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Hypercalcitoninaemia in pseudohypo-parathyroidism type 1A and type 1B.

Abstract

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.

Authors+Show Affiliations

1st Propaedeutic Department of Internal Medicine, LAIKO General Hospital of Athens.2nd Orthopaedic Department, Konstantopouleio General Hospital.Laboratory for Research of the Musculoskeletal System, Th Garofalidis, National and Kapodistrian University of Athens, Athens, Greece.2nd Orthopaedic Department, Konstantopouleio General Hospital.Endocrinology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.Endocrinology Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece.1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30703064

Citation

Yavropoulou, Maria P., et al. "Hypercalcitoninaemia in Pseudohypo-parathyroidism Type 1A and Type 1B." Endocrinology, Diabetes & Metabolism Case Reports, vol. 2019, 2019.
Yavropoulou MP, Chronopoulos E, Trovas G, et al. Hypercalcitoninaemia in pseudohypo-parathyroidism type 1A and type 1B. Endocrinol Diabetes Metab Case Rep. 2019;2019.
Yavropoulou, M. P., Chronopoulos, E., Trovas, G., Avramidis, E., Elli, F. M., Mantovani, G., ... Yovos, J. G. (2019). Hypercalcitoninaemia in pseudohypo-parathyroidism type 1A and type 1B. Endocrinology, Diabetes & Metabolism Case Reports, 2019, doi:10.1530/EDM-18-0125.
Yavropoulou MP, et al. Hypercalcitoninaemia in Pseudohypo-parathyroidism Type 1A and Type 1B. Endocrinol Diabetes Metab Case Rep. 2019 Jan 31;2019 PubMed PMID: 30703064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypercalcitoninaemia in pseudohypo-parathyroidism type 1A and type 1B. AU - Yavropoulou,Maria P, AU - Chronopoulos,Efstathios, AU - Trovas,George, AU - Avramidis,Emmanouil, AU - Elli,Francesca Marta, AU - Mantovani,Giovanna, AU - Zebekakis,Pantelis, AU - Yovos,John G, Y1 - 2019/01/31/ PY - 2018/12/20/received PY - 2019/01/09/accepted PY - 2019/2/1/entrez PY - 2019/2/1/pubmed PY - 2019/2/1/medline KW - 2019 KW - Adult KW - Bone KW - Brachydactyly KW - Calcitonin KW - Calcium (serum) KW - Calcium (urine) KW - Calcium gluconate KW - Facies - moon KW - Fatigue KW - Fine needle aspiration biopsy KW - Goitre KW - Greece KW - Headache KW - Insight into disease pathogenesis or mechanism of therapy KW - January KW - Levothyroxine KW - Male KW - Molecular genetic analysis KW - Myasthaenia KW - Obesity KW - Osteopenia KW - PTH KW - Parathyroid KW - Pentagastrin KW - Phosphate (serum) KW - Pseudohypoparathyroidism KW - Short stature KW - Skeletal deformity KW - Tetany KW - Thyroid antibodies KW - Thyroidectomy KW - Ultrasound scan KW - Uric acid (blood) KW - Vitamin D KW - White KW - X-ray JF - Endocrinology, diabetes & metabolism case reports JO - Endocrinol Diabetes Metab Case Rep VL - 2019 N2 - 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. SN - 2052-0573 UR - https://www.unboundmedicine.com/medline/citation/30703064/Hypercalcitoninaemia_in_pseudohypo-parathyroidism_type_1A_and_type_1B L2 - https://edm.bioscientifica.com/doi/10.1530/EDM-18-0125 DB - PRIME DP - Unbound Medicine ER -