Pseudohypoparathyroidism (PHP) is a rare disease characterized by hormone resistance due to defect of the α subunit of the stimulatory G protein (Gsα). Hypocalcemia due to parathyroid hormone (PTH) resistance is common. PHP1a determined by maternal LoF mutations in GNAS, presents severe obesity as early feature with increased risk of developing metabolic derangement during life. The aim of the study was to evaluate the metabolic alteration in a population of PHP1a from our center. To our Knowledge very few studies have addressed this topic. All subjects affected by genetically confirmed PHP1a were included. Auxological parameters (BMI; BMI S.D.), metabolic and hormonal parameters and HOMA-IR, ISI were also calculated. Data were analyzed to find correlation also with ongoing therapies (vitamin D and hormonal replacement). To date 21 patients (6 pts> 18 years) were included (mean age: 15.3±11.6 years; range: 1-41 years; 13 males). Out of 21, 16 were on Calcitriol and 15 on Levothyroxine. None were on sex steroid or GH therapy, hypolipidic or antihypertensive drugs. Mean BMI was 25.6±6.3 (+2.1±0.9 S.D.); biochemical parameters showed: calcium 9.3±0.9 mg/dl; P 5.3±1.5 mg/dl; uric acid 4.8±1.6 mg/dl; Total cholesterol 172±25 mg/dl; HDL 46.2±14 mg/dl; GPT 28.1±25.6 U/ml; HbA1c 33.7±1.9 mmol/mol; HOMAIR 3.6±3.4; ISI 8.6±8.5; TSH 2.3±1.5 mUi/l; PTH 292±276 U/ml; 25OHvitD 43.2±40.9 U/ml IGF1 150±40.2 ng/ml. None is affected by Metabolic Syndrome according to international criteria for children and adults. Although with limit of sample size, we compared all the parameters between pts on (n.16) vs without (n.5) vitamin D and only age was statistically significant (6.3 yrs vs 18.1 yrs). Univariate analysis among all variables did not show any significant correlation, also considered according to sex or age (<18 yrs vs >18 yrs). Our preliminary data confirm the increasing of obesity (BMI>2 S.D.) among patients affected by PHP1a and altered insulin resistance measured as HOMA-IR (>2.4). None of the patients showed metabolic syndrome. Either Vitamin D or levothyroxine therapy did not seem to influence metabolic parameters. At the moment recruitment of patients is ongoing in order to confirm these data on larger population stratified for gender, BMI and age.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology