Journal of Pediatric Endocrinology and Metabolism

A 14-year-old girl with premature ovarian insufficiency but with a positive pregnancy test

Abstract Objectives Childhood cancer survivors are at risk for premature ovarian insufficiency, especially after treatment with alkylating agents. The objective of this report is to highlight a case in which this phenomenon caused a false-positive pregnancy test. Case presentation A workup was performed in a 14-year-old girl with a positive pregnancy test. She was diagnosed with stage IV neuroblastoma of the left adrenal gland at the age of 4 years. She received extensive treatment, including alkylating agents, and had been diagnosed with premature ovarian insufficiency. An LH/hCG suppression test was performed using high dose 17 bèta-estradiol: hCG levels normalized. Conclusions The pregnancy test was false-positive due to production of low amounts of hCG by the pituitary gland as a result of high LH concentrations following premature ovarian insufficiency. It may be helpful to perform the LH/hCG suppression test to prove pituitary origin of the hCG overproduction.

Hormone-active ovarian steroid cell tumor in a 2-year-old girl

Abstract Objectives Steroid cell tumors are very rare in children. During the past 25 years, only 3 cases have been reported in Germany. Symptoms may vary from virilization to signs of precocious puberty and increased growth velocity, making it diagnostically challenging. Due to rarity and the wide morphologic as well as differential diagnostic spectrum, initial clinical features may be misleading. Case presentation We report on a 2-year-old girl, who initially presented with symptoms of virilization and precocious puberty, i.e., pubertal hair growth equivalent to Tanner stage P3. Basal hormone profile yielded 10-fold increased testosterone and androstenedione as well as markedly increased estradiol levels in serum. Diagnostic imaging procedures (ultrasound, MRI of the abdomen) revealed a solid tumor in the left ovary, without any signs of peritoneal dissemination or metastases. After salpingo-oophrectomy of the left ovary (en bloc via laparoscopic surgery, without spillage), the diagnosis of an ovarian steroid cell tumor sized 40 × 25 × 22 mm producing both testosterone and estradiol was confirmed. The increased serum levels of androgens as well as estradiol decreased toward prepubertal values within 1 week after surgery. Conclusions Hormone-active steroid cell tumors of the ovary are extremely rare in infancy. In our patient, the tumor was classified as clinical stage Ia. We thus opted for clinical, biochemical, and sonographical controls without chemotherapy. We herein present follow-up data until 18 months after surgery and discuss them within the context of international literature.

Premature ovarian insufficiency in pediatric cancer patients: a 10 year Rady Children’s Hospital experience

Abstract Objectives To highlight the occurrence of premature ovarian insufficiency in pediatric cancer patients and determine which patient characteristics or treatment modalities are associated with ovarian failure and recovery. Methods Between August 2011–August 2021, 36 of 2,661 patients with cancer were identified to have subsequent ovarian failure. Data collected included cancer type, diagnosis age, types of chemotherapy, bone marrow transplant or radiation treatment, peak follicle-stimulating hormone (FSH), peak anti-Mullerian hormone (AMH), gonadotropin releasing hormone agonist (GnRHa) treatment, type of hormone replacement therapy, and if ovarian function recovery occurred. Results The most common cancer type identified was ALL. The mean age of diagnosis was 8.5±4.3 years and mean age of peak FSH value was 12.6±2.8 years. Most patients (97.2 %) were treated with alkylating agents and 72.2 % received radiation. Most patients (72.2 %) received hormone therapy, and 15.8 % of patients received GnRHa Lupron. Ten patients (27.8 %) had ovarian function recovery. Diagnosis age and treatment type were recovery predictors in multivariate regression modeling. Each year older in age was associated with a 30 % decrease in odds of recovery (OR: 0.7, CI: 0.5–0.95, p=0.035), and alkylating agent treatment without transplant was associated with a 3-fold increase in odds of recovery (OR: 3, CI: 2.7–564, p=0.007). Conclusions This retrospective review demonstrates that POI can occur in pediatric cancer survivors, emphasizing the importance of educating patients on potential long-term effects of cancer treatment and importance of routine surveillance. This study confirmed that recovery of ovarian function is possible, especially when diagnosed at a younger age, making continued monitoring essential.

Gonadal changes in children and adolescents with congenital adrenal hyperplasia

Abstract Objectives Testicular adrenal rest tumours (TARTs) are a common cause of infertility in males with congenital adrenal hyperplasia (CAH). Ovarian adrenal rest tumours (OARTs) and polycystic ovaries (PCO) can impair ovarian function in female patients with CAH. We aim to detect gonadal changes in children and adolescents with CAH. Methods This study was conducted on 50 CAH patients (30 females and 20 males) with 21-hydroxylase deficiency (21-OHD), with a mean age of 10.35 ± 2.36 years. Testicular ultrasonography and pelvic magnetic resonance imaging (MRI) were done in males and females respectively. Glucocorticoid doses and biochemical data were obtained from the patients’ medical records. Results TARTs were detected in 10/20 male patients (50 %). There was a significant relation between presence of TARTs, body mass index (BMI) standard deviation score (SDS), and bone age (p=0.017 and 0.023; respectively). There was no significant relation between presence of TARTs, laboratory parameters, or treatment received (p>0.05). Of those subjected to genetic analysis, 48 % had I2 splice (c.290-13A/C>G) followed by P30L (c.89C>T) (40.7 %). P30L (c.89C>T) was the most common allele among the patients with TARTs (42.9 %). There was no significant relation between presence of TARTs, the genotype, alleles, or the genotype groups (p>0.05). Only one female patient had radiological evidence of bilateral polycystic ovaries and none had OARTs. Conclusions The prevalence of TARTs in our study was high (50 %). Screening for TARTs in males with CAH is crucial; however, routine ovarian imaging in CAH females is not indicated unless ovarian dysfunction is present.

Novel pathogenic variant of DICER1 in an adolescent with multinodular goiter, ovarian Sertoli–Leydig cell tumor and pineal parenchymal tumor of intermediate differentiation

Abstract Objectives To present a case of a new pathogenic variant of DICER1. Case presentation 13-year-old female with non-toxic multinodular goiter and ovarian Sertoli–Leydig cell tumor, in whom a pineal parenchymal tumor of intermediate differentiation was diagnosed. Next-generation sequencing revealed a new germline mutation in the DICER1 gene (exon 16, c2488del [pGlu830Serfs*2] in heterozygosis), establishing the diagnosis of DICER1 syndrome. Conclusions Mutations in the DICER1 gene cause genetic predisposition to a wide spectrum of benign or malignant tumors from childhood to adulthood.

SRY-positive 45,X/46,XY karyotype in a phenotypically Turner-like Chinese adolescent female with ovarian dysgerminoma and gonadoblastoma

Abstract Objectives 45,X/46,XY mosaicism is a rare condition with clinical and genetic heterogeneity and have a greatly increased risk of developing germ cell tumors. We describe a rare 45,X/46,XY Chinese girl with malignant tumors, especially focusing on the molecular genetics of gonadal tumor. Case presentation We report a phenotypically Turner-like Chinese adolescent girl who presented primary amenorrhea and a pelvic mass as the chief complaint, which finally demonstrated dysgerminoma replacing the left gonad and gonadoblastoma arising from right gonad respectively. Her chromosome karyotype was 45,X(4)/46,XY(46); Y-chromosome microdeletions in AZFb regions were found on gonadal DNA rather than peripheral blood lymphocyte (PBL) DNA, while no variants were found in the promoter and coding region of SRY gene in both PBL and gonadal tissues. She underwent bilateral gonadectomy; no recurrence or serious complications were identified after 3 years of follow-up. Conclusions This case emphasizes the probable correlation between Y chromosome microdeletions in gonadal tissue and the severity of the phenotype in patients with 45,X/46,XY mosaicism and highlights the importance of clinical genetic testing at the chromosomal and molecular level.