Biomedical subjects

Federico Baronio

Publications and source records attributed to Federico Baronio.

6 recordsLinked to original sources

PubMed2026

Genetic testing and reporting: What the endocrinologists should know and can expect (Joint position paper of the ENDO-ERN).

Over the last decade, next generation sequencing (NGS) has become an essential tool for diagnostic DNA testing in human genetics. To improve the understanding of available genetic testing strategies and to facilitate the request of genetic testing in daily endocrine practice, clinical and laboratory experts in the field have summarized the major issues which should be known and considered. In this joint position paper of the ENDO-ERN, the roles and responsibilities of the health care professionals involved in the diagnostic workflow are described, and the major issues concerning genetic testing workflows are overviewed. These issues encompass all relevant steps, including test request and pre-analytical procedures, laboratory and data processing workflows, quality assurance, and reporting. As NGS procedures result in an increasing number of variants of unknown significance and incidental findings, these aspects are addressed as well. Accompanied by illustrations of the genetic diagnostic workflow and of concise reports for a fast orientation about the major aspects of genetic testing, this joint paper should support the health care professionals during a request for genetic testing.

VUS↗

PubMed2006

Effect on adult height of pubertal growth hormone retesting and withdrawal of therapy in patients with previously diagnosed growth hormone deficiency.

CONTEXT: GH replacement therapy in GH-deficient (GHD) patients is usually continued until adult height despite the fact that most of these subjects display a normal secretion when retested at the end of growth. Puberty is the most likely time for normalization of GH secretion. OBJECTIVES: The objectives of this study are to establish the characteristics and the percentage of the subjects with isolated GHD who normalized secretion at puberty and to compare their statural outcomes with those of the subjects with persistent deficiency treated also after retesting. DESIGN AND SETTING: This was a prospective, nonrandomized, open-label study conducted in a university research hospital. PATIENTS AND INTERVENTION: Sixty-nine subjects (40 male, 29 female) with a diagnosis before puberty of isolated GHD by means of arginine and l-dopa tests were reevaluated with the same tests after at least 2 yr of therapy and after puberty onset. If GH peak at retesting was more than 10 microg/liter, therapy was withdrawn. MAIN OUTCOME MEASURES: Percentage and characteristics of normalized subjects at retesting, outcome of treatment in the subjects treated or untreated to adult height, and factors predictive of growth outcome were measured. RESULTS: At retesting, 44 subjects (63.7%) confirmed a GH peak less than 10 microg/liter (24 of 40 male and 20 of 29 female). Apart from a less delayed bone age at diagnosis in females, the subjects with confirmed GHD were not different at diagnosis from the other group for height deficit at diagnosis, first year growth response to GH, age and height at puberty onset, height, and IGF-I at retesting. Mean adult height was 165.1 +/- 4.5 cm in the male group treated until adult height vs. 164.0 +/- 3.4 cm in the group who suspended therapy at retesting. Mean adult height was 153.2 +/- 4.1 cm in the female group treated until adult height vs. 152.9 +/- 5.2 cm in the group that suspended therapy at retesting. As regards the parameters expressing the final outcome, the only difference was found in the mean increment adult height-target height sd score in favor of the male group treated until adult height. In both sexes, therapy duration and GH levels at diagnosis and at retesting were unrelated to adult height parameters and to height increments during the period of observation. CONCLUSIONS: One third of our GHD subjects diagnosed before puberty presented a normal secretion at puberty. The withdrawal of GH therapy in these subjects after retesting was not associated with a catch down growth, and they obtained an adult height similar to those obtained by the GHD subjects treated until adult height. It seems convenient, in subjects with nonsevere GHD, to retest GH secretion at midpuberty and to withdraw treatment for the subjects that are no longer deficient.

Adolescent↗

PubMed2006

Birth length and weight in congenital adrenal hyperplasia according to the different phenotypes.

UNLABELLED: The aims of this study were to: (1) retrospectively investigate the birth length and weight of our patients with congenital adrenal hyperplasia (CAH); (2) compare these parameters with standards for birth length and weight recently assessed in an Italian control population; (3) evaluate whether neonatal auxological data may change depending on the different clinical forms of CAH. Birth length and weight were retrospectively evaluated in 101 children with different clinical forms of CAH and compared with standards for birth length and weight assessed in an Italian control population. In both sexes the average birth length of patients with classical CAH was greater than the mean birth length of the controls, and both length and weight were greater in children with classical CAH than in those with the non-classical form. Among the patients with classical CAH, those with the salt-wasting form were longer but also weighed less than those with the simple-virilizing form. CONCLUSIONS: (1) fetal length velocity in patients with CAH may be increased only in those infants with classical forms of the syndrome, while it is unaffected in those with the non-classical form; (2) the greater the enzymatic activity impairment, the longer the birth length of newborns with CAH.

Adrenal Hyperplasia, Congenital↗

PubMed2005

A new DAX1 gene mutation associated with congenital adrenal hypoplasia and hypogonadotropic hypogonadism.

We report on a DAX1 gene investigation in a patient with X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) in order to identify mutations causing this disorder and to confirm the clinical diagnosis. The description of the clinical course of the condition with a detailed documentation of longitudinal data is also reported. A male newborn was referred at 45 days of life because of vomiting, dehydration, and weight loss. The diagnosis was primary adrenal insufficiency. The appropriateness of glucocorticoid therapy during the prepubertal period was difficult to judge because of elevated ACTH levels on one hand and progressive retardation of bone age on the other hand. Basal and GnRH stimulated gonadotropin levels remained low during the entire period of examination and exogenous gonadotropin treatment was begun. This had to be interrupted at age 14.6 years because of the occurrence of a 3rd degree anaplastic ependimoma of the left posterior-parietal region, without apparent lepto-meningeal involvement. The molecular analysis of DAX1 gene of the propositus showed deletion of nucleotides AAT in exon 2, resulting in the loss of the Asn430. No alterations were found in the mother and grandmother. This deleted residue lies in one of the helices forming the hydrophobic core of the ligand-binding domain (LBD); thus this mutation may be the cause of the observed phenotype. Further investigations are needed to verify its causal role in AHC associated with HH.

Adolescent↗

PubMed2005

Height as a risk factor for osteosarcoma.

Previous investigations have suggested that osteosarcoma may be associated with a taller stature, but the relationship between height and osteosarcoma remains controversial. Height at diagnosis was evaluated in a continuous series of 962 osteosarcoma subjects treated between 1981 and 2001. Patients diagnosed during growth (group 1) were separated from those diagnosed in adulthood (group 2). Height (H) and final height (FH) were expressed as standard deviation scores (SDS), calculated by national reference data. Group 1 subjects were above the 50th centile and their mean H-SDS values (0.31 +/- 1.1) were significantly higher than the mean FH-SDS values (P < 0.0001) of the group 2 subjects, both in males and females. In contrast, the mean FH-SDS (0.01 +/- 1.1) of group 2 did not differ from that of the reference population. The highest incidence of osteosarcoma was at 12.5 years in females, 14.5 years in males. These data confirm previous observations of an association between osteosarcoma development and height, at least in growing individuals. The higher incidence during the pubertal spurt, in the anatomic sites of greater growth and in taller individuals, suggests that growth factors play an important role in the pathogenesis of this bone cancer.

Adolescent↗

PubMed2003

CYP21 genotype, adult height, and pubertal development in 55 patients treated for 21-hydroxylase deficiency.

In a retrospective study we evaluated long-term growth, pubertal developmental patterns to final height (FH), and medication in 55 patients (35 females) affected by 21-hydroxylase deficiency. The patients were classified into 3 groups according to predicted mutation severity: group A (11 women and 9 men), homozygous or compound heterozygous for null or In2 splice mutations [residual enzymatic activity (RA), <1%]; group B (11 women and 4 men), homozygous for I172N or R341P or R426H mutations (RA, approximately 2-3%) or compound heterozygous with any of the group A or B mutations; and group C (13 women and 7 men), homozygous for P30L or V281L or P453S mutations (RA, >30%) or compound heterozygous with any of the group A, B, or C mutations. Three patients showed unclassifiable genotypes. FH was similar in the female groups, whereas male patients in group B were shorter than males in groups A and C. Fifty-five percent of patients in group A, 33% in group B, and 40% in group C reached an FH within 0.5 SD of target height. Four of the 7 patients diagnosed via neonatal screening achieved an FH equal to or above the target height. In the entire group, early diagnosis (<1 yr) improved height outcome. Early diagnosed CAH patients who received lower cortisol equivalent doses during the first year of life reached a better FH. Our results underline the importance of mineralocorticoid therapy, as CAH subjects in groups A and B who did not receive this treatment showed reduced FH. Early diagnosis, the use of more physiological cortisol equivalent dosages during the first year of life, and the extension of mineralocorticoid therapy to all classical patients are shown to improve the auxological outcome. Genotypic analysis helped to interpret the height results of our cases and prospectively may represent a useful tool for improving the therapeutic choice and the height outcome.

Adrenal Hyperplasia, Congenital↗