Evaluation of Thyroid Diseases in Hospitalized Geriatric Patients: a Retrospective Review

Acta Medica Mediterranea, 2019, 35: 1145

EVALUATION OF THYROID DISEASES IN HOSPITALIZED GERIATRIC PATIENTS: A RETROSPECTIVE REVIEW

Mustafa Behçet Demirbaş, Sema Uçak, Zehra Sarikaya Demirbaş Internal Medicine , Umraniye Trainig and Research Hospital, Istanbul, Turkey

ABSTRACT

Introduction: To analyse the clinical characteristics and understand the resistance mechanism of bacteria and the independent risk factors of carIntroduction: This study aimed to evaluate the prevalence of thyroid diseases and subgroups in hospitalized geriatric patients. Materials and methods: We retrospectively reviewed demographic characteristics, thyroid function tests, hemogram parameters, thyroid imaging, and thyroid pathology records of 500 inpatients aged >65 years at Umraniye Training and Research Hospital Internal Medicine Clinic between 2013 and 2014. All patients were categorized into two groups for comparison, those aged 65–75 years and those aged >75 years. Results: In this study, the prevalence of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, and subclinical hypothyroidism was 0.6%, 16%, 0.6%, and 2.8%, respectively. In 31 patients who underwent thyroid ultrasound, the thyroid nodule prevalence was 77%. In geriatric patients with hyperthyroidism, the platelet count was low. Anti-thyroglobulin levels were higher in the >74 years group compared with the <75 years group (P = 0.009 and P < 0.01, respectively). Conclusion: This study reveals that subclinical hyperthyroidism is the leading thyroid pathology in elderly inpatients and that anti-thyroglobulin levels increase as the age advances.

Keywords: thyroid diseases, geriatrics, hospitalized elderly.

DOI: 10.19193/0393-6384_2019_2_177

Received November 30, 2018; Accepted January 20, 2019

Introduction and subclinical hypothyroidism (SCH). Typical symptoms of hyperthyroidism, such as nervousness, During the aging process, the thyroid gland tachycardia, and tremor, are relatively less reported undergoes various crucial functional changes; its size in elderly patients. Remarkably, the loss of weight remains the same, but its density increases with age. and tachypnea are more frequent in the elderly than The interpretation of thyroid function test in elderly in young patients(3). In geriatric patients, treatment patients differs from that in young patients. With aging, modalities of hyperthyroidism include medical while thyroid-stimulating hormone (TSH) secretion, therapy (preferably methimazole), radioactive iodine blood level, and reverse triiodothyronine (rT3) level uptake (RAI) treatment, and surgery. SHyper is increases, triiodothyronine (T3) level decreases. defined by low TSH and normal sT4 and sT3 levels; Reportedly, thyroxine (T4) synthesis decreases but however, it is a laboratory, and not clinical, diagnosis. serum sT4 levels remain unchanged in the elderly SHyper is further divided into 2 categories: grade 1 because of the increased half-life (t1/2)(1). In addition, SHyper with low but detectable TSH (01-4.9 mIU/L) the aging process results in an increased thyroid nodule and grade 2 SHyper with suppressed TSH levels (<0.1 prevalence. Based on the function, thyroid diseases mIU/L)(5, 6). Patients with SHyper encounter some can be categorized as hyperthyroidism, subclinical risks such as progression to overt hyperthyroidism, hyperthyroidism (SHyper), hypothyroidism, atrial fibrillation, osteoporosis, heart failure, and 1146 Mustafa Behçet Demirbaş, Sema Uçak et Al increased mortality(7, 8). A study analyzing 10 globin, WBC ( white blood cell count) , and platelet prospective cohorts reported a correlation between count), thyroid imaging (e.g., thyroid scintigraphy SHyper and increased total mortality(7). Clinical and thyroid ultrasound), and fine-needle aspiration manifestations of hypothyroidism such as fatigue, biopsy reports were retrospectively evaluated. dry skin, cold intolerance, and hair loss are typically attributed to other causes or aging. Therefore, Statistical analysis the clinical diagnosis of hypothyroidism is challenging in elderly patients. While the treatment In this study, statistical analyses were per- of hypothyroidism is same for young and elderly formed using IBM SPSS Statistics 22 (IBM SPSS) patients, overt hypothyroid patients should be on program. We used descriptive statistical methods levothyroxine treatment. However, lower doses such as mean, standard deviation, and frequency; of levothyroxine are usually adequate for elderly we used the Kruskal-Wallis test for group compari- patients because of declined drug metabolism. son of parameters and the Mann-Whitney U-test for SCH is defined as having high TSH (4-10 mI- the determination of differential groups. For the be- U/L) and normal T4 and T3 levels and is highly tween-group comparison, we used the Mann-Whit- prevalent in the elderly. For the diagnosis of SCH, ney U-test. For the comparison of qualitative data, age-specific reference TSH values should be con- the Ki-Kare, Fisher’s exact Ki-Kare, and Fish- sidered(1). In the presence of co-morbidities, thyroid er-Freeman-Halton tests were used. We considered function tests could show abnormal results without statistical significance at P < 0.05. any thyroid disease, a condition also known as euthyroid sick syndrome (non-thyroidal illness), in Results which laboratory findings include low T3, low T4, and high rT3 levels. Of note, TSH levels might be In this study, we reviewed the hospital records low, normal, or elevated. Apparently, acute and of 500 hospitalized patients aged >65 years (mean chronic illnesses, such as pneumonia, liver disease, age: 77.29±7.13 years; 49.8% females and 50.2% kidney disease, high-dose steroid treatment, long- males). While 182 patients (36.4%) were in the 65- term starving, diabetic ketoacidosis, and myocar- 75 years group, 318 (63.6%) were in the >75 years dial infarction, are the causes of the laboratory di- group. Table 1 summarizes the demographic find- agnosis of SCH that requires no specific treatment. ings and thyroid nodule status of patients. Regard- In the literature, very few studies have investi- ing age and sex, we observed no difference in the gated thyroid diseases in hospitalized geriatric pa- distribution of diagnosis (P > 0.05). tients. In Turkey, we could not find a single study n % Female 249 49.8 Sex on this topic. Therefore, this study aimed to assess Male 251 50.2 65–75 182 36.4 the thyroid disease prevalence and thyroid function Age (years) ≥75 318 63.6 status and their correlation with hemogram param- Nodule (+) 24 4.8 eters in hospitalized geriatric patients. Ultrasound + Nodule (–) 7 1.4 Ultrasound (–) 469 93.8 Nodule (+) 2 0.4 Materials and methods Scintigraphy Nodule (–) 3 0.6

Not performed 495 99 In this study, we retrospectively reviewed the <1 cm 7 29.2 medical records of hospitalized geriatric patients Nodule size >1 cm 17 70.8 who were followed up at an internal medicine clin- Benign 7 29.2 ic between 2013 and 2014. The medical records Malignancy Malign 17 70.8 were reviewed through the hospital’s data automa- tion system. We assessed thyroid function tests and Table 1: Patients’ characteristics and the thyroid nodule status. thyroid imaging records of 500 patients aged >65 years. All patients were divided into 2 subgroups: Of 31 (6.2%) patients who underwent thyroid 65-75 years and >75 years. In addition, thyroid ultrasound, 24 (77%) were found to have thyroid function tests (e.g., TSH, sT4, sT3, and rT3), thy- nodules. Only 5 patients had thyroid scintigraphy roid autoantibodies (e.g., anti-TPO (anti thyroid (0.4%), 2 of whom displayed hyperactivity. Of peroxidase antibody) and anti-TG ( anti thyroglob- 24 patients with thyroid nodules, 7 (29.2%) had a ulin antibody), hemogram parameters (e.g., hemo- nodule of <1-cm diameter and 17 (70.8%) >1-cm Evaluation of thyroid diseases in hospitalized geriatric patients: A retrospective review 1147

a diameter. Furthermore, nodules were benign and Benign Malignancy P Malign malign in 7 (29.2%) and 17 (70.8%) patients, respectively. Overall, the thyroid nodule prevalence n (%) n (%) 65–75 2 (22.2%) 7 (77.8%) in this study was 77%. Table 2 summarizes the lab- Age oratory findings. ≥75 5 (33.3%) 10 (66.7%) Female 5 (31.3%) 11 (68.7%) n Min–Max Mean ± SD Sex Male 2 (25%) 6 (75%) TSH 414 0–31.9 1.7 ± 2.87 Hyperthyroidism 1 (50%) 1 (50%) T3 253 0.01–4.84 1.93 ± 0.77 Subclinical 1 (12.5%) 7 (87.5%) T4 388 0.53–5.56 1.17 ± 0.38 hyperthyroidism Diagnosis Subclinical Antitpo 34 0–22 3.53 ± 5.61 1 (25%) 3 (75%) hypothyroidism Anti-TG 21 0.38–13.51 2.91 ± 3.89 Normal 3 (33.3%) 6 (66.7%)

ESR 400 1–140 38.97 ± 28.44 Nodule <1 cm 1 (14.3%) 6 (85.7%) >1 cm 6 (35.3%) 11 (64.7%) Hb 485 3.57–16.5 10.62 ± 2.27 size

Hct 485 12.5–54.8 32.78 ± 6.87

WBC 483 0.13–162 9.7 ± 10.21 Table 4: Table 4. Malignancy and its correlation with thyroid disease and patientpatients’ demographic cha- Plt 485 2.84–918 241.92 ± 117.23 racteristics. RBC 485 0.93–202 4.44 ± 10.86 aFisher’s exact test. Table 2: Thyroid and hemogram parameters. In the >75 years group, anti-TG levels were higher than that in the 65-75 years group (P < 0.05). The platelet count was lower in patients with hy- In our study cohort, the prevalence of hyper- perthyroidism than that in patients with hypothy- thyroidism, SHyper, hypothyroidism, SCH, and roidism and euthyroid sick syndrome (P < 0.01). euthyroid sick syndrome was 0.6%, 16%, 0.6%, In addition, the hemoglobin count was lower in 2.8%, and 9.2%, respectively. In addition, 48.8% patients with euthyroid sick syndrome than that in of the patients had a normal thyroid function. Of patients with hyperthyroidism and hypothyroidism note, we could not establish a diagnosis in 22% of (P < 0.01). Furthermore, we found that 43.5% of the patients owing to the lack of thyroid function patients with a thyroid nodule had hyperthyroid- test records (Table 3). ism, 17.4% had hypothyroidism, and 39.1% had Diagnosis n % euthyroid sick syndrome (Table 5). Hyperthyroidism 3 0.6 Benign Malign Subclinical hyperthyroidism 80 16 Med ± SD (median) Med ± SD (median) aP Hypothyroidism 3 0.6 TSH 1.67 ± 3.06 (0.67) 2.7 ± 4.87 (0.58) Subclinical hypothyroidism 14 2.8 T3 2.45 ± 1.54 (1.74) 2.43 ± 0.77 (2.5) Euthyroid Sick Syndrome 46 9.2 T4 1.49 ± 0.53 (1.53) 1.27 ± 0.39 (1.16) Normal 244 48.8 Anti-TG 1.37 ± 0.19 (1.37) 1.61 ± 0.92 (1.82) Not evaluated 110 22 Sedim 33.14 ± 22.59 (26) 45.69 ± 27.28 (41) Table 3: Distribution of the diagnosis in the study. Hb 10.46 ± 2.32 (10.9) 10.73 ± 1.85 (10.6) TSH: Thyroid stimulating hormone, T3: triiodothyronine, T4: tetraiodothyronine, Anti tpo: anti thyroid peroxidase antibody, Hct 32.43 ± 7.39 (34.1) 32.64 ± 4.88 (32) anti-TG: anti thyroglobulin antibody, ESR: erythrocyte sedimen- WBC 6.92 ± 3.44 (7.1) 10.96 ± 11.11 (6.3) tation rate, Hb: hemoglobin, Htc: hematocrit, WBC: white blood Plt 207.43 ± 83.61 (202) 261.36 ± 136.56 (4.44) cell count, Plt: platelet count, RBC: red blood cell count RBC 3.95 ± 0.97 (229) 3.72 ± 0.58 (3.78) Regarding the thyroid malignancy prevalence, Table 5: Malignancy and its correlation with laboratory we observed no difference between the 65-75 years findings. TSH: Thyroid stimulating hormone, T3: triiodothyronine, T4: and >75 years groups, and the prevalence was equiv- tetraiodothyronine, Anti tpo: anti thyroid peroxidase antibody, alent in males and females. In addition, 68.7% of anti-TG: anti thyroglobulin antibody, ESR: erythrocyte sedimen- female patients and 75% of male patients with thy- tation rate, Hb: hemoglobin, Htc: hematocrit, WBC: white blood roid nodules were diagnosed with thyroid carcinoma. cell count, Plt: platelet count, RBC: red blood cell count Table 4 presents thyroid malignancy and correlation with laboratory and demographic status. 1148 Mustafa Behçet Demirbaş, Sema Uçak et Al

Discussion The European Thyroid Association recom- mends following up patients with SCH aged >80 This study established that sHyper is the lead- years without treatment(1). ing thyroid disease in hospitalized geriatric patients. In this study, hemoglobin and hematocrit The prevalence of thyroid disease in the elderly is levels were low in patients with euthyroid sick as high the young population and, based on some syndrome, which could be attributed to increased studies, more prevalent than younger patients. As co-morbid diseases in this group. In patients with a person draws closer to the end of life, the preva- chronic diseases, anemia is typically observed be- lence of co-morbidities increases. In the elderly, the cause of the inflammatory suppression of eryth- interpretation of the thyroid function test becomes ropoiesis. However, we could not establish any difficult because of non-thyroid illnesses. Typical- correlation between anemia and hypothyroidism ly, the treatment of thyroid diseases in the elderly in this study. Notably, thyroid hormones, directly is similar to that in young adults. Thyroid disease and indirectly, affect the hemoglobin count by the can easily be misdiagnosed or omitted in the elder- direct stimulation of the erythropoietin produc- ly population because of the lack of some clinical tion. Therefore, we typically encounter anemia in findings. In this study, the thyroid disease preva- cases with low thyroid hormone levels, as in hy- lence was 20% in hospitalized geriatric patients. A pothyroidism. A study including 100 patients with study reviewing thyroid function tests of 1210 pa- overt hypothyroidism, 100 with SCH, and 100 in tients aged >65 years reported that the prevalence the control group reported that the prevalence of of hypothyroidism, SCH, overt hyperthyroidism, anemia was 43% in the hypothyroid group, 39% in and SHyper was 1.4%, 6%, 0.08%, and 11.8%, re- the SCH group, and 26% in the control group(12). spectively(11). Although the prevalence of anemia according In another study, the hyperthyroidism preva- to the thyroid status differs by study, the general lence in the elderly was approximately 0.5%-4%(2). finding in this study is that anemia is more com- In addition, the prevalence of hypothyroidism in mon in patients with hypothyroidism. In a large the elderly was found to be 4.4% in the Framing- population-based study including 8791 people with ham study on the elderly (>60 years)(9). Moreover, a previously unknown thyroid status, anemia was the SCH prevalence in elderly females was report- found in 4.7% of euthyroid participants, 14.6% of ed to be as high as 20% and up to 8% in elderly patients with hypothyroidism, and 5% in patients males(10). In these studies, the population comprised with SCH(13). Another hemogram parameter that elderly outpatients. In this study, the prevalence of we determined a correlation with thyroid functions hyperthyroidism, SHyper, hypothyroidism, and was the platelet count. Thrombocytopenia can be SCH was 0.6%, 16%, 0.6%, and 2.8%, respectively, observed in patients with hyperthyroidism and can and no difference was observed between the 65-75 be explained by sharing a common immunological years and >75 years groups regarding the incidence stimulus and decreased survival of platelets be- and diagnostic distribution of thyroid disease (P > cause of thyrotoxicity. 0.05). The therapeutic approach of thyroid diseases In this study, the platelet count was lower in in elderly patients might differ from that in young patients with hyperthyroidism. A study investigat- patients. Owing to increased morbidity and mor- ing the platelets in hyperthyroidism reported that tality in the elderly, surgery is usually considered the platelet lifespan markedly shortened in the hy- only for malignancy and goiter with obstructive perthyroid group compared with the control euthy- symptoms(4). roid group(14). In this study, we determined that the However, the RAI treatment can be safely pre- levels of anti-thyroglobulin antibodies were high- ferred in the elderly. Although the medical treat- er in the >75 years group than in the 65-75 years ment is the same as young patients, age-specific group. Although autoimmunity increases with age, TSH levels should be considered. In addition, overt autoimmune disorders are less prevalent in the el- hyperthyroidism and hypothyroidism are similarly derly; even if it exists, its course is usually mild and treated in both young and elderly patients. Howev- self-controlled. One of the possible explanations of er, SHyper should be treated when TSH < 0.1 mI- this is advanced protective mechanisms and the in- U/L or in patients with atrial fibrillation or osteopo- creased production of peripheral regulatory T cells rosis(7, 8). To date, the treatment of SCH in elderly in the elderly(15). patients remains debatable. Evaluation of thyroid diseases in hospitalized geriatric patients: A retrospective review 1149

Regarding thyroid malignancy between the References 65-75 and >75 years groups, no difference was observed in this study. Of 500 geriatric inpatients, 31 1) Atzmon G, Barzilai N, Hollowell JG, et al. Extreme lon- had thyroid ultrasound and 24 had a thyroid nod- gevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab 2009; 94(4): 1251-54. ule. The thyroid nodule prevalence was 77% in 2) Diez JJ. Hyperthyroidism in patients older than 55 this study; however, upon dividing patients with years: an analysis of the etiology and management. Ger- thyroid ultrasound to the whole population of our ontology 2003; 49(5): 316-23. study (500 patients), the prevalence was 4.8%. A 3) Boelaert K, Torlinska B, Holder RL, et al. Older subjects with hyperthyroidism present with a paucity of symp- study evaluating subjects aged >65 years reported toms and signs: a large cross-sectional study. J Clin En- (16) the thyroid nodule prevalence as 50% . In our docrinol Metab 2010; 95(6): 2715-26. study, the thyroid nodule prevalence was same in 4) Shakaib U, Rehman MD, Dennis W, et al. Thyroid dis- females and males. In addition, a study in Ger- orders in elderly patients: Hyperthyroidism. South Med many examining 635 patients aged >60 years and J 2005; 98(5): 543-49. 5) Surks MI, Ortiz E, Daniels GH, et al: Subclinical thyroid performing thyroid ultrasound reported that 80% disease: scientific review and guidelines for diagnosis of females and 74% of males had a thyroid nod- and management. JAMA 2004; 291(2): 228-38. ule(17). As the age advances, the thyroid nodule 6) Biondi B, Palmieri EA, Klain M, Schlumberger M, Fi- prevalence increases; however, the malignancy risk letti S, Lombardi G. Subclinical hyperthyroidism: clin- (18) ical features and treatment options. Eur J Endocrinol of each newly detected nodule decreases . In this 2005; 152(1): 1-9. study, of the 24 patients with a nodule, 17 (79%) 7) Collet TH, Gussekloo J, Bauer DC, et al. Thyroid stud- cases were malign and 7 (21%) were benign; this ies collaboration: subclinical hyperthyroidism and the malignancy ratio is very high compared with sim- risk of coronary heart disease and mortality. Arch Intern ilar studies. Because only 31 of 500 patients had Med 2012; 172(10): 799-809. 8) Gencer B, Collet TH, Virgini V, et al. Thyroid studies thyroid ultrasound, the thyroid malignancy ratios collaboration: subclinical thyroid dysfunction and the were high, making it difficult to precisely state the risk of heart failure events: an individual participant data malignancy prevalence. A study retrospectively analysis from 6 prospective cohorts. Circulation 2012; analyzed 6653 patients and reported that the young 126(9): 1040-9. 9) Sawin CT, Castelli WP, Hershman JM, McNamara P, group malignancy ratios per year were 14.8% and Bacharach P. The aging thyroid. thyroid deficiency in 5.6% in the elderly group; in addition, the thyroid the Framingham study. Arch Intern Med 1985; 145(8): cancer prevalence was 26.3% in patients aged >60 1386-8. years (18). In this study, we observed a slightly 10) Benseñor IM, Goulart AC, Lotufo PA, et al. Prevalence male predominance in thyroid malignancy; 68.7% of thyroid disorders among older people: results from the São Paulo Ageing & Health Study. Cad Saude Publi- of females and 75% of male elderly patients with ca 2011; 27(1): 155-61. a nodule had thyroid carcinoma, but this was not 11) Parle JV1, Franklyn JA, Cross KW, Jones SC, Sheppard statistically significant (P > 0.05). MC. Prevalence and follow up of abnormal thyrotrophin Thyroid disease in the elderly can result in se- (TSH) concentrations in the elderly in the United King- dom. Clin Endocrinol (Oxf) 1991; 34: 77-83. vere co-morbidities and trigger several life-threat- 12) Erdogan M1, Kösenli A, Ganidagli S, Kulaksızoglu M. ening diseases, including atrial fibrillation, Characteristics of anemia in subclinical and overt hy- cardiovascular events, osteoporosis, cognitive im- pothyroid patients. Endoct J 2012; 59(3): 213-20. Epub pairment, myxedema coma, and atherosclerosis. In 2011 Dec 27. the 21st century, the life expectancy has increased 13) M'Rabet-Bensalah K, Aubert CE, Coslovsky M, et al. Thyroid dysfunction and anaemia in a large popula- worldwide, and elderly patients have the right to be tion-based study. Clin Endocrinol (Oxf) 2016; 84(4): treated as young patients irrespective of age. There- 627-31. doi: 10.1111/cen.12994. Epub 2016 Jan 19. fore, awareness of thyroid disease should be raised 14) Panzer S1, Haubenstock A, Minar E. Platelets in hy- by the elderly patients themselves, healthcare pro- perthyroidism: studies on platelet counts, mean platelet volume, 111-indium-labeled platelet kinetics, and plate- viders, and the families of the elderly patients. let-associated immunoglobulins G and M. J Clin Endo- crinol Metab 1990; 70(2): 491-6. 15) Haj T, Vadasz Z, Toubi E. Age-related autoimmunity. BMC Med 2013; 11: 94. doi: 10.1186/1741-7015-11-94. 16) Mazzaferri E. Management of a solitary thyroid nodule. N Engl J Med 1993; 328: 553-9. 17) Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest 2009; 39: 699-706. 1150 Mustafa Behçet Demirbaş, Sema Uçak et Al

18) Kwong N, Medici M, Angell TE, et al. The influence ––––––––– of patient age on thyroid nodule formation, multinodu- Corresponding Author: larity, and thyroid cancer risk. J Clin Endocrinol Metab Mustafa Behçet Demirbaş 2015; 100(12): 4434-40. Umraniye Trainig and Research Hospital, Istanbul, Turkey Internal Medicine Elmalıkent Mah. Adem Yavuz Cad No: 1 Ümraniye Eğitim ve Araştirma Hastanesi, Ümraniye, İstanbul Email: [email protected] (Turkey)