Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2019, Vol. 10 Issue (3) : 520-529     DOI: 10.14336/AD.2018.0817
Orginal Article |
Subclinical Hypothyroidism: is it Really Subclinical with Aging?
Robin Gourmelon1, Sandrine Donadio-Andréi2, Karim Chikh1,3,4,5, Muriel Rabilloud6, Elisabetta Kuczewski3, Anne-Sophie Gauchez5,7,8,10, Anne Charrié1,3,4,5, Pierre-Yves Brard10, Raphaëlle Andréani10, Jean-Cyril Bourre10, Christine Waterlot8, Domitille Guédel8, Anne Mayer8, Emmanuel Disse1, Charles Thivolet1, Hélène Du Boullay8, Claire Falandry1, Thomas Gilbert1, Anne François-Joubert8, Antoine Vignoles1, Catherine Ronin2, Marc Bonnefoy1,*
1Service de Gériatrie, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.
2Siamed’Xpress, Hôtel Technologique Morandat, 13120 Gardanne, France.
3Hospices Civils de Lyon, 69002 Lyon, France.
4Laboratoire de Biochimie et Biologie Moléculaire, Centre de Biologie Sud, Centre Hospitalier Lyon Sud 69 495 Pierre Bénite Cedex, France.
5Société Française de Médecine Nucléaire, Groupe de Biologie Spécialisée, 75237 Paris Cedex 05, France.
6Service de Biostatistiques, Hospices Civils de Lyon, Lyon, France.
7UMR-S INSERM 1039, 38000 Grenoble, France.
8Service de Médecine Nucléaire, Centre Hospitalier Métropole Savoie, 73000 Chambéry, France.
9Pôle de Biologie, Centre Hospitalier et Universitaire de Grenoble, CS 10217 38043 Grenoble Cedex 9, France.
10Service d’Endocrinologie, Centre Hospitalier Métropole Savoie, 73000 Chambéry, France
Download: PDF(683 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

No recent study has focused on clinical features of subclinical hypothyroidism (SCH), especially in older patients. TSH measurement has remarkably evolved these last 20 years and thus reconsideration is needed. In our prospective multicenter study (2012-2014) including 807 subjects aged <60 years (<60y) and 531 subjects ≥60 years (≥60y), we have monitored 11 hypothyroidism-related clinical signs (hCS) together with TSH, FT4, FT3 and anti-thyroperoxidase antibodies values. hCS expression has been compared in patients with SCH vs euthyroidism in each age group. The number of hCS above 60y of age were found to be more elevated in the euthyroid population (1.9 vs 1.6, p<0.01) than in the SCH population (2.3 vs 2.6, p=0.41) while increase in hCS is limited to SCH subjects in the <60y group (p<0.01). The percentage of subjects with at least 3 signs increased with SCH in the <60y group (42.6% vs 25.0%, p<0.01) but not ≥60y (34.4% vs 33.9%, p=0.96). In older individuals, only three hCS could be related to both SCH and a decreased T3/T4-ratio (0.26 vs 0.27, p<0.01), suggesting either a reduced activity of TSH, or an adaptive response with aging. While hCS are clearly associated with SCH in patients <60y, they are not so informative in older subjects. TSH measurements carried out on the basis of hCS need to be interpreted with caution in aged patients. A reassessment of the TSH reference range in older patients is clearly needed and should be associated to more appropriate monitoring of thyroid dysfunction

Keywords thyroid deficiency      aging      symptoms      TSH     
Corresponding Authors: Bonnefoy Marc   
About author:

These authors contributed equally to this work

Just Accepted Date: 07 September 2018   Online First Date: 06 September 2018    Issue Date: 07 September 2018
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Robin Gourmelon
Sandrine Donadio-Andréi
Karim Chikh
Muriel Rabilloud
Elisabetta Kuczewski
Anne-Sophie Gauchez
Anne Charrié
Pierre-Yves Brard
Raphaëlle Andréani
Jean-Cyril Bourre
Christine Waterlot
Domitille Guédel
Anne Mayer
Emmanuel Disse
Charles Thivolet
Hélène Du Boullay
Claire Falandry
Thomas Gilbert
Anne François-Joubert
Antoine Vignoles
Catherine Ronin
Marc Bonnefoy
Cite this article:   
Robin Gourmelon,Sandrine Donadio-Andréi,Karim Chikh, et al. Subclinical Hypothyroidism: is it Really Subclinical with Aging?[J]. Aging and disease, 2019, 10(3): 520-529.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2018.0817     OR     http://www.aginganddisease.org/EN/Y2019/V10/I3/520
Figure 1.  Flowchart of the recruitment, selection and exclusion process of the cohort.
Groups & Classes<60 years≥60 years
Euthyroid**1.6±1.6(n=739) ††1.9±1.7(n=469)
SCH2.6±2.1(n=68)2.3±2.3(n=62)

4.1-10.0mIU/L range:
TPOAbs (-)2.4±1.9(n=37)1.8±2.0(n=42)
TPOAbs (+)3.0±2.3(n=28)2.7±2.3(n=16)
Table 1  Mean number of overall clinical signs.
Figure 2.  Mean TSH (A), FT3 (B), FT4 (C) levels and FT3/FT4 ratios (D) as a function of TSH levels

Asterisks indicate significant differences between age groups (**, p<0.01) and crosses indicate significant differences between normal (0.17-4.05 mIU/L) and elevated (>4.05 mIU/L) TSH groups or difference between the absence/presence of TPOAbs when TSH is in the 4.1-10.0mIU/L range (†, p<0.05; ††, p<0.01).

Figure 3.  Percentage of subjects with 0, 1, 2, or 3 or more clinical signs by TSH groups

Data from all subjects (A), subjects <60y (B) and ≥60y (C) are presented.

Figure 4.  Prevalence of individual hypothyroidism-related clinical signs according to age

Age groups are <60y (white bars) and ≥60y (black bars). A) euthyroid subjects (TSH, 0.17-4.05mIU/L); B) subclinical hypothyroid subjects (TSH, >4.05mIU/L). Bars with an asterisk are significantly different between <60y and ≥60y groups (*p<0.05; **p<0.01).

[1] Canaris GJ, Manowitz NR, Mayor G.,Ridgway EC (2000). The Colorado thyroid disease prevalence study. Arch Intern Med,160:526-534.
[2] Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE (2002). Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab, 87:489-499.
[3] Asvold BO, Vatten LJ, Bjøro T (2013). Changes in the prevalence of hypothyroidism: the HUNT Study in Norway. Eur J Endocrinol, 169:613-620.
[4] Deshmukh V, Behl A, Iyer V, Joshi H, Dholye JP, Varthakavi PK (2013). Prevalence, clinical and biochemical profile of subclinical hypothyroidism in normal population in Mumbai. Indian J Endocrinol Metab, 17:454-459.
[5] Delitala AP, Pilia MG, Ferreli L, Loi F, Curreli N, Balaci L, Schlessinger D, Cucca F (2014). Prevalence of unknown thyroid disorders in a Sardinian cohort. Eur J Endocrinol, 171:143-149.
[6] Mariscal Hidalgo AI, Lozano Alonso JE, Vega Alonso T; nombre del Grupo de Investigación del Hipotiroidismo Subclínico en Castilla y León (2015). Prevalence and clinical characteristics of subclinical hypothyroidism in an opportunistic sample in the population of Castile-León (Spain). Gac Sanit, 29:105-111.
[7] Kim WG, Kim WB, Woo G, Kim H, Cho Y, Kim TY, Kim SW, Shin MH, Park JW, Park HL, Oh K, Chung JH (2017). Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015. Endocrinol Metab (Seoul), 32:e4.
[8] Hennessey JV, Espaillat R (2015). Diagnosis and Management of Subclinical Hypothyroidism in Elderly Adults: A Review of the Literature. J Am Geriatr Soc, 63:1663-1673.
[9] Iglesias P, Muñoz A, Prado F, Guerrero MT, Macías MC, Ridruejo E, Tajada P, Díez JJ (2009). Alterations in thyroid function tests in aged hospitalized patients: prevalence, aetiology and clinical outcome. Clin Endocrinol (Oxf), 70:961-967.
[10] Donadio-Andréi S, Chikh K, Iss C, Kuczewski E, Gauchez AS, Ronin C, Charrié A (2013). How significant is the TSH level in the circulation? Immuno-Anal Biol Spéc, 28:223-239.
[11] Yeap BB, Manning L, Chubb SA, Hankey GJ, Golledge J, Almeida OP, Flicker L (2017). Reference ranges for Thyroid-Stimulating Hormone and Free Thyroxine in older men: Results from the Health In Men Study. J Gerontol A Biol Sci Med Sci, 72:444-449.
[12] Veltri F, Rocha FO, Willems D, Praet JP, Grabczan L, Kleynen P, Pepersack T, Poppe K (2017). Prevalence of thyroid dysfunction and autoimmunity in the older population and implications of age-specific reference ranges. Clin Chim Acta, 465:34-39.
[13] Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP, Sattar N, Aubert CE, Aujesky D, Bauer DC, Baumgartner C, Blum MR, Browne JP, Byrne S, Collet TH, Dekkers OM, den Elzen WPJ, Du Puy RS, Ellis G, Feller M, Floriani C, Hendry K, Hurley C, Jukema JW, Kean S, Kelly M, Krebs D, Langhorne P, McCarthy G, McCarthy V, McConnachie A, McDade M, Messow M, O’Flynn A, O’Riordan D, Poortvliet RKE, Quinn TJ, Russell A, Sinnott C, Smit JWA, Van Dorland HA, Walsh KA, Walsh EK, Watt T, Wilson R, Gussekloo J; TRUST Study Group (2017).Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.N Engl J Med, 376:2534-2544.
[14] Kalra S, Khandelwal SK, Goyal A (2011). Clinical scoring scales in thyroidology: A compendium. Indian J Endocrinol Metab, 15:S89-94.
[15] Zulewski H, Müller B, Exer P, Miserez AR, Staub JJ (1997). Estimation of tissue hypothyroidism by a new clinical score: evaluation of patients with various grades of hypothyroidism and controls. J Clin Endocrinol Metab, 82:771-776.
[16] Pearce SH, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, Wemeau JL (2013). 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J, 2:215-228.
[17] Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Andersen S, Laurberg P (2016). Hypothyroid Symptoms Fail to Predict Thyroid Insufficiency in Old People: A Population-Based Case-Control Study. Am J Med, 129:1082-1092.
[18] Doucet J, Trivalle C, Chassagne P, Perol MB, Vuillermet P, Manchon ND, Menard JF, Bercoff E (1994). Does age play a role in clinical presentation of hypothyroidism? J Am Geriatr Soc, 42:984-986.
[19] Watt T, Bjorner JB, Groenvold M, Cramon P, Winther KH, Hegedüs L, Bonnema SJ, Rasmussen ÅK, Ware JE Jr, Feldt-Rasmussen U (2015). Development of a short version of the Thyroid-Related Patient-Reported Outcome ThyPRO. Thyroid, 25:1069-1079.
[20] Bensenor IM, Olmos RD, Lotufo PA (2012). Hypothyroidism in the elderly: diagnosis and management. Clin Interv Aging, 7:97-111.
[21] Bemben DA, Hamm RM, Morgan L, Winn P, Davis A, Barton E (1994). Thyroid disease in the elderly. Part 2. Predictability of subclinical hypothyroidism. J Fam Pract, 38:583-588.
[22] Deary M, Buckey T, Soldin OP (2012). TSH - Clinical aspects of its use in determining thyroid disease in the elderly. How does it impact the practice of medicine in aging? Adv Pharmacoepidemiol Drug Saf, 1(119). pii: 9369.
[23] Recommandations professionnelles. Hypothyroïdies frustes chez l’adulte: diagnostic et prise en charge. HAS-SFE; 2007. http://www.has-sante.fr/portail/upload/docs/application/932_pdf/hypothyroidies_frustes_recommandations_vf.pdf 933
[24] Surks MI, Hollowell JG (2007). Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab, 92:4575-4582.
[25] Bremner AP, Feddema P, Leedman PJ, Brown SJ, Beilby JP, Lim EM, Wilson SG, O’Leary PC, Walsh JP (2012). Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J Clin Endocrinol Metab, 97:1554-1562.
[26] Kahapola-Arachchige KM, Hadlow N, Wardrop R, Lim EM, Walsh JP (2012). Age-specific TSH reference ranges have minimal impact on the diagnosis of thyroid dysfunction. Clin Endocrinol, 77:773-779.
[27] Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruf J, Smyth PP, Spencer CA, Stockigt JR; Guidelines Committee, National Academy of Clinical Biochemistry (2003). Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid, 13:3-126.
[28] Fatourechi V (2009). Subclinical hypothyroidism: an update for primary care physicians. Mayo Clin Proc, 84:65-71.
[29] Wulc AE, Sharma P, Czyz CN (2012). The anatomic basis of midfacial aging. In: Hartstein ME, Wulc AE, Holck DEE, editors. Midfacial Rejuvenation. New York: Springer Science, 15-28.
[30] Yamasoba T, Lin FR, Someya S, Kashio A, Sakamoto T, Kondo K (2013). Current concepts in age-related hearing loss: epidemiology and mechanistic pathways. Hear Res, 303:30-38.
[31] Camilleri M, Lee J, Viramontes B, Bharucha AE, Tangalos EG (2000). Insights into the pathophysiology and mechanisms of constipation, irritable bowel syndrome, and diverticulosis in older people. J Am Geriatr Soc, 48:1142-1150.
[32] Makrantonaki E., Zouboulis C. C., William J (2007). Cunliffe Scientific Awards. Characteristics and pathomechanisms of endogenously aged skin. Dermatology (Basel, Switzerland), 214:352-360.
[33] Tarafder KH, Datta PG, Tariq A (2012). The aging voice. BSMMU J, 5:83-86.
[34] Ono Y, Ono S, Yasunaga H, Matsui H, Fushimi K, Tanaka Y (2017). Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan. J Epidemiol, 27:117-122.
[35] Jaffiol C, Baldet L (2001). Symptomatologie de l’hypothyroïdie. In: Leclère J, Orgiazzi J, Rousset B, Schlienger JL, Wémeau JL, editors. Manuel de psychologie et de psychopathologie clinique Générale. Paris: Elsevier Masson, 434-439.
[36] Sender Palacios MJ, Vernet Vernet M, Pérez López S, Faro Colomés M, Rojas Blanc M, Pallisa Gabriel L (2004). Functional thyroid pathology in the elderly. Aten Primaria, 34:192-197.
[37] Atzmon G, Barzilai N, Hollowell JG, Surks MI, Gabriely I (2009). Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab, 94:1251-1254.
[38] Waring AC, Arnold AM, Newman AB, et al. (2012) Longitudinal changes in thyroid function in the oldest old and survival: the Cardiovascular Health Study All-Stars Study. J Clin Endocrinol Metab, 97:3944-3950.
[39] Monzani F, Del Guerra P, Caraccio N, Del Corso L, Casolaro A, Mariotti S, Pentimone F (1996). Age-related modifications in the regulation of the hypothalamic-pituitary-thyroid axis. Horm Res, 46:107-112.
[40] Vitale G, Salvioli S, Franceschi C (2013). Oxidative stress and the ageing endocrine system. Nat Rev Endocrinol, 9:228-240.
[41] Estrada JM, Soldin D, Buckey TM, Burman KD, Soldin OP (2014). Thyrotropin isoforms: implications for thyrotropin analysis and clinical practice. Thyroid, 24:411-423.
[42] Strich D, Karavani G, Edri S, Gillis D (2016). TSH enhancement of FT4 to FT3 conversion is age dependent. Eur J Endocrinol, 175:49-54.
[43] Andersen-Ranberg K, Høier-Madsen M, Wiik A, Jeune B, Hegedus L (2004). High prevalence of autoantibodies among Danish centenarians. Clin Exp Immunol, 138:158-163.
[44] Watad A, Bragazzi NL, Adawi M, Amital H, Toubi E, Porat BS, Shoenfeld Y (2017). Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review. Gerontology. 63:515-523.
[45] Donadio-Andréi S, Chikh K, Heuclin C, Kuczewski E, Charrié A, Gauchez AS, Ronin C (2017). Variability among TSH measurements can be reduced by combining a glycoengineered calibrator to epitope-defined immunoassays. Eur Thyr J, 6:3-11.
[46] Donadio-Andréi S, Ronin C (2017). New immunoassays of bioactive TSH improve detection of thyroid disorders. Thyroid Disorders Ther, 6:4.
[1] Supplemental data Download
[1] Fuellen Georg, Jansen Ludger, Cohen Alan A, Luyten Walter, Gogol Manfred, Simm Andreas, Saul Nadine, Cirulli Francesca, Berry Alessandra, Antal Peter, Köhling Rüdiger, Wouters Brecht, Möller Steffen. Health and Aging: Unifying Concepts, Scores, Biomarkers and Pathways[J]. Aging and disease, 2019, 10(4): 883-900.
[2] Xu Dingqiao, Liao Shanting, Li Pei, Zhang Qian, Lv Yan, Fu Xiaowei, Yang Minghua, Wang Junsong, Kong Lingyi. Metabolomics Coupled with Transcriptomics Approach Deciphering Age Relevance in Sepsis[J]. Aging and disease, 2019, 10(4): 854-870.
[3] Wang Min-jun, Chen Jiajia, Chen Fei, Liu Qinggui, Sun Yu, Yan Chen, Yang Tao, Bao Yiwen, Hu Yi-Ping. Rejuvenating Strategies of Tissue-specific Stem Cells for Healthy Aging[J]. Aging and disease, 2019, 10(4): 871-882.
[4] Cho Kyoungjoo. Emerging Roles of Complement Protein C1q in Neurodegeneration[J]. Aging and disease, 2019, 10(3): 652-663.
[5] Jin Kunlin. A Microcirculatory Theory of Aging[J]. Aging and disease, 2019, 10(3): 676-683.
[6] Chung Hae Young, Kim Dae Hyun, Lee Eun Kyeong, Chung Ki Wung, Chung Sangwoon, Lee Bonggi, Seo Arnold Y., Chung Jae Heun, Jung Young Suk, Im Eunok, Lee Jaewon, Kim Nam Deuk, Choi Yeon Ja, Im Dong Soon, Yu Byung Pal. Redefining Chronic Inflammation in Aging and Age-Related Diseases: Proposal of the Senoinflammation Concept[J]. Aging and disease, 2019, 10(2): 367-382.
[7] Li Haibin, Wang Anxin, Feng Wei, Zheng Deqiang, Gao Qi, Tao Lixin, Guo Jin, Wang Xiaonan, Li Xia, Wang Wei, Guo Xiuhua. Prospective Study of Glycated Hemoglobin and Trajectories of Depressive Symptoms: The China Health and Retirement Longitudinal Study[J]. Aging and disease, 2019, 10(2): 249-257.
[8] Sarkar Saumyendra N., Russell Ashley E., Engler-Chiurazzi Elizabeth B., Porter Keyana N., Simpkins James W.. MicroRNAs and the Genetic Nexus of Brain Aging, Neuroinflammation, Neurodegeneration, and Brain Trauma[J]. Aging and disease, 2019, 10(2): 329-352.
[9] Cyprien Fabienne, Courtet Philippe, Maller Jerome, Meslin Chantal, Ritchie Karen, Ancelin Marie-Laure, Artero Sylvaine. Increased Serum C-reactive Protein and Corpus Callosum Alterations in Older Adults[J]. Aging and disease, 2019, 10(2): 463-469.
[10] Lana Alberto, Struijk Ellen A., Arias-Fernandez Lucía, Graciani Auxiliadora, Mesas Arthur E., Rodriguez-Artalejo Fernando, Lopez-Garcia Esther. Habitual Meat Consumption and Changes in Sleep Duration and Quality in Older Adults[J]. Aging and disease, 2019, 10(2): 267-277.
[11] Murtha Lucy A., Morten Matthew, Schuliga Michael J., Mabotuwana Nishani S., Hardy Sean A., Waters David W., Burgess Janette K., Ngo Doan TM., Sverdlov Aaron L., Knight Darryl A., Boyle Andrew J.. The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis[J]. Aging and disease, 2019, 10(2): 419-428.
[12] Shetty Ashok K., Upadhya Raghavendra, Madhu Leelavathi N., Kodali Maheedhar. Novel Insights on Systemic and Brain Aging, Stroke, Amyotrophic Lateral Sclerosis, and Alzheimer’s Disease[J]. Aging and disease, 2019, 10(2): 470-482.
[13] Tingting Sui,Di Liu,Tingjun Liu,Jichao Deng,Mao Chen,Yuanyuan Xu,Yuning Song,Hongsheng Ouyang,Liangxue Lai,Zhanjun Li. LMNA-mutated Rabbits: A Model of Premature Aging Syndrome with Muscular Dystrophy and Dilated Cardiomyopathy[J]. Aging and disease, 2019, 10(1): 102-115.
[14] Dong Liu,Liqun Xu,Xiaoyan Zhang,Changhong Shi,Shubin Qiao,Zhiqiang Ma,Jiansong Yuan. Snapshot: Implications for mTOR in Aging-related Ischemia/Reperfusion Injury[J]. Aging and disease, 2019, 10(1): 116-133.
[15] Wanying Duan, Yuehua Pu, Haiyan Liu, Jing Jing, Yuesong Pan, Xinying Zou, Yilong Wang, Xingquan Zhao, Chunxue Wang, Yongjun Wang, Ka Sing Lawrence Wong, Ling Wei, Liping Liu, . Association between Leukoaraiosis and Symptomatic Intracranial Large Artery Stenoses and Occlusions: the Chinese Intracranial Atherosclerosis (CICAS) Study[J]. Aging and disease, 2018, 9(6): 1074-1083.
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd