Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy

Abstract

Purpose

There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy, but the mechanism of cognitive dysfunction has not been delineated. We assessed if cerebrovascular function is impaired in PHPT, improves post-parathyroidectomy and is associated with PTH level and cognitive dysfunction.

Methods

This is an observational study of 43 patients with mild hypercalcemic or normocalcemic PHPT or goiter. At baseline, cerebrovascular function (dynamic cerebral autoregulation and vasomotor reactivity) by transcranial Doppler and neuropsychological function were compared between all three groups. A subset underwent parathyroidectomy or thyroidectomy, and was compared 6 months post-operatively.

Results

Mean cerebrovascular and neuropsychological function was normal and no worse in PHPT compared to controls preoperatively. Higher PTH was associated with worse intracerebral autoregulation (r = − 0.43, p = 0.02) and worse cognitive performance on some tests. Post-parathyroidectomy, mood improved significantly, but changes did not differ compared to those having thyroidectomy (p = 0.84). There was no consistent improvement in cognition or change in vascular function in either surgical group.

Conclusions

Although higher PTH was associated with worse intracerebral autoregulation, cerebrovascular function, cognition and mood were normal in mild PHPT. PTX did not improve vascular or cognitive function. The observed improvement in mood cannot be clearly attributed to PTX. Notwithstanding the small sample size, the results do not support changing current criteria for parathyroidectomy to include cognitive complaints. However, the associations between PTH, cognition and cerebral autoregulation merit future studies in those with more severe hyperparathyroidism.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. 1.

    Silverberg SJ, Shane E, Jacobs TP, Siris E, Bilezikian JP (1999) A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med 341:1249–1255

  2. 2.

    Walker MD, Silverberg SJ (2018) Primary hyperparathyroidism. Nat Rev Endocrinol 14:115–125

  3. 3.

    Walker MD, Bilezikian JP (2018) Primary hyperparathyroidism: recent advances. Curr Opin Rheumatol 30:427–439

  4. 4.

    Chiodini I, Cairoli E, Palmieri S, Pepe J, Walker MD (2018) Non classical complications of primary hyperparathyroidism. Best Pract Res Clin Endocrinol Metab 32:805–820

  5. 5.

    Walker MD, McMahon DJ, Inabnet WB, Lazar RM, Brown I, Vardy S, Cosman F, Silverberg SJ (2009) Neuropsychological features in primary hyperparathyroidism: a prospective study. J Clin Endocrinol Metab 94:1951–1958

  6. 6.

    Sheldon DG, Lee FT, Neil NJ, Ryan JA Jr (2002) Surgical treatment of hyperparathyroidism improves health-related quality of life. Arch Surg 137:1022–1026 (discussion 1026–1028)

  7. 7.

    Amstrup AK, Rejnmark L, Mosekilde L (2011) Patients with surgically cured primary hyperparathyroidism have a reduced quality of life compared with population-based healthy sex-, age-, and season-matched controls. Eur J Endocrinol 165:753–760

  8. 8.

    Bollerslev J, Jansson S, Mollerup CL, Nordenstrom J, Lundgren E, Torring O, Varhaug JE, Baranowski M, Aanderud S, Franco C, Freyschuss B, Isaksen GA, Ueland T, Rosen T (2007) Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial. J Clin Endocrinol Metab 92:1687–1692

  9. 9.

    Ambrogini E, Cetani F, Cianferotti L, Vignali E, Banti C, Viccica G, Oppo A, Miccoli P, Berti P, Bilezikian JP, Pinchera A, Marcocci C (2007) Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial. J Clin Endocrinol Metab 92:3114–3121

  10. 10.

    Talpos GB, Bone HG 3rd, Kleerekoper M, Phillips ER, Alam M, Honasoge M, Divine GW, Rao DS (2000) Randomized trial of parathyroidectomy in mild asymptomatic primary hyperparathyroidism: patient description and effects on the SF-36 health survey. Surgery 128:1013–1020 (discussion 1011–1020)

  11. 11.

    Roman SA, Sosa JA, Mayes L, Desmond E, Boudourakis L, Lin R, Snyder PJ, Holt E, Udelsman R (2005) Parathyroidectomy improves neurocognitive deficits in patients with primary hyperparathyroidism. Surgery 138:1121–1128 (discussion 1128–1129)

  12. 12.

    Benge JF, Perrier ND, Massman PJ, Meyers CA, Kayl AE, Wefel JS (2009) Cognitive and affective sequelae of primary hyperparathyroidism and early response to parathyroidectomy. J Int Neuropsychol Soc 15:1002–1011

  13. 13.

    Perrier ND, Balachandran D, Wefel JS, Jimenez C, Busaidy N, Morris GS, Dong W, Jackson E, Weaver S, Gantela S, Evans DB, Grubbs EG, Lee JE (2009) Prospective, randomized, controlled trial of parathyroidectomy versus observation in patients with “asymptomatic” primary hyperparathyroidism. Surgery 146:1116–1122

  14. 14.

    Chiang CY, Andrewes DG, Anderson D, Devere M, Schweitzer I, Zajac JD (2005) A controlled, prospective study of neuropsychological outcomes post parathyroidectomy in primary hyperparathyroid patients. Clin Endocrinol (Oxf) 62:99–104

  15. 15.

    Numann PJ, Torppa AJ, Blumetti AE (1984) Neuropsychologic deficits associated with primary hyperparathyroidism. Surgery 96:1119–1123

  16. 16.

    Babinska D, Barczynski M, Stefaniak T, Oseka T, Babinska A, Babinski D, Sworczak K, Lachinski AJ, Nowak W, Sledzinski Z (2012) Evaluation of selected cognitive functions before and after surgery for primary hyperparathyroidism. Langenbecks Arch Surg 397:825–831

  17. 17.

    Walker MD, Silverberg SJ (2007) Parathyroidectomy in asymptomatic primary hyperparathyroidism: improves “bones” but not “psychic moans”. J Clin Endocrinol Metab 92:1613–1615

  18. 18.

    Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, Potts JT Jr (2014) Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab 99:3561–3569

  19. 19.

    Walker MD, Fleischer J, Rundek T, McMahon DJ, Homma S, Sacco R, Silverberg SJ (2009) Carotid vascular abnormalities in primary hyperparathyroidism. J Clin Endocrinol Metab 94:3849–3856

  20. 20.

    Rubin MR, Maurer MS, McMahon DJ, Bilezikian JP, Silverberg SJ (2005) Arterial stiffness in mild primary hyperparathyroidism. J Clin Endocrinol Metab 90:3326–3330

  21. 21.

    Judd BW, Meyer JS, Rogers RL, Gandhi S, Tanahashi N, Mortel KF, Tawaklna T (1986) Cognitive performance correlates with cerebrovascular impairments in multi-infarct dementia. J Am Geriatr Soc 34:355–360

  22. 22.

    Marshall RS, Festa JR, Cheung YK, Chen R, Pavol MA, Derdeyn CP, Clarke WR, Videen TO, Grubb RL, Adams HP, Powers WJ, Lazar RM (2012) Cerebral hemodynamics and cognitive impairment: baseline data from the RECON trial. Neurology 78:250–255

  23. 23.

    Marshall RS (2012) Effects of altered cerebral hemodynamics on cognitive function. J Alzheimers Dis 32:633–642

  24. 24.

    Balestrini S, Perozzi C, Altamura C, Vernieri F, Luzzi S, Bartolini M, Provinciali L, Silvestrini M (2013) Severe carotid stenosis and impaired cerebral hemodynamics can influence cognitive deterioration. Neurology 80:2145–2150

  25. 25.

    Alosco ML, Spitznagel MB, Cohen R, Raz N, Sweet LH, Josephson R, Hughes J, Rosneck J, Gunstad J (2014) Reduced cerebral perfusion predicts greater depressive symptoms and cognitive dysfunction at a 1-year follow-up in patients with heart failure. Int J Geriatr Psychiatry 29:428–436

  26. 26.

    Eastell R, Brandi ML, Costa AG, D’Amour P, Shoback DM, Thakker RV (2014) Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the fourth international workshop. J Clin Endocrinol Metab 2014:jc20141414

  27. 27.

    Eastell R, Arnold A, Brandi ML, Brown EM, D’Amour P, Hanley DA, Rao DS, Rubin MR, Goltzman D, Silverberg SJ, Marx SJ, Peacock M, Mosekilde L, Bouillon R, Lewiecki EM (2009) Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab 94:340–350

  28. 28.

    Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ (2007) Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype. J Clin Endocrinol Metab 92:3001–3005

  29. 29.

    Walker MD, Cong E, Kepley A, Di Tullio MR, Rundek T, Homma S, Lee JA, Liu R, Young P, Zhang C, McMahon DJ, Silverberg SJ (2014) Association between serum 25-hydroxyvitamin D level and subclinical cardiovascular disease in primary hyperparathyroidism. J Clin Endocrinol Metab 99:671–680

  30. 30.

    Marshall RS, Rundek T, Sproule DM, Fitzsimmons BF, Schwartz S, Lazar RM (2003) Monitoring of cerebral vasodilatory capacity with transcranial Doppler carbon dioxide inhalation in patients with severe carotid artery disease. Stroke 34:945–949

  31. 31.

    Marshall RS, Pavol MA, Cheung YK, Strom I, Slane K, Asllani I, Lazar RM (2016) Dissociation among hemodynamic measures in asymptomatic high grade carotid artery stenosis. J Neurol Sci 367:143–147

  32. 32.

    Ortega-Gutierrez S, Petersen N, Masurkar A, Reccius A, Huang A, Li M, Choi JH, Marshall RS (2014) Reliability, asymmetry, and age influence on dynamic cerebral autoregulation measured by spontaneous fluctuations of blood pressure and cerebral blood flow velocities in healthy individuals. J Neuroimaging 24:379–386

  33. 33.

    Ogino K, Burkhoff D, Bilezikian JP (1995) The hemodynamic basis for the cardiac effects of parathyroid hormone (PTH) and PTH-related protein. Endocrinology 136:3024–3030

  34. 34.

    Collip JB, Clark EP (1925) Further studies on the physiological action of a parathyroid hormone. J Biol Chem 64:485–507

  35. 35.

    Pang PK, Tenner TE Jr, Yee JA, Yang M, Janssen HF (1980) Hypotensive action of parathyroid hormone preparations on rats and dogs. Proc Natl Acad Sci USA 77:675–678

  36. 36.

    Reinhard M, Schwarzer G, Briel M, Altamura C, Palazzo P, King A, Bornstein NM, Petersen N, Motschall E, Hetzel A, Marshall RS, Klijn CJ, Silvestrini M, Markus HS, Vernieri F (2014) Cerebrovascular reactivity predicts stroke in high-grade carotid artery disease. Neurology 83:1424–1431

  37. 37.

    Walker MD, Rundek T, Homma S, Ditullio M, Iwata S, Lee JA, Choi J, Liu R, Zhang C, McMahon DJ, Sacco RL, Silverberg SJ (2012) Effect of parathyroidectomy on subclinical cardiovascular disease in mild primary hyperparathyroidism. Eur J Endocrinol 167:277–285

  38. 38.

    Cansu GB, Yilmaz N, Ozdem S, Balci MK, Suleymanlar G, Arici C, Boz A, Sari R, Altunbas HA (2016) Parathyroidectomy in asymptomatic primary hyperparathyroidism reduces carotid intima-media thickness and arterial stiffness. Clin Endocrinol (Oxf) 84:39–47

  39. 39.

    Schillaci G, Pucci G, Pirro M, Monacelli M, Scarponi AM, Manfredelli MR, Rondelli F, Avenia N, Mannarino E (2011) Large-artery stiffness: a reversible marker of cardiovascular risk in primary hyperparathyroidism. Atherosclerosis 218:96–101

  40. 40.

    Carrelli A, Walker M, Tullio D, Homma S, Zhang C, McMahon D, Silverberg S (2012) Endothelial function in mild primary hyperparathyroidism. Clin Endocrinol (Oxf) 78(2):204–209

  41. 41.

    Ejlsmark-Svensson H, Rolighed L, Rejnmark L (2019) Effect of Parathyroidectomy on cardiovascular risk factors in primary hyperparathyroidism: a randomised clinical trial. J Clin Endocrinol Metab 104:3223–3232

  42. 42.

    Mjaland O, Normann E, Halvorsen E, Rynning S, Egeland T (2003) Regional cerebral blood flow in patients with primary hyperparathyroidism before and after successful parathyroidectomy. Br J Surg 90:732–737

  43. 43.

    Cermik TF, Kaya M, Ugur-Altun B, Bedel D, Berkarda S, Yigitbasi ON (2007) Regional cerebral blood flow abnormalities in patients with primary hyperparathyroidism. Neuroradiology 49:379–385

  44. 44.

    Cogan MG, Covey CM, Arieff AI, Wisniewski A, Clark OH, Lazarowitz V, Leach W (1978) Central nervous system manifestations of hyperparathyroidism. Am J Med 65:963–970

  45. 45.

    Goyal A, Chumber S, Tandon N, Lal R, Srivastava A, Gupta S (2001) Neuropsychiatric manifestations in patients of primary hyperparathyroidism and outcome following surgery. Indian J Med Sci 55:677–686

  46. 46.

    Mittendorf EA, Wefel JS, Meyers CA, Doherty D, Shapiro SE, Lee JE, Evans DB, Perrier ND (2007) Improvement of sleep disturbance and neurocognitive function after parathyroidectomy in patients with primary hyperparathyroidism. Endocr Pract 13:338–344

  47. 47.

    Prager G, Kalaschek A, Kaczirek K, Passler C, Scheuba C, Sonneck G, Niederle B (2002) Parathyroidectomy improves concentration and retentiveness in patients with primary hyperparathyroidism. Surgery 132:930–935 (discussion 935–936)

  48. 48.

    Lourida I, Thompson-Coon J, Dickens CM, Soni M, Kuzma E, Kos K, Llewellyn DJ (2015) Parathyroid hormone, cognitive function and dementia: a systematic review. PLoS One 10:e0127574

Download references

Funding

NIH R21 DK104105, UL1RR024156, Endocrine Fellows Foundation, Columbia University Aging Center Grant.

Author information

Correspondence to M. D. Walker.

Ethics declarations

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

This study was approved by the CUMC IRB.

Informed consent

All participants provided written informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, M., Sum, M., Cong, E. et al. Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy. J Endocrinol Invest 43, 369–379 (2020). https://doi.org/10.1007/s40618-019-01128-0

Download citation

Keywords

  • Primary hyperparathyroidism
  • Cognition
  • Vascular stiffness
  • Vasomotor reactivity
  • Autoregulation