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Journal of Clinical Research in... Jun 202417α‑hydroxylase/17,20‑lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia that causes decreased cortisol and sex steroid levels and leads to...
17α‑hydroxylase/17,20‑lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia that causes decreased cortisol and sex steroid levels and leads to high production of adrenocorticotropic hormone (ACTH). Although affected patients have absolute cortisol deficiency, they do not show clinical signs of cortisol deficiency or hyperpigmentation. These patients most commonly present with delayed puberty and amenorrhea at late pubertal age. Impaired production of sex steroids leads to ambiguous or female external genitalia in affected 46, XY individuals. In this report, we describe a patient with 17OHD who presented with hyperpigmentation and hypergonodotropic hypogonadism while receiving chemotherapy.
PubMed: 38912718
DOI: 10.4274/jcrpe.galenos.2024.2024-3-13 -
JCEM Case Reports Jun 2024Turner syndrome (TS) is the most common sex chromosome disorder affecting females and is usually diagnosed within the first 3 decades of life. It can present with...
Turner syndrome (TS) is the most common sex chromosome disorder affecting females and is usually diagnosed within the first 3 decades of life. It can present with primary amenorrhea or infertility and often has a typical phenotype, with associated medical conditions that require lifelong surveillance. We report the case of a 76-year-old female with a history of osteoporosis and vertebral fractures who presented to our specialist osteoporosis clinic following a neck of femur fracture. She revealed a history of short stature and primary amenorrhea as a young woman, with limited investigation and treatment. Her other medical history included coeliac disease, hypertension, and hearing and vision abnormalities. Given her phenotype, the patient was referred for a karyotype at age 76, which was consistent with mosaic TS (45, X in 78% of cells and 46, X, r(Y) in the remaining cells). We review reports of other cases of marked delay in TS diagnosis and discuss the consequences of a late diagnosis.
PubMed: 38911360
DOI: 10.1210/jcemcr/luae104 -
Reproductive Biology and Endocrinology... Jun 2024Premutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, defined as between 55 and 200 CGGs, have been implicated in fragile X-associated primary ovarian...
BACKGROUND
Premutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, defined as between 55 and 200 CGGs, have been implicated in fragile X-associated primary ovarian insufficiency (FXPOI). Only 20% of female premutation carriers develop early ovulatory dysfunction, the reason for this incomplete penetrance is unknown. This study validated the mathematical model in premutation alleles, after assigning each allele a score representing allelic complexity. Subsequently, allelic scores were used to investigate the impact of allele complexity on age at amenorrhea for 58 premutation cases (116 alleles) previously published.
METHODS
The allelic score was determined using a formula previously described by our group. The impact of each allelic score on age at amenorrhea was analyzed using Pearson's test and a contour plot generated to visualize the effect.
RESULTS
Correlation of allelic score revealed two distinct complexity behaviors in premutation alleles. No significant correlation was observed between the allelic score of premutation alleles and age at amenorrhea. The same lack of significant correlation was observed regarding normal-sized alleles, despite a nearly significant trend.
CONCLUSIONS
Our results suggest that the use of allelic scores combination have the potential to explain female infertility, namely the development of FXPOI, or ovarian dysfunction, despite the lack of correlation with age at amenorrhea. Such a finding is of great clinical significance for early identification of females at risk of ovulatory dysfunction, enhancement of fertility preservation techniques, and increasing the probability for a successful pregnancy in females with premutations. Additional investigation is necessary to validate this hypothesis.
Topics: Humans; Female; Fragile X Mental Retardation Protein; Amenorrhea; Alleles; Primary Ovarian Insufficiency; Adult; Heterozygote; Mutation; Fragile X Syndrome; Age Factors; Young Adult; Adolescent
PubMed: 38907244
DOI: 10.1186/s12958-024-01227-5 -
African Journal of Reproductive Health Apr 2024Given the scarce data on DSD in Sudan, we aimed to characterize DSD's clinical and genetic profile in Sudanese patients. We studied 60 patients with DSD using clinical... (Comparative Study)
Comparative Study
Given the scarce data on DSD in Sudan, we aimed to characterize DSD's clinical and genetic profile in Sudanese patients. We studied 60 patients with DSD using clinical data, cytogenetics, and PCR for the SRY gene. The results showed that 65% grew up as females and 35% as males. There was a high percentage of consanguineous parents (85%). Female genital mutilation (FGM) was performed in 75% of females. Patients who presented after pubertal age were 63%, with ambiguous genitalia in 61.7%, followed by primary amenorrhea (PA) in 30%. The SRY gene was positive in 3.3% of patients with 46,XX karyotype and negative in 6.7% of patients with 46,XY karyotype. 5αR2D-DSD was seen in 43.3%, gonadal dysgenesis in 21.7%, Ovotesticular syndrome in 6.7%, Swyer and Turner syndrome in 5% each, and Androgen Insensitivity Syndrome (AIS) in 3.3%. In conclusion, DSD in Sudan has a distinct profile with late presentation, dominated by 5αR2D-DSD due to the increased consanguineous marriage, and FGM represents a significant risk for DSD patients.
Topics: Humans; Male; Female; Sudan; Middle Aged; Adult; Exercise; Diet; Disorders of Sex Development; Consanguinity; Aged; Adolescent; Reproduction; Gonadal Dysgenesis
PubMed: 38904941
DOI: 10.29063/ajrh2024/v28i4.2 -
Reproductive Medicine and Biology 2024In this unselected population of women referred to a center specialized in gynecologic endocrinology for suspicion of PCOS, a minimum rate of misdiagnosed FHA patients...
In this unselected population of women referred to a center specialized in gynecologic endocrinology for suspicion of PCOS, a minimum rate of misdiagnosed FHA patients of about 2% was found. It is necessary to evaluate reliable markers for the differential diagnosis between PCOS and FHA to avoid incorrect treatment, which might lead to negative long-term effects in women with undiagnosed FHA.
PubMed: 38898999
DOI: 10.1002/rmb2.12591 -
Frontiers in Pediatrics 2024This study represents the first documentation of the coexistence of complete androgen insensitivity syndrome (CAIS) with Müllerian duct remnants (MDRs) in mainland...
This study represents the first documentation of the coexistence of complete androgen insensitivity syndrome (CAIS) with Müllerian duct remnants (MDRs) in mainland China. Additionally, we provide a comprehensive review of the existing literature concerning CAIS with MDRs resulting from gene mutations. This study broadens the clinical spectrum of CAIS and offer novel insights for further exploration into Müllerian duct regression. A 14-year-old patient, initially raised as female, presented to the clinic with complaints of "primary amenorrhea." Physical examination revealed the following: armpit hair (Tanner stage 2), breast development (Tanner stage 4 with bilateral breast nodule diameter of 7 cm), sparse pubic hair (Tanner stage 3), clitoris measuring 0.8 cm × 0.4 cm, separate urethral and vaginal openings, and absence of palpable masses in the bilateral groin or labia majora. The external genital virilization score was 0 points. Serum follicle-stimulating hormone level was 13.43 IU/L, serum luteinizing hormone level was 31.24 IU/L, and serum testosterone level was 14.95 nmol/L. Pelvic magnetic resonance imaging (MRI) did not reveal a uterus or bilateral fallopian tubes, but nodules on both sides of the pelvic wall indicated cryptorchidism. The karyotype was 46,XY. Genetic testing identified a maternal-derived hemizygous variation c.2359C > T (p.Arg787*) in the gene. During abdominal exploration, dysplastic testicles and a dysplastic uterus were discovered. Histopathological analysis revealed the presence of fallopian tube-like structures adjacent to the testicles. The CAIS patient documented in this study exhibited concurrent MDRs, thus expanding the spectrum of clinical manifestations of AIS. A review of prior literature suggests that the incidence of CAIS combined with histologically MDRs is not uncommon. Consequently, the identification of MDRs in AIS cases may represent an integral aspect of clinical diagnosis for this condition.
PubMed: 38895190
DOI: 10.3389/fped.2024.1400319 -
Geburtshilfe Und Frauenheilkunde Jun 2024Breast cancer (BC) stands as a global concern, given its high incidence and impact on women's mortality. This complex disease has roots in various risk factors, some...
Breast cancer (BC) stands as a global concern, given its high incidence and impact on women's mortality. This complex disease has roots in various risk factors, some modifiable and others not. Understanding and identifying these factors can be instrumental in both preventing BC and improving survival rates. Remarkably, women's reproductive behaviors have emerged as critical determinants of BC susceptibility. Numerous studies have shed light on how aspects including age of menarche, first pregnancy and menopause along with number of pregnancies, hormone replacement therapies, can influence one's risk of developing BC. Furthermore, the act of breastfeeding and its duration have shown an inverse relationship with BC risk. This review delves into the biological and molecular mechanisms associated with breastfeeding that contribute to BC protection. It highlights the role of endocrine processes triggered by suckling stimulation, the gradual onset of lactational amenorrhea, delayed weaning, reduced lifetime menstrual cycles, chromosomal repair mechanisms, and immunological events throughout the lactation cycle. These insights provide a potential explanation for the protective effects conferred by breastfeeding against breast carcinomas.
PubMed: 38884025
DOI: 10.1055/a-2313-0637 -
International Journal of Surgery Case... Jul 2024Ectopic pituitary neuroendocrine tumor (EPNET) is a very rare entity, seldom with apoplexy evolution. Only three cases of intracranial ectropic pituitary neuroendocrine...
INTRODUCTION AND IMPORTANCE
Ectopic pituitary neuroendocrine tumor (EPNET) is a very rare entity, seldom with apoplexy evolution. Only three cases of intracranial ectropic pituitary neuroendocrine tumor apoplexy were reported in the literature.
CASE PRESENTATION
We report the case of a 45-year-old woman with a history of amenorrhea, and headaches. Neuroimaging showed a very aggressive giant mass within the clivus with the invasion of the sphenoidal sinus and encasement of internal carotid arteries with an empty sella. Endocrinology work-up revealed an exceedingly high level of prolactin surprisingly without galactorrhea. Immunohistochemical analysis after an endonasal biopsy confirmed the diagnosis of prolactinoma. One month after Cabergoline initiation, an apoplexy of the ectopic pituitary neuroendocrine tumor occurred. Conservational management with a decrease in cabergoline dose was performed.
DISCUSSION
This article highlights data from various cases reported in the literature in addition to our case to confirm the extreme rarity of apoplexy as a complication of EPNET.
CONCLUSION
Pituitary apoplexy in ectopic pituitary neuroendocrine tumor is extremely rare. Therefore, in case of unusual localization of pituitary neuroendocrine tumor, a thorough follow-up is necessary to detect complications and ensure early management.
PubMed: 38878728
DOI: 10.1016/j.ijscr.2024.109874 -
The Journal of Clinical Endocrinology... Jun 2024Teprotumumab is the only drug approval by The US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED), which targets the insulin-like growth...
PURPOSE
Teprotumumab is the only drug approval by The US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED), which targets the insulin-like growth factor-1 receptor. This study aimed to identify potential safety signals of teprotumumab by analyzing post-marketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023.
METHODS
The case/non-case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered three or more.
RESULTS
Total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), deafness permanent (ROR [95% CI] = 1552.35 [789.07-3053.98]), deafness bilateral (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycaemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]) and amenorrhoea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals of teprotumumab.
CONCLUSIONS
This study identified ear and labyrinth disorders, reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue.
PubMed: 38878281
DOI: 10.1210/clinem/dgae417 -
American Journal of Obstetrics and... Jun 2024While many transgender and gender diverse individuals rapidly achieve amenorrhea on testosterone, emerging data has identified that breakthrough bleeding (BTB) can occur...
BACKGROUND
While many transgender and gender diverse individuals rapidly achieve amenorrhea on testosterone, emerging data has identified that breakthrough bleeding (BTB) can occur in up to one third of individuals with long term use. BTB can worsen dysphoria and patients may seek management to reattain amenorrhea. Because of this, there is a need to assess efficacy of management approaches.
OBJECTIVES
The primary aim of the study was to evaluate methods used by patients and their providers to manage BTB which arises after one year of testosterone use. Secondary aims included describing the diagnostic approaches to BTB, and proposing an algorithm for classification and management of BTB in this patient population.
STUDY DESIGN
This was an IRB-approved single tertiary center, retrospective chart review of transgender and gender diverse individuals on testosterone gender affirming hormone therapy who experienced BTB after one year of use. Charts were reviewed to determine patient characteristics, testosterone use, and BTB management approaches.
RESULTS
Of the 96 individuals who had been on testosterone for one year and experienced BTB, 97% (n=93) engaged in at least one approach to management. The mean age at initiation of testosterone was 21.9 (SD 5.4) and the median duration of time on testosterone was 54.5 months (IQR 33.5,82). Only 16% (n=15) were using menstrual suppression at the time of their BTB episode. BTB was successfully managed in 77 (79%), following between 1-4 attempted approaches. More than half of management attempts (63%) were successful on the first try. When management approaches were analyzed independently, the range of success associated with any particular approach was between 33-100%. Other than hysterectomy, which was fully successful at managing BTB, no approach was significantly better than no intervention. This was true both for individuals who did and did not bleed with missed testosterone doses. Regardless of what approach was used, after a failed attempt, the next attempt was successful in more than half of individuals. Of the 16 who underwent hysterectomy, one did so in part as a first line approach to manage BTB.
CONCLUSION
In this study, use of medical management methods was not found to be superior to observation alone in the management of BTB. In the absence of data supporting superiority of any method, we recommend tailoring method attempts to patients' goals.
PubMed: 38876414
DOI: 10.1016/j.ajog.2024.06.004