Increased incidence of precocious and accelerated puberty in females during and after the Italian lockdown for the coronavirus 2019 (COVID-19) pandemic.

BACKGROUND: The timing of puberty in girls is occurring at an increasingly early age. While a positive family history is recognised as a predisposing factor for early or precocious puberty, the role of environmental factors is not fully understood. AIMS OF THE STUDY: To make a retrospective evaluation of the incidence of newly diagnosed central precocious puberty (CPP) and the rate of pubertal progression in previously diagnosed patients during and after the Italian lockdown for COVID-19, comparing data with corresponding data from the previous 5 years. To determine whether body mass index (BMI) and the use of electronic devices increased during lockdown in these patients. PATIENTS AND METHODS: The study included 49 females with CPP. We divided the patients into two groups: group 1, patients presenting a newly diagnosed CPP and group 2, patients with previously diagnosed slow progression CPP whose pubertal progression accelerated during or after lockdown. We collected auxological, clinical, endocrinological and radiological data which were compared with data from two corresponding control groups (patients followed by our Unit, March to July 2015-2019). Patients' families completed a questionnaire to assess differences in the use of electronic devices before and during lockdown. RESULTS: Thirty-seven patients presented newly diagnosed CPP (group 1) and 12, with previously diagnosed but untreated slow progression CPP presented an acceleration in the rate of pubertal progression (group 2). The number of new CPP diagnoses was significantly higher than the mean for the same period of the previous 5 years (p < 0.0005). There were no significant differences between patients in group 1 and control group 1 regarding time between appearance of B2 and CPP diagnosis, although group 1 patients had a significantly earlier chronological age at B2, a more advanced Tanner stage at diagnosis (p < 0.005), higher basal LH and E2 levels, higher LH peak after LHRH test (p < 0.05) and increased uterine length (p < 0.005) and ovarian volume (p < 0.0005). The number of patients with previously diagnosed CPP whose pubertal development accelerated was also statistically higher compared to controls (p < 0.0005). In this group, patients' basal LH (p < 0.05) and E2 levels (p < 0.0005) became more markedly elevated as did the LH peak after LHRH test (p < 0.05). These patients also showed a significantly accelerated progression rate as measured by the Tanner scale (p < 0.0005), uterine length (p < 0.005), and ovarian volume (p < 0.0005). In both group 1 and group 2, BMI increased significantly (p < 0.05) and patients' families reported an increased use of electronic devices (p < 0.0005). CONCLUSION: Our data show an increased incidence of newly diagnosed CPP and a faster rate of pubertal progression in patients with a previous diagnosis, during and after lockdown compared to previous years. We hypothesize that triggering environmental factors, such as the BMI and the use of electronic devices, were enhanced during lockdown, stressing their possible role in triggering/influencing puberty and its progression. However, more studies are needed to determine which factors were involved and how they interacted.

Anaphylactic reaction to gonadotropin-releasing hormone analogues: a pediatric case report.

Gonadotropin-releasing hormone (GnRH) analogues represent the gold standard treatment for precocious puberty. Allergic-type reactions in children due to this type of treatment are very rare. However, caregivers should be aware of the potential GnRH analogue systemic reactions.

Retrospective Evaluation of Metformin and/or Metformin Plus a New Polysaccharide Complex in Treating Severe Hyperinsulinism and Insulin Resistance in Obese Children and Adolescents with Metabolic Syndrome.

Background: Pharmacological treatment of obesity and glucose-insulin metabolism disorders in children may be more difficult than in adults. Thus, we evaluate the effects of metformin in comparison with metformin plus a polysaccharide complex (Policaptil Gel Retard®, PGR) on body weight and metabolic parameters in obese children and adolescents with metabolic syndrome (MetS). Patients and methods: We retrospectively collected 129 children and adolescents (67 girls, 62 boys; median age 12.6 years) treated for a minimum of two years with metformin and low glycemic index (LGI) diet. Of these, 71 patients were treated with metformin plus PGR after at least 12 months of metformin alone. To minimize the confounding effect of the LGI on auxological and metabolic parameters, the patients were compared with age-, sex-, and BMI-matched control group with obesity and MetS (51 subjects; 24 males, 27 females) treated only with a LGI diet. Assessments included lipids, glucose and insulin (fasting and after oral glucose tolerance test) concentrations. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Matsuda, insulinogenic and disposition indices were calculated. Results: Metformin treatment led to a significant reduction in BMI SDS (p < 0.0001), with a significant difference in ΔBMI SDS between patients and controls (p < 0.0001). Moreover, metformin treated patients showed a reduction in HOMA-IR (p < 0.0001), HbA1c levels (p < 0.0001) and a significant increase in Matsuda index (p < 0.0001) in respect to the reduction discovered in controls (p < 0.05). Moreover, in contrast to the group treated with metformin alone and controls, patients treated with metformin plus PGR showed a further reduction in BMI SDS (p < 0.0001), HOMA-IR (p < 0.0001), HbA1c (p < 0.0001), total, HDL and LDL cholesterol (p < 0.0001), as well as an increase in Matsuda (p < 0.0001), disposition (p < 0.005) and insulinogenic (respectively, p < 0.05 and p < 0.0001) indices. Conclusions: Metformin appears to show short-term efficacy in reducing BMI, adiposity and glucose and insulin parameters in obese children and adolescents with MetS. However, PGR added to metformin may be useful to potentiate weight loss and to improve glucose-insulin metabolism and adiposity parameters in these patients.

Hydrocortisone malabsorption due to polyethylene glycols (Macrogol 3350) in a girl with congenital adrenal insufficiency.

BACKGROUND: Primary adrenal insufficiency is relatively rare in children and, if unrecognized, may present with cardiovascular collapse, making it a potentially life-threatening entity. CASE PRESENTATION: The proposita, 11 months old of age, was admitted for lethargy and severe dehydration. Blood pressure was 62/38 mm Hg, and biochemical measurements showed hyponatraemia, hypochloraemia, hyperkalaemia, and metabolic acidaemia. Renin activity was 1484 µU/mL; cortisol, 1.03 µg/dL (normal, 5-25 µg/dL); and corticotropin (ACTH), 4832 ng/L (normal, 9-52 ng/L). Adrenal deficiency was diagnosed, and replacement therapy with glucocorticoids and mineralocorticoids was initiated. After 40 days, ACTH was 797 ng/L. During follow-up, the patient started taking macrogol twice daily for constipation and experienced a significant increase in ACTH (3262 ng/L), which dropped to 648 ng/L when macrogol was stopped. After arbitrary reintroduction of macrogol, the child presented with hypoglycaemia, lethargy, weakness, and hypotonia; ACTH was 3145 ng/L. After again stopping macrogol, her ACTH was near normalized (323 ng/L). CONCLUSION: Hydrocortisone malabsorption may be caused by macrogol use. Because chronic constipation is frequently reported in children, the possibility that macrogol contributes to adrenal crisis should be taken in account.

The impact of long-term exposure to space environment on adult mammalian organisms: a study on mouse thyroid and testis.

Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis.In thyroids, volumetric ratios between thyrocytes and colloid were measured. cAMP production in 10(-7)M and 10(-8)M thyrotropin-treated samples was studied. Thyrotropin receptor and caveolin-1 were quantitized by immunoblotting and localized by immunofluorescence. In space-exposed animals, both basal and thyrotropin-stimulated cAMP production were always higher. Also, the structure of thyroid follicles appeared more organized, while thyrotropin receptor and caveolin-1 were overexpressed. Unlike the control samples, in the space samples thyrotropin receptor and caveolin-1 were both observed at the intracellular junctions, suggesting their interaction in specific cell membrane microdomains.In testes, immunofluorescent reaction for 3ß- steroid dehydrogenase was performed and the relative expressions of hormone receptors and interleukin-1ß were quantified by RT-PCR. Epididymal sperm number was counted. In space-exposed animals, the presence of 3ß and 17ß steroid dehydrogenase was reduced. Also, the expression of androgen and follicle stimulating hormone receptors increased while lutenizing hormone receptor levels were not affected. The interleukin 1 ß expression was upregulated. The tubular architecture was altered and the sperm cell number was significantly reduced in spaceflight mouse epididymis (approx. -90% vs. laboratory and ground controls), indicating that the space environment may lead to degenerative changes in seminiferous tubules.Space-induced changes of structure and function of thyroid and testis/epididymis could be responsible for variations of hormone levels in human during space missions. More research, hopefully a reflight of MDS, would be needed to establish whether the space environment acts directly on the peripheral glands or induces changes in the hypotalamus-pituitary-glandular axis.