Endocrine Abstracts

Introduction: Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of rare metabolic diseases, all characterized by end-organ resistance to the action of different hormones, primarily PTH. Main clinical characteristics are hypocalcemia and hyperphosphoremia associated with elevated parathyroid hormone (PTH) levels, frequently encompassing additional heterogeneous features, known as Albright’s hereditary osteodystrophy. A molecular cause can be identified in 80–90% of patients with PHP. The most common underlying mechanisms are de novo or autosomal dominantly inherited genetic mutations within of GNAS. Most of these cases are diagnosed during childhood.

Case report: A 28-year-old male was referred by the general practitioner to study episodes of hypoglycaemia. Born in the Dominican Republic, he moved to Mallorca (Spain) at the age of 10. His medical record included active drug use (cannabis, cocaine, alcohol) and intellectual disability not clarified. He explained symptoms of weakness, dizziness and cramps in his legs since adolescence. The physical exam showed a peculiar phenotype: stocky body, rounded face, brachydactyly, obesity. A glucometer was delivered and no hypoglycemia was documented. The blood test showed normoglycemia, normomagnesemia, hypocalcemia, hyperphosphatemia, 25-OH-vitamin D levels slightly decreased and elevated levels of PTH. Calcium levels had not been carried out before. Based on these findings, a PHP was supposed and other tests were requested. CT scan showed basal ganglia calcification, HAND X-rays showed severe brachydactyly. DEXA scan revealed normal bone density. Hormonal blood test showed a subclinical hypothyroidism, low levels of IGF-1, normal testosterone and hypercalcitoninemia. An insulin-induced hypoglycemia test validated a growth hormone deficiency. The genetic study confirmed heterozygous mutation in the GNAS gene and the features are consistent with a PHP1A. Treatment was started with oral calcium and calcitriol.

Conclusions: It is important to diagnose, classify and properly treat hypocalcemia at an early age to avoid future complications. PHP requires, in most cases, a multidisciplinary approach with an endocrinologist to screen and treat the hormonal disorders.