Hypogonadism in Adult Males with Prader-Willi Syndrome—Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion

Prader–Willi syndrome (PWS) is a complex genetic syndrome characterized by hyperphagia, intellectual disability, hypotonia and hypothalamic dysfunction. Adults with PWS often have hormone deficiencies, hypogonadism being the most common. Untreated male hypogonadism can aggravate PWS-related health issues including muscle weakness, obesity, osteoporosis, and fatigue. Therefore, timely diagnosis and treatment of male hypogonadism is important. In this article, we share our experience with hypogonadism and its treatment in adult males with PWS and present a review of the literature. In order to report the prevalence and type of hypogonadism, treatment regimen and behavioral issues, we retrospectively collected data on medical interviews, physical examinations, biochemical measurements and testosterone replacement therapy (TRT) in 57 Dutch men with PWS. Fifty-six (98%) of the patients had either primary, central or combined hypogonadism. Untreated hypogonadism was associated with higher body mass index and lower hemoglobin concentrations. TRT was complicated by behavioral challenges in one third of the patients. Undertreatment was common and normal serum testosterone levels were achieved in only 30% of the patients. Based on the Dutch cohort data, review of the literature and an international expert panel discussion, we provide a practical algorithm for TRT in adult males with PWS in order to prevent undertreatment and related adverse health outcomes.

Impact of the ACOSOG Z0011 Trial on Surgical Practice in Asian Patients: Comparison of Trends in Axillary Surgery for Breast Cancer Between Korean and Dutch Cohorts

PurposeSince the publication of the Z0011 trial, practice-changing clinical guidelines for breast surgery have been developed. Although recent studies confirmed the feasibility of the Z0011 strategy in Asian populations, there has been no study on the trends of axillary surgery in Asian cohort. This study aimed to investigate the time trend of axillary surgery for breast cancer in Korea and compare it with that in Dutch cohort to understand the impact of the Z0011 trial.MethodsWe collected prospectively constructed data from the nationwide Korean Breast Cancer Registry (KBCR). We identified patients who underwent sentinel node biopsy followed by breast-conserving surgery from 2011 to 2018 and were found to have pathological stage T1-2N1-3M0 disease. Regression analyses were performed to compare the downward trend of axillary lymph node dissection (ALND) in our cohort with that previously reported in a Dutch cohort.Results From KBCR data, 7,478 patients met the inclusion criteria. The proportion of ALND significantly decreased from 2011 (76.6%) to 2018 (47.5%). Multivariate analysis revealed that earlier year at diagnosis, larger tumor size, and lymphatic invasion were associated with a higher odds ratio of performing ALND. Compared to Dutch cohort, the downward trend of ALND in Korea was significantly more gradual (annual percent change: 30.1% vs. 5.8%, P < 0.001).ConclusionsThis study demonstrated a downward trend of ALND in Korean patients with breast cancer. However, the rate of decrease was significantly slower than that in Dutch cohort, indicating the need to spread the Z0011 strategy in Asia.

Evident hypopigmentation without other ocular deficits in Dutch patients with oculocutaneous albinism type 4

To describe the phenotype of Dutch patients with oculocutaneous albinism type 4 (OCA4), we collected data on pigmentation (skin, hair, and eyes), visual acuity (VA), nystagmus, foveal hypoplasia, chiasmal misrouting, and molecular analyses of nine Dutch OCA4 patients from the Bartiméus Diagnostic Center for complex visual disorders. All patients had severely reduced pigmentation of skin, hair, and eyes with iris transillumination over 360 degrees. Three unrelated OCA4 patients had normal VA, no nystagmus, no foveal hypoplasia, and no misrouting of the visual pathways. Six patients had poor visual acuity (0.6 to 1.0 logMAR), nystagmus, severe foveal hypoplasia and misrouting. We found two novel variants in the SLC45A2 gene, c.310C > T; (p.Pro104Ser), and c.1368 + 3_1368 + 9del; (p.?). OCA4 patients of this Dutch cohort all had hypopigmentation of skin, hair, and iris translucency. However, patients were either severely affected with regard to visual acuity, foveal hypoplasia, and misrouting, or visually not affected at all. We describe for the first time OCA4 patients with an evident lack of pigmentation, but normal visual acuity, normal foveal development and absence of misrouting. This implies that absence of melanin does not invariably lead to foveal hypoplasia and abnormal routing of the visual pathways.