American Association of Endocrine Surgeon| Volume 146, ISSUE 6, P1116-1122, December 2009

Prospective, randomized, controlled trial of parathyroidectomy versus observation in patients with “asymptomatic” primary hyperparathyroidism

Published:November 02, 2009DOI:


      Disruptions in cognitive function have been described in the constellation of symptoms associated with “asymptomatic” primary hyperparathyroidism (PHPT). The aim of this study was to determine the impact of parathyroidectomy (PTX) on brain function and sleep in “asymptomatic” PHPT patients.


      We conducted a prospective, randomized trial comparing immediate PTX with observation in patients with asymptomatic PHPT. We performed functional magnetic resonance imaging (fMRI) of the brain, sleep assessment, and validated neuropsychological battery at baseline, 6 weeks, and 6 months. Wilcoxon rank-sum and Pearson and Spearman correlations were used.


      A total of 18 patients were randomized. Subjective sleepiness correlated with worse performance on executive function tests during fMRI at 6 weeks (Pearson, −0.473; P = .047) and 6 months (Pearson, −0.673; P = .002). Total sleep time correlated with PTH levels at both 6 weeks (Pearson, 0.518; P = .048) and 6 months (Pearson, 0.567; P = .018). At 6 weeks, hypersomnolence as measured subjectively was decreased in the PTX group, but increased in those observed (−2.56 vs 2.22; P = .03)


      This prospective, randomized trial for asymptomatic PHPT patients demonstrated an association of sleep with brain function. Sleep seemed to be an indicator of brain activation in the anterior cingulate gyrus and precentral cortex. Subjective sleepiness was associated with executive function. The results of this pilot study suggest that decreased serum PTH levels correlate with improved sleep and that PTX decreases sleepiness in patients with asymptomatic PHPT.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Heath III, H.
        • Hodgson S.F.
        • Kennedy M.A.
        Primary hyperparathyroidism. Incidence, morbidity, and potential economic impact in a community.
        N Engl J Med. 1980; 302: 189-193
        • Bilezikian J.P.
        Primary hyperparathyroidism. When to observe and when to operate.
        Endocrinol Metab Clin North Am. 2000; 29: 465-478
        • Silverberg S.J.
        • Lewiecki E.M.
        • Mosekilde L.
        • Peacock M.
        • Rubin M.R.
        Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop.
        J Clin Endocrinol Metab. 2009; 94: 351-365
        • Coker L.H.
        • Rorie K.
        • Cantley L.
        • Kirkland K.
        • Stump D.
        • Burbank N.
        • et al.
        Primary hyperparathyroidism, cognition, and health-related quality of life.
        Ann Surg. 2005; 242: 642-650
        • Euser S.M.
        • Schram M.T.
        • Hofman A.
        • Westendorp R.G.
        • Breteler M.M.
        Measuring cognitive function with age: the influence of selection by health and survival.
        Epidemiology. 2008; 19: 440-447
        • Eigelberger M.S.
        • Cheah W.K.
        • Ituarte P.H.
        • Streja L.
        • Duh Q.Y.
        • Clark O.H.
        The NIH criteria for parathyroidectomy in asymptomatic primary hyperparathyroidism: are they too limited?.
        Ann Surg. 2004; 239: 528-535
        • Pasieka J.L.
        • Parsons L.L.
        • Demeure M.J.
        • Wilson S.
        • Malycha P.
        • Jones J.
        • et al.
        Patient-based surgical outcome tool demonstrating alleviation of symptoms following parathyroidectomy in patients with primary hyperparathyroidism.
        World J Surg. 2002; 26: 942-949
        • Prager G.
        • Kalaschek A.
        • Kaczirek K.
        • Passler C.
        • Scheuba C.
        • Sonneck G.
        • et al.
        Parathyroidectomy improves concentration and retentiveness in patients with primary hyperparathyroidism.
        Surgery. 2002; 132: 930-935
        • Mittendorf E.A.
        • Wefel J.S.
        • Meyers C.A.
        • Doherty D.
        • Shapiro S.E.
        • Lee J.E.
        • et al.
        Improvement of sleep disturbance and neurocognitive function after parathyroidectomy in patients with primary hyperparathyroidism.
        Endocr Pract. 2007; 13: 338-344
        • Joborn C.
        • Hetta J.
        • Johansson H.
        • Rastad J.
        • Agren H.
        • Akerstrom G.
        • et al.
        Psychiatric morbidity in primary hyperparathyroidism.
        World J Surg. 1988; 12: 476-481
        • Numann P.J.
        • Torppa A.J.
        • Blumetti A.E.
        Neuropsychologic deficits associated with primary hyperparathyroidism.
        Surgery. 1984; 96: 1119-1123
        • Perrier N.D.
        • Coker L.H.
        • Rorie K.D.
        • Burbank N.S.
        • Kirkland K.A.
        • Passmore L.V.
        • et al.
        Preliminary report: functional MRI of the brain may be the ideal tool for evaluating neuropsychologic and sleep complaints of patients with primary hyperparathyroidism.
        World J Surg. 2006; 30: 686-696
        • Roberts K.L.
        • Hall D.A.
        Examining a supramodal network for conflict processing: a systematic review and novel functional magnetic resonance imaging data for related visual and auditory Stroop tasks.
        J Cogn Neurosci. 2008; 20: 1063-1078
        • Johns M.W.
        A new method for measuring daytime sleepiness: the Epworth sleepiness scale.
        Sleep. 1991; 14: 540-545
        • Lezak M.D.
        Neuropsychological assessment.
        Oxford University Press, New York1995
        • Cox R.W.
        AFNI: software for analysis and visualization of functional magnetic resonance neuroimages.
        Comput Biomed Res. 1996; 29: 162-173
        • Leung H.C.
        • Skudlarski P.
        • Gatenby J.C.
        • Peterson B.S.
        • Gore J.C.
        An event-related functional MRI study of the Stroop Color Word Interference Task.
        Cereb Cortex. 2000; 10: 552-560
        • Talairach J.
        • Tourneoux P.
        3-dimensional proportional system: an approach to cerebral imaging. Co-planar stereotaxic atlas of the human brain.
        Thieme Medical Publishers, New York1988
        • Roman S.A.
        • Sosa J.A.
        • Mayes L.
        • Desmond E.
        • Boudourakis L.
        • Lin R.
        • et al.
        Parathyroidectomy improves neurocognitive deficits in patients with primary hyperparathyroidism.
        Surgery. 2005; 138: 1121-1128
        • Fuleihan G.E.-H.
        • Klerman E.B.
        • Brown E.N.
        • Choe Y.
        • Brown E.M.
        • Czeisler C.A.
        The parathyroid hormone circadian rhythm is truly endogenous—a general clinical research center study.
        J Clin Endocrinol Metab. 1997; 82: 281-286
        • Safley S.A.
        • Villinger F.
        • Jackson E.H.
        • Tucker-Burden C.
        • Cohen C.
        • Weber C.J.
        Interleukin-6 production and secretion by human parathyroids.
        Clin Exp Immunol. 2004; 136: 145-156
        • Opp M.R.
        Cytokines and sleep.
        Sleep Med Rev. 2005; 9: 355-364
        • Grey A.
        • Mitnick M.A.
        • Shapses S.
        • Ellison A.
        • Gundberg C.
        • Insogna K.
        Circulating levels of interleukin-6 and tumor necrosis factor-alpha are elevated in primary hyperparathyroidism and correlate with markers of bone resorption—a clinical research center study.
        J Clin Endocrinol Metab. 1996; 81: 3450-3454
        • Talpos G.B.
        • Bone 3rd, H.G.
        • Kleerekoper M.
        • Phillips E.R.
        • Alam M.
        • Honasoge M.
        • et al.
        Randomized trial of parathyroidectomy in mild asymptomatic primary hyperparathyroidism: patient description and effects on the SF-36 health survey.
        Surgery. 2000; 128: 1013-1020
        • Beyer T.D.
        • Solorzano C.C.
        • Prinz R.A.
        • Babu A.
        • Nilubol N.
        • Patel S.
        Oral vitamin D supplementation reduces the incidence of eucalcemic PTH elevation after surgery for primary hyperparathyroidism.
        Surgery. 2007; 141: 777-783
        • Tung A.
        • Mendelson W.
        Anesthesia and sleep.
        Sleep Medicine Reviews. 2004; 8: 213-225
        • Knill R.L.
        • Moote C.A.
        • Rose E.A.
        Anesthesia with abdominal surgery lead to intense REM sleep during the first postoperative week.
        Anesthesiology. 1990; 73: 52-61
        • Moote C.A.
        • Knill R.L.
        Isoflorane anesthesia causes a transient alteration in nocturnal sleep.
        Anesthesiology. 1988; 69: 327-331