Endocrine Function of Granulosa Cell Tumors in vivo

Abstract

Two patients with granulosa cell tumors of the ovary, endometrial hyperplasia, elevated serum estradiol (E₂) concentrations and depressed FSH levels were studied preoperatively using intravenous administration of FSH, LH and gonadotropin-releasing hormone. In patient 1 serum E₂ increased from a baseline of 72.7 to 116.8 pg/ml 60 min after hCG stimulation, with a peak level of 571.4 pg/ml 96 h after hCG administration; there was a rapid postoperative decline to 16 pg/ml. Ovarian venous E₂ on the tumor side was 6,979 pg/ml. In patient 2, E₂ increased from a baseline of 91 to 449 pg/ml at 20 h after FSH administration. Intraoperative ovarian venous E₂ was 9,788 pg/ml. Inhibin, which was elevated in patient 1 prior to stimulation (736 fmol/ml), peaked 96 h after hCG administration. Ovarian venous inhibin concentration in patient 1 was 2,911 fmol/ml. The baseline inhibin concentration in patient 2 was not elevated (249 fmol/ml), but there was an elevation of inhibin in response to FSH administration (757 fmol/ml), but no response to hCG. Ovarian inhibin concentration was not different between the tumor and contralateral sides in patient 2. Both granulosa cell tumors were responsive to exogenous gonadotropin stimulation. Although only one tumor made significant baseline levels of inhibin, the production of inhibin by both tumors was apparently stimulated by FSH.

Serum biomarkers of tubal ectopic pregnancy: current candidates and future possibilities

“…A preliminary study in 205 women confirmed that all of the ectopic pregnancies (nZ100) had an E 2 level !650 pg/ml and all but one of the intrauterine pregnancies had a value O650 pg/ml (Guillaume et al 1990) giving a sensitivity of 100% and specificity of 99%. However, again there was no difference in serum E 2 when women with tubal ectopic pregnancy were compared with those with nonviable intrauterine pregnancies (Witt et al 1990). There are differences in serial serum E 2 concentrations in tubal ectopic pregnancy when compared with viable intrauterine pregnancies measured up to 11 weeks of gestation (Mantzavinos et al 1991).…”

“…Guillaume et al (1990) investigated a larger population of 205 women with tubal ectopic pregnancy (nZ100), viable intrauterine pregnancy (nZ69) and threatened abortion (nZ36) and found that all but one of the women with a tubal ectopic pregnancy had serum P levels !23 ng/ml and this had a sensitivity of 99% and a specificity of 100%. However, serum progesterone levels are significantly lower in both tubal ectopic pregnancies (nZ32; P!0.001) and spontaneous abortions (P!0.001) than viable intrauterine pregnancies (Witt et al 1990). Crucially, there was no significant difference in serum progesterone concentrations in women with an ectopic pregnancy when compared with those who had a spontaneous abortion and this reduced the predictive value of progesterone.…”

“…Early studies showed that the concentration of PAPPA was lower in patients with a tubal ectopic pregnancy when compared with normal intrauterine pregnancy (Bischof et al 1983, Sinosich et al 1985. Indeed, the serum concentration of PAPPA of ectopic pregnancy was sometimes within the Seppala & Purhonen (1987), Riss et al (1989), Garcia et al (1990), Guillaume et al (1990), Witt et al (1990), Mantzavinos et al (1991), Grosskinsky et al (1993), Kuscu et al (1993), Cacciatore et al (1994), Daily et al (1994), Korhonen et al (1996), O'Leary et al (1996), Mol et al (1997), Marill et al (1999) Kirk et al (2008) Serum biomarkers of tubal ectopic pregnancy non-pregnant range (Bischof et al 1983). A subsequent larger study found that PAPPA was undetectable in 84.8% of samples from women (nZ102) with tubal ectopic pregnancy, but it was also undetectable in 55% of intrauterine spontaneous abortions (Sjoberg 1987).…”

“…However, in some cases, serum SP-1 was within the normal range (nZ10) and the pregnancy still had an abnormal outcome. Serum SP-1 concentrations do tend to be lower in tubal ectopic pregnancy (Tornehave et al 1987), but again larger studies have confirmed that there is poor discrimination between tubal ectopic pregnancy (nZ32) and spontaneous abortion (nZ42; Witt et al 1990). In tubal ectopic pregnancy, serial SP-1 measurements reached a plateau, while in ongoing pregnancy they continue to increase (Mantzavinos et al 1991, Mueller et al 2004) and the differences were most marked after 7 weeks of gestation.…”

“…Florio et al (2007) examined the blood samples of 486 women (viable intrauterine pregnancy (nZ155), first-trimester spontaneous miscarriage (nZ305), tubal ectopic pregnancy (nZ76)) and found that activin A levels in women with tubal ectopic pregnancy were markedly lower than those with intrauterine pregnancy and spontaneous miscarriage (P!0.0001). More importantly, it performed better Yeko et al (1987), Buck et al (1988), Riss et al (1989), Guillaume et al (1990), Witt et al (1990) (1998) and Segal et al (2008) than a single measurement of hCG in discriminating between the different groups (Florio et al 2007). When using activin A as a single marker, the authors calculated that for their study population (tubal ectopic pregnancy prevalence 14.18%), a tubal ectopic pregnancy could be identified with a sensitivity of 100% and specificity of 99.6% if the cut-off was !0.37 ng/ml.…”