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Growth hormone deficiency (GHD) is the most frequent pituitary hormone deficiency in childhood, with an incidence of 1 in 4000–10,000 live births. GHD can be congenital (genetic or due to hypothalamic/pituitary abnormalities) or acquired and can be isolated (IGHD) or associated with other pituitary hormone deficiencies, but most cases are idiopathic. GH stimulation testing is commonly used in the diagnostic workup of GHD, except for some clinical conditions that do not require GH stimulation tests for the diagnosis. Children with GHD receive replacement therapy with daily injections of recombinant human GH (rhGH). RhGH therapy is effective in increasing short-term height gain and adult height in patients with GHD. The safety of long term GH therapy has been confirmed in many large international studies. Recently, long-acting weekly GH formulations have been introduced, showing good efficacy and safety profiles.

Before 1985, growth hormone (GH) was extracted from human pituitaries, and its therapeutic use was limited to children with severe GH deficiency (GHD). The availability of an unlimited amount of recombinant GH (rhGH) allowed for investigating the efficacy of its therapeutic use in a number of conditions other than GHD. Nowadays, patients with Turner syndrome, SHOX deficiency, Noonan syndrome, Prader–Willi syndrome, idiopathic short stature, chronic kidney disease, and children born small for gestational age can be treated with rhGH in order to improve adult height. In patients with Prader–Willi syndrome, rhGH therapy also improves body composition and cognitive function. Large post-marketing multinational studies in a large number of pediatric patients demonstrated a good safety profile for rhGH. Recently, long-acting formulations of rhGH have been approved and licensed for GHD, and clinical trials are ongoing for other conditions. In this paper, we review the rhGH therapy in children with conditions other than GHD.

Background: Several studies have evaluated the role of IGF-1 in the diagnosis of growth hormone deficiency (GHD). According to a recent study, an IGF-1 concentration of a −1.5 standard deviation score (SDS) appeared to be the best cut-off for distinguishing between children with GHD and normal children. This value should always be interpreted in conjunction with other clinical and biochemical parameters for the diagnosis of GHD, since both stimulation tests and IGF-1 assays have poor diagnostic accuracy by themselves. Our study was designed to evaluate the adult height (AH) in children with short stature and baseline IGF-1 concentration ≤ −1.5 SDS. Design: This retrospective analysis included 52 children and adolescents evaluated over the last 30 years for short stature and/or deceleration of the growth rate who underwent diagnostic procedures to evaluate a possible GHD. Only the patients who had baseline IGF-1 values ≤−1.5 SDS at the time of the first test were included in the study. Patients with genetic/organic GHD or underlying diseases were not included. Method: The case group consisted of 24 patients (13 boys and 11 girls) with non-permanent, idiopathic, and isolated GHD (peak GH < 10 μg/L after two provocative tests with arginine (Arg), insulin tolerance test (ITT), and clonidine (Clo), or Results: AH and height gain in both groups were comparable. In the group of cases, mean IGF-1 SDS at the time of diagnosis was significantly lower than the levels found at the time of retesting. Conclusions: In this study, both treated patients with idiopathic GHD and untreated patients with ISS reached similar near-AHs (within target height) and showed similar increases in SDS for their height. Thus, the efficacy of treatment with rhGH in these patients may be questionable. This could be due to the fact that children with ISS are frequently misdiagnosed with GHD.

Objective: This retrospective study aimed to evaluate children observed for suspected precocious puberty in five Italian centers of Pediatric Endocrin ology during the first wave of coronavirus disease 2019 pandemic (March–September 2020), compared to subjects observed in the same period of the previous year. Design: The study population (490 children) was divided according to the year of observation and final diagnosis: transient thelarche, non-progressive precocious puberty, central precocious puberty (CPP), or early puberty. Results: Between March and September 2020, 338 subjects were referred for suspected precocious puberty, compared to 152 subjects in the same period of 2019 (+122%). The increase was observed in girls (328 subjects in 2020 vs 140 in 2019, P < 0.05), especially during the second half of the period considered (92 girls from March to May vs 236 girls from June to September); while no difference was observed in boy s (10 subjects in 2020 vs 12 in 2019). The percentage of girls with confirmed CPP was h igher in 2020, compared to 2019 (135/328 girls (41%) vs 37/140 (26%), P < 0.01). Anthropometric and hormonal parameters in 2019 and 2020 CPP girls were not different; 2020 C PP girls showed more prolonged use of electronic devices and a more sedentary lifestyle both before and during the pandemic, compared to the rest of the 2020 population. Conclusions: The present findings corroborate the recently reported associat ion between the complex lifestyle changes related to the lockdown and a higher incidence of CPP in Italian girls.

A number of studies have evaluated the role of IGF1 measurement in the diagnosis of growth hormone deficiency (GHD). This study aimed to evaluate th e accuracy and the best cut-off of IGF1 SDS in the diagnosis of GHD in a large coho rt of short children and adolescents. One-hundred and forty-two children and adolescents with GHD ((63 organic/ genetic (OGHD), 79 idiopathic (IGHD)) and 658 short non-GHD chi ldren (median age 10.4 years) were included in the analysis. The two groups were subdi vided according to age (G1

Newborn screening (NBS) for inborn errors of metabolism is one of the most advanced tools for secondary prevention in medicine, as it allows early diagnosis and prompt treatment initiation. The expanded newborn screening was introduced in Italy between 2016 and 2017 (Law 167/2016; DM 13 October 2016; DPCM 12-1-2017). A total of 1,586,578 infants born in Italy were screened between January 2017 and December 2020. For this survey, we collected data from 15 Italian screening laboratories, focusing on the metabolic disorders identified by tandem mass spectrometry (MS/MS) based analysis between January 2019 and December 2020. Aminoacidemias were the most common inborn errors in Italy, and an equal percentage was observed in detecting organic acidemias and mitochondrial fatty acids beta-oxidation defects. Second-tier tests are widely used in most laboratories to reduce false positives. For example, second-tier tests for methylmalonic acid and homocysteine considerably improved the screening of CblC without increasing unnecessary recalls. Finally, the newborn screening allowed us to identify conditions that are mainly secondary to a maternal deficiency. We describe the goals reached since the introduction of the screening in Italy by exchanging knowledge and experiences among the laboratories.

Objective: Thyroid function may recover in patients with Hashimoto’s thyroiditis (HT). Design: To investigate thyroid function and the need to resume l-thyroxine treatment after its discontinuation. Setting: Nine Italian pediatric endocrinology centers. Patients: 148 children and adolescents (25 m and 123 f) with HT on treatment with l-thyroxine for at least one year. Intervention and main outcome measure: Treatment was discontinued in all patients, and serum TSH and fT4 concentrations were measured at the time of treatment discontinuation and then after 2, 6, 12 and 24 months. Therapy with l-thyroxine was re-instituted when TSH rose >10 U/L and/or fT4 was below the normal range. The patients were followed up when TSH concentrations were between 5 and 10 U/L and fT4 was in the normal range. Results: At baseline, TSH was in the normal range in 139 patients, and was between 5 and 10 U/L in 9 patients. Treatment was re-instituted after 2 months in 37 (25.5%) patients, after 6 months in 13 patients (6.99%), after 12 months in 12 patients (8.6%), and after 24 months in an additional 3 patients (3.1%). At 24 months, 34 patients (34.3%) still required no treatment. TSH concentration >10 U/L at the time of diagnosis was the only predictive factor for the deterioration of thyroid function after l-thyroxine discontinuation. Conclusions: This study confirms that not all children with HT need life-long therapy with l-thyroxine, and the discontinuation of treatment in patients with a TSH level

Objectives: To evaluate the effect of gender and puberty on cardiovascular risk factors (CVRF) in obese children and adolescents.Methods: One thousand four hundred and nine obese patients [age 9.7 (2.2–17.9) y; 646 Male] were studied. Subjects were stratified according to Tanner pubertal staging and age into prepubertal ≤ and >6 ys (G1 and G2), pubertal stage 2–3 (G3), and pubertal stage 4–5 (G4). Waist circumference (WC), systolic and diastolic blood pressure (SP, DP), fasting plasma glucose, insulin, post Oral Glucose Tolerance Test glucose and insulin, and lipids were evaluated. Insulin resistance was evaluated by HOMA index. Patients with no CVRF were considered metabolically healthy (MHO).Results: The percentage of MHO patients was 59.8% in G1 while was consistently around 30% in the other groups. WC was more frequently abnormal in G2 males. Pubertal progression was associated with a decrease in WC abnormalities. SP was more frequently abnormal in G4 males and pubertal progression was associated with higher prevalence of abnormal SP in males. Pubertal progression was associated with an increase in hypertension rate in both sexes. HOMA was more frequently abnormal in G2 and G3 females. HDL, LDL, and TG were more frequently abnormal in G2 females. Dyslipidemia rate was higher in G2 females. Pubertal progression was associated with higher prevalence of abnormal HDL in males.Conclusions: Sex and pubertal status influence the frequency of abnormalities of CVRF in obese children and adolescents. CVRF are already present in prepubertal age. Identifying patients with higher risk of metabolic complications is important to design targeted and effective prevention strategies.

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.