https://www.labmed.theclinics.com/article/S0272-2712(04)00005-8/pdf

Steroid hormones: relevance and measurement in the clinical laboratory.

Steroid profiles using liquid chromatography-tandem mass spectrometry with atmospheric pressure photoionization source.

Pediatric reference intervals for aldosterone, 17α-hydroxyprogesterone, dehydroepiandrosterone, testosterone and 25-hydroxy vitamin D3 using tandem mass spectrometry

Endogenous digitalis-like factor(s), originally proposed as a vasoconstrictor natriuretic hormone, was discovered in fetal and neonatal blood accidentally because it cross-reacts with antidigoxin antibodies (ADAs). Early studies using immunoassays with ADA identified the digoxin-like immuno-reactive factor(s) (EDLF) in maternal blood as well, and suggested it originated in the feto-placental unit. Mammalian digoxin-like factors have recently been identified as at least two classes of steroid compounds, plant derived ouabain (O), and several toad derived bufodienolides, most prominent being marinobufagenin (MBG). A synthetic pathway for MBG has been identified in mammalian placental tissue. Elevated maternal and fetal EDLF, O and MBG have been demonstrated in preeclampsia (PE), and inhibition of red cell membrane sodium, potassium ATPase (Na, K ATPase (NKA)) by EDLF is reversed by ADA fragments (ADA-FAB). Accordingly, maternal administration of a commercial ADA-antibody fragment (FAB) was tested in several anecdotal cases of PE, and two, small randomized, prospective, double-blind clinical trials. In the first randomized trial, ADA-FAB was administered post-partum, in the second antepartum. In the post-partum trial, ADA-FAB reduced use of antihypertensive drugs. In the second trial, there was no effect of ADA-FAB on blood pressure, but the fall in maternal creatinine clearance (CrCl) was prevented. In a secondary analysis using the pre-treatment maternal level of circulating Na, K ATPase (NKA) inhibitory activity (NKAI), ADA-FAB reduced the incidence of pulmonary edema and, unexpectedly, that of severe neonatal intraventricular hemorrhage (IVH). The fall in CrCl in patients given placebo was proportional to the circulating level of NKAI. The implications of these findings on the pathophysiology of the clinical manifestations PE are discussed, and a new model of the respective roles of placenta derived anti-angiogenic (AAG) factors (AAGFs) and EDLF is proposed.

Role of endogenous digitalis-like factors in the clinical manifestations of severe preeclampsia: a sytematic review.

In blacks and whites of similar socioeconomic background, the incidence of pregnancy-induced hypertension (PIH) is probably the same. In underdeveloped coutries, however, PIH is often a life-threatening complication of pregnancy. Recent theories as to the etiology of PIH include the suggestion that vascular tone may be increased as a result of inhibition of active sodium transport in vascular smooth muscle. This may be the result of an inhibitor of sodium transport present in the serum. The literature concerning the demonstration of endogenous sodium transport inhibitors and endogenous digoxinlike immunoreactivity (EDLI) in PIH is reviewed and discussed.

Sodium transport inhibitors in pregnancy-induced hypertension.

We assessed the existence of endogenous digoxin-like substance(s) (EDLS) in mother-neonate pairs using a routine radioimmunoassay for digoxin. None of those studied had been treated with cardiac glycosides during or before pregnancy. In uneventful pregnancies, cord EDLS levels (0.31 +/- 0.02 ng/ml mean +/- SEM) were significantly higher (p less than 0.001) than both antepartum and postpartum maternal levels (0.14 +/- 0.02 and 0.17 +/- 0.02 mg/ml, respectively). This observation was in contrast with findings in high-risk pregnancies. In general, EDLS levels in the high-risk group were significantly higher than in normal pregnancies (cord 0.94 +/- 0.38 ng/ml; antepartum 1.63 +/- 0.54 ng/ml; postpartum 0.89 +/- 0.73 ng/ml). In the high-risk group there was a remarkably wide range of maternal and cord EDLS concentrations. The present studies suggest that following pregnancies of high risk for a variety of reasons, EDLS determination may be commonly high in the perinatal period and may affect the determination of 'true' digoxin. Consequently, digoxin dosing based on monitoring drug concentration may be futile.

Grundmann H

Papers

Endogenous digoxin-like substance(s) associated with uneventful and high-risk pregnancies.