ETD2-2019
En personas con hipercolesterolemia e hipotiroidismo subclínico el Ministerio de Salud SUGIERE no tratar con levotiroxina
El problema ha sido definido como prioritario en el marco de las Garantías Explícitas en Salud (GES), régimen integral de salud que prioriza un grupo de patologías o problemas de salud, garantizando el acceso a tratamiento oportuno y de calidad.
A continuación se presenta la “Tabla de la evidencia a la decisión” con el resumen de los juicios, la evidencia de investigación evaluada, consideraciones adicionales y comentarios planteados por el panel.
| No | Probablemente no | Probablemente sí | Sí | Varía | No lo sé |
|---|
El problema o condición de salud abordado en la pregunta ha sido definido como prioritario en el marco de las Garantías Explícitas en Salud (GES), régimen integral de salud que prioriza un grupo de patologías o problemas de salud, garantizando el acceso a tratamiento oportuno y de calidad. Además, particularmente, la pregunta «En personas con hipercolesterolemia e hipotiroidismo subclínico ¿Se debe usar levotiroxina en comparación a no usar?» fue priorizada por un panel de expertos en la materia. Ver detalle en Informe de Priorización de Preguntas de Práctica Clínica.
| Trivial | Pequeño | Moderado | Grande | Varía | No lo sé |
|---|
Triviales: Tomando en cuenta la evidencia identificada, la experiencia clínica y de las personas con el problema de salud, el equipo elaborador de la guía estimó que la magnitud de los efectos deseables de «usar levotiroxina» en comparación a «no usar» son triviales o no relevantes para las personas.
Evidencia de investigación
LEVOTIROXINA PARA PERSONAS CON HIPERCOLESTEROLEMIA E HIPOTIROIDISMO SUBCLÍNICO
Pacientes Personas con hipotiroidismo subclínico e hipercolesterolemia.
Intervención Usar levotiroxina.
Comparación No usar.
|
Desenlaces |
Efecto relativo (IC 95%) — Pacientes/ estudios |
Efecto absoluto estimado* |
Certeza de la evidencia (GRADE) |
Mensajes clave en términos sencillos |
||
|
SIN |
CON |
Diferencia (IC 95%) |
||||
|
Mortalidad (seguimiento a 12 meses) |
RR 2,01 — 737 pacientes/ 1 ensayo [79] |
14 |
27 por 1000 |
Diferencia: 13 más (4 menos a 65 más) |
Muy baja |
El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría aumentar la mortalidad. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
|
Eventos cardiovasculares** |
RR 0,90 — 737 pacientes/ 1 ensayo [79] |
54 |
49 |
Diferencia: |
Muy baja |
El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en el riesgo de desarrollar eventos cardiovasculares. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
|
Niveles de LDL-C*** (seguimiento entre 5 y 12 meses) |
— 320 pacientes/ 6 ensayos [19,20,24,30,32,34] |
DME****: 0,31 menos |
Muy baja |
El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en los niveles de LDL-C. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
||
|
Calidad de vida (seguimiento 3 a 12 meses) |
— |
DME****: 0,31 menos |
Muy baja |
El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en la calidad de vida. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
||
IC 95%: Intervalo de confianza del 95%. || RR: Riesgo relativo. || DME: Diferencia de media estandarizada.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo SIN levotiroxina está basado en el riesgo del grupo control en los estudios. El riesgo CON levotiroxina (y su intervalo de confianza) está calculado a partir del efecto relativo (y su intervalo de confianza).
**Incluye eventos cardiovasculares fatales y no fatales, tales como infarto agudo al miocardio, accidente cerebrovascular, amputaciones, revascularización por aterosclerosis vascular, entre otros.
***Evaluado con LDL-C medido en mmol/l y mg/dl.
****La diferencia media estandarizada se utiliza cuando el desenlace ha sido medido en diferentes escalas, siendo difícil su interpretación clínica. Comúnmente se acepta que valores cercanos a 0,2 tendrían poca relevancia clínica, valores de 0,5 tendrían relevancia moderada (se reconoce clínicamente) y valores superiores a 0,8 tendrían relevancia alta.
1 Se disminuyó dos niveles de certeza de la evidencia por tratarse de evidencia indirecta, ya que la evidencia utilizada proviene de un estudio cuyos participantes eran adultos de 74 años de edad promedio con hipotiroidismo subclínico, sin especificar perfil lipídico.
2 Se disminuyó un nivel de certeza de la evidencia por
imprecisión, debido a que a cada extremo del intervalo de confianza se tomarían decisiones diferentes.
3 Se disminuyó un nivel de certeza de la evidencia por inconsistencia, dado que se observó heterogeneidad significativa (I2=71%).
4 Se disminuyó un nivel de certeza de la evidencia por riesgo de sesgo, debido a que en la mayoría de los ensayos no estaba clara la generación ni el ocultamiento de la secuencia de aleatorización.
Referencias
2. Aziz M, Kandimalla Y, Machavarapu A, Saxena A, Das S, Younus A, Nguyen M, Malik R, Anugula D, Latif MA, Humayun C, Khan IM, Adus A, Rasool A, Veledar E, Nasir K. Effect of Thyroxin Treatment on Carotid Intima-Media Thickness (CIMT) Reduction in Patients with Subclinical Hypothyroidism (SCH): a Meta-Analysis of Clinical Trials. Journal of atherosclerosis and thrombosis. 2017;24(7):643-659.
3. Danese MD, Ladenson PW, Meinert CL, Powe NR. Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. The Journal of clinical endocrinology and metabolism. 2000;85(9):2993-3001.
4. Feller M, Snel M, Moutzouri E, Bauer DC, de Montmollin M, Aujesky D, Ford I, Gussekloo J, Kearney PM, Mooijaart S, Quinn T, Stott D, Westendorp R, Rodondi N, Dekkers OM. Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis. JAMA. 2018;320(13):1349-1359.
5. He W, Li S, Zhang JA, Zhang J, Mu K, Li XM. Effect of Levothyroxine on Blood Pressure in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis. Frontiers in endocrinology. 2018;9(AUG):454.
6. Helfand M. Screening for Thyroid Disease. U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews. 2004;
7. Li X, Meng Z, Jia Q, Ren X. Effect of L-thyroxine treatment versus a placebo on serum lipid levels in patients with sub-clinical hypothyroidism. Biomedical reports. 2016;5(4):443-449.
8. Li X, Wang Y, Guan Q, Zhao J, Gao L. The lipid-lowering effect of levothyroxine in patients with subclinical hypothyroidism: a systematic review and meta-analysis of randomized controlled trials. Clinical endocrinology. 2017;87(1):1-9.
9. Loh HH, Lim LL, Yee A, Loh HS. Association between subclinical hypothyroidism and depression: an updated systematic review and meta-analysis. BMC psychiatry. 2019;19(1):12.
10. Rugge B, Balshem H, Sehgal R, Relevo R, Gorman P, Helfand M. Screening and Treatment of Subclinical Hypothyroidism or Hyperthyroidism. AHRQ Comparative Effectiveness Reviews; Rockville (MD): Agency for Healthcare Research and Quality (US); Report No.: 11(12)-EHC033-EF. 2011;
11. Rugge JB, Bougatsos C, Chou R. Screening and treatment of thyroid dysfunction: an evidence review for the u.s. Preventive services task force. Annals of internal medicine. 2015;162(1):35-45.
12. Rugge JB, Bougatsos C, Chou R. Screening for and Treatment of Thyroid Dysfunction: An Evidence Review for the U.S. Preventive Services Task Force. U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews. 2014;
13. Tanis BC, Westendorp GJ, Smelt HM. Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies. Clinical endocrinology. 1996;44(6):643-9.
14. van Harten AC, Leue C, Verhey FR. Should depressive symptoms in patients with subclinical hypothyroidism be treated with thyroid hormone?. Tijdschrift voor psychiatrie. 2008;50(8):539-43.
15. Villar HC, Saconato H, Valente O, Atallah AN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane database of systematic reviews (Online). 2007;(3):CD003419.
16. Zhao T, Chen BM, Zhao XM, Shan ZY. Subclinical hypothyroidism and depression: a meta-analysis. Translational psychiatry. 2018;8(1):239.
17. Zhao T., Chen B., Zhou Y., Wang X., Zhang Y., Wang H., Shan Z.. Effect of levothyroxine on the progression of carotid intima-media thickness in subclinical hypothyroidism patients: A meta-analysis. BMJ Open. 2017;7(10):e016053.
18. 5th Tromsø study. Jorde R, Waterloo K, Storhaug H, Nyrnes A, Sundsfjord J, Jenssen TG. Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment. The Journal of clinical endocrinology and metabolism. 2006;91(1):145-53.
19. Cabral MD, Teixeira P, Soares D, Leite S, Salles E, Waisman M. Effects of thyroxine replacement on endothelial function and carotid artery intima-media thickness in female patients with mild subclinical hypothyroidism. Clinics (São Paulo, Brazil). 2011;66(8):1321-8.
20. Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. The Journal of clinical endocrinology and metabolism. 2002;87(4):1533-8.
21. Christ-Crain M, Morgenthaler NG, Meier C, Müller C, Nussbaumer C, Bergmann A, Staub JJ, Müller B. Pro-A-type and N-terminal pro-B-type natriuretic peptides in different thyroid function states. Swiss medical weekly. 2005;135(37-38):549-54.
22. Cooper DS, Halpern R, Wood LC, Levin AA, Ridgway EC. L-Thyroxine therapy in subclinical hypothyroidism. A double-blind, placebo-controlled trial. Annals of internal medicine. 1984;101(1):18-24.
23. Duman D, Demirtunc R, Sahin S, Esertas K. The effects of simvastatin and levothyroxine on intima-media thickness of the carotid artery in female normolipemic patients with subclinical hypothyroidism: a prospective, randomized-controlled study. Journal of cardiovascular medicine (Hagerstown, Md.). 2007;8(12):1007-11.
24. Duman D, Sahin S, Esertas K, Demirtunc R. Simvastatin improves endothelial function in patents with subclinical hypothyroidism. Heart and vessels. 2007;22(2):88-93.
25. Jaeschke R, Guyatt G, Gerstein H, Patterson C, Molloy W, Cook D, Harper S, Griffith L, Carbotte R. Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?. Journal of general internal medicine. 1996;11(12):744-9.
26. Kong WM, Sheikh MH, Lumb PJ, Naoumova RP, Freedman DB, Crook M, Doré CJ, Finer N, Naoumova P. A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. The American journal of medicine. 2002;112(5):348-54.
27. Martins RM, Fonseca RH, Duarte MM, Reuters VS, Ferreira MM, Almeida C, Buescu A, Teixeira Pde F, Vaisman M. Impact of subclinical hypothyroidism treatment in systolic and diastolic cardiac function. Arquivos brasileiros de endocrinologia e metabologia. 2011;55(7):460-7.
28. Meier C, Staub JJ, Roth CB, Guglielmetti M, Kunz M, Miserez AR, Drewe J, Huber P, Herzog R, Müller B. TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study). The Journal of clinical endocrinology and metabolism. 2001;86(10):4860-6.
29. Mikhail GS, Alshammari SM, Alenezi MY, Mansour M, Khalil NA. Increased atherogenic low-density lipoprotein cholesterol in untreated subclinical hypothyroidism. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2008;14(5):570-5.
30. Monzani F, Caraccio N, Kozàkowà M, Dardano A, Vittone F, Virdis A, Taddei S, Palombo C, Ferrannini E. Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study. The Journal of clinical endocrinology and metabolism. 2004;89(5):2099-106.
31. Monzani F, Di Bello V, Caraccio N, Bertini A, Giorgi D, Giusti C, Ferrannini E. Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. The Journal of clinical endocrinology and metabolism. 2001;86(3):1110-5.
32. Nagasaki T, Inaba M, Yamada S, Shirakawa K, Nagata Y, Kumeda Y, Hiura Y, Tahara H, Ishimura E, Nishizawa Y. Decrease of brachial-ankle pulse wave velocity in female subclinical hypothyroid patients during normalization of thyroid function: a double-blind, placebo-controlled study. European journal of endocrinology / European Federation of Endocrine Societies. 2009;160(3):409-15.
33. Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. The Journal of clinical endocrinology and metabolism. 2007;92(5):1715-23.
34. Teixeira. Teixeira PF, Reuters VS, Ferreira MM, Almeida CP, Reis FA, Melo BA, Buescu A, Costa AJ, Vaisman M. Treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a placebo-controlled double-blind clinical trial. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 2008;40(1):50-5.
35. Zhao M, Liu L, Wang F, Yuan Z, Zhang X, Xu C, Song Y, Guan Q, Gao L, Shan Z, Zhang H, Zhao J. A Worthy Finding: Decrease in Total Cholesterol and Low-Density Lipoprotein Cholesterol in Treated Mild Subclinical Hypothyroidism. Thyroid : official journal of the American Thyroid Association. 2016;26(8):1019-29.
36. Pollock MA, Sturrock A, Marshall K, Davidson KM, Kelly CJ, McMahon AD, McLaren EH. Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial. BMJ (Clinical research ed.). 2001;323(7318):891-5.
37. Nyström E, Caidahl K, Fager G, Wikkelsö C, Lundberg PA, Lindstedt G. A double-blind cross-over 12-month study of L-thyroxine treatment of women with ‘subclinical’ hypothyroidism. Clinical endocrinology. 1988;29(1):63-75.
38. Adamarczuk-Janczyszyn M, Zdrojowy-Wełna A, Rogala N, Zatońska K, Bednarek-Tupikowska G. Evaluation of Selected Atherosclerosis Risk Factors in Women with Subclinical Hypothyroidism Treated with L-Thyroxine. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2016;25(3):457-63.
39. Adrees M, Gibney J, El-Saeity N, Boran G. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism. Clinical endocrinology. 2009;71(2):298-303.
40. Akkoca, Ayşe Neslin, Özdemir, Zeynep Tuğba, Özler, Gül Soylu, Karabulut, Laika. The evaluation of carotid intima thickness in clinical and subclinical hypothyroidism and effects of thyroid hormone treatment. American Journal of Clinical and Experimental Medicine. 2014;2:59.
41. Anagnostis P, Efstathiadou ZA, Slavakis A, Selalmatzidou D, Poulasouchidou M, Katergari S, Karathanasi E, Dogramatzi F, Kita M. The effect of L-thyroxine substitution on lipid profile, glucose homeostasis, inflammation and coagulation in patients with subclinical hypothyroidism. International journal of clinical practice. 2014;68(7):857-63.
42. Arem R, Escalante DA, Arem N, Morrisett JD, Patsch W. Effect of L-thyroxine therapy on lipoprotein fractions in overt and subclinical hypothyroidism, with special reference to lipoprotein(a). Metabolism: clinical and experimental. 1995;44(12):1559-63.
43. Arem R, Patsch W. Lipoprotein and apolipoprotein levels in subclinical hypothyroidism. Effect of levothyroxine therapy. Archives of internal medicine. 1990;150(10):2097-100.
44. Baldini IM, Vita A, Mauri MC, Amodei V, Carrisi M, Bravin S, Cantalamessa L. Psychopathological and cognitive features in subclinical hypothyroidism. Progress in neuro-psychopharmacology & biological psychiatry. 1997;21(6):925-35.
45. Bantle JP, Oppenheimer JH, Schwartz HL, Hunninghake DB, Probstfield JL, Hanson RF. TSH response to TRH in euthyroid, hypercholesterolemic patients treated with graded doses of dextrothyroxine. Metabolism: clinical and experimental. 1981;30(1):63-6.
46. Bell GM, Todd WT, Forfar JC, Martyn C, Wathen CG, Gow S, Riemersma R, Toft AD. End-organ responses to thyroxine therapy in subclinical hypothyroidism. Clinical endocrinology. 1985;22(1):83-9.
47. Bogner U, Arntz HR, Peters H, Schleusener H. Subclinical hypothyroidism and hyperlipoproteinaemia: indiscriminate L-thyroxine treatment not justified. Acta endocrinologica. 1993;128(3):202-6.
48. Caron P, Calazel C, Parra HJ, Hoff M, Louvet JP. Decreased HDL cholesterol in subclinical hypothyroidism: the effect of L-thyroxine therapy. Clinical endocrinology. 1990;33(4):519-23.
49. Cerbone M, Capalbo D, Wasniewska M, Alfano S, Mattace Raso G, Oliviero U, Cittadini A, De Luca F, Salerno M. Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism. European journal of endocrinology. 2016;175(1):11-9.
50. Christ-Crain M, Meier C, Guglielmetti M, Huber PR, Riesen W, Staub JJ, Müller B. Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial. Atherosclerosis. 2003;166(2):379-86.
51. Elder J, McLelland A, O’Reilly DS, Packard CJ, Series JJ, Shepherd J. The relationship between serum cholesterol and serum thyrotropin, thyroxine and tri-iodothyronine concentrations in suspected hypothyroidism. Annals of clinical biochemistry. 1990;27 ( Pt 2):110-3.
52. Franklyn JA, Daykin J, Betteridge J, Hughes EA, Holder R, Jones SR, Sheppard MC. Thyroxine replacement therapy and circulating lipid concentrations. Clinical endocrinology. 1993;38(5):453-9.
53. Guang-Da X, Hui-Ling S, Zhi-Song C, Lin-Shuang Z. Alteration of plasma concentrations of OPG before and after levothyroxine replacement therapy in hypothyroid patients. Journal of endocrinological investigation. 2005;28(11):965-72.
54. Gulseren S, Gulseren L, Hekimsoy Z, Cetinay P, Ozen C, Tokatlioglu B. Depression, anxiety, health-related quality of life, and disability in patients with overt and subclinical thyroid dysfunction. Archives of medical research. 2006;37(1):133-9.
55. Johnston J, McLelland A, O’Reilly DS. The relationship between serum cholesterol and serum thyroid hormones in male patients with suspected hypothyroidism. Annals of clinical biochemistry. 1993;30 ( Pt 3):256-9.
56. Kebapcilar L, Comlekci A, Tuncel P, Solak A, Secil M, Gencel O, Sahin M, Sari I, Yesil S. Effect of levothyroxine replacement therapy on paraoxonase-1 and carotid intima-media thickness in subclinical hypothyroidism. Medical science monitor : international medical journal of experimental and clinical research. 2010;16(1):CR41-7.
57. Kim SK, Kim SH, Park KS, Park SW, Cho YW. Regression of the increased common carotid artery-intima media thickness in subclinical hypothyroidism after thyroid hormone replacement. Endocrine journal. 2009;56(6):753-8.
58. Kowalska I, Borawski J, Nikołajuk A, Budlewski T, Otziomek E, Górska M, Strączkowski M. Insulin sensitivity, plasma adiponectin and sICAM-1 concentrations in patients with subclinical hypothyroidism: response to levothyroxine therapy. Endocrine. 2011;40(1):95-101.
59. Krysiak R, Szkróbka W, Okopień B. The effect of l-thyroxine treatment on sexual function and depressive symptoms in men with autoimmune hypothyroidism. Pharmacological reports : PR. 2017;69(3):432-437.
60. Lithell H, Boberg J, Hellsing K, Ljunghall S, Lundqvist G, Vessby B, Wide L. Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein-lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy. European journal of clinical investigation. 1981;11(1):3-10.
61. Miura S, Iitaka M, Yoshimura H, Kitahama S, Fukasawa N, Kawakami Y, Sakurai S, Urabe M, Sakatsume Y, Ito K. Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy. Internal medicine (Tokyo, Japan). 1994;33(7):413-7.
62. Nagasaki T, Inaba M, Yamada S, Kumeda Y, Hiura Y, Nishizawa Y. Changes in brachial-ankle pulse wave velocity in subclinical hypothyroidism during normalization of thyroid function. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2007;61(8):482-7.
63. Niknam N, Khalili N, Khosravi E, Nourbakhsh M. Endothelial dysfunction in patients with subclinical hypothyroidism and the effects of treatment with levothyroxine. Advanced biomedical research. 2016;5:38.
64. Nilsson G, Nordlander S, Levin K. Studies on subclinical hypothyroidism with special reference to the serum lipid pattern. Acta medica Scandinavica. 1976;200(1-2):63-67.
65. Pandrc MS, Ristić A, Kostovski V, Stanković M, Antić V, Milin-Lazović J, Ćirić J. The Effect of Early Substitution of Subclinical Hypothyroidism on Biochemical Blood Parameters and the Quality of Life. Journal of medical biochemistry. 2017;36(2):127-136.
66. Paoli M, Bellabarba G, Velazquez E, Mendoza S, Molina C, Wang P, Glueck CJ. Sex steroids, lipids, and lipoprotein cholesterols in women with subclinical and overt hypothyroidism before and after L-thyroxine therapy. Clinica chimica acta; international journal of clinical chemistry. 1998;275(1):81-91.
67. Powell JT, Wiseman SA, Carter G, Alaghband Zadeh J, Fowler PB, Greenhalgh RM. Can thyroxine halt the progression of peripheral arterial disease?. European journal of vascular surgery. 1989;3(1):85-7.
68. Razvi S, Weaver JU, Butler TJ, Pearce SH. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Archives of internal medicine. 2012;172(10):811-7.
69. Ridgway EC, Cooper DS, Walker H, Rodbard D, Maloof F. Peripheral responses to thyroid hormone before and after L-thyroxine therapy in patients with subclinical hypothyroidism. The Journal of clinical endocrinology and metabolism. 1981;53(6):1238-42.
70. Stratigou T, Dalamaga M, Antonakos G, Marinou I, Vogiatzakis E, Christodoulatos GS, Karampela I, Papavassiliou AG. Hyperirisinemia is independently associated with subclinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors. Endocrine. 2018;61(1):83-93.
71. Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, Salvetti A, Ferrannini E, Monzani F. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. The Journal of clinical endocrinology and metabolism. 2003;88(8):3731-7.
72. Traub-Weidinger T, Graf S, Beheshti M, Ofluoglu S, Zettinig G, Khorsand A, Nekolla SG, Kletter K, Dudczak R, Pirich C. Coronary vasoreactivity in subjects with thyroid autoimmunity and subclinical hypothyroidism before and after supplementation with thyroxine. Thyroid : official journal of the American Thyroid Association. 2012;22(3):245-51.
73. Unal O, Erturk E, Ozkan H, Kiyici S, Guclu M, Ersoy C, Yener F, Imamoglu S. Effect of levothyroxine treatment on QT dispersion in patients with subclinical hypothyroidism. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2007;13(7):711-5.
74. Unsal, Ilknur Ozturk, Topaloglu, Oya, Cakir, Evrim, Bozkurt, Nujen Colak, Karbek, Basak, Gungunes, Askin, Arslan, Muyesser Sayki, Akkaymak, Esra Tutal, Ucan, Bekir, Demirci, Taner. Effect of L-thyroxin therapy on thyroid volume and carotid artery lntima-media thickness in the patients with subclinical hypothyroidism. Journal of Medical Disorders. 2014;2(1):1.
75. Vishnoi G, Chakraborty B, Garda H, Gowda SH, Goswami B. Low mood and response to Levothyroxine treatment in Indian patients with subclinical hypothyroidism. Asian journal of psychiatry. 2014;8:89-93.
76. Liu XL, He S, Zhang SF, Wang J, Sun XF, Gong CM, Zheng SJ, Zhou JC, Xu J. Alteration of lipid profile in subclinical hypothyroidism: a meta-analysis. Medical science monitor : international medical journal of experimental and clinical research. 2014;20((Liu X.-L.; He S.; Gong C.-M.; Zheng S.-J.; Zhou J.-C.) Molecular Biology Lab, Shenzhen Center for Chronic Disease Control, Shenzhen, China):1432-41.
77. Tagami T, Kimura H, Ohtani S, Tanaka T, Tanaka T, Hata S, Saito M, Miyazaki Y, Araki R, Tanaka M, Yonezawa K, Sawamura M, Ise T, Ogo A, Shimbo T, Shimatsu A, Naruse M; PHPH study group. Multi-center study on the prevalence of hypothyroidism in patients with hypercholesterolemia. Endocr J. 2011;58(6):449-57.
78. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000 Feb 28;160(4):526-34.
79. 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. Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. The New England journal of medicine. 2017;376(26):2534-2544.
80. Zhao M, Liu L, Wang F, Yuan Z, Zhang X, Xu C, Song Y, Guan Q, Gao L, Shan Z, Zhang H, Zhao J. A Worthy Finding: Decrease in Total Cholesterol and Low-Density Lipoprotein Cholesterol in Treated Mild Subclinical Hypothyroidism. Thyroid. 2016 Aug;26(8):1019-29.
81. Blum MR, Gencer B, Adam L, Feller M, Collet TH, da Costa BR, Moutzouri E, Dopheide J, Depairon M, Sykiotis GP, Kearney P, Gussekloo J, Westendorp R, Stott DJ, Bauer DC, Rodondi N. Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism: A Randomized Trial. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2988-2997.
82. Pergialiotis V, Konstantopoulos P, Prodromidou A, Florou V, Papantoniou N, Perrea DN. MANAGEMENT OF ENDOCRINE DISEASE: The impact of subclinical hypothyroidism on anthropometric characteristics, lipid, glucose and hormonal profile of PCOS patients: a systematic review and meta-analysis. Eur J Endocrinol. 2017 Mar;176(3):R159-R166.
Búsqueda y Síntesis de Evidencia
Búsqueda y síntesis de evidencia de efectos deseables e indeseables
| Grande | Moderado | Pequeño | Trivial | Varía | No lo sé |
|---|
Moderados: Tomando en cuenta la evidencia identificada, la experiencia clínica y la vivencia de las personas con el problema de salud, el equipo elaborador de la guía estimó que la magnitud de los efectos indeseables de «usar levotiroxina» en comparación a «no usar» son moderados, y probablemente es importante para la mayoría de las personas.
Consideraciones Adicionales
El panel de expertos considera que la mortalidad podría aumentar.
Evidencia de investigación
LEVOTIROXINA PARA PERSONAS CON HIPERCOLESTEROLEMIA E HIPOTIROIDISMO SUBCLÍNICO
Pacientes Personas con hipotiroidismo subclínico e hipercolesterolemia.
Intervención Usar levotiroxina.
Comparación No usar.
|
Desenlaces |
Efecto relativo (IC 95%) — Pacientes/ estudios |
Efecto absoluto estimado* |
Certeza de la evidencia (GRADE) |
Mensajes clave en términos sencillos |
||
|
SIN |
CON |
Diferencia (IC 95%) |
||||
|
Mortalidad (seguimiento a 12 meses) |
RR 2,01 — 737 pacientes/ 1 ensayo [79] |
14 |
27 por 1000 |
Diferencia: 13 más (4 menos a 65 más) |
Muy baja |
El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría aumentar la mortalidad. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
|
Eventos cardiovasculares** |
RR 0,90 — 737 pacientes/ 1 ensayo [79] |
54 |
49 |
Diferencia: |
Muy baja |
El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en el riesgo de desarrollar eventos cardiovasculares. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
|
Niveles de LDL-C*** (seguimiento entre 5 y 12 meses) |
— 320 pacientes/ 6 ensayos [19,20,24,30,32,34] |
DME****: 0,31 menos |
Muy baja |
El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en los niveles de LDL-C. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
||
|
Calidad de vida (seguimiento 3 a 12 meses) |
— |
DME****: 0,31 menos |
Muy baja |
El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en la calidad de vida. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
||
IC 95%: Intervalo de confianza del 95%. || RR: Riesgo relativo. || DME: Diferencia de media estandarizada.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo SIN levotiroxina está basado en el riesgo del grupo control en los estudios. El riesgo CON levotiroxina (y su intervalo de confianza) está calculado a partir del efecto relativo (y su intervalo de confianza).
**Incluye eventos cardiovasculares fatales y no fatales, tales como infarto agudo al miocardio, accidente cerebrovascular, amputaciones, revascularización por aterosclerosis vascular, entre otros.
***Evaluado con LDL-C medido en mmol/l y mg/dl.
****La diferencia media estandarizada se utiliza cuando el desenlace ha sido medido en diferentes escalas, siendo difícil su interpretación clínica. Comúnmente se acepta que valores cercanos a 0,2 tendrían poca relevancia clínica, valores de 0,5 tendrían relevancia moderada (se reconoce clínicamente) y valores superiores a 0,8 tendrían relevancia alta.
1 Se disminuyó dos niveles de certeza de la evidencia por tratarse de evidencia indirecta, ya que la evidencia utilizada proviene de un estudio cuyos participantes eran adultos de 74 años de edad promedio con hipotiroidismo subclínico, sin especificar perfil lipídico.
2 Se disminuyó un nivel de certeza de la evidencia por
imprecisión, debido a que a cada extremo del intervalo de confianza se tomarían decisiones diferentes.
3 Se disminuyó un nivel de certeza de la evidencia por inconsistencia, dado que se observó heterogeneidad significativa (I2=71%).
4 Se disminuyó un nivel de certeza de la evidencia por riesgo de sesgo, debido a que en la mayoría de los ensayos no estaba clara la generación ni el ocultamiento de la secuencia de aleatorización.
Referencias
2. Aziz M, Kandimalla Y, Machavarapu A, Saxena A, Das S, Younus A, Nguyen M, Malik R, Anugula D, Latif MA, Humayun C, Khan IM, Adus A, Rasool A, Veledar E, Nasir K. Effect of Thyroxin Treatment on Carotid Intima-Media Thickness (CIMT) Reduction in Patients with Subclinical Hypothyroidism (SCH): a Meta-Analysis of Clinical Trials. Journal of atherosclerosis and thrombosis. 2017;24(7):643-659.
3. Danese MD, Ladenson PW, Meinert CL, Powe NR. Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. The Journal of clinical endocrinology and metabolism. 2000;85(9):2993-3001.
4. Feller M, Snel M, Moutzouri E, Bauer DC, de Montmollin M, Aujesky D, Ford I, Gussekloo J, Kearney PM, Mooijaart S, Quinn T, Stott D, Westendorp R, Rodondi N, Dekkers OM. Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis. JAMA. 2018;320(13):1349-1359.
5. He W, Li S, Zhang JA, Zhang J, Mu K, Li XM. Effect of Levothyroxine on Blood Pressure in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis. Frontiers in endocrinology. 2018;9(AUG):454.
6. Helfand M. Screening for Thyroid Disease. U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews. 2004;
7. Li X, Meng Z, Jia Q, Ren X. Effect of L-thyroxine treatment versus a placebo on serum lipid levels in patients with sub-clinical hypothyroidism. Biomedical reports. 2016;5(4):443-449.
8. Li X, Wang Y, Guan Q, Zhao J, Gao L. The lipid-lowering effect of levothyroxine in patients with subclinical hypothyroidism: a systematic review and meta-analysis of randomized controlled trials. Clinical endocrinology. 2017;87(1):1-9.
9. Loh HH, Lim LL, Yee A, Loh HS. Association between subclinical hypothyroidism and depression: an updated systematic review and meta-analysis. BMC psychiatry. 2019;19(1):12.
10. Rugge B, Balshem H, Sehgal R, Relevo R, Gorman P, Helfand M. Screening and Treatment of Subclinical Hypothyroidism or Hyperthyroidism. AHRQ Comparative Effectiveness Reviews; Rockville (MD): Agency for Healthcare Research and Quality (US); Report No.: 11(12)-EHC033-EF. 2011;
11. Rugge JB, Bougatsos C, Chou R. Screening and treatment of thyroid dysfunction: an evidence review for the u.s. Preventive services task force. Annals of internal medicine. 2015;162(1):35-45.
12. Rugge JB, Bougatsos C, Chou R. Screening for and Treatment of Thyroid Dysfunction: An Evidence Review for the U.S. Preventive Services Task Force. U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews. 2014;
13. Tanis BC, Westendorp GJ, Smelt HM. Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies. Clinical endocrinology. 1996;44(6):643-9.
14. van Harten AC, Leue C, Verhey FR. Should depressive symptoms in patients with subclinical hypothyroidism be treated with thyroid hormone?. Tijdschrift voor psychiatrie. 2008;50(8):539-43.
15. Villar HC, Saconato H, Valente O, Atallah AN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane database of systematic reviews (Online). 2007;(3):CD003419.
16. Zhao T, Chen BM, Zhao XM, Shan ZY. Subclinical hypothyroidism and depression: a meta-analysis. Translational psychiatry. 2018;8(1):239.
17. Zhao T., Chen B., Zhou Y., Wang X., Zhang Y., Wang H., Shan Z.. Effect of levothyroxine on the progression of carotid intima-media thickness in subclinical hypothyroidism patients: A meta-analysis. BMJ Open. 2017;7(10):e016053.
18. 5th Tromsø study. Jorde R, Waterloo K, Storhaug H, Nyrnes A, Sundsfjord J, Jenssen TG. Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment. The Journal of clinical endocrinology and metabolism. 2006;91(1):145-53.
19. Cabral MD, Teixeira P, Soares D, Leite S, Salles E, Waisman M. Effects of thyroxine replacement on endothelial function and carotid artery intima-media thickness in female patients with mild subclinical hypothyroidism. Clinics (São Paulo, Brazil). 2011;66(8):1321-8.
20. Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. The Journal of clinical endocrinology and metabolism. 2002;87(4):1533-8.
21. Christ-Crain M, Morgenthaler NG, Meier C, Müller C, Nussbaumer C, Bergmann A, Staub JJ, Müller B. Pro-A-type and N-terminal pro-B-type natriuretic peptides in different thyroid function states. Swiss medical weekly. 2005;135(37-38):549-54.
22. Cooper DS, Halpern R, Wood LC, Levin AA, Ridgway EC. L-Thyroxine therapy in subclinical hypothyroidism. A double-blind, placebo-controlled trial. Annals of internal medicine. 1984;101(1):18-24.
23. Duman D, Demirtunc R, Sahin S, Esertas K. The effects of simvastatin and levothyroxine on intima-media thickness of the carotid artery in female normolipemic patients with subclinical hypothyroidism: a prospective, randomized-controlled study. Journal of cardiovascular medicine (Hagerstown, Md.). 2007;8(12):1007-11.
24. Duman D, Sahin S, Esertas K, Demirtunc R. Simvastatin improves endothelial function in patents with subclinical hypothyroidism. Heart and vessels. 2007;22(2):88-93.
25. Jaeschke R, Guyatt G, Gerstein H, Patterson C, Molloy W, Cook D, Harper S, Griffith L, Carbotte R. Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?. Journal of general internal medicine. 1996;11(12):744-9.
26. Kong WM, Sheikh MH, Lumb PJ, Naoumova RP, Freedman DB, Crook M, Doré CJ, Finer N, Naoumova P. A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. The American journal of medicine. 2002;112(5):348-54.
27. Martins RM, Fonseca RH, Duarte MM, Reuters VS, Ferreira MM, Almeida C, Buescu A, Teixeira Pde F, Vaisman M. Impact of subclinical hypothyroidism treatment in systolic and diastolic cardiac function. Arquivos brasileiros de endocrinologia e metabologia. 2011;55(7):460-7.
28. Meier C, Staub JJ, Roth CB, Guglielmetti M, Kunz M, Miserez AR, Drewe J, Huber P, Herzog R, Müller B. TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study). The Journal of clinical endocrinology and metabolism. 2001;86(10):4860-6.
29. Mikhail GS, Alshammari SM, Alenezi MY, Mansour M, Khalil NA. Increased atherogenic low-density lipoprotein cholesterol in untreated subclinical hypothyroidism. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2008;14(5):570-5.
30. Monzani F, Caraccio N, Kozàkowà M, Dardano A, Vittone F, Virdis A, Taddei S, Palombo C, Ferrannini E. Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study. The Journal of clinical endocrinology and metabolism. 2004;89(5):2099-106.
31. Monzani F, Di Bello V, Caraccio N, Bertini A, Giorgi D, Giusti C, Ferrannini E. Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. The Journal of clinical endocrinology and metabolism. 2001;86(3):1110-5.
32. Nagasaki T, Inaba M, Yamada S, Shirakawa K, Nagata Y, Kumeda Y, Hiura Y, Tahara H, Ishimura E, Nishizawa Y. Decrease of brachial-ankle pulse wave velocity in female subclinical hypothyroid patients during normalization of thyroid function: a double-blind, placebo-controlled study. European journal of endocrinology / European Federation of Endocrine Societies. 2009;160(3):409-15.
33. Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. The Journal of clinical endocrinology and metabolism. 2007;92(5):1715-23.
34. Teixeira. Teixeira PF, Reuters VS, Ferreira MM, Almeida CP, Reis FA, Melo BA, Buescu A, Costa AJ, Vaisman M. Treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a placebo-controlled double-blind clinical trial. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 2008;40(1):50-5.
35. Zhao M, Liu L, Wang F, Yuan Z, Zhang X, Xu C, Song Y, Guan Q, Gao L, Shan Z, Zhang H, Zhao J. A Worthy Finding: Decrease in Total Cholesterol and Low-Density Lipoprotein Cholesterol in Treated Mild Subclinical Hypothyroidism. Thyroid : official journal of the American Thyroid Association. 2016;26(8):1019-29.
36. Pollock MA, Sturrock A, Marshall K, Davidson KM, Kelly CJ, McMahon AD, McLaren EH. Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial. BMJ (Clinical research ed.). 2001;323(7318):891-5.
37. Nyström E, Caidahl K, Fager G, Wikkelsö C, Lundberg PA, Lindstedt G. A double-blind cross-over 12-month study of L-thyroxine treatment of women with ‘subclinical’ hypothyroidism. Clinical endocrinology. 1988;29(1):63-75.
38. Adamarczuk-Janczyszyn M, Zdrojowy-Wełna A, Rogala N, Zatońska K, Bednarek-Tupikowska G. Evaluation of Selected Atherosclerosis Risk Factors in Women with Subclinical Hypothyroidism Treated with L-Thyroxine. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2016;25(3):457-63.
39. Adrees M, Gibney J, El-Saeity N, Boran G. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism. Clinical endocrinology. 2009;71(2):298-303.
40. Akkoca, Ayşe Neslin, Özdemir, Zeynep Tuğba, Özler, Gül Soylu, Karabulut, Laika. The evaluation of carotid intima thickness in clinical and subclinical hypothyroidism and effects of thyroid hormone treatment. American Journal of Clinical and Experimental Medicine. 2014;2:59.
41. Anagnostis P, Efstathiadou ZA, Slavakis A, Selalmatzidou D, Poulasouchidou M, Katergari S, Karathanasi E, Dogramatzi F, Kita M. The effect of L-thyroxine substitution on lipid profile, glucose homeostasis, inflammation and coagulation in patients with subclinical hypothyroidism. International journal of clinical practice. 2014;68(7):857-63.
42. Arem R, Escalante DA, Arem N, Morrisett JD, Patsch W. Effect of L-thyroxine therapy on lipoprotein fractions in overt and subclinical hypothyroidism, with special reference to lipoprotein(a). Metabolism: clinical and experimental. 1995;44(12):1559-63.
43. Arem R, Patsch W. Lipoprotein and apolipoprotein levels in subclinical hypothyroidism. Effect of levothyroxine therapy. Archives of internal medicine. 1990;150(10):2097-100.
44. Baldini IM, Vita A, Mauri MC, Amodei V, Carrisi M, Bravin S, Cantalamessa L. Psychopathological and cognitive features in subclinical hypothyroidism. Progress in neuro-psychopharmacology & biological psychiatry. 1997;21(6):925-35.
45. Bantle JP, Oppenheimer JH, Schwartz HL, Hunninghake DB, Probstfield JL, Hanson RF. TSH response to TRH in euthyroid, hypercholesterolemic patients treated with graded doses of dextrothyroxine. Metabolism: clinical and experimental. 1981;30(1):63-6.
46. Bell GM, Todd WT, Forfar JC, Martyn C, Wathen CG, Gow S, Riemersma R, Toft AD. End-organ responses to thyroxine therapy in subclinical hypothyroidism. Clinical endocrinology. 1985;22(1):83-9.
47. Bogner U, Arntz HR, Peters H, Schleusener H. Subclinical hypothyroidism and hyperlipoproteinaemia: indiscriminate L-thyroxine treatment not justified. Acta endocrinologica. 1993;128(3):202-6.
48. Caron P, Calazel C, Parra HJ, Hoff M, Louvet JP. Decreased HDL cholesterol in subclinical hypothyroidism: the effect of L-thyroxine therapy. Clinical endocrinology. 1990;33(4):519-23.
49. Cerbone M, Capalbo D, Wasniewska M, Alfano S, Mattace Raso G, Oliviero U, Cittadini A, De Luca F, Salerno M. Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism. European journal of endocrinology. 2016;175(1):11-9.
50. Christ-Crain M, Meier C, Guglielmetti M, Huber PR, Riesen W, Staub JJ, Müller B. Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial. Atherosclerosis. 2003;166(2):379-86.
51. Elder J, McLelland A, O’Reilly DS, Packard CJ, Series JJ, Shepherd J. The relationship between serum cholesterol and serum thyrotropin, thyroxine and tri-iodothyronine concentrations in suspected hypothyroidism. Annals of clinical biochemistry. 1990;27 ( Pt 2):110-3.
52. Franklyn JA, Daykin J, Betteridge J, Hughes EA, Holder R, Jones SR, Sheppard MC. Thyroxine replacement therapy and circulating lipid concentrations. Clinical endocrinology. 1993;38(5):453-9.
53. Guang-Da X, Hui-Ling S, Zhi-Song C, Lin-Shuang Z. Alteration of plasma concentrations of OPG before and after levothyroxine replacement therapy in hypothyroid patients. Journal of endocrinological investigation. 2005;28(11):965-72.
54. Gulseren S, Gulseren L, Hekimsoy Z, Cetinay P, Ozen C, Tokatlioglu B. Depression, anxiety, health-related quality of life, and disability in patients with overt and subclinical thyroid dysfunction. Archives of medical research. 2006;37(1):133-9.
55. Johnston J, McLelland A, O’Reilly DS. The relationship between serum cholesterol and serum thyroid hormones in male patients with suspected hypothyroidism. Annals of clinical biochemistry. 1993;30 ( Pt 3):256-9.
56. Kebapcilar L, Comlekci A, Tuncel P, Solak A, Secil M, Gencel O, Sahin M, Sari I, Yesil S. Effect of levothyroxine replacement therapy on paraoxonase-1 and carotid intima-media thickness in subclinical hypothyroidism. Medical science monitor : international medical journal of experimental and clinical research. 2010;16(1):CR41-7.
57. Kim SK, Kim SH, Park KS, Park SW, Cho YW. Regression of the increased common carotid artery-intima media thickness in subclinical hypothyroidism after thyroid hormone replacement. Endocrine journal. 2009;56(6):753-8.
58. Kowalska I, Borawski J, Nikołajuk A, Budlewski T, Otziomek E, Górska M, Strączkowski M. Insulin sensitivity, plasma adiponectin and sICAM-1 concentrations in patients with subclinical hypothyroidism: response to levothyroxine therapy. Endocrine. 2011;40(1):95-101.
59. Krysiak R, Szkróbka W, Okopień B. The effect of l-thyroxine treatment on sexual function and depressive symptoms in men with autoimmune hypothyroidism. Pharmacological reports : PR. 2017;69(3):432-437.
60. Lithell H, Boberg J, Hellsing K, Ljunghall S, Lundqvist G, Vessby B, Wide L. Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein-lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy. European journal of clinical investigation. 1981;11(1):3-10.
61. Miura S, Iitaka M, Yoshimura H, Kitahama S, Fukasawa N, Kawakami Y, Sakurai S, Urabe M, Sakatsume Y, Ito K. Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy. Internal medicine (Tokyo, Japan). 1994;33(7):413-7.
62. Nagasaki T, Inaba M, Yamada S, Kumeda Y, Hiura Y, Nishizawa Y. Changes in brachial-ankle pulse wave velocity in subclinical hypothyroidism during normalization of thyroid function. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2007;61(8):482-7.
63. Niknam N, Khalili N, Khosravi E, Nourbakhsh M. Endothelial dysfunction in patients with subclinical hypothyroidism and the effects of treatment with levothyroxine. Advanced biomedical research. 2016;5:38.
64. Nilsson G, Nordlander S, Levin K. Studies on subclinical hypothyroidism with special reference to the serum lipid pattern. Acta medica Scandinavica. 1976;200(1-2):63-67.
65. Pandrc MS, Ristić A, Kostovski V, Stanković M, Antić V, Milin-Lazović J, Ćirić J. The Effect of Early Substitution of Subclinical Hypothyroidism on Biochemical Blood Parameters and the Quality of Life. Journal of medical biochemistry. 2017;36(2):127-136.
66. Paoli M, Bellabarba G, Velazquez E, Mendoza S, Molina C, Wang P, Glueck CJ. Sex steroids, lipids, and lipoprotein cholesterols in women with subclinical and overt hypothyroidism before and after L-thyroxine therapy. Clinica chimica acta; international journal of clinical chemistry. 1998;275(1):81-91.
67. Powell JT, Wiseman SA, Carter G, Alaghband Zadeh J, Fowler PB, Greenhalgh RM. Can thyroxine halt the progression of peripheral arterial disease?. European journal of vascular surgery. 1989;3(1):85-7.
68. Razvi S, Weaver JU, Butler TJ, Pearce SH. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Archives of internal medicine. 2012;172(10):811-7.
69. Ridgway EC, Cooper DS, Walker H, Rodbard D, Maloof F. Peripheral responses to thyroid hormone before and after L-thyroxine therapy in patients with subclinical hypothyroidism. The Journal of clinical endocrinology and metabolism. 1981;53(6):1238-42.
70. Stratigou T, Dalamaga M, Antonakos G, Marinou I, Vogiatzakis E, Christodoulatos GS, Karampela I, Papavassiliou AG. Hyperirisinemia is independently associated with subclinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors. Endocrine. 2018;61(1):83-93.
71. Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, Salvetti A, Ferrannini E, Monzani F. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. The Journal of clinical endocrinology and metabolism. 2003;88(8):3731-7.
72. Traub-Weidinger T, Graf S, Beheshti M, Ofluoglu S, Zettinig G, Khorsand A, Nekolla SG, Kletter K, Dudczak R, Pirich C. Coronary vasoreactivity in subjects with thyroid autoimmunity and subclinical hypothyroidism before and after supplementation with thyroxine. Thyroid : official journal of the American Thyroid Association. 2012;22(3):245-51.
73. Unal O, Erturk E, Ozkan H, Kiyici S, Guclu M, Ersoy C, Yener F, Imamoglu S. Effect of levothyroxine treatment on QT dispersion in patients with subclinical hypothyroidism. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2007;13(7):711-5.
74. Unsal, Ilknur Ozturk, Topaloglu, Oya, Cakir, Evrim, Bozkurt, Nujen Colak, Karbek, Basak, Gungunes, Askin, Arslan, Muyesser Sayki, Akkaymak, Esra Tutal, Ucan, Bekir, Demirci, Taner. Effect of L-thyroxin therapy on thyroid volume and carotid artery lntima-media thickness in the patients with subclinical hypothyroidism. Journal of Medical Disorders. 2014;2(1):1.
75. Vishnoi G, Chakraborty B, Garda H, Gowda SH, Goswami B. Low mood and response to Levothyroxine treatment in Indian patients with subclinical hypothyroidism. Asian journal of psychiatry. 2014;8:89-93.
76. Liu XL, He S, Zhang SF, Wang J, Sun XF, Gong CM, Zheng SJ, Zhou JC, Xu J. Alteration of lipid profile in subclinical hypothyroidism: a meta-analysis. Medical science monitor : international medical journal of experimental and clinical research. 2014;20((Liu X.-L.; He S.; Gong C.-M.; Zheng S.-J.; Zhou J.-C.) Molecular Biology Lab, Shenzhen Center for Chronic Disease Control, Shenzhen, China):1432-41.
77. Tagami T, Kimura H, Ohtani S, Tanaka T, Tanaka T, Hata S, Saito M, Miyazaki Y, Araki R, Tanaka M, Yonezawa K, Sawamura M, Ise T, Ogo A, Shimbo T, Shimatsu A, Naruse M; PHPH study group. Multi-center study on the prevalence of hypothyroidism in patients with hypercholesterolemia. Endocr J. 2011;58(6):449-57.
78. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000 Feb 28;160(4):526-34.
79. 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. Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. The New England journal of medicine. 2017;376(26):2534-2544.
80. Zhao M, Liu L, Wang F, Yuan Z, Zhang X, Xu C, Song Y, Guan Q, Gao L, Shan Z, Zhang H, Zhao J. A Worthy Finding: Decrease in Total Cholesterol and Low-Density Lipoprotein Cholesterol in Treated Mild Subclinical Hypothyroidism. Thyroid. 2016 Aug;26(8):1019-29.
81. Blum MR, Gencer B, Adam L, Feller M, Collet TH, da Costa BR, Moutzouri E, Dopheide J, Depairon M, Sykiotis GP, Kearney P, Gussekloo J, Westendorp R, Stott DJ, Bauer DC, Rodondi N. Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism: A Randomized Trial. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2988-2997.
82. Pergialiotis V, Konstantopoulos P, Prodromidou A, Florou V, Papantoniou N, Perrea DN. MANAGEMENT OF ENDOCRINE DISEASE: The impact of subclinical hypothyroidism on anthropometric characteristics, lipid, glucose and hormonal profile of PCOS patients: a systematic review and meta-analysis. Eur J Endocrinol. 2017 Mar;176(3):R159-R166.
Búsqueda y Síntesis de Evidencia
Búsqueda y síntesis de evidencia de efectos deseables e indeseables
| Muy baja | Baja | Moderada | Alta | Ningún estudio incluido |
|---|
Muy Baja: Existe considerable incertidumbre de que la evidencia identificada es suficiente para apoyar una recomendación determinada, dado que existen muy pocos estudios o estos tienen limitaciones importantes.
Evidencia de investigación
|
Desenlaces |
Importancia |
Certainty of the evidence |
|
Mortalidad (seguimiento 12 meses) |
CRITICO |
⨁◯◯◯ |
|
Eventos cardiovasculares |
CRITICO |
⨁◯◯◯ |
|
Niveles de LDL-C (seguimiento entre 5 y 12 meses)) |
CRITICO |
⨁◯◯◯ |
|
Eventos cardiovasculares (seguimiento 5 y 12 meses) |
CRITICO |
⨁◯◯◯ |
|
Calidad de vida |
CRITICO |
⨁◯◯◯ |
a. Se disminuyó dos niveles de certeza de la evidencia por tratarse de evidencia indirecta, ya que la evidencia utilizada proviene de un estudio cuyos participantes eran adultos de 74 años de edad promedio con hipotiroidismo subclínico, sin especificar perfil lipídico.
b. Se disminuyó un nivel de certeza de la evidencia por imprecisión, debido a que a cada extremo del intervalo de confianza se tomarían decisiones diferentes.
c. Se disminuyó un nivel de certeza de la evidencia por inconsistencia, dado que se observó heterogeneidad significativa (I2=71%).
d. Se disminuyó un nivel de certeza de la evidencia por riesgo de sesgo, debido a que en la mayoría de los ensayos no estaba clara la generación ni el ocultamiento de la secuencia de aleatorización.
| Variabilidad importantes | Posiblemente hay incertidumbre o variabilidad importantes | Probablemente no hay incertidumbre ni variabilidad importantes | No hay variabilidad o incertidumbre importante |
|---|
No hay variabilidad importante: Tomando en cuenta la evidencia identificada, la experiencia clínica y la vivencia de las personas con el problema de salud, el equipo elaborador de la guía consideró que no existe variabilidad importante en como las personas, correctamente informadas, valoran los efectos deseables e indeseables de «usar levotiroxina».
Consideraciones Adicionales
El panel de expertos decidió no considerar la evidencia presentada ya que los resultados del estudio se relacionan con los síntomas del hipotiroidismo y no aborda exactamente la población con hipercolesterolemia e hipotiroidismo.
Búsqueda y Síntesis de Evidencia
Búsqueda y síntesis de evidencia de valores y preferencias de los pacientes
| Favorece la comparación | Probablemente favorece la comparación | No favorece la intervención ni la comparación | Probablemente favorece la intervención | Favorece la intervención | Varía | No lo sé |
|---|
Favorece la comparación: Tomando en cuenta la magnitud de los efectos deseables e indeseables , así como los valores y preferencias de las personas, el equipo elaborador de la guía consideró que «no usar» es la major alternativa.
| Costos extensos | Costos moderados | Costos y ahorros pequeños | Ahorros moderados | Ahorros extensos | Varía | No lo sé |
|---|
Costos y ahorros pequeños: La diferencia del costo o ahorros entre » usar levotiroxina» y » no usar» es inferior a $674.672. Por lo cual el equipo elaborador de la guía consideró que implementar »usar levotiroxina» no significaría un cambio importante en el gasto o ahorro del sistema de salud.
Evidencia de investigación
A continuación se muestran los costos referenciales de la prestación sanitaria “usar levotiroxina”, de modo que el equipo elaborador de la Guía se pudiese pronunciar al respecto y no debe ser utilizado para otros fines.
Tabla N° 1 Precios referenciales
|
ítem |
Posología |
Cantidad |
Precio unitario |
Precio anual de utilizar levotiroxina de 25ug |
Precio anual de utilizar levotiroxina de 50ug |
Precio anual de utilizar levotiroxina de 100ug |
|
No realizar |
|
Consulta médica electiva1 |
– |
1 |
$9.610 |
$9.610 |
$9.610 |
$9.610 |
|
$9.610 |
|
Levotiroxina 25ug2 |
1 comp. De 25ug al día, permanente |
365 |
$84 |
$30.660 |
– |
– |
|
– |
|
levotiroxina 50ug2 |
1 comp. De 50ug al día, permanente |
365 |
$86 |
– |
$31.390 |
– |
|
– |
|
Levotiroxina 100ug2 |
1 comp. De 100ug al día, permanente |
365 |
$11 |
– |
– |
$4.015 |
|
– |
|
TOTAL |
$40.270 |
$41.000 |
$13.625 |
|
$9.610 |
|||
(1) Precio total para prestador Nivel 3 obtenido de Arancel FONASA Modalidad Libre Elección (MLE) 2019
(2) Precio de compra por Establecimiento de Salud Público a través de plataforma Mercado Público 2019 (Incluye IVA)
Búsqueda y Síntesis de Evidencia
Búsqueda de costos
| Favorece la comparación | Probablemente favorece la comparación | No favorece la intervención ni la comparación | Probablemente favorece la intervención | Favorece la intervención | Varía | Ningún estudio incluido |
|---|
Ningún estudio incluido: No se identificaron estudios evaluando costo-efectividad.
Búsqueda y Síntesis de Evidencia
Informe de búsqueda y síntesis de costo-efectividad
| Reducido | Probablemente reducido | Probablemente ningún impacto | Probablemente aumentado | Aumentado | Varía | No lo sé |
|---|
Probablemente ningún impacto: El equipo elaborador de la guía consideró que esta recomendación probablemente no tendría ningún impacto en la equidad en salud, dado que que en la actualidad existe amplio acceso a ambas alternativas, ya sea en términos económicos, geográficos u otros.
| No | Probablemente no | Probablemente sí | Sí | Varía | No lo sé |
|---|
No: El equipo elaborador de la guía consideró que »usar levotiroxina» NO es aceptable para las partes interesadas (profesionales de la salud, gestores de centros de salud, directivos de centros de salud, pacientes, cuidadores, seguros de salud, otros).
| No | Probablemente no | Probablemente sí | Sí | Varía | No lo sé |
|---|
Sí: Tomando en cuenta la capacidad de la red asistencial y los recursos humanos y materiales disponibles, el equipo elaborador de la guía consideró que SI es factible implementar »usar levotiroxina» .