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.

Hypercalcitoninaemia in pseudohypo-parathyroidism type 1A and type 1B / M.P. Yavropoulou, E. Chronopoulos, G. Trovas, E. Avramidis, F.M. Elli, G. Mantovani, P. Zebekakis, J.G. Yovos. - In: ENDOCRINOLOGY, DIABETES & METABOLISM CASE REPORTS. - ISSN 2052-0573. - 2019:1(2019 Jan 31).

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

F.M. Elli
Membro del Collaboration Group
;
G. Mantovani
Membro del Collaboration Group
;
2019

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.
2019; Adult; Bone; Brachydactyly; Calcitonin; Calcium (serum); Calcium (urine); Calcium gluconate; Facies - moon; Fatigue; Fine needle aspiration biopsy; Goitre; Greece; Headache; Insight into disease pathogenesis or mechanism of therapy; January; Levothyroxine; Male; Molecular genetic analysis; Myasthaenia; Obesity; Osteopenia; PTH; Parathyroid; Pentagastrin; Phosphate (serum); Pseudohypoparathyroidism; Short stature; Skeletal deformity; Tetany; Thyroid antibodies; Thyroidectomy; Ultrasound scan; Uric acid (blood); Vitamin D; White; X-ray
Settore MED/13 - Endocrinologia
31-gen-2019
Article (author)
File in questo prodotto:
File Dimensione Formato  
EDM180125.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 695.29 kB
Formato Adobe PDF
695.29 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/636019
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 3
social impact