Title: Neuropsychological Features in Primary Hyperparathyroidism ...

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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, 4
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 5
Page 1 and 2: J Clin Endocrin Metab. First publis
Page 3: Introduction Classical PHPT was a s
Page 7 and 8: 7. Non-verbal Abstraction: This was
Page 9 and 10: PHPT, mean performance levels on th
Page 11 and 12: RCT results have been inconsistent
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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