Chiara Gertosio

Hereditary multiple exostoses and solitary osteochondroma associated with growth hormone deficiency: to treat or not to treat?

BackgroundOsteochondroma generally occurs as a single lesion and it is not a heritable disease. When two or more osteochondroma are present, this condition represents a genetic disorder named hereditary multiple exostoses (HME). Growth hormone deficiency (GHD) has rarely been found in HME patients and a few data about growth therapy (GH) therapy effects in development/growth of solitary or multiple exostoses have been reported.Case presentationWe describe the clinical features of 2 patients (one with osteochondroma and one with HME) evaluated before and after GH therapy. In the first patient, the single osteochondroma was noticed after the start of treatment; the other patient showed no evidence of significant increase in size or number of lesions related to GH therapy.ConclusionIt is necessary to investigate GH secretion in patients with osteochondroma or HME and short stature because they could benefit from GH replacement therapy. Moreover, careful clinical and imaging follow-up of exostoses is mandatory.

Is retesting in growth hormone deficient children really useful

BACKGROUND Patients with childhood-onset GH deficiency (GHD) are usually retested after achievement of near final height, to verify whether they need to continue GH treatment. We investigated if GH stimulation test is necessary to confirm a persistent status of GHD or if other parameters could be a reliable predictor of GHD persistence. METHODS One-hundred and sixty-four children with idiopathic GHD (55 females and 109 males) were retested when they reached near final height using GH releasing hormone (GHRH)+arginine test or arginine alone. RESULTS At diagnosis, 23.8% of patients showed severe GHD (GH peak at diagnosis <5 ng/mL) and 76.2% showed partial GHD (GH peak <10 ng/mL). At time of retesting, 82.1% of severe GHD and 82.4% of partial GHD patients showed transient GHD. IGF-I levels were not different between persistent (0.18±1.18 SDS) and transient GHD subjects (0.17±0.82 SDS). Furthermore, among persistent severe GHD patients only two showed very reduced levels of IGF-I (<-2.0 SDS). CONCLUSIONS The majority of patients idiopathic GHD proved to be transient. IGF-I levels alone do not discriminate subjects with persistent from those with transient GHD. Therefore, after the end of GH substitutive treatment, a re-evaluation of GH secretion is mandatory to verify the persistence of GHD in adulthood.

Central Precocious Puberty and Granulosa Cell Ovarian Tumor in An 8-Year Old Female

Ovarian tumors associated with hormonal changes of the peripheral iso-sexual precocious puberty are of common presentation. We describe here a rare case of juvenile granulosa cell tumor in a female with central precocious puberty (CPP). An 8-year old girl with CPP presented with vaginal bleeding four months after the diagnosis and before starting treatment with gonadotropin-releasing hormone (GnRH)-analogs. Suppression of basal follicle-stimulating hormone (FSH) level, elevation of serum estradiol, progesterone and Cancer Antigen-125 were documented. Abdominal ultrasound examination (US) and magnetic resonance imaging showed a pelvic mass affecting the left ovary. A left salpingo-oophorectomy was performed and the mass was totally resected. Juvenile granulosa cell ovarian tumor was diagnosed. One month post surgery, estradiol and progesterone decreased to values of the first evaluation and FSH increased; Cancer Antigen-125 resulted normal while ultrasound pelvic examination showed absence of pelvic masses. In our patient, the tumor had grown very quickly since hormonal data demonstrated a CPP without any evidence of ovarian mass on US only four months before diagnosis. The overstimulation of the FSH or aberrant activation of FSH receptors may have contributed to the development of the mass.

Tall stature: a difficult diagnosis?

Referral for an assessment of tall stature is less common than for short stature. Tall stature is defined as a height more than two standard deviations above the mean for age. The majority of subjects with tall stature show a familial tall stature or a constitutional advance of growth (CAG), which is a diagnosis of exclusion. After a careful physical evaluation, tall subjects may be divided into two groups: tall subjects with normal appearance and tall subjects with abnormal appearance. In the case of normal appearance, the paediatric endocrinologist will have to evaluate the growth rate. If it is normal for age and sex, the subject may be classified as having familial tall stature, CAG or obese subject, while if the growth rate is increased it is essential to evaluate pubertal status and thyroid status. Tall subjects with abnormal appearance and dysmorphisms can be classified into those with proportionate and disproportionate syndromes.A careful physical examination and an evaluation of growth pattern are required before starting further investigations. Physicians should always search for a pathological cause of tall stature, although the majority of children are healthy and they generally do not need treatment to cease growth progression.The most accepted and effective treatment for an excessive height prediction is inducing puberty early and leading to a complete fusion of the epiphyses and achievement of final height, using testosterone in males and oestrogens in females. Alternatively, the most common surgical procedure for reducing growth is bilateral percutaneous epiphysiodesis of the distal femur and proximal tibia and fibula.This review aims to provide up-to-date information and suggestions about the diagnosis and management of children with tall stature.

Celiac disease and short stature in children

Celiac disease (CD) is a genetically determined gluten-sensitive enteropathy resulting in nutrient malabsorption, with an increasing incidence worldwide. In CD children, short stature may be the only presenting clinical feature, even in the absence of gastrointestinal symptoms. Generally, a gluten-free diet (GFD) leads to rapid catch-up growth within 1–2 years. The pathogenesis of CD-associated short stature is still unclear. Besides the involvement of the growth hormone (GH)/IGF-I axis, other pathogenetic mechanisms may include autoimmune disorders of the pituitary gland and altered ghrelin secretion. Furthermore, some CD patients do not show catch-up growth during a GFD, despite reversion to seronegativity for CD markers. These subjects may have GH deficiency and could benefit from GH therapy. This review deals with the problem of linear growth in CD children and points to the importance of the evaluation of GH secretion in those children who show no catch-up growth after the introduction of a GFD.

Attività fisica adattata: possibili benefici in bambini e adolescenti obesi

L’obesita infantile e una condizione patologica in continua crescita responsabile di gravi ripercussioni sulla salute degli affetti e in grado di determinare ingenti costi sanitari diretti e indiretti. La prevenzione e il trattamento dell’eccesso ponderale si basano primariamente su una dieta bilanciata e su una costante attivita fisica; i soggetti obesi tuttavia lamentano spesso difficolta fisiche e psichiche a partecipare ai corsi sportivi offerti alla popolazione generale. Il nostro studio ha proposto un programma di attivita controllato di 12 settimane a carattere ricreativo, adattato alle capacita funzionali dei soggetti obesi e basato su una strategia multistep. Un programma di attivita di questo tipo si e dimostrato efficace nel migliorare i parametri metabolici e funzionali dei partecipanti, favorendo la partecipazione all’esercizio e riducendo gli iniziali abbandoni.

Failure to thrive as presentation in a patient with 22q11.2 microdeletion.

BackgroundAbnormalities of chromosome 22q11, including deletions and translocations, have been described in association with different birth defects and malformations occurring in many combinations and degrees of severity.Case presentationWe describe the case of an 8 month-old infant with no dysmorphic signs who showed progressive postnatal growth failure and no chronic systemic diseases. We found a 22q11.2 microdeletion, inherited from the mother, suggesting the diagnosis of DiGeorge syndrome. The patient had an isolated growth hormone (GH) deficiency and a significant increase in linear growth during the first and the second year of GH therapy, and a recovery of weight was shown.ConclusionsSometimes, in infants with growth failure a genetic analysis is strongly suggested, since chromosomal abnormalities may be present.

Espressione del recettore dell’ormone della crescita nelle malattie infiammatorie croniche

L’artrite idiopatica giovanile (AIG) e una malattia infiammatoria cronica dell’eta pediatrica che colpisce le articolazioni, caratterizzata da alti livelli circolanti di citochine infiammatorie. Poiche un ritardo di crescita e stato riscontrato in bambini affetti da tale patologia, sono stati valutati i fattori implicati in tale ritardo di crescita, analizzando i valori di alcune molecole coinvolte nell’asse GH/IGF, quali l’IGF-I, la GHBP e l’espressione genica del GHR sia al momento della diagnosi che due anni dopo l’inizio del trattamento della malattia. Sono stati quindi arruolati diciotto pazienti (12 maschi e 6 femmine) prepuberi che soddisfacevano i criteri diagnostici per la JIA. In tutti i soggetti sono stati inoltre valutati gli indici infiammatori (VES e PCR) e i valori sierici di IL-6. I risultati ottenuti mostrano come al secondo anno di follow up, l’altezza media e risultata essere aumentata anche se non significativamente, mentre risultavano ridotti gli indici infiammatori e i valori di IL-6. Il dato tuttavia piu interessante e stato l’aumento significativo dell’espressione dell’mRNA del GHR in tutti i pazienti al follow-up rispetto al valore basale e l’aumento significativo della media dei valori di IGF-I confrontata con i livelli all’esordio di malattia. I valori sierici di IGF-I e l’espressione genica del GHR monitorati durante il corso della terapia correlano quindi con il quadro clinico, suggerendo una stretta correlazione tra fattori di crescita e processo infiammatorio.

Studio sulla prevalenza della sindrome metabolica nella sindrome di Turner

La sindrome di Turner (ST) e una condizione clinica causata dalla completa o parziale assenza di un cromosoma X, che interessa 1/2500-3000 neonate femmine. Essa e caratterizzata, in piu del 90% dei casi, da bassa statura e disgenesia gonadica, oltre che da diverse malformazioni e anomalie a carico di vari organi e apparati. Le pazienti con questa sindrome presentano, rispetto alla popolazione generale, un incremento del rischio di sviluppare diabete mellito, malattie cardiache ischemiche, aterosclerosi e ipertensione e risultano particolarmente predisposte al sovrappeso e all’obesita. La sindrome metabolica (SM) e invece una condizione patologica che si caratterizza per l’associazione tra aumento dell’adiposita viscerale, anomalie del metabolismo dei carboidrati, ipertensione e dislipidemia. La sindrome metabolica rappresenta inoltre un fattore di rischio per patologie cardiovascolari e diabete mellito di tipo 2. Lo scopo del nostro studio e stato quello di determinare la prevalenza della sindrome metabolica nella sindrome di Turner e di valutare la relazione tra SM e composizione corporea, adiposita viscerale e caratteristiche cliniche nelle pazienti con sindrome di Turner analizzate.

Sviluppo puberale precoce in una paziente con deficit ipofisari multipli e displasia setto-ottica

La displasia setto ottica (SOD) e una rara condizione clinica caratterizzata dall’ipoplasia dei nervi ottici, da difetti di sviluppo della linea mediana (agenesia del setto pellucido e/o alterazioni del corpo calloso) e da deficit di secrezione degli ormoni ipofisari. Numerosi sono i difetti endocrini associati a questa patologia e sono legati ad una disfunzione a livello ipotalamico. Le alterazioni ormonali non necessariamente devono essere presenti alla nascita ma possono svilupparsi successivamente. Descriviamo un caso clinico di puberta precoce in una paziente affetta da SOD, nella quale erano gia stati diagnosticati deficit della funzione tiroidea, corticosurrenalica, deficit di ormone della crescita e diabete insipido.