Skip to main content

The association between hypoparathyroidism and cognitive impairment: a systematic review


Context and purpose

Hypocalcemia and low parathyroid hormone levels have been commonly suggested as factors able to induce central nervous system disturbances. However, evidences on the occurrence of cognitive impairment are limited or underestimated. The aim of this review is, therefore, to systematically summarize the available evidence concerning the occurrence of cognitive impairment among subjects suffering from idiopathic or secondary hypoparathyroidism.


A systematic selection of the available literature was performed by searching the online databases PubMed, Scopus and Web of Knowledge.


The present systematic review included sixteen case report articles and one cross-sectional controlled study. Case reports were the most representative literature sources and involved ten women and seven men. The presence of cognitive impairment was mostly discussed in association with idiopathic hypoparathyroidism (HPT); five articles described the occurrence of cognitive impairment following postsurgical HPT. The case-controlled study reported a significant presence of peculiar cognitive deficits (e.g. reduced inhibitory control, impairment in visuo-spatial functioning among, and psychomotor retardation) among HPT subjects compared to healthy controls, with serum total calcium and its product with phosphorus as independent predictors of neuropsychological dysfunctions.


Even though mostly based on single case reports, the presence of neuropsychological dysfunctions in the context of HPT appears to be a consistent core finding.

This is a preview of subscription content, access via your institution.

Fig. 1



Subjective cognitive decline


Mild cognitive impairment


Parathyroid hormone


Blood brain barrier




Mini Mental State Examination


Montreal Cognitive Assessment


Wechsler Adult Intelligence Scale


PTH 2 receptor


G protein-coupled receptors


Tuber infundibular peptide of 39 residues


  1. 1.

    Fisher GG, Chaffee DS, Tetrick LE, Davalos DB, Potter GG (2017) Cognitive functioning, aging, and work: a review and recommendations for research and practice. J Occup Health Psychol 22(3):314–336.

    Article  PubMed  Google Scholar 

  2. 2.

    Mungas D, Beckett L, Harvey D et al (2010) Heterogeneity of cognitive trajectories in diverse older persons. Psychol Aging 25(3):606–619.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Bezdicek O, Červenková M, Georgi H et al (2020) Long-term cognitive trajectory and activities of daily living in healthy aging. Clin Neuropsychol.

    Article  PubMed  Google Scholar 

  4. 4.

    Hartshorne JK, Germine LT (2015) When does cognitive functioning peak? The asynchronous rise and fall of different cognitive abilities across the life span. Psychol Sci 26(4):433–443.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Ampadu J, Morley JE (2015) Heart failure and cognitive dysfunction. Int J Cardiol 178:12–23.

    Article  PubMed  Google Scholar 

  6. 6.

    Morley JE (2016) The complexities of diabetes in older persons. J Am Med Dir Assoc 17(10):872–874.

    Article  PubMed  Google Scholar 

  7. 7.

    Lee S, Shimada H, Park H et al (2015) The association between kidney function and cognitive decline in community-dwelling, elderly Japanese people. J Am Med Dir Assoc 16(4):349.e1–349.e3495.

    Article  Google Scholar 

  8. 8.

    Catalano A, Sardella A, Bellone F, Lasco CG, Martino G, Morabito N (2019) Executive functions predict fracture risk in postmenopausal women assessed for osteoporosis. Aging Clin Exp Res.

    Article  PubMed  Google Scholar 

  9. 9.

    Usdin TB, Gruber C, Bonner TI (1995) Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. J Biol Chem 270(26):15455–15458.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Bühler G, Balabanova S, Milowski S et al (1997) Detection of immunoreactive parathyroid hormone-related protein in human cerebrospinal fluid. Exp Clin Endocrinol Diabetes 105(6):336–340.

    Article  PubMed  Google Scholar 

  11. 11.

    Lourida I, Thompson-Coon J, Dickens CM et al (2015) Parathyroid hormone, cognitive function and dementia: a systematic review. PLoS ONE 10(5):e0127574.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Powers J, Joy K, Ruscio A, Lagast H (2013) Prevalence and incidence of hypoparathyroidism in the United States using a large claims database. J Bone Miner Res 28(12):2570–2576.

    Article  PubMed  Google Scholar 

  13. 13.

    Cianferotti L, Parri S, Gronchi G et al (2018) Prevalence of chronic hypoparathyroidism in a Mediterranean region as estimated by the analysis of anonymous healthcare database. Calcif Tissue Int 103(2):144–150.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Cipriani C, Pepe J, Biamonte F et al (2017) The epidemiology of hypoparathyroidism in Italy: an 8-year register-based study. Calcif Tissue Int 100(3):278–285.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Clarke BL, Brown EM, Collins MT et al (2016) Epidemiology and diagnosis of hypoparathyroidism. J Clin Endocrinol Metab 101(6):2284–2299.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Bilezikian JP, Khan A, Potts JT Jr et al (2011) Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J Bone Miner Res 26(10):2317–2337.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Bilezikian JP (2020) Hypoparathyroidism. J Clin Endocrinol Metab 105(6):1722–1736.

    Article  Google Scholar 

  18. 18.

    Pepe J, Colangelo L, Biamonte F et al (2020) Diagnosis and management of hypocalcemia. Endocrine.

    Article  PubMed  Google Scholar 

  19. 19.

    Kim SM, Zhao D, Schneider ALC et al (2017) Association of parathyroid hormone with 20-year cognitive decline: the ARIC study. Neurology 89(9):918–926.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Lenzo V, Sardella A, Martino G, Quattropani MC (2020) A systematic review of metacognitive beliefs in chronic medical conditions. Front Psychol 10:2875.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Robinson KC, Kallberg MH, Crowley MF (1954) Idiopathic hypoparathyroidism presenting as dementia. Br Med J 2(4898):1203–1206.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Eraut D (1974) Idiopathic hypoparathyroidism presenting as dementia. Br Med J 1(5905):429–430.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Mateo D, Giménez-Roldán S (1982) Dementia in Idiopathic hypoparathyroidism. Rapid efficacy of alfacalcidol. Arch Neurol 39(7):424–425.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Lorusso S, Poli V, Casmiro M (1994) Cognitive improvement following treatment in a case of idiopathic hypoparathyroidism. Eur Neurol 34(5):292–294.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Nicolai A, Lazzarino LG (1994) Dementia syndrome in patients with postsurgical hypoparathyroidism and extensive brain calcifications. Eur Neurol 34(4):230–235.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Roca B, Mínguez C, Sáez-Royuela A, Simón E (1995) Dementia, myopathy, and idiopathic hypoparathyroidism. Postgrad Med J 71(841):702.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Stuerenburg HJ, Hansen HC, Thie A, Kunze K (1996) Reversible dementia in idiopathic hypoparathyroidism associated with normocalcemia. Neurology 47(2):474–476.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Gálvez-Jiménez N, Hanson MR, Cabral J (2000) Dopa-resistant parkinsonism, oculomotor disturbances, chorea, mirror movements, dyspraxia, and dementia: the expanding clinical spectrum of hypoparathyroidism. A case report. Mov Disord 15(6):1273–1276.<1273:aid-mds1038>;2-o

    Article  PubMed  Google Scholar 

  29. 29.

    Heckmann JG, Lang CJ, Neundörfer B (2000) Reversible dementia due to coexisting disease. Lancet 355(9220):2075.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Adorni A, Lussignoli G, Geroldi C, Zanetti O (2005) Extensive brain calcification and dementia in postsurgical hypoparathyroidism. Neurology 65(9):1501.

    Article  PubMed  Google Scholar 

  31. 31.

    Titlic M, Tonkic A, Jukic I, Filipovic-Grcic P, Kolic K (2008) Cognitive impairment and epilepsy seizure caused by hypoparathyroidism. Bratisl Lek Listy 109(2):79–81

    CAS  PubMed  Google Scholar 

  32. 32.

    Katsidzira L, Machiridza T, Ndlovu A (2010) A potentially treatable cause of dementia. Cent Afr J Med 56(5–8):41–44

    CAS  PubMed  Google Scholar 

  33. 33.

    Kumar G, Kaur D, Aggarwal P, Khurana T (2013) Hypoparathyroidism presenting as cognitive dysfunction. BMJ Case Rep 2013:bcr2013009220.

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Moreno Ó, García PT, Sánchez D, Sancho T, Lecumberri B (2015) Cognitive impairment and severe hypocalcemia in a patient with hypoparathyroidism and systemic sclerosis. Report of a case. Endocrinol Nutr 62(7):356–358.

    Article  PubMed  Google Scholar 

  35. 35.

    Terada T, Kakimoto A, Yoshikawa E et al (2015) The possible link between GABAergic dysfunction and cognitive decline in a patient with idiopathic hypoparathyroidism. Intern Med 54(17):2245–2250.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Dos Santos VM, Da Mata AM, Ribeiro KR, Calvo IC (2016) Fahr's syndrome and secondary hypoparathyroidism. Rom J Intern Med 54(1):63–65.

    Article  PubMed  Google Scholar 

  37. 37.

    Aggarwal S, Kailash S, Sagar R et al (2013) Neuropsychological dysfunction in idiopathic hypoparathyroidism and its relationship with intracranial calcification and serum total calcium. Eur J Endocrinol 168(6):895–903.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Goswami R, Sharma R, Sreenivas V, Gupta N, Ganapathy A, Das S (2012) Prevalence and progression of basal ganglia calcification and its pathogenic mechanism in patients with idiopathic hypoparathyroidism. Clin Endocrinol (Oxf) 77(2):200–206.

    CAS  Article  Google Scholar 

  39. 39.

    Cusano NE, Bilezikian JP (2018) Signs and symptoms of hypoparathyroidism. Endocrinol Metab Clin N Am 47(4):759–770.

    Article  Google Scholar 

  40. 40.

    Zavatta G, Clarke BL (2020) Basal ganglia calcification in hypoparathyroidism and pseudohypoparathyroidism: local and systemic metabolic mechanisms. J Endocrinol Investig.

    Article  Google Scholar 

  41. 41.

    Ropper AH (2005) Abnormalities of movement and posture due to disease of the Basal Ganglia. In: Ropper AH, Brown RH (eds) Adams and Victor’s principles of neurology. Mc Graw Hill, New York, pp 55–71

    Google Scholar 

  42. 42.

    Hoare SR, Bonner TI, Usdin TB (1999) Comparison of rat and human parathyroid hormone 2 (PTH2) receptor activation: PTH is a low potency partial agonist at the rat PTH2 receptor. Endocrinology 140(10):4419–4425.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Bagó AG, Dimitrov E, Saunders R et al (2009) Parathyroid hormone 2 receptor and its endogenous ligand tuberoinfundibular peptide of 39 residues are concentrated in endocrine, viscerosensory and auditory brain regions in macaque and human. Neuroscience 162(1):128–147.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Usdin TB, Hoare SR, Wang T, Mezey E, Kowalak JA (1999) TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus. Nat Neurosci 2(11):941–943.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Dobolyi A, Palkovits M, Usdin TB (2010) The TIP39-PTH2 receptor system: unique peptidergic cell groups in the brainstem and their interactions with central regulatory mechanisms. Prog Neurobiol 90(1):29–59.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Coutellier L, Logemann A, Kuo J, Rusnak M, Usdin TB (2011) TIP39 modulates effects of novelty-induced arousal on memory. Genes Brain Behav 10(1):90–99.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Meola A, Vignali E, Matrone A, Cetani F, Marcocci C (2018) Efficacy and safety of long-term management of patients with chronic post-surgical hypoparathyroidism. J Endocrinol Investig 41(10):1221–1226.

    CAS  Article  Google Scholar 

  48. 48.

    Bollerslev J, Schalin-Jäntti C, Rejnmark L et al (2019) MANAGEMENT OF ENDOCRINE DISEASE: unmet therapeutic, educational and scientific needs in parathyroid disorders. Eur J Endocrinol 181(3):P1–P19.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Cusano NE, Rubin MR, Irani D, Sliney J Jr, Bilezikian JP (2013) Use of parathyroid hormone in hypoparathyroidism. J Endocrinol Investig 36(11):1121–1127.

    CAS  Article  Google Scholar 

  50. 50.

    Brandi ML (2011) Genetics of hypoparathyroidism and pseudohypoparathyroidism. J Endocrinol Investig 34(7 Suppl):27–34

    CAS  Google Scholar 

  51. 51.

    Sardella A, Catalano A, Lenzo V, Bellone F, Corica F, Quattropani MC, Basile G (2020) The association between cognitive reserve dimensions and frailty among elderly: a structured narrative review. Geriatr Gerontol Int.

    Article  PubMed  Google Scholar 

Download references



Author information




AS: methodology, acquisition, screening and interpretation of data, drafting of the manuscript; AC: conceptualization, interpretation of data, drafting of the manuscript, final revision of the manuscript; FB, NM and GB: acquisition and screening of data; SM and FC: supervision.

Corresponding author

Correspondence to A. Catalano.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not involve any human subjects or animal work.

Informed consent.


Additional information

Publisher's Note

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

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 31 kb)

Supplementary file2 (DOC 26 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sardella, A., Bellone, F., Morabito, N. et al. The association between hypoparathyroidism and cognitive impairment: a systematic review. J Endocrinol Invest 44, 905–919 (2021).

Download citation


  • Hypoparathyroidism
  • Parathyroid
  • Hypocalcaemia
  • Cognitive functions
  • Cognitive impairment