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Vitamin D and thyrotropin in type 2 diabetic patients
G Model DSX 673 No. of Pages 2
Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Diabetes & Metabolic Syndrome: Clinical Research & Reviews journal homepage: www.elsevier.com/locate/dsx
Case Report
Vitamin D and thyrotropin in type 2 diabetic patients José María Calvo-Romero* , José Manuel Ramiro-Lozano Internal Medicine Service, Hospital Ciudad de Coria, Coria (Cáceres), Spain
A R T I C L E I N F O
Article history: Available online xxx
Keywords: Thyrotropin Vitamin D Type 2 diabetes mellitus
A B S T R A C T
Vitamin D status and thyroid function may be related. Using our data from two previous studies in type 2 diabetic patients, we found slightly higher serum thyrotropin levels in patients with vitamin D deficiency (at the limit of statistical significance) and no effect of correction of vitamin D deficiency in serum thyrotropin levels. © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.
In recent years, there is great interest in extra-skeletal effects of vitamin D [1]. Recent evidences suggest that vitamin D may have a role in thyroid diseases [2]. To explore the relation between vitamin D and thyrotropin, we used our data of two previous studies in type 2 diabetic patients [3,4]. In our first study, we consecutively studied outpatients with type 2 diabetes mellitus attended in Internal Medicine offices of one hospital in Extremadura, Southwest Spain [3]. After patients with thyroid diseases were excluded, data of a total of 60 patients were re-analyzed. The mean age of patients was 72.5 8.8 years (range 53–92 years) and 29 (48.3%) were females. Forty patients (66.7%) had vitamin D deficiency (serum level of 25-hydroxyvitamin D (25(OH)D) lower than 20 ng/ml). Serum thyrotropin levels in patients with and without vitamin D deficiency are shown in Table 1. In our second study [4], type 2 diabetic patients with vitamn D deficiency were treated with 16,000 IU of calcifediol orally once a week during a minimum of eight weeks. After the treatment period with calcifediol, we determine the same parameters using the same analytical methods. We re-analyzed the data of 25 patients without thyroid diseases. The mean age of patients was 70.6 9.3 years (range 48–83 years) and 15 (60%) were females. After the treatment period, all patients achieved a serum level of 25(OH)D higher than 20 ng/ml and 22 (88%) higher than 30 ng/ml. No patient developed hypercalcemia after the treatment period. Table 2 shows the parameters studied before and after the treatment period. In both studies serum levels of thyrotropin and 25(OH)D were measured by chemiluminescence. Statistical
* Corresponding author at: Internal Medicine Service, Hospital Ciudad de Coria, Cervantes 75, 10800, Coria (Cáceres), Spain. E-mail addresses: [email protected] (J.M. Calvo-Romero), [email protected] (J.M. Ramiro-Lozano).
analysis was performed using Student's t-test. The study protocol was approved by the ethics committee in our hospital and informed consent was obtained from all patients. The serum level of 25(OH)D is the best method to determine vitamin D status [1]. A consensus has defined vitamin D deficiency as a serum level of 25(OH)D lower than 20 ng/ml [5]. We found slightly higher serum thyrotropin levels in patients with vitamin D deficiency, at the limit of statistical significance. A populationbased study in Thailand showed that high vitamin D status is associated with low circulating TSH only in younger individuals (aged 15–44 years) [6]. Our patients were considerably older with a mean age of almost 73 years. In our study we found significantly higher thyrotropin levels in females but not in males with vitamin D deficiency. On the contrary, a population-based health survey of 1424 Chinese adults, aged 41–78 years, has showed that high vitamin D status is associated with low circulating TSH levels in males but not in females [7]. Our patients were once again older. We cannot rule out that in other populations or with larger samples, we would have obtained other results. It is remarkable that all our patients were type 2 diabetic patients attended in Internal Medicine offices of a hospital, therefore with higher comorbidity than general population. Our data demonstrate an association of vitamin D deficiency with higher thyrotropin levels in females, but a causal relationship cannot be stablished because this is an observational study. All our patients were caucasians and ethnic differences in the thyrotropin levels may explain the conflicting results [7]. Moreover, it seems that estrogens have a complex relationship with thyrotropin secretion and may justify differences between both sexes and between pre-menopausal and menopausal females [7]. We found no effect of correction of vitamin D deficiency in serum thyrotropin levels in type 2 diabetic patients. In our knowledge, there are no studies investigating this subject. Some authors suggest that possible extra-skeletal benefits of vitamin D would require levels of 25(OH)D higher than
http://dx.doi.org/10.1016/j.dsx.2016.12.010 1871-4021/© 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: J.M. Calvo-Romero, J.M. Ramiro-Lozano, Vitamin D and thyrotropin in type 2 diabetic patients, Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.org/10.1016/j.dsx.2016.12.010
G Model DSX 673 No. of Pages 2
2
J.M. Calvo-Romero, J.M. Ramiro-Lozano / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2016) xxx–xxx
Table 1 Serum thyrotropin levels in patients with and without vitamin D deficiency.
Thyotropin (mU/l) all, n = 60 Thyrotropin (mU/l) females, n = 29 Thyrotropin (mU/l) males, n = 31
25(OH)D < 20 ng/ml
25(OH)D 20 ng/ml
P
2.87 1.48 3.27 1.59 2.21 0.99
2.15 1.34 1.91 0.39 2.34 1.49
0.06 0.001 NS
25(OH)D: 25-hydroxyvitamin D. NS: non significative.
References
Table 2 Changes of pre-treatment and post-treatment parameters.
Vitamin D (ng/ml) Calcium (mg/dl) Thyrotropin (mU/l)
Pre-treatment
Post-treatment
Difference
P
10.9 3.7 9.5 0.4 2.96 1.59
51.8 14.3 9.5 0.4 2.92 1.60
40.9 14.5 0 0.4 0.04 1.16
<0.001 NS NS
NS: non significative.
28–32 ng/ml [1], but in our study almost 90% of our patients reached these levels. Further studies are requied to clarify the relationship between vitamin D and thyrotropin in type 2 diabetic patients and in other populations. Conflict of interests The authors declare that there is no conflict of interests.
[1] Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc 2013;88:720–55. [2] Muscogiuri G, Tirabassi G, Bizzaro G, Orio F, Paschou SA, Vryonidou A, et al. Vitamin D and thyroid disease: to D or not to D? Eur J Clin Nutr 2015;69:291–6. [3] Calvo-Romero JM, Ramiro-Lozano JM. Vitamin D levels in patients with type 2 diabetes mellitus. J Investig Med 2015;63:921–3. [4] Calvo-Romero JM, Ramiro-Lozano JM. Metabolic effects of supplementation with vitamin D in type 2 diabetic patients with vitamin D deficiency. Diabetes Metab Syndr 2016;10:72–4. [5] Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911–30. [6] Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. High vitamin D status in younger individuals is associated with low circulating thyrotropin. Thyroid 2013;23:25–30. [7] Zhang Q, Wang Z, Sun M, Cao M, Zhu Z, Fu Q, et al. Association of high vitamin D status with low circulating thyroid-stimulating hormone independent of thyroid hormone levels in middle-aged and elderly males. Int J Endocrinol 2014;2014:631819.
Please cite this article in press as: J.M. Calvo-Romero, J.M. Ramiro-Lozano, Vitamin D and thyrotropin in type 2 diabetic patients, Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.org/10.1016/j.dsx.2016.12.010
Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Diabetes & Metabolic Syndrome: Clinical Research & Reviews journal homepage: www.elsevier.com/locate/dsx
Case Report
Vitamin D and thyrotropin in type 2 diabetic patients José María Calvo-Romero* , José Manuel Ramiro-Lozano Internal Medicine Service, Hospital Ciudad de Coria, Coria (Cáceres), Spain
A R T I C L E I N F O
Article history: Available online xxx
Keywords: Thyrotropin Vitamin D Type 2 diabetes mellitus
A B S T R A C T
Vitamin D status and thyroid function may be related. Using our data from two previous studies in type 2 diabetic patients, we found slightly higher serum thyrotropin levels in patients with vitamin D deficiency (at the limit of statistical significance) and no effect of correction of vitamin D deficiency in serum thyrotropin levels. © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.
In recent years, there is great interest in extra-skeletal effects of vitamin D [1]. Recent evidences suggest that vitamin D may have a role in thyroid diseases [2]. To explore the relation between vitamin D and thyrotropin, we used our data of two previous studies in type 2 diabetic patients [3,4]. In our first study, we consecutively studied outpatients with type 2 diabetes mellitus attended in Internal Medicine offices of one hospital in Extremadura, Southwest Spain [3]. After patients with thyroid diseases were excluded, data of a total of 60 patients were re-analyzed. The mean age of patients was 72.5 8.8 years (range 53–92 years) and 29 (48.3%) were females. Forty patients (66.7%) had vitamin D deficiency (serum level of 25-hydroxyvitamin D (25(OH)D) lower than 20 ng/ml). Serum thyrotropin levels in patients with and without vitamin D deficiency are shown in Table 1. In our second study [4], type 2 diabetic patients with vitamn D deficiency were treated with 16,000 IU of calcifediol orally once a week during a minimum of eight weeks. After the treatment period with calcifediol, we determine the same parameters using the same analytical methods. We re-analyzed the data of 25 patients without thyroid diseases. The mean age of patients was 70.6 9.3 years (range 48–83 years) and 15 (60%) were females. After the treatment period, all patients achieved a serum level of 25(OH)D higher than 20 ng/ml and 22 (88%) higher than 30 ng/ml. No patient developed hypercalcemia after the treatment period. Table 2 shows the parameters studied before and after the treatment period. In both studies serum levels of thyrotropin and 25(OH)D were measured by chemiluminescence. Statistical
* Corresponding author at: Internal Medicine Service, Hospital Ciudad de Coria, Cervantes 75, 10800, Coria (Cáceres), Spain. E-mail addresses: [email protected] (J.M. Calvo-Romero), [email protected] (J.M. Ramiro-Lozano).
analysis was performed using Student's t-test. The study protocol was approved by the ethics committee in our hospital and informed consent was obtained from all patients. The serum level of 25(OH)D is the best method to determine vitamin D status [1]. A consensus has defined vitamin D deficiency as a serum level of 25(OH)D lower than 20 ng/ml [5]. We found slightly higher serum thyrotropin levels in patients with vitamin D deficiency, at the limit of statistical significance. A populationbased study in Thailand showed that high vitamin D status is associated with low circulating TSH only in younger individuals (aged 15–44 years) [6]. Our patients were considerably older with a mean age of almost 73 years. In our study we found significantly higher thyrotropin levels in females but not in males with vitamin D deficiency. On the contrary, a population-based health survey of 1424 Chinese adults, aged 41–78 years, has showed that high vitamin D status is associated with low circulating TSH levels in males but not in females [7]. Our patients were once again older. We cannot rule out that in other populations or with larger samples, we would have obtained other results. It is remarkable that all our patients were type 2 diabetic patients attended in Internal Medicine offices of a hospital, therefore with higher comorbidity than general population. Our data demonstrate an association of vitamin D deficiency with higher thyrotropin levels in females, but a causal relationship cannot be stablished because this is an observational study. All our patients were caucasians and ethnic differences in the thyrotropin levels may explain the conflicting results [7]. Moreover, it seems that estrogens have a complex relationship with thyrotropin secretion and may justify differences between both sexes and between pre-menopausal and menopausal females [7]. We found no effect of correction of vitamin D deficiency in serum thyrotropin levels in type 2 diabetic patients. In our knowledge, there are no studies investigating this subject. Some authors suggest that possible extra-skeletal benefits of vitamin D would require levels of 25(OH)D higher than
http://dx.doi.org/10.1016/j.dsx.2016.12.010 1871-4021/© 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: J.M. Calvo-Romero, J.M. Ramiro-Lozano, Vitamin D and thyrotropin in type 2 diabetic patients, Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.org/10.1016/j.dsx.2016.12.010
G Model DSX 673 No. of Pages 2
2
J.M. Calvo-Romero, J.M. Ramiro-Lozano / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2016) xxx–xxx
Table 1 Serum thyrotropin levels in patients with and without vitamin D deficiency.
Thyotropin (mU/l) all, n = 60 Thyrotropin (mU/l) females, n = 29 Thyrotropin (mU/l) males, n = 31
25(OH)D < 20 ng/ml
25(OH)D 20 ng/ml
P
2.87 1.48 3.27 1.59 2.21 0.99
2.15 1.34 1.91 0.39 2.34 1.49
0.06 0.001 NS
25(OH)D: 25-hydroxyvitamin D. NS: non significative.
References
Table 2 Changes of pre-treatment and post-treatment parameters.
Vitamin D (ng/ml) Calcium (mg/dl) Thyrotropin (mU/l)
Pre-treatment
Post-treatment
Difference
P
10.9 3.7 9.5 0.4 2.96 1.59
51.8 14.3 9.5 0.4 2.92 1.60
40.9 14.5 0 0.4 0.04 1.16
<0.001 NS NS
NS: non significative.
28–32 ng/ml [1], but in our study almost 90% of our patients reached these levels. Further studies are requied to clarify the relationship between vitamin D and thyrotropin in type 2 diabetic patients and in other populations. Conflict of interests The authors declare that there is no conflict of interests.
[1] Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc 2013;88:720–55. [2] Muscogiuri G, Tirabassi G, Bizzaro G, Orio F, Paschou SA, Vryonidou A, et al. Vitamin D and thyroid disease: to D or not to D? Eur J Clin Nutr 2015;69:291–6. [3] Calvo-Romero JM, Ramiro-Lozano JM. Vitamin D levels in patients with type 2 diabetes mellitus. J Investig Med 2015;63:921–3. [4] Calvo-Romero JM, Ramiro-Lozano JM. Metabolic effects of supplementation with vitamin D in type 2 diabetic patients with vitamin D deficiency. Diabetes Metab Syndr 2016;10:72–4. [5] Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911–30. [6] Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. High vitamin D status in younger individuals is associated with low circulating thyrotropin. Thyroid 2013;23:25–30. [7] Zhang Q, Wang Z, Sun M, Cao M, Zhu Z, Fu Q, et al. Association of high vitamin D status with low circulating thyroid-stimulating hormone independent of thyroid hormone levels in middle-aged and elderly males. Int J Endocrinol 2014;2014:631819.
Please cite this article in press as: J.M. Calvo-Romero, J.M. Ramiro-Lozano, Vitamin D and thyrotropin in type 2 diabetic patients, Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.org/10.1016/j.dsx.2016.12.010