Jakub Mieszczak's scientific contributionswhile working at Riley Hospital for Children (Indianapolis, United States) and other institutions

Publications (5)

Publications citing this author (79)

    • However, mean ovarian volumes tended to increase over time, and one patient experienced ovarian torsion. A systemic prospective study of anastrozole for the treatment of peripheral PP in 27 girls with MAS over one year found that it was ineffective in halting vaginal bleeding, attenuating rates of skeletal maturation, and increasing linear growth [8]. Tamoxifen, a selective estrogen receptor modulator, was found to have positive results in a year-long multicenter trial of 25 girls with peripheral PP and MAS [9] .
    [Show abstract] [Hide abstract] ABSTRACT: Background McCune–Albright syndrome (MAS) is a rare disease defined by the triad of fibrous dysplasia (FD), café au lait spots, and peripheral precocious puberty (PP). Because of the rarity of this disease, only a few individuals with MAS have been reported in Korea. We describe the various clinical and endocrine manifestations and genetic analysis of 14 patients with MAS in Korea. Methods Patients’ clinical data—including peripheral PP, FD, and other endocrine problems—were reviewed retrospectively. In addition, treatment experiences of letrozole in five patients with peripheral PP were described. Mutant enrichment with 3′-modified oligonucleotides - polymerase chain reaction (MEMO-PCR) was performed on eight patients to detect mutation in GNAS using blood. MEMO-PCR is a simple and practical method that enables the nondestructive selection and enrichment of minor mutant alleles in blood. ResultsThe median age at diagnosis was 5 years 2 months (range: 18 months to 16 years). Eleven patients were female, and three were male. Thirteen patients showed FD. All female patients showed peripheral PP at onset, and three patients subsequently developed central PP. There was a significant decrease in estradiol levels after two years of letrozole treatment. However, bone age was advanced in four patients. Two patients had clinical hyperthyroidism, and two patients had growth hormone (GH) excess with pituitary microadenoma. c.602G > A (p.Arg201His) in GNAS was detected in two patients in blood, and c.601C > T (p.Arg201Cys) in GNAS was detected in one patient in pituitary adenoma. Conclusions This study described the various clinical manifestations of 14 patients with MAS in a single center in Korea. This study first applied MEMO-PCR on MAS patients to detect GNAS mutation. Because a broad spectrum of endocrine manifestations could be found in MAS, multiple endocrinopathies should be monitored in MAS patients. Better treatment options for peripheral PP with MAS are needed.
    Full-text · Article · Dec 2016
    • Meanwhile, deficiency of DHT in males (46, XY disorders) caused by 5α-reductase 2 deficiency has significant clinical implications, as marked virilisation can occur at the time of puberty, due to increased testosterone substrate acting with a partially active enzyme and increased activity of the isoenzyme 5α-reductase 1 [5][6][7]. In DSD patients, assessment of 5α-reductase deficiency 2 on a hormonal level comprises determination of the ratio of testosterone to DHT in serum [8]. There are also a number of DSD patients where a definitive diagnosis has not been possible.
    [Show abstract] [Hide abstract] ABSTRACT: Background: Serum dihydrotestosterone (DHT) is an important analyte for the clinical assessment of disorders of sex development. It is also reportedly a difficult analyte to measure. Currently, there are significant gaps in the standardisation of this analyte, including no external quality assurance (EQA) program available worldwide to allow for peer review performance of DHT. We therefore proposed to establish a pilot EQA program for serum DHT. Methods: DHT was assessed in the 2015 Royal College of Pathologists of Australasia Quality Assurance Programs' Endocrine program material. The material's target (i.e. "true") values were established using a measurement procedure based on isotope dilution gas chromatography (GC) tandem mass spectrometry (MS/MS). DHT calibrator values were based on weighed values of pure DHT material (>97.5% purity) from Sigma. The allowable limits of performance (ALP) were established as ±0.1 up to 0.5 nmol/L and ±15% for targets >0.5 nmol/L. Results: Target values for the six levels of RCPAQAP material for DHT ranged from 0.02 to 0.43 nmol/L (0.01-0.12 ng/mL). The material demonstrated linearity across the six levels. There were seven participating laboratories for this pilot study. Results of the liquid chromatography (LC) MS/MS methods were within the ALP; whereas the results from the immunoassay methods were consistently higher than the target values and outside the ALP. Conclusions: This report provides the first peer comparison of serum DHT measured by mass spectrometry (MS) and immunoassay laboratories. Establishment of this program provides one of the pillars to achieve method harmonisation. This supports accurate clinical decisions where DHT measurement is required.
    Article · May 2016