Mayer-Rokitansky-Kuster-Hauser Syndrome Presented with Diabetes Mellitus and Primary Amenorrhea: A Case Report.

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare congenital disorder that affects the female reproductive system and is characterized by an underdeveloped or absent uterus and vagina. A 17-year-old unmarried female was admitted into the Department of Endocrinology, Mymensingh Medical College Hospital, Bangladesh in November 2023 for evaluation of primary amenorrhea and poorly controlled diabetes mellitus. She was the 5th issue of non-consanguineous marriage delivered at term by normal vaginal delivery. Her growth pattern and developmental milestones were normal. She had no history of galactorrhea, chronic or cyclic pelvic pain, thyroid dysfunction, excessive exercise, psychiatric illness, or drug abuse. There was no history of such type of illness in her family. She was diagnosed with diabetes mellitus two years back without classic symptoms, and at that time, her blood glucose was 22 mmol/L. She was prescribed metformin and gliclazide. She had no history of hypoglycemia, hyperglycemic crises, or hospital admission. On examination, her body build and nutritional status were normal. Anemia, jaundice, edema, dehydration, lymphadenopathy, acne, hirsutism, acanthosis nigricans, abdominal striae and vitiligo were absent. Her blood pressure was 110/70 without the postural drop, thyroid gland was not enlarged, anthropometric measurements were normal and BMI was 18.4 kg/m2. Her tanner stage was P5 & B4. Genital examination revealed normal female external genitalia, and a blind vaginal pouch was found. Other systemic examinations revealed no abnormality. On laboratory reports, her blood glucose was uncontrolled (HbA1c-10.2%) with glycosuria. Thyroid function test and gonadal hormones were normal. Ultrasonogram of the abdomen revealed uterus, cervix, and upper part of the vagina are absent, and an ectopic left kidney.

Diagnosis and management of non-CAH 46,XX disorders/differences in sex development.

Prenatal-onset androgen excess leads to abnormal sexual development in 46,XX individuals. This androgen excess can be caused endogenously by the adrenals or gonads or by exposure to exogenous androgens. The most common cause of 46,XX disorders/differences in sex development (DSD) is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, comprising >90% of 46,XX DSD cases. Deficiencies of 11ß-hydroxylase, 3ß-hydroxysteroid dehydrogenase, and P450-oxidoreductase (POR) are rare types of CAH, resulting in 46,XX DSD. In all CAH forms, patients have normal ovarian development. The molecular genetic causes of 46,XX DSD, besides CAH, are uncommon. These etiologies include primary glucocorticoid resistance (PGCR) and aromatase deficiency with normal ovarian development. Additionally, 46,XX gonads can differentiate into testes, causing 46,XX testicular (T) DSD or a coexistence of ovarian and testicular tissue, defined as 46,XX ovotesticular (OT)-DSD. PGCR is caused by inactivating variants in NR3C1, resulting in glucocorticoid insensitivity and the signs of mineralocorticoid and androgen excess. Pathogenic variants in the CYP19A1 gene lead to aromatase deficiency, causing androgen excess. Many genes are involved in the mechanisms of gonadal development, and genes associated with 46,XX T/OT-DSD include translocations of the SRY; copy number variants in NR2F2, NR0B1, SOX3, SOX9, SOX10, and FGF9, and sequence variants in NR5A1, NR2F2, RSPO1, SOX9, WNT2B, WNT4, and WT1. Progress in cytogenetic and molecular genetic techniques has significantly improved our understanding of the etiology of non-CAH 46,XX DSD. Nonetheless, uncertainties about gonadal function and gender outcomes may make the management of these conditions challenging. This review explores the intricate landscape of diagnosing and managing these conditions, shedding light on the unique aspects that distinguish them from other types of DSD.

A rare variant of mullerian agenesis: a case report and review of the literature.

INTRODUCTION: Menstruation is a developmental milestone and usually marks healthy and normal pubertal changes in females. Menarche refers to the onset of first menstruation in a female. The causes of primary amenorrhea include outflow tract abnormalities, resistant endometrium, primary ovarian insufficiency, and disorders of the hypothalamus, pituitary, or other endocrine glands. A rare variant of mullerian agenesis, which warrants an individualized approach to management, is presented here. CASE REPORT: We present here the case of a 25-year-old Indian female with pain in the lower abdomen and primary amenorrhea. After a thorough history, clinical examination, imaging, and diagnostic laparoscopy, two small uteri, a blind upper half vagina, bilateral polycystic ovaries, and a blind transverse connection between the two uteri-a horseshoe band cervix-were detected, which confirmed the diagnosis of mullerian agenesis. There was evidence of adenomyosis in the mullerian duct element. This is a rare form of Müllerian abnormality with an unusual presentation. CONCLUSION: Mullerian agenesis is the most common cause of primary amenorrhea with well-developed secondary sexual characteristics. There are various forms of mullerian agenesis. Most of the cases are managed by a multidisciplinary team. Rare variants warrant an individualized approach to management.

Understanding the Diagnostic Odyssey of Women with Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome in Denmark: A Qualitative Interview Study.

STUDY OBJECTIVE: The diagnosis of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is often a lengthy process that typically occurs during late adolescence. To support optimized and patient-centered care, this study aimed to investigate how women with MRKH syndrome experience the diagnostic process. METHODS: From January 2021 to March 2021, we conducted in-depth interviews with 18 Danish women (≥25 years) diagnosed with MRKH syndrome. The interviews lasted a median of 92 minutes (range: 67-117). Data were analyzed using thematic analysis. RESULTS: As teenagers or young women at the time, all women had experienced the diagnostic process in the nonspecialized healthcare sector as deeply upsetting due to distressing gynecological examinations, use of inappropriate language, and considerable diagnostic delay. When reaching the specialized health care sector, questions could finally be answered, but this information and support did not significantly alter their feelings of being "deviant" or "flawed". The women continued their diagnostic odyssey beyond the health care system and found online communities that gave them valuable support in living with MRKH syndrome. CONCLUSION: Women experience the diagnostic odyssey of MRKH syndrome as upsetting and potentially traumatizing beyond the diagnosis. Healthcare professionals can influence young women's understanding and experience of MRKH syndrome by using inclusive language (eg, avoiding "deformity") and addressing all that is normal and functioning (eg, external genitalia and potential for sexual pleasure). In nonurgent conditions, young women should be given the choice to delay a genital examination.