Title: Neuropsychological Features in Primary Hyperparathyroidism ...

J Clin Endocrin Metab. First published ahead of print March 31, 2009 as doi:10.1210/jc.2008-2574
Title: Neuropsychological Features in Primary Hyperparathyroidism: A Prospective Study
Short title: Neuropsychological Features in Primary Hyperparathyroidism
Authors: Marcella D. Walker 1 , Donald J. McMahon 1 , William B. Inabnet 2 , Ronald M. Lazar 3 , Ijeoma
Brown 1 , Susan Vardy 4 , Felicia Cosman 4 , and Shonni J. Silverberg 1
Affiliations: 1 Department of Medicine, Columbia University College of Physicians & Surgeons, New York,
New York; 2 Department of Surgery, Columbia University College of Physicians & Surgeons, New York,
New York; 3 Department of Neurology, Columbia University College of Physicians & Surgeons, New York,
New York; 4 Helen Hayes Hospital, Regional Bone Center, West Haverstraw, New York
Corresponding author:
Marcella D. Walker, MD
630 West 168 th Street
PH8 West – 864
New York, NY 10032
212-305-6238 (telephone)
212-305-6486 (fax)
mad2037@columbia.edu
Disclosure statement: The authors have nothing to disclose.
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A précis: Mild primary hyperparathyroidism is associated with cognitive changes affecting verbal memory
and non-verbal abstraction that improve after parathyroidectomy and are independent of anxiety and
depressive symptoms
Key words: primary hyperparathyroidism, cognition, psychiatric, depression, parathyroidectomy
Word Count (text): 3629
Word Count (abstract): 247
Number of tables and figures: 6
Address reprint requests to Marcella D. Walker, MD
Funding: This work was supported by NIH R01 DK32333, K24 DK74457, and UL1 RR024156
1
Copyright (C) 2009 by The Endocrine Society

Abstract
Context: Data regarding the presence, extent and reversibility of psychological and cognitive features of
primary hyperparathyroidism (PHPT) are conflicting.
Objective: This study evaluated psychological and cognitive function symptoms in PHPT.
Design: This is a case-control study in which symptoms and their improvement 6 months after surgical cure
of PHPT were assessed.
Settings: University hospital metabolic bone disease unit and endocrine surgery practice.
Participants: 39 postmenopausal women with PHPT and 89 postmenopausal controls without PHPT.
Intervention: Parathyroidectomy
Outcome Measures: Beck Depression Inventory (BDI); State-Trait Anxiety Inventory, Form Y (STAI-Y);
North American Adult Reading Test (NAART); Wechsler Memory Scale Logical Memory Test, Russell
revision (LM); Buschke Selective Reminding Test (SRT); Rey Visual Design Learning Test (RVDLT);
Booklet Category Test, Victoria revision (BCT); Rosen Target Detection Test (RTD); Wechsler Adult
Intelligence Scale-Revised Digit Symbol Subtest (DSy); Wechsler Adult Intelligence Scale Digit Span
Subtest (DSpan).
Results: At baseline, women with PHPT had significantly higher symptom scores for depression and anxiety
than controls, and worse performance on tests of verbal memory (LM and SRT) and non-verbal abstraction
(BCT). Depressive symptoms, non-verbal abstraction and some aspects of verbal memory (LM) improved
after parathyroidectomy to the extent that scores in these domains were no longer different from controls.
Baseline differences and postoperative improvement in cognitive measures were independent of anxiety and
depressive symptoms, and were not linearly associated with serum levels of calcium or parathyroid hormone.
Conclusions: Mild PHPT is associated with cognitive features affecting verbal memory and non-verbal
abstraction that improve after parathyroidectomy.
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Introduction
Classical PHPT was a symptomatic disease with commonly recognized neurologic, cognitive and
psychiatric manifestations (1, 2). Many patients with PHPT are now asymptomatic or report only non-
specific symptoms, including weakness, easy fatigability, depression, intellectual weariness, loss of initiative,
anxiety, irritability, and sleep disturbance (3). While these symptoms are concerning, they are difficult to
quantify and there is debate about whether they are directly attributable to the underlying disease. At the
Third International Workshop on Asymptomatic Primary Hyperparathyroidism (4), studies on the
psychological and cognitive features of PHPT were reviewed and not considered to be an indication for
parathyroidectomy (5). The workshop recognized inconsistencies in the abnormalities described, their
association with the underlying disease, and the extent to which these features were reversible after
parathyroidectomy.
A number of studies have attempted to delineate the psychological and cognitive features of PHPT,
and their resolution with surgical cure (6-24). Most have focused on psychological symptoms, such as
depression, anxiety, or quality of life (QOL), rather than cognitive function such as logic, memory,
abstraction, attention/concentration, and mental manipulation. Most have suggested that there are
psychological features of the disease. A number of observational studies, some without control groups, report
improved psychological symptoms or QOL with parathyroidectomy. Findings of the 3 randomized controlled
trials (RCTs) of parathyroidectomy in mild PHPT were inconsistent; two found improved QOL after surgery
(18, 25) while one did not (17).
A smaller number of studies have examined cognitive function in PHPT (6, 9, 12, 14, 15, 26-28).
Explanations for the conflicting results from these studies include: small sample sizes; investigation of only
one or two aspects of cognition, making generalization difficult; lack of control groups or validated measures
in some studies and failure to take into account demographic differences in others. Some studies monitored
subjects shortly after parathyroidectomy, an experimental design which introduces biases due to non-specific
benefits of surgery. Finally, no studies examining cognitive function have assessed the influence of
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psychological symptoms upon cognition, which is critical since depression and anxiety are known to affect
cognitive function (29).
Therefore, it remains unclear whether cognitive impairment is a feature of modern PHPT. The
purpose of this study was (1) to examine whether cognitive function is affected in mild PHPT using a battery
of tests that measure many different facets of cognition; (2) to evaluate psychological symptoms in order to
adjust for the potentially confounding effect of depression or anxiety on performance (3) to assess
improvement in measures with surgical cure; and (4) to explore relationships between cognitive function and
biochemical indices of disease severity.
Subjects and Methods
This case-control study compared cognitive function and psychological symptoms between 2 groups
of postmenopausal women: 1) those with PHPT who decided to undergo parathyroidectomy (either because
they met 2002 surgical guidelines (30) or preferred surgery over observation, despite not meeting surgical
indications) and 2) normal controls. The prospective arm of the study assessed changes in these features
after parathyroidectomy. All patients gave written, informed consent. Patients were paid for participation in
the study and travel expenses. This study was approved by the Institutional Review Boards of Columbia
University Medical Center and Helen Hayes Hospital.
Subjects
Subjects were female, age ≥ 45 years, menopausal for ≥ 1 years, English speaking, and were
recruited at Columbia University College of Physicians & Surgeons hospitals. PHPT patients were referred
from the Metabolic Bone Diseases and Endocrine Surgery Units at Columbia University Medical Center.
Normal controls, recruited by newspaper advertisements, fliers and direct mailing, were studied at Helen
Hayes Hospital, West Haverstraw, NY. PHPT patients had hypercalcemia and an elevated or inappropriately
normal parathyroid hormone (PTH) level. Exclusion criteria (in order to eliminate the potential confounding
effects of sex, menopausal status, or significant co-morbidities on study outcomes) included male sex,
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malignancy other than non-melanoma skin cancer, alcoholism, significant liver or kidney disease, illnesses
requiring greater than 2 weeks of corticosteroids per year, traumatic brain injury or neurosurgery, seizure
disorders, untreated mood disorders and use of lithium, hydrochlorothiazide, estrogen or other medications
known to affect mineral metabolism. Between September 2003 and December 2007, 119 women with PHPT
were screened for enrollment, 46 were eligible and agreed to participate. The 73 women with PHPT who
declined participation were similar to those enrolled (mean±SEM): age 64.3±1.3 years, 98.6% white (97.2%
non-Hispanic, 2.8 % Hispanic), 1.4% black. Three women in the PHPT group never underwent
parathyroidectomy, two were not cured, and two were lost to follow-up, leaving 39 evaluable cases. The
control group included 89 subjects without PHPT.
The study was designed to have 80% power with 1% alpha-level to detect a between group
difference of 0.62 standard deviations in the post- minus pre- change in at least one of 4 test measures (Rosen
Target Symbol, WAIS Logical Recall Immediate and Delayed and total score on Beck Depression
Inventory). Cases and controls were enrolled in a 1:2 ratio to improve the precision of the estimate of change
in cognitive functioning.
Study Design
The PHPT group was evaluated pre-operatively with 9 standardized, validated cognitive and
psychological tests. A serum sample was collected for measurement of biochemistries. Demographic factors
and information on co-morbid conditions, and clinical symptoms were assessed by history. The PHPT group
was re-evaluated using the same procedures six months post-operatively. This interval was chosen to obviate
biases that might be due to the non-specific benefits of surgery. The control group underwent testing with the
same test battery at an identical interval.
Biochemical Evaluation
Serum calcium, albumin, phosphate, blood urea nitrogen, creatinine, and alkaline phosphatase
activity were measured with colorimetric or spectrophotometric methods. Intact PTH was measured by
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immunochemiluminometric assay (Scantibodies Laboratories, Inc.). Vitamin D metabolites were measured
by radioimmunoassay (DiaSorin, Inc).
Cognitive and Psychological Testing
Testing, conducted by 3 individuals using identical procedures, lasted approximately 1.5 hours. Test
administrators were not blinded to disease state or time of testing. Psychological tests refer to those
measuring depression (BDI) and anxiety (STAI) while the remainder of the tests measured cognitive
function.
1. Estimated Intellectual Quotient (IQ): The NAART provides an estimate of intellectual ability. Estimated
full-scale IQ (FSIQ) scores are obtained: Estimated FSIQ=127.8 – (.78)(NAART errors) (31, 32). The mean
normal value (±SD) is 100±15 (33).
2. Depression: The BDI (2 nd ed.) is a 21-item depression severity scale for adults. Higher scores indicate
more symptoms: 0-13 indicates no or minimal depression, 14-19 mild depression, 20-28 moderate
depression, 29-63 severe depression (34).
3. Anxiety: The STAI-Y (35) measures anxiety and consists of two 20-item scales, measuring trait anxiety
(anxiety proneness), and state anxiety (a current emotional condition). Mean raw values (± SD) for working
adults, ages 50-69, are 32.2±8.7 for state anxiety and 31.8±7.8 for trait anxiety.
4. Memory for Contextually Related Material: LM requires examinees to repeat two brief, orally-presented
stories immediately and after a 30-min delay. Results indicate idea units recalled in the two stories (36).
Immediate recall mean values (±SD) for individuals age 50-59 and 60-69 are 23.6±6.1 and 20.5±6.4
respectively. Delayed recall mean values (±SD) for individuals age 50-59 and 60-69 are 20.1±6.5 and
17.3±6.7 respectively (37).
5. Word List Memory: The SRT (38, 39) assesses recall and learning for a word list. Results indicate words
correctly recalled over six trials (maximum=72) and after a 30-min delay (maximum=12).
6. Visual Memory: The RVDLT requires subjects to recall and draw visually-presented geometric designs.
Results are scored as number of correctly reproduced designs during three learning trials (40).
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7. Non-verbal Abstraction: This was assessed with the BCT, Victoria Revision (41), an 81-item version of
the Halstead Category Test (HCT) (42), requiring examinees to infer the governing principle for sets of
visual stimuli. Errors are summed and full HCT performance is predicted: 4.335 + [1.839 x (Victoria
Revision errors)] (43), then converted to a T-score adjusting for age, education and gender (42). T-scores are
interpreted as follows: ≥55 above average, 45-54 average, 40-44 below average, 35-39 mildly impaired, 30-
34 mildly to moderately impaired, 25-29 moderately impaired, 20-24 moderately to severely impaired, and
≤19 severely impaired.
8. Visual Concentration/Attention: The RTD examines sustained visual concentration and attention.
Examinees find a target among similar items. Results indicate time to completion and errors. The mean
normal value (±SD) for the symbol version of the test and errors are 35.7±8.4 and 3.8±2.8 respectively. The
DSy (33) measures response speed and visual attention. Examinees fill in the blank squares with a nonsense
symbol corresponding to a digit. Results are scored as symbols transcribed in 90 seconds. Raw scores are
converted to scaled scores, which adjusts for age differences. The mean scaled score (±SD) is 10±3 (33).
9. Auditory Attention and Mental Manipulation: The DSpan tests immediate span of auditory attention and
mental manipulation (mean scaled score (±SD) is 10±3) (33).
Statistics
Differences between PHPT and control test performance at baseline and after 6-months were
evaluated for each outcome with linear mixed models for repeated measures with fixed effects for group,
time and their interaction, random effect of subjects and an unstructured covariance structure. Model
estimated means + SEM adjusted for covariates are reported. The method of simultaneous confidence limits
was used to assess between-groups differences at baseline or 6-months when the effects of group or the
group-by-time interaction attained statistical significance, and again for within-groups differences between
times when the fixed effects of time or group-by-time interaction achieved statistical significance. Test
scores were adjusted for age, education and sex as suggested by the test manual when methods of adjustment
were available. Since not all tests had methods of correction, all scores were additionally adjusted
statistically for age, education and estimated IQ. Scores were not adjusted for years since menopause due to
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its co-linearity with age. Education level was coded as number of years of schooling completed. Cognitive
measures were also evaluated with adjustment for levels of anxiety and depression to minimize the influence
of affective factors on cognition. Linear associations between biochemical measures and cognitive and
psychological test scores were assessed with Pearson correlation coefficients. For all analyses, a two-tailed
p≤0.05 was considered to indicate statistical significance. Statistical analysis was performed using SAS,
Version 9.1.3 (Cary, NC).
Results
Clinical and Biochemical Results
Cases had biochemical evidence of PHPT (serum calcium: 10.6±0.1 mg/dl; PTH: 77±4 pg/ml; Table
1). At baseline, PHPT patients were slightly older (61.3±1.0 vs. 55.6±0.4 years; p

PHPT, mean performance levels on these tests were not in a range suggestive of clinical depression or
anxiety. Depressive symptoms improved - the pattern of change in depressive symptoms over time differed
between the groups (group by time interaction; p=0.024) such that there was no difference between the
control and postoperative groups (PHPT 5.2±1.0 versus control 3.7±0.8, p=0.28) after parathyroidectomy.
Trait anxiety but not state anxiety decreased after parathyroidectomy in the PHPT group compared to
baseline. However, there were no differences in change over time between the groups for either trait or state
anxiety (p=0.152 and p=0.184, respectively).
Cognitive Function
Memory: Those with PHPT had worse scores for both immediate and delayed recall of contextually related
material (immediate: 17.2±0.9 versus 20.6±0.8, p=0.01; delayed: 12±0.9 versus 16.0±0.7, p=0.002; Figure
2). Both tests improved to levels that were no longer different from control subjects after parathyroidectomy
(immediate: 20.0±0.8 versus 20.0±0.7, p=0.97; delayed: 14.5±0.9 versus 15.7±0.8, p=0.36), and the change
over time differed between normal and PHPT subjects (p=0.003 immediate and p=0.009 delayed recall).
Immediate, but not delayed, word list recall (SRT) was also worse at baseline in the PHPT group (immediate:
49.2±1.3 versus 53±1.1, p=0.04; delayed: 6.8±0.4 versus 7.9±0.4, p=0.064). Neither immediate nor delayed
recall changed with surgery (Figure 3). No differences were found between PHPT and controls in visual
memory (Table 3). Both groups improved to similar extents over time, consistent with a learning effect.
Other cognitive functions: Non-verbal abstraction was worse in the PHPT group (39.9±1.9 versus 45.6±1.6,
p=0.041, Figure 4). While scores in both PHPT and control subjects improved over time, those with PHPT
improved to a greater extent, so that they were indistinguishable from normal subjects (49.5±2.3 versus
50.5±1.9, p=0.74; group by time interaction: p=0.036). Visual concentration and attention as measured by the
RTD or Digit Symbol test was similar in the PHPT and control groups (Table 3). While target detection did
not change over time, the PHPT group improved compared to baseline on one test of visual concentration
and attention (Digit Symbol test), while the control group did not (between groups change over time,
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p=0.014). There was no difference on performance on the Digit Span test of auditory attention and mental
manipulation and neither group improved compared to baseline (Table 3).
Association of psychological and cognitive test results with disease severity
No linear associations were observed between any psychological or cognitive variable that was
abnormal at baseline and serum calcium, PTH, or vitamin D metabolite concentration, nor was a relationship
observed between changes in psychological or cognitive variables and change in biochemical measures.
Discussion
The nature and extent of psychological and cognitive involvement in PHPT remains an area of great
interest. While earlier studies have arbitrarily selected one or two aspects of cognitive function, this study
used a wide array of tests because the facets of cognition that could be affected by PHPT were unclear a
priori. We sought to document the presence of any abnormalities, to determine their reversibility, and their
relationship to ambient serum calcium, PTH, and other biochemical indices of the disease. A control
population allowed for assessment of learning effects on repeated testing. The results of statistical analyses
demonstrate that PHPT in post-menopausal women is associated with alterations in cognition that are
independent of depression and anxiety. Those with PHPT performed less well than control subjects on some
tests of cognitive function, including tests of verbal memory and non-verbal abstraction. Non-verbal
abstraction and some aspects of verbal memory improved after parathyroidectomy. Visual memory and
concentration and auditory attention and mental manipulation were not impaired. Finally, while patients with
PHPT were not clinically depressed or anxious, they had more symptoms of depression and anxiety than
control subjects. Depressive symptoms decreased after parathyroidectomy, while anxiety did not.
Many case-control studies (7, 11, 16, 22, 23) and a recent RCT (17) support the presence of
psychological symptoms, including depression, anxiety, fearfulness, inferiority, lassitude, lack of initiative,
fatigability, and apathy (11, 16, 23), or decreased QOL (7, 17, 22) in PHPT. While observational studies
have tended to show improvement of these symptoms with parathyroidectomy (7, 11, 13, 16, 19, 21, 22, 24),
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RCT results have been inconsistent (17, 25, 44). Rao et al. (44) found (using SF-36 and SCL-90R) a
worsening of social functioning and emotional problem domains in patients followed without intervention for
2 years, although there was little improvement in the operative group. Those who had surgery, however, had
a decline in anxiety and phobic symptoms. Bollerslev et al. found significantly lower baseline QOL (SF-36)
and more psychological symptoms, but did not demonstrate postoperative improvement (17). Ambrogini et
al. reported a modest benefit of surgery in four QOL domains (SF-36), including bodily pain, general health,
vitality, and mental health, but found no difference in SCL-90R measures (25). Possible explanations for the
conflicting results of these studies could include differences in the size and composition of the populations
sampled, type of analyses performed or differential attrition in the studies. Our study specifically measured
depression and anxiety, because they are known confounders of neuropsychological testing. Together with
the findings of the current report, the available results support the presence of some depressive and anxiety
symptoms in PHPT.
Few other studies have examined cognitive function in PHPT. The clear learning effect over testing
trials, as was evident in our investigation, limits the interpretation of studies without control groups (6, 14,
26, 45). Comparison of this report to the few existing controlled studies is difficult because each employed a
different battery of tests, assessed individuals at different intervals from surgery and included populations
with varying calcium levels. Furthermore, no prior studies have adjusted for the presence of anxiety or
depression symptoms. Numann et al. used a large battery of tests and found post-parathyroidectomy
improvement in verbal memory as we did. Their positive findings despite a very small sample size (10
patients undergoing parathyroidectomy and 10 normocalcemic orthopedic controls) may be due to the more
severe disease in their patients (12). Roman et al. compared 2 tests of cognitive function in patients with
PHPT and those with benign goiter preoperatively 2 and 4 weeks post-operatively (15). In contrast to our
study, they did not find impaired memory for word lists compared to controls, but did find changes in spatial
learning and memory, which our study did not assess. Two other studies found no cognitive impairment in
PHPT or postoperative improvement, but may have been underpowered to do so (n=14 and n=20) (27, 28).
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We found no linear association between serum calcium or PTH and cognitive abnormalities. This
may be because the study had limited power to evaluate this relationship or the range of serum calcium and
PTH levels was too narrow to be able to discern the association. Studies in which the mean serum calcium
values were much higher reported a relationship between preoperative neuropsychological symptoms and
extent of hypercalcemia (19). Several studies from our group and others support the presence of increased
vascular stiffness and endothelial dysfunction in PHPT (46-49). If present in the carotid or cerebral
vasculature, vascular stiffness could represent a pathophysiological pathway leading to cognitive impairment.
The study has several limitations. First, the PHPT and control groups differed with regard to two
important parameters: estimated IQ and education level. The direction of the differences (PHPT subjects
were better educated and with a higher estimated IQ), however, should have biased against our finding of
worse cognitive function in the PHPT group. Although these differences were taken into account in the
statistical analysis, adjustment may not fully account for these disparities. It is therefore possible, that if cases
could have been ideally matched, the results may have differed. Although specific socioeconomic data were
not available, the communities from which the samples were obtained are similar in this regard. We also
suspect an association between socioeconomic level and education, for which we adjusted.
There were also limitations inherent in the study design. An RCT of surgery versus no surgery is a
superior design compared to a case-control study, but is extremely difficult to carry-out. Additionally, test
administrators were not blinded to disease state and time of testing, which could have influenced results.
Because we did not have a surgical control group, it is also possible that the pre-operative increase in
symptoms of anxiety and depression could be explained by anticipation of surgery. Improvement in
psychiatric symptoms may have been due to the knowledge of being free of disease or a non-specific effect
of surgery rather than the correction of PHPT itself. However, if preoperative anxiety findings were related
to impending surgery, an improvement would have been expected. Finally, we studied a convenience sample
of PHPT patients including patients who did and did not meet 2002 criteria for surgery. The size of the
cohort precludes a sub-group analysis (of those meeting versus those not meeting indications for surgery) to
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address the issue of differing responses in these groups. However, it allowed us to achieve our main goal: to
document the existence of cognitive symptoms among patients with mild PHPT.
The clinical significance of the cognitive improvement after surgery is unclear, since the magnitude
of changes was within one standard deviation of the group mean. It is notable, however, that the mean value
for nonverbal abstraction, logic and problem solving was within 1 point of the mildly impaired range, a
finding that was unexpected given participants’ high level of education. In addition, we do not know if these
results apply to premenopausal women and men with PHPT.
In spite of these limitations, the study has several notable strengths. We characterized cognitive
function in a moderate sized group of patients with mild PHPT. Control data are available and a large battery
of validated tests, which evaluated many aspects of cognition, was used. Patients and controls were studied
at two identical time points, obviating confounding by learning effects known to exist in cognitive testing.
Additionally, we studied patients well after the immediate post-operative period in order to prevent biases
due to the non-specific benefits of surgery. Finally, we controlled for variables known to affect cognitive
performance, including age, education and estimated IQ, and the presence of anxiety and depressive
symptoms.
We conclude that mild PHPT in postmenopausal women is associated with weaker performance in
the cognitive domains of verbal memory and non-verbal abstraction. This is independent of anxiety and
depressive symptoms, which are also more common in PHPT than in a control population.
Parathyroidectomy leads to improvement in some of the psychiatric and cognitive deficits. While these
results cannot be extrapolated to predict clinical expectations in any given patient, they may provide an
explanation for the improved sense of well-being reported by many, but not all, patients after successful
parathyroidectomy. Furthermore, these results may be useful in further research into specific
neuroanatomical regions that may be specifically affected by the hyperparathyroid process.
Acknowledgments
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We are grateful to Dr. John Bilezikian for his counsel and support throughout this project.
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16

Figure legends
Figure 1. A) Depression measured by BDI; B) State and C) Trait anxiety as measured by STAI-Y.
Higher scores indicate more symptoms. Scores are adjusted for age, IQ and education. *,
p

Table 1. Biochemical variables pre- and post-operatively PHPT group
Normal
range
Pre-
Parathyroidectomy
18
Mean ± SEM
PHPT
Post-
Parathyroidectomy
Mean ± SEM
Pre- vs.
Post-op
P-value
Serum calcium (mg/dl) 8.5-10.2 10.6 ± 0.1 9.5 ± 0.1

Table 2. Cognitive Testing Adjusted for Age, IQ, Education, Anxiety and Depression
Cognitive Test
Time 1
(Pre-op)
Mean ± SEM
PHPT group Control group
Time 2
(Post-op)
Mean ± SEM
19
Time 1
Mean ± SEM
Time 2
Mean ± SEM
PHPT vs.
Controls
(Time 1)
p-value
PHPT vs.
Controls
(Time 2)
p-value
Visual Memory
RVDLT Total Trials 1-3 16.6 ± 1.0 19.3 ± 0.9* 17.3 ± 0.86 19.1 ± 0.8* 0.639 0.886
Response Speed/Visual Concentrations
Rosen Detection Test - Symbol Time 43.0 ± 2.3 40.5 ± 1.9 40.6 ± 1.9 42.6 ± 1.7 0.440 0.465
Rosen Detection Test - Symbol Error 2.5 ± 0.5 3.2 ± 0.5 3.1 ± 0.4 2.9 ± 0.5 0.423 0.709
WAIS-R Digit Symbol Standard Score 13.0 ± 0.4 13.5 ± 0.4* 13.3 ±0.3 13.1 ± 0.3 0.662 0.406
Auditory Attention/Mental Manipulation
Digit Span Total Standard Score 12.3 ± 0.4 12.0 ± 0.4 11.4 ± 0.3 11.7 ± 0.4 0.089 0.622
*indicates p

Figure 1
A.
B.
C.
Beck Depression Inventory
STAI-Y
STAI-Y
12.00
10.00
8.00
6.00
4.00
2.00
38.00
36.00
34.00
32.00
30.00
28.00
26.00
24.00
22.00
20.00
40.00
38.00
36.00
34.00
32.00
30.00
28.00
26.00
24.00
22.00
20.00
*
†
†
Depression
1 2
Time
State Anxiety
1 2
Tim e
Tra it Anx ie ty
1 2
Tim e
+
+
PHPT
Control
PHPT
Control
PHPT
Control

Figure 2
A.
Wechsler Logical
Memory
B.
Wechsler Logical
Memory
22.00
20.00
18.00
16.00
14.00
12.00
10.00
18.00
17.00
16.00
15.00
14.00
13.00
12.00
11.00
10.00
9.00
8.00
Verbal Memory
Contextually Related Material (Immediate)
Verbal Memory
Contextually Related Material (Delayed)
*
*
1 2
Time
1 2
Time
+
+
PHPT
Control
PHPT
Control

Figure 3
A.
Bushke SRT Total Recall
B.
Bushke SRT Total Recall
55.00
54.00
53.00
52.00
51.00
50.00
49.00
48.00
47.00
46.00
9.00
8.00
7.00
6.00
5.00
4.00
Verbal Memory - Immediate Word List
†
1 2
Time
Verbal Memory - Delayed Word List
1 2
Time
*
PHPT
Control
PHPT
Control

Figure 4
Booklet Category Test
T-score
55.00
50.00
45.00
40.00
35.00
30.00
†
Non-verbal Abstraction
1 2
Time
+
+
PHPT
Control