Persistent hyperbilirubinemia in a 1-week-old male

An 8-day-old male infant presented with jaundice and poor feeding after an elevated transcutaneous bilirubin. He was born at 371/7 weeks via vacuum-assisted vaginal delivery after an uncomplicated pregnancy. Apgar scores were 5 and 9. Cord gases (arterial pH 7.23/base excess-2, venous pH 7.35/base excess-5) and newborn screen were normal. Birth weight was 3230 g (78.3 percentile). After discharge on day 7 of life, he presented to the emergency department for increased jaundice, abdominal distension, and not waking for feeds. He was afebrile with stable vitals. Jaundice was noted, but no bruising or cephalohematoma. His abdomen was soft with no palpable masses. Investigations revealed a normal complete blood count, C-reactive protein, procalcitonin, and electrolytes. Serum bilirubin was 398 mmol/L (indirect 390 mmol/L). His blood type was A+ and direct antiglobulin test (DAT) negative, with reticulocytes 62 × 109/L. Lactate dehydrogenase (LDH) was 2016 U/L (range 225 to 600 U/L). He received intravenous fluids and intensive phototherapy. His bilirubin trended down but rebounded as fluids were weaned. Hematology consultation for the persistent hyperbilirubinemia and elevated LDH recommended testing for bleeding diathesis and an abdominal ultrasound. The latter showed a normal liver and spleen, but did reveal the cause of the patient's presentation. Bilateral 5 cm cystic adrenal lesions were identified on ultrasound and felt to be consistent with adrenal hemorrhage. An important differential diagnosis to consider was congenital neuroblastoma. However, due to the bilateral nature of the lesions, this was felt to be less likely. Given the importance of ruling out this diagnosis, random urine vanillylmandelic acid testing was sent and returned negative. Hyperbilirubinemia is a common presentation in neonates. The common causes are physiologic hyperbilirubinemia, isoimmune hemolytic disease of newborns, congenital hemolytic anemias, sepsis, hypothyroidism, and breast milk jaundice. Hemorrhage is an important cause of persistent hyperbilirubinemia, although adrenal glands are an unusual location. The patient’s reticulocyte count was not increased, DAT was negative, and detailed hematologic investigations for bleeding diathesis (INR, PTT, fibrinogen, von Willebrand antigen and activity) in addition to congenital hemolytic anemia were negative. A head ultrasound to assess for significant occult bleeding was normal. Blood and urine cultures were negative. Based on the otherwise normal workup, his hyperbilirubinemia was attributed to adrenal hemorrhage. Neonatal adrenal hemorrhages are rare and affect 0.2% of newborns (1). They are usually unilateral with 70% occurring on the right side (1). Adrenal hemorrhage may be asymptomatic or may present with jaundice, abdominal mass, shock, and/or anemia. Rarely, adrenal insufficiency can also occur. Though not seen in our case, a significant hemorrhage can also disrupt the surrounding capsule and manifest as a scrotal hematoma (2). At birth, the adrenal glands are large and highly vascular, resulting in increased vulnerability to vascular damage. Neonatal adrenal glands are relatively large as the fetal cortex produces large amounts of steroid hormone precursors utilized by the placenta to maintain pregnancy and inhibit uterine contraction (2). Therefore, at birth, the adrenal glands are larger than adult adrenals but go on to regress by a third during the first month of life (2). Vaginal delivery, macrosomia, and fetal acidemia following birth asphyxia are important risk factors for neonatal adrenal hemorrhage, yet adrenal hemorrhage can occur in the absence of any significant risk factors (2). Adrenal hemorrhage is more commonly associated with being term and male sex (1). In our case, the only risk factor was vaginal delivery. At birth, he received resuscitation with 2 min of positive pressure ventilation and 10 s of continuous positive airway pressure. Cord gases were unremarkable. Abdominal ultrasound is the imaging of choice for neonatal adrenal hemorrhages. Radiological appearance varies depending on the age of the hematoma. Initially, acute hematomas appear echogenic on ultrasound, and over time liquefy and appear cystic (2). The cystic appearance of the adrenal glands on day 7 of life raises the possibility the hemorrhages occured in-utero as the cystic transformation typically occurs over 10-14 days. They may also calcify with age as they decrease in size. Computed tomography scans add unnecessary radiation and magnetic resonance imaging can be cost-prohibitive and may require sedation. The management of adrenal hemorrhages is primarily nonsurgical as they will typically resolve without treatment over 3 weeks to 6 months (2). Pediatric surgery was consulted to review and advised no surgical management as hemorrhages were stable in size and not requiring transfusion with his lowest hemoglobin being 98 g/L. Abdominal ultrasounds were repeated and showed the bilateral hemorrhages decreasing in size. An adrenocorticotropic hormone (ACTH) stimulation test recommended by endocrinology was abnormal (baseline cortisol 117 nmol/L, peak at 30 min 246 nmol/L), while mineralocorticoid status was normal (normal sodium, potassium, renin, and aldosterone). Hypocortisolemia presumably contributed to the prolonged hyperbilirubinemia as it subsequently resolved with hydrocortisone initiation (Figure 1), and he was discharged on a hydrocortisone weaning schedule. At 3 months of life, our patient had complete resolution of symptoms with a normal follow-up ACTH stimulation test and normal abdominal ultrasound. Evolution of the hyperbilirubinemia with various treatment modalities. Clinical Pearls: Although hyperbilirubinemia is common, less common causes such as occult bleeding must be considered as a cause of unexplained persistent hyperbilirubinemia in a neonate. In addition to head ultrasound, consideration should be given to abdominal ultrasound. Adrenal hemorrhage is an uncommon but important cause of persistent hyperbilirubinemia. The mechanism of action can be occult bleeding with hemoglobin breakdown and/or hypocortisolemia. Management of adrenal hemorrhage is primarily nonsurgical and includes assessing for and treating adrenal insufficiency, as well as serial monitoring for resolution of both hemorrhage and recovery of adrenal status. No funding to report. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Written informed consent to share this case was obtained from the family.

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