Clinical Overview > Condition/ Syndrome

You are looking at 1 - 1 of 1 items for :

  • Pseudohypoparathyroidism x
Clear All
Maria P Yavropoulou 1st Propaedeutic Department of Internal Medicine, LAIKO General Hospital of Athens

Search for other papers by Maria P Yavropoulou in
Google Scholar
PubMed
Close
,
Efstathios Chronopoulos 2nd Orthopaedic Department, Konstantopouleio General Hospital

Search for other papers by Efstathios Chronopoulos in
Google Scholar
PubMed
Close
,
George Trovas Laboratory for Research of the Musculoskeletal System, Th Garofalidis, National and Kapodistrian University of Athens, Athens, Greece

Search for other papers by George Trovas in
Google Scholar
PubMed
Close
,
Emmanouil Avramidis 2nd Orthopaedic Department, Konstantopouleio General Hospital

Search for other papers by Emmanouil Avramidis in
Google Scholar
PubMed
Close
,
Francesca Marta Elli Endocrinology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

Search for other papers by Francesca Marta Elli in
Google Scholar
PubMed
Close
,
Giovanna Mantovani Endocrinology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

Search for other papers by Giovanna Mantovani in
Google Scholar
PubMed
Close
,
Pantelis Zebekakis 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

Search for other papers by Pantelis Zebekakis in
Google Scholar
PubMed
Close
, and
John G Yovos 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

Search for other papers by John G Yovos in
Google Scholar
PubMed
Close

Summary

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.

Learning points:

  • We describe a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1 as the cause of PHP1A.

  • Hypercalcitoninaemia in PHP1A is considered an associated resistance to calcitonin, as suggested by the generalised impairment of Gsα-mediated hormone signalling.

  • GNAS methylation defects, as in type PHP1B, without thyroid pathology can also present with hypercalcitoninaemia.

Open access