E. Cacciari

Congenital heart disease in patients with Turner’s syndrome

Abstract Objective: There is a high prevalence of congenital heart defects in patients with Turners syndrome. Few studies have reported echocardiographic data in unselected patients according to the different chromosomal patterns. The aim of our study was to evaluate a large series of patients with Turners syndrome, comparing these data with those of the general population. Methods: Five hundred ninety-four patients with Turners syndrome, aged 1 month to 24 years, in the Italian Study Group for Turner Syndrome underwent full cardiologic evaluation. Karyotype distribution was: 45,X (54%), X-mosaicism (13%), and X-structural abnormalities (33%). Results: The prevalence of cardiac malformations was 23%. Bicuspid aortic valve (12.5%), aortic coarctation (6.9%), and aortic valve disease (3.2%) were the most prevalent malformations. In comparison with the general population, partial anomalous pulmonary venous drainage had the highest relative risk. A correlation was found between type of congenital heart defect and karyotype. The patients with 45,X karyotype had the greatest prevalence of partial anomalous pulmonary venous drainage and aortic coarctation, whereas bicuspid aortic valve and aortic valve disease were more common in the patients with X-structural abnormalities. The patients with severe dysmorphic signs showed a significantly higher relative risk of cardiac malformations. Conclusion: X-linked factors may be involved in determining cardiac defects in Turners syndrome. (J Pediatr 1998;133:688-92)

Pelvic ultrasonography in premenarcheal girls: relation to puberty and sex hormone concentrations.

Real time ultrasonography of the pelvic organs was performed on 114 normal premenarcheal girls aged between 2 years and 13 years 11 months. Values were obtained for total uterine length, anteroposterior diameters of the corpus and cervix, corpus/cervix ratio, and uterine and ovarian volumes and the resultant data were grouped according to age. It was concluded that there is no change in uterine size until approximately 7 years of age. Then the uterus begins to enlarge, both in prepubertal girls, in whom this is an age related function, and in pubertal girls, whose uterine growth is influenced not only by age but also by size and, independently of these two factors, by oestradiol concentrations. The onset of a modification in uterine morphology with a greater enlargement of the corpus than the cervix is also seen at age 7 years. Ovarian maturation begins in the very first years of life and, even in pubertal girls, seems to be influenced by age only and not by hormonal stimuli.

Endocrine function and morphological findings in patients with disorders of the hypothalamo-pituitary area: a study with magnetic resonance.

Evaluation of the sellar area was performed with magnetic resonance imaging in 101 patients (age range 0.8-27 years) with hypopituitarism, isolated diabetes insipidus, hypogonadotrophic hypogonadism, and central precocious puberty. The hypopituitary patients (n = 70) included multiple pituitary deficiency (n = 23), pituitary deficiency with diabetes insipidus (n = 5), and isolated growth hormone deficiency (n = 42). The patients with multiple pituitary deficiency showed pathological morphological findings in all cases, with stalk and posterior lobe always involved. The group with associated diabetes insipidus had abnormal stalk in four of five cases and posterior lobe not visible in all cases. Only five of 42 (12%) patients with isolated growth hormone deficiency had abnormalities of the sellar area. In two out of four patients with isolated diabetes insipidus posterior lobe was not seen. All patients with hypogonadotrophic hypogonadism (three with Kallmanns syndrome, one Prader-Willi syndrome, and two idiopathic hypogonadism) appeared normal. In precocious puberty (n = 21) the three patients with onset of symptoms before age 2 years exhibited a hypothalamic hamartoma, whereas in the others with onset of puberty between age 2 and 7 the magnetic resonance image was normal in 17 of 18 patients. The probability of finding a pathological magnetic resonance image was considerably high in our patients with multiple pituitary deficiency, isolated diabetes insipidus, and precocious puberty with very early onset of symptoms. On the contrary, purely functional abnormality is suggested in most patients with isolated growth hormone deficiency, hypogonadotrophic hypogonadism, and precocious puberty with later onset of symptoms.

Gonadoblastoma in Turner syndrome and Y-chromosome-derived material.

The identification of Y‐chromosome material is important in females with Ullrich–Turner syndrome (UTS) due to the risk of developing gonadoblastoma or other gonadal tumors. There is controversy regarding the frequency of the Y‐chromosome‐derived material and the occurrence of gonadoblastoma in these patients. The aim of our study was to evaluate a large number of patients with UTS, followed before and during the pubertal age for the prevalence of Y‐chromosome derived material, the occurrence of gonadoblastoma, and the incidence of possible neoplastic degeneration. An unselected series of 171 patients with UTS (1–34 years old), diagnosed cytogenetically, was studied for Y‐chromosome markers (SRY and Y‐centromeric DYZ3 repeats). The follow‐up was of 2–22 years; 101 of these patients were followed during pubertal age. Y‐chromosome material was found in 14 patients (8%): 12 of these were gonadectomized (2.8–25.9 years). A gonadoblastoma was detected in four patients under 16 years of age: in two, Y‐material was detected only at molecular analysis (at conventional cytogenetic analysis, one was included in the 45,X group and one in the X + mar group) and one had also an immature teratoma and an endodermal sinus carcinoma. The prevalence of gonadoblastoma in our series of gonadectomized UTS patients with Y‐positive material was of 33.3% (4/12). Our data suggest that the age of appearance and the possibility of malignant degeneration of gonadoblastoma can occur early in life. These patients, in particular those with 45,X or a marker chromosome may benefit from molecular screening to detect the presence of Y‐chromosome material; PCR is a rapid and inexpensive technique. At the moment, laparoscopy and preventive gonadectomy performed as soon as possible remain the procedures of choice for patients with UTS, when Y‐chromosome has been identified, as we are still unable to predict a future malignant evolution of gonadoblastoma.

Selecting girls with precocious puberty for brain imaging: Validation of european evidence-based diagnosis rule

OBJECTIVES To test the sensitivities of recently published American recommendations predicting occult intracranial lesion (OICL) in girls with central precocious puberty (CPP), and to validate a previously derived diagnosis rule predicting OICL based on age at puberty onset and estradiol (E2) level. STUDY DESIGN A retrospective, multicenter, hospital-based, cohort study was performed, including all girls with CPP seen in 7 centers in 6 European countries during given periods. American recommendations and the previously derived diagnosis rule were tested. RESULTS Girls with CPP (n=443), including 35 with OICL, were recruited. American recommendations did not identify all OICL. Previously identified independent risk factors for OICL were confirmed: age <6 years (adjusted odds ratio 20.5; 95% CI, 8.1-52.1) and E2 >45th percentile (3.0; 95% CI, 1.3-7.1). The previously derived diagnosis rule had 100% sensitivity (95% CI, 90-100): all girls with OICL had either an age <6 years or an E2 level >45th percentile. The specificity was 39% (95% CI, 34-44). CONCLUSIONS American recommendations do not seem safe to select European girls with CPP who require brain imaging. In settings where systematic brain imaging is not possible, the proposed diagnosis rule could safely help to avoid more than one third of unnecessary brain imaging.

Short stature and celiac disease: A relationship to consider even in patients with no gastrointestinal tract symptoms

To determine the incidence of celiac disease in a group of nonselected children with short stature, duodenal biopsy was performed in 60 unselected children with short stature (below third centile) and absence of gastrointestinal tract symptoms. Examination revealed probable celiac disease in five children (8.3%). Analysis of the results of other tests that might possibly be considered as alternatives to biopsy (e.g., xylose test, antireticulin antibodies, gastrointestinal tract symptoms in the first two years of life, bone age, serum iron, iron load, triglyceride load) led us to conclude that no test or clinical measurement could have allowed us 100% certainty in making the correct diagnosis. None of the children with celiac disease had growth hormone deficiency. We conclude that asymptomatic celiac disease represents a cause of short stature that cannot be ignored, and that only by intestinal biopsy can all such patients be identified.

Turner's syndrome: cardiologic profile according to the different chromosomal patterns and long-term clinical follow-Up of 136 nonpreselected patients.

The preferential association between Turners syndrome and congenital heart defects (CHD) have been well known since the first description by Morgagni. There are few studies about the different cardiologic problems stemming from different chromosomal patterns of X monosomies. We reviewed a large series of 136 patients with Turner syndrome without cardiologic preselection, 29 of whom had some kind of CHD (21.5%). Partial anomalous pulmonary venous drainage (PAPVD; 2.9%), aortic valve disease (stenosis and/or incompetence) (AoVD; 5.1%), aortic coarctation (AoCo; 4.4%), and bicuspid aortic valve (BicAo; 14.7%) are much more frequent in Turners syndrome than in the normal population, with the difference being statistically highly significant. In our cases, only the 45, X subjects showed severe CHD and multiple lesions, whereas the X-ring pattern was associated with an elevated prevalence of BicAo. Patients with X-deletion showed no signs of congenital heart malformations. Eleven patients, all with 45, X pattern, and significant CHD, underwent cardiac surgery at a mean age of 7.7 ± 5.3 years (range 7 days–18 years) without complications. At follow-up of 3–18 years (8.6 ± 5.2), we were unable to observe any type of evolution of the remaining untreated cardiovascular anomalies.

Randomised trial of LHRH analogue treatment on final height in girls with onset of puberty aged 7.5–8.5 years

OBJECTIVE To study the effectiveness of luteinising hormone releasing hormone (LHRH) analogues in improving final height in girls affected by early puberty. PATIENTS Forty six consecutive girls with onset of puberty aged 7.5–8.5 years randomly divided into two groups: one treated with 3.75 mg triptorelin intramuscularly every four weeks (group 1); and the other with no treatment (group 2). RESULTS Mean (SD) chronological age at onset of menarche was significantly higher in group 1 than in group 2 (11.9 (1.0) v 10.8 (0.7) years). However, mean (SD) height at menarche (152.7 (7.2)v 152.5 (5.7) cm) and mean (SD) growth after menarche (4.9 (3.0) v 5.4 (2.2) cm) were similar in both groups. The mean (SD) final height was similar in the two groups (group 1, 158.1 (6.2) cm; group 2, 158.6 (6.0) cm) and not significantly different from target height. Fourteen of 20 patients in group 1 and 12 of 18 patients in group 2 showed final height equal to or higher than target height. Final heights of girls with poor initial height prognosis were significantly lower than those of girls with good prognosis, but in patients with the same initial height prognosis, both groups showed final heights similar and not significantly different from their target heights. CONCLUSIONS LHRH analogue has no apparent effect on final height in subjects with onset of puberty between 7.5 and 8.5 years.

Growth and growth factors in diabetes mellitus.

Growth of 79 children with diabetes was analysed at diagnosis and again after one to 10.7 years of treatment with insulin. Both sexes were tall at onset, whereas at the last observation boys alone showed significant growth retardation. Height standard deviation score (SDS), however, showed no significant fall either in 32 subjects reassessed after five years of disease or in 18 subjects examined at full stature. Skeletal maturity was not significantly impaired after treatment. Pubertal growth spurt was reduced, especially in girls and in subjects with onset of disease at or around puberty. We found no significant correlation between height and height velocity SDS and glycosylated haemoglobin values or secretion of growth hormone during the arginine test. Somatomedin C values were correlated with height velocity SDS in prepubertal boys. The results of this study suggest that there are interferences in the growth of children with diabetes but that they do not seem to have a significant influence on adult height.

Pelvic ultrasonography in girls with precocious puberty, congenital adrenal hyperplasia, obsesity, or hirsutism

Real-time ultrasonography of the pelvic organs was performed on 151 girls with various complete and incomplete forms of precocious puberty, 20 girls with congenital adrenal hyperplasia, 20 with hirsutism, 18 with obesity, and 133 age-matched normal girls. Uterine and ovarian volumes were calculated and the ovarian morphologic picture was classified as homogeneous, nonhomogeneous (less than three small cystic areas), microcystic (four or more small cystic areas less than 9 mm in diameter), follicular (at least one cystic area greater than 9 mm), and macrocystic (large cystic area greater than 20 mm). Ultrasound imaging allowed an easy distinction between true precocious puberty and premature thelarche or idiopathic premature adrenarche. It was also helpful in the diagnosis of transient sexual precocity, although in these cases the differential diagnosis of precocious puberty can be difficult. In postmenarcheal patients with congenital adrenal hyperplasia, ultrasound study showed a low uterine volume and, frequently, a macrocyst in the ovary. In hirsute girls and in a few obese patients, ovaries had an increased volume and a microcystic structure, similar to those in polycystic ovary syndrome. Pelvic ultrasonography can be useful not only in diagnosing disorders in sexual development but also for greater understanding of the pathogenesis of these and other disorders.