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Barbora Obermannova,
Roland Pfaeffle,
Agata Zygmunt-Gorska,
Jerzy Starzyk, Rasa Verkauskiene,
Natalija Smetanina,
Olga Bezlepkina,
Valentina Peterkova,
Herwig Frisch,
Ondrej Cinek,
Christopher J Child,
Werner F Blum,
Jan Lebl
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ABSTRACT: Defects of the PROP1 gene are the most prevalent genetic cause of combined pituitary hormone deficiency. Previous observations in affected patients have shown pituitary size ranging from hypoplasia to overt pituitary mass and evolution of size over the lifespan.
We evaluated pituitary size and morphology in PROP1-mutation carriers who originated from Central and Eastern Europe. We analyzed 112 pituitary magnetic resonance imaging (MRI) scans from 82 patients (42 males) aged 2.5-72.7 (median 16.6) years from 60 kindreds.
Among the 120 independent PROP1 alleles, the most prevalent mutations were delGA301/302 (99 alleles) and delA150 (13 alleles). Median pituitary height at first MRI was 4.7 mm (range 1.0-20.7) and median volume was 127.6 mm(3) (range 7.5-3,087.0). Pituitary size did not differ between sexes and did not correlate with hormonal phenotype, but significantly decreased with increasing age. However, evaluation of individual values suggested a biphasic mode with increasing volume during childhood, peak in adolescence, and subsequent regression in adulthood.
Although pituitary size was increased in a number of PROP1-deficient patients, none of them suffered permanent damage from pituitary mass; therefore, any proposed surgery should be postponed as long as possible and ultimately may not be necessary due to the self-limiting nature of the pituitary enlargement.
Hormone Research in Paediatrics 01/2011; 76(5):348-54.
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ABSTRACT: Fetal growth restriction (FGR) followed by rapid weight gain during early life has been suggested to be the initial sequence promoting central adiposity and insulin resistance. However, the link between fetal and early postnatal growth and the associated anthropometric and metabolic changes have been poorly studied.
Over the first year of post-natal life, changes in body mass index, skinfold thickness and hormonal concentrations were prospectively monitored in 94 infants in whom the fetal growth velocity had previously been measured using a repeated standardized procedure of ultrasound fetal measurements. 45 infants, thinner at birth, had experienced previous FGR (FGR+) regardless of birth weight. Growth pattern in the first four months of life was characterized by greater change in BMI z-score in FGR+ (+1.26+/-1.2 vs +0.58 +/-1.17 SD in FGR-) resulting in the restoration of BMI and of fat mass to values similar to FGR-, independently of caloric intakes. Growth velocity after 4 months was similar and BMI z-score and fat mass remained similar at 12 months of age. At both time-points, fetal growth velocity was an independent predictor of fat mass in FGR+. At one year, fasting insulin levels were not different but leptin was significantly higher in the FGR+ (4.43+/-1.41 vs 2.63+/-1 ng/ml in FGR-).
Early catch-up growth is related to the fetal growth pattern itself, irrespective of birth weight, and is associated with higher insulin sensitivity and lower leptin levels after birth. Catch-up growth promotes the restoration of body size and fat stores without detrimental consequences at one year of age on body composition or metabolic profile. The higher leptin concentration at one year may reflect a positive energy balance in children who previously faced fetal growth restriction.
PLoS ONE 02/2009; 4(4):e5343. · 4.09 Impact Factor
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ABSTRACT: We present our experience in diagnosing, gender assignment, and surgical management of sexual ambiguity in 46,XY mixed gonadal dysgenesis.
A retrospective study of five cases treated from 2003 to 2006 was performed. Clinical picture, operative findings, testosterone levels, and immunohistochemistry of gonads for the expression of FOXL2, SOX9, AMH, AMHr, C-kit, and PLAP were analyzed.
All patients had ambiguous genitalia, urogenital sinus, uterus, testicle on one side, and a streak gonad on the other. Four patients were reared as male and one as female. Stimulation by human chorionic gonadotropin showed good penile size and testosterone response. All patients underwent laparoscopic gonadal biopsy and/or gonadectomy. Histological studies showed the presence of sparse primordial follicles surrounded by embryonic sex cords in the streak portion of gonads. Germ cells were C-kit positive in all and PLAP positive in four patients. FOXL2 expression was detected in four streak gonads and in none of testes. AMH expression was found only in testes. SOX9 expression was found in both investigated testes and in three out of four streak gonads investigated.
46,XY mixed gonadal dysgenesis should be differentiated from ovotesticular and other types of 46,XY disorders of sexual differentiation by the typical gonadal histology and internal genital structure. High testosterone level after stimulation and good response to testosterone treatment in 46,XY mixed gonadal dysgenesis could orient toward male sex assignment. There are different patterns of gene expression in testicular and streak gonads with a switch to FOXL2 positivity in streak gonads. Early gonadal and genital surgery is recommended.
Medicina (Kaunas, Lithuania) 02/2009; 45(5):357-64. · 0.42 Impact Factor
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ABSTRACT: The most common genetically determined cause of multiple pituitary hormone deficiency is PROP-1 gene mutation. PROP-1 is a transcription factor involved in the development of pituitary gland and affects hormonal synthesis of anterior pituitary. The aim of our study was to evaluate radiological aspects of the pituitary region in patients with PROP-1 gene mutation. Pituitary imaging studies were performed in 12 patients with a confirmed PROP-1 gene mutation. Pituitary hyperplasia was found in 5 (42%) and pituitary hypoplasia in 4 (33%) patients. Changes in pituitary size were not associated with the type of PROP-1 gene mutation.
Medicina (Kaunas, Lithuania) 01/2009; 45(9):693-8. · 0.42 Impact Factor
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ABSTRACT: The aim of the study was to evaluate growth pattern of small- and appropriate-for-gestational-age children and to identify prenatal and postnatal risk factors for short stature and development of components of metabolic syndrome. A total of 109 small- and 239 appropriate-for-gestational-age infants were enrolled in the study. Within 24 hours after birth and at 2, 5, 9, 12, 18, 24 months, and 6 years of age, anthropometric data were recorded for study children. Cord blood samples from study infants were collected, and insulin-like growth factor-1 (IGF), IGF-binding protein-3, and leptin levels were measured. Birth weight and height (P<0.001) and insulin-like growth factor-1, IGF-binding protein-3, and leptin levels (P<0.05) were lower in children born small for gestational age vs. children born appropriate for gestational age. At 2, 5, 12, 18, and 24 months and 6 years of age, children born small for gestational age remained shorter and weighed less (P<0.001). Waist-to-hip ratio, heart rate at 6 years of age and gain in body mass index from birth up to 6 years of age was higher in children born small for gestational age. Height gain during the first year of life was mainly influenced by birth length and target height. Maternal weight before pregnancy and cord leptin levels were the most significant factors influencing postnatal weight gain during the first years of life. CONCLUSIONS: During the first 6 years of life, children born small for gestational age remained shorter and lighter. A greater catch-up in body mass index and tendency towards central pattern of fat distribution during the first years of life might be predisposing factors for the development of long-term metabolic complications in these individuals.
Medicina (Kaunas, Lithuania) 01/2009; 45(1):51-60. · 0.42 Impact Factor
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ABSTRACT: Birth weight (BW) is usually taken as a surrogate of fetal growth. However, BW per se is not relevant enough in assessing fetal growth restriction, which by itself may alter body composition, metabolic, and hormonal profiles at birth (irrespective of BW), reflecting the necessary adaptive changes in metabolism under poor fetal environment.
Our objective was to measure body composition, hormonal, and metabolic parameters at birth in relation to both BW and fetal growth velocity.
A total of 235 pregnancies at risk of low BW were included, and newborns were observed at birth. Fetal growth velocity was calculated as the change in customized percentiles of estimated fetal weight between 22 wk gestational age and birth. Newborns were ranked in descending order of fetal growth velocity and divided in three equal tertiles.
The lower fetal growth velocity tertile showed a severe fetal growth restriction (-52% +/- 21%) and was significantly associated with reduced lean and fat mass (P < 0.001 and 0.02, respectively). Insulin concentration was significantly related to fetal growth velocity (P = 0.006) and fat mass (P = 004) but not to BW (grams), whereas fetal growth velocity (P = 0.002) and BW (P < 0.001) but not fat mass had a significant effect on IGF-I concentration at birth.
Fetal growth restriction induces changes in body composition and metabolism suggestive of a higher insulin sensitivity independently from BW itself, reflecting adaptive changes to an adverse fetal nutritional environment.
Journal of Clinical Endocrinology & Metabolism 09/2008; 93(10):4027-32. · 6.50 Impact Factor
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ABSTRACT: Adult peak bone mass is related to birth weight, suggesting it could be affected by fetal growth pattern. Small-for-gestational-age (SGA) newborns have lower bone mineral content (BMC), but what about adapted-for-gestational-age (AGA) newborns with fetal growth restriction? The purpose of the study was to determine the respective role of birth weight and fetal growth pattern on BMC. Full-term newborns from SGA high-risk pregnancies were included (n = 185). Estimated fetal weight percentiles were measured monthly from mid-gestation to birth, and restricted fetal growth (FGR) was defined as a loss by more than 20 percentiles. BMC was measured at birth, using dual x-ray absorptiometry. Newborns were SGA (n = 56) or AGA (n = 129). Newborns with FGR (n = 111) were AGA (n = 71) or SGA (n = 41). BMC was significantly lower in SGA than AGA (1.48 +/- 0.02 vs. 1.87 +/- 0.04 g/cm) and lower when FGR irrespective of birth weight (1.66 g/cm +/- 0.03 vs. 1.89 g +/- 0.05). In multivariate analysis, FGR and SGA were significant and independent predictors of low BMC. In conclusion, fetal growth pattern affects BMC not only in SGA infants but also when birth weight is maintained in the normal range.
Pediatric Research 08/2008; 64(1):86-90. · 2.70 Impact Factor
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ABSTRACT: The aim of this study was to evaluate leptin concentration at birth and in early postnatal life in small- and appropriate-for-gestational-age infants and to assess its relationship with infants' anthropometry at birth and some characteristics of maternal pregnancy.
A total of 367 infants born after 32-42 weeks of gestation were enrolled in the study. Umbilical cord blood samples were collected from 80 small- and 287 appropriate-for-gestational-age newborns. Altogether, 166 venous blood samples were taken from these neonates on days 2-6 of life.
Cord leptin levels were significantly lower in small- compared to appropriate-for-gestational-age infants. We observed a positive correlation between cord leptin and birth weight, all neonatal anthropometric parameters, placental weight, and some maternal nutritional factors. In multivariate analysis, cord leptin concentration explained up to 15% of the variation in sum of newborn's skinfold thickness but only 5% of the variation in birth weight. Postnatally, leptin concentration decreased markedly to the similar low levels in both infant groups and remained so during the first postnatal week.
Significantly lower cord leptin concentration in small-for-gestational-age neonates reflects a lower fat mass content compared to appropriate-for-gestational-age infants. However, an abrupt decrease in leptin levels shortly after birth in both groups suggests that placenta could be an important source of leptin in fetal circulation. The impact of low leptin levels at birth in small-for-gestational-age infants on their postnatal appetite and weight gain remains to be elucidated in future studies.
Medicina (Kaunas, Lithuania) 02/2007; 43(10):784-91. · 0.42 Impact Factor
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ABSTRACT: Human immunodeficiency virus (HIV)-related lipodystrophy is characterized by adipose tissue redistribution, dyslipidemia, and insulin resistance. We hypothesized that fat redistribution and metabolic abnormalities in HIV-infected children are related to alterations in endocrine function of adipose tissue. A multicenter study was conducted in 130 HIV-infected children. Lipodystrophy definition was based on the central to peripheral skinfold ratio. Fasting adiponectin, leptin, insulin concentrations, glycemia, and lipid profile were measured in all children. Fat redistribution syndrome was apparent in 32 children: 14 with atrophic (LPDA) and 18 with hypertrophic lipodystrophy (LPDH). Mean serum adiponectin levels were significantly decreased in LPDA and LPDH groups compared with the group with no lipodystrophy (LPD-). Fasting insulin concentration was significantly higher in LPDA and LPDH groups versus LPD-. Mean serum leptin concentration was significantly increased only in LPDH compared with LPDA and LPD- groups. Triglyceride levels were significantly increased and high-density lipoprotein (HDL)-cholesterol concentration decreased in the LPDA versus LPD- group. Controlling for puberty stage, gender, percentage of total fat mass, serum lipids, HIV treatment, and disease severity, adiponectin was significantly and inversely associated with central obesity and insulin/glucose ratio. Fat redistribution had no significant effect on leptin concentration, which was directly related to the percentage of body fat, female gender, and insulin/glucose ratio. In conclusion, HIV-infected children with symptoms of fat redistribution have decreased levels of adiponectin, associated with insulin resistance and dyslipidemia.
Pediatric Research 09/2006; 60(2):225-30. · 2.70 Impact Factor
