ESPE Abstracts

Background: Pseudohypoparathypoidism (PHP) type 1A is a rare endocrine disorders caused by GNAS mutation. Patients phenotype with PHP type 1A include obesity, round facies, brachydactyly, subcutaneous ossifications, short stature. The resistance of action of parathyroid hormone (PTH) leads to hyperphosphatemia, hypocalcaemia and secondary hyperparathyroidism. Hypercalcitoninaemia has been described in limited patients with PHP without thyroid pathology, but pathogenetic mechanism remain unknown. Hypercalcitoninaemia is considered an associated resistance to calcitonin.

Results: A 2,7 years girl presented to our clinic primarily with complaints of high level of calcitonin and obesity. She was born at 38 week gestational age with a normal birth length (52 cm, SDS +1,71) and weight (3250 g, SDS +0,36). She had excessive weight gain in the first two years of life. Hypothyroidism was diagnosed at 2 years (TSH 12,45 mIU/L (reference range: 0,35-4,0), free T4 0,63 ng/dl (reference range: 0,6-1,12), anti-TPO ab was normal). Levothyroxine was started with a dose 12,5 mkg once a day. Ultrasound didn’t not excluded focal change in the left thyroid lobe, of approximately 0.5 cm. Calcitonin level was 60,1pg/ml (reference range: 0-7,0). The girl was referred to our department due to suspicion of medullary thyroid carcinoma On physical examination in our clinic: height 95 cm (SDS = +1,03), weight 25,6 kg, BMI 28,4 kg/m2 (SDS = +4,6). Family history was without endocrine conditions. We found no changes in biochemical and hormonal parameters, excluding calcitonine and thyroid hormone. Fasting glucose, insulin, cortisol and adrenocorticotropic hormone levels were within normal range. Also laboratory showed normal level calcium and PTH (ionized calcium 1,14 mmol/l (1,03-1,29), phosphorus 1,9 mmol/l (1,45-1,78), PTH 50,86 pg/ml (15-65) and high level calcitonin – 90,7pg/ml and 79,9pg/ml on re-analysis. Subclinical hypothyroidism (TSH 7,014 mIU/L, free T4 10,98pmol/l) persisted on therapy, the dose of levothyroxine was increased to 25 mkg once a day. Ultrasound showed normal thyroid gland without nodules. Abdomen ultrasound and MRI examination demonstrated no tumors. Molecular genetic study of the RET gene did not reveal any anomalies. Due to the presence of obesity from early age, hypothyroidism and hypercalcitoninaemia Albright's syndrome was suspected. The molecular genetic study of the GNAS gene was carried out and revealed a heterozygous pathogenic variant c. 493C>T (p. Arg165Cys) affecting GNAS exon 6, described in literature before.

Conclusion: The present case represents patient with PHP1A and hypercalcitoninaemia without thyroid nodules that could be related to resistance to calcitonin.