Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

A real case of Pseudohypoparathyroidism (#372)

Rohit Rajagopal 1 , Jane Estrella 1 , Andrew Bonura 2 , Naomi Eastwood-Wilshere 1
  1. Endocrinology Department, Campbelltown Hospital, Sydney, NSW, Australia
  2. Radiology Department, Campbelltown Hospital, Sydney, NSW, Australia

We present a 45yo woman with hypocalcemia-related seizures and an as yet-unreported phenotypic presentation of pseudohypoparathyroidism 1b (PHP1b) with crossover features of PHP1a. She had a 15-year history of hypocalcemia prior to presentation at our institution, with adherence difficulties to prescribed replacement, for which she had been given a diagnosis of Gitelmans Syndrome by her treating physician. Her clinical picture includes resistance to multiple hormonal axes, recurrent pancreatitis with calcification and duct stones, learning difficulties and some features of Albright’s Hereditary Osteodystrophy (AHO) including round facies, hypertelorism, and an acrodysostotic nose but no skeletal heterotopic ossification or brachydactyly. There was no history of head or neck surgery/irradiation or autoimmune disease, nor was there family history of hypocalcaemia, although the proband has lost contact with other members of her family. Striking abnormalities included renal resistance to raised PTH, hypocalcaemia, hyperphosphatarmia, low urinary calcium and decreased PTH-phosphaturic response. Testing for involvement of other endocrine axes revealed resistance in the hypothalamic-pituitary-gonadal axis (the clinical effects are unclear due to previous hysterectomy and she did not describe vasomotor symptoms of menopause) and TSH resistance for which she treated with thyroxine. The ACTH/cortisol axis was intact. AHO and involvement of multiple endocrine axes to this degree is commonly seen in PHP1a but is unusual in PHP1b. In contrast to renal PTH-resistance, she had radiologic evidence of hyperparathyroid bone disease with cortical thinning of the radius, a “salt-and-pepper” appearance on skull Xray and severe osteoporosis with preferential loss of bone at the distal radius, with resultant rib fractures on bone scan. Sequencing of the GNAS gene did not show any sequence variants as would be seen in PHP1a, but methylation analysis of exon 1A of the GNAS locus showed partial loss of methylation consistent with PHP1b. (27%; normal >43%, complete loss <8%).




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