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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EHypoparathyroidism is a rare endocrine disorder with a wide range of etiologies, including surgery and radioactive iodine therapy. It can be acquired or genetic; curable or permanent. This article describes the differential diagnosis of the disease, summarizes the latest knowledge about the various causes of acquired hypoparathyroidism, and reviews recognized genetic mutations. The article also discusses skeletal and nonskeletal hypoparathyroidism.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EThyroid Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMetabolic Bone Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EThyroid Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMetabolic Bone Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EHypoparathyroidism is a rare endocrine disorder with a wide range of etiologies, including surgery and radioactive iodine therapy. It can be acquired or genetic; curable or permanent. Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota, USA, described the differential diagnosis of the disease, summarized the latest knowledge about the various causes of acquired hypoparathyroidism, and briefly reviewed recognized genetic mutations.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe most common cause of chronic (\u0026gt;6 months) and acute (\u22646 months) acquired hypoparathyroidism is iatrogenic in the setting of anterior neck surgery [Al-Azem H, Khan AA. \u003Cem\u003EBest Pract Res Clin Endocrinol Metab\u003C\/em\u003E 2012]. Postsurgical hypoparathyroidism, said Dr. Clarke, is usually due to inadvertent removal of, or damage to, parathyroid glands or their blood supply.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EAlthough neck surgery on the thyroid or parathyroid glands or major surgery for head and neck cancer are the most likely causes, hypoparathryoidism can also occur due to congenital or acquired disorders; autoimmune diseases; genetic abnormalities; and destruction or infiltrative disorders of the parathyroids [Al-Azem H, Khan AA. \u003Cem\u003EBest Pract Res Clin Endocrinol Metab\u003C\/em\u003E 2012]. Impaired secretion of parathyroid hormone (PTH) may also be seen with hypomagnesemia or hypermagnesemia.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EExcept for autoimmune polyglandular syndrome type 1, the parathyroid glands are an infrequent target for autoimmunity [Brown EM. \u003Cem\u003EEndocrinol Metab Clin North Am\u003C\/em\u003E 2009]. However, antibodies directed against the parathyroid cell surface calcium-sensing receptor have been identified in the serum of patients with autoimmune hypoparathyroidism.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe disease is challenging and multifactorial, with profound effects on the human skeleton [Bilezikian JP et al. \u003Cem\u003EJ Bone Miner Res\u003C\/em\u003E 2011]. Mishaela R. Rubin, MD, Columbia University, College of Physicians and Surgeons, New York, New York, USA, presented information on the clinical presentation of skeletal and nonskeletal hypoparathyroidism.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EPTH is a key regulator of the bone remodeling rate. A reduction or absence of circulating PTH initially leads to a decrease in bone resorption, followed by a coupled reduction in bone formation [Bilezikian JP et al. \u003Cem\u003EJ Bone Miner Res\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThe typical biochemical constellation in untreated hypoparathyroidism includes low circulating PTH levels, hyperphosphatemia, hypocalcemia, relatively high urinary calcium excretion, and reduced levels of 1,25-dihydroxyvitamin D [Rubin MR et al. \u003Cem\u003EJ Bone Miner Res\u003C\/em\u003E 2008]. Nonskeletal features include renal, biochemical and neuropsychological effects, along with extraskeletal calcifications. The skeletal features are structural and dynamic.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003ERenal compromise is common. In a long-term follow-up of patients with hypoparathyroidism, Mitchell et al. [\u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2012] showed that of patients with 24-hour urine collection for calcium (n=53), 38% had at least one measurement \u0026gt;300 mg\/day. Of those with renal imaging (n=54), 31% had renal calcifications. Rates of chronic kidney disease stage 3 or higher were 2- to 17-fold greater than age-appropriate norms.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EHypoparathyroidism is also associated with extraskeletal calcifications. Mitchell et al. [\u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2012] found that 52% of individuals with head imaging (n=31) had basal ganglia calcifications. These may be related, in some way, to reduced quality of life (QoL) that patients with the disease often suffer [Cusano NE et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2013].\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EIn a recent study, individuals with hypoparathyroidism completed the RAND 36-item Health Survey, a measure of health-related QoL that covers eight domains of physical and mental health. At baseline, participants\u0027 scores were significantly lower than the normative reference range in all eight domains (scores \u22121.35 to \u22120.78; p\u0026lt;0.001 for all) [Cusano NE et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2013].\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EManifestations of hypoparathyroidism are not fully addressed by conventional treatment with calcium and vitamin D. The condition is the only classic hormone deficiency state for which there is no approved hormone replacement treatment [Mazziotti G et al. \u003Cem\u003EEndocrine\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003ENonetheless, new therapeutic options have become available, including two formulations of PTH: teriparatide [human PTH(1\u201334)] and the full-length molecule, PTH(1\u201384) [Cusano NE et al. \u003Cem\u003EEndocrine\u003C\/em\u003E 2012]. Aliya A. Khan, MD, McMaster University, Hamilton, Ontario, Canada, reviewed the impact of PTH therapy on the disease.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EBoth treatments lower supplemental vitamin D requirements and increase markers of bone turnover. The pharmacokinetics of PTH(1\u201384) are substantially slower than those for PTH(1\u201334), which may help explain why dosing with the latter calls for multiple injections per day versus single or every other day dosing with PTH(1\u201384) [Cusano NE et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2013].\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EIn a study of PTH(1\u201384), Rubin et al. [\u003Cem\u003EJ Bone Miner Res\u003C\/em\u003E 2011] reported that subcutaneous administration reversed abnormal bone remodeling dynamics and structure, with bone turnover markers peaking at 5 to 9 months. In a prospective 4-year safety and efficacy study, Cusano et al. [\u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2013] found that PTH(1\u201384) treatment improved biochemical control as well as mental and physical functioning.\u003C\/p\u003E\u003Cp id=\u0022p-16\u0022\u003EThe Use of NPSP558 in the Treatment of Hypoparathyroidism study [REPLACE] is the first and largest randomized, double-blind, placebo-controlled, Phase 3 multinational trial to investigate the use of rhPTH(1\u201384), a recombinant human parathyroid hormone, for the treatment of adults with hypoparathyroidism [Oral Presentation at the Annual Meeting of The Endocrine Society 2012: June 23\u201326,2012. Houston TX]. It randomized 134 patients to rhPTH(1\u201384) or placebo. The primary endpoint was \u226550% reduction in oral calcium and active vitamin D while maintaining Ca(c) at Week 24.\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EOutcomes showed a significant difference in favor of rhPTH(1\u201384): 53% versus 2% placebo (p\u0026lt;0.001; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The adverse event rate was similar with rhPTH(1\u201384) and placebo (90% vs 96%, respectively), with a lower discontinuation rate (7% vs 16%, respectively).\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003ECurrent approaches to the management of hyperparathyroidism are based on severity, acuity, and underlying cause. The goals of accepted practice algorithms are to minimize risk and treat symptoms using large doses of calcium and activated vitamin D\u2014a strategy that can cause ills that range from nephrocalcinosis and renal failure to cognitive dysfunction or brain fog [Bilezikian JP et al. \u003Cem\u003EJ Bone Miner Res\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/20\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022REPLACE Study Primary Endpoint: Responder Rate at Week 24\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1537812482\u0022 data-figure-caption=\u0022REPLACE Study Primary Endpoint: Responder Rate at Week 24\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/20\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/20\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/20\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13317\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-19\u0022 class=\u0022first-child\u0022\u003EREPLACE Study Primary Endpoint: Responder Rate at Week 24\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ESource: Bilezikian JP. ENDO 2012, Houston, TX. Abstract Number: S18\u20133.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-20\u0022\u003EThe REPLACE study, the largest randomized controlled trial to date on rhPTH(1\u201384), offers not only hope, but also great promise of a more effective therapeutic option, with more to follow.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/10\/20.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzm0k2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm0k2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}