BACKGROUND 5α-Reductase 2 deficiency (5ARD) is a known cause of 46,XY disorders of sex development (DSD). Traditionally, the diagnosis relies on dihydrotestosterone (DHT) measurement, but the results are often equivocal, potentially leading to misdiagnosis. We reviewed alternative approaches for diagnosis of 5ARD. METHODS We conducted a retrospective review of the results of urinary steroid profiling (USP) by GC-MS and mutational analysis of SRD5A2 [steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2)] by PCR and direct DNA sequencing of all 46,XY DSD patients referred to our laboratory with biochemical and/or genetic findings compatible with 5ARD. We also performed a literature review on the laboratory findings of all 5ARD cases reported in the past 10 years. RESULTS Of 16 patients diagnosed with 5ARD between January 2003 and July 2012, 15 underwent USP, and all showed characteristically low 5α- to 5β-reduced steroid metabolite ratios. Four patients had DHT measured, but 2 did not reach the diagnostic cutoff. In all 12 patients who underwent genetic analysis, 2 mutations of the SRD5A2 gene were detected to confirm the diagnosis. Twenty-four publications involving 149 patients with 5ARD were published in the review period. Fewer than half of these patients had DHT tested. Nearly 95% of them had the diagnosis confirmed genetically. CONCLUSIONS 5ARD can be confidently diagnosed by USP at 3 months postnatally and confirmed by mutational analysis of SRD5A2. Interpretation of DHT results may be problematic and is not essential in the diagnosis of 5ARD. We propose new diagnostic algorithms for 46,XY DSD.
Purpose To evaluate the long-term biochemical, clinical, and recurrence outcomes of radiofrequency (RF) ablation in treating primary aldosteronism due to aldosterone-producing adenoma (APA). Materials and Methods Institutional review board approval and written informed consent were obtained. The use of computed tomographically (CT) guided percutaneous RF ablation was evaluated in 36 patients (19 men; mean age ± standard deviation, 52.1 years ± 10.4) with APA (17 right and 19 left side; mean size, 15.5 mm ± 5.0). Primary aldosteronism was confirmed by using the oral sodium-loading test. After RF ablation, CT images, aldosterone-to-renin ratio (ARR), serum potassium level, and blood pressure control were assessed at 3 months and at the latest follow-up examination. Long-term treatment success was defined as normalization of ARR at the latest assessment. Comparison of ARR, potassium, and blood pressure levels before and after RF ablation was performed by using the Wilcoxon signed-rank test. Results Primary technical success was achieved in 33 (92%) patients who underwent a single RF ablation session. Secondary technical success was achieved in three (8%) patients who required a second RF ablation. At 3-month follow-up, primary aldosteronism was resolved in 33 (92%) patients, with a starting median ARR of 8583 pmol/L per µg/(L · h) that normalized to 97 pmol/L per µg/(L · h) (P < .01). Mean serum potassium levels increased from 2.6 mmol/L ± 0.4 to 4.0 mmol/L ± 0.3 (P = .01). At long-term follow-up (mean, 6.2 years ± 2.5), treatment success was maintained in 33 patients (92%), all of whom had ARRs in the normal range (P < .01). The long-term recurrence rate was 0%. Hypokalemia was resolved in all patients (2.6 mmol/L ± 0.4 to 4.1 mmol/L ± 0.3, P = .01). Hypertension was resolved in 13 (36%) patients, and its control was improved in seven (19%) patients. One (3%) patient had major complications and six (17%) had minor complications. Conclusion CT-guided RF ablation is an effective treatment for APA, with high sustainable long-term treatment success. It may serve as a justifiable treatment alternative to surgery and medical therapy for APA. RSNA, 2016.
Familial hypocalciuric hypercalcaemia (FHH) is a genetic disorder of altered calcium homeostasis. Mutations in the CASR, GNA11 and AP2S1 genes have been reported to cause FHH. We report a Hong Kong Chinese kindred with FHH type 3 (FHH3) caused by mutations in AP2S1. The proband, a 51-year-old woman with hypercalcaemia, was initially diagnosed to have primary hyperparathyroidism but repeated parathyroidectomy failed to normalize her plasma calcium concentrations. Later, FHH was suspected and yet no mutations were identified in the CASR gene which causes FHH type 1 (FHH1), the most common form of FHH. Genetic testing of AP2S1 revealed a heterozygous c.43C>T (p.Arg15Cys) mutation, confirming the diagnosis of FHH3. The elder brother and niece of the proband, who both have hypercalcaemia, were found to harbour the same mutation. To our knowledge, this is the first Chinese kindred of FHH3 reported in the English literature.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.