Thyroid Status, Quality of Life, and Mental Health in Patients on Hemodialysis
Connie M Rhee, Yanjun Chen, Amy S You, Steven M Brunelli, Csaba P Kovesdy, Matthew J Budoff, Gregory A Brent, Kamyar Kalantar-Zadeh, Danh V Nguyen, Connie M Rhee, Yanjun Chen, Amy S You, Steven M Brunelli, Csaba P Kovesdy, Matthew J Budoff, Gregory A Brent, Kamyar Kalantar-Zadeh, Danh V Nguyen
Abstract
Background and objectives: In the general population, there is increasing recognition of the effect of thyroid function on patient-centered outcomes, including health-related quality of life and depression. Although hypothyroidism is highly prevalent in hemodialysis patients, it is unknown whether thyroid status is a risk factor for impaired health-related quality of life or mental health in this population.
Design, setting, participants, & measurements: We examined the association of thyroid status, defined by serum thyrotropin, with health-related quality of life and depressive symptoms over time in a prospective cohort of 450 patients on hemodialysis from 17 outpatient dialysis facilities from May of 2013 to May of 2015 who underwent protocolized thyrotropin testing, Short-Form 36 surveys, and Beck Depression Inventory-II questionnaires every 6 months. We examined the association of baseline and time-dependent thyrotropin categorized as tertiles and continuous variables with eight Short-Form 36 domains and Beck Depression Inventory-II scores using expanded case mix plus laboratory adjusted linear mixed effects models.
Results: In categorical analyses, the highest baseline thyrotropin tertile was associated with a five-point lower Short-Form 36 domain score for energy/fatigue (P=0.04); the highest time-dependent tertile was associated with a five-point lower physical function score (P=0.03; reference: lowest tertile). In continuous analyses, higher baseline serum thyrotropin levels (+Δ1 mIU/L) were associated with lower role limitations due to physical health (β=-1.3; P=0.04), energy/fatigue (β=-0.8; P=0.03), and pain scores (β=-1.4; P=0.002), equivalent to five-, three-, and five-point lower scores, respectively, for every 1-SD higher thyrotropin. Higher time-dependent thyrotropin levels were associated with lower role limitations due to physical health scores (β=-1.0; P=0.03), equivalent to a three-point decline for every 1-SD higher thyrotropin. Baseline and time-dependent thyrotropin were not associated with Beck Depression Inventory-II scores.
Conclusions: In patients on hemodialysis, higher serum thyrotropin levels are associated with impaired health-related quality of life across energy/fatigue, physical function, and pain domains. Studies are needed to determine if thyroid-modulating therapy improves the health-related quality of life of hemodialysis patients with thyroid dysfunction.
Keywords: Depressive Disorder; Fatigue; Humans; Hypothyroidism; Mental Health; Mental health; Outpatients; Pain; Prospective Studies; Surveys and Questionnaires; Thyroid function; Thyrotropin; depression; hemodialysis; quality of life; renal dialysis; risk factors.
Copyright © 2017 by the American Society of Nephrology.
Figures
References
- Lo JC, Chertow GM, Go AS, Hsu CY: Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease. Kidney Int 67: 1047–1052, 2005
- Mariani LH, Berns JS: The renal manifestations of thyroid disease. J Am Soc Nephrol 23: 22–26, 2012
- Rhee CM, Alexander EK, Bhan I, Brunelli SM: Hypothyroidism and mortality among dialysis patients. Clin J Am Soc Nephrol 8: 593–601, 2013
- Rhee CM, Kalantar-Zadeh K, Streja E, Carrero JJ, Ma JZ, Lu JL, Kovesdy CP: The relationship between thyroid function and estimated glomerular filtration rate in patients with chronic kidney disease. Nephrol Dial Transplant 30: 282–287, 2015
- Rhee CM, Kim S, Gillen DL, Oztan T, Wang J, Mehrotra R, Kuttykrishnan S, Nguyen DV, Brunelli SM, Kovesdy CP, Brent GA, Kalantar-Zadeh K: Association of thyroid functional disease with mortality in a national cohort of incident hemodialysis patients. J Clin Endocrinol Metab 100: 1386–1395, 2015
- Targher G, Chonchol M, Zoppini G, Salvagno G, Pichiri I, Franchini M, Lippi G: Prevalence of thyroid autoimmunity and subclinical hypothyroidism in persons with chronic kidney disease not requiring chronic dialysis. Clin Chem Lab Med 47: 1367–1371, 2009
- Zoccali C, Mallamaci F: Thyroid function and clinical outcomes in kidney failure. Clin J Am Soc Nephrol 7: 12–14, 2012
- Rhee CM, Brent GA, Kovesdy CP, Soldin OP, Nguyen D, Budoff MJ, Brunelli SM, Kalantar-Zadeh K: Thyroid functional disease: An under-recognized cardiovascular risk factor in kidney disease patients. Nephrol Dial Transplant 30: 724–737, 2015
- Feldman AZ, Shrestha RT, Hennessey JV: Neuropsychiatric manifestations of thyroid disease. Endocrinol Metab Clin North Am 42: 453–476, 2013
- Samuels MH: Psychiatric and cognitive manifestations of hypothyroidism. Curr Opin Endocrinol Diabetes Obes 21: 377–383, 2014
- Bauer M, Heinz A, Whybrow PC: Thyroid hormones, serotonin and mood: Of synergy and significance in the adult brain. Mol Psychiatry 7: 140–156, 2002
- Dayan CM, Panicker V: Hypothyroidism and depression. Eur Thyroid J 2: 168–179, 2013
- Gordon JT, Kaminski DM, Rozanov CB, Dratman MB: Evidence that 3,3′,5-triiodothyronine is concentrated in and delivered from the locus coeruleus to its noradrenergic targets via anterograde axonal transport. Neuroscience 93: 943–954, 1999
- Henley WN, Koehnle TJ: Thyroid hormones and the treatment of depression: An examination of basic hormonal actions in the mature mammalian brain. Synapse 27: 36–44, 1997
- Kirkegaard C, Faber J: The role of thyroid hormones in depression. Eur J Endocrinol 138:1–9, 1998
- Mason GA, Bondy SC, Nemeroff CB, Walker CH, Prange AJ Jr.: The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain. Psychoneuroendocrinology 12: 261–270, 1987
- Whybrow PC, Prange AJ Jr.: A hypothesis of thyroid-catecholamine-receptor interaction. Its relevance to affective illness. Arch Gen Psychiatry 38: 106–113, 1981
- Bauer M, London ED, Silverman DH, Rasgon N, Kirchheiner J, Whybrow PC: Thyroid, brain and mood modulation in affective disorder: Insights from molecular research and functional brain imaging. Pharmacopsychiatry 36[Suppl 3]: S215–S221, 2003
- Samuels MH, Schuff KG, Carlson NE, Carello P, Janowsky JS: Health status, mood, and cognition in experimentally induced subclinical hypothyroidism. J Clin Endocrinol Metab 92: 2545–2551, 2007
- Kalantar-Zadeh K, Unruh M: Health related quality of life in patients with chronic kidney disease. Int Urol Nephrol 37: 367–378, 2005
- Evans RW, Manninen DL, Garrison LP Jr., Hart LG, Blagg CR, Gutman RA, Hull AR, Lowrie EG: The quality of life of patients with end-stage renal disease. N Engl J Med 312: 553–559, 1985
- Feroze U, Martin D, Reina-Patton A, Kalantar-Zadeh K, Kopple JD: Mental health, depression, and anxiety in patients on maintenance dialysis. Iran J Kidney Dis 4: 173–180, 2010
- Hedayati SS, Bosworth HB, Kuchibhatla M, Kimmel PL, Szczech LA: The predictive value of self-report scales compared with physician diagnosis of depression in hemodialysis patients. Kidney Int 69: 1662–1668, 2006
- Hedayati SS, Finkelstein FO: Epidemiology, diagnosis, and management of depression in patients with CKD. Am J Kidney Dis 54: 741–752, 2009
- Watnick S, Wang PL, Demadura T, Ganzini L: Validation of 2 depression screening tools in dialysis patients. Am J Kidney Dis 46: 919–924, 2005
- Boulware LE, Liu Y, Fink NE, Coresh J, Ford DE, Klag MJ, Powe NR: Temporal relation among depression symptoms, cardiovascular disease events, and mortality in end-stage renal disease: Contribution of reverse causality. Clin J Am Soc Nephrol 1: 496–504, 2006
- Hedayati SS, Grambow SC, Szczech LA, Stechuchak KM, Allen AS, Bosworth HB: Physician-diagnosed depression as a correlate of hospitalizations in patients receiving long-term hemodialysis. Am J Kidney Dis 46: 642–649, 2005
- Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH: Association among SF36 quality of life measures and nutrition, hospitalization, and mortality in hemodialysis. J Am Soc Nephrol 12: 2797–2806, 2001
- Lopes AA, Albert JM, Young EW, Satayathum S, Pisoni RL, Andreucci VE, Mapes DL, Mason NA, Fukuhara S, Wikström B, Saito A, Port FK: Screening for depression in hemodialysis patients: Associations with diagnosis, treatment, and outcomes in the DOPPS. Kidney Int 66: 2047–2053, 2004
- Finkelstein FO, Wuerth D, Finkelstein SH: Health related quality of life and the CKD patient: Challenges for the nephrology community. Kidney Int 76: 946–952, 2009
- Naik N, Hess R, Unruh M: Measurement of health-related quality of life in the care of patients with ESRD: Isn’t this the metric that matters? Semin Dial 25: 439–444, 2012
- Beck AT, Steer RA, Ball R, Ranieri W: Comparison of beck depression inventories -IA and -II in psychiatric outpatients. J Pers Assess 67: 588–597, 1996
- Benjamini Y, Hochberg Y: Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 57: 289–300, 1995
- McHorney CA, Ware JE Jr., Raczek AE: The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 31: 247–263, 1993
- Samuels MH, Schuff KG, Carlson NE, Carello P, Janowsky JS: Health status, psychological symptoms, mood, and cognition in L-thyroxine-treated hypothyroid subjects. Thyroid 17: 249–258, 2007
- Klaver EI, van Loon HC, Stienstra R, Links TP, Keers JC, Kema IP, Kobold AC, van der Klauw MM, Wolffenbuttel BH: Thyroid hormone status and health-related quality of life in the LifeLines Cohort Study. Thyroid 23:1066–1073, 2013
- Vigário PS, Vaisman F, Coeli CM, Ward L, Graf H, Carvalho G, Júnior RM, Vaisman M: Inadequate levothyroxine replacement for primary hypothyroidism is associated with poor health-related quality of life-a Brazilian multicentre study. Endocrine 44: 434–440, 2013
- Finkelstein FO, Schiller B, Daoui R, Gehr TW, Kraus MA, Lea J, Lee Y, Miller BW, Sinsakul M, Jaber BL: At-home short daily hemodialysis improves the long-term health-related quality of life. Kidney Int 82: 561–569, 2012
- Leaf DE, Goldfarb DS: Interpretation and review of health-related quality of life data in CKD patients receiving treatment for anemia. Kidney Int 75: 15–24, 2009
- DeOreo PB: Hemodialysis patient-assessed functional health status predicts continued survival, hospitalization, and dialysis-attendance compliance. Am J Kidney Dis 30: 204–212, 1997
- Knight EL, Ofsthun N, Teng M, Lazarus JM, Curhan GC: The association between mental health, physical function, and hemodialysis mortality. Kidney Int 63: 1843–1851, 2003
- Painter P, Roshanravan B: The association of physical activity and physical function with clinical outcomes in adults with chronic kidney disease. Curr Opin Nephrol Hypertens 22: 615–623, 2013
- Anand S, Johansen KL, Kurella Tamura M: Aging and chronic kidney disease: The impact on physical function and cognition. J Gerontol A Biol Sci Med Sci 69: 315–322, 2014
- McDermott MT: Overview of the clinical manifestations of hypothyroidism. In: Werner and Ingbar’s The Thyroid, 10th Ed., edited by Braverman LE, Cooper DS, Philadelphia, Lippincott Williams and Wilkins, 2013, pp 569–574
- Lee JW, Kim NH, Milanesi A: Thyroid hormone signaling in muscle development, repair and metabolism. J Endocrinol Diabetes Obes 2: 1046, 2014
- Mainenti MR, Vigário PS, Teixeira PF, Maia MD, Oliveira FP, Vaisman M: Effect of levothyroxine replacement on exercise performance in subclinical hypothyroidism. J Endocrinol Invest 32: 470–473, 2009
- Ravanbod M, Asadipooya K, Kalantarhormozi M, Nabipour I, Omrani GR: Treatment of iron-deficiency anemia in patients with subclinical hypothyroidism. Am J Med 126: 420–424, 2013
- Reuters VS, Teixeira PF, Vigário PS, Almeida CP, Buescu A, Ferreira MM, de Castro CL, Gold J, Vaisman M: Functional capacity and muscular abnormalities in subclinical hypothyroidism. Am J Med Sci 338: 259–263, 2009
- Boutin A, Neumann S, Gershengorn MC: Multiple transduction pathways mediate thyrotropin receptor signaling in preosteoblast-like cells. Endocrinology 157: 2173–2181, 2016
- Burgos JR, Iresjö BM, Wärnåker S, Smedh U: Presence of TSH receptors in discrete areas of the hypothalamus and caudal brainstem with relevance for feeding controls-support for functional significance. Brain Res 1642: 278–286, 2016
- Moon MK, Kang GH, Kim HH, Han SK, Koo YD, Cho SW, Kim YA, Oh B-C, Park DJ, Chung SS, Park KS, Park YJ: Thyroid-stimulating hormone improves insulin sensitivity in skeletal muscle cells via cAMP/PKA/CREB pathway-dependent upregulation of insulin receptor substrate-1 expression. Mol Cell Endocrinol 436: 50–58, 2016
- Reuters VS, Almeida CP, Teixeira PF, Vigário PS, Ferreira MM, Castro CL, Brasil MA, Costa AJ, Buescu A, Vaisman M: Effects of subclinical hypothyroidism treatment on psychiatric symptoms, muscular complaints, and quality of life. Arq Bras Endocrinol Metabol 56: 128–136, 2012
- Davison SN: Chronic kidney disease: Psychosocial impact of chronic pain. Geriatrics 62: 17–23, 2007
- Shayamsunder AK, Patel SS, Jain V, Peterson RA, Kimmel PL: Sleepiness, sleeplessness, and pain in end-stage renal disease: Distressing symptoms for patients. Semin Dial 18: 109–118, 2005
- American Psychiatric Association : Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Washington, DC, American Psychiatric Association, 1994
- Ladenson PW: Diagnosis of hypothyroidism. In: Werner and Ingbar’s The Thyroid, 10th Ed., edited by Braverman LE, Cooper DS, Philadelphia, Lippincott Williams and Wilkins, 2013, pp 606–611
- Soldin OP: Measuring serum thyroid-stimulating hormone, thyroid hormones, thyroid-directed antibodies, and transport proteins. In: Werner and Ingbar’s The Thyroid, 10th Ed., edited by Braverman LE, Cooper DS, Philadelphia, Lippincott Williams and Wilkins, 2013, pp 279–297
Source: PubMed