Endocrine Abstracts

Introduction

Pseudohypoparathyroidism (PHP) is the first example of hormonal resistance observed in human pathology characterized by a great variability of clinical and genetic expression. We present a case of PHP in a Tunisian family.

Observation

The index case is a 31-year-old man. He was burn out of a consanguineous marriage (distant consanguinity) followed since the age of 15 for convulsive seizures. Three months earlier, complex partial seizures became reccurent and refractory to medication. The brain MRI revealed the presence of calcifications of the central gray nuclei. Serum biochemical analysis presented severe hypocalcemia (1.15 mmol/l), hyperphosphatemia (2.76 mmol/l) and an elevated serum parathyroid hormone level (320 pg/ml) (normal range 10–60 pg/ml). On general physical examination, there was a short stature, facial dysmorphia, android obesity, bradymetacarpia of fourth and fifth fingers bilaterally, bradymetatarsia and subcutaneous ectopic calcifications. Signs of latent tetany in the form of Chvostek’s and Trousseau’s sign were present. Renal function and 25 (OH) vitamin D levels were normal with no biological signs of malabsorption. The ophthalmologic examination showed a bilateral subcapsular cataract.Thyroid profile revealed normal T3, T4 levels with slightly elevated TSH levels (8.5 uIU/ml), suggestive of TSH resistance. Patient was diagnosed as PHP type 1a. He was treated with oral calcium (3 g/day) and calcitriol (1 µg/day). He responded to the treatment, and is presently asymptomatic with maintenance of normal calcium levels and no recurrent epileptic seizures. Family investigation revealed the presence of the same abnormal regulation of calcium and phosphate homeostasis in his sister and his younger brother (older brother would be unharmed ), and the discovery of asymptomatic hypocalcemia in the mother and maternal uncle. The biomolecular study of the Gs protein is in progress.

Conclusion

PHP is a rare, deeply impairing disorder of calcium metabolism, characterized by end-organ resistance to the action of paratyroid hormone. This group of disorders is caused by different and complex genetic and epigenetic defects. There is an urgent need to improve knowledge on the natural history of the diseases, to better understand the bridges between these clinically heterogeneous and to develop new therapies.