Hypoparathyroidism (hypoPT) results in an impairment of quality of life (QoL), an increase in fatigue and a higher risk of mortality. Cardiovascular autonomic neuropathy (CAN) is an impairment of the cardiovascular autonomic system and is associated with increased mortality and fatigability. Patients with hypoPT show an increased risk of CAN. However, no previous studies have investigated the association between CAN and QoL in hypoPT. To test whether CAN is associated with fatigue and impaired QOL in hypoPT patients.
We enrolled 48 subjects with postsurgical hypoPT treated with calcium and calcitriol and 38 healthy subjects who underwent thyroidectomy. Subjects completed the RAND 36-Item Short Form (SF-36) Health Survey, evaluating physical (PCS) and mental (MCS) health, and fatigue score. CAN was assessed using cardiovascular autonomic reflex tests (CARTs). Participants were considered to have “early CAN” (EC) if they had one abnormal CART and “definite CAN” (DC) with two or more abnormal CARTs.
Compared with controls, hypoPT population had lower fatigue scores (44.5 IQRː9 vs 38.5 IQRː12.3, P = 0.031). In the hypoPT group, only participants with DC had a lower fatigue score than subjects without CAN (DC: β: −9.55, P = 0.005) after adjusting for age, duration of disease, calcium concentration, TSH, calcitriol and calcium supplementation. No differences were found in the PCS and MCS scores in the hypoPT group.
CAN may explain fatigue, a common complaint of postsurgical hypoPT patients. Further larger and prospective investigations are needed to confirm our findings.
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T. Sikjaer, E. Moser, L. Rolighed, L. Underbjerg, L.S. Bislev, L. Mosekilde, L. Rejnmark, Concurrent hypoparathyroidism is associated with impaired physical function and quality of life in hypothyroidism. J. Bone Miner. Res. 31, 1440–1448 (2016). https://doi.org/10.1002/jbmr.2812
D.M. Shoback, J.P. Bilezikian, A.G. Costa, D. Dempster, H. Dralle, A.A. Khan, M. Peacock, M. Raffaelli, B.C. Silva, R.V. Thakker, T. Vokes, R. Bouillon, Presentation of hypoparathyroidism: etiologies and clinical features. J. Clin. Endocrinol. Metabol. 101, 2300–2312 (2016). https://doi.org/10.1210/jc.2015-3909
T.J. Vokes, Quality of life in hypoparathyroidism. Endocrinol. Metabol. Clin. North Am. 47, 855–864 (2018). https://doi.org/10.1016/j.ecl.2018.07.010
M. Almquist, K. Ivarsson, E. Nordenström, A. Bergenfelz, Mortality in patients with permanent hypoparathyroidism after total thyroidectomy. Br. J. Surg. (2018). https://doi.org/10.1002/bjs.10843
R. Pop-Busui, What do we know and we do not know about cardiovascular autonomic neuropathy in diabetes. J. Cardiovasc. Transl. Res. 5, 463–478 (2013). https://doi.org/10.1007/s12265-012-9367-6
G. Tabacco, A.M. Naciu, D. Maggi, A. Santonati, C. Pedone, R. Cesareo, D. Bosco, G. Gaspa, N. Napoli, P. Pozzilli, S. Manfrini, A. Palermo, Cardiovascular autonomic neuropathy as a new complication of postsurgical chronic hypoparathyroidism. J. Bone Miner. Res. 34, 475–481 (2019). https://doi.org/10.1002/jbmr.3623
C. Cardone, I test che valutano la risposta riflessa cardiovascolare. Neuropatia diabetica. Rass. Bibliogr. 2, 151–160 (1990)
V. Spallone, D. Ziegler, R. Freeman, L. Bernardi, S. Frontoni, R. Pop-Busui, M. Stevens, P. Kempler, J. Hilsted, S. Tesfaye, P. Low, P. Valensi, Toronto consensus panel on diabetic neuropathy, cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metabol. Res. Rev. 27, 639–653 (2011). https://doi.org/10.1002/dmrr.1239
J.E. Ware, C.D. Sherbourne, The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med. Care 30, 473–83 (1992). http://www.ncbi.nlm.nih.gov/pubmed/1593914 (Accessed 13 Feb 2018)
K. Webster, D. Cella, K. Yost, The functional assessment of chronic illness therapy (FACIT) measurement system: properties, applications, and interpretation. Health Qual. Life Outcomes 1, 79 (2003). https://doi.org/10.1186/1477-7525-1-79
M.T. James, J. Zhang, A.W. Lyon, B.R. Hemmelgarn, Derivation and internal validation of an equation for albumin-adjusted calcium. BMC Clin. Pathol. 8, 12 (2008). https://doi.org/10.1186/1472-6890-8-12
M. Büttner, T.J. Musholt, S. Singer, Quality of life in patients with hypoparathyroidism receiving standard treatment: a systematic review. Endocrine 58, 14–20 (2017). https://doi.org/10.1007/s12020-017-1377-3
A. Santonati, A. Palermo, E. Maddaloni, D. Bosco, A. Spada, F. Grimaldi, B. Raggiunti, R. Volpe, S. Manfrini, F. Vescini, PTH(1-34) for surgical hypoparathyroidism: a prospective, open-label investigation of efficacy and quality of life. J. Clin. Endocrinol. Metabol. 100, 3590–3597 (2015). https://doi.org/10.1210/jc.2015-1855
A. Palermo, A. Santonati, G. Tabacco, D. Bosco, A. Spada, C. Pedone, B. Raggiunti, T. Doris, D. Maggi, F. Grimaldi, S. Manfrini, F. Vescini, PTH(1–34) for surgical hypoparathyroidism: a 2-year prospective, open-label investigation of efficacy and quality of life. J. Clin. Endocrinol. Metabol. 103, 271–280 (2018). https://doi.org/10.1210/jc.2017-01555
N.E. Cusano, M.R. Rubin, D.J. McMahon, D. Irani, L. Anderson, E. Levy, J.P. Bilezikian, PTH(1-84) is associated with improved quality of life in hypoparathyroidism through 5 years of therapy. J. Clin. Endocrinol. Metabol. 99, 3694–3699 (2014). https://doi.org/10.1210/jc.2014-2267
N.E. Cusano, M.R. Rubin, D.J. McMahon, D. Irani, A. Tulley, J. Sliney, J.P. Bilezikian, The effect of PTH(1-84) on quality of life in hypoparathyroidism. J. Clin. Endocrinol. Metabol. 98, 2356–2361 (2013). https://doi.org/10.1210/jc.2013-1239
V.A. Serhiyenko, A.A. Serhiyenko, Cardiac autonomic neuropathy: risk factors, diagnosis and treatment. World J. Diabetes 9, 1–24 (2018). https://doi.org/10.4239/wjd.v9.i1.1
T. Nakamura, M. Hirayama, T. Hara, T. Hama, H. Watanabe, G. Sobue, Does cardiovascular autonomic dysfunction contribute to fatigue in Parkinson’s disease? Mov. Disord. 26, 1869–1874 (2011). https://doi.org/10.1002/mds.23744
S. Merkelbach, U. Dillmann, C. Ko, È. Lmel, J. Holz, M. Mu, È. Ller, Cardiovascular autonomic dysregulation and fatigue in multiple sclerosis. Mult. Scelerosis. 7, 320–326 (2011). http://journals.sagepub.com/doi/pdf/10.1177/135245850100700508 (Accessed 18 Apr 2018)
J.L. Newton, O. Okonkwo, K. Sutcliffe, A. Seth, J. Shin, D.E.J. Jones, Symptoms of autonomic dysfunction in chronic fatigue syndrome. QJM 100, 519–26 (2007). https://doi.org/10.1093/qjmed/hcm057
R. Freeman, A.L. Komaroff, Does the chronic fatigue syndrome involve the autonomic nervous system? Am. J. Med. 102, 357–64 (1997). http://www.ncbi.nlm.nih.gov/pubmed/9217617 (Accessed 13 Dec 2018)
T.J. Vokes, M. Mannstadt, M.A. Levine, B.L. Clarke, P. Lakatos, K. Chen, R. Piccolo, A. Krasner, D.M. Shoback, J.P. Bilezikian, Recombinant human parathyroid hormone effect on health-related quality of life in adults with chronic hypoparathyroidism. J. Clin. Endocrinol. Metabol. 103, 722–731 (2018). https://doi.org/10.1210/jc.2017-01471
G. Tabacco, Y.-K.D. Tay, N.E. Cusano, J. Williams, B. Omeragic, R. Majeed, M.G. Almonte, M.R. Rubin, J.P. Bilezikian, Quality of life in hypoparathyroidism improves with rhPTH(1-84) throughout 8 years of therapy. J. Clin. Endocrinol. Metabol. (2019). https://doi.org/10.1210/jc.2018-02430
Study design: GT, AP. Study conduct: GT, AMN, AMDT, PP, SM, and AP. Data collection: GT, AMN, AMDT, DM, AS, RC, DB, and AP. Data analysis: CP and DL. Data interpretation: GT, AMN, CP, DL, and AP. Drafting manuscript: GT, AMN, and AP. Revising manuscript content: GT, AMN, AMDT, DM, AS, RC, DB, PP, SM, and AP. Approving final version of manuscript: GT, AMN, DM, AMDT, AS, RC, DB, GG, PP, SM, and AP. GT, AMN, and AP take responsibility for the integrity of the data analysis.
Conflict of interest
The authors declare that they have no conflict of interest.
The study was conducted in compliance with the Declaration of Helsinki and its later amendments or comparable ethical standards. The research protocol was approved by the Ethics Committee at the University Campus Bio-Medico of Rome.
Informed consent was obtained from all individual included in the study.
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Tabacco, G., Naciu, A.M., Cesareo, R. et al. Cardiovascular autonomic neuropathy as a cause of fatigue in chronic hypoparathyroidism. Endocrine 67, 198–203 (2020). https://doi.org/10.1007/s12020-019-02101-w
- Cardiovascular Autonomic Neuropathy
- Quality of life, PTH