Ivana Zec

Macroprolactinemia: new insights in hyperprolactinemia

Hypersecretion of prolactin by lactotroph cells of the anterior pituitary may lead to hyperprolactinemia in physiological, pathological and idiopathic conditions. Most patients with idiopathic hyperprolactinemia may have radiologically undetected microprolactinomas, but some may present other causes of hyperprolactinemia described as macroprolactinemia. This condition corresponds to the predominance of higher molecular mass prolactin forms (big-big prolactin, MW > 150 kDa), that have been postulated to represent prolactin monomer complexed with anti-prolactin immunoglobulins or autoantibodies. The prevalence of macroprolactinemia in hyperprolactinemic populations between 15–46% has been reported. In the pathophysiology of macroprolactinemia it seems that pituitary prolactin has antigenicity, leading to the production of anti-prolactin autoantibodies, and these antibodies reduce prolactin bioactivity and delay prolactin clearance. Antibody-bound prolactin is big enough to be confined to vascular spaces, and therefore macroprolactinemia develops due to the delayed clearance of prolactin rather than increased production. Although the clinical symptoms are less frequent in macroprolactinemic patients, they could not be diff erentiated from true hyperprolactinemic patients, on the basis of clinical features alone. Although gel filtration chromatography (GFC) is known to be the gold standard for detecting macroprolactin, the polyethylene glycol precipitation (PEG) method has off ered a simple, cheap, and highly suitable alternative. In conclusion, macroprolactinemia can be considered a benign condition with low incidence of clinical symptoms and therefore hormonal and imaging investigations as well as medical or surgical treatment and prolonged follow-up are not necessary.

Anti-Müllerian hormone: A unique biochemical marker of gonadal development and fertility in humans

Anti-Müllerian hormone (AMH) is a glycoprotein belonging to the transforming growth factors (TGF-P). AMH plays a fundamental role in the regression of Müllerian ducts in male embryo. In its absence, Müllerian ducts develop into female inner reproductive organs. In boys, it is significantly produced in Sertoli cells of testes until puberty and then slowly decreases to residual values for the rest of the mens life. AMH serves as a biochemical marker of the presence of testes in cryptorchidic males. In females, AMH is secreted by granulosa cells of small follicles in the ovary. Serum values are almost undetectable during infancy and then rapidly increase with the onset of puberty, reflecting the initial recruitment of primordial follicles. AMH is produced in growing follicles until they reach a stage when dominant follicle is detached from a cohort of antral follicles. The measurement of serum AMH levels during womans reproductive life represents an ideal tool for the assessment of the ovarian follicular reserve. The advantage of AMH in relation to the ovarian steroid hormones is that serum levels do not fluctuate significantly during the menstrual cycle. In addition, circulating AMH strongly correlates with antral follicle count (AFC), visualized by ultrasound in the follicular phase of the cycle. As the number and quality of the oocytes diminish throughout the womans reproductive life, serum concentrations of AMH gradually decrease and fall below detectable levels in menopause. This could be of particular interest in subfertile and infertile women undergoing assisted reproductive techniques (ART) in achieving pregnancy.

Reference intervals for reproductive hormones in prepubertal children on the automated Roche cobas e 411 analyzer.

OBJECTIVES To establish reference intervals for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), progesterone (P), total and free testosterone (T) and sex-hormone binding globulin (SHBG) in prepubertal children and to assess age- and gender-related differences. DESIGN AND METHODS A total of 948 subjects, 480 girls and 468 boys, between 1 and 11 years of age, were included in this study. All assays were performed on a Roche cobas e 411 immunoassay analyzer. Reference intervals have been evaluated according to the most recent CLSI guidelines. RESULTS Median values of LH, FSH and T were significantly higher in subgroups ranging from ≥ 8 to < 11 years, for both genders. In girls of that age, reference values of E2 were significantly higher than in younger ones, and in boys of the corresponding age. CONCLUSION Established reference intervals are applicable to other laboratories that use the same instrumentation.

The impact of temporal variability of biochemical markers PAPP-A and free β-hCG on the specificity of the first-trimester Down syndrome screening: a Croatian retrospective study

BackgroundThe variability of maternal serum biochemical markers for Down syndrome, free β-hCG and PAPP-A can have a different impact on false-positive rates between the 10+0 and 13+6 week of gestation. The study population comprised 2883 unaffected, singleton, spontaneously conceived pregnancies in Croatian women, who delivered apparently healthy child at term. Women were separated in 4 groups, dependently on the gestational week when the analyses of biochemical markers were performed. The concentrations of free β-hCG and PAPP-A in maternal serum were determined by solid-phase, enzyme-labeled chemiluminiscent immunometric assay (Siemens Immulite). Concentrations were converted to MoMs, according to centre-specific weighted regression median curves for both markers in unaffected pregnancies. The individual risks for trisomies 21, 18 and 13 were computed by Prisca 4.0 software.FindingsThere were no significant differences between the sub-groups, regarding maternal age, maternal weight and the proportion of smokers. The difference in log10 MoM free β-hCG values, between the 11th and 12th gestational week, was significant (p = 0.002). The difference in log10 MoM PAPP-A values between the 11th and 12th, and between 12th and 13th week of gestation was significant (p = 0.006 and p = 0.003, respectively). False-positive rates of biochemical risk for trisomies were 16.1% before the 11th week, 12.8% in week 12th, 11.9% in week 13th and 9.9% after week 13th. The differences were not statistically significant.ConclusionsBiochemical markers (log10 MoMs) showed gestation related variations in the first-trimester unaffected pregnancies, although the variations could not be attributed either to the inaccuracy of analytical procedures or to the inappropriately settled curves of median values for the first-trimester biochemical markers.