Endocrine Abstracts

JOINT2709

A premature baby born at 30 weeks and 6 days with a birth weight of 0.9kilograms presented on day 20 of life with diuresis symptoms. The urine output was 4-6ml/kg/hour and associated hypernatraemia with sodium of over 150mmol/l[RR 137-144], serum osmolality 320mOsmkg [RR 275-295], urine osmolality 160mOsmkg. The diuresis was responsive to intravenous desmopressin initially (0.04micrograms/kg/dose as required). The initial working diagnosis was Arginine vasopressin deficiency. Magnetic resonance imaging pituitary performed on day 37 showed an unremarkable anterior pituitary gland and bright spot of the posterior pituitary gland not well delineated. No destructive pituitary lesion or suprasellar mass. The desmopressin was later changed to sublingual (Nocdurna 6.25micrograms daily equivalent to 4micrograms/kg/dose). At one month of life, a spot copeptin showed a level of 31.5pmol/l[RR ≥21.4 diagnostic of AVP resistance]. This became a bit of a diagnostic dilemma therefore further work up was performed. At 2 months of age a DDAVP test was performed which showed a mixed picture of Arginine vasopressin deficiency and resistance. It was noted after regular sublingual desmopressin was given up to 2-3 times a day there was still diuresis noted. Diuresis was noted with single therapy of desmopressin. A trial of hydrochlorothiazide (1mg/kg/day) and restricted renal solute load (<14mosmo/kgH2O/kg) was unsuccessful due to hypontraemia of sodium 128mmol/l[RR 137-144]. After some titration, the diuresis was well controlled with sublingual desmopressin 6.25micrograms three times a day equivalent to 2 micrograms/kg/dose. Regarding the other pituitary axis, this baby’s cord thyroid stimulating hormone was normal and on day 21, noted to have increased thyroid stimulating hormone 15.3 mIU/l[RR 0.72-11] with low free thyroxine 9.8 pmol/l[RR 11.5-28.3] and thyroxine supplement was started. There was a history of low cortisol level at 1 week life. A short synacthen test was performed on 1 month which showed a peak cortisol level of 217nmol/l[RR ≥380 nmol/L] ACTH <1.6 pmol/l[RR <10.2]. Hydrocortisone replacement was started at 10mg/m²/day. A whole exome sequence result at 2 months of age showed 2 compound heterozygous variant of uncertain significance in PCSK1 gene. Maternal variant inherited showed Heterozygous NM_000439.5(PCSK1):c.844C>T p.(Arg282Trp). Paternal variant inherited showed Heterozygous NM_000439.5(PCSK1):c.493G>A p.(Val165Ile). This baby did not show other phenotypic features of the PCSK1 gene including neonatal diarrhoea and proinsulin was normal. We will need to observe further for possibility of future obesity and hypogonadotrophic hypogonadism.