{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:53:23Z","timestamp":1753883603549,"version":"3.41.2"},"reference-count":17,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK101689","DK119733","DK118407"],"award-info":[{"award-number":["DK101689","DK119733","DK118407"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000862","name":"Doris Duke Charitable Foundation","doi-asserted-by":"publisher","award":["UL1 TR002243"],"award-info":[{"award-number":["UL1 TR002243"]}],"id":[{"id":"10.13039\/100000862","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pseudohypoparathyroidism (PHP) is a rare hormone resistance syndrome caused by mutations in GNAS. This cross-sectional study investigated whether PHP patients with parathyroid hormone (PTH), thyrotropin (thyroid stimulating hormone; TSH), and free thyroxine (T4) levels at goal required higher doses of levothyroxine and calcitriol than recommended by current guidelines to overcome mineral ion abnormalities due to hormone resistance.<\/jats:p>\n               <jats:p>Baseline demographic and clinical data of participants enrolled in PHP research studies between 2012-2021 were collected via retrospective chart review. Longitudinally, data were recorded at a maximum frequency of once a year starting at 1 year of age. The PTH at goal (PAG) group was defined as PTH\u2005&amp;lt;\u2005150 pg\/mL and calcium \u2265 8.4 mg\/dL, and the TSH and free T4 at goal (TAG) group was defined as TSH\u2005&amp;lt;\u20055 mIU\/L and free T4\u2005\u2265\u20050.8 ng\/dL.<\/jats:p>\n               <jats:p>The PAG group (n\u2005=\u200574) was prescribed higher calcitriol doses than the PTH not at goal (PNAG) group (n\u2005=\u200550) (0.9\u2005\u00b1\u20051.1 vs 0.5\u2005\u00b1\u20050.9 mcg\/day, P\u2005=\u20050.04) and 21% of individual patients were prescribed \u2265 1.5 mcg of calcitriol daily. This remained true after normalization for body weight (0.013\u2005\u00b1\u20050.015 vs 0.0067\u2005\u00b1\u20050.0095 mcg\/kg\/day, P\u2005=\u20050.008). There was no statistically significant difference in levothyroxine dosing between the TAG group (n\u2005=\u2005122) and TSH and free T4 not at goal (TNAG) group (n\u2005=\u200545) when normalized for weight (2.0\u2005\u00b1\u20050.7 vs 1.8\u2005\u00b1\u20050.7 mcg\/kg\/day, P\u2005=\u20050.2).<\/jats:p>\n               <jats:p>More than one-third of patients with PHP had PTH levels not at goal and some patients required calcitriol doses \u2265 1.5 mcg\/day to meet current treatment goals.<\/jats:p>","DOI":"10.1210\/jendso\/bvab161","type":"journal-article","created":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T11:40:33Z","timestamp":1635680433000},"source":"Crossref","is-referenced-by-count":1,"title":["Calcitriol and Levothyroxine Dosing for Patients With Pseudohypoparathyroidism"],"prefix":"10.1210","volume":"5","author":[{"given":"Jacqueline","family":"Antoun","sequence":"first","affiliation":[{"name":"Vanderbilt University School of Medicine, Nashville, TN 37212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dylan","family":"Williamson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Vanderbilt University Medical Center, Nashville, TN 37212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8011-6596","authenticated-orcid":false,"given":"Merla","family":"Hubler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Tennessee Health Science Center, Chattanooga, TN 37403, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1628-3677","authenticated-orcid":false,"given":"Ashley H","family":"Shoemaker","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Vanderbilt University Medical Center, Nashville, TN 37212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2021,10,27]]},"reference":[{"issue":"6","key":"2021111015224879500_CIT0001","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1210\/jc.2016-3544","article-title":"Progressive development of PTH resistance in patients with inactivating mutations on the maternal allele of GNAS","volume":"102","author":"Usardi","year":"2017","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021111015224879500_CIT0002","doi-asserted-by":"crossref","first-page":"E508","DOI":"10.1210\/jc.2013-3086","article-title":"Quantitative analysis of methylation defects and correlation with clinical characteristics in patients with Pseudohypoparathyroidism type I and GNAS epigenetic alterations","volume":"99","author":"Elli","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"2021111015224879500_CIT0003","doi-asserted-by":"crossref","first-page":"4697","DOI":"10.1210\/en.2005-0681","article-title":"A mouse model of Albright hereditary osteodystrophy generated by targeted disruption of exon 1 of the Gnas gene","volume":"146","author":"Germain-Lee","year":"2005","journal-title":"Endocrinology."},{"issue":"20","key":"2021111015224879500_CIT0004","doi-asserted-by":"crossref","first-page":"7386","DOI":"10.1073\/pnas.0408268102","article-title":"Alternative Gnas gene products have opposite effects on glucose and lipid metabolism","volume":"102","author":"Chen","year":"2005","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"6","key":"2021111015224879500_CIT0005","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.cmet.2009.05.004","article-title":"Central nervous system imprinting of the G protein G(s)alpha and its role in metabolic regulation","volume":"9","author":"Chen","year":"2009","journal-title":"Cell Metab."},{"issue":"9","key":"2021111015224879500_CIT0006","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1172\/JCI10431","article-title":"A GNAS1 imprinting defect in pseudohypoparathyroidism type IB","volume":"106","author":"Liu","year":"2000","journal-title":"J Clin Invest."},{"issue":"10","key":"2021111015224879500_CIT0007","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1210\/jc.2015-4310","article-title":"The prevalence of GNAS deficiency-related diseases in a large cohort of patients characterized by the EuroPHP network","volume":"101","author":"Elli","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021111015224879500_CIT0008","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/jbmr.2070","article-title":"Postnatal establishment of allelic G\u03b1s silencing as a plausible explanation for delayed onset of parathyroid hormone resistance owing to heterozygous G\u03b1s disruption","volume":"29","author":"Turan","year":"2014","journal-title":"J Bone Miner Res."},{"issue":"9","key":"2021111015224879500_CIT0009","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1210\/jc.2012-1655","article-title":"Development and treatment of tertiary hyperparathyroidism in patients with pseudohypoparathyroidism type 1B","volume":"97","author":"Neary","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"issue":"15","key":"2021111015224879500_CIT0010","doi-asserted-by":"crossref","first-page":"8715","DOI":"10.1073\/pnas.95.15.8715","article-title":"Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the gsalpha gene","volume":"95","author":"Yu","year":"1998","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"8","key":"2021111015224879500_CIT0011","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/s41574-018-0042-0","article-title":"Diagnosis and management of pseudohypoparathyroidism and related disorders: first international consensus statement","volume":"14","author":"Mantovani","year":"2018","journal-title":"Nat Rev Endocrinol."},{"issue":"3","key":"2021111015224879500_CIT0012","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1159\/000508985","article-title":"Recommendations for diagnosis and treatment of pseudohypoparathyroidism and related disorders: an updated practical tool for physicians and patients","volume":"93","author":"Mantovani","year":"2020","journal-title":"Horm Res Paediatr"},{"issue":"4","key":"2021111015224879500_CIT0013","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/oby.21782","article-title":"BMI z-Scores are a poor indicator of adiposity among 2- to 19-year-olds with very high BMIs, NHANES 1999-2000 to 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Pediatr."},{"issue":"8","key":"2021111015224879500_CIT0017","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s00431-017-2930-z","article-title":"Determinants of levothyroxine dose required to achieve euthyroidism in pediatric population-a hospital-based prospective follow-up study","volume":"176","author":"Singh","year":"2017","journal-title":"Eur J Pediatr."}],"container-title":["Journal of the Endocrine 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