Puberty Blocker and Aging Impact on Testicular Cell States and Function.

Spermatogonial stem cell (SSC) acquisition of meiotogenetic state during puberty to produce genetically diverse gametes is blocked by drugs collectively referred as 'puberty blocker' (PB). Investigating the impact of PB on juvenile SSC state and function is challenging due to limited tissue access and clinical data. Herein, we report largest clinically annotated juvenile testicular biorepository with all children with gender dysphoria on chronic PB treatment highlighting shift in pediatric patient demography in US. At the tissue level, we report mild-to-severe sex gland atrophy in PB treated children. We developed most extensive integrated single-cell RNA dataset to date (>100K single cells; 25 patients), merging both public and novel (52 month PB-treated) datasets, alongside innovative computational approach tailed for germ cells and evaluated the impact of PB and aging on SSC. We report novel constitutional ranges for each testicular cell type across the entire age spectrum, distinct effects of treatments on prepubertal vs adult SSC, presence of spermatogenic epithelial cells exhibiting post-meiotic-state, irrespective of age, puberty status, or PB treatment. Further, we defined distinct effects of PB and aging on testicular cell lineage composition, and SSC meiotogenetic state and function. Using single cell data from prepubertal and young adult, we were able to accurately predict sexual maturity based both on overall cell type proportions, as well as on gene expression patterns within each major cell type. Applying these models to a PB-treated patient that they appeared pre-pubertal across the entire tissue. This combined with the noted gland atrophy and abnormalities from the histology data raise a potential concern regarding the complete 'reversibility' and reproductive fitness of SSC. The biorepository, data, and research approach presented in this study provide unique opportunity to explore the impact of PB on testicular reproductive health.

Ovarian Steroid Cell Tumor Masquerading as Steroid-Unresponsive Congenital Adrenal Hyperplasia.

OBJECTIVE: Ovarian neoplasms in children are rare. The objective of this report is to emphasize the importance of considering those neoplasms in the differential diagnosis of hyperandrogenism even with negative diagnostic imaging. METHODS: We report the case of a 12-year-old girl who presented with virilization and elevated 17 hydroxyprogesterone (17-OHP) and who was subsequently diagnosed with an ovarian neoplasm. RESULTS: The patient was initially seen for hirsutism and deepening of the voice. Elevated 17-OHP, androstenedione, and testosterone prompted the initial diagnosis of nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, but those levels failed to suppress on corticosteroid therapy. Ultrasound, computed tomography scan, and magnetic resonance imaging of the abdomen and pelvis were normal. Genetic testing for congenital adrenal hyperplasia was negative. Bilateral selective adrenal and ovarian venous sampling confirmed the ovarian origin of her hyperandrogenism. A unilateral salpingo-oophorectomy revealed a steroid cell tumor. Postoperatively there was normalization of testosterone and 17-OHP. CONCLUSION: This report highlights the utility of selective adrenal and ovarian sampling when suspecting a primary androgen-secreting neoplasm, even in the setting of elevated 17-OHP levels and negative imaging studies, as early diagnosis can prevent manifestation of irreversible symptoms of virilization.

A rare case of childhood mucous membrane pemphigoid involving the oral and genital mucosa.

Mucous membrane pemphigoid (MMP) is a rare chronic immunobullous disease that involves the mucous membranes and may result in significant scarring and complications if diagnosis is delayed. MMP typically occurs in elderly patients, with very few cases reported in children. Here, we present a 12-year-old female patient with childhood-onset oral and genital MMP, clinically suspected to be lichen sclerosus, but eventually diagnosed as MMP after multiple supportive biopsies and confirmatory direct immunofluorescence. Although treatment was challenging, the combined use of systemic corticosteroids, dapsone, and mycophenolate mofetil was ultimately successful in achieving disease control.

Oral Contraceptive Use in Obese Adolescents: A Cautionary Tale.

Venous thromboembolism (VTE) is a life-threatening complication rarely encountered with the use of combined oral contraceptives (COCs). Obesity is an additional thrombosis risk factor that has been shown to further increase the risk of VTE with the use of COCs. We present 5 cases of obese adolescents (body mass index >30 kg/m2) who encountered thrombosis complications while on COCs. Although the absolute risk of VTE events in the setting of COCs is rare, caution should be observed when choosing hormonal therapy and safer COCs alternatives discussed with adolescents who are obese.

Consult and procedure incidence outcomes following establishment of a fertility preservation program for children with cancer.

PURPOSE: Fertility is a quality of life outcome adversely affected by cancer therapy. Many childhood cancer patients, however, are not offered options to preserve their fertility. Providers acknowledge difficulty discussing impaired fertility to patients due to lack of knowledge of available options. Our objective was to review the impact of a pediatric multidisciplinary fertility preservation program on providers' fertility preservation counseling and discussion of options. METHODS: A retrospective medical chart review was conducted for pediatric cancer patients prior to and following program establishment. Fertility preservation discussions, consults, and incidence were noted. Following filtering and stratification, 198 and 237 patients were seen prior to and following program establishment, respectively. RESULTS: Following program establishment, provider-patient discussions of impaired fertility (p = 0.007), fertility preservation consults (p = 0.01), and incidence of fertility preservation procedures (p < 0.001) increased among patients. Furthermore, the number of patients who received fertility preservation consults after receiving gonadotoxic treatment decreased (p < 0.001). This trend was particularly noted in pre-pubertal and female patients, for whom fertility preservation options are limited without an established program. CONCLUSION: The establishment of a formal program greatly improved access to fertility preservation consults and procedures in children with cancer.

Autoimmune progesterone dermatitis in the adolescent population.

BACKGROUND/OBJECTIVE: Autoimmune progesterone dermatitis (APD) is a rare autoimmune hypersensitivity reaction that occurs cyclically at the peak of endogenous progesterone production during the menstrual cycle in women. No study characterizing APD in the adolescent population is found; it appears likely to be underdiagnosed and undertreated. METHODS: A retrospective, single-center, review of all adolescent and pediatric patients (<20 years old at onset) with documented diagnosis of APD. RESULTS: Seventeen adolescent APD patients were included (mean age at diagnosis: 14.4 ± 2 years, mean interval of 13.6 ± 11.1 months between symptom onset and diagnosis). Twelve patients presented with urticaria, two with fixed drug eruption. Erythema multiforme, eczema, and recurrent aphthous stomatitis were present in one patient each. Exposure to exogenous progestin was present in two patients prior to disease onset. Progesterone skin test was performed in six patients with positive results in two. Fourteen patients received antihistamines and/or a topical corticosteroid. Combined oral contraceptives (COCs) were given to eleven patients, in seven via continuous daily dosing. Gonadotropin-releasing hormone agonist (GnRHa) was used in five, progesterone desensitization in four, omalizumab in two, and danazol in one patient. CONCLUSIONS: Adolescent APD is associated with a significant delay in diagnosis. The most common manifestation is urticaria. Exogenous exposure to progestins is uncommon in adolescent APD. Continuous COC, GnRHa, and progesterone desensitization have been used to control symptoms. Large, multicenter studies are required to better define, diagnose, and treat this under recognized condition among adolescent patients.