Pituitary stalk interruption syndrome (PSIS) is a congenital pituitary anatomical defect. This syndrome is an antenatal developmental defect belonging to the holoprosencephaly phenotype spectrum. It is heterogeneous regarding clinical, biological and radiological presentation and is characterized by the following triad: thin (<1 mm) or interrupted pituitary stalk connecting the hypothalamus to the pituitary gland, no eutopic posterior lobe, and hypoplasia or aplasia of the anterior lobe. This review reports current knowledge about the composite pathogenesis, for which underlying mechanisms remain unclear. Current data suggest genetic origins involving early developmental gene mutations with complex inheritance patterns and environmental influence, placing PSIS at the crossroads between Mendelian and multifactorial diseases. The phenotype associated with PSIS is highly heterogeneous with a high incidence of various combinations of hormonal deficiencies, sometimes associated with extra-pituitary birth defects. The age at onset is variable, but typical presentation is evolutive combined anterior pituitary hormone deficiencies at pediatric age, which progress even during adulthood to panhypopituitarism. Therefore, patients’ follow-up throughout life is essential for adequate management.
ContextThe international GENHYPOPIT network collects phenotypical data and screens genetic causes of non‐acquired hypopituitarism.AimsTo describe main phenotype patterns and their evolution through life.DesignPatients were screened according to their phenotype for coding sequence variations in 8 genes: HESX1, LHX3, LHX4, PROP1, POU1F1, TBX19, OTX2 and PROKR2.ResultsAmong 1213 patients (1143 index cases), the age of diagnosis of hypopituitarism was congenital (24%), in childhood (28%), at puberty (32%), in adulthood (7.2%) or not available (8.8%). Noteworthy, pituitary hormonal deficiencies kept on evolving during adulthood in 49 of patients. Growth Hormone deficiency (GHD) affected 85.8% of patients and was often the first diagnosed deficiency. AdrenoCorticoTropic Hormone deficiency rarely preceded GHD, but usually followed it by over 10 years. Pituitary Magnetic Resonance Imaging (MRI) abnormalities were common (79.7%), with 39.4% pituitary stalk interruption syndrome (PSIS). The most frequently associated extrapituitary malformations were ophthalmological abnormalities (16.1%). Prevalence of identified mutations was 7.3% of index cases (84/1143) and 29.5% in familial cases (n = 146). Genetic analysis in 449 patients without extrapituitary phenotype revealed 36 PROP1, 2 POU1F1 and 17 TBX19 mutations.ConclusionThis large international cohort highlights atypical phenotypic presentation of constitutional hypopituitarism, such as post pubertal presentation or adult progression of hormonal deficiencies. These results justify long‐term follow‐up, and the need for systematic evaluation of associated abnormalities. Genetic defects were rarely identified, mainly PROP1 mutations in pure endocrine phenotypes.
Objective
Turner syndrome (TS) is responsible for gonadal dysgenesis with high risk of premature ovarian insufficiency. Little is known about fertility preservation (FP) strategies is this population.
Design
Data from women with TS consulting with a fertility specialist in our FP centre from 2014 to 2018 were retrospectively collected.
Measurement
Total number of mature oocytes cryopreserved using vitrification.
Patients
Nine women with TS were referred. Three women with different karyotypes underwent controlled ovarian stimulation (COS) for oocyte vitrification. Mean age at TS diagnosis was 13.7 years [9‐20]. Mean referral delay between TS diagnosis and fertility consultation was 9.7 years [7‐14]. First counselling for FP was provided at 23.7 years [18‐28]. Mean AMH serum level prior to COS was 53.8 pmol/L [3.6‐95].
Results
All three women succeeded in obtaining cryopreserved oocytes with a mean number of 15.3 per woman [9‐20] and 9.2 per COS cycle [2‐20]. Ovarian response to COS was unexpectedly remarkable for the woman with a complete 45,X monosomy. Procedure was well tolerated for all women. None of them have used oocytes for in vitro fertilization yet.
Conclusions
Independently of karyotype, antral follicular count, AMH and FSH levels seemed to be reliable predictive markers of oocyte cryopreservation success. In a monosomic TS woman, cryptic ovarian mosaicism could explain a successful ovarian response to stimulation with a high number of retrieved oocytes. In case of spontaneous menarche, TS adolescents should be referred during transition to adulthood for FP counselling to avoid referral delay and limit time‐related diminished ovarian reserve.
Purpose
After childhood leukemia and hematopoietic stem cell transplantation, hormone replacement therapy is often required to induce puberty because of premature ovarian insufficiency. Observance of this kind of treatment in adolescents and young women seems quite poor, and literature about its acceptance remains scarce; in order to learn about their experience and to better understand their attitude towards hormone replacement therapy, we used qualitative methods.
Design and patients
13 young women childhood cancer survivors completed an individual interview.
Results
We report that the negative experience of leukemia may cause rejection of the treatment, closely related to infertility unacceptance. Misconceptions and lack of adequate information of hormonal treatment effects are also major barriers to a good compliance.
Conclusions and implications for cancer survivors
Observance of hormone replacement therapy for young women childhood cancer survivors can be improved with a confidential patient-physician relationship, patient education, choice of galenic formulation according to personal preference, and psychological support during the long-time follow up.
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.