Efficacy and safety of low-dose versus high-dose hydrocortisone to treat hypotension in neonates: a protocol for a systematic review and meta-analysis

BackgroundImpaired adrenal function is a well-described entity in critically ill term and preterm neonates with systemic hypotension. The standard treatment for neonatal hypotension includes volume expanders and vasopressors. Recent evidence supports the use of glucocorticoids for the primary or rescue treatment of neonatal hypotension associated with impaired adrenal function. However, inconsistency regarding the prescribed dosing regimen to provide the best balance between efficacy and safety in this vulnerable population remains an area of concern.MethodsWe will conduct a systematic review and meta-analysis to evaluate low-dosing compared with high-dosing regimens of hydrocortisone for the treatment of hypotension in critically ill term, preterm and very low birth weight neonates. Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and Web of Science will be searched from inception to November 2021. Study screening and selection will be completed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Our primary outcomes will be (1) an improvement in end-organ perfusion, defined as an increase in blood pressure along with an increase in urine output or a reduction in serum lactate and (2) mortality prior to discharge. Our secondary outcomes will be the development of (1) major neurosensory abnormality, (2) bronchopulmonary dysplasia and (3) the occurrence of adverse events.DiscussionHydrocortisone may be beneficial in the treatment of hypotension associated with impaired adrenal function among critically ill neonates. However, its optimal dosing to balance desired efficacy with the risk of adverse events is yet to be determined. Our systematic review and meta-analysis aims to address this evidence gap, providing valuable knowledge for a large audience, including guideline developers, policy-makers and clinicians.PROSPERO registration numberThis protocol is submitted for registration to the international database of prospectively registered systematic reviews (PROSPERO, awaiting registration number).

Outcomes of nephron sparing surgery and cortical sparing adrenalectomy in the management of Von Hippel–Lindau syndrome

Background The management of Von Hippel–Lindau syndrome (VHLS) is multidisciplinary. The urologist is involved in treating the renal, epididymal tumors and often adrenal pheochromocytoma. Preservation of renal and adrenal function is a challenge. We present 17 cases of VHLS in a tertiary care center in South India. Methods A retrospective review of the patients who underwent surgical treatment under urology for VHLS from January 2009 to November 2018 was conducted. The demographic data, the spectrum of manifestation, treatment, change in glomerular filtration rate, adrenal insufficiency, and recurrence-free survival were analyzed. Results There were 17 patients diagnosed with VHLS. The median age of diagnosis was 39 years (range 23–41). The spectrum of clinical manifestation was: multifocal RCC (88%), pancreatic cysts/tumors (70%), cerebellar hemangioblastoma (59%), retinal angiomas (47%), epididymal cysts/tumors (47%), pheochromocytomas (41%), and spinal hemangiomas (30%). There were seven patients with ten pheochromocytoma lesions. Three underwent cortical sparing and seven total adrenalectomies; 13 patients underwent nephron sparing surgery (NSS), of which seven patients had bilateral tumors. The median duration of follow-up was 6.5 years (range 2–12 years). Following NSS, seven patients had a local recurrence, and one developed pancreatic metastasis. Two patients (11%) were lost to follow-up. Renal function was preserved in all patients at the last follow-up, and there was no postoperative adrenal crisis or mortality. Conclusion Nephron sparing surgery and cortical sparing adrenalectomy are the treatment of choice for multifocal RCC and pheochromocytomas in patients with VHLS providing good oncological outcomes and preservation of renal and adrenal function.

P.097 Adrenal Insufficiency among Children treated with Hormonal Therapy for Infantile Spasms

Background: Hormonal therapy is a standard treatment for infantile spasms. The high doses given and long treatment duration expose patients to the risk of adrenal insufficiency (AI). This study aims to quantify the incidence of AI among children with infantile spasms treated with corticosteroids and/or adrenocorticotropic hormone (ACTH). Methods: A retrospective chart review of patients treated for infantile spasms was performed between January 2009 to March 2020 in one pediatric specialized hospital. Variables collected included patient and treatment characteristics, risk factors of AI and adrenal function testing. Analysis included descriptive statistics. Results: Thirty-one patients met the inclusion criteria and received a total of 33 separated courses of treatment. Adrenal function following each course of treatment was evaluated in all patients. AI occurred in 25/33 (76% [95CI 58-89]) children. There was no predictive factor of AI. No drug regimen was deemed safe. The two patients (6%) with an acute adrenal crisis were the youngest of the cohort. Conclusions: Adrenal suppression is frequent and can lead to adrenal crisis after standard hormonal therapy for infantile spasms. A routine laboratory assessment of adrenal function should be done for all patients. Hydrocortisone replacement therapy should be given until testing results are obtained, particularly for younger infants.

Endocrinology and ageing

Ageing causes changes in many hormonal areas. This chapter begins with an overview of these changes, and goes on to bone disease in the elderly, changes in growth hormones and IGF-1, differences in gonadal function and adrenal function, and then thyroid and pituitary disease in the ageing patient.

71 Adrenal Insufficiency among Children treated with Hormonal Therapy for Infantile Spasms

Primary Subject area Endocrinology and Metabolism Background Hormonal therapy is a standard treatment for children with infantile spasms. However, the high doses given and long treatment duration exposes patients to the potential risk of adrenal insufficiency (AI). There is, presently, limited data on occurrence of AI after hormonal therapy in this population. Objectives This study aims to quantify the incidence of AI among children with infantile spasms treated with high-dose corticosteroids and/or adrenocorticotropic hormone (ACTH). Design/Methods A retrospective chart review of patients less than 2 years old treated for infantile spasms was performed between January 2009 to March 2020 in one pediatric specialized hospital. Variables collected included sex, age, etiology, age at treatment initiation, type of hormonal treatment, dose and duration of treatment, concomitant medication and illness, other corticosteroid uses, hydrocortisone replacement therapy use, adrenal function testing, and signs of AI. Analysis included descriptive statistics, such as incidence and bivariate analysis. Results Thirty-one patients met the inclusion criteria and received a total of 33 separated courses of hormonal treatment. Adrenal function following each course of treatment was evaluated in all patients, either by tests or by the presence of adrenal crisis. Oral hydrocortisone replacement therapy was received by 32/33 (97%) children. AI occurred in 25/33 (76% [95% CI 58-89]) children. There was no predictive factor for adrenal insufficiency after hormonal treatment, and no drug regimen (duration or total received dose) was safe. Two patients (6%) presented to the emergency room with an acute adrenal crisis the day following the weaning off of hormonal treatment. They were the youngest children of the cohort, with an age of 1,6 and 2,7 months at the initiation of treatment. All other patients were aged 4 months and older. Conclusion This study suggests that adrenal suppression is frequent after standard hormonal therapy regimen for infantile spasms. This can lead to serious complications, such as adrenal crisis, if not supplemented. A routine laboratory assessment of adrenal function should be done after hormonal therapy for all patients. We suggest that hydrocortisone replacement therapy should be given at the end of hormonal therapy and until testing results for adrenal function are obtained, particularly for younger patients.