A Pilot Study of Cognition Among Hypoparathyroid Adults

Mishaela R. Rubin; Gaia Tabacco; Beatriz Omeragic; Rukshana Majeed; Christiane Hale; Adam M. Brickman


J Endo Soc. 2022;6(3) 

In This Article

Abstract and Introduction


Purpose: Hypoparathyroid patients describe cognitive deficits, yet data regarding objective assessment of cognitive function are limited. We assessed cognition in a pilot study of hypoparathyroid patients using the National Institutes of Health Toolbox® Adult Cognitive Battery (NIHTB-CB). We also sought to determine whether cognition relates to emotion, quality of life, and hypoparathyroidism-related biochemistries.

Methods: Nineteen hypoparathyroid patients were studied. Objective cognition was assessed with NIHTB-CB. Impairment was defined as fully demographically adjusted T-score < 1.5 SD in at least 1 cognitive domain or < 1 SD in 2 or more domains.

Results: Of the 19 participants (17 women; median age 49; 18 postsurgical), impaired demographically adjusted NIHTB-CB cognition scores were observed in 13 subjects (68%). Cognition scores correlated with self-reported perception of general health. Processing speed was the most commonly impaired cognitive domain, with T-scores that were ≤2 SD in 6 subjects (32%). Processing speed correlated with serum calcium (r = 0.53, P = 0.023) and inversely with serum phosphate (r = −0.48, P = 0.042) levels.

Conclusions: Impaired cognition using the NIHTB-CB was common in this small pilot cohort of hypoparathyroid patients. Slower processing speed was present and associated with lower serum calcium and higher serum phosphate levels. Larger controlled studies with additional neuropsychological testing are needed to investigate cognitive function in hypoparathyroidism.


Hypoparathyroidism is a rare endocrine disorder that leads to hypocalcemia, hypercalciuria, and hyperphosphatemia.[1] Cognitive deficits are frequently reported by hypoparathyroid patients. A common complaint is "brain fog," with slowed thinking and an inability to perform day-to-day tasks.[2] Yet data regarding objective assessments of cognitive function in hypoparathyroidism are scarce. Most of the available reports have used the Short Form Health Survey (SF-36) scale,[3–10] which is a self-report of impaired quality of life (QoL). It is thus unclear to what extent objective, performance-based, and clinically meaningful measures of cognitive function are abnormal in hypoparathyroidism.

The National Institutes of Health (NIH) Toolbox® Cognition Battery (NIHTB-CB) is a validated and reliable method for objective assessment of cognitive function.[11–14] This instrument assesses the cognitive domains of language, episodic memory, executive function, attention, working memory, and processing speed. It has been validated with the item response theory method and is considered to have comparable precision with traditional neuropsychological measures.[15,16] It generates cognitive outcomes that are adjusted for age, sex, race, ethnicity, and education based on normative data collected in a large US nationally representative sample. We hypothesized that the NIHTB-CB would provide preliminary data regarding cognition in a pilot cohort of hypoparathyroid individuals.

Given that depression and anxiety are increased in hypoparathyroidism,[17–19] we also questioned whether cognitive abilities relate to emotional function. The NIH Toolbox® Emotion Battery (NIHTB-EB), also normed on large US nationally representative samples, was created to assess emotional functioning.[20,21] We anticipated that the NIHTB-EB would reveal psychological symptoms that would relate to cognition and to QoL as measured by the SF-36.

We also considered that serum calcium levels relate to neurological findings in hypoparathyroidism, with hypocalcemia causing neuromuscular irritability.[1] We therefore further hypothesized that cognition as a continuous construct would be associated with hypoparathyroidism-related biochemical abnormalities.