ORIGINAL ARTICLE Nocturnal hypoglycaemia in ACTH and GH deficient children: role of continuous glucose monitoring Paola Cambiaso*, Riccardo Schiaffini*, Giuseppe Pontrelli†, Chiara Carducci*, Graziamaria Ubertini*, Francesca Crea* and Marco Cappa* *Division of Endocrinology and Diabetology, University-Hospital Pediatric Department, Bambino Ges u Children’s Hospital, IRCCS and †Clinical Trial Centre, University-Hospital Pediatric Department, Bambino Ges u Children’s Hospital, IRCCS, Rome, Italy Summary Objectives To evaluate the usefulness of continuous glucose monitoring (CGM) to identify nocturnal hypoglycaemia in chil- dren affected by combined ACTH and GH deficiency and to optimize the hydrocortisone replacement therapy in these patients. Study design Eleven patients with ACTH and GH deficiency (five boys and six girls, age 1 6–16 8 years) underwent CGM for 36 h, including two nights. At least two consecutive glucose lev- els <2 78 mM were considered hypoglycaemic episodes. The dif- ferences in age and doses of hydrocortisone and recombinant human growth hormone (rhGH) between children with and without hypoglycaemia were analysed. The percentage of the glucose values <3 33 mM and the mean glucose levels were also evaluated. Results Continuous glucose monitoring demonstrated noctur- nal hypoglycaemia lasting from 30 to 155 min (1 5% of the total monitoring time) in three cases (27%). No statistically signifi- cant differences in age and rhGH dose were observed between children with or without hypoglycaemia. Conversely, the differ- ence in the hydrocortisone doses between the patients with and without hypoglycaemia resulted statistically significant (5 9 vs 8 5 mg/m²/day; P = 0 04). Eight patients presented glucose val- ues less than 3 33 mM during 5% of the total monitoring time. Hydrocortisone dose showed significant positive linear relation with mean glucose level (r = 0 79, P = 0 0035) and inverse rela- tion with time lags of glucose levels under 3 33 mM (r = 0 65, P = 0 03). Conclusions Our study shows that CGM may represent a valu- able tool to detect nocturnal asymptomatic hypoglycaemic epi- sodes and optimize the hydrocortisone therapeutic regimen in children with ACTH and GH deficiency. (Received 11 September 2012; returned for revision 3 October 2012; finally revised 19 November 2012; accepted 30 November 2012) Introduction Congenital central adrenal insufficiency (CAI), presenting alone or, more frequently, associated with GH deficiency (GHD), is a rare condition. It is characterized either by impaired synthesis and release of ACTH from the pituitary gland, or by impaired release or action of hypothalamic corticotropin-releasing factor, eventually leading to blunted cortisol secretion. It can be associ- ated with abnormalities in hypothalamus-pituitary development, isolated or part of more complex cerebral malformations, such as septo-optic dysplasia (SOD). 1 In children affected by CAI, isolated or associated with GHD, the optimal regimen of glucocorticoid replacement therapy is still controversial. The most important reason is the inability to repro- duce the physiological cortisol circadian rhythm, characterized by very low or undetectable circulating levels at midnight, increasing between 2:00 AM and 4:00 AM, peaking early in the morning, and then declining over the day. 2 Hydrocortisone, at a dose of 6–8 mg/m 2 /day, subdivided into three oral doses, is now considered the optimal regimen of replacement therapy in adults and children with CAI. 3–5 However, this currently recommended regimen reduces, but does not eliminate, nocturnal hypocortisolaemia. 5 Consequently, children with CAI may have nocturnal hypoglyca- emia. This is especially true in children with associated GHD, which represents an additional risk factor for hypoglycaemia. 6,7 Continuous glucose monitoring (CGM) is a sophisticated method, which measures interstitial glucose concentrations. Recently, a Consensus Statement about the use of CGM in chil- dren and adolescents with diabetes was published. 8 The useful- ness of this method was also evaluated in very low birth weight infants, 9 in newborn babies at risk of hypoglycaemia 10 and in children with other hypoglycemic disorders, such as hyperinsu- linism or glycogen storage diseases. 11–13 Only one study recently described the use of CGM in adults affected by Addison’s Dis- ease. 14 So far, no experience with CGM in children with CAI and GHD has been described. Correspondence: Paola Cambiaso, Division of Endocrinology and Diabe- tology, University-Hospital Pediatric Department, Bambino Ges u Chil- dren’s Hospital, IRCCS, P.za Sant’Onofrio n. 4, 00165 Rome, Italy. Tel.: +3906 6859 3071; Fax: +3906 6859 2508; E-mail: paola.cambiaso@opbg. net 232 © 2012 John Wiley & Sons Ltd Clinical Endocrinology (2013) 79, 232–237 doi: 10.1111/cen.12123