Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy

Liu, M; Sum, Melissa; Cong, Elaine; Colon, Ilma; Bucovsky, Mariana; Williams, John M.; Kepley, Anna; Kuo, Jennifer H.; Lee, J A; Lazar, Ronald M.; Marshall, Randolph S.; Silverberg, Shonni J.; Walker, Marcella D.

doi:10.1007/s40618-019-01128-0

Cited by 21 publications

(21 citation statements)

References 47 publications

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“…(50) Another recent study showed no improvement in cerebrovascular or neuropsychological function in patients with NHPT after parathyroidectomy. (51) One study has examined the relationship between NHPT and quality of life. (52) This study addressed both physical and mental aspects of patients with NHPT and PHPT.…”

Section: Nonclassical Manifestationsmentioning

confidence: 99%

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Normocalcemic Hyperparathyroidism: A Heterogeneous Disorder Often Misdiagnosed?

Zavatta

Clarke

2020

JBMR Plus

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Normocalcemic primary hyperparathyroidism (NHPT) was first described over 10 years ago, but uncertainties still remain about its definition, prevalence, and rates of complications. As a result, consensus management guidelines for this condition have not yet been published. Several hypotheses have been proposed for the pathophysiology of NHPT, but it may be a heterogeneous disorder with multiple causes, rather than a single etiology that explains this biochemical phenotype. A common clinical concern is whether NHPT should be treated surgically when complications are already present at first recognition of the disorder, rather than following patients clinically over time. The literature on NHPT is based mostly on larger studies of population‐based cohorts and smaller studies from referral centers. Lack of rigorous diagnostic criteria and selection bias inherent in populations seen at tertiary referral centers may explain the heterogeneity of reported rates of bone and renal complications in relation to consistently mild laboratory alterations. Unresolved questions remain about the significance of NHPT when it is diagnosed biochemically without evident bone or kidney complications. Moreover, its natural history remains to be elucidated because a proportion of what is classified as NHPT may revert to normal spontaneously, thus revealing previously unrecognized secondary hyperparathyroidism. These issues indicate that caution should be used in recommending surgery for NHPT. This review will focus on recent issues regarding the pathophysiology, evaluation, and management of NHPT. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Section: Nonclassical Manifestationsmentioning

confidence: 99%

“…( 50 ) Another recent study showed no improvement in cerebrovascular or neuropsychological function in patients with NHPT after parathyroidectomy. ( 51 )…”

Section: Nonclassical Manifestationsmentioning

confidence: 99%

Normocalcemic Hyperparathyroidism: A Heterogeneous Disorder Often Misdiagnosed?

Zavatta

Clarke

2020

JBMR Plus

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“…We cannot further isolate the individual roles of calcium vs. PTH in the pathophysiology with the current analysis given the design and associations with both biochemistries. Both PTH and calcium have been associated with worse cognition in other studies (5,17,31,32,33). The exact pathways by which PTH and calcium affect cognition have not been fully delineated.…”

Section: Discussionmentioning

confidence: 78%

“…Hypercalcemia could interfere with that process. PTH may also have effects on cerebrovascular function (32). Both may act through other mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Functional magnetic resonance imaging in primary hyperparathyroidism

Gazes

Liu

Sum

et al. 2020

European Journal of Endocrinology

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Objective The neurophysiological mechanisms underlying cognitive dysfunction in primary hyperparathyroidism (PHPT) and the brain regions affected are not clear. We assessed neural activation during cognitive testing (matrix reasoning, paired associates, and logical memory) using functional MRI (fMRI) in 23 patients with PHPT and 23 healthy controls. A subset with PHPT was re-assessed 6 months post-parathyroidectomy (PTX). Design This is an observational study comparing neural activation by fMRI in patients with PHPT to normative controls. Postmenopausal women were studied at a tertiary referral center. Results There were no between-group differences in cognitive task performance. Patients with PHPT had lower neural activation vs controls (max Z = 4.02, all P < 0.01) during matrix reasoning in brain regions involved in executive function (left frontal lobe (k = 57) and right medial frontal gyrus (k = 72)) and motor function (right precentral gyrus (k = 51)). During paired associates (verbal memory), those with PHPT had greater activation in the right inferior parietal lobule (language/mathematical operations; k = 65, P < 0.01). Greater activation in this region bilaterally correlated with higher PTH (k = 96, P < 0.01). Post-PTX, activation decreased during matrix reasoning, but in different regions than those affected pre-PTX. Conclusions PHPT is associated with differences in task-related neural activation patterns, but no difference in cognitive performance. While this may indicate compensation to maintain the same cognitive function, there was no clear improvement in neural activation after PTX. Larger, longitudinal studies that include PHPT patients followed without surgery are needed to determine if PTX could prevent worsening of altered neural activation patterns in PHPT.

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“…While most patients today are "asymptomatic", lacking the classical skeletal and renal manifestations of PHPT, nonspecific neuropsychological symptoms are also investigated (2)(3)(4)(5). Several studies suggested that PHPT was associated with impaired quality of life (QoL), anxiety, and depression as evaluated by questionnaires (6)(7)(8). Although these symptoms are concerning, there is a debate upon whether these symptoms are directly and specifically attributable to PHPT (7).…”

Section: Introductionmentioning

confidence: 99%

The Associations of Serum Osteocalcin and Cortisol Levels With the Psychological Performance in Primary Hyperparathyroidism Patients

Wang

Zhu

et al. 2021

Front. Endocrinol.

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ObjectivesThe aim of this study was to investigate factors responsible for the psychological performance in primary hyperparathyroidism (PHPT) patients.MethodsA group of 38 PHPT patients receiving questionnaires, including Beck Depression Inventory (BDI), State–Trait Anxiety Inventory (STAI), and 36-Item Short Form Survey (SF-36), was evaluated. The relationships between scores of questionnaires and clinical biomarkers were examined. Collinearity and linear regression model were applied to examine variables determining the scores of the questionnaire. In 192 PHPT patients, bivariate and partial correlation were used to analyze the relationships between serum concentrations of parathyroid hormone (PTH), calcium, osteocalcin (OCN), and cortisol.ResultsAmong 38 patients receiving questionnaire tests, 50% (19/38) of the patients developed state anxiety, 60.5% (23/38) of the patients had the trait of developing anxiety. In addition, 18.4% (7/38) of the patients developed mild to severe depression. Serum cortisol at 8:00 was negatively and significantly correlated with social function (r = -0.389, p = 0.041) after controlling for age, sex, disease duration, serum PTH, calcium, phosphorus, and 25-hydroxyvitamin D [25(OH)D] concentration. OCN was significantly and negatively correlated with score of STAI-S (r = -0.426, p = 0.027). In the linear regression model for BDI score, variables with statistical significance were serum OCN (β = -0.422, p = 0.019) and cortisol at 0:00 (β = 0.371, p = 0.037). In 192 PHPT patients, the serum concentration of OCN (r = 0.373, p = 0.000) was positively correlated with PTH level. After controlling for age, sex, disease duration, serum 25(OH)D, phosphorus, and calcium concentration, the positive correlation between OCN and PTH was still statistically significant (r = 0.323, p = 0.000). The serum concentration of cortisol at 0:00 was significantly and positively correlated with serum calcium (r = 0.246, p = 0.001) in bivariate correlation analysis. After controlling for age, sex, disease duration, serum PTH, 25(OH)D, and phosphorus concentration, serum cortisol at 0:00 was still positively and significantly correlated with serum calcium (r = 0.245, p = 0.001).ConclusionSerum levels of OCN and cortisol, rather than PTH and calcium, are associated with the development of anxiety and depression symptoms in PHPT patients.

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Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy

Cited by 21 publications

References 47 publications

Normocalcemic Hyperparathyroidism: A Heterogeneous Disorder Often Misdiagnosed?

Normocalcemic Hyperparathyroidism: A Heterogeneous Disorder Often Misdiagnosed?

Functional magnetic resonance imaging in primary hyperparathyroidism

The Associations of Serum Osteocalcin and Cortisol Levels With the Psychological Performance in Primary Hyperparathyroidism Patients

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