Endocrine Abstracts

Introduction: The pseudohypoparathyroidism (PHP) encompasses a heterogeneous group of diseases characterized by end-organ resistance to parathyroid hormone (PTH). PHB type 1b (PHP1b) presents with PTH resistance at the renal proximal tubule, sometimes with TSH resistance, usually in the absence of Albright’s hereditary osteodystrophy (AHO) clinical features.

Case report: A 64-year-old male was referred to endocrinology department for hypocalcemia. He was the third of eight children of non-consanguineous parents. His psychomotor development was unremarkable. He had a stroke at the age of 50 and suffers from anxiety disorder, hypertension and dyslipidemia. He complains of arthralgia, muscle contractures and paresthesias. A physical examination revealed overweight and short stature (weight 76 kg and height 160 cm), short neck and rounded face, without brachydactyly, subcutaneous calcifications or other signs of AHO. Laboratory tests confirmed hypocalcemia (ionized calcium 0.9 mmol/l) and hyperphosphatemia (5.7 mg/dl) in the presence of elevated PTH (287.3 pg/ml), low calciuria and phosphaturia with normal renal function. Thyroid function tests revealed no abnormalities. Spinal X-ray showed osteophytosis with ossification of the posterior longitudinal ligament. Renal ultrasound revealed nephrolithiasis and brain computed tomography presented calcification of basal ganglia and cerebellum. Five of his brothers (living abroad) have similar analytical results. Routine laboratory tests of the oldest brother, who died in our hospital from brain cancer, also shows hypocalcemia (ionized calcium 0.51 mmol/l) and hyperphosphatemia (6.1 mg/dl). The genetic study of our patient revealed abnormal methylation pattern of exon A/B in GNAS1 gene associated with heterozygous deletion within STX16 (the gene encoding syntaxin-16), cause of PHP1b, autosomal dominant.

Conclusion: PHP1b is an uncommon disorder that should be considered if there is hypocalcemia, hyperphosphatemia and elevated PTH, particularly in the absence of physical findings consistent with OHA. The autosomal dominant familial form is relatively rare and its recognition may allow early diagnosis and treatment of the disease in other family members.