Vincenzo De Sanctis

Subclinical hypothyroidism in children and adolescents: a wide range of clinical, biochemical, and genetic factors involved.

OBJECTIVE The aim of the study was to examine clinical characteristics, biochemical parameters, and TSH-R gene variations in children and adolescents with subclinical hypothyroidism (SH) in order to evaluate their pattern of distribution in SH. PATIENTS We enrolled 88 patients, each having at least two TSH measurements above the upper limit of the reference range with normal free thyroid hormones and negative thyroid autoantibodies. MAIN OUTCOME MEASURES Clinical characteristics included height, weight, family history of thyroid diseases, thyroid volume, and echogenicity at ultrasonography. Biochemical parameters included TSH, free thyroid hormones, thyroid autoantibodies, and adjusted daily urinary iodine excretion (UIE). Genetic variations in the TSH-R gene were assessed. RESULTS The prevalence of overweight/obesity, positive family history of thyroid diseases, and thyroid hypoechogenicity was 28.4, 45.5, and 22.7%, respectively. Median TSH was higher in overweight/obese patients than in normal-weight ones (7.4 vs. 5.7 muIU/ml; P = 0.04) and in overweight/obese patients with hypoechogenicity than in those with normal ultrasound pattern (8.5 vs. 6.8 muIU/ml; P = 0.04). Adjusted daily UIE was lower in subjects without than in those with a positive family history of thyroid diseases (81 vs. 120 mug/d; P = 0.001). The prevalence of a positive family history of thyroid diseases was 1.9-fold higher in patients with nonsynonymous mutations in the TSH-R gene than in patients without any mutation (80 vs. 42%; P = 0.03). A novel mutation at position 1559 in exon 10 (W520X) was detected in one child. CONCLUSIONS Overweight/obesity, thyroid hypoechogenicity, and nonsynonymous mutations in the TSH-R gene are characterizing features of a large portion of SH children.

Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I‑CET) position statement and guidelines

The current management of thalassemia includes regular transfusion programs and chelation therapy. It is important that physicians be aware that endocrine abnormalities frequently develop mainly in those patients with significant iron overload due to poor compliance to treatment, particularly after the age of 10 years. Since the quality of life of thalassemia patients is a fundamental aim, it is vital to monitor carefully their growth and pubertal development in order to detect abnormalities and to initiate appropriate and early treatment. Abnormalities should be identified and treatment initiated in consultation with a pediatric or an adult endocrinologist and managed accordingly. Appropriate management shall put in consideration many factors such as age, severity of iron overload, presence of chronic liver disease, thrombophilia status, and the presence of psychological problems. All these issues must be discussed by the physician in charge of the patients care, the endocrinologist and the patient himself. Because any progress in research in the field of early diagnosis and management of growth disorders and endocrine complications in thalassemia should be passed on to and applied adequately to all those suffering from the disease, on the 8 May 2009 in Ferrara, the International Network on Endocrine Complications in Thalassemia (I-CET) was founded in order to transmit the latest information on these disorders to the treating physicians. The I-CET position statement outlined in this document applies to patients with transfusion-dependent thalassemia major to help physicians to anticipate, diagnose, and manage these complications properly.

Effect of different treatment regimes on linear growth and final height in β‐thalassaemia major

OBJECTIVE The clinical picture of thalassaemia major has changed progressively over the years. Our study is a retrospective analysis of data on growth in a group of patients who have completed puberty spontaneously and have attained their adult height. Our objective was to evaluate the effect of different transfusion regimes and desferrioxamine administration on the growth pattern in β thalassaemia major.

Induction of spermatogenesis in thalassaemia

In an attempt to induce or to augment pubertal development and to achieve spermatogenesis, 10 gonadotropin-deficient thalassemic patients 15 to 23 years of age (mean 18.9 years) were treated with exogenous gonadotropins for 1 to 4 years (mean 2.1 years). Seven patients produced sperm during human chorionic gonadotropin (hCG) treatment given for 6 to 14 months. However, full spermatogenesis was achieved only when human menopausal gonadotropin was added to hCG regimen. In one patient, despite cessation of gonadotropin treatment, sexual potency, libido, and spermatogenetic capacity were maintained during the past 2 1/2 years. Our study indicates that it is possible to induce or to restore spermatogenesis in the majority of thalassemic patients and that gonadotrope cells may not be irreversibly damaged by iron deposition.

Menstrual pattern and menstrual disorders among adolescents: an update of the Italian data

BackgroundThe most striking event in the whole process of female puberty is the onset of menstruation. To our knowledge, no large population-based studies have been performed on the topic of menstrual health among Italian adolescents in recent years.The aims of this study were to produce up-to-date information on the menstrual pattern of Italian girls attending secondary school, and to estimate the prevalence of menstrual cycle abnormalities in this population.MethodsThis was a cross-sectional study on a population-based sample of Italian adolescents aged 13–21 years attending secondary school. Only girls who had already started menstruating were requested to participate. Information was collected by means of a questionnaire that included items on the girls’ demographic details, anthropometrics, smoking and drinking habits, use of contraceptive pills, and socioeconomic status. The questions on the girls’ menstrual pattern concerned their age at menarche, duration of the most recent menstruation intervals (<21, 21–35, >35 days, variable), average days of bleeding (<4, 4–6, >6 days), and any menstrual problems and their frequency.ResultsA total of 6,924 questionnaires were administered and 4,992 (71%) were returned. One hundred girls failed to report their date of birth, so 4,892 subjects were analyzed. The girls’ mean age was 17.1 years (SD ±1.4); their mean age at menarche was 12.4 (±1.3) years, median 12.4 years (95%CI 12.3–12.5).In our sample population, 3.0% (95%CI 2.5%-3.4%) of the girls had menstruation intervals of less than 21 days, while it was more than 35 days in 3.4% (95%CI 2.9%-3.9%). About 9% of the girls (95%CI 7.7%-9.4%) said the length of their menstruation interval was currently irregular. Short bleeding periods (<4 days) were reported in 3.2% of the sample population (95%CI 2.7%-3.7%), long periods (>6 days) in 19% (95%CI 17.9%-20.1%). Menstruation-related abdominal pain was reported by about 56% of our sample. About 6.2% of the girls (95%CI 5.4%-7.0%) were suffering from dysmenorrhea.ConclusionsIn conclusion, to the best of our knowledge, this is one of the largest studies on menstrual patterns and menstrual disorders among Italian adolescent girls. Adolescent girls referring persistent oligomenorrhoea, in first two years from menarche, had a higher risk for developing a persistent menstrual irregularity. They had longer bleeding periods (>6 days) and this has practical implications because it makes these adolescents potentially more susceptible to iron deficiency anemia. Clinicians need to identify menstrual abnormalities as early as possible in order to minimize their possible consequences and sequelae, and to promote proper health information.We recommend that adolescents should be encouraged to chart their menstrual frequency and regularity prospectively from the menarche onwards.

Nutrition and pubertal development

Nutrition is one of the most important factors affecting pubertal development. Puberty entails a progressive nonlinear process starting from prepubescent to full sexual maturity through the interaction and cooperation of biological, physical, and psychological changes. Consuming an adequate and balanced healthy diet during all phases of growth (infancy, childhood and puberty) appears necessary both for proper growth and normal pubertal development. Girls begin puberty at an earlier age compared to past decades. Excessive eating of many processed, high-fat foods, may be the cause of this phenomenon. Overweight or obese children are more likely to enter puberty early. Some evidence suggests that obesity can accelerate the onset of puberty in girls and may delay the onset of puberty in boys. Moreover, the progression of puberty is affected by nutrition. On the other hand, puberty triggers a growth spurt, which increases nutritional needs including macro and micronutrients. Increased caloric, protein, iron, calcium, zinc and folate needs have to be provided during this critical period of rapid growth. Severe primary or secondary malnutrition also can delay the onset and progression of puberty. The higher incidence of anorexia nervosa and bulimia in adolescents imposes a nutritional risk on pubertal development. Moreover, many environmental endocrine disruptors (EDs) have been identified that can significantly impair the normal course of puberty. This mini-review sums up some important findings in this important complex that link nutrition and pubertal development.

Iron Overload and Glucose Metabolism in Subjects with β-thalassaemia Major : An Overview

Thalassaemia is one of the most common genetic disorders caused by a reduction of the globin chains leading to chronic haemolytic anaemia from birth. The mainstay of treatment is blood transfusion to maintain adequate levels of the haemoglobin. Iron overload in β-thalassaemia major patients is secondary to multiple blood transfusions and increased iron absorption. Excess iron potentially catalyzes free-radicals generation and impairment in cellular function and integrity. Extensive iron-induced injury develops in the heart, liver, pancreas and endocrine system. Pancreatic iron loading in thalassaemia major patients begins at early childhood, and the prevalence of diabetes mellitus (DM) ranges from 6.4% to 14.1% in cross-sectional studies. Both insulin resistance and decreased insulin secretion contribute to DM in thalassaemia major patients. This has been shown by oral glucose tolerance test, euglycemic insulin clamp, homeostatic model assessment, intravenous glucose tolerance test and continuous glucose monitoring system. The prevalence of DM in thalassaemia has been shown to correlate with serum ferritin concentration, hepatitis C infection, and pancreatic and cardiac iron measured by imaging techniques. Therefore the incidence of disturbed glucose homeostasis depends on adherence to chelation treatment, the adequacy of the dosage, the chemical properties of the chelating agent and the prevention of liver infections.

Growth hormone secretion in adult patients with thalassaemia

Background and Objectives  Growth retardation and short stature are frequent clinical features of patients with beta‐thalassaemia major. Dysfunction of the GH–IGF‐1 axis has been described in many thalassaemic children and adolescents with short stature and reduced growth velocity. Several studies have demonstrated that recombinant GH treatment improves growth velocity in these patients, although response to the treatment is variable and not predictable. A reassessment of the GH–IGF‐1 axis must be performed in young adults with childhood‐onset GH deficiency (GHD), after attainment of final height, to select those who are candidates for replacement therapy as adults. To our knowledge there are no data available on retesting the GH–IGF‐1 axis in adult thalassaemic patients with childhood‐onset GHD. The aim of our study was to investigate GH secretion in adult thalassaemic patients with childhood‐onset GHD.

Growth hormone - insulin-like growth factor-I axis and bone mineral density in adults with thalassemia major.

Introduction: Bone disease and short stature are frequent clinical features of patients with beta-thalassaemia major. Dysfunction of the GH-IGF-1 axis has been described in many thalassemics children and adolescents with short stature and reduced growth velocity. Assessment of the GH-IGF-1 axis in short adults with TM after attainment of final height may be required to select those who are candidates for replacement therapy and to prevent the development of bone disease. The aim of our study was to investigate GH secretion in adult thalassemic patients in relation to their bone mineral density (BMD) and serum ferritin concentrations. Materials and Methods: We performed clonidine stimulation test in 30 thalassemic patients (18 males, 12 females) with a mean age of 31.5± 7.2 years. The cut-off level for GH response was set at 7ug/l, according to the literature. Serum ferritin, IGF-I, liver enzymes, alkaline phosphatase (ALP) and type 1 Collagen Carboxy Telopeptide (CCT1) were also determined. Results: We diagnosed GH deficiency (GHD) in 12 patients (40%) and IGF-I deficiency (IGF-I SDS <-2) was diagnosed in 20 patients (67%). Adult patients with TM had significantly decreased IGF-I concentrations and bone mineral density (BMD) at the femur neck and lumbar spine compared to normal controls. Thalassemic patients with GHD and IGF-I deficiency had significantly lower BMD T score at the lumbar spine compared to patients with normal GH and IGF-I levels. Thalassemic patients had higher serum CCT1 concentrations compared to normal controls. Peak GH levels were correlated significantly with IGF- I concentrations and IGF-I levels were correlated significantly with the height SDS (HtSDS) of thalassemic patients. Neither GH peak nor IGF-I concentrations were correlated to serum ferritin concentrations. Conclusions: We conclude that GH status should be tested in adult thalassemic patients especially those with short stature and/or decreased BMD. Clonidine test appears to be effective and safe in adults with TM. If the diagnosis of adult GHD is established, GH treatment may be considered for possible improvement of bone mineral density and heart function in patients with TM.

No Difference in Pubertal Growth and Final Height between Treated Hypogonadal and Non-Hypogonadal Thalassemic Patients

Background: Many factors can negatively affect growth in thalassemic patients, and hypogonadism has been considered as the main factor responsible for their pubertal growth failure. Objective: To evaluate the influence of hypogonadism and its treatment on pubertal growth and final height in thalassemic patients. Methods: We compared the growth of 28 hypogonadal thalassemic patients in whom puberty was induced to that of 25 patients in whom puberty occurred spontaneously. Results: In both groups of patients we observed reduced peak height velocity (induced puberty: females 4.9 ± 2.1, males 6.0 ± 1.8 cm/year; spontaneous puberty: females 6.1 ± 1.5, males 7.3 ± 2.1 cm/year) and pubertal height gain (induced puberty: females 11.3 ± 4.0, males 18.0 ± 4.5 cm/year; spontaneous puberty: females 15.8 ± 2.7, males 18.1 ± 5.3 cm/year) and a short final height (induced puberty: females –1.8 ± 0.7, males –2.1 ± 1.0 SDS; spontaneous puberty: females –2.3 ± 1.0, males –1.9 ± 1.0 SDS). Conclusions: Poor pubertal growth is present in thalassemic patients regardless of hypogonadism. Other factors are responsible for the reduced growth spurt and the final short stature observed in these patients.