{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:16:47Z","timestamp":1784557007894,"version":"3.55.0"},"reference-count":24,"publisher":"Bioscientifica","license":[{"start":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T00:00:00Z","timestamp":1548892800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/deed.en_GB"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,1,31]]},"abstract":"Summary<\/jats:title>\n Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterised by normal renal function and renal resistance to the action of the parathyroid hormone. Type 1A (PHP1A), which is the most common variant, also include developmental and skeletal defects named as Albright hereditary osteodystrophy (AHO). We present two cases, a 54- and a 33-year-old male diagnosed with PHP who were referred to us for persistently high levels of serum calcitonin. AHO and multinodular goitre were present in the 54-year-old male, while the second patient was free of skeletal deformities and his thyroid gland was of normal size and without nodular appearance. We performed GNAS molecular analysis (methylation status and copy number analysis by MS-MLPA) in genomic DNA samples for both patients. The analysis revealed a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1, in the patient with the clinical diagnosis of PHP1A. This amino acid change appears to be in accordance with the clinical diagnosis of the patient. The genomic DNA analysis of the second patient revealed the presence of the recurrent 3-kb deletion affecting the imprinting control region localised in the STX16 region associated with the loss of methylation (LOM) at the GNAS A\/B differentially methylated region and consistent with the diagnosis of an autosomal dominant form of PHP type 1B (PHP1B). In conclusion, hypercalcitoninaemia may be encountered in PHP1A and PHP1B even in the absence of thyroid pathology.<\/jats:p>\n \n Learning points:<\/jats:title>\n \n \n \n We describe a novel missense variant c.131T>G p.(Leu44Pro) affecting\n GNAS<\/jats:italic>\n exon 1 as the cause of PHP1A.\n <\/jats:p>\n <\/jats:list-item>\n \n Hypercalcitoninaemia in PHP1A is considered an associated resistance to calcitonin, as suggested by the generalised impairment of Gs\u03b1-mediated hormone signalling.<\/jats:p>\n <\/jats:list-item>\n \n \n GNAS<\/jats:italic>\n methylation defects, as in type PHP1B, without thyroid pathology can also present with hypercalcitoninaemia.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-18-0125","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T11:24:14Z","timestamp":1548933854000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":8,"title":["Hypercalcitoninaemia in pseudohypo\u00adparathyroidism type 1A and type 1B"],"prefix":"10.1530","volume":"2019","author":[{"given":"Maria P","family":"Yavropoulou","sequence":"first","affiliation":[{"name":"11st Propaedeutic Department of Internal Medicine, LAIKO General Hospital of Athens"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathios","family":"Chronopoulos","sequence":"additional","affiliation":[{"name":"22nd Orthopaedic Department, Konstantopouleio General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Trovas","sequence":"additional","affiliation":[{"name":"3Laboratory for Research of the Musculoskeletal System, Th Garofalidis, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanouil","family":"Avramidis","sequence":"additional","affiliation":[{"name":"22nd Orthopaedic Department, Konstantopouleio General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Marta","family":"Elli","sequence":"additional","affiliation":[{"name":"4Endocrinology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Mantovani","sequence":"additional","affiliation":[{"name":"4Endocrinology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantelis","family":"Zebekakis","sequence":"additional","affiliation":[{"name":"51st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G","family":"Yovos","sequence":"additional","affiliation":[{"name":"51st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref231","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/humu.22265","article-title":"Pseudohypoparathyroidism type Ia and pseudo-pseudohypoparathyroidism: the growing spectrum of GNAS inactivating mutations","volume":"34","year":"2013","journal-title":"Human Mutation"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4158\/EP14020.CR","article-title":"ChaubeySKSanglaKS sporadic case of pseudohypoparathyroidism type and idiopathic primary adrenal insufficiency associated with a novel mutation in the GNAS gene Practices https org","journal-title":"Endocrine"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.beem.2006.09.001","article-title":"Mutations in the Gs alpha gene causing hormone resistance","volume":"20","year":"2006","journal-title":"Best Practice and Research: Clinical Endocrinology and Metabolism"},{"key":"ref121","first-page":"1","article-title":"From pseudohypoparathyroidism to inactivating PTH PTHrP signalling disorder iPPSD a novel classification proposed by the EuroPHP network of https org","journal-title":"European Journal Endocrinology"},{"key":"ref01","first-page":"1","article-title":"From pseudohypoparathyroidism to inactivating PTH PTHrP signalling disorder iPPSD a novel classification proposed by the EuroPHP network of https org","journal-title":"European Journal Endocrinology"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"3738","DOI":"10.1210\/jc.2007-0869","article-title":"Genetic analysis and evaluation of resistance to thyrotropin and growth hormone-releasing hormone in pseudohypoparathyroidism type Ib","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1086\/320117","article-title":"Paternal uniparental isodisomy of chromosome 20q \u2013 and the resulting changes in GNAS1 methylation \u2013 as a plausible cause of pseudohypoparathyroidism","volume":"68","year":"2001","journal-title":"American Journal of Human Genetics"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/jbmr.2785","article-title":"Screening of PRKAR1A and PDE4D in a large Italian series of patients clinically diagnosed with Albright hereditary osteodystrophy and\/or pseudohypoparathyroidism","volume":"31","year":"2016","journal-title":"Journal of Bone and Mineral Research"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1055\/s-2002-23492","article-title":"Abnormal pentagastrin response in a patient with pseudohypoparathyroidism","volume":"110","year":"2002","journal-title":"Experimental and Clinical Endocrinology and Diabetes"},{"key":"ref101","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","year":"2018","journal-title":"Nature Reviews Endocrinology"},{"key":"ref21","first-page":"4622","article-title":"The stimulatory G protein alpha-subunit gene: mutations and imprinting lead to complex phenotypes","volume":"86","year":"2001","journal-title":"Journal of Clinical Endocrinology and 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