Title: Neuropsychological Features in Primary Hyperparathyroidism ...

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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), 10
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). 11
Page 1 and 2: J Clin Endocrin Metab. First publis
Page 3 and 4: Introduction Classical PHPT was a s
Page 5 and 6: malignancy other than non-melanoma
Page 7 and 8: 7. Non-verbal Abstraction: This was
Page 9: PHPT, mean performance levels on th
Page 13 and 14: address the issue of differing resp
Page 15 and 16: 14. Prager G, Kalaschek A, Kaczirek
Page 17 and 18: Figure legends Figure 1. A) Depress
Page 19 and 20: Table 2. Cognitive Testing Adjusted
Page 21 and 22: Figure 2 A. Wechsler Logical Memory
Page 23: Figure 4 Booklet Category Test T-sc

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