Compensated hypothyroidism and statin administration: the symptoms of muscle damage and muscle metabolism disorders

BACKGROUND. There is no unequivocal opinion regarding the safety of statin in patients with hypothyroidism. However, based on some new data, it can be assumed that hypothyroidism, even in a stage of compensation, may cause muscle damage in patients receiving statins. As part of this study, this hypothesis was tested, and was confirmed.

AIMS: To study the possibility of muscle damage and the nature of muscle metabolism in patients with compensated hypothyroidism who takes statin.

MATERIALS AND METHODS. The study is transverse and observational with the inclusion of 120 women, subdivided on three groups (n=40). The main group of patients with hypothyroidism who took statins (group 1) was compared with two control groups, including those who took statins without hypothyroidism (group 2), and who did not take statins with hypothyroidism (group 3).

RESULTS. Patients taking statins and have compensated hypothyroidism are more likely to develop complaints of muscle pain, which are often associated with the elevation of muscle lesion markers, as well as the presence of the C allele in the SLCO1B1*5 gene (c.521T>C). In patients with compensated hypothyroidism, relative frequency of occurance of muscle pain syndrome associated with CPK elevation increases with TSH levels above 2.86 mU/L. Compensated hypothyroidism increases the possibility of development of SPM-ATP by 2.7 times.

CONCLUSIONS. Compensated hypothyroidism is not a contraindication for statin therapy. However, the presence of even compensated hypothyroidism in patients taking statins increases the possibility of the development of muscle symptoms associated with taking statins, and requires additional monitoring of the clinical and biochemical parameters of muscle metabolism (especially the level of CPK).

hypothyroidism, statins, muscle damadge

1. Дедов И.И., Семичева Т.В., Петеркова В.А. Половое развитие детей: норма и патология. М.: Колор Ит Студио; 2002. Dedov II, Semicheva TV, Peterkova VA. Polovoe razvitie detei: nor¬ma i patologia. M.: Color It Studio; 2002. (In Russ.).

2. Шабалов Н.П., Лисс В.Л., Нагорная И.И. Диагностика и ле¬чение эндокринных заболеваний у детей и подростков. Под ред. Шабалова Н.П. М.: МЕДпресс; 2002. Shabalov NV, Liss VL, Nagornaya II. Diagnostica i lechenie en¬dokrinnuch zabolevanyi u detei i podrostkov. Ed by Shabalov N.V. M.: MEDpress; 2002. (In Russ.).

3. Boehm U, Bouloux PM, Dattani MT, et al. Expert consensus doc¬ument: European Consensus Statement on congenital hypogonad¬otropic hypogonadism-pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11(9):547-564. doi: https://doi.org/10.1038/nrendo.2015.112

4. Harrington J, Palmert MR. Clinical review: distinguishing consti¬tutional delay of growth and puberty from isolated hypogonado¬tropichypogonadism: critical appraisal of available diagnostic tests. J Clin Endocrinol Metab. 2012;97(9):3056-3067. doi: https://doi.org/10.1210/jc.2012-1598

5. Varimo T, Miettinen PJ, Känsäkoski J, et al. Congenital hypogo¬nadotropic hypogonadism, functional hypogonadotropism or con¬stitutional delay of growth and puberty? An analysis of a large pa¬tient series from a single tertiary center. Hum Reprod. 2017;32(1): 147-153. doi: https://doi.org/10.1093/humrep/dew294

6. Coutant R, Biette-Demeneix E, Bouvattier C, et al. Baseline inhib¬in B and anti-Mullerian hormone measurements for diagnosis of hypogonadotropic hypogonadism (HH) in boys with delayed pu¬berty. J Clin Endocrinol Metab. 2010;95(12):5225-5232. doi: https://doi.org/10.1210/jc.2010-1535

7. Rohayem J, Nieschlag E, Kliesch S, Zitzmann M. Inhibin B, AMH, but not INSL3, IGF1 or DHEAS support differentiation between constitutional delay of growth and puberty and hypogonadotropic hypogonadism. Andrology. 2015;3(5):882-887. doi: https://doi.org/10.1111/andr.12088

8. Андрианова Е.А., Безлепкина О.Б., Васюкова О.В. и др. Фе¬деральные клинические рекомендации (протоколы) по ведению детей с эндокринными заболеваниями. Под ред. Дедова И.И., Петерковой В.А. М.: Практика; 2014. Andrianova EA, Bezlepkina OB, Vasyukova OV i dr. Federal’nye klinicheskie rekomendatsii (protokoly) po vedeniy detei s endokrinn¬umi zabolevaniiami. Ed by Dedov I.I., Peterkova V.A. M.: Prakti¬ka; 2014. (In Russ.).

9. Binder G, Schweizer R, Blumenstock G, Braun R. Inhibin B plus LH vs GnRH agonist test for distinguish constitutional delay of growth and puberty from isolated hypogonadotropic hypogonad¬ism in boys. Clin Endocrinol. 2015;82(1):100-105. doi: https://doi.org/10.1111/cen.12613

10. Дедов И.И., Тюльпаков А.Н., Петеркова В.А. Соматотропная недостаточность. М.: ИндексПринт; 1998. Dedov II, Tulpakov AN, Peterkova VA. Somatotropnaia nedostato¬chnost’. M.: IndexPrint; 1998. (In Russ.).

11. Sun QH, Zheng Y, Zhang XL, Mu YM. Role of gonadotropin-re¬leasing hormone stimulation test in diagnosing gonadotropin deficiency in both males and females with delayed puberty. Chin Med J. 2015;128(18):2439-2443. doi: https://doi.org/10.4103/0366-6999.164926

12. Kauschansky A, Dickerman Z, Phillip M, et al. Use of GnRH ag¬onist and human chorionic gonadotropin tests for differentiating constitutional delayed puberty from gonadotropin deficiency in boys. Clin Endocrinol (Oxf). 2002;56(5):603-607. doi: https://doi.org/10.1046/j.1365-2265.2002.01520.x

13. Martin MM, Martin AL. Constitutional delayed puberty in males and hypogonadotropic hypogonadism: a reliable and cost-effective approach to differential diagnosis. J Pediatr Endocrinol Metab. 2005;18(9):909-916. doi: https://doi.org/10.1515/jpem.2005.18.9.909

14. Segal TY, Mehta A, Anazodo A, et al. Role of gonadotropin-re¬leasing hormone and human chorionic gonadotropin stimulation tests in differentiating patients with hypogonadotropic hypogonad¬ism from those with constitutional delay of growth and puberty. J Clin Endocrinol Metab. 2009;94(3):780-785. doi: https://doi.org/10.1210/jc.2008-0302

15. Grinspon RP, Ropelato MG, Gottlieb S, et al. Basal follicle-stim¬ulating hormone and peak gonadotropin levels after gonadotropin-releasing hormone infusion show high diagnostic accuracy in boys with suspicion of hypogonadotropic hypogonadism. J Clin Endo¬crinol Metab. 2010;95(6):2811-2818. doi: https://doi.org/10.1210/jc.2009-2732

16. Sequera AM, Fideleff HL, Boquete HR, et al. Basal ultrasensitive LH assay: a useful tool in the early diagnosis of male pubertal de¬lay. J Pediatr Endocrinol Metab. 2002;15(5):589-596. doi: https://doi.org/10.1515/jpem.2002.15.5.589

17. Yazici M, Sahin M, Bolu EJ, et al. Prediction of testosterone re¬sponse to human chorionic gonadotropin in isolated hypogonadotropic hypogonadism patients. J Natl Med Assoc. 2009;101(1):71-76. doi: https://doi.org/10.1016/s0027-9684(15)30814-2

18. Seminara SB, Hayes FJ, Crowley WF. Gonadotropin-releasing hormone deficiency in the human (Idiopathic Hypogonadotropic Hypogonadism and Kallmann’s Syndrome): pathophysiological and genetic considerations. Endocr Rev. 1998;19(5):521-539. doi: https://doi.org/10.1210/edrv.19.5.0344

19. Degros V, Cortet-Rudelli C, Soudan B, et al. The human chorion¬ic gonadotropin test is more powerful than the gonadotropin-re¬leasing hormone agonist test to discriminate male isolated hypo¬gonadotropic hypogonadism from constitutional delayed puberty. Eur J Endocrinol. 2003;149(1):23-29. doi: https://doi.org/10.1530/eje.0.1490023

20. Odink RJ, Schoemaker J, Schoute E, et al. Predictive value of se¬rum follicle-stimulating hormone levels in the differentiation be¬tween hypogonadotropic hypogonadism and constitutional delay of puberty. Hormone Research in Paediatrics. 1998;49:279-287. Horm Res. 1998;49(6):279-287. doi: https://doi.org/10.1159/000023187

21. Sukumar SP, Bhansali A, Sachdeva N, et al. Diagnostic utility of testosterone priming prior to dynamic tests to differentiate constitutional delay in puberty from isolated hypogonadotropic hypogo¬nadism. Clin Endocrinol (Oxf). 2017;86(5):717-724. doi: https://doi.org/10.1111/cen.13321