Patients with Proximal Hypospadias Warrant Multi-System Newborn Evaluation Irrespective of Concomitant Cryptorchidism - Insights from a Multicenter Research Network
Andrew Gabrielson, MD1, Logan Galansky, MD1, Taylor Kohn, MD, MPhil1, Nora Haney, MD, MBA1, Hayley Sparks, MD2, Charlotte Wu, MD1, John Gearhart, MD1, Heather Di Carlo, MD1.
1Johns Hopkins Hospital, Baltimore, MD, USA, 2Childrens National Medical Center, Washington, DC, USA.
BACKGROUND: Disorders of sexual differentiation (DSD) is a heterogeneous group of diagnoses associated with atypical chromosomal, gonadal, or anatomic development. The updated 2016 DSD consortium consensus statement recommends that among patients with proximal hypospadias, only those with at least one undescended testis (UDT) undergo diagnostic evaluation for DSD. However, patients with proximal hypospadias and bilateral descended testes that are diagnosed with DSD may still benefit from multi-system evaluation to reduce morbidity from non-genitourinary congenital anomalies and gender dysphoria. We evaluated the utility of UDT as a marker for DSD as well as non-genitourinary congenital anomalies among patients with proximal hypospadias.
METHODS: The TriNetX Research network database, a US health research network consisting of 85 million patients from 2009-2021, was queried in this retrospective cohort study. Age, UDT status, DSD, congenital anomalies, and endocrine and genetic evaluation characteristics were extracted using applicable ICD-10 and LOINC codes in children 18 years or younger diagnosed with proximal hypospadias.
RESULTS: From 2014-2021, 1,025 children had proximal hypospadias, of which 117 (11%) were diagnosed with DSD and 318 (32%) diagnosed with at least one non-genitourinary congenital anomaly. UDT was diagnosed in 137 (14%) patients (Table 1). Rates of DSD among the patient groups were as follows: 0.25% without hypospadias, 8.8% with proximal hypospadias and bilateral descended testes, and 34.3% with proximal hypospadias and at least one UDT (Table 2). Patients with at least one UDT had a significantly higher risk of chromosomal anomaly on karyotype or microarray (RR 5.23 [3.3, 8.3]), any DSD (RR 3.91 [2.9, 5.4]), and any non-genitourinary congenital anomaly (RR 1.98 [1.6, 2.4]) compared to patients with bilateral descended testes (Table 2). Interestingly, patients with proximal hypospadias and bilateral descended testes had significantly higher risk of concomitant congenital cardiac, neurologic, respiratory, and digestive system anomalies compared to patients without hypospadias (Table 2).
CONCLUSIONS: Results from this study both question the utility of UDT as a correlate for DSD and reinforce UDT as a correlate for non-genitourinary congenital anomalies among patients with proximal hypospadias. We noted significantly higher concurrent rates of non-genitourinary congenital anomalies in virtually every organ system among patients with proximal hypospadias with bilateral descended testes when compared to patients without hypospadias. These data suggest that all patients with proximal hypospadias could benefit from evaluation for DSD, regardless of UDT status. However, UDT may serve as an adjunct in deciding whether to pursue evaluation for non-genitourinary congenital anomalies, namely neurologic and cardiac anomalies that were seen at rates 25-fold and 10-fold higher than patients without proximal hypospadias, respectively.
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