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Thyroid disease in the elderly

Thyroid disease in the elderly

Research has encouraged several changes to the treatment of thyroid disease in the elderly in recent years. However, controversy still exists regarding the association between hypothyroidism and mortality in older patients. Although it was previously shown that octogenarians survive longer when hypothyroid,1 an individual participant meta-analysis by the Thyroid Collaboration Study found there was a neutral effect of age on the association between hypothyroidism and mortality in 55,287 patients.2


Evidence of benefit from treatment of subclinical hypothyroidism is only available from observational data due to the lack of randomized control trials (RCT). A study performed on the United Kingdom General Practitioner Research Database showed a lower rate of ischemic heart disease events in patients <70 years with subclinical hypothyroidism (TSH 5-10 MU/L) and treated with levothyroxine versus those not treated. This effect was not evident in those >70 years.However, a register-based cohort study of 235,168 individuals in Denmark found an increase in mortality in untreated but not in treated hypothyroid individuals and this effect was independent of age.4 Therefore, more studies are needed to determine whether treating elderly patients with mild subclinical hypothyroidism reduces mortality. Most guidelines agree that patients >65 years should only be treated when TSH levels rise above 10 mU/L.5-7 A randomized clinical trial by the TRUST study group in elderly patients with subclinical hypothyroidism showed no clinical benefit in terms of quality of life with levothyroxine replacement after 12 months. The primary trial outcomes were changes in the Hypothyroid Symptoms Score and Tiredness Score as part of the Thyroid Related Quality of Life Patient Reported Outcome (ThyPRO) measure, and both scores were similar to the placebo group scores at the end of the study.8

In light of these studies, levothyroxine cannot be recommended for the potential relief of hypothyroid symptoms in elderly patients with subclinical hypothyroidism, and more studies are needed to assess whether levothyroxine reduces mortality in this population. In the meantime, treatment should be considered when TSH >10 mU/L and at doses appropriate to return TSH values to within normal ranges according to the age of the individual.

Age is also important in thyroid nodule and cancer outcomes. As age increases, so does the prevalence of clinically-relevant nodules and multinodularity compared with rates in younger patients.9 Paradoxically, the proportion of malignant cytology reports decreases when compared with a younger age cohort but those nodules identified as cancerous are of a more aggressive histological type and are more advanced at diagnosis.10 These findings are in line with those of a recent quantitative analysis of the benefits and risks of thyroid nodule evaluation in patients ≥70 years. In this study, “significant-risk” thyroid cancer was only found in 1.5% of all nodules detected and this group was the only one with thyroid cancer deaths. This suggests that efforts should be made to find these high risk nodules, but also, that surgery can be avoided in the more benevolent type of nodules.11

Due to differences in disease-specific survival between younger and older patients with thyroid cancer, the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) had initially included a different staging system for thyroid cancer for patients aged less than or more than 45 years at diagnosis. However, the 8th edition of the AJCC/TNM staging system published in October 2016 with implementation planned for January 2018 (available from: www.cancerstaging.org) now recommends a higher age cutoff of 55 years. This modification was based on evidence provided by studies on the significance of age as a prognostic factor,10,12,13 and will result in down staging of patients 45-55 years to either Stage I or II of disease. The net result predicted is that older patients that remain at low risk of disease-specific death will be more accurately classified.13

The American Thyroid Association (ATA) classification for thyroid cancer recurrence does not take age into consideration.14 Most interestingly, and as for younger patients, elderly patients can be accurately re-stratified according to their response to initial treatment as proposed by the ATA thyroid cancer guidelines.15,16 Furthermore, it has been recently shown that the ATA recurrence risk classification in combination with age group could help to improve prognosis of disease-specific survival when combined with AJCC/UICC staging, especially in ATA high risk patients17

In conclusion, in some areas of thyroid treatment, older patients require a different approach - in line with the new role of personalized medicine as a tailored treatment for patient care.

References

  1. Gussekloo J, van Exel E, de Craen AJ, et al. Thyroid status, disability and cognitive function, and survival in old age. JAMA 2004;292:2591-9.
  2. Rodondi N, den Elzen WP, Bauer DC, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010;304:1365-74.
  3. Razvi S, Weaver JU, Butler TJ, Pearce SH. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch Intern Med 2012;172:811-7.
  4. Lillevang-Johansen M, Abrahamsen B, Jorgensen HL, et al. Over- and under-treatment of hypothyroidism is associated with excess mortality: A register-based cohort study. Thyroid 2018;28:566-74.
  5. Brenta G, Vaisman M, Sgarbi JA, et al. Clinical practice guidelines for the management of hypothyroidism. Arq Bras Endocrinol Metabol 2013;57:265-91.
  6. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012;18:988-1028.
  7. Pearce SH, Brabant G, Duntas LH, et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J 2013;2:215-28.
  8. Stott DJ, Rodondi N, Bauer DC. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med 2017;377:e20.
  9. Kwong N, Medici M, Angell TE, et al. The influence of patient age on thyroid nodule formation, multinodularity, and thyroid cancer risk. J Clin Endocrinol Metab 2015 Dec;100(12):4434-40.
  10. Ganly I, Nixon IJ, Wang LY, et al. Survival from differentiated thyroid cancer: What has age got to do with it? Thyroid 2015;25:1106-14.
  11. Wang Z, Vyas CM, Van Benschoten O, et al. Quantitative analysis of the benefits and risk of thyroid nodule evaluation in patients ≥70 years old. Thyroid 2018 Apr;28(4):465-71.
  12. Nixon IJ, Wang LY, Migliacci JC, et al. An international multi-institutional validation of age 55 years as a cutoff for risk stratification in the AJCC/UICC staging system for well-differentiated thyroid cancer. Thyroid 2016;26:373-80.
  13. Tuttle RM, Haugen B, Perrier ND. Updated American Joint Committee on Cancer/Tumor-Node-Metastasis Staging System for Differentiated and Anaplastic Thyroid Cancer (Eighth Edition): What changed and why? Thyroid 2017;27:751-6.
  14. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2019 Jan;26(1):1-133.
  15. Morosan YJ, Parisi C, Urrutia MA, et al. Dynamic prediction of the risk of recurrence in patients over 60 years of age with differentiated thyroid carcinoma. Arch Endocrinol Metab 2016 Aug;60(4):348-54.
  16. Pitoia F, Jerkovich F, Smulever A, et al. Should age at diagnosis be included as an additional variable in the risk of recurrence classification system in patients with differentiated thyroid cancer. Eur Thyroid J 2017 Jul;6(3):160-6.
  17. Ghaznavi SA, Ganly I, Shaha AR, et al. Using the ATA risk stratification system to refine and individualize the AJCC 8th edition disease specific survival estimates in differentiated thyroid cancer. Thyroid 2018 Jun 13. [Epub ahead of print]

Gabriela Brenta

Department of Endocrinology and Metabolism
Milstein Hospital
Buenos Aires University
Buenos Aires, Argentina
thyroid disease
Elderly
subclinical hypothyroidism
nodules
thyroid cancer
age