Rasa Verkauskiene

Bone mineral content at birth is determined both by birth weight and fetal growth pattern.

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.

Puberty in children born small for gestational age.

Small for gestational age (SGA) children are more prone to have precocious pubarche and exaggerated precocious adrenarche, an earlier onset of pubertal development and menarche, and faster progression of puberty than children born of appropriate for gestational age (AGA) size. The majority of studies investigating the onset of puberty in children born SGA and AGA established that, although puberty begins at an appropriate time (based on chronological age and actual height) in SGA children, onset is earlier relative to AGA children. Evaluating pubertal growth in SGA children, a more modest bone age delay from chronological age at the onset of puberty and more rapid bone maturation during puberty compared to AGA children were reported. Peak height velocity in adolescence is reached at an earlier pubertal stage and lasts for a shorter period in children born SGA than in those born AGA. These differences lead to an earlier fusion of the growth plates and a shorter adult height. The pathophysiological mechanism underlying the unique pubertal growth pattern of children born SGA remains unclear. However, it seems that this is not only related to birth weight, gestational age, adiposity or obesity, but that there may also be an influence of rapid weight gain in early childhood on pubertal onset: excess weight gain in childhood may be related to central adiposity, decreased insulin sensitivity, and increased IGF-I levels and might thus predispose to precocious pubarche.

Mutations and pituitary morphology in a series of 82 patients with PROP1 gene defects.

Background/Aims: 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. Methods: 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. Results: 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 mm3 (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. Conclusion: 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.

Genesis of two most prevalent PROP1 gene variants causing combined pituitary hormone deficiency in 21 populations

Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single-nucleotide variant markers flanking the 9.6-Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations – a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated the ancestral origin of both variants – c.[301_302delAG] was carried on 0.2 Mb-long haplotype in a majority of European patients arising ~101 generations ago (confidence interval 90.1–116.4). Patients from the Iberian Peninsula displayed a different haplotype, which was estimated to have emerged 23.3 (20.1–29.1) generations ago. Subsequently, the data indicated that both the haplotypes were transmitted to Latin American patients ~13.8 (12.2–17.0) and 16.4 (14.4–20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3 Mb was estimated to appear 43.7 (38.4–52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot spots as previously assumed, but are founder variants.

Factors Associated with the Prevalence of Thyroid Nodules and Goiter in Middle-Aged Euthyroid Subjects

The aim of the present study was to determine associations of thyroid hormone levels and different metabolic parameters and anthropometric measurements with volume of nodular and nonnodular thyroid as well as with prevalence of goiter and thyroid nodules in middle-aged euthyroid subjects. Methods. The study consisted of 317 euthyroid subjects aged 48-49 from the Kaunas Cardiovascular Risk Cohort study. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and antithyroid peroxidase antibody (ATPO) levels, as well as anthropometric and metabolic parameters and smoking information, were evaluated. Results. In subjects with and without thyroid nodules, thyroid volume correlated with components of metabolic syndrome, body mass index (BMI), smoking, and TSH levels. In the nonnodular thyroid group, thyroid volume was also positively related to serum insulin and HOMA-IR, whereas a negative correlation between thyroid volume and leptin was identified in the nodular thyroid group. The goiter was identified in 12.3% of subjects. Female gender, thyroid nodules, smoking, BMI, and levels of TSH were independent predictors for goiter. Thyroid nodules were found in 31.2% of participants. Female gender, higher TSH levels, and thyroid volume were independent risk factors for thyroid nodules. Conclusions. Female gender, thyroid nodules, smoking, BMI, and TSH levels were identified as potential predictors of goiter. Female gender, TSH levels, and thyroid volume predicted the presence of thyroid nodules.

A description of clinician reported diagnosis of type 2 diabetes and other non-type 1 diabetes included in a large international multicentered pediatric diabetes registry (SWEET).

Although type 1 diabetes (T1D) remains the most frequent form of diabetes in individuals aged less than 20 years at onset, other forms of diabetes are being increasingly recognized.

Variation in size at birth in infants born small for gestational age in Lithuania.

The aim of this study was to describe the heterogeneity in body proportions of infants born small for gestational age (SGA), defined by birthweight, and to study the relationship of placental size with neonatal anthropometric measurements. Anthropometry was evaluated in 107 symmetrically and asymmetrically growth‐retarded infants born SGA (birthweight <−2 SD) and compared with 181 appropriate‐for‐gestational age infants (AGA; birthweight and length ± 2 SD). Study children were born at Kaunas University Hospital during the period from 1 January 1998 to 25 August 2000. Two‐thirds of SGA children were light (SGAW) and one‐third was both light and short (SGAWL) for gestational age. Infants in both SGA groups were significantly leaner than AGA children. SGAWL infants had significantly larger heads in relation to their length compared with SGAW and even AGA children, probably indicating a brain‐sparing effect. SGAWL children had the lowest mean placental weight, but the highest placental weight to birthweight (PW/BW) ratio. The PW/BW ratio was inversely correlated with most infant measurements; the strongest negative relationship was observed with birthlength and lower leg length.

Functional Adrenocortical Oncocytoma Presenting with Hyperandrogenism andSeizures

A 38-year-old woman was referred to an Endocrinologist with sudden onset of a variety of clinical symptomsepileptic seizures, amenorrhea, weight gain, hirsutism and sexual dysfunction. Her physical examination and biochemical investigations, including blood sugar were normal. Blood pressure was 110/80 mmHg. A right adrenal tumor was detected on ultrasonography and computed tomography. Blood levels of dehydroepiandrosteronesulphate, testosterone and aldosterone were increased 2.2, 7.6 and 1.6 times higher than maximal normal values respectively. The aldosterone/renin ratio was 176. The laparoscopic excised tumors of the right adrenal gland weighed 137 g and was red-yellowish-brown with the intact capsule. Histology of the tumor showed round, oval or polygonal cells with abundant granular eosinophilic cytoplasm. Nuclei were oval, basophilic and with nucleoli. Focally pleomorphic nuclei were noticed. The cells formed nests and trabeculae. Histological picture was suggestive for oncocytoma. Immunohistochemical investigations showed: alpha-inhibin-diffusely positive in tumor cells, synaptophysin-positive in zones of tumor cells, melan A-diffusely positive in tumor cells, Ki-67-positive in 10% of tumor cells, Chromograninnegative in tumor cells but positive in medullary zone. After the surgery, almost all the hormones returned to normal and were maintained at this level for 12 months post operation. An exception was aldosterone, which was increased, but without symptoms of hyperaldosteronism. The patient did not report any seizures after the surgical treatment. Sexual function regained 6-12 months post-surgery.