Endocrine Abstracts

Introduction: Pseudohypoparathyroidism (PHP) is a rare disorder characterized by parathormone (PTH) resistance, caused primarily by genetic defects involving the alpha-subunit of the stimulatory G protein. Biochemical and molecular analysis classify pseudohypoparathyroidism into types I-a, I-b, I-c and 2. We report a case of PHP I-b in an adolescent presenting with a neurological disorder.

Case Report: 11 years old female patient, with no relevant personal or family history, referred to a Neurology appointment for paroxysmal episodes of dystonia of the feet. She had hypocalcemia (corrected serum calcium 6.4 (8.6-10) mg/dl), hyperphosphatemia (serum phosphate 8.6 (2.5-4.5) mg/dl), elevated parathormone (PTH 438 (15-65)pg/ml); low urinary calcium (<9 mg/24H), normal D vitamin (1,25-diOH-calciferol and 25-OH-calciferol), magnesium and kidney function. Thyroid function showed TSH 7,21, uU/ml (0.4-4.6), free T4 11,1 pmol/l (12-22) and negative thyroid antibodies (TPO, TG). The laboratory results were suggestive of PTH resistance and partial TSH resistance. Supplementation with calcitriol, calcium carbonate and levothyroxine was initiated. No typical features of Albright hereditary osteodystrophy (AHO) were observed. A cerebral computed tomography scan revealed bilateral symmetrical calcifications of the cranial base nuclei involving the lenticular nucleus, globus pallidus, posteroexternal aspect of the thalamus and the cerebellar nuclei, especially dentate nucleus, suggestive of Fahr syndrome. Renal ultrasound revealed nephrolithiasis; thyroid ultrasound showed no alterations. Oftalmologic evaluation excluded cataracts. Genetic study was requested revealing a maternally inherited 3-kb STX16 deletion, with loss of methylation restricted to the GNAS exon A/B, cause of autosomal dominant PHP I-b. Currently, the patient shows little compliance to therapy, despite the risks, and remains with asymptomatic hypocalcemia.

Conclusion: PHP I-b is most often a sporadic disorder, but sex-linked autosomal dominant inheritance has been reported. Patients with PHP I-b show, occasionally, thyroid stimulating hormone (TSH) resistance and typically lack of Albright hereditary osteodystrophy features.