A Novel De novo Heterozygous Mutation in the SON Gene Associated with Septo-optic Dysplasia: A New Phenotype.

Septo-optic dysplasia (SOD) syndrome is a rare congenital disorder characterized by a classic triad of optic nerve/chiasm hypoplasia, agenesis of septum pellucidum and corpus callosum, and hypoplasia of the hypothalamic-pituitary axis.Herein, we report the clinical case of 2-year-old boy presenting with psychomotor delay, nystagmus, congenital hypothyroidism, and a clinically relevant growth delay. The neuroradiological examination showed partial segmental agenesis of the corpus callosum, agenesis of the septum pellucidum, optic nerve hypoplasia, and a small pituitary gland with a small median pituitary stalk. A whole-exome sequencing analysis detected a novel heterozygous de novo variant c.1069_1070delAG in SON, predicted as likely pathogenic.To date, SON pathogenic variants have been described as responsible for Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, a multisystemic neurodevelopmental disorder mainly characterized by intellectual disability, facial dysmorphisms, visual abnormalities, brain malformations, feeding difficulties, and growth delay. The herein described case is the first recognized clinic-radiological occurrence of SOD syndrome with hypothalamic-pituitary dysfunction in a patient carrying a SON gene variant, considered responsible of ZTTK syndrome, suggesting a possible relationship between SOD and SON gene alterations, never described so far, making the search for SON gene mutations advisable in patients with SOD.

Implications of deferred diagnosis of paediatric intracranial germ cell tumours.

AIMS: This study analysed the clinical features of a cohort of children with intracranial germ cell tumours (IC-GCTs). We retrospectively reviewed timelag between symptoms onset, clinic-radiological findings, diagnosis and outcomes. METHODS: Symptoms at diagnosis were divided into four groups: (1) raised intracranial pressure (RICP); (2) visual impairment; (3) endocrinopathies; (4) other. Total diagnostic interval (TDI), defined as the interval between symptom onset (including retrospective recall of symptoms) and definitive diagnosis of IC-GCT, was calculated and compared to survival rates. RESULTS: Our cohort included 55 children with median follow-up of 78.9 months (0.5-249.9). The majority (63.6%) had germinomas and 10.9% were metastatic at diagnosis. IC-GCTs were suprasellar (41.8%), pineal (36.4%), bifocal (12.7%) or in atypical sites (9.1%). The most common presenting symptoms were related to RICP (43.6%); however, by the time of tumour diagnosis, 50.9% of patients had developed endocrine dysfunctions. All pineal GCTs manifested with RICP or visual impairment. All suprasellar GCTs presented with endocrinopathies. TDI ranged between 0.25 and 58.5 months (median 4 months). Pineal GCTs had the shortest TDI (median TDI 1 month versus 24 months in suprasellar GCTs, p < .001). TDI > 6 months was observed in 47.3% of patients and was significantly associated with endocrine presenting symptoms. No statistically significant difference was found in progression-free survival and overall survival between patients with TDI > 6 months and with TDI ≤ 6 months. CONCLUSION: Approximately half of the IC-GCT patients in this cohort had TDI > 6 months. These presented mostly with endocrine deficits. TDI > 6 months was not associated with increased relapse or mortality rates.

Expert Opinion on the Management of Growth Hormone Deficiency in Brain Tumor Survivors: Results From an Italian Survey.

Background: Growth hormone deficiency (GHD) is the first and most common endocrine complication in pediatric brain tumor survivors (BTS). GHD can occur due to the presence of the tumor itself, surgery, or cranial radiotherapy (CRT). Aims: This study aimed to evaluate management and adherence to current guidelines of the Italian centers engaged in the diagnosis and follow-up of GHD patients with BTS. Methods: A multidisciplinary scientific board of pediatric endocrinologists, oncologists and radiologists with neuroimaging expertise discussed and reviewed the main issues relating to the management of GHD in pediatric BTS and developed a survey. The survey included questions relating to organizational aspects, risk factors, diagnosis, definition of stable disease, and treatment. The online survey was sent to an expanded panel of specialists dedicated to the care of pediatric BTS, distributed among the three specialty areas and throughout the country (23 Italian cities and 37 Centers). Results: The online questionnaire was completed by 86.5% (32 out of 37) of the Centers involved. Most had experience in treating these patients, reporting that they follow more than 50 BTS patients per year. Responses were analyzed descriptively and aggregated by physician specialty. Overall, the results of the survey showed some important controversies in real life adherence to the current guidelines, with discrepancies between endocrinologists and oncologists in the definition of risk factors, diagnostic work-up, decision-making processes and safety. Furthermore, there was no agreement on the neuroimaging definition of stable oncological disease and how to manage growth hormone therapy in patients with residual tumor and GHD. Conclusions: The results of the first Italian national survey on the management of GHD in BTS highlighted the difference in management on some important issues. The time to start and stop rhGH treatment represent areas of major uncertainty. The definition of stable disease remains critical and represents a gap in knowledge that must be addressed within the international guidelines in order to increase height and to improve metabolic and quality of life outcomes in cancer survivors with GHD.

Endocrine manifestations of paediatric intracranial germ cell tumours: from diagnosis to long-term follow-up.

PURPOSE: We examined endocrine manifestations in a cohort of paediatric patients with IC-GCTs at diagnosis and during follow-up, integrating clinical, radiological, histopathological and laboratory data. METHODS: Diabetes insipidus (DI), growth hormone deficiency (GHD), hypothyroidism, adrenal insufficiency, precocious puberty (PP)/hypogonadism were diagnosed clinically and biochemically. The prevalence of endocrine manifestations was compared to survival rates. RESULTS: Our population included 55 children (37 males, 18 females) diagnosed with IC-GCT with a median follow-up of 78.9 months from diagnosis (range 0.5-249.9). At tumour diagnosis, 50.9% patients displayed endocrinopathies: among them, 85.7% were affected by DI, 57.1% central adrenal insufficiency, 50% central hypothyroidism, 28.5% GHD, 10.7% hypogonadotrophic hypogonadism, 10.7% PP. These patients presented predominantly with suprasellar germinoma. If not diagnosed previously, endocrine disorders arose 15.15 months (1.3-404.2) after end of treatment (EOT) in 16.4% patients. At least one endocrinopathy was identified in 67.3% of subjects at last follow-up visit, especially GHD and adrenal insufficiency. DI, hypothyroidism, and adrenal insufficiency occurred earlier than other abnormalities and frequently preceded tumour diagnosis. Subjects with and without endocrine manifestations who survived beyond 12 months after EOT did not show significant difference in overall survival and progression-free survival (p = 0.28 and p = 0.88, respectively). CONCLUSION: Endocrinopathies were common presenting symptoms in our population. If present at diagnosis, they often persisted hence after. The spectrum of endocrinopathies expanded during follow-up up to 33.7 years after EOT. Although they did not seem to affect survival rate in our cohort, close lifelong surveillance is mandatory to provide the best care for these patients.

The clinical characteristics, biochemical parameters and insulin response to oral glucose tolerance test (OGTT) in 25 transfusion dependent ß-thalassemia (TDT) patients recently diagnosed with diabetes mellitus (DM).

BACKGROUND: Patients with transfusion dependent ß-thalassemia (TDT) are at high risk for developing, over the time, a form of diabetes distinct from type 1 and type 2 diabetes, but with similarities to both. AIMS OF STUDY: The aim of this study is to describe the clinical and laboratory data, and the insulin secretion and sensitivity, in TDT patients , recently diagnosed with diabetes mellitus (DM). MATERIALS AND METHODS: The medical records of 25 TDT patients with DM, diagnosed by standardized oral glucose tolerance test (OGTT) and insulin secretion, were analysed; data were compared to TDT patients without diabetes and to a group of healthy subjects. Natural history of glucometabolic status before the diagnosis of DM was also reviewed. RESULTS: On average, the TDT patients with DM were younger compared to TDT patients without diabetes. The mean age at diagnosis of  DM in female and male TDT patients was 24.0 ± 7.1 years and 31.9 ± 5.6 years, respectively (P: 0.007). Serum alanine aminotransferase values, basal insulin levels and prevalence of hypogonadism were consistently higher in TDT patients with DM compared to those without diabetes. Decreased insulin secretion and increased insulin resistance was observed in patients with DM. CONCLUSION: The natural history of glucometabolic status in TDT patients is characterized by a deterioration of glucose tolerance over time. Iron overload and liver dysfuction are the main factors responsible for glucose disturbances (GD) in TDT patients. The therapeutic approach must be individualized and followed by a multidisciplinary team.

Management of Childhood-onset Craniopharyngioma in Italy: A Multicenter, 7-Year Follow-up Study of 145 Patients.

CONTEXT: Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy. OBJECTIVE: This work aimed to identify patients' characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits, and number of patients starting growth hormone (GH) treatment. METHODS: A retrospective multicenter collection took place of 145 patients aged 0 to 18 years who underwent surgery for CP between 2000 and 2018, and followed up in 17 Italian centers of pediatric endocrinology. RESULTS: Age at diagnosis was 8.4 ± 4.1 years. Duration of symptoms was 10.8 ± 12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%), and histology was adamantinomatous in all cases but two. Surgical approach was transcranial (TC) in 67.5% of cases and transsphenoidal (TS) in 31.%. The TC approach was prevalent in all age groups. Postsurgery complications occurred in 53% of cases, with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented with at least one hormone pituitary deficiency, with thyrotropin deficiency most frequent (98.3%), followed by adrenocorticotropin (96.8%), arginine vasopressin (91.1%), and GH (77.4%). Body mass index (BMI) significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years, and 54 developed a recurrence or regrowth of the residual lesion. CONCLUSION: CP is often diagnosed late in Italy, with TC more frequent than the TS surgical approach. Postsurgery complications were not rare, and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime.

A study of isolated hyperglycemia (blood glucose ≥155 mg/dL) at 1-hour of oral glucose tolerance test (OGTT) in patients with ß-transfusion dependent thalassemia (ß-TDT) followed for 12 years.

OBJECTIVE: Subjects with normal glucose tolerance (NGT) but 1-hour post-load plasma glucose (1-h OGTT) ≥ 155 mg/dl (8.6 mmol/L; H-NGT) have an increased risk for developing Type 2 diabetes mellitus (T2DM), determining a new risk factor category with deeper metabolic impairment. The aim of this study was to evaluate the H-NGT as a diagnostic predictor of future dysglycemia in ß-transfusion dependent thalassemia (ß-TDT). Indices of insulin secretion and insulin sensitivity derived at baseline from OGTTs, were also reviewed. STUDY DESIGN AND METHODS: OGTT and indices of insulin secretion and insulin sensitivity, derived at baseline during OGTT, in 17 ß-TDT with H-NGT and 29 ß-TDT with normal OGTT (NGT) and without H-NGT followed for 12 years were studied. RESULTS: H-NGT was associated with decreased insulin sensitivity and progressive deterioration of glucose tolerance. At baseline, serum ferritin and serum alanine aminotransferase (ALT) levels were higher in patients with H-NGT compared to patients with NGT. A strong correlation was observed between ALT and 1-hour plasma glucose value during OGTT in the total group of 36 patients . Compliance to iron chelation therapy was poor in ß-TDT patients with H-NGT. An inverse correlation was found between 1-hour plasma glucose value during OGTT and insulin secretion-sensitivity index-2 (ISSI-2) (r: -0.3298; p: 0.025), between ISSI-2 and ALT (r: -0.3262; p: 0.027), and between 1-hour plasma glucose value and ISSI-2 (r: -0.537; p: 0.005) in the whole group of ß-TDT patients enrolled in our study. CONCLUSIONS: This retrospective study displayed that finding an isolated high 1-hour post-load glucose level (≥155 mg/dL; H-NGT) during the OGTT may serve as a simple biomarker to detect high-risk patients, with chronic liver disease and/or iron overload, who need periodic glycemic surveillance. Measuring the ISSI 2 represented another valuable predictive marker in the assessment of glycemia in these patients.

Polycystic ovary syndrome in pediatric obesity and diabetes.

Polycystic ovary syndrome is characterized by anovulation (amenorrhea, oligomenorrhea, irregular menstrual cycles) combined with symptoms of androgen excess (hirsutism, acne, alopecia). The clear definition and diagnosis in adolescents could be challenging considering that most of symptoms occur as part of the expected physiological hormonal imbalance of puberty. Therefore, different diagnostic criteria have been elaborated. Polycystic ovary syndrome could be associated to obesity, diabetes mellitus, and metabolic syndrome. In adolescents with polycystic ovary syndrome, adiposity is associated with higher androgen concentrations and greater menstrual irregularity. Polycystic ovary syndrome in youth is considered a risk factor for type 2 diabetes mellitus in adulthood. On the other hand, increased prevalence of polycystic ovary syndrome has been shown in type 1 diabetes mellitus. The treatment of polycystic ovary syndrome in adolescents is controversial considering that adequate trials are lacking. First-line treatment comprises lifestyle modification (preferably multicomponent including diet, exercise and behavioral strategies) that should be recommended overall in the patients with polycystic ovary syndrome and overweight, central obesity and insulin resistance. Beyond non-pharmacological therapy, pharmacological agents include combined hormonal contraceptives, metformin and anti-androgens, used separately or in combination. The aim of therapy is to bring back ovulation, to normalize menses, to reduce hirsutism and acne, to reduce weight. Other important goal is the treatment of hyperlipidemia and of hyperglycemia. This narrative review aimed to review the most pertinent literature about polycystic ovary syndrome in adolescents with obesity or diabetes. We overviewed the diagnostic criteria, the pathophysiology and the possible treatment approaches.

Inhaled corticosteroids use in childhood respiratory diseases: an italian survey on pediatricians' prescription habits.

BACKGROUND: A national consensus document on inhaled corticosteroids (ICS) use in childhood, produced by the main Italian pediatric scientific societies, has been recently released. The aim of this study was to gather information on the current pediatricians' ICS prescription habits in Italy for the management of the most common pediatric respiratory diseases, namely allergic rhinitis (AR), asthma, preschool wheezing and laryngitis. METHODS: From the 1st October 2018 to the 31st January 2019 a link to an online questionnaire was sent monthly through a newsletter to the members of the Italian Society of Pediatrics. The questionnaire included 18 items on ICS use in the most common pediatric respiratory diseases. Data collection and reporting was based on STROBE Statement Checklist for cross-sectional studies. RESULTS: One thousand-two questionnaires were returned from primary care pediatricians (39.1%), hospital pediatricians (38.7%), private practicers (16.4%), university pediatricians (3.1%) and Pediatrics residents (2.7%). We found a good adherence to the international guidelines on AR, with prevalent use of oral antihistamine (60.6%) in the secretive phenotype and nasal ICS in the obstructive phenotype (64.8%). In asthma exacerbations ICS are not used in 53.4% of cases, but they are used at high dose in 27.9% and at low dose in 18.7% of cases. In intermittent asthma, ICS are not chosen as a daily controller therapy in 54.1% of cases, while they are chosen as a low dose daily therapy in 44.5% of cases (high dose in 1.4%). In children with persistent asthma, ICS are chosen as a daily low dose therapy in 67.4% of cases and as a daily high dose therapy in 31%. In the management of preschool wheezing, when a long-term treatment is needed, ICS are chosen both alone and in association with antileukotrienes in 71.4% of cases. Children affected by recurrent asthma exacerbations and wheezing are closely followed up, in particular by their primary care pediatricians. The preference for certain molecules in the treatment of different respiratory diseases also emerged. CONCLUSIONS: Pediatricians' ICS prescription habits in Italy should be improved, especially in the management of asthma. Future surveys on a more numerous sample will be useful to analyze differences in prescription habits on the basis of pediatricians' work settings and geographical distribution.

Point of view of the Italians pediatric scientific societies about the pediatric care during the COVID-19 lockdown: what has changed and future prospects for restarting.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to have a milder disease course and better prognosis than adults. However, SARS-Cov-2 pandemic has indirectly caused problems in pediatric medical assistance. In view of this we wanted to draw a picture of what happened during health emergency and analyze future prospects for restarting. METHODS: We involved the Italian pediatric scientific societies institutionally collected in the Italian Federation of Associations and Scientific Societies of the Pediatric Area (FIARPED); We sent a questionnaire to all scientific societies about the pediatric care activity during the COVID-19 emergency and future perspectives for the phase of post-containment. RESULTS: The analysis of the questionnaires showed significant decrease of:admission, outpatient visits and specialist consultancy activities during the COVID-19 emergency, primarily linked to the fear of infection. Instead it was increased the serious degree of diseases admitted. Most of scientific societies maintained the relationship with chronic patients through some form of telemedicine, reporting a strong positive opinion about this modality. Finally showed the need to give life a new approach for hospitalizations and outpatient visits through a greater use of telemedicine, educational programs on families and a more decisive role of family pediatricians. CONCLUSIONS: Our study highlighted many aspects that can be improved in pediatric care. We think that It will be necessary a new shared strategy to improve the management and continuity of care for pediatric patients, primarily developing a network of collaboration between families, family pediatrician and hospitals and by enhancing the use of new methods of telecommunications.

Growth hormone therapy in children: predictive factors and short-term and long-term response criteria.

PURPOSE: The definition of growth response in growth hormone (GH)-treated children is controversial. This study aims at: (1) evaluating short-term and long-term efficacy of GH treatment in a cohort of short children with GH deficiency (GHD); (2) assessing and compare various poor response criteria; (3) identifying predictive factors of growth response. METHODS: Our study included 94 children, affected by isolated GHD and treated with GH until they reached final height. Criteria used for calculating the proportion of poor responders to GH for the first year were gain in height (ΔHt) SDS < 0.5 ("Bang criterion"), <0.3 or <0.4 SDS for less-severe and severe GHD, respectively ("Ranke criterion"), height velocity (HV) < mean -1 SDS ("Bakker criterion"); for adult height "Cianfarani criterion" was total ΔHt < 1 SDS. RESULTS: After 1 year of treatment we defined "poor responders" 55.3% of patients according to Bang criterion, 40.9% according to Bakker criterion and 23.4% according to Ranke criterion. At the end of the treatment, poor responders according to Cianfarani criterion were 22.34%; almost everyone in our population (97.9%) achieved mMid-parental height (MPH). Median final Ht was -1.11 SDS. Our analysis revealed a significant negative association between ΔHt and age at diagnosis. CONCLUSIONS: Bang criterion generated the highest number of poor responders, but had a low negative predictive value (67.5%); Ranke and Cianfarani criteria displayed similar rate of poor response. There is no reliable predictive factor of growth hormone response. However, almost all children treated reached MPH, suggesting good treatment efficacy.

Review of the Literature on Current Changes in the Timing of Pubertal Development and the Incomplete Forms of Early Puberty.

Puberty is a sensitive period of life characterized by the appearance of secondary sex characteristics which leads to a complete sexual maturation. It physiologically starts between the age of 8 and 13 years in girls and 9 and 14 years in boys. In the last two decades, several studies have showed that start of puberty has moved up to younger ages by 12-18 months, and some of the hypotheses trying to explain this change include the role of nutritional status and obesity and the influence of extrinsic factors such as exposure to endocrine-disrupting chemicals (EDCs), as well. The hypothalamic-hypophysis-gonadal axis develops during embryogenesis, and except for a period of activation immediately after birth, remains suppressed until the onset of pubertal development. At the beginning of puberty, the pulse generator is reactivated, probably due to progressive stimulatory influences on GnRH neurons from glial signals and neurotrasmitters. Kisspeptin and its receptor play a fundamental role in this phase. Premature Pubarche/Adrenarche, Premature Thelarche, and Premature Menarche are incomplete forms of precocious pubertal development that have their origin in endocrine mechanisms that only recently have started to be understood. It is important to distinguish these forms from the complete ones in order to reassure patients and parents about the non-evolution of pubertal progression and avoid non-useful treatments with analogous LHRH.

Combined therapy with insulin and growth hormone in 17 patients with type-1 diabetes and growth disorders.

BACKGROUND/AIM: Combined growth hormone (GH) and insulin therapy is rarely prescribed by pediatric endocrinologists. We investigated the attitude of Italian physicians to prescribing that therapy in the case of short stature and type-1 diabetes (T1DM). METHODS: A questionnaire was sent and if a patient was identified, data on growth and diabetes management were collected. RESULTS: Data from 42 centers (84%) were obtained. Of these, 29 centers reported that the use of combined therapy was usually avoided. A total of 17 patients were treated in 13 centers (GH was started before T1DM onset in 9 patients and after the onset of T1DM in 8). Height SDS patterns during GH therapy in the 11 patients affected by GH deficiency ranged from -0.3 to +3.1 SDS. In the 8 diabetic patients in whom GH was added subsequently, mean insulin dose increased during the first 6 months of therapy from 0.7 ± 0.2 to 1.0 ± 0.2 U/kg (p = 0.004). HbA1c was unchanged during the first 6 months of combined therapy. CONCLUSIONS: Most Italian physicians do not consider prescribing the combined GH-insulin therapy in diabetic children with growth problems. However, the results of the 17 patients identified would confirm that the combined therapy was feasible and only caused mild insulin resistance. GH therapy was effective in promoting growth in most patients and did not affect diabetes metabolic control.

Suprasellar granular cell tumor of the neurohypophysis in a child: unusual presentation in pediatric age of a rare tumor.

PURPOSE: Granular cell tumors (GCT) of the neurohypophysis are rare, solitary, nodular-shaped lesions, mostly presenting in the adult age with a female predilection. They rarely grow to a sufficient size to cause mass effect related symptoms and they may be found in most cases incidentally at autopsy of older patients. Few cases of symptomatic GCT of the neurohypophysis have been reported in the literature and only one of these in a pediatric patient in the first decade of life, who presented with central precocious puberty. METHODS: We report the case of a 11-year-old boy with a large suprasellar GCT of the neurohypophysis, complaining severe headache and pituitary insufficiency. Before our referral, the child was operated at another insitution through a pterional approach for tumor biopsy and underwent chemotherapy because of the misleading diagnosis of glioma. RESULTS: The patient was operated on by a fronto-orbito-zygomatic approach with subtotal tumor resection. At last follow-up examination, a partial hypopituitarism was detected. The quality of life with replacement therapy was excellent. Fractionated radiotherapy on tumor remnant was advised. CONCLUSIONS: The reported case is exceptional because the tumor developed in a male pediatric patient, causing clinical symptoms related to intracranial hypertension and unusual endocrinological features. GCT has to be considered in the differential diagnosis of suprasellar masses, to avoid misleading interpretation and consequent wrong therapeutic management.

Neurosurgical treatment of craniopharyngioma in adults and children: early and long-term results in a large case series.

OBJECT: Craniopharyngioma accounts for 2%-5% of all primary intracranial neoplasms. The optimal management of craniopharyngioma remains controversial. The authors evaluated the early results of surgery and the longterm risk of tumor recurrence in a large series of patients undergoing resection of craniopharyngiomas. METHODS: Between 1990 and 2008, 112 consecutive patients (57 male and 55 female patients with a mean [± SEM] age of 33.3 ± 1.8 years) underwent resection of craniopharyngiomas at the authors' hospital. Recurrence or growth of residual tumor tissue during follow-up was assessed using MR imaging. RESULTS: There were 3 perioperative deaths (2.7%). Severe adverse events were more frequent in patients who underwent operations via the transcranial route (37%) than the transsphenoidal approach (5.6%; p < 0.001). Magnetic resonance imaging showed radical resection of the tumor in 78 (71.6%) of the remaining 109 patients. Previous surgery and maximum tumor diameter were associated with persistence of disease after surgery. Craniopharyngioma recurred in 26 (24.5%) of 106 patients. Presence of residual tumor on the first postoperative MR imaging, male sex, and no postoperative radiation therapy were associated with a risk of tumor recurrence. Quality-of-life data were assessed in the 91 patients who attended the authors' institution for follow-up visits. Among them, 8.8% patients were partially or completely dependent on others for daily living activities before surgery. This percentage increased to 14.3% at the last follow-up visit. The 5- and 10-year overall survival rates were 94.4% (95% CI 90.0%-98.8%) and 90.3% (95% CI 83.4%-97.3%), respectively. CONCLUSIONS: Complete surgical removal of craniopharyngioma can be achieved with reasonable safety in more than 70% of patients. Recurrence of craniopharyngioma may occur even after apparent radical excision. Prompt management of residual or recurring disease by radiotherapy, repeat surgery, or a combination of both is usually successful in controlling further tumor growth.

Bilateral cavo-ilio-femoral thrombosis in an adolescent with transient anti-phospholipid antibodies and factor V heterozygous mutation: a case report.

We report a case of bilateral cavo-ilio-femoral thrombosis in an adolescent with factor V heterozygous mutation and transient antiphospholipid antibodies secondary Varicella infection.The clinical significance of finding transient antiphospholipid antibodies in the sera of infectious disease is unclear. We here report a case of bilateral cavo-ilio-femoral thrombosis in an adolescent with newly diagnosed factor V heterozygous mutation and transient antiphospholipid antibodies secondary to Varicella infection.

Pediatric otorhinolaryngologic manifestations of endocrinological pathologies.

OBJECTIVE: Aim of the present review is to offer a concise but complete discussion about pathologies with pediatric otorhinolaryngological interest recognizing: (i) growth disorders, (ii) chromosomal disorders, and (iii) tumors. METHODS: Pathologies characterized by a growth anomaly have been grouped, underlining the characteristics of otorhinolaryngological interest. Numerous syndromes typical of the pediatric age have been reported and classified according to the ailments of the orofacial district. Tumoral pathologies, for which the otorhinolaryngological operation is fundamental, have been descripted. We reviewed recent literature and older papers. We did not find recent literature regarding otorhinolaryngological features related to some of the pathologies described. RESULTS/CONCLUSIONS: Otorhinolaryngologists should be familiar with pediatric disorders, since many of them have head and neck manifestations. This knowledge allows to treat them with a correct surgical approach, in order to implore children's quality of life.

Adult height in patients with permanent growth hormone deficiency with and without multiple pituitary hormone deficiencies.

CONTEXT: It has been reported that patients with multiple pituitary hormone deficiencies (MPHDs) achieve a greater final height, compared with patients with isolated GH deficiency (IGHD). However, the outcome of patients with permanent GH deficiency (GHD) has not yet been reported. OBJECTIVES: The objectives of the study were to evaluate and compare adult height data and the effect of spontaneous or induced puberty after long-term treatment with GH in young adults with either permanent IGHD or MPHD. DESIGN AND SETTING: This was a retrospective multicenter study conducted in university research hospitals and a tertiary referral endocrine unit. PATIENTS AND METHODS: Thirty-nine patients with IGHD (26 males, 13 females) and 49 with MPHD (31 males, 18 females), diagnosed at a median age of 7.7 and 6.9 yr, respectively, were reevaluated for GH secretion after adult height achievement (median age 17.6 and 19.8 yr). The diagnosis of permanent GHD was based on peak GH levels less than 3 microg/liter after an insulin tolerance test or peak GH levels less than 5 microg/liter after two different tests. Fifteen subjects had idiopathic GHD and seventy-three had magnetic resonance imaging evidence of congenital hypothalamic-pituitary abnormalities. Height sd score (SDS) was analyzed at diagnosis, the onset of puberty (either spontaneous or induced), and the time of GH withdrawal. RESULTS: The subjects with IGHD entered puberty at a median age of 12.6 yr (females) and 13.4 yr (males). Puberty was induced at a median age of 13.5 and 14.0 yr, respectively, in males and females with MPHD. Median height SDS at the beginning of puberty was similar in the IGHD and MPHD subjects. Total pubertal height gain was similar between patients with IGHD or MPHD. Median adult height was also not significantly different between IGHD and MPHD patients (males, 168.5 vs. 170.3 cm; females, 160.0 vs. 157.3 cm). The adult height SDS of the IGHD subjects was positively correlated with height at the time of diagnosis and with total pubertal height gain. Conversely, the adult height SDS of the MPHD subjects was positively correlated with both the duration of GH treatment and height SDS at the time of GHD diagnosis. CONCLUSIONS: Adult height in patients with permanent IGHD and spontaneous puberty is similar to adult height in patients with MPHD and induced puberty.