Endocrine Abstracts

Introduction: Pseudohypoparathyroidism (PHP) is a rare cause of hypocalcaemia due to parathyroid hormone (PTH) resistance in the proximal renal tubules. In contrast to PHP type 1A, PHP type 1B is characterised by the absence of the characteristic skeletal abnormalities and is transmitted in an autosomal dominant manner, but in the maternal line. Patients may have resistance to the action of other G-protein signaling hormones, like thyroid stimulating hormone (TSH).

Case Presentation: A 28-year-old male was admitted with intermittent bilateral arm pains, tingling and carpopedal spasms, ongoing for a few years. His calcium was 1.4 mmol/l (2.20-2.60); phosphate, 1.56 mmol/l (0.8-1.5); PTH, 26.3 pmol/l (1.6-6.9) and 25-hydroxy-vitamin D, 24 nmol/l (25-125). Alkaline phosphatase, magnesium, TSH and renal function were normal. There were no phenotypic features of Albright’s Hereditary Osteodystrophy (notably normal 4th/5th metacarpals and height). There was no family history of calcium disorders. He reported being treated previously with Alfacalcidol, but had not taken this for years and remained asymptomatic. The hyperphosphataemia in the presence of elevated PTH with normal renal function suggested PTH resistance. His symptoms resolved with Alfacalcidol and calcium supplements. Genetic testing revealed he had pseudohypoparathyroidism type 1B: heterozygous deletion of exons 5-7 of the STX16 gene and complete loss of maternal methylation pattern at the GNAS A/B: TSS-differentiated-methylated region, the latter meaning this was maternally inherited. He had low 24-hour urinary calcium and phosphate: 0.3 mmol/24 hr (2.5-7.5) and 3.4 mmol/24 hr (15-50), respectively. The renal PTH resistance is confined to the proximal tubules with lack of PTH resistance in distal renal tubules or skeleton. This causes reduced urinary calcium and phosphate excretion with preserved skeletal calcium and phosphate mobilisation. This results in partial protection from symptomatic hypocalcaemia and an absence of skeletal abnormality.

Conclusion: PTH resistance should be suspected in patients with chronic hypocalcaemia, hyperphosphataemia, elevated PTH levels and normal renal function, prompting genetic confirmation.

Reference: 1. Poradosu S, Bravenboer B, Takatani R and Jüppner H, Pseudohypoparathyroidism type 1B caused by methylation changes at the GNAS complex locus, BMJ Case Rep.2016;2016:bcr20162146