Thyroid in the elderly. Akbar Soltani M.D. Endocrinology and Metabolism Research Center (EMRC) Shariati Hospital

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1 Thyroid in the elderly Akbar Soltani M.D. Endocrinology and Metabolism Research Center (EMRC) Shariati Hospital

2 Case 1 A 79 year old female is seen because of a 6 month history of fatigue, nervousness and depression. She has history of some enlargement of her neck since Physical examination reveals: B.P. 130/60 mm Hg., pulse 96/minute, asymmetric thyroid enlargement with SSN fullness Her TSH=0.2 (0.4-4) T4=10( ) T3=185 ( ) what is your explanation?

3 Case 2 A 79 year old female is seen because of a 6 month history of fatigue, nervousness and depression. Her history is unremarkable. Physical examination reveals: B.P. 130/60 mm Hg., pulse 96/minute, and normal thyroid Her TSH=0.2 (0.4-4) T4=10( ) T3=150 ( ) what is your explanation?

4 Thyroid Function and Prevalence of Anti-Thyroperoxidase Antibodies in a Population with Borderline Sufficient Iodine Intake: Influences of Age and Sex Clinical Chemistry 52, No. 1, 2006

5 National Health and Nutrition Examination Survey (NHANES III) J Clin Endocrinol Metab, February 2002, 87(2):

6 Thyroid and Other Organ-Specific Autoantibodies in Healthy Centenarians The Lancet; Jun 20, 1992; 339, 8808; ProQuest pg. 1506

7 What Is Normal Thyroid Function in the Elderly? Recent reports have shown increased serum TSH levels with increasing age, independent of antithyroid antibody presence In contrast : others have shown decreased serum TSH in older adults Populations in which the dominant thyroid pathology is Hashimotos thyroiditis display a trend of TSH upper limit to increase with age In contrast : In iodine-deficient populations in which the dominant thyroid pathology is nodularity and increasing thyroid autonomy with age an inverse relationship between TSH and age is seen

8 Disease-Free Thyroid Function Levels: May Narrow in Young But widens in Elderly Using an upper limit of 4.5 mu/l, up to 15% of subjects older than 70 y are classified having an increased TSH. The reference ranges for older people shift to the right. The 97.5 percentiles derived from studies indicate an upper normal limit of around 7 mu/l TSH distribution by age groups in the UnitedStates. on Disease-free population Surks MI, Hollowell JG. J Clin Endocrinol Metab. 2007;92: FROM LADENSON

9 summary HAZZARD S GERIATRIC MEDICINE AND GERONTOLOGY Sixth Edition

10 Hyperthyroidism in older adults The prevalence is 0.5 4% Graves disease remains the most common etiology one-third of older adults will present with apathetic Hyperthyroidism with weight loss, apathy and tachycardia, shortness of breath (p<0.001) Subclinical hyperthyroidism have a prevalence of 3 8% and is more common in women than men, especially in patients over the age of 70.

11 Frequency of Symptoms and Signs of Hyperthyroidism Griffin MA, Solomon DH. Hyperthyroidism in the elderly. J Am Geriatr Soc 1986

12 Syndrome of "Apathetic" or "Nonactivated" Thyrotoxicosis Represents potentially dangerous degree of hyperthyroidism masked by other preexistent chronic conditions or illnesses High mortality if not recognized & patient has surgery or another new illness Most cases in elderly or patients with compromised communication ability

13 Clinical Features of Apathetic Thyrotoxicosis May present with any of these seemingly isolated symptoms : Congestive heart failure Atrial fibrillation Recent weight loss > 20 kg Somnolence, apathy Irritability and uncooperative behavior If not recognized and treated, patients may slip into coma and die

14 Increased incidence of atrial fibrillation in subclinical hyperthyroidism N Engl J Med 1994; 331:1249.

15 Total mortality, coronary heart disease (CHD) mortality, in endogenous subclinical hyperthyroidism vs euthyroidism. Nicolas Rodondi, et al, Arch Intern Med. 2012

16 Effects of Subclinical Hyperthyroidism on Bone -The SOF Study- Case-control study of Caucasian women > 65 years old followed for up to 6 years for fractures < 0.1 * * * 2 Increased risk of hip fracture if 1 baseline TSH undetectable; 0 increased risk of Hip Spine vertebral fracture if TSH low or undetectable Bauer 01

17 Subclinical Hyperthyroidism and Dementia Women Men TSH TSH 2-50 Baseline TSH levels vs. risk of developing Alzheimer s Disease during mean follow-up of 13 years (Framingham study, Tan 08)

18 Treatment of hyperthyroidism Older adults may be at greater risk of recurrence after drug therapy Older adults taking PTUor high doses of MTZ may be at greater risk for side effects. o Agranulocytosis is the major adverse event in this population,(0.5%) o Rash, arthralgias and myalgias occur more frequently. Pretreatment with methimazole prior to radioactive iodine therapy for TMNG or TA should be considered in the elderly

19 overt hypothyroidism in older adults Frequency of overt from 0.1% to 2%, increase up to 5% in > 60 y 5 to 8 times more common in women than men. Higher prevalence in iodine-sufficient regions most frequent cause :Autoimmune thyroiditis, then iatrogenic Iodine-induced hypothyroidism is more frequently seen in older patients Endocrinol Metab Clin N Am 42 (2013)

20 Endocrinol Metab Clin N Am 42 (2013) Frequency of Symptoms and Signs of Hypothyroidism 1)Acute vs. Chronic hypothyroidism?

21 Percentage of Euthyroid, Subclinical and Hypothyroid Patients Reporting Symptoms 60% euthyroid have 1 symptom 15% 4 symptoms R5. Clinical scoring systems should not be used to diagnose hypothyroidism. Grade A Canaris et al.

22 The Starting Dose of Levothyroxine in Primary Hypothyroidism Treatment A RCT Mean symptoms and clinical scores for full-dose and low-dose groups during treatment. P=.4 and P=.8 for the symptoms score and clinical score, respectively, for the full-dose vs low-dose group. ARCH INTERN MED/ VOL 165, AUG 8/22, 2005

23 The Starting Dose of Levothyroxine in Primary Hypothyroidism Treatment A RCT ARCH INTERN MED/ VOL 165, AUG 8/22, 2005

24 Treatment: Hypothyroidism Ann Intern Med. 1986;105:11-15.

25 Treatment: Hypothyroidism Regardless of the degree of hypothyroidism, patients older than years without CHD may be started on doses of 50 μg daily. known CHD μg/day. L-thyroxine should be taken with water consistently 30 to 60 minutes before breakfast or at bedtime 4 hours after the last meal Clinical monitoring for the onset of anginal symptoms is essential Ann Intern Med. 1986;105:11-15.

26 Frequency : Subclinical Hypothyroidism o 4% to 10% in different populations o more prevalent in iodine-sufficient countries o up to 20% in elderly women and in 8% of elderly men In patients > 55 y,tsh levels may also normalize in almost 50% of patients ( after 3 to 6 m ) So recheck to rule out a temporary increase in TSH Endocrinol Metab Clin N Am 42 (2013)

27 Subclinical Hypothyroidism symptoms In the elderly it may very well be asymptomatic In >65 y, was not associated with cognitive dysfunction or depression in 2 large studies In subjects >70 y it was even associated with a better preservation of physical function compared with euthyroid controls Endocrinol Metab Clin N Am 42 (2013)

28 Does Subclinical Hypothyroidism Protect the Oldest Old? Low TSH Normal TSH Hypothesis: CV risk of subclinical hypothyroidism depends on age (Biondi and Cooper 08): SCHypo Overt Hypo 558 subjects, aged 85 years at entry, followed for 4 years Gussekloo 04

29 Best to Date NON RCT--Observational: Benefit of Treatment? UK General Practitioner : In ~50% of individuals yrs old treated with L- thyroxine,(tsh ) hazard ratio cardiac events reduced (0.67, CI ). Cleveland Clinic: high risk ASCVD Clinic ( TSH and >10) who were under 65 yrs old and not treated with LT4 had higher all-cause mortality Arch IM 2012 McQuade, Thyroid 2011

30 Heart Failure Events by TSH risk risk Until RCTs performed, data favors treating younger, higher TSH values (>10) Gencer Circulation 2012; 126:1040

31 Thyroid Nodules A survey by Cavaliere R et al. AGE Frequency of thyroid nodule % % % management is the same as that in a younger patient

32 In well-differentiated thyroid cancer (i.e. papillary, follicular, and Hurthle cell cancer), age is the most important prognostic factor. Casara et al., Aging Clin Exp Res 1992;4a Age at the time the tumor was found Less than 39 years = 3.1 over 40 = 0.08 x age

33 Case 1 A 79 year old female is seen because of a 6 month history of fatigue, nervousness and depression. She has history of some enlargement of her neck since Physical examination reveals: B.P. 130/60 mm Hg., pulse 96/minute, asymmetric thyroid enlargement with SSN fullness Her TSH=0.2 (0.4-4) T4=10( ) T3=185 ( ) what is your explanation?

34 Case 2 A 79 year old female is seen because of a 6 month history of fatigue, nervousness and depression. Her history is unremarkable. Physical examination reveals: B.P. 130/60 mm Hg., pulse 96/minute, and normal thyroid Her TSH=0.2 (0.4-4) T4=10( ) T3=150 ( ) what is your explanation?

35 Recommendations of Six Organizations Regarding Screening of Asymptomatic Adults for Thyroid Dysfunction AACE 2010

36 summary Changes in thyroid function tests occur in the physiology of aging. Normal T3 may be high! Application of age-specific (TSH) reference ranges may avoid misclassification of elderly subjects without thyroid disease. Watchful waiting is an appropriate strategy for older patients with subclinical hypothyroidism (for TSH levels up to 10 mu/l) After exclusion of other causes of low TSH such as NTI, treatment of subclinical hyperthyroidism may be considered in older subjects. Clinical manifestations can not differentiate hypothyroidism from normal Apathetic hyperthyroidism need alert physician to be detect Thyroid nodule and aggressive thyroid cancer are more common