Endocrine Abstracts

Introduction: Pseudohypoparathyroidism (PHP) constitutes a heterogenous group of disorders characterized by end-organ resistance to parathyroid hormone (PTH), due to a defect in the stimulatory G protein-activated cAMP formation. PHP type Ib is characterized by renal resistance to PTH, without the phenotypic features of Albright hereditary osteodystrophy (AHO).

Case report: A 31-year old woman was referred to our clinic for investigation of severe hypocalcemia, detected on routine laboratory examination. Apart from mild hand numbness, no further symptoms of hypocalcemia or signs of AHO were evident. There was no relevant family history and both proband’s parents were normocalcemic and unrelated. Her serum calcium levels were 6.6 mg/dl (normal range 8.8–10.6), serum phosphate: 4.9 mg/dl (normal range: 2.5–4.5), PTH: 1629 pg/ml (normal range: 10–52), 25-hydroxyvitamin-D: 15.7 ng/ml (normal >30 ng/ml), 1,25-dihydrohyvitamin-D3: 31 ng/ml (normal range: 19.6–54.3), 24 h-urinary calcium: 45 mg (normal range 0–250) and 24 h-urinary phosphate: 681 mg (normal range: 400–1300). Thyrotropin levels were 5.67 mIU/ml (normal range 0.4–4), and anti-thyroid autoantibodies were negative.

GNAS methylation analysis showed a methylation defect in the maternally derived exon A/B, with a normal methylation pattern of the paternal NESP55-DM allele, presumably caused by microdeletions disrupting the upstream STX16 gene. Treatment with alfacalcidol and calcium was initiated, which restored calcium and PTH levels.

One year after diagnosis, the patient successfully carried a twin pregnancy to term, following in vitro fertilization for idiopathic infertility. During pregnancy, she remained metabolically stable. GNAS methylation analysis in the offspring, revealed the same methylation defect in the male infant, establishing an autosomal dominant mode of inheritance pattern.

Conclusions: PHP Ib is a rare disease that can remain undetected to mid life. Establishing the diagnosis is important not only for appropriate case management but also for genetic counseling.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.