A 33-year-old woman, gravida 2 para 2, comes to the office for evaluation of abnormal uterine bleeding. Ten months ago, the patient had a spontaneous vaginal delivery complicated by a postpartum hemorrhage that required a blood transfusion and emergent suction curettage. Since the delivery, the patient has had increasingly irregular menses and has been amenorrheic for the past 3 months. She is bottle-feeding her infant and is not taking contraceptives. The patient has lost 13.6 kg (30 lb) since the delivery and is now below her prepregnancy weight. BMI is 22 kg/m². Blood pressure is 110/60 mm Hg and pulse is 62/min. Visual fields are intact. The thyroid has no palpable masses. Cardiopulmonary examination is unremarkable. Pelvic examination shows a minimally rugated vagina; the uterus and cervix are small and nontender to palpation. Urine pregnancy test is negative. Serum TSH and prolactin levels are normal; FSH is elevated. Pelvic ultrasound shows a uterus with a thin endometrium and no adnexal masses. Which of the following is the most likely cause of this patient's presentation?

Question

Quizplus · Accepted Answer

11ec25c8_d9a2_44e9_bc81_0156db90a19d_MD0003_00 This patient's secondary amenorrhea (ie, lack of menses for ≥3 months in those with previously regular cycles), signs of estrogen deficiency (eg, minimally rugated vagina), and elevated FSH are consistent with diminished ovarian function. In women age <40, this hypergonadotropic hypogonadism is likely due to primary ovarian insufficiency (POI). POI is associated with a variety of causes, such as Turner syndrome (45,XO) or a fragile X syndrome premutation; however, most cases have an unknown etiology. POI primarily affects the ovarian primordial follicles, which are composed of oocytes and granulosa cells (which convert testosterone to estrogen). Therefore, accelerated ovarian primordial follicle depletion results in a lack of oocytes, which causes anovulation (ie, infertility, amenorrhea). The decrease in granulosa cells results in estrogen deficiency (eg, thin endometrium, vaginal atrophy) and lack of feedback inhibition to the hypothalamus and pituitary (ie, elevated FSH level). Patients diagnosed with POI undergo further evaluation with autoimmune evaluation, karyotype analysis, and bone mineral density testing. Treatment includes estrogen-containing therapy for cardiovascular and bone loss protection. (Choice B) Polycystic ovary syndrome (PCOS) causes abnormal uterine bleeding due to chronic anovulation; patients with PCOS are typically overweight, have a low/normal FSH level, and enlarged ovaries with multiple peripheral follicles on ultrasound-not seen in this patient. (Choice C) Functional hypothalamic amenorrhea can present in women with significant weight loss due to decreased hypothalamic GnRH secretion. However, this would result in low (rather than high) FSH levels. (Choice D) Endometrial cavity adhesions and fibrosis (Asherman syndrome) can form after an intrauterine procedure (eg, suction curettage) and cause secondary amenorrhea and a thin endometrium. However, these patients have normal estrogen and FSH levels, making this diagnosis unlikely. (Choice E) Infarction of the pituitary gland (ie, Sheehan syndrome) can occur after a postpartum hemorrhage that results in hypovolemic shock. Women typically present with an inability to breastfeed (low prolactin); however, amenorrhea is due to low FSH levels (ie, hypogonadotropic hypogonadism). Educational objective: Primary ovarian insufficiency (POI) is diagnosed in women age <40 with secondary amenorrhea and signs of ovarian failure (ie, elevated FSH). POI occurs due to accelerated ovarian primordial follicle depletion, resulting in estrogen deficiency (eg, vaginal atrophy, thin endometrium). References: Primary ovarian insufficiency. (http://www.ncbi.nlm.nih.gov/pubmed/20708256) An update on primary ovarian insufficiency. (http://www.ncbi.nlm.nih.gov/pubmed/22932883) Autoimmune primary ovarian insufficiency. (http://www.ncbi.nlm.nih.gov/pubmed/24418305)

A 33-Year-Old Woman, Gravida 2 Para 2, Comes to the Office