The landscape of retesting in childhood-onset idiopathic growth hormone deficiency and its reversibility: a systematic review and meta-analysis.

Objective: Children diagnosed with idiopathic isolated growth hormone deficiency (IGHD) are frequently observed to no longer be GH-deficient at a later stage of growth as a result of 'GHD reversal'. Reevaluation of GH status by stimulation test is currently incorporated into management guidelines at attainment of final height (FH). Over the past three decades, numerous studies have evaluated reversal rates using different methodologies including crucial parameters like GHD aetiology, GH cut-off and retesting time point, with heterogeneous results. We aimed to systematically analyse the reversibility of childhood-onset IGHD dependent on retesting GH cut-offs and retesting time points. Methods: PubMed, Cochrane Library, TRIP database and NHS Evidence were searched for publications investigating the reversibility of IGHD from database initiation to 30 June 2020 following PRISMA recommendations. Study cohorts were pooled according to retesting GH cut-off and time point. Reversal rates were calculated using random-effects models. Results: Of the 29 studies initially identified, 25 provided sufficient detail for IGHD analysis, resulting in 2030 IGHD patient data. Reversal rates decreased significantly as the retesting GH cut-off increased (P = 0.0013). Pooled (95% CI) reversal rates were 80% (59-92%, n = 227), 73% (62-81%, n = 516) and 55% (41-68%, n = 1287) for cohorts using retesting GH cut-offs of 3-4 ng/mL, 5-6 ng/mL and 7.7-10 ng/mL, respectively. Individuals retested at FH (n = 674) showed a pooled reversal rate of 74% (64-82%) compared to 48% (25-71%) when retested before FH (n = 653). Conclusion: Provided evidence supports reevaluation of current IGHD management guidelines. The high reversal rates should instigate consideration of early retesting.

Recombinant human parathyroid hormone (1-84) replacement therapy in a child with hypoparathyroidism.

First line conventional therapy of hypoparathyroidism comprises oral calcium and active vitamin D analogues. This approach may fail to correct hypocalcemia and hyperphosphatemia caused by the absence of parathyroid hormone and carries the risk of long-term complications including ectopic calcifications and renal damage. Full-length recombinant human parathyroid hormone (rhPTH[1-84]) is approved for the treatment of hypoparathyroidism in adults refractory to conventional therapy. To date, there is no data in children. Here, we report the successful use of rhPTH(1-84) in a 5-year old girl with hypoparathyroidism and concomitant chronic diarrhea manifesting as part of the autoimmune polyglandular syndrome type 1. Prior to starting rhPTH(1-84), the patient had been on conventional and later on rhPTH(1-34) continuous pump therapy. Conventional therapy failed to meet serum and urinary calcium target levels, whilst the pump therapy wasn't well tolerated and posed handling difficulties. Dose optimization for rhPTH(1-84) was informed by serum ionized calcium, spot urinary calcium-to-creatinine ratio and 24-hour urinary calcium excretion. Twice-daily subcutaneous injections of rhPTH(1-84) with a total dose of 3.35 µg/kg/d was well-tolerated, raised serum ionized calcium to target range (1.05-1.15 mmol/L) and normalized serum phosphate levels. Urinary calcium excretion was slightly above the recommended limit of 4 mg/kg/24 h, but improved compared to conventional therapy, with no evidence of nephrocalcinosis. Twice-daily administration stabilized serum calcium and phosphate levels compared to once-daily injections. rhPTH(1-84) treatment was well tolerated and the girl did not manifest any acute clinical complications of hypoparathyroidism throughout the entire observation period. Our experience with this case indicates that rhPTH(1-84) may be a physiological hormone replacement for managing hypoparathyroidism in children.