Does elevated morning prolactin concentration in children always mean the diagnosis of hyperprolactinemia?

AIM: It has recently been suggested that prolactin (Prl) level above the upper limit of normal range, recorded in a single measurement in serum is enough to diagnose hyperprolactinemia (HPrl). The aim of the study was the analysis of the circadian rhythm of Prl secretion in children with an increased morning Prl concentration in order to establish whether it is a real hyperprolactinemic state or not. MATERIAL AND METHODS: The analysis comprised a group of 44 children (32 boys and 12 girls, aged from 4.2 to 14.1 years, mean±SD: 10.4±3.5 years) with either short stature or precocious puberty, with an elevated Prl concentration at 8:00 a.m., suggesting hyperprolactinemic state. In all patients the circadian Prl secretion profile was assessed on the basis of Prl concentrations in 9 blood samples, collected in 3-h intervals. An analysis of the circadian Prl rhythm was performed. Depending on the medical history and the magnetic resonance imaging result, the children were divided into the following groups: A - congenital disorders of hypothalamic-pituitary region (n=10); B - acquired disorders of hypothalamic-pituitary region (other than pituitary adenomas) (n=15), C - pituitary adenomas (n=19). The control group consisted of 14 healthy children (9 boys and 5 girls), aged from 5.2 to 14.3 years, mean±SD: 10.8±3.2 years. RESULTS: In only 18 children (41%), apart from a higher morning Prl concentration, an elevated Prl concentration at other time points was observed and the circadian rhythm was disturbed, implying hyperprolactinemic state (2 children from Group A, 8 from Group B and 8 form Group C). In the remaining 26 children (59%), higher morning Prl concentrations were not accompanied by elevated Prl concentrations at other time points of the circadian profile. CONCLUSIONS: In children with elevated Prl concentrations in the morning, a circadian Prl secretion profile should be performed in order to avoid overdiagnosing of continuous HPrl. In children with the presence of pituitary adenoma and increased morning Prl concentrations, the diagnosis of Prl-secreting adenoma is not completely obvious.

Secondary IGF-I deficiency as a prognostic factor of growth hormone (GH) therapy effectiveness in children with isolated, non-acquired GH deficiency.

OBJECTIVE: Growth hormone (GH) deficiency (GHD) has recently been classified as secondary IGF-I deficiency but the significance of IGF-I measurement in diagnosing GHD is still discussed. The aim of the study was to assess the relationships between IGF-I secretion and GH therapy effectiveness in children with GHD. PATIENTS AND METHODS: The analysis comprised 300 children with isolated, non-acquired GHD (GH peak below 10 µg/l) who completed GH therapy and attained final height (FH). In all patients IGF-I concentration was measured before the treatment and IGF-I deficiency was diagnosed if IGF-I SDS for age and sex was below -1.0. The following auxological indices were assessed: patients' height SDS before treatment (H0SDS), FH SDS and improvement of FHSDS vs. H0SDS (ΔHSDS). RESULTS: In the patients with IGF-I deficiency when compared with those with normal IGF-I secretion before treatment, significantly better FH SDS (-1.42±0.90 vs. -1.74±0.86, p=0.004) and ΔHSDS (1.64±1.01 vs. 1.32±1.05, p=0.010) were observed, despite similar H0SDS (- 3.07±0.78 vs. - 3.11±0.77, p=0.63) and GH peak (7.0±3.1 µg/l vs. 6.8±2.1 µg/l, p=0.55). The patients who achieved FH over 10(th) centile had significantly lower IGF-I SDS before treatment than those with FH below 10(th) centile (- 1.59±1.54 vs. - 1.20±1.64, p=0.04), despite similar GH peak (7.0±2.3 µg/l vs. 6.7±3.1 µg/l, p=0.45). The patients with ΔHSDS over the median value had significantly lower IGF-I SDS than those with ΔHSDS below the median value (- 1.59±1.71 vs. - 1.09±1.47, p<0.0001), despite similar GH peak (6.8±2.5 µg/l vs. 7.0±2.7 µg/l, p=0.86). CONCLUSION: In children with isolated, non-acquired GHD, secondary IGF-I deficiency is an important predictor of better GH therapy effectiveness.

Probing the interaction of trans-resveratrol with bovine serum albumin: a fluorescence quenching study with Tachiya model.

The interaction of trans-resveratrol (TRES) and bovine serum albumin (BSA) was investigated using fluorescence spectroscopy (FS) with Tachiya model. The binding number maximum of TRES was determined to be 8.86 at 293.15 K, 23.42 at 303.15 K and 33.94 at 313.15 K and the binding mechanism analyzed in detail. The apparent binding constants (K (a)) between TRES and BSA were 5.02 x 10(4) (293.15 K), 8.89 x 10(4) (303.15 K) and 1.60 x 10(5) L mol(-1) (313.15 K), and the binding distances (r) between TRES and BSA were 2.44, 3.01, and 3.38 nm at 293.15, 303.15, and 313.15 K, respectively. The addition of TRES to BSA solution leads to the enhancement in RLS intensity, exhibiting the formation of the aggregate in solution. The negative entropy change and enthalpy change indicated that the interaction of TRES and BSA was driven mainly by van der Waals interactions and hydrogen bonds. The process of binding was a spontaneous process in which Gibbs free energy change was negative.

Substitution of M398T in the second transmembrane helix of the LH receptor in a patient with familial male-limited precocious puberty.

Familial male-limited precocious puberty (MPP) is described in a 10 year old patient with typical symptoms of the disease. Sequence analysis of genomic DNA clearly demonstrated a heterozygous T1193C transition in exon 11 of the LH receptor (LHR) gene, which results in M398T substitution in the second transmembrane helix of the protein product of this gene. The same mutation was found in the patient's mother and in her brother. The grandmother and the relatives of the patient's father were free of the mutation. The boy was successfully treated with inhibitors of steroid biosynthesis and androgen antagonists. It is suggested that this mutation caused constitutive activation of the LHR, which results in excessive formation of androgens in Leydig cells and is responsible for the symptoms of precocious puberty in this patient. This is the second case of the familial form of MPP that was maternally inherited.

Premature menarche--a legend or a defined clinical syndrome.

The properness of diagnosing the premature menarche as isolated clinical syndrome is often questioned. A long-term observation od 2 girls with premature menarche has been described. A discussion is presented about the role of imbalance within the hypothalamus-pituitary-gonads axis and the role of disturbances in peripheral responsiveness to sex hormones in the patho-mechanism of premature menarche.