually do not cause hyperthyroidism until they are larger than 3 em in diameter, and they may present as "T3 toxicosis" (preferential secre-
tion ofT3 with normal serum T 4 levels). THERAPY-After 6 to 18 months of antithyroid drug therapy, a lasting remission is seen in only 20% to 50% of patients with Graves' disease. Thus, a more satisfactory option in elderly patients with hyperthyroidism is definitive ablation of the thyroid gland with 131 1. Our practice is to ablate the gland completely to reduce the risk of relapse and to facilitate T 4 replacement without concern for varying residual endogenous hormone production. A beta blocker such as propranolol hydrochloride (Inderal) should be started in a symptomatic patient (if there are no contraindications at the time of diagnosis) and continued until the patient is euthyroid. Some clinicians prefer to administer 131 1 without first rendering patients euthyroid with antithyroid drugs. This approach avoids toxic effects of the drugs and requires less time to achieve a euthyroid state and less monitoring with blood tests. Nevertheless, transient worsening of hyperthyroidism after using 131 1 and thyroid storm are unpredictable events, and it is our practice to use antithyroid drugs routinely beforehand, particularly in the elderly, who are more susceptible
THYROID DISOIIDmtl • VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRAOUATE MEDICINE
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Iodine-induced hyperthyroidism is rare in the elderly but may be increasing in incidence.
to the latter complication. 8 The major adverse side effects9 of the thioamide derivatives (propylthiouracil and methimazole [Tapazole]) occur in 1% to 5% of patients and include fever, rash, urticaria, and arthralgia. Leukopenia is common, affecting 12% of adults, but is usually benign. Agranulocytosis occurs in 0.5% of patients, and all patients should be advised to have a complete blood cell count if they have symptoms of fever or sore throat. Clinically, it is imponant to recognize that the rates of drug clearance and endogenous protein metabolism decrease as hypetthyroidism abates, and the reduced metabolic rate may require adjustments in medication dosages. In patients with atrial fibrillation, it is imponant to monitor and reduce dosages for digoxin (Lanoxicaps, Lanoxin) and warfarin sodium (Coumadin, Panwarfin, Sofarin) because their respective drug clearance and clotting-factor catabolism decline as hypenhyroidism is controlled. Atrial fibrillation in the context of hypenhyroidism carries a 10% risk of causing embolic cerebrovascular accident, 10 and, unless contraindicated, anticoagulants should be given to all patients. Iodine-induced
CPT Thomas Francis, MC, USA Dr Francis is instructor in medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and is assigned to the endocrinology division, Walter Reed Army Medical Center, Washington, DC.
hypetthyroidism in the elderly is rare but is probably increasing in incidence with the more widespread use of amiodarone and of radiographic studies with iodine-rich contrast agents. The patient's clinical history and results of an RAIU test (uptake is immeasurable in persons with normal thyroid function exposed to iodine but inappropriately normal in persons with hyperthyroidism) help in the detection of iodine-induced disease.
VOL 92/NO 3/SEPTEMBER 1. 1992/POSTGRADUATE MEDICINE • THYROID DISORDERS
COL Leonard Wartofsky, MC, USA Dr Wartofsky is professor of medicine and physiology and chief, department of medicine, Walter Reed Army Medical Center.
Hypothyroidism The prevalence of hypothyroidism varies widely, but one recent US studi 1 revealed that the results of supersensitive TSH assays were above 6 1-LU/mL in 7_8% of outpatients 55 years of age or older. In another study, 12 12% of patients routinely screened on hospital admission had elevated TSH levels. SYMPTOMS AND SIGNs--Awareness of the insidious nature of hypothyroidism, the subtle sympcontinued
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Hypothyroidism in the elderly has an insidious nature and, when untreated, may progress to profound myxedema, coma, and even death.
Table 4. Results of thyroid function tests in patients with euthyroid sick syndrome and with hypothyroidism
Patient group
TSH
FT4I or freeT4
TRH stimulation
rT3
Primary hypothyroidism
i
.j,
i
.j,
Subclinical hypothyroidism
~r
~
i
.j,
Secondary or tertiary hypothyroidism
~.j,
.j,
.j,
.j,
Low-T4 ETS
~.j,
.j,
~.j,
i
ETS, euthyroid sick syndrome; T3 , triiodothyronine; T4 , thyroxine; FT41, free T4 index; rT3 , reverse T3 ; TRH, thyrotropin-releasing hormone; TSH, thyrotropin (thyroidstimulating hormone).
toms and signs of which can be mistaken for normal aging, and of the potential for progression to profound myxedema, coma, and even death when untreated should foster aggressive screening with TSH to exclude this disorder in populations at higher risk. Less than one third of patients show typical symptoms, and two thirds present with nothing more than debilitation and apathy. 13 An excellent recent review 14 described in detail the presentations of hypothyroidism in the elderly. Neuropsychiatric symptoms may include confusion, memory loss, disorientation, apathy, depression, paranoia, and
frank delirium (myxedema madness). Other complaints include dyspnea, dry skin, constipation, anorexia with weight loss, ataxia, and musculoskeletal disorders. Frequent falls, peripheral neuropathy, carpal runnel syndrome, and hearing loss may occur. OBJECI1VE FINDIN~bjec
tive physical and laboratory findings include diastolic hypertension, bradycardia, cardiomegaly, congestive heart failure with reversible cardiomyopathy, hyperlipidemia, hyponatremia, anemia, and elevated creatine kinase and aspartate aminotransferase (previously SCOT) levels. The definitive laboratory parameters for diagnosis of primary hypo-
thyroidism (table 4) include an elevated TSH level with a low free T 4 concentration or free T 4 index. A low T 3 level alone is insensitive for diagnosis; in addition, there may be a normal physiologic decline either with age or as part of the euthyroid sick syndrome . A mildly elevated or normal TSH level and enhanced TRH response with a normal free T 4 index in an asymptomatic patient defines "subclinical" or "chemical" hypothyroidism. Authorities disagree as to whether this is really hypothyroidism. Some believe that increased basal TSH secretion and TRH responsiveness completely compensate for compromised thyroid output. However, on careful questioning, many patients are found to have subtle symptoms and objectively impaired cognitive functions, as well as demonstrably decreased cardiac contractility and higher low-density lipoprotein cholesterol levels, all of which can be treated by T 4 supplementation. 15 Secondary (pituitary) and tertiary (hypothalamic) hypothyroidism with an "inappropriately" low TSH level for the accompanying low free T 4 level or T 4 index should be differentiated from subclinical primary hypothyroidism. This is so be-
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THYROID DIIIORDmiS • VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRAOUATE MEDICINE
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The most frequent cause of primary hypothyroidism in all age-groups is Hashimoto's disease.
cause of the theoretical risk of precipitating adrenal insufficiency by treating combined hypothyroidism and hypoadrenalism with only T 4 and no glucocorticoid. The TRH stimulation test reveals an exaggerated response in subclinical hypothyroidism, a blunted to absent response in secondary hypothyroidism, and a blunted and delayed response in tertiary hypothyroidism. CAUSFS--The most frequent cause of primary hypothyroidism across all age-groups is autoimmune destruction (Hashimoto's disease). The next most frequent cause is surgical or medical ablation of the thyroid gland for preexisting thyroid disease. Hypothyroidism may also present in the elderly after the use of iodinecontaining medications, amiodarone, and lithium, which variably block intrathyroidal T 4 synthesis and release. lHERAPY-Regardless of cause, replacement therapy must be carefully guided by considering (I) coexisting disease processes, (2) medications being used, and (3) magnitude of the initial hypothyroidism. Unmasking or exacerbating underlying coronary artery disease or dysrhythmias is generally the biggest concern. A guiding principle is to "start low and go slow."
In the context of known or suspected heart disease, we recommend starting with 12.5 to 25 jJ.g of synthetic T 4 (levothyroxine sodium [Levothroid, Levoxine, Synthroid]) a day and adjusting the dose upward in the same increment every 4 to 6 weeks. Because the half-life ofT4 is 1 week, it can take at least 4 weeks for serum levels to equilibrate; hence, tests should not be repeated any more often than every 5 to 6 weeks unless there is an absorption or a compliance problem. In a patient with a history of prolonged hypothyroidism, pituitary thyrotropes are hypertrophied, and as a result, a longer period may be needed for TSH to fall to a level that reflects equilibrium ofT4 and T 3 levels. The final dosage is empirically determined when the TSH level is restored to normal range without hyperthyroid or hypothyroid symptoms or aggravation of other medical problems, such as angina pectoris. The target replacement dose for elderly patients is lower than that for younger patients, approximating 0.7 to 0.8 jJ.g/lb a day, based on lean body mass. In the case of mild initial hypothyroidism without strongly suspected heart disease, T 4 therapy can be started in a total daily dose of
VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE • THYROID
D~RS
50 to 75 jJ.g and increased every 4 to 6 weeks, with serial monitoring ofTSH as just described. Subclinical hypothyroidism requires a more careful risk-benefit analysis, but we recommend gentle supplementation to restore TSH levels to the mid-normal range if there are no frank contraindications. At the very least, patients should be carefully followed by serial TSH monitoring every 4 to 6 months, because progression to overt hypothyroidism is common. The concern for worsening of osteoporosis is real, 16 yet no study has documented an increased fracture risk when suppressive or replacement-level doses are used, and there can be clear clinical improvement in lipid and cardiovascular parameters with treatment of subclinical hypothyroidism. The use of desiccated thyroid, USP, synthetic T 3 (liothyronine sodium [Cytomel]), or T 4-T3 combinations in varying ratios is not recommended.
Goiter and nodules Discussion of the diagnosis and management of goiters and thyroid nodules is outside the scope of this article. The fundamental differences in managing elderly patients versus younger patients can be understood in the context continued
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Elderly patients are likely to die before a newly recognized goiter becomes massive or obstructive.
of the following key points: • Most single nodules that are seen on physical examination are actually part of a multinodular goiter. • Nodules may be present in up to 90% of women over age 60 and in 60% of men over age 80. 17 • Most nodules (90%) are bemgn. • Goiters rarely cause obstructive symptoms and grow very slowly. • Most goiters in older patients are old goiters newly recognized. • Some 20% to 50% of nontoxic nodular goiters are functionally nonsuppressible. 18 The clinical question in patients with multinodular goiters is whether to attempt TSH suppression. In younger patients, it should be attempted because (1) the goiter has a long time to grow and may become an obstructive mass requiring surgery, (2) the risk for carcinoma over time is unknown, and (3) the goiter is often cosmetically bothersome. Elderly patients, in contrast, are far more likely to die before a newly recognized goiter ever becomes massive or obstructive, and they may be at greater risk for the negative effects ofT4 therapy (iatrogenic hyperthyroidism with cardiovascular morbidity and possible worsening of osteoporosis). Also, because T 4
therapy may not completely suppress endogenous T 4 output from most goiters, even a small dose of exogenous T 4 can lead to overt hyperthyroidism. For this reason, clinical observation is often the best course. If the goiter should grow during this period, a cautious trial ofT4 therapy is appropriate in the event that growth of the goiter demonstrates significant dependence on TSH. 19 When growth is rapid or when the presence of a dominant cold solitary nodule suggests the presence of carcinoma, fine-needle aspiration biopsy is indicated to guide management.
Summary Thyroid disease in the elderly is common but often has an insidious onset with symptoms that mimic those of normal aging. Understanding the significance of thyroid function test results requires an appreciation of the normal physiologic variations of aging and the complicating effects of diseases and medications; only then can one accurately discriminate between various disease processes, order additional appropriate tests, and deliver rational management. The increasing preva-
lence of thyroid disorders with age, coupled with the current and future dramatic growth of the elderly population, demands that primary care providers be vigilant to the likelihood of thyroid disease and informed as to its most proper, expedient, and cost-effective diagnosis and management. FlQ\11
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The views expressed herein are those of the authors and do not necessarily reflect the views of the US Army or the Department of Defense. Address for correspondence: COL Leonard Wartofsky, MC, USA, Department of Medicine, Walter Reed Army Medical Center, Washington, DC 20307. References 1. Crantz JG, Crantz FR. Thyroid disease in the elderly. Pract Gastroenterol1983;7(2):41-5 2. Hurley JR. Thyroid disease in the elderly. Med Clin North Am 1983;67(2):497-516 3. Levy EG. Thyroid disease in the elderly. Med Clin North Am 1991;75(1):151-67 4. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977;7(6):481-93 5. Wartofsky L, Burman KD. Alterations in thyroid function in patients with systemic illness: the "euthyroid sick syndrome." Endocr Rev 1982;3(2):164-217 6. Ronnov-Jessen V, Kirkegaanl C. Hyper-
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thyroidism: a disease of old age? BMJ 1973; 1(844):41-3 7. Thomas FB, Mazzafari EL, Skillman TG. Apathetic thyrotoxicosis: a distinctive clinical and laboratory entiry. Ann Intern Med 1970; 72(5 ):679-85 8. McDennott Mf, Kidd GS, Dodson I..E Jr, et al. Radioiodine-induced thyroid storm: case report and literature review. Am J Med 1983; 75(2):353-9 9. Cooper DS. Antithyroid drugs. N Eng! J Med 1984;311(21):1353-62 10. StaffiuthJS, Gibbcrd MC, SNgTang Fui. Arterial embolism in thyrotoxicosis with atrial fibrillation. BMJ 1977;2(6088):688-90 11. Bagchi N, Brown ~Parish RF. Thyroid dysfunction in adults over age 55 years: a srudy in an urban US community. Arch Intern Med 1990;150(4):785-7 12. Livingston EH, Henhman JM, Sawin Cf, et al. Prevalence of thyroid disease and abnormal thyroid tests in older hospitalized and ambulatory persons. JAm Geriarr Soc 1987; 35(2):109-14 13. Bahemuka M, Hodkinson HM. Screening for hypothyroidism in elderly inpatients. BMJ 1975;2(5971):601-3 14. Griffin JE. Hypothyroidism in the elderly. Am J Med Sci 1990;299(5):334-45 15. Ridgway Ec, Cooper DS, Walker H, et al. Peripheral responses to thyroid hormone before and after L-thyroxine therapy in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 1981 ;53(6): 1238-42 16. Stall GM, HarrisS, SokoU LJ, et al. Accelerated bone loss in hypothyroid patients overtreated with L-thyroxine. Ann Intern Med 1990;113(4):265-9 17. Chopra IJ, Chopra U, Smith SR, et al. Reciprocal changes in serum concentrations of 3,3'.5'-rriiodothyronine (reverse T 3) and 3,3'5rriiodothyronine (T3) in systemic illnesses. J Clin Endocrinol Merab 1975;4 1(6): 1043-9 18. Smeulen J, Docter R, Vuser1J, et al. Response to thyrotrophin-releasing hormone and triiodothyronine suppressibiliry in euthyroid multinodular goitre. Clin Endocrinol (Oxf) 1977;7(5):389-97 19. Shimaoka K, Sokal JE. Suppressive therapy of nontoxic goiter. Am J Med 1974;57(4): 576-83
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ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Common thyroid disorders in the elderly CPT Thomas Francis MC, USA & COL Leonard Wartofsky MC, USA To cite this article: CPT Thomas Francis MC, USA & COL Leonard Wartofsky MC, USA (1992) Common thyroid disorders in the elderly, Postgraduate Medicine, 92:3, 225-236, DOI: 10.1080/00325481.1992.11701452 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701452
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [University of Technology Sydney]
Date: 23 July 2016, At: 01:42
-®CME credit article
Common thyroid disorders in the elderly
Downloaded by [University of Technology Sydney] at 01:42 23 July 2016
CPT Thomas Francis, MC, USA
COL Leonard Wartofsky, MC, USA
Preview Diagnosing a thyroid disorder in an elderly patient can be a challenge: Onset is insidious, symptoms and signs are often masked by those of other diseases, and commonly taken medications confound the results of thyroid function tests. Treatment may be complicated by underlying heart disease or osteoporosis. In this article, the authors undertake the task of demystifying the perplexities of accurate diagnosis and rational management of thyroid disease in the elderly.
Although primary care physicians are aware that thyroid disease and abnormalities on thyroid function tests are common in the elderly, the presence of hyperthyroidism or hypothyroidism may be overlooked because "classic" symptoms and signs typically seen in younger patients are absent. Furthermore, common geriatric illnesses (eg, Parkinson's and Alzheimer's disease, depression, psychosis, renal failure) may mask symptoms that might otherwise spur evaluation of the thyroid gland. Because the onset of thyroid disease is often insidious, it is possible that neither patient nor clinician will recognize a "change" other than that attributable to normal aging. Even when thyroid function tests are obtained, results can be misleading because of the effects of malnutrition, medications, and protein-binding abnormalities that accompany
various acute and chronic diseases. Although newer free thyroxine (T4), free triiodothyronine (T3), and supersensitive thyrotropin (thyroid-stimulating hormone [TSH]) assays facilitate specific diagnosis in patients with systemic illness, interpretation of thyroid function tests may still be difficult because of thyroidbinding protein perturbations and otherwise altered thyroid hormone economy (euthyroid sick syndrome). Drugs such as amiodarone hydrochloride (Cordarone) and iodinated radiographic contrast agents, which are often used in elderly patients, provide additional challenge to the accurate clinical interpretation of thyroid function tests. Also, the decision to treat goiter, thyroid nodules, or carcinoma with suppressive doses of synthetic T 4 is of especial concern in elderly patients with underlying cardiac disease or osteoporosis,
both of which could be worsened by T 4 therapy.
Thyroid function tests By secreting TSH, the pituitary gland maintains tight homeostatic feedback control of thyroid T 4 synthesis and release. Thereleased T 4 is immediately bound to binding proteins in the serum, and less than 0.01% remains free. However, T 4 is bioinactive in relation to T 3 and is converted to T 3 by an activating pathway (mediated by 5'-monodeiodinase), predominantly in peripheral tissues (liver, kidney, muscle). Reduced activity of this deiodinase in multiple clinical situations often causes perturbations in both total and free T 4 and T 3 levels. Eighty percent of circulating T 3 is derived from T 4 in peripheral tissues, and only 20% is directly secreted from the thyroid. T 3 is also tightly bound by binding proteins, and binding alterations that affect total T 4 concentrations also affect serum T 3 levels. Consequently, direct measurement of free (rather than total) T 4 or T 3 represents a more precise estimate of thyroid status. With the recent availability of supersensitive TSH assays (and assuming normal pituitary function), clinicians can more readily determine the thyroid status of a patient: A sup-
continued
VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE • THYROID DI80RDIIRS
225
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Low T 3 concentrations in the elderty may be due to the increased prevalence of disease processes and use of certain medications.
Table 1. Variations in results of thyroid function tests in the elderly
Unchanged RT3 U
rT3 1evel T4 concentration TBG level Increased Serum iodide levels TSH levels Thyroid antibody levels TRH stimulation of TSH (women only) Decreased Iodine trapping by thyrocytes T3 concentration T4-T3 production TRH stimulation of TSH (men only) Diminished TSH response to dropping T4 RAIU
RAIU, radioactive iodine uptake; T3 , triiodothyronine; T4, thyroxine; RT3U, resin T3 uptake (thyroid hormone-binding ratio); rT3 , reverse T3 ; TBG, thyroxinebinding globulin; TRH, thyrotropinreleasing hormone; TSH, thyrotropin (thyroid-stimulating hormone).
pressed TSH level signifies hyperthyroidism, whereas an elevated level signifies hypothyroidism. There are only a few instances in which a normal TSH concentration could be misleading. Glu-
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cocorticoids and dopamine hydrochloride (Dopastat, lntropin), which are often used in intensive care units, suppress TSH production and give artificially low values even when a patient is actually hypothyroid. When a patient has a history of disease, previous surgery, or irradiation of the pituitary, the validity of using TSH levels to document thyroid status becomes questionable. Although TSH levels are the most sensitive indicators of hypothyroidism or hyperthyroidism, total and/ or free T 4 and T 3 concentrations are often measured to help gauge the magnitude of hyperthyroid or hypothyroid function; knowledge of the free T 4 level is also useful to follow the clinical course of (I) patients taking antithyroid drugs, (2) those who have had ablation of the thyroid gland with iodine 131 (1 3 '1) treatment, and (3) those receiving replacement or suppressive T 4 therapy. Because many clinicians still rely on these and other parameters to assess thyroid function, this article reviews their use in elderly populations.
Tests in the elderly Typical alterations of thyroid function seen in the elderly (table 1) have been well described
and reviewed. '·3 An age-related decrease in iodine trapping by thyrocytes may be expressed as a slight decrease in 24-hour radioactive iodine uptake (RAIU). TSH levels tend to be higher in the elderly, especially in women, and one study4 correlated this rise with increasing prevalence of thyroid antibodies, implying that TSH levels correlate with autoimmune disease rather than age per se. Stimulation testing with synthetic thyrotropin-releasing hormone (TRH) (protirelin [Thypinone, Relefact TRH]) may disclose gender differences, with men showing a slightly decreased and women a slightly enhanced response, again possibly related to differences in autoimmune disease. Depending on the population studied, T 3 concentrations tend to be lower in the elderly. It has been theorized that this is due to the increased prevalence of disease processes and use of medications that inhibit 5'-monodeiodinase, which, as mentioned, converts T 4 to T 3• Such conditions include malnutrition, diabetes, hepatic or renal disease, and a wide variety of acute and chronic illnesses associated with the euthyroid sick syndrome. 5 Inhibition of5'-monodeiodinase also results in reduced dear-
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Studies show that hyperthyroidism is about seven times more prevalent in the elderly than in younger age-groups.
Table 2. Results of thyroid function tests in the elderly compared with those in patients with euthyroid sick syndrome
Patient group
Ta
rT3
Elderly
.!.
H
Low-T4 ETS
.!.
High-T4 ETS
.!.
TSH
TRH stimulation
Free T4
RT3 U
T4
Total
Free T4 index
H
H
H
H
H
H
i
HJ.
HJ.
.!.
.!.
i
.!.
i
H
H
i
i
Hi
i
ETS, euthyroid sick syndrome; T3 , triiodothyronine; T4 , thyroxine; RT3 U, resin T3 uptake; rT3 , reverse T3 ; TRH, thyrotropin-releasing hormone; TSH, thyrotropin (thyroid-stimulating hormone).
ance of reverse T 3 (rT3); hence, serum rT 3 levels are usually elevated in patients with euthyroid sick syndrome but should be normal in a healthy elderly population. Distinguishing laboratory results from those of the euthyroid sick syndrome is especially relevant here in view of the greater frequency of illnesses in the elderly. Misinterpretation of laboratory data to suggest either hypothyroidism or hyperthyroidism could lead to inappropriate management. Characteristic findings in cases of euthyroid sick syndrome include the following: a low T 3 level, a high rT3 level, a low to normal T 4 level, and an increased resin T 3 uptake (RT3U). The RT3U is often elevated as a con-
sequence of decreased T 4 protein binding due to circulating inhibitors ofT4 binding, with an associated high-normal free T 4 index and free T 4 level. This should not be mistaken for hyperthyroidism, because the TSH level is usually measurable. TRH stimulation may be blunted and, in more seriously ill patients with low total and free T 4 concentrations, TSH production may be decreased. Although rare as a cause for a low TSH level, secondary hypothyroidism should be considered. A normal result on the TRH stimulation test excludes this, as does measurement of the rT3 level, which is high in cases of euthyroid sick syndrome but low in any hypothyroid state. Summarized in table 2 are
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some of the key similarities and differences seen between the thyroid function tests of the elderly and those of patients with two common subtypes of the euthyroid sick syndrome.
Hyperthyroidism According to various studies, the prevalence of hyperthyroidism in the elderly is between 0.5% and 2.3%. 3 This is roughly seven times higher than in younger age-groups. 6 SYMP'IDMS AND SIGNs-As
noted, manifestations of hyperthyroidism that are common in younger patients are often absent in the elderly (table 3). Decreased energy, fatigue, and heat intolerance are reported only half as often. Anorexia and weight loss
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Most geriatric hyperthyroidism is caused by either Graves' disease or autonomous toxic nodular disease of the thyroid gland.
Table 3. Signs and symptoms of hyperthyroidism in the elderly
Less common Nervousness and irritability Heat intolerance Muscle weakness Polyphagia and hyperdefecation Tachycardia Goiter Ophthalmopathy More common Tremor Malaise Muscle wasting Anorexia Atrial fibrillation and/or atrioventricular block Angina and/or congestive heart failure
are common, whereas polyphagia and hyperdefecation are rare. Nervous complaints (eg, irritability) occur less often, and muscle weakness is often absent. Toxic multinodular goiter causes about 50% of hyperthyroidism in the elderly but does not result in autoimmune ophthalmopathy, which explains the decreased incidence of eye symptoms. Lahey coined the term "apathetic hyperthyroidism" in 1931, when he observed that elderly patients were presenting with nothing more than lethargy and that up
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to 30% lacked physical findings of goiter and tachycardia. 7 However, symptoms of cardiovascular disturbance, including atrial fibrillation, angina, and congestive heart failure, frequently herald the existence of underlying hyperthyroidism. CAUSES-Most geriatric hyperthyroidism is caused by either Graves' disease or autonomous toxic nodular disease of the thyroid gland. Autonomous nodular disease can present as either a solitary autonomously functioning thyroid nodule (AFTN) or as multinodular goiter. In either case, the autonomous thyroid tissue may or may not be producing quantities of thyroid hormone sufficient to cause thyrotoxicosis. When the tissue is hyperfunctioning, the nodule is designated as "toxic" and the goiter is designated as "toxic multinodular goiter" (Plummer's disease). Generally, AFTNs and Plummer's disease progress slowly to thyrotoxicosis and patients require therapy only if they have nodules that are producing hyperthyroidism or are growing large enough to cause obstructive symptoms. AFTNs usually do not cause hyperthyroidism until they are larger than 3 em in diameter, and they may present as "T3 toxicosis" (preferential secre-
tion ofT3 with normal serum T 4 levels). THERAPY-After 6 to 18 months of antithyroid drug therapy, a lasting remission is seen in only 20% to 50% of patients with Graves' disease. Thus, a more satisfactory option in elderly patients with hyperthyroidism is definitive ablation of the thyroid gland with 131 1. Our practice is to ablate the gland completely to reduce the risk of relapse and to facilitate T 4 replacement without concern for varying residual endogenous hormone production. A beta blocker such as propranolol hydrochloride (Inderal) should be started in a symptomatic patient (if there are no contraindications at the time of diagnosis) and continued until the patient is euthyroid. Some clinicians prefer to administer 131 1 without first rendering patients euthyroid with antithyroid drugs. This approach avoids toxic effects of the drugs and requires less time to achieve a euthyroid state and less monitoring with blood tests. Nevertheless, transient worsening of hyperthyroidism after using 131 1 and thyroid storm are unpredictable events, and it is our practice to use antithyroid drugs routinely beforehand, particularly in the elderly, who are more susceptible
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Iodine-induced hyperthyroidism is rare in the elderly but may be increasing in incidence.
to the latter complication. 8 The major adverse side effects9 of the thioamide derivatives (propylthiouracil and methimazole [Tapazole]) occur in 1% to 5% of patients and include fever, rash, urticaria, and arthralgia. Leukopenia is common, affecting 12% of adults, but is usually benign. Agranulocytosis occurs in 0.5% of patients, and all patients should be advised to have a complete blood cell count if they have symptoms of fever or sore throat. Clinically, it is imponant to recognize that the rates of drug clearance and endogenous protein metabolism decrease as hypetthyroidism abates, and the reduced metabolic rate may require adjustments in medication dosages. In patients with atrial fibrillation, it is imponant to monitor and reduce dosages for digoxin (Lanoxicaps, Lanoxin) and warfarin sodium (Coumadin, Panwarfin, Sofarin) because their respective drug clearance and clotting-factor catabolism decline as hypenhyroidism is controlled. Atrial fibrillation in the context of hypenhyroidism carries a 10% risk of causing embolic cerebrovascular accident, 10 and, unless contraindicated, anticoagulants should be given to all patients. Iodine-induced
CPT Thomas Francis, MC, USA Dr Francis is instructor in medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and is assigned to the endocrinology division, Walter Reed Army Medical Center, Washington, DC.
hypetthyroidism in the elderly is rare but is probably increasing in incidence with the more widespread use of amiodarone and of radiographic studies with iodine-rich contrast agents. The patient's clinical history and results of an RAIU test (uptake is immeasurable in persons with normal thyroid function exposed to iodine but inappropriately normal in persons with hyperthyroidism) help in the detection of iodine-induced disease.
VOL 92/NO 3/SEPTEMBER 1. 1992/POSTGRADUATE MEDICINE • THYROID DISORDERS
COL Leonard Wartofsky, MC, USA Dr Wartofsky is professor of medicine and physiology and chief, department of medicine, Walter Reed Army Medical Center.
Hypothyroidism The prevalence of hypothyroidism varies widely, but one recent US studi 1 revealed that the results of supersensitive TSH assays were above 6 1-LU/mL in 7_8% of outpatients 55 years of age or older. In another study, 12 12% of patients routinely screened on hospital admission had elevated TSH levels. SYMPTOMS AND SIGNs--Awareness of the insidious nature of hypothyroidism, the subtle sympcontinued
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Hypothyroidism in the elderly has an insidious nature and, when untreated, may progress to profound myxedema, coma, and even death.
Table 4. Results of thyroid function tests in patients with euthyroid sick syndrome and with hypothyroidism
Patient group
TSH
FT4I or freeT4
TRH stimulation
rT3
Primary hypothyroidism
i
.j,
i
.j,
Subclinical hypothyroidism
~r
~
i
.j,
Secondary or tertiary hypothyroidism
~.j,
.j,
.j,
.j,
Low-T4 ETS
~.j,
.j,
~.j,
i
ETS, euthyroid sick syndrome; T3 , triiodothyronine; T4 , thyroxine; FT41, free T4 index; rT3 , reverse T3 ; TRH, thyrotropin-releasing hormone; TSH, thyrotropin (thyroidstimulating hormone).
toms and signs of which can be mistaken for normal aging, and of the potential for progression to profound myxedema, coma, and even death when untreated should foster aggressive screening with TSH to exclude this disorder in populations at higher risk. Less than one third of patients show typical symptoms, and two thirds present with nothing more than debilitation and apathy. 13 An excellent recent review 14 described in detail the presentations of hypothyroidism in the elderly. Neuropsychiatric symptoms may include confusion, memory loss, disorientation, apathy, depression, paranoia, and
frank delirium (myxedema madness). Other complaints include dyspnea, dry skin, constipation, anorexia with weight loss, ataxia, and musculoskeletal disorders. Frequent falls, peripheral neuropathy, carpal runnel syndrome, and hearing loss may occur. OBJECI1VE FINDIN~bjec
tive physical and laboratory findings include diastolic hypertension, bradycardia, cardiomegaly, congestive heart failure with reversible cardiomyopathy, hyperlipidemia, hyponatremia, anemia, and elevated creatine kinase and aspartate aminotransferase (previously SCOT) levels. The definitive laboratory parameters for diagnosis of primary hypo-
thyroidism (table 4) include an elevated TSH level with a low free T 4 concentration or free T 4 index. A low T 3 level alone is insensitive for diagnosis; in addition, there may be a normal physiologic decline either with age or as part of the euthyroid sick syndrome . A mildly elevated or normal TSH level and enhanced TRH response with a normal free T 4 index in an asymptomatic patient defines "subclinical" or "chemical" hypothyroidism. Authorities disagree as to whether this is really hypothyroidism. Some believe that increased basal TSH secretion and TRH responsiveness completely compensate for compromised thyroid output. However, on careful questioning, many patients are found to have subtle symptoms and objectively impaired cognitive functions, as well as demonstrably decreased cardiac contractility and higher low-density lipoprotein cholesterol levels, all of which can be treated by T 4 supplementation. 15 Secondary (pituitary) and tertiary (hypothalamic) hypothyroidism with an "inappropriately" low TSH level for the accompanying low free T 4 level or T 4 index should be differentiated from subclinical primary hypothyroidism. This is so be-
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The most frequent cause of primary hypothyroidism in all age-groups is Hashimoto's disease.
cause of the theoretical risk of precipitating adrenal insufficiency by treating combined hypothyroidism and hypoadrenalism with only T 4 and no glucocorticoid. The TRH stimulation test reveals an exaggerated response in subclinical hypothyroidism, a blunted to absent response in secondary hypothyroidism, and a blunted and delayed response in tertiary hypothyroidism. CAUSFS--The most frequent cause of primary hypothyroidism across all age-groups is autoimmune destruction (Hashimoto's disease). The next most frequent cause is surgical or medical ablation of the thyroid gland for preexisting thyroid disease. Hypothyroidism may also present in the elderly after the use of iodinecontaining medications, amiodarone, and lithium, which variably block intrathyroidal T 4 synthesis and release. lHERAPY-Regardless of cause, replacement therapy must be carefully guided by considering (I) coexisting disease processes, (2) medications being used, and (3) magnitude of the initial hypothyroidism. Unmasking or exacerbating underlying coronary artery disease or dysrhythmias is generally the biggest concern. A guiding principle is to "start low and go slow."
In the context of known or suspected heart disease, we recommend starting with 12.5 to 25 jJ.g of synthetic T 4 (levothyroxine sodium [Levothroid, Levoxine, Synthroid]) a day and adjusting the dose upward in the same increment every 4 to 6 weeks. Because the half-life ofT4 is 1 week, it can take at least 4 weeks for serum levels to equilibrate; hence, tests should not be repeated any more often than every 5 to 6 weeks unless there is an absorption or a compliance problem. In a patient with a history of prolonged hypothyroidism, pituitary thyrotropes are hypertrophied, and as a result, a longer period may be needed for TSH to fall to a level that reflects equilibrium ofT4 and T 3 levels. The final dosage is empirically determined when the TSH level is restored to normal range without hyperthyroid or hypothyroid symptoms or aggravation of other medical problems, such as angina pectoris. The target replacement dose for elderly patients is lower than that for younger patients, approximating 0.7 to 0.8 jJ.g/lb a day, based on lean body mass. In the case of mild initial hypothyroidism without strongly suspected heart disease, T 4 therapy can be started in a total daily dose of
VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRADUATE MEDICINE • THYROID
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50 to 75 jJ.g and increased every 4 to 6 weeks, with serial monitoring ofTSH as just described. Subclinical hypothyroidism requires a more careful risk-benefit analysis, but we recommend gentle supplementation to restore TSH levels to the mid-normal range if there are no frank contraindications. At the very least, patients should be carefully followed by serial TSH monitoring every 4 to 6 months, because progression to overt hypothyroidism is common. The concern for worsening of osteoporosis is real, 16 yet no study has documented an increased fracture risk when suppressive or replacement-level doses are used, and there can be clear clinical improvement in lipid and cardiovascular parameters with treatment of subclinical hypothyroidism. The use of desiccated thyroid, USP, synthetic T 3 (liothyronine sodium [Cytomel]), or T 4-T3 combinations in varying ratios is not recommended.
Goiter and nodules Discussion of the diagnosis and management of goiters and thyroid nodules is outside the scope of this article. The fundamental differences in managing elderly patients versus younger patients can be understood in the context continued
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Elderly patients are likely to die before a newly recognized goiter becomes massive or obstructive.
of the following key points: • Most single nodules that are seen on physical examination are actually part of a multinodular goiter. • Nodules may be present in up to 90% of women over age 60 and in 60% of men over age 80. 17 • Most nodules (90%) are bemgn. • Goiters rarely cause obstructive symptoms and grow very slowly. • Most goiters in older patients are old goiters newly recognized. • Some 20% to 50% of nontoxic nodular goiters are functionally nonsuppressible. 18 The clinical question in patients with multinodular goiters is whether to attempt TSH suppression. In younger patients, it should be attempted because (1) the goiter has a long time to grow and may become an obstructive mass requiring surgery, (2) the risk for carcinoma over time is unknown, and (3) the goiter is often cosmetically bothersome. Elderly patients, in contrast, are far more likely to die before a newly recognized goiter ever becomes massive or obstructive, and they may be at greater risk for the negative effects ofT4 therapy (iatrogenic hyperthyroidism with cardiovascular morbidity and possible worsening of osteoporosis). Also, because T 4
therapy may not completely suppress endogenous T 4 output from most goiters, even a small dose of exogenous T 4 can lead to overt hyperthyroidism. For this reason, clinical observation is often the best course. If the goiter should grow during this period, a cautious trial ofT4 therapy is appropriate in the event that growth of the goiter demonstrates significant dependence on TSH. 19 When growth is rapid or when the presence of a dominant cold solitary nodule suggests the presence of carcinoma, fine-needle aspiration biopsy is indicated to guide management.
Summary Thyroid disease in the elderly is common but often has an insidious onset with symptoms that mimic those of normal aging. Understanding the significance of thyroid function test results requires an appreciation of the normal physiologic variations of aging and the complicating effects of diseases and medications; only then can one accurately discriminate between various disease processes, order additional appropriate tests, and deliver rational management. The increasing preva-
lence of thyroid disorders with age, coupled with the current and future dramatic growth of the elderly population, demands that primary care providers be vigilant to the likelihood of thyroid disease and informed as to its most proper, expedient, and cost-effective diagnosis and management. FlQ\11
-®
Earn credit on this article. See CME Quiz.
The views expressed herein are those of the authors and do not necessarily reflect the views of the US Army or the Department of Defense. Address for correspondence: COL Leonard Wartofsky, MC, USA, Department of Medicine, Walter Reed Army Medical Center, Washington, DC 20307. References 1. Crantz JG, Crantz FR. Thyroid disease in the elderly. Pract Gastroenterol1983;7(2):41-5 2. Hurley JR. Thyroid disease in the elderly. Med Clin North Am 1983;67(2):497-516 3. Levy EG. Thyroid disease in the elderly. Med Clin North Am 1991;75(1):151-67 4. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977;7(6):481-93 5. Wartofsky L, Burman KD. Alterations in thyroid function in patients with systemic illness: the "euthyroid sick syndrome." Endocr Rev 1982;3(2):164-217 6. Ronnov-Jessen V, Kirkegaanl C. Hyper-
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thyroidism: a disease of old age? BMJ 1973; 1(844):41-3 7. Thomas FB, Mazzafari EL, Skillman TG. Apathetic thyrotoxicosis: a distinctive clinical and laboratory entiry. Ann Intern Med 1970; 72(5 ):679-85 8. McDennott Mf, Kidd GS, Dodson I..E Jr, et al. Radioiodine-induced thyroid storm: case report and literature review. Am J Med 1983; 75(2):353-9 9. Cooper DS. Antithyroid drugs. N Eng! J Med 1984;311(21):1353-62 10. StaffiuthJS, Gibbcrd MC, SNgTang Fui. Arterial embolism in thyrotoxicosis with atrial fibrillation. BMJ 1977;2(6088):688-90 11. Bagchi N, Brown ~Parish RF. Thyroid dysfunction in adults over age 55 years: a srudy in an urban US community. Arch Intern Med 1990;150(4):785-7 12. Livingston EH, Henhman JM, Sawin Cf, et al. Prevalence of thyroid disease and abnormal thyroid tests in older hospitalized and ambulatory persons. JAm Geriarr Soc 1987; 35(2):109-14 13. Bahemuka M, Hodkinson HM. Screening for hypothyroidism in elderly inpatients. BMJ 1975;2(5971):601-3 14. Griffin JE. Hypothyroidism in the elderly. Am J Med Sci 1990;299(5):334-45 15. Ridgway Ec, Cooper DS, Walker H, et al. Peripheral responses to thyroid hormone before and after L-thyroxine therapy in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 1981 ;53(6): 1238-42 16. Stall GM, HarrisS, SokoU LJ, et al. Accelerated bone loss in hypothyroid patients overtreated with L-thyroxine. Ann Intern Med 1990;113(4):265-9 17. Chopra IJ, Chopra U, Smith SR, et al. Reciprocal changes in serum concentrations of 3,3'.5'-rriiodothyronine (reverse T 3) and 3,3'5rriiodothyronine (T3) in systemic illnesses. J Clin Endocrinol Merab 1975;4 1(6): 1043-9 18. Smeulen J, Docter R, Vuser1J, et al. Response to thyrotrophin-releasing hormone and triiodothyronine suppressibiliry in euthyroid multinodular goitre. Clin Endocrinol (Oxf) 1977;7(5):389-97 19. Shimaoka K, Sokal JE. Suppressive therapy of nontoxic goiter. Am J Med 1974;57(4): 576-83
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