Urinary prolactin as a reliable marker for preeclampsia, its severity, and the occurrence of adverse pregnancy outcomes.

CONTEXT: It has been proposed that preeclampsia may result from of an imbalance in angiogenic factors. Although prolactin (PRL) is mainly related to lactation, it is also involved in other biological functions, including angiogenesis. OBJECTIVE: Our objective was to determine the relationship among preeclampsia, serum and urinary PRL (uPRL) levels, and excretion of antiangiogenic PRL fragments in urine. STUDY DESIGN: Using a cross-sectional design, uPRL and serum PRL levels, and the presence of PRL isoforms were determined in 546 pregnant women: 207 healthy pregnant, 124 with gestational hypertension, 48 with mild preeclampsia, and 167 with severe preeclampsia (sPE). RESULTS: uPRL concentrations were significantly (P < 0.001) higher in preeclampsia (11.99 ng/mg creatinine) than in healthy pregnancy (0.20 ng/mg creatinine) and gestational hypertension (0.19 ng/mg creatinine), and were even higher in sPE compared with mild preeclampsia (21.20 vs. 2.77 ng/mg creatinine, respectively; P < 0.001). Antiangiogenic PRL fragments (14-16 kDa) were detected in 21.6% of urine samples from women with sPE but in none from other groups. Patients with hemolysis, elevated liver enzymes, low platelet count syndrome, and/or eclampsia, placental abruption, acute renal failure, and pulmonary edema exhibited highest uPRL concentrations (P < or = 0.028) and frequency of antiangiogenic PRL fragments in urine (P < or = 0.036). High-serum PRL levels were associated with sPE independently of gestational age, proteinuria, and prolactinuria (P = 0.032). CONCLUSIONS: Preeclampsia is characterized by increased uPRL excretion. uPRL concentrations and their isoforms appear to be suitable markers to assess the severity of preeclampsia and occurrence of adverse outcomes. PRL and and/or its isoforms might be involved in the pathophysiology of preeclampsia.

Elevated serum bioactive prolactin concentrations in patients with systemic lupus erythematosus are associated with disease activity as disclosed by homologous receptor bioassays.

OBJECTIVE: To assess the bioactivity of circulating prolactin (PRL) in serum samples from patients with systemic lupus erythematosus (SLE) using 2 novel homologous in vitro bioassays, and to correlate PRL bioactivity with lupus activity. METHODS: Serum samples from 98 SLE patients with and without disease activity were tested for immunoreactive and bioactive concentrations of PRL. RESULTS: Patients with active disease exhibited higher bioactive serum PRL levels in homologous bioassays (p

Protein:creatinine ratio in random urine samples is a reliable marker of increased 24-hour protein excretion in hospitalized women with hypertensive disorders of pregnancy.

BACKGROUND: The protein:creatinine ratio in random, untimed urine samples correlates with 24-h protein excretion in pregnant women with and without hypertension. Nevertheless, whether this ratio is appropriate as a screening test for proteinuria is still unclear, in part because of the paucity of large studies. METHODS: We measured protein:creatinine ratios in random urine samples and protein contents of 24-h urine samples in a cross-sectional study of 927 hospitalized pregnant women at >/=20-weeks of gestational age and in a 2nd cohort of 161 pregnant women. In the 2nd group, urine specimens were obtained before and after completion of the 24-h collections, avoiding 1st-morning void specimens. RESULTS: Protein excretion was >/=300 mg/24 h in 282 patients (30.4%). The urine protein:creatinine ratio and the 24-h protein excretion were significantly correlated (r = 0.98, P <0.001). The protein:creatinine ratio as an indicator of protein excretion >/=300 mg/24 h was >/=0.3. The sensitivity and specificity were 98.2% and 98.8%, respectively. Positive and negative predictive values were 97.2% and 99.2%, respectively, and positive and negative likelihood ratios were 79.2 and 0.02, respectively. The diagnostic accuracy of the urinary protein:creatinine ratio was corroborated in the 2nd cohort of patients, which also showed no statistically significant difference in protein:creatinine ratio between samples obtained >24 h apart. CONCLUSIONS: Random urinary protein:creatinine ratio is a reliable indicator of significant proteinuria (>300 mg/day) in nonambulatory pregnant women, irrespective of sampling time during the daytime. The protein:creatinine ratio may be reasonably used as an alternative to the 24-h urine collection method.

Application of new homologous in vitro bioassays for human lactogens to assess the actual bioactivity of human prolactin isoforms in hyperprolactinaemic patients.

BACKGROUND: Prolactin (PRL) plays a central role in mammary gland development and lactation. Due to its molecular heterogeneity, measurement of PRL immunoreactivity does not necessarily reflect its intrinsic bioactivity. For many years the Nb2 rat lymphoma cell bioassay has been the only reference bioassay for human lactogens. This bioassay, however, does not always correlate with the clinical features found in some patients exhibiting normal or elevated immunoreactive serum PRL concentrations. OBJECTIVES: (1) To determine the concentrations of bioactive PRL in serum samples from individuals with normoprolactinaemia or with different forms of hyperprolactinaemia using two recently described homologous in vitro bioassays (i.e. a transcriptional bioassay in HEK-293 cells and a proliferation assay in Ba/F3 cells); and (2) to compare these results with those generated by the classical Nb2 cell bioassay. DESIGN: Cross-sectional study. SETTING: An institutional biomedical research laboratory. PARTICIPANTS: Ten patients with symptomatic hyperprolactinaemia due to prolactinoma, 11 patients with asymptomatic hyperprolactinaemia and macroprolactinaemia, and nine normal women. MAIN OUTCOME MEASURES: Measurement of immunoreactive and bioactive concentrations of serum PRL. RESULTS: Samples from normal women and patients with tumoral hyperprolactinaemia due to prolactinoma exhibited similar within-group concentration values of bioactive and immunoreactive serum PRL when tested by the three bioassays and the immunoradiometric assay employed. By contrast, measurement of bioactive PRL in samples from patients with macroprolactinaemia revealed that macroprolactin was poorly active in the homologous receptor bioassays, while it was more active in the Nb2 bioassay. CONCLUSIONS: The reduced bioactivity of PRL in patients with macroprolactinaemia may further explain the absence of clinical features of hyperprolactinaemia in these individuals. In addition, our findings indicate that species-specificity and sensitivity of the bioassays are determinant factors in the measurement of the intrinsic biological activity of circulating PRL.