Table 1.

Acute management and follow-up of major endocrine features.

	Pathogenic mechanisms	Management	Follow-up
Hypoglycemia ( 32 – 33)	Increased or inappropriate insulin secretion, delayed feeding, depletion of glycogen stores, reduced counter-regulatory response	iv bolus 2 ml/kg 10% dextrose, followed by glucose delivery 5-6 mg/kg/min In the absence of iv access, rescue SC or IM glucagon bolus 100-200 mg/kg/dose Hyperinsulinism Start diazoxide 5-20 mg/kg/day orally, with incremental doses eventually combined with chlorothiazide.	Monitor plasma glucose levels regularly, especially during HT and weaning from TPN Modify glucose supply according to glucose monitoring (if the osmolality of the infused solution is >600 mOsm/L, place a central line) Monitor for side effects of diazoxide and try to discontinue when appropriate
Hyperglycemia ( 34, 35)	Interventions aimed at increasing glucose levels, hepatic and pancreatic islet dysfunction	Maintain optimal hydration to counteract osmotic diuresis Decrease glucose supply up to a minimum of 3-4 mg/kg/min If blood glucose persistently >180 mg/dl despite reduction in glucose supply, or the neonate has signs of plasma hyperosmolarity, consider starting sc or iv insulin as a continuous infusion or in boluses 0.05-0.1 UI/kg/dose every 4-6 hours Insulin infusion rate adjustments of 0.01 U/kg/h Withdraw insulin if plasma glucose levels persistently <15 mg/dl	Monitor blood glucose initially every 30 minutes and then hourly Check for rebound hyperglycemia, after insulin discontinuation Monitor for sodium and potassium abnormalities, especially during insulin infusion
Hyponatremia ( 36–39)	Acute brain injury, acute kidney damage, SIADH, fluid overload, hypothyroidism, hypocortisolism	Fluid restriction 50-70 ml/kg/day in the first 24h of life with further increase by 10 ml/kg/day Evaluate and replace concomitant overt hypothyroidism or hypocortisolism Consider vaptans if persistent hyponatremia or challenging management of fluid restriction	Water balance and hydration status monitoring Electrolytes monitoring every 8 hours over the first 24-48 hours
Hypernatremia ( 38, 39)	Severe brain damage leading to central diabetes insipidus	Avoid Hypotonic solutions Initial dose of Desmopressin at 1 mcg/kg/day, then adjust the dose according to water balance and electrolytes	Water balance monitoring Electrolytes monitoring every 8 hours over the first 24-48 hours and then regularly
Hypocalcemia ( 40, 41)	Altered PTH response or increased calcitonin, increased phosphate or bicarbonate load, low calcium intake, acute renal injury	Mild, asymptomatic hypocalcemia If possible, oral supplementation of 10% calcium gluconate calcium gluconate 10% iv at 1.5-2 ml/kg continuously or in divided doses every 6-8 hours Severe, symptomatic hypocalcemia calcium gluconate 10% iv infusion at 0.5-1 ml/kg slowly in 10 min, followed by calcium gluconate 10% iv at 1.5-2 ml/kg every 6-8 hours	Calcium measurements every 6-8 hours, especially during and after weaning calcium supplements Cardiac monitoring Try to gradually discontinue calcium supplementation if serum calcium persistently stable
Hypercalcemia ( 42–44)	SFN secondary to HT and/or traumatic delivery	Mild, asymptomatic hypercalcemia - Discontinue Vitamin D - Low-calcium formula - If persistent hypercalcemia, consider glucocorticoids Severe hypercalcemia (>12 mg/dl) or overt symptoms - Hospital admission - Discontinue Vitamin D - Low-calcium formula or parenteral nutrition - iv hydration with saline and then furosemide infusion - Consider subcutaneous Calcitonin - If persistent hypercalcemia, consider iv Pamidronate, one or more doses	Maintain adequate hydration Regular monitoring of serum and urine calcium and urine calcium/creatinine ratio, especially after dietary changes ECG monitoring Repeated abdomen US, looking for signs of nephrocalcinosis
Primary adrenal insufficiency ( 45–47)	Adrenal hemorrhage, dystocic delivery, macrosomia, fetal acidemia	Hydrocortisone 50-100 mg/m2, followed by 50-100 mg/m2/day, iv, as a continuous infusion or divided in 4 doses. When oral intake is possible, 10-12 mg/m2/day oral hydrocortisone, in 3 daily doses Consider oral fludrocortisone if persistently low sodium, high potassium, and high serum renin concentrations	Strict clinical monitoring (fluid balance, blood pressure, blood glucose) Frequent electrolytes monitoring Try to discontinue hydrocortisone and fludrocortisone if adrenal lesions resolve in US follow-up and clinical and biochemical parameters are stable.
Hypotension refractory to fluids and amines ( 48, 49)	Relative adrenocortical insufficiency	Hydrocortisone iv 1 mg/kg bolus test. In case of improvement of cardiovascular parameters, continue 1 mg/kg hydrocortisone every 8-12 hours for 3-5 days	Monitor blood glucose and urinary output

ECG, electrocardiogram; HT, hypothermic treatment; iv, intravenous; PTH, parathyroid hormone; SC, subcutaneous; SFN, subcutaneous fat necrosis; SIADH, syndrome of inappropriate antidiuretic hormone; TPN, total parenteral nutrition; US, ultrasound.