Pertti Koskinen

Maternal midtrimester serum AFP and free β-hCG levels in in vitro fertilization twin pregnancies

We aimed to compare the levels of alpha‐fetoprotein (AFP) and free β‐human chorionic gonadotrophin (β‐hCG) levels as multiples of the median (MoM) values between spontaneous and in vitro fertilized (IVF) twin pregnancies. The control group of spontaneous singleton pregnancies was used for calculating the gestational age specific median levels of the values. Within a cohort of 19u2009310 pregnancies, 145 twin pregnancies were identified. The data were collected from Down syndrome (DS) screening programmes in four University catchment areas in Finland between 1994–98. Maternal midtrimester serum marker levels were measured across gestational weeks 14–18. There were no fetal chromosome anomalies in either of the twin groups or the singleton group. Serum AFP of 145 and β‐hCG values of 39 spontaneous twin pregnancies were compared to the values of 6548 singleton pregnancies. In IVF twins 30 AFP and 29 β‐hCG values were compared to the levels of the control group. Both AFP and β‐hCG values were twice as high in the spontaneous twin pregnancies (medians 2.18 and 1.83 MoM respectively) as in the singleton group (medians 1.00 and 1.00 MoM respectively). In IVF twin pregnancies β‐hCG levels were higher (median 2.20 MoM) than in spontaneous twins (p=0.08), whereas no significant difference was found in AFP levels (2.30 MoM). In conclusion, the higher levels of β‐hCG levels in IVF twin pregnancies should be considered in DS screening to avoid high false positive rates. Copyright

Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries *

OBJECTIVEnTo examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women.nnnDESIGNnComparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD).nnnSETTINGnOpen patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland.nnnPATIENTSnSeventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD.nnnMAIN OUTCOME MEASURESnSerum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG.nnnRESULTSnThe levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG.nnnCONCLUSIONSnThe serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

Plasma and urinary C-peptide in the classification of adult diabetics

Plasma and urinary C-peptide determinations in the discrimination between insulin-requiring and non-insulin-requiring diabetes were elevated in 61 adult diabetics. Specimens for C-peptide determinations were taken on two consecutive days: on the first day plasma C-peptide concentrations were determined before and 6 min after intravenous glucagon administration. On the second day 2- and 4-h urinary C-peptide excretion was measured after an individual breakfast. Results of urinary C-peptide analyses were expressed as molar concentration and also as molar quantity excreted (without any corrections and related to creatinine excretion). Glucagon-stimulated plasma C-peptide turned out to be a reliable criterion for the detection of insulin requirement. Sixty-nine per cent of diabetics included in this study were classifiable by basal plasma C-peptide concentrations. Two-hour postprandial urinary C-peptide/creatinine quotient turned out to be slightly less sensitive (89%) than the glucagon test (94%) and of equal specificity (96%). Glucagon-stimulated plasma C-peptide and postprandial urinary C-peptide excretion correlated significantly among insulin-requiring diabetics (r = 0.73), but not among non-insulin-requiring diabetics (r = 0.23). We regard determination of stimulated plasma C-peptide as a primary investigation for the direct assessment of endogenous insulin secretory reserves for clinical management decisions. Determination of postprandial urinary C-peptide is applicable in selected situations for non-invasive assessment of insulin secretion.

Serum total renin is elevated in women with polycystic ovarian syndrome

OBJECTIVEnTo examine the serum total renin in women with polycystic ovarian syndrome (PCOS) and in controls.nnnSETTINGnOutpatient clinic of reproductive endocrinology at Turku University Central Hospital, Turku, Finland.nnnPATIENTSnForty-four oligomenorrheic women with PCOS (body mass index [BMI] 18.0 to 49.0 kg/m2) and 25 control women with regular menstrual cycles (BMI 18.0 to 53.5 kg/m2).nnnMAIN OUTCOME MEASURESnThe concentrations of total renin, LH, FSH, T, androstenedione (A), sex hormone-binding globulin (SHBG), and insulin in serum.nnnRESULTSnThe concentration of total renin in serum was higher in PCOS women than in healthy women independently of BMI, age, or serum insulin. The serum total renin measurement discriminated PCOS patients and control women to a similar extent as the previously used hormonal parameters (LH:FSH, T, A, and T:SHBG) as judged by receiver-operating characteristic analysis. Positive correlations were found between the serum total renin level and LH concentration, LH:FSH ratio, T and A levels, and T:SHBG ratio. Analysis of serum total renin in PCOS patients during oligomenorrhea and after menstruation did not reveal any significant changes.nnnCONCLUSIONSnThe elevated concentration of serum total renin suggests an enhanced activity of ovarian renin-angiotensin system in PCOS. The determination of serum total renin may provide a novel tool in the diagnostics of PCOS, because its serum level is elevated in PCOS women independently of BMI and serum insulin.

Glucagon-Stimulated and Postprandial Plasma C-Peptide Values as Measures of Insulin Secretory Capacity

Basal, postprandial (2 h after breakfast), and glucagonstimulated plasma C-peptide concentrations were determined in a group of 36 adult diabetic patients. Basal and postprandial C-peptide values were measured on consecutive days to estimate the degree of variation of C-peptide secretion. In a subgroup of 15 diabetic patients treated chronically with diet and oral hypoglycemic agents (sulfonylureas or a combination of sulfonylureas and metformin), we studied whether administration of sulfonylureas immediately before breakfast had any effect on postprandial C-peptide values. Absolute differences between two consecutive fasting C-peptide concentrations in insulin-requiring patients were <0.1 nM in all but 1 patient, in whom the difference was 0.18 nM. In subjects treated with oral hypoglycemic agents the median difference was 0.12 nM (range 0-0.38 nM). Absolute differences between two consecutive postprandial C-peptide concentrations were all <0.1 nM in insulin-requiring patients. No significant difference was found between postprandial C-peptide concentrations with or without preceding administration of oral hypoglycemic agents (medians 1.35 and 1.30 nM, respectively). Glucagon-stimulated C-peptide concentrations were somewhat higher than the postprandial values. However, equal discrimination between insulin-requiring and non-insulin-requiring diabetic patients was found by measuring postprandial or glucagon-stimulated C-peptide concentrations.

Hormonal responses to physical exercise in patients with polycystic ovarian syndrome

OBJECTIVEnTo examine the effects of obesity and polycystic ovarian syndrome (PCOS) on the endocrine responses to physical exercise.nnnSETTINGnOutpatient clinic of reproductive endocrinology at the University Central Hospital of Turku and the Department of Pharmacology, University of Turku, Turku, Finland.nnnPATIENTSnNine oligomenorrheic women with PCOS (body mass index [BMI] 19.5 to 46.0 kg/m2) and eight control women with regular menstrual cycles (BMI 20.0 to 53.5 kg/m2).nnnINTERVENTIONSnA bicycle ergometer test was performed at 8 A.M.nnnRESULTSnThe only hormone response that was different between PCOS patients and controls was the exercise-induced increase in circulating GH levels. This response was significantly greater in controls than in PCOS patients. There was also a negative correlation between the GH response and BMI. The increases in the concentrations of adrenaline, noradrenaline, 3,4-dihydroxyphenylglycol, glucose, and insulin:C-peptide ratios during the bicycle ergometer test were correlated negatively to BMI.nnnCONCLUSIONnObesity is an important determinant of the hormonal responses to physical exercise. This applies also to women with PCOS. Taking obesity into account in the analysis of exercise-induced hormone responses, only little, if any, of the variation in the hormonal responses measured by us could be attributed to PCOS per se. The only hormone response that was different between PCOS patients and controls was the GH response.

Serum fructosamine in the assessment of glycaemic control in diabetes mellitus.

Serum fructosamine determination was evaluated in the assessment of glycaemic control in diabetes mellitus. Intra- and inter-assay variation of the method was 0.5-0.8 and 1.5-2.9%, respectively. The fructosamine concentration in serum was found to be stable for at least 10 days independent of prevailing serum glucose concentration is stored at +4 degrees C or colder. Stability of serum fructosamine with respect to rapid fluctuations of blood glucose was of the same order as that of HbA1c. The reference interval (mean +/- 2 SD) for 92 non-diabetic individuals was 1.9-2.7 mmol/l. Good correlation was found between HbA1c and serum fructosamine (r = 0.79). Serum fructosamine and HbA1c correlated well with the mean blood glucose values of the preceding week (r = 0.88 and 0.75, respectively, p less than 0.001). Significant correlations of fructosamine and HbA1c with fasting blood glucose were also found (r = 0.53 and 0.55, respectively, p less than 0.001). Fructosamine determined simultaneously with fasting blood glucose in 65 oral glucose tolerance tests (OGTT) did not separate normal subjects from those with impaired glucose tolerance. Two of the three subjects with diabetic response in the OGTT had, however, elevated fructosamine concentrations. Determination of serum fructosamine is a technically simple, reproducible and moderately inexpensive method for the assessment of glycaemic control in diabetes mellitus. Standardization of the method is, however, not without problems. Uniformity of the calibration and assay protocol is essential for reliable interlaboratory comparison of results. Physiological states altering the rate of synthesis or elimination of serum proteins should be considered in the interpretation of fructosamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

A method for measurement of free testosterone in premenopausal women involving equilibrium dialysis, chromatography, and radioimmunoassay

A three-step procedure to evaluate the quantity of true free testosterone in female serum was established. Unbound and bound testosterone were first separated by equilibrium dialysis using undiluted serum. Testosterone in dialysate was extracted and separated from cross-reactive steroids by column chromatography and finally quantified with a sensitive radioimmunoassay. The detection limit of the radioimmunoassay was 2.7 pmol/L and the detection limit of the whole method was 6 pmol/L. The intra-assay coefficients of variation of the method were 20.6%, 16.8%, and 9.5% for free testosterone concentrations 12.0 pmol/L, 21.4 pmol/L, and 31.4 pmol/L, respectively. The interassay coefficients of variation were 26.3% and 14.8% for free testosterone concentrations 10.4 pmol/L and 21.3 pmol/L, respectively. Serum free testosterone concentrations were determined in 27 regularly menstruating control women. The mean concentration of actual free testosterone was 10.0 +/- 4.9 pmol/L (mean +/- SD, range from below 6 to 19 pmol/L, n = 27).

Serum testosterone, androstenedione and luteinizing hormone levels after short‐term medroxyprogesterone acetate treatment in women with polycystic ovarian disease

Background. Medroxyprogesterone acetate (MPA) ‐treatment suppresses serum gonadotropin and androgen concentrations in women with polycystic ovarian disease (PCOD). This study ws designed to determine serum testosterone (T), androstenedione (A) and luteinizing hormone (LH) patterns in a group of oligomenorrheic PCOD patients after MPA‐treatment.

Blood glycated haemoglobin, serum fructosamine, serum glycated albumin and serum glycated total protein as measures of glycaemia in diabetes mellitus

Blood glycated haemoglobin (HbAlc), serum fructosamine (FA), serum glycated albumin (GA), and serum glycated total protein (GTP) were determined in 61 subjects (19 pregnant women with gestational diabetes, 24 pregnant women with insulin-dependent diabetes mellitus [IDDM] and 18 nonpregnant subjects with IDDM). FA, GA, and GTP correlated with HbAlc similarly (r = 0.791, 0.816, and 0.794, respectively, p < 0.001). In a subgroup of 22 subjects data on blood glucose home monitoring was recorded and used for calculating mean blood glucose as an index of average glycaemia preceding sampling of the glycation products. Mean blood glucose levels preceding sampling of HbAlc by 2 months and FA, GA, or GTP by three weeks correlated significantly with HbAlc (r = 0.668, p < 0.001) and GA (r = 0.441, p < 0.05) whereas no significant correlation was found between mean blood glucose and FA (r = 0.003) or GTP (r = 0.252). In conclusion, such methods which measure specifically the non-enzymatic glycation of a single species of protein (i.e. FPLC for HbAlc and affinity chromatography for GA) are to be preferred for assessing glycaemia.