Anil, Cuneyd

Atesagaoglu, Berna

Gursoy, Alptekin

Kut, Altug

Nar, Asli

Tutuncu, Neslihan Bascil

Medical Principles and Practice

English

Baskent Universtiy

E-Mail karger@karger.com
 Letter to the Editor / Reply 
as in a younger population could be harmful to the adults  [2] . Sec-
ondly, using only body mass index (BMI) in such a heterogeneous 
group could lead to false results. Sarcopenic obesity which acceler-
ates insulin resistance is a common condition in elderly popula-
tion; therefore, BMI should be supported by additional measure-
ments  [3] . A third matter is that a hypocaloric diet, weight loss, and 
lifestyle changes are also well-known factors that affect thyroid 
nodules  [4] . These factors also have to be ruled out to reveal the 
separate effect of metformin treatment on thyroid volume and 
nodule.
 
 Dear Editor, 
 The study by Anil et al.  [1] deserves attention for investigating 
2 common health problems: insulin resistance and thyroid nod-
ules. From a geriatric perspective it is more remarkable because of 
the high incidence of these 2 conditions. 
 Firstly, it is understood that choosing an upper limit of TSH 4.0 
mU/L may not be appropriate for older adults. Aging by itself is 
associated with elevated TSH, and keeping treatment targets tight 
Published online: October 31, 2016
 © 2016 S. Karger AG, Basel 
 www.karger.com/mpp 
 Med Princ Pract 2017;26:199–200 
 DOI: 10.1159/000452955 
 Comment on “Metformin Decreases Thyroid 
Volume and Nodule Size in Subjects with Insulin 
Resistance: A Preliminary Study” 
 Umit Cintosun, Mehmet Ilkin Naharci, Huseyin Doruk  
 Department of Geriatrics, Gulhane School of Medicine, 
 Ankara, Turkey 
 
 Umit Cintosun 
 Department of Geriatrics, Gulhane School of Medicine 
 TR–06018 Ankara (Turkey) 
 E-Mail drumitcintosun   @   gmail.com 
 
 References 
 1 Anil C, Kut A, Atesagaoglu B, et al: Metformin decreases thyroid volume 
and nodule size in subjects with insulin resistance: a preliminary study. 
Med Princ Pract 2016; 25: 233–236. 
 2 Atzmon G, Barzilai N, Hollowell, JG, et al: Extreme longevity is associ-
ated with increased serum thyrotropin. J Clin Endocrinol Metab 2009; 
 94: 1251–1254. 
 3 Wells JCK: The Evolutionary Biology of Human Fatness. Cambridge, 
Cambridge University Press, 2009. 
 4 Hua J, Yongfeng T, Wenhua Y, et al: The prevalence of thyroid nodules 
and an analysis of related lifestyle factors in Beijing Communities. Int J 
Environ Res Public Health 2016; 13: 442. 
 
 Dear Editor, 
 We have examined the comments of Cintosun et al. on our 
published manuscript entitled “Metformin Decreases Thyroid 
Volume and Nodule Size in Subjects with Insulin Resistance: A 
Preliminary Study” [1].
 The first issue was about the reference range of TSH in a geri-
atric population. We agree that target TSH should be set higher in 
this population, but the target reference range of TSH levels has 
not been strictly defined in recent endocrine guidelines and endo-
crine textbooks [2, 3]. However, this is generally valid for (sub-
clinical) hypothyroidism cases who are on levothyroxine therapy, 
which was not a subject of our study. No randomized controlled 
trial of LT 4 treatment in elderly patients with hypothyroidism 
compared to different TSH target values are available [2]. In one 
up-to-date guideline regarding hypothyroidism published by the 
American Thyroid Association [2], it has been finally reported that 
based on the current evidence it is reasonable to raise the target 
serum TSH to 4–6 mIU/L in persons older 70–80 years. Therefore, 
using the upper limit of normal for TSH level as 4 IU/mL, in a study 
population aged maximum 75 years, seems reasonable. 
 As to the second issue, we are aware that sarcopenic obesity, a 
common pathology in aging population, is closely associated with 
metabolic syndrome and related conditions [4]. This condition 
might have contributed to the development of insulin resistance 
(IR) in this small subgroup of our study population of early geri-
atric age. We studied some possible outcomes of IR such as thyroid 
morphology and function, not the etiology or its mechanisms. Be-
sides, diagnostic measures of sarcopenic obesity require different 
methods and instruments (including muscle mass, muscle strength, 
and physical performance) [4]. However, a universal consensus for 
a standard, objective, and unique parameter of sarcopenic obesity 
has not been reported yet, as far as we know. Thus, universally well-
known and scientifically accepted parameters such as BMI and 
waist circumference are commonly and favorably used in research 
 Reply 
 Cuneyd Anil a , Altug Kut b , Berna Atesagaoglu a , Asli Nar a , Neslihan Bascil Tutuncu a , Alptekin Gursoy a 
 Departments of  a Endocrinology and Metabolism, and  b Family Medicine, Baskent University Faculty of 
Medicine, Ankara, Turkey
Th is is an Open Access article licensed under the terms of the
Creative Commons Attribution-NonCommercial 3.0 Un-
ported license (CC BY-NC) (www.karger.com/OA-license), 
applicable to the online version of the article only. Distribu-
tion permitted for non-commercial purposes only.
 Cintosun/Naharci/Doruk
 
Med Princ Pract 2017;26:199–200
DOI: 10.1159/000452955
200
like ours [1, 5]. In a previous study by our group, which helped to 
form the basis for the present study, the study population also in-
cluded cases from early geriatric age (e.g., up to 75 years) [5]. An 
analysis we performed has revealed that the level of significance of 
the findings did not change when we excluded cases older than 65 
years. 
 Concerning the third issue, we think that omission of the effect 
of lifestyle factors in such intervention studies is only possible with 
inclusion of a control group. Otherwise, leaving the cases without 
a standard diet would probably affect the outcomes unpredictably. 
Lack of a control group has been expressed as a limitation of this 
unique work, which was preliminary. Our ongoing prospective 
study with a higher number of cases, longer follow-up period, and 
including a control group will probably address these concerns. In 
any case, as the authors have cited, the effects and the mechanisms 
of those effects of lifestyle changes on the thyroid gland have not 
been prospectively reported, and merely depend on epidemiologi-
cal and prevalence data. Lifestyle changes probably act mainly 
through weight loss, which decreases IR; some other factors may 
be operative. We may all appreciate that lifestyle factors probably 
did not predominate the effect of losing such weight and decreas-
ing IR in a time span of 6 months.
 References 
 1 Anil C, Kut A, Atesagaoglu B, et al: Metformin decreases thyroid volume 
and nodule size in subjects with insulin resistance: a preliminary study. 
Med Princ Pract 2016;  25: 233–236. 
 2 Jonklaas J, Bianco AC, Bauer AJ, et al; American Thyroid Association 
Task Force on Thyroid Hormone Replacemen: Guidelines for the treat-
ment of hypothyroidism: prepared by the American Thyroid Association 
task force on thyroid hormone replacement. Thyroid 2014; 24: 1670–
1751.  
 3 Brent GA, Weetman AP: Hypothyroidism and Thyroiditis; in Melmed 
S, Polonsky KS, et al. (eds): Williams Textbook of Endocrinology. Phila-
delphia, Elsevier, 2016, pp 416–448. 
 4 Lim S, Kim JH, Yoon JW, et al: Sarcopenic obesity: prevalence and as-
sociation with metabolic syndrome in the Korean Longitudinal Study on 
Health and Aging (KLoSHA). Diabetes Care 2010; 33: 1652–1654. 
 5 Ayturk S, Gursoy A, Kut A, et al: Metabolic syndrome and its compo-
nents are associated with increased thyroid volume and nodule preva-
lence in a mild-to-moderate iodine-deficient area. Eur J Endocrinol 
2009;161: 599–605. 
 Cuneyd Anil
 Department of Endocrinology and Metabolism
 Baskent University Faculty of Medicine
 5. Sokak No. 48, TR–06490 Bahcelievler, Ankara (Turkey)
 E-Mail cuneydanil   @   yahoo.com
 


Comment on "Metformin Decreases Thyroid Volume and Nodule Size in Subjects with Insulin Resistance: A Preliminary Study"

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