Endocrine Abstracts

Introduction: Pseudohypoparathyroidism is a rare disorder characterized by end-organ resistance to parathyroid hormone, caused by molecular defects of the PTH receptor. Resulting chronic hypocalcemia and hyperphosphatemia require lifelong treatment with active vitamin D metabolites and monitoring, representing a challenge especially in difficult living conditions.

Case report: A 19-year-old woman presented to our clinic with carpopedal spasms and tetany. Living in Switzerland since 5 years as a refugee from Eritrea, she reported having been treated with “pills” because of an undefined condition diagnosed in her early infancy. Her treatment was inevitably stopped when fleeing her native country and medical reports were not available. Clinical examination was unremarkable (61 kg, 164 cm, BMI 22.7 kg/m²), normal pubertal development and menstrual history. Her parents and the four siblings were asymptomatic. Laboratory tests showed hypocalcemia of 1.59 mmol/l, serum albumin-corrected calcium 1.35 mmol/l [reference range 2.15-2.55], with an elevated parathyroid hormone (PTH) of 389 pg/ml [reference range 15-65], accompanied by hyperphosphatemia of 1.94 mmol/l [reference range 0.87-1.45] and vitamin D deficiency (25-OH-vitamin D3 17 nmol/l [<50]). Renal function, magnesium- and TSH-levels were normal. Hypercalciuria was absent. Brain MRI revealed severe calcification of basal ganglia. Molecular genetic analysis showed reduced methylation at the GNAS gene locus, which, in combination with the unremarkable clinical phenotype, pointed to pseudohypoparathyroidism type 1 B. Treatment with calcium carbonate, cholecalciferol and calcitriol was started and symptoms resolved with correction of serum calcium.

Comment and conclusion: Pseudohypoparathyroidism type 1 B is defined by predominantly renal resistance to parathyroid hormone, resulting in hypocalcemia and hyperphosphatemia with elevated PTH, caused by molecular defects (sporadic or inherited) at the GNAS locus of PTH receptor, a G-protein–coupled receptor (Gsα). As various endocrine receptors depend on stimulatory G-protein-coupled transduction, other hormonal resistance (TSH, gonadotropins, GHRH) can result, typically found in different subtypes in the heterogenous group of pseudohypoparathyroidism disorders. The hormone resistance syndromes, in combination with specific somatic features (round facies, heterotrophic subcutaneous ossifications, brachydactyly) and development abnormalities, were first described by F. Albright in 1942, therefore known as Albright hereditary osteodystrophy. Although a rare disease (estimated prevalence: 0.79/100’000), pseudohypoparathyroidism must be suspected in symptomatic hypocalcemia with elevated PTH. Our case report highlights the importance of correct diagnosis, medical treatment and patient information to avoid potentially fatal consequences. Unfortunately, this was delayed for several years in our patient due to difficult living conditions as a refugee and asylum seeker.