Precocious puberty and other pubertal disorders in females during the Italian lockdown and the coronavirus 2019 (COVID-19) pandemic

Background: Adrenal insufficiency (AI) is a rare condition caused by an inadequate production of glucocorticoids. Preliminary data in adults suggest that AI could be associated with an increased susceptibility to infections; moreover, AI patients are at risk to develop a severe course of infectious diseases and to experience a life-threatening adrenal crisis. The aim of our study is to evaluate the severity and the outcome of COVID-19 in pediatric AI patients in comparison to subjects affected with other endocrinopathies not involving adrenal gland. Patients and Methods: This was a retrospective, multicenter study involving 11 Italian tertiary-centers of pediatric endocrinology. Data regarding symptoms, severity and duration of the disease, the need to increase the dose or receive parenteral administration of hydrocortisone and the outcome were collected through a telephone interview and review of patient’s medical files. From March 2020 to October 2021, 80 children with a history of COVID-19 were collected: 49 subjects affected by AI (42 primary AI, 7 central AI) and 31 subjects as controls. Results: Mean age was comparable between patients and controls (11.4±4.4 years vs 10±3.5 years, respectively). The frequency of signs/symptoms during COVID-19 in AI patients was as follows: fever 68%, rhinorrhea 34%, headache 34%, sore-throat 30%, cough 28%, anosmia/ageusia 21%. Less common symptoms were characterized by arthralgia, abdominal pain, diarrhea and vomiting. The severity of infection was comparable between patients and controls: paucisymptomatic 40.8% vs 25.8%; mild 55.1% vs 61.3%; severe 4.1% vs 12.9%, respectively (Chi-square=0.19). Time between the first positive nasopharyngeal swab and the first negative one in patients vs controls was: ≤15 days, 39% vs 56.6%; >15 days, 61% vs 43.3%, showing a tendency to longer infection in AI children, although this difference did not reach statistical significance (Chi-square=0.14). In 64% of AI patients the dose of hydrocortisone was increased during the infection and in 6.4% parenteral hydrocortisone was needed. 94% of AI subjects did not require hospitalization while only 6% were hospitalized with a complete recovery in 100% of cases. Within the entire cohort of AI subjects, 2 children (4%) experienced an adrenal crisis during infection. No fatal events occurred. Conclusion: Our data, suggest that children with AI adequately treated are not at increased risk of severe course of COVID-19. In comparison to controls, subjects with AI have a slightly longer duration of the disease, although this data need to be confirmed on larger sample of patients.