Influence of Hashimoto thyroiditis on the development of thyroid nodules and cancer in children and adolescents

It is unclear whether patients with Hashimoto thyroiditis (HT) are predisposed to develop thyroid nodules and/or thyroid cancer. The objective of our study was therefore to assess the prevalence of thyroid nodules and/or cancer in patients with HT and to look for possible prognostic factors. A retrospective survey of 904 children/adolescents with HT (709 females, 195 males) regularly followed in nine Italian centers of pediatric endocrinology was performed. Median period of follow-up was 4.5 years (1.2 to 12.8 years). We evaluated free T4, TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibodies, and thyroid ultrasound yearly. One hundred seventy-four nodules were detected, with an annual incidence rate of 3.5%. Ten nodules were malignant (8 papillary and 2 papillary follicular variant), giving a 5.7% prevalence of cancer among patients with nodules. The severity of hypo-echogenity at ultrasound, TPOAb, and free T4 serum concentrations were predictive for the appearance of new nodules. Furthermore, a positive correlation was observed between TPOAb titer and the development of thyroid cancer. In conclusion, HT seems to influence the development of thyroid nodules, but not cancer in children and adolescents

Safety Outcomes During Pediatric GH Therapy : Final Results From the Prospective GeNeSIS Observational Program

Altres ajuts: Financial Support: GeNeSIS was sponsored by Eli Lilly and Company (Indianapolis, IN). In compliance with the Uniform Requirements for Manuscripts, established by the International Committee of Medical Journal Editors, the sponsor of this study did not impose any impediment, directly or indirectly, on the publication of the study's results. Disclosure Summary: C.J.C. and N.J. are employees and stockholders ofEliLilly and Company (Indianapolis, IN).W.F.B. and A.G.Z. are former employees and are stockholders of Lilly. C.L.D., T.H., M.M., and R.G.R. are former members of the GeNeSIS International Advisory Board; S.L., J.P.S., A.R.-U., and M.P. have served as regional advisors. B.P. has consulted for Eli Lilly Italia SpA, and E.C. has received grant support from Lilly. W.F.B. also reports heis aconsultant forAmmonett Pharma,Lilly Germany, and Merck KGaA Darmstadt. C.L.D. also reports receipt of grants, consultancy honoraria, and speaker fees from Lilly,EMD Serono, and Sandoz; grants fromOpko Prolor, Pfizer, and Versatis; honoraria and speaker fees from Roche; honoraria from Pfizer; and speaker fees from Novo Nordisk. The remaining authors have nothing to disclose.Safety concerns have been raised regarding premature mortality, diabetes, neoplasia, and cerebrovascular disease in association with GH therapy. To assess incidence of key safety outcomes. Prospective, multinational, observational study (1999 to 2015). A total of 22,311 GH-treated children from 827 investigative sites in 30 countries. Children with growth disorders. GH treatment. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) with 95% CIs for mortality, diabetes, and primary cancer using general population registries. Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean ± SD follow-up of 4.2 ± 3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with an SMR (95% CI) of 0.61 (0.44, 0.82); the SMR was elevated for patients with cancer-related organic GH deficiency [5.87 (3.21, 9.85)]. Based on 18 cases, type 2 diabetes mellitus (T2DM) risk was elevated [SIR: 3.77 (2.24, 5.96)], but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed [SIR: 0.71 (0.39, 1.20)]. Second neoplasms occurred in 31 of 622 cancer survivors [5.0%; 10.7 (7.5, 15.2) cases/1000 PY] and intracranial tumor recurrences in 67 of 823 tumor survivors [8.1%; 16.9 (13.3, 21.5) cases/1000 PY]. All three hemorrhagic stroke cases had risk factors. GeNeSIS (Genetics and Neuroendocrinology of Short Stature International Study) data support the favorable safety profile of pediatric GH treatment. Overall risk of death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared with the general population, but most cases had diabetes risk factors. Safety of GH therapy was assessed in a pediatric observational study. Death and primary cancer rates were not higher than in the general population; T2DM rate was higher owing to risk factors

Growth hormone treatment in non-growth hormone-deficient children

Until 1985 growth hormone (GH) was obtained from pituitary extracts, and was available in limited amounts only to treat severe growth hormone deficiency (GHD). With the availability of unlimited quantities of GH obtained from recombinant DNA technology, researchers started to explore new modalities to treat GHD children, as well as to treat a number of other non-GHD conditions. Although with some differences between different countries, GH treatment is indicated in children with Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome, deletions/mutations of the SHOX gene, as well as in short children born small for gestational age and with idiopathic short stature. Available data from controlled trials indicate that GH treatment increases adult height in patients with Turner syndrome, in patients with chronic renal insufficiency, and in short children born small for gestational age. Patients with SHOX deficiency seem to respond to treatment similarly to Turner syndrome. GH treatment in children with idiopathic short stature produces a modest mean increase in adult height but the response in the individual patient is unpredictable. Uncontrolled studies indicate that GH treatment may be beneficial also in children with Noonan syndrome. In patients with Prader-Willi syndrome GH treatment normalizes growth and improves body composition and cognitive function. In any indication the response to GH seems correlated to the dose and the duration of treatment. GH treatment is generally safe with no major adverse effects being recorded in any condition

THE EFFECT OF AN ENKEPHALIN ANALOG ON ALDOSTERONE SECRETION IN NORMAL SUBJECTS

The effect of FK33 824, a stable analogue of methionine-enkephalin, on aldosterone (A), plasma renin activity (PRA) and cortisol (F) secretion were studied in 4 normal subjects. A significantly increased while PRA was unaffected and F decreased afted the drug adrninistration. We suggest that enkephalins may play a role in the control of A secretion by a mechanism of action independent on angiotensin II and ACTH

Growth Hormone Deficiency in the Transition Age

Growth hormone (GH) is essential not only for normal growth during childhood, but also for the acquisition of bone mass and muscle strength in both sexes. This process is completed after the achievement of adult height in the phase of transition from adolescence to adulthood. Adolescents with childhood onset GH deficiency (GHD) show reduction of bone mineral density, decrease in lean body mass, increase in fat mass, and deterioration of the lipid profile. For this reason, continuation of GH replacement therapy in the transition age is recommended in all patients with a confirmed diagnosis of GHD. To confirm the diagnosis of GHD, GH treatment should be discontinued for at least 1 month after the attainment of adult height, and the patient should be re-evaluated for GH secretion. Current guidelines indicate that retesting is not required for those with a transcription factor mutation, more than 3 pituitary hormone deficits, or isolated GHD associated with an identified mutation. The key predictors of persistent GHD are its severity, the presence of additional pituitary hormone deficits, low insulin-like growth factor I (IGF-I) concentration, and the presence of structural hypothalamic-pituitary abnormalities Treatment should be initiated with a low dose (0.2-0.5 mg/day s.c.) and then adjusted according to IGF-I concentrations

Central adrenal insufficiency in children and adolescents

Central adrenal insufficiency (CAI) is a life-threatening condition caused by either pituitary disease (secondary adrenal insufficiency) or impaired hypothalamic function with inadequate CRH production (tertiary adrenal insufficiency). ACTH deficiency may be isolated or, more frequently, occur in conjunction with other pituitary hormone deficiencies and midline defects. Genetic mutations of the TBX19 causing isolated CAI are rare but a number of genes encoding transcription factors involved in hypothalamic-pituitary gland development, as well as other genes including POMC and PC1, are associated with ACTH deficiency. CAI is frequently identified in congenital, malformative, genetic, and epigenetic syndromes as well as in several acquired conditions of different etiologies. The signs and symptoms vary considerably and depend on the age of onset and the number and severity of associated pituitary defects. They may include hypoglycemia, lethargy, apnea, poor feeding, prolonged cholestatic jaundice, jitteriness, seizures, and sepsis in the neonate, or nonspecific signs such as fatigue, hypotension, vomiting and hyponatremia without hyperkalemia in children. The diagnosis of CAI relies on the measurement of morning cortisol concentrations along with dynamic test for cortisol release with different stimulating agents. Early recognition of CAI and its correct management are mandatory in order to avoid both morbidity and mortality in affected neonates, children and adolescents

Advances in differential diagnosis and management of growth hormone deficiency in children

Growth hormone (GH) deficiency (GHD) in children is defined as impaired production of GH by the pituitary gland that results in growth failure. This disease might be congenital or acquired, and occurs in isolation or in the setting of multiple pituitary hormone deficiency. Isolated GHD has an estimated prevalence of 1 patient per 4000-10,000 live births and can be due to multiple causes, some of which are yet to be determined. Establishing the correct diagnosis remains key in children with short stature, as initiating treatment with recombinant human GH can help them attain their genetically determined adult height. During the past two decades, our understanding of the benefits of continuing GH therapy throughout the transition period from childhood to adulthood has increased. Improvements in transitional care will help alleviate the consequent physical and psychological problems that can arise from adult GHD, although the consequences of a lack of hormone replacement are less severe in adults than in children. In this Review, we discuss the differential diagnosis in children with GHD, including details of clinical presentation, neuroimaging and genetic testing. Furthermore, we highlight advances and issues in the management of GHD, including details of transitional care