Jakub Mieszczak's scientific contributionswhile working at Riley Hospital for Children (Indianapolis, United States) and other institutions
- Abstract: McCune-Albright syndrome (MAS) is typically defined as a triad of precocious puberty (PP), café au lait spots and fibrous dysplasia of bone. PP is the most common endocrinological manifestation of this rare disease and is much more common in girls than in boys. The treatment options for PP associated with MAS have evolved over the last twenty plus years. Therapy in girls typically includes the use of an anti-estrogen, while treatment options in boys include an antiandrogen in combination... Show More
- Abstract: Precocious puberty (PP) in girls with McCune-Albright syndrome (MAS) is characterized by episodic development of large unilateral ovarian cysts followed by sudden onset of vaginal bleeding. Some patients experience frequent bleeding as well as accelerated linear growth and advanced skeletal maturation. The use of anastrozole for the treatment of PP in this condition has not been well studied. The objective of the study was to determine the safety and efficacy of the aromatase inhibitor... Show More
- Abstract: Infants born with ambiguous genitalia [henceforth referred to as Disorder of Sex Development (DSD)] present a unique set of clinical challenges requiring an organized yet practical approach. Given the low frequency with which these types of patients are encountered, their management is best accomplished by practitioners experienced with DSDs. The goal is to discuss, in light of recent publications, information required to make rational management decisions and provide our perspective. An... Show More
Article: Management of Disordered PubertyAbstract: Precocious pubertyDelayed pubertyTreatment of other forms of disordered pubertyReferences
- Abstract: It is estimated that more than 70% of children diagnosed with a pediatric malignancy will survive,(1) but this improvement in prognosis has been accompanied by serious late endocrine complications.(2) Pubertal disorders after cancer therapy are common and include precocious puberty, as well as hypogonadism. However, the simultaneous coexistence of central precocious puberty (CPP) and primary gonadal failure (PGF) in the same patient is atypical and unexpected. Here we describe two boys with... Show More
Publications citing this author (79)
[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.
- 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 . 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  .
[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.
- 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 . In DSD patients, assessment of 5α-reductase deficiency 2 on a hormonal level comprises determination of the ratio of testosterone to DHT in serum . There are also a number of DSD patients where a definitive diagnosis has not been possible.