Abstract
Fetal adrenal abnormalities can arise from either structural or functional anomalies. Structural abnormalities can be visualized on ultrasound as solid or cystic structures, such as neuroblastoma or hemorrhage. Congenital adrenal hyperplasia arises from enzymatic dysfunction and can sometimes be seen as enlarged adrenal glands and/or ambiguous genitalia. Adrenal abnormalities can have serious implications on antenatal and postnatal management of the offspring, and appropriate referrals should be made.
Keywords
neuroblastoma, adrenal hemorrhage, adrenal hematoma, congenital adrenal hyperplasia, ambiguous genitalia
Introduction
The fetal adrenal glands can be reliably imaged on prenatal ultrasound. The adrenal glands are located in a retroperitoneal, paraspinous location, cephalad to the upper renal poles. The gland is composed of a hypoechogenic cortex and a thin echogenic medulla ( Fig. 17.1 ).
Adrenal abnormalities can be divided into three categories and are listed in Table 17.1 :
- 1.
masses (neuroblastoma)
- 2.
bleeding (hemorrhage or hematoma)
- 3.
congenital adrenal hyperplasia
| Intrinsic Adrenal Anomalies | Differential Diagnoses |
|---|---|
|
|
Neuroblastoma
Definition
Neuroblastomas are a clinically heterogeneous group of malignant neuroendocrine tumors arising from pluripotent embryonic neuroectodermal cells. They are found in the adrenal glands in 40% of cases, but may also be found anywhere throughout the sympathetic nervous system (e.g., abdomen in 25%, thorax in 15%, neck in 5%, and retroperitoneal sympathetic ganglia in 5%). Of cases that are diagnosed prenatally, approximately 93% of cases are adrenal in origin.
Prevalence and Epidemiology
Neuroblastoma is the most common extracranial malignant solid tumor in infants younger than 1 year old, with an incidence rate of 60 per million live births. The median age at diagnosis is 17.3 months of age, and 40% of patients are diagnosed before 1 year of age.
The prognosis of neuroblastoma is inversely related to the age at diagnosis. Prenatal diagnosis of neuroblastoma allows detection at the earliest stages, enables prompt postnatal therapy with surgical resection and chemotherapy, and confers a survival advantage. They are accountable for 15% of pediatric oncologic fatalities.
Etiology and Pathophysiology
During embryogenesis, pluripotent neuroblasts migrate from the neural crest to form primitive sympathetic ganglia and adrenal medulla. Between 15 and 20 weeks of gestation, neuroblasts undergo an obligatory transition through a stage that is histologically similar to an in situ neuroblastoma. These lesions may follow a natural course of spontaneous regression by birth, or develop into clinically pathologic lesions via an oncogenic defect in control of cell division.
Chromosomal deletions of 1p, 11q, and 14q are found in approximately 50% of neuroblastomas. Neuroblastomas are also found to have a higher incidence rate in fetuses with Turner syndrome, and in disorders affecting neural crest cells, known collectively as neurocristopathies (Hirschsprung disease, central hypoventilation, and neurofibromatosis type 1). Folate has also been implicated in a population-based study investigating the effect of dietary folate fortification. The incidence of neuroblastoma declined from 1.6 to 0.6 cases per 10,000 births before and after folate fortification, respectively. In 1% to 2% of cases, neuroblastoma may exhibit a familial pattern, with autosomal dominant inheritance, incomplete penetrance, and a broad spectrum of clinical behaviors.
Manifestations of Disease
Clinical Presentation
Neuroblastomas have a wide spectrum of clinical presentations in the neonate, and may be difficult to diagnose. Signs and symptoms can be localized (e.g., palpable mass, pain, bowel or bladder compression, respiratory compromise, Horner syndrome) or systemic (e.g., hypertension, secretory diarrhea, anemia, vague systemic symptoms). Neuroblastomas can metastasize via the hematogenous or lymphatic routes to bone, bone marrow, skin, liver, lung, brain, and placenta. In advanced stages of disease in the fetus, the mother may also display signs of elevated catecholamine, including hypertension, tachycardia, or preeclampsia. Neonatal imaging and laboratory correlation, with urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA), are helpful in the confirmation of diagnosis. In children with neuroblastoma, 90% will have abnormal HVA, while 72.5% will have abnormal VMA.
Imaging Technique and Findings
Ultrasound.
The fetal adrenal glands can be easily identified on ultrasound (US) imaging. They have a discoid shape on a transverse view, and appear as Y – or V -shaped structures at the superior border of the kidney on an axial view. They can be imaged from the end of the first trimester.
Prenatal diagnosis of neuroblastoma by ultrasound was first reported in 1983. Adrenal neuroblastoma is typically seen as a suprarenal or paraspinal mass with cystic, solid, or mixed echogenicity. The kidney may be displaced inferiorly. Associated focal hemorrhage or calcification can be seen. Ultrasound detection usually happens during the third trimester. The right side appears to be affected more often, with 90% of right-sided suprarenal masses proving to be neuroblastoma. The presence of a systemic arterial supply on Doppler US may suggest a diagnosis of bronchopulmonary sequestration over a neuroblastoma. A fetal adrenal mass suspicious for neuroblastoma is seen in Fig. 17.2 .
Magnetic Resonance Imaging.
Adrenal glands present with marked hypointense signals on T2-weighted sequences and are demarcated from the adjacent organs by the hyperintense perirenal adipose tissues. Fetal magnetic resonance imaging (MRI) can be used as an adjunct to better localize and characterize tissue characteristics of fetal abdominal masses and presence of hepatic metastases, although this may also be delayed until the postnatal period. Table 17.2 describes the differences between MRI and US findings in various adrenal pathologies.
The classic ultrasound findings of neuroblastoma are a suprarenal mass of solid, cystic, or mixed echogenicity. Rarely, maternal signs and symptoms of elevated circulating catecholamines may be present, including hypertension, tachycardia, preeclampsia, and mirror syndrome.
| Lesion | US Characteristics | MRI Characteristics |
|---|---|---|
| Neuroblastoma | Variable (echogenic, solid, cystic, or heterogeneous) | Heterogeneous or high T2 signal intensity (SI) |
| Extralobar sequestration | Solid, echogenic, “reverse teardrop” appearance | High T2 SI |
| Adrenal hemorrhage | Cystic or complex with septations | Heterogeneous SI on T1 and T2 |
| Lymphatic malformation | Cystic with septations | High T1, infiltrating the retroperitoneum |
| Dysplastic duplex kidney | Heterogeneous, echogenic mass with cysts | Cystic changes in the upper pole of a duplex kidney |
| Adrenal hyperplasia | Bilateral masslike adrenals | Bilateral, same SI as adrenals |
Synopsis of Treatment Options
Prenatal
In utero fetal survival rate is high. Spontaneous regression is seen in 40% of cases. Expectant management is recommended, with serial fetal ultrasounds to screen for fetal hydrops, adrenal enlargement, or metastases. Mode and timing of delivery is dictated by size of adrenal mass, as abdominal dystocia and fetal hemoperitoneum have been reported after vaginal delivery. Mothers should also be monitored for development of hypertensive disorders or mirror syndrome.
Postnatal
Surgery alone is the primary therapy for adrenal neuroblastoma. Neoadjuvant chemotherapy may be used in cases whose tumors cannot be resected, such as spinal cord or respiratory tract involvement. Given the possibility of regression, some specialized centers allow for needle biopsy to select for lower grade, less aggressive tumors that may be amenable to expectant management and observation over a 4–6 week period.
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