Exacerbation of ovarian hyperstimulation by leuprolide reveals a gonadotroph adenoma

OBJECTIVE: To report a case of a gonadotroph adenoma diagnosed after a dramatic increase in estradiol level and ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist. DESIGN: Case report. SETTING: Outpatient practice and university hospital. PATIENT(S): A 35-year-old woman who presented with infertility, amenorrhea, and an elevated basal estradiol concentration. INTERVENTION(S): Ultrasonography, laparoscopy, endocrinologic assays, magnetic resonance imaging, transsphenoidal surgery, and immunocytochemical staining. MAIN OUTCOME MEASURE(S): Ultrasonography and laparoscopy demonstrated bilaterally enlarged ovaries containing multiple preovulatory follicles, similar in appearance in those women undergoing controlled ovarian hyperstimulation with exogenous FSH. The serum estradiol level was moderately elevated, the FSH level was within the normal range, and LH was suppressed. Administration of leuprolide acetate resulted in very elevated estradiol concentrations and even larger ovarian cysts. Magnetic resonance imaging demonstrated a sellar mass. Examination of the tissue excised by transsphenoidal excision of the mass showed a pituitary adenoma that stained strongly for FSH. RESULT(S): Regular menses resumed soon after excision of the gonadotroph adenoma, followed by a spontaneous pregnancy. CONCLUSIONS: Gonadotroph adenoma should be suspected in a reproductive age woman with oligomenorrhea or amenorrhea, infertility, multiple preovulatory follicles, and a persistently elevated serum estradiol concentration. Exacerbation of the ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist in this setting also strongly suggests a gonadotroph adenoma but can be avoided by recognizing the presenting features of this condition.     

Use of integrins to date the endometrium

OBJECTIVE: To compare traditional histologic dating criteria of the endometrium with immunohistochemical criteria based on epithelial integrin expression during the menstrual cycle. DESIGN: Prospective clinical study. SETTING: An academic teaching hospital. PATIENT(s): Fertile and infertile women undergoing endometrial biopsy. MAIN OUTCOME MEASURE(s): Immunohistochemical staining intensity and distribution (HSCORE) of three integrins and traditional histologic endometrial dating. RESULT(s): In 1,501 endometrial specimens, phase assignment-based integrin staining was 95% and 85% concordant with histology for the proliferative and early secretory phase, respectively, but only 54% and 49% concordant for the middle and late secretory phase, respectively. The greatest disagreement occurred during the midluteal phase. Of 1,090 patients who underwent sampling 6-10 days after detection of a urinary LH surge (corresponding to cycle days 20-24), multiple logistic regression analysis revealed that endometriosis was positively correlated and male factor infertility was negatively correlated with absent beta3 integrin subunit expression. Diagnosis and absent epithelial alpha4beta1 expression were not related. Patient age was not correlated with the incidence of abnormalities in integrin expression. CONCLUSION(s): Traditional histologic dating of the endometrium has remained the gold standard for nearly 50 years. Although the use of marker proteins provides additional information and may reflect endometrial function or receptivity, such markers cannot yet replace traditional methods of endometrial assessment.     

Integrins and Implantation in the Human

Reviews in Endocrine and Metabolic Disorders -     

Distribution of integrin cell adhesion molecules in endometrial cancer.

Integrins are ubiquitous cell adhesion molecules that are involved in maintaining normal tissue morphology and have been implicated in the behavior of certain malignancies. We examined the expression of nine integrin subunits in 38 endometrial adenocarcinomas using immunohistochemistry. The pattern of integrin expression in the cancers was compared with that seen in the endometrium of 20 normal cycling women and 7 postmenopausal women. Integrin expression was correlated with grade, stage, nodal status, depth of invasion, steroid receptor status, and histological pattern. In endometrial cancers there was an inverse relationship between the number of integrins expressed and histological grade (P = 0.011). Of the normally expressed, constitutive endometrial epithelial integrin subunits (alpha 2, alpha 3, alpha 6, and beta 4), the least frequently seen in the cancers was the alpha 3 subunit (44.7%) and the most frequently found was alpha 6 (81.6%). The alpha 5 beta 1 integrin, a fibronectin receptor normally found only on endometrial stromal cells, was seen in 17.8% of cases of these epithelial cancers. In addition, a significant association was found between the loss of the alpha 2 beta 1 integrin and the presence of lymph node metastases (P < 0.001). These data suggest that a decline in integrin expression occurs more frequently in poorly differentiated endometrial cancers and that the loss of specific integrins may be associated with metastatic nodal spread.