The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple physiological functions of this hormone in rodents. In contrast, information regarding the roles of this hormone in humans is limited. Three morbidly obese children, who were congenitally deficient in leptin, were treated with daily subcutaneous injections of recombinant human leptin for up to 4 years with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia. Leptin therapy resulted in a rapid and sustained increase in plasma thyroid hormone levels and, through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development. Leptin deficiency was associated with reduced numbers of circulating CD4(+) T cells and impaired T cell proliferation and cytokine release, all of which were reversed by recombinant human leptin administration. The subcutaneous administration of recombinant human leptin has major and sustained beneficial effects on the multiple phenotypic abnormalities associated with congenital human leptin deficiency.

The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple physiological functions of this hormone in rodents. In contrast, information regarding the roles of this hormone in humans is limited. Three morbidly obese children, who were congenitally deficient in leptin, were treated with daily subcutaneous injections of recombinant human leptin for up to 4 years with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia. Leptin therapy resulted in a rapid and sustained increase in plasma thyroid hormone levels and, through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development. Leptin deficiency was associated with reduced numbers of circulating CD4 + T cells and impaired T cell proliferation and cytokine release, all of which were reversed by recombinant human leptin administration. The subcutaneous administration of recombinant human leptin has major and sustained beneficial effects on the multiple phenotypic abnormalities associated with congenital human leptin deficiency. Nonstandard abbreviations used: recombinant human leptin (r-metHuLeptin); lean body weight (LBW); dual-energy x-ray absorptiometry (DXA); basal metabolic rate (BMR); folliclestimulating hormone (FSH); luteinizing hormone (LH); murine IL-3 (mIL-3); phytohemagglutinin (PHA); total energy expenditure (TEE); SD score (SDS); bone mineral content (BMC); bone mineral density (BMD); free tri-iodothyronine (fT3); free thyroxine (fT4); thyrotropin (TSH); tuberculin purified protein derivitive (PPD).

The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple physiological functions of this hormone in rodents. In contrast, information regarding the roles of this hormone in humans is limited. Three morbidly obese children, who were congenitally deficient in leptin, were treated with daily subcutaneous injections of recombinant human leptin for up to 4 years with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia. Leptin therapy resulted in a rapid and sustained increase in plasma thyroid hormone levels and, through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development. Leptin deficiency was associated with reduced numbers of circulating CD4 + T cells and impaired T cell proliferation and cytokine release, all of which were reversed by recombinant human leptin administration. The subcutaneous administration of recombinant human leptin has major and sustained beneficial effects on the multiple phenotypic abnormalities associated with congenital human leptin deficiency. Nonstandard abbreviations used: recombinant human leptin (r-metHuLeptin); lean body weight (LBW); dual-energy x-ray absorptiometry (DXA); basal metabolic rate (BMR); folliclestimulating hormone (FSH); luteinizing hormone (LH); murine IL-3 (mIL-3); phytohemagglutinin (PHA); total energy expenditure (TEE); SD score (SDS); bone mineral content (BMC); bone mineral density (BMD); free tri-iodothyronine (fT3); free thyroxine (fT4); thyrotropin (TSH); tuberculin purified protein derivitive (PPD).

Background: Coronavirus diasease (COVID-19) is an infectious disease that started in Wuhan, China in late 2019 and later spread around the world. Diabetes has been recognized as a possible risk factor for COVID-19 complications. Objective: International Society for Pediatric and Adolescent Diabetes (ISPAD) investigated perceptions, challenges and experience of health care professionals (HCP) taking care of children and young people with diabetes worldwide during COVID-19 pandemic. Methods: From 21st April to 17th May 2020, during COVID-19 pandemic, a webbased survey was sent to ISPAD members and former participants of ISPAD conferences by email. Results: Responders from 215 diabetes centers from 75 countries completed the survey. Majority were from UK (35; 16.3%), USA (20; 9.3%), and India (15; 7%). HCP were mostly pediatric endocrinologists (64%). During COVID-19 pandemic, 16.5% of responders continued face-to-face consultation while most changed to telephone (32%) or video (18%) consultations. 19% reported a shortage of medical supplies. 22% reported a delay in diagnosis of patients with new-onset diabetes, while 15% reported a higher incidence of DKA. 12% reported having one or more patients with COVID-19. Most of the 86 children and adolescents with diabetes and COVID-19 had only mild/moderate symptoms, while 5 required admission to an intensive care unit. No deaths were reported. Conclusions: This large global survey during COVID-19 pandemic showed that many HCP adapted to the pandemic by resorting to telemedicine. One fourth of HCP reported delays in diagnosis and an increased rate of DKA. The emergence of COVID-19 pandemic had an important impact on family's behavior that might have led to increase in diabetic ketoacidosis presentation. K E Y W O R D S children, COVID-19, diabetes, diabetic ketoacidosis, telemedicine 1 | INTRODUCTION Coronaviruses are a large family of viruses that can cause disorders ranging from a mild cold to severe diseases. In December 2019, a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused an outbreak of Coronavirus diasease (COVID-19). Typical symptoms of COVID-19 include fever, cough, shortness of breath, and muscle pain. 1 In the time frame studied, a large cohort with COVID-19 from China showed that illness severity can range from mild (81%), severe (14%) to critical (5%). All

Aim-In suspected adrenal insuYciency, the ideal test for assessing the hypothalamo-pituitary-adrenal axis is controversial. Therefore, three tests were compared in patients presenting with symptoms suggestive of adrenal insuYciency. Method-Responses to the standard short Synacthen test (SSST), the low dose Synacthen test (LDST), and the 08:00 hour serum cortisol concentration were measured in 32 patients. A normal response to the synacthen test was defined as a peak serum cortisol of > 500 nmol/l and/or incremental concentration of > 200 nmol/l. The sensitivity and specificity of the 08:00 hour serum cortisol concentration compared with other tests was calculated. Results-Three patients had neither an adequate peak nor increment after the SSST and LDST. All had a serum 08:00 hour cortisol concentration of < 200 nmol/l. Eight patients had abnormal responses by both criteria to the LDST but had normal responses to the SSST. Three reported amelioration of their symptoms on hydrocortisone replacement. Twenty one patients had a normal response to both tests (of these, 14 achieved adequate peak and increment after both tests and seven did not have an adequate peak after the LDST but had a normal increment). The lowest 08:00 hour serum cortisol concentration above which patients achieved normal responses to both the LDST and SSST was 500 nmol/l. At this cut oV value (compared with the LDST), the serum 08:00 hour cortisol concentration had a sensitivity of 100% but specificity was only 33%. Conclusion-The LDST revealed mild degrees of adrenal insuYciency not detected by the SSST. The value of a single 08:00 hour serum cortisol concentration is limited. (Arch Dis Child 1999;80:330-333)