Growth Hormone Deficiency Research Articles

Outcomes of late endocrinologic evaluation in adult patients with thalassemia major: case series

AThalassemia is a group of inherited disorders characterized by the reduced or absent synthesis of the globin chains that make up hemoglobin. Transfusion-dependent thalassemia (TDT) is the most severe form, which requires lifelong transfusion. Complications related to the heart, liver and endocrine glands caused by the accumulation of excess iron in different organs due to transfusions are seen in adult patients. Of these complications, endocrine gland complications are widespread in adult patients. Hypogonadism is the most commonly reported endocrine complication, which affects 70-80% of thalassemia major patients. In this case series, we will present three female patients, aged 37, 18 and 27, who were followed up with the diagnosis of TDT and who underwent endocrinological evaluation in adulthood. We aim to emphasize that the diagnosis of hypogonadotropic hypogonadism and growth hormone (GH) deficiency was made late because the endocrinological evaluation of these patients was performed at an adult age, and we discussed the consequences of this. The survival of TDT patients has improved significantly in the last decade due to the introduction of transfusion, oral iron chelation therapies, and bone marrow transplantation, and these patients live into adulthood. Therefore, endocrinologic evaluation should be performed in pre-pubertal and pubertal periods. Early recognition of endocrine complications and early initiation of treatment are important to prevent irreversible sequelae.

Nutritional Status and Growth Outcomes in Pediatric Idiopathic Growth Hormone Deficiency: A Retrospective Study in Turkey

Objective: Growth and development in children are significantly influenced by nutritional status. Nutritional deficiencies such as low hemoglobin (Hb), ferritin, vitamin B12, and vitamin D have been linked to impaired growth. This study aims to evaluate the impact of these nutritional markers on growth outcomes in children with idiopathic growth hormone deficiency (IGHD) undergoing recombinant growth hormone therapy (rhGH). Material and Methods: A cross-sectional, retrospective study was conducted on 100 children with IGHD, aged under 16, diagnosed between 2000 and 2023. Data were collected from medical records, including height, body mass index (BMI), pubertal status, bone age, and nutritional markers [Hb, ferritin, vitamin B12, 25-hydroxy-vitamin D3 (25(OH)D3]. Growth parameters were assessed at the start and end of the first year of rhGH treatment. Results: The cohort had a median age of 11.3 years; 30% were female, and 50% were prepubertal. The median height standard deviation score (SDS) was -2.8, and median BMI SDS was -0.7. Prevalence of nutritional deficiencies included 23% with low Hb, 31% with low ferritin, 44% with low 25(OH)D3, and 15% with low vitamin B12. Despite these deficiencies, no significant differences were observed in height SDS or growth velocity when grouped by nutritional markers or supplementation status. Growth velocity showed a significant positive correlation with Hb levels and mid-parental height (MPH). Conclusion: Nutritional deficiencies were common among IGHD patients; there was no significant difference in terms of growth-related metrics in the first year of the rhGH therapy in comparisons between the groups with and without common nutritional deficiencies. This finding underscores the resilience of growth in the presence of these deficiencies. In contrast, growth velocity correlated positively with Hb levels and MPH, suggesting that these factors may play a significant role in influencing growth. Further research with larger samples and extended follow-up is needed to explore the long-term impact of nutritional supplementation on growth in IGHD.

Liver-specific actions of GH and IGF1 that protect against MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD; also known as nonalcoholic fatty liver disease) is a chronic condition associated with metabolic syndrome, a group of conditions that includes obesity, insulin resistance, hyperlipidaemia and cardiovascular disease. Primary growth hormone (GH) deficiency is associated with MASLD, and the decline in circulating levels of GH with weight gain might contribute to the development of MASLD. Raising endogenous GH secretion or administering GH replacement therapy in the context of MASLD enhances insulin-like growth factor 1 (IGF1) production and reduces steatosis and the severity of liver injury. GH and IGF1 indirectly control MASLD progression by regulating systemic metabolic function. Evidence supports the proposal that GH and IGF1 also have a direct role in regulating liver metabolism and health. This Review focuses on how GH acts on the hepatocyte in a sex-dependent manner to limit lipid accumulation, reduce stress, and promote survival and regeneration. In addition, we discuss how GH and IGF1 might regulate non-parenchymal cells of the liver to control inflammation and fibrosis, which have a major effect on hepatocyte survival and regeneration. Development of a better understanding of how GH and IGF1 coordinate the functions of specific, individual liver cell types might provide insight into the aetiology of MASLD initiation and progression and suggest novel approaches for the treatment of MASLD.

Challenge Treatment GH with Turner Syndrome Having Cardiac and Renal Malformation: About A Case Report

In GH deficiency, rhGH is deemed appropriate when epiphyses are open, while Turner's syndrome poses unique considerations due to associated malformations like cardiac aortic bicuspidity and aortic coarctation. Renal malformations, including Horseshoe kidney and hydronephrosis, further highlight the complexity of Turner's syndrome, requiring a comprehensive, multidisciplinary approach to care. We report the case about of an elderly child 3 years and 5 months old patient with cardiac and renal malformations notably a tight postductal isthmic coarctation and a left pyeloureteral junction syndrome with dilatation of the pyelocalic cavities, admitted for further management of a staturo-ponderal delay. She presented with functional signs of constipation, no chills, no digestive disorders and no hypoglycemic malaise. On physical examination, dysmorphic features included low hairline and short neck, pterygium coli, low ear implant, hypertelorism, nipple spread, keloid lesion on face. Test results showed a 45x karyotype in favour of Turner syndrome, HBA1c: 5.6%, the rest of the tests were normal. GH was indicated in the patient after cardiac surgery for coarctation of the aorta and pyelo-caliceal junction. The patient was referred for heart and kidney surgery. It is crucial to closely monitor height velocity during catch-up growth, particularly in patients with concurrent conditions leading to short stature. Additionally, there is an emphasis on educating parents about the potential impact of Turner syndrome on aspects such as growth, growth hormone (GH) substitution, ovarian failure, malformations, and related health risks.

Unveiling the psychiatric dimensions of hypopituitarism: investigating associations, challenges, and treatment strategies.

Dear Editor, Hypopituitarism is a disorder characterized by insufficient hormone production from the pituitary gland,1,2 manifesting as either pan or partial dysfunction.2 Hypopituitarism is considered a rare disorder by National Institute of Health and there is limited information on its occurrence. A study in Spain demonstrated prevalence of 45.5 cases per 100,000 people.2 Hypopituitarism can be caused by pituitary tumours, head injury, infections, radiation therapy, autoimmune conditions, and genetic abnormalities.2 Hypopituitarism occurs when about 75% of the pituitary gland is affected, causing a spectrum of clinical features from mild to severe.2 Sheehan syndrome, resulting from anterior pituitary ischaemia typically after postpartum haemorrhage, occurs in approximately 5/10,000 births in developing countries.3 Hypopituitarism diagnosis may take a decade or longer due to its diverse clinical presentations.3 As of now, the link between psychotic disorders and hypopituitarism is not completely understood.1 While a few case reports have documented a link between pituitary insufficiency and mental health issues, larger-scale studies are limited in number. Hypopituitarism raises depression and anxiety risk, especially in females and those over 18, with females having tenfold higher risk of depression than males.1 Growth hormone deficiency (GHD) is linked to cognitive impairments, and atypical depression.4 In their 1949 report, Sheehan and Summer noted that one-third of total 143 hypopituitarism patients displayed loss of drive and initiative, and disinterest in social connections.5 Acute psychosis as an initial presentation of hypopituitarism has been reported in cases involving Sheehan's syndrome, traumatic brain injury, and glucocorticoid therapy.5 A 37-year-old pregnant woman diagnosed with Sheehan syndrome exhibited neuropsychiatric symptoms, prompting early diagnosis.3 The 2010 study found that growth hormone therapy improved cognitive function and reduced depression severity in traumatic brain injury patients with GHD. However, discontinuation of therapy led to worsened cognitive function and increased psychiatric symptoms, highlighting the potential benefits of growth hormone therapy and the need for more experimental studies to confirm its effects on neurophysiological and psychiatric wellbeing.4 Adults with Childhood Onset Multiple Pituitary Hormone Deficiency have a notably lower quality of life, underscoring the importance of addressing psychosocial and psychosexual challenges in this population.6 A 60-year-old man with macroprolactinoma and hypopituitarism developed acute psychosis due to non-adherence to cabergoline, treatment with hydrocortisone, and thyroxine lead to full recovery within 48 hours.5 A 41-year-old man with osmophobia improved with sertraline transiently. Later, he was diagnosed with partial hypopituitarism with adrenocorticotropic hormone deficiency. Prednisolone supplementation significantly improved his condition.7 ---Continue

Establishment of IGF-1 and IGFBP-3 continuous reference percentiles from data of healthy children using three kinds of immunoassay systems

Background and aimsAppropriate continuous reference intervals (RIs) for serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are important for diagnosing growth hormone deficiency or excess. Material and methodsWe retrospectively reviewed serum IGF-1 and IGFBP-3 levels in Korean children aged 0–17 years who were diagnosed as healthy during a short stature workup in the outpatient clinics of three hospitals. IGF-1 and IGFBP-3 levels were measured using various immunoassays, including Liaison XL for IGF-1, an immunoradiometric assay (IRMA) for IGFBP-3 (n = 5522), and Immulite 2000 (n = 3036) and cobas e801 (n = 314). We established RIs from the 2.5th to 97.5th percentile RI curves using the lambda–mu–sigma (LMS) method for each sex group. ResultsPediatric serum continuous IGF-1 and IGFBP-3 reference percentiles by LMS method were found to be immunoassay method-dependent, but aligned relatively well with the manufacturers’ RIs. IGFBP-3 levels displayed notable discrepancies among the different immunoassay methods. ConclusionAge- and sex-specific pediatric LMS based continuous reference intervals are method dependent and they should be calculated for dynamic parameters that show variations throughout childhood.

Long-term metabolic effectiveness and safety of growth hormone replacement therapy in patients with adult growth hormone deficiency: a single-institution study in Japan.

To elucidate the long-term efficacy and safety of growth hormone replacement therapy (GHRT) in Japanese patients with adult growth hormone deficiency (AGHD). We conducted a retrospective study. A total of 110 patients with AGHD receiving GHRT were enrolled. Clinical and laboratory data were collected annually from the beginning of the study. Statistical analysis was performed using a linear mixed-effects model. Of all patients, 46.4% were males, 70.9% had adult-onset GHD, and follow-up was up to 196 months, with a median of 68 months. The insulin-like growth factor-1 standard deviation score increased after the start of GHRT and remained constant for more than 11 years. Seventeen patients were followed up for more than 11 years. The body mass index increased. Waist circumference decreased in the short term but increased in the long term. The diastolic blood pressure decreased 1-5 years after the start of GHRT, and the systolic blood pressure increased 11 years after GHRT. Moreover, a long-term decrease in low-density lipoprotein cholesterol, an increase in high-density lipoprotein cholesterol, and a decrease in aspartate aminotransferase and alanine aminotransferase levels were observed. The glycosylated hemoglobin level increased after 3 years. The bone mineral density in the lumbar spine and total hip increased significantly 3 years after the start of GHRT. Finally, the number of adverse events was eight. We demonstrated the metabolic effectiveness and safety of GHRT in Japanese patients with AGHD over a long follow-up period of 16 years.

Accuracy of arginine testing as first test for diagnosing growth hormone deficiency in children

Accuracy of arginine testing as first test for diagnosing growth hormone deficiency in children

Expanding the Spectrum of Endocrine Abnormalities Associated with SOX11-related Disorders.

SOX11 variants cause Coffin-Siris Syndrome (CSS), characterized by developmental delay, hypogonadotropic hypogonadism (HH), skeletal and facial defects. To examine the contribution of SOX11 variants to the pathogenesis of Idiopathic Hypogonadotropic Hypogonadism (IHH), a disorder caused by hypothalamic GnRH deficiency. The Reproductive Endocrine Unit and the Pediatric Endocrinology Division, Massachusetts General Hospital. A cohort of 1810 unrelated IHH probands. Exome sequencing data from the entire cohort were examined for SOX11 rare single nucleotide variants (SNVs) [minor allele frequency in the gnomAD database <0.1%]. Rare SOX11 variant association testing was performed between the IHH and gnomAD population. Phenotyping of individuals harboring pathogenic/likely pathogenic SNVs (determined by the ACMG criteria) was performed. Four pathogenic SOX11 SNVs were identified in 5 IHH probands. The IHH cohort was enriched for SOX11 protein truncating SNVs (frameshift/nonsense) across the entire protein (2 SNVs in 3 IHH cases [p.S303X (de-novo); p.S345Afs*13]; p 0.0004981) and for SOX11 missense SNVs within the SOX11-high-mobility group (HMG) domain (2 SNVs in 2 IHH cases p.G84D[de-novo]; p.P114S; p=0.00313922). The phenotypic spectrum of SOX11 variant carriers revealed additional endocrine defects including anosmic and normosmic forms of IHH, growth-hormone deficiency, pituitary and hypothalamic structural defects, and hypothyroidism. A pathogenic SOX11 SNV was also identified in a patient with functional HH (FHH, p.R100Q). CSS-associated features were present in 4/5 probands. Deleterious SOX11 variants cause IHH and other pituitary hormone deficiencies, suggesting that the human SOX11-associated disorder may stem from both hypothalamic and pituitary level defects.

Slow growth and short stature in children with attention deficit hyperactivity disorder (ADHD): aretrospective study of 493 children who underwent growth hormone provocation testing at one tertiary paediatric endocrine centre.

We hypothesised that growth hormone (GH) deficiency (GHD) in children with attention deficit hyperactivity disorder (ADHD) is rare. This study aimed to determine any distinct clinical or biochemical parameters, including GH provocation testing, in children with ADHD on psychostimulants or idiopathic short stature (ISS). Retrospective cross-sectional study of children who had GH provocative testing between 1998 and 2013 at one tertiary paediatric endocrine centre. Clinical data included age, sex, anthropometry, pubertal staging, bone age, diagnostic code as per the European Society Paediatric Endocrinology (ESPE), GH provocation test results, thyroid function tests, serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels. Four hundred ninety-three subjects underwent GH provocation testing for investigation of short stature to exclude GHD during the study period. Fifty-one children hada diagnosis of ADHD. In the remaining children, the diagnosis was Idiopathic short stature (n=240), GHD +/- hypopituitarism (n=60), and 142 subjects had other causes of short stature. Children with ADHD were older, had higher height and weight SDS and were GH-sufficient. All 51 children with ADHD had a normal serum IGFBP-3, while 20 out of these 51 subjects had a low serum IGF-1. GHD in children with ADHD on psychostimulant medication is rare. GH testing in children with ADHD may not be necessary, particularly if serum IGFBP-3 is in thenormal range. We suggest IGFBP-3 could be used as a surrogate marker of GH sufficiency in children with ADHD. However, this needs to be confirmed with a larger study group.

Pituitary Gland Morphology: A Novel Diagnostic Marker for Differentiating Growth Hormone Deficiency from Idiopathic Short Stature in Children

Background: The primary causes of short stature (SS) are idiopathic short stature (ISS) and growth hormone deficiency (GHD). The diagnosis of GHD relies on growth hormone stimulation tests (GHSTs), while the diagnosis of ISS is achieved through exclusion. Objectives: Growth hormone (GH) and insulin-like growth factor-I are the best therapeutic drugs for treating GHD, but their suitability for ISS remains controversial. Therefore, distinguishing between these two causes of SS is crucial. Currently, the diagnosis of GHD depends on GHSTs, whereas the diagnosis of ISS is achieved through exclusion, which is an invasive process. Thus, developing a noninvasive and convenient method to differentiate between GHD and ISS would be of great importance. Patients and Methods: We enrolled patients aged 3 - 14 years who presented with SS and underwent GHSTs and pituitary gland (PG) magnetic resonance imaging (MRI) at our hospital from January 2020 to October 2022 for a cross-sectional study. A total of 205 patients were included, comprising 83 with ISS and 122 with GHD. The GHD patients were further divided into two groups based on the peak GH level in GHSTs. All patients underwent routine physical examinations, GHSTs, PG MRI, and X-rays of the left wrist. Two authors independently recorded the PG features (height, length, width, volume, pituitary stalk diameter, pituitary stalk length, and morphology). The PG morphology was categorized into three types: Convex, flat, and concave. Bone age was estimated from X-rays of the left wrist, which were reviewed by an experienced radiologist. Comparisons between the two groups were conducted using two independent samples t-tests or chi-square (χ²) tests. Results: There were no differences between the two groups regarding baseline clinical characteristics, except for the GH peak in GHSTs (P &lt; 0.05). Pituitary stalk diameter, PG height, PG volume, and the dorsum sellae were significantly lower, while the tuberculum sellae was higher in the GHD group compared to the ISS group (all P &lt; 0.05). The proportion of concave PG was higher, and the proportion of flat PG was lower in the GHD group (all P &lt; 0.05). In subgroup analysis, PG height and PG volume were significantly lower in the absolute GHD (AGHD) group compared to the partial GHD (PGHD) group (all P &lt; 0.05). Correlation analysis showed that PG height (r = 0.635, P &lt; 0.01) and PG volume (r = 0.786, P &lt; 0.01) were positively correlated with the GH peak level. Further analysis also demonstrated the differential diagnostic accuracy of PG height and PG volume, with high sensitivity (PG height: 66.3%; PG volume: 84.3%) and specificity (PG height: 85.2%; PG volume: 77.9%). Conclusion: pituitary gland height, PG volume, and the concave type of PG morphology may be very helpful in the differential diagnosis of GHD and ISS.

Endocrinopathy due to proproteinkovertase 1/3 deficiency: primary enteropathy, diabetes insipidus, secondary hypothyroidism

Proprotein convertase 1/3 (PC1/3) deficiency is an autosomal recessive disease caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK 1)gene, associated with severe malabsorptive diarrhea, obesity and some endocrine abnormalities. Proprotein convertase 1/3 is acalcium-dependent serine endoprotease involved in the proteolytic processing of various prohormones (peptide hormones in enteroendocrine cells that are necessary for the absorption of nutrients and is also expressed in the arcuate and paraventricular nuclei of the hypothalamus, in the beta cells of the pancreas) in their bioactive forms. The onset of the disease in the neonatal period of life is characterized by aclinical picture of severe malabsorption diarrhea, accompanied by developmental delays, and requires long-term parenteral nutrition. As the disease progresses, additional endocrine abnormalities develop, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, hypothyroidism, and obesity. We conducted aprospective observation of apatient with agenetic disease due to proprotein convertase 1/3 deficiency confirmed during follow-up. The patient was examined and treated at the State Novosibirsk Regional Clinical Hospital in Novosibirsk for 11 months, with repeated (3-fold) hospitalizations. Purpose: to demonstrate the features of the onset and course of the disease, as well as the difficulties in verifying the clinical diagnosis of an ultra-rare genetic disease from the category of endocrinopathies, the complexity of medical support and therapy. Apeculiarity of this case is the fact that the identified mutation in the gene was not previously registered in control Russian samples of the genetic mutation of proprotein convertase 1/3 deficiency, as well as apreviously undescribed variant of the nucleotide sequence in exon 4 of the PCSK1 gene in aheterozygous state and was not registered in control samples gnomAD and RUSeq. Proprotein convertase 1/3 deficiency is adisease that is amultidisciplinary problem, since etiopathogenetic therapy has not yet been developed. The disease has achronic course with constant relapses of intestinal syndrome, is difficult to manage with symptomatic treatments and, as it progresses, has ahigh risk of developing additional endocrinopathies and death. All of the above emphasizes the need for early diagnosis and selection of rational replacement and accompanying therapy to save the lives of patients.

Anterior pituitary hormone dysfunction among individuals with complete heart block requiring pacemaker.

Background & objectives Neuronal hypoxia associated with conditions like traumatic brain injury and cardiac tachyarrhythmia has been implicated in causing hypopituitarism. Individuals with complete heart block (CHB) may be predisposed to develop anterior pituitary hormone dysfunction in the long term. The objective of this study was to investigate anterior pituitary hormone functions in individuals after CHB. Methods This prospective cohort study included 30 individuals (21 men and 9 women) with CHB requiring pacemaker implantation, who were evaluated at admission and then at a mean follow up of 12.4 ± 2.2 months to look for development of any degree of hypopituitarism. In addition to the measurement of hormones like follicle-stimulating hormone (FSH), luteinising hormone (LH), thyroid stimulating hormone (TSH), total tetra iodothyronines (TT4), free tetraiodothyronines (FT4), cortisol, insulin-like growth factor-1 (IGF-1), testosterone and estradiol, a fixed-dose glucagon stimulation test (GST) was performed to assess growth hormone (GH) and adrenocorticotrophic hormone (ACTH) axis. Results The mean age of the participants was 64.9 ± 11.3 yr. At follow up evaluation, 17 (56.7%) had low serum IGF-1, and among them, seven (23%) had growth hormone deficiency (GHD) (peak GH <1.0 ng/ml after GST). Six participants (20%) had ACTH deficiency (peak cortisol <9 ug/dl after GST) and one had TSH deficiency. None had prolactin (PRL) or gonadotropin deficiency. Overall, hormone deficiencies were observed in nine patients (30%). Interpretation & conclusions This pilot study detected loss of anterior pituitary hormones in a significant number of individuals of CHB at 12 months follow up. Unrecognised hypopituitarism may have resulted in significant morbidity and mortality in these individuals.

Sembra un deficit di GH, e invece non lo è!

A 2.5-year-old girl was evaluated for poor growth. Despite low IGF-1 levels, GH deficiency was excluded. Further investigation revealed celiac disease, diagnosed via EGDS. After starting a gluten-free diet, catch-up growth was observed. The patient remained under follow-up to monitor her growth progress.

Authors’ response to a critical appraisal on “Assessing the cost-effectiveness of once-weekly somatrogon vs. daily somatropin for pediatric growth hormone deficiency”

Authors’ response to a critical appraisal on “Assessing the cost-effectiveness of once-weekly somatrogon vs. daily somatropin for pediatric growth hormone deficiency”

Spexin level in growth hormone deficiency Iraqi children

Spexin (SPX) is a newly discovered brain adipokine implicated in various homeostatic functions including metabolism, energy balance, endocrine processes and growth hormone (GH) production in particular. At the same time, the growth-promoting effects of GH are influenced by Insulin-like growth factor-1 (IGF‑1) and vitamin D3. The aim of this study was to investigate the possible involvement of SPX in growth hormone deficiency (GHD) in children. The research involved 90 children (40 with growth hormone deficiency and 50 healthy controls aged 5-14). Serum levels of GH, IGF and vitamin D3 were tested using a chemiluminescent immunoassay, that of SPX – by Elabscience ELISA Kit. The results revealed that children with GHD had significantly higher SPX levels compared to the control group. No significant difference in IGF-1 and vitamin D3 levels between patients and control groups was observed. In the GHD group, we found a significant negative correlation between SPX and GH levels; at the same time, there was no correlation between SPX and D3 levels. These findings suggest that the changes in SPX levels may contribute to growth hormone deficiency. Keywords: growth hormone deficiency, IGf-1, Iraqi children, spexin, vitamin D3

Traumatic brain injury and prolactin.

Traumatic brain injury (TBI) is a well-known etiologic factor for pituitary dysfunctions, with a prevalence of 15% during long-term follow-up. The most common hormonal disruption is growth hormone deficiency, followed by central adrenal insufficiency, central hypogonadism, and central hypothyroidism in varying order across studies. The prevalence of serum prolactin disturbances ranged widely from 0 to 85%. Prolactin release is mainly regulated by hypothalamic dopamine inhibition, and mediators such as TRH, serotonin, cytokines, and neurotransmitters have modulatory effects. Many factors, such as hypothalamic and/or pituitary gland injuries, as well as fluctuations in dopaminergic activity and other mediators and stress response, may cause derangements in serum prolactin levels after TBI. Although it is challenging to investigate the direct effects of TBI on serum prolactin levels due to many confounders, basal prolactin measurements and stimulation tests provide insight into the functionality of the hypothalamus and pituitary gland after TBI. Moreover, during the acute phase of TBI, prolactin levels appear to correlate with TBI severity. In contrast, in the chronic phase, hypoprolactinemia may function as an indirect indicator of pituitary dysfunction and reduced pituitary volume. Further investigations are needed to elucidate the pathophysiologic mechanisms underlying the prolactin trend following TBI, its significance, and its associations with other pituitary hormone dysfunctions. In this article, we re-evaluated our patients' TBI data regarding prolactin levels during prospective long-term follow-up, and reviewed the literature regarding the prevalence, pathophysiology, and clinical implications of serum prolactin disturbances during acute and chronic phases following TBI.

Minimizing unnecessary brain magnetic resonance imaging in pediatric endocrinology: a retrospective cohort analysis.

Brain magnetic resonance imaging (MRI) is mandatory or highly recommended in many pediatric endocrinological conditions to detect causative anatomic anomalies and rule out neoplastic lesions. However, MRI can also show findings associated with the underlying clinical condition, as well as unrelated "incidentalomas". These latter findings are often abnormalities with a high incidence in the general population for which there is no clear literature regarding their management, especially in pediatric patients. The present study aimed to evaluate the number of unnecessary performed MRIs in pediatric endocrinology. Retrospective analysis on 584 MRI scans performed in 414 patients (254 growth hormone deficiency, 41 other causes of short stature, 116 central precocious puberty). The MRI scans were completely normal in 67% of the individuals, and the prevalence of individuals who underwent more than one MRI was 18%, with no significant differences among the groups. The overall prevalence of incidentalomas was 17%. Among 170 repeated MRI scans, 147 (86%) were not required according to a dedicated protocol. Only five patients (four GHD, one Noonan) correctly repeated the MRI. All the repeated MRI scans did not reveal any progression in the findings. If we include the MRIs performed in cases of OCSS other than Noonan syndrome (n=32) and girls with CPP older than 6 years (n=89), an additional 121 MRIs could have been avoided, leading to a total number of unnecessary MRIs to 268 (46%). Only a few specific neuroimaging findings in endocrinologic pediatric patients warrant further investigation, while too often repeated imaging is carried out unnecessarily. We advocate the importance of guidelines to reduce costs for both the healthcare system and patients' families, as well as to alleviate physical and psychological distress for patients and caregivers.

L-DOPA Test in the Diagnosis of Childhood Short Stature: Evaluation of Growth Hormone Peaks Over Time.

In childhood, growth hormone (GH) deficiency (GHD) diagnosis is based on auxological assessment and biochemical provocative tests, whose reliability remains disputed. Recently, several papers have been published on standardising the duration of some tests. The aim of our study was to analyse the possible length reduction of the L-DOPA provocative test. We retrospectively investigated the response of GH to L-DOPA in 256 children, analysing 267 tests (some patients were retested over time for the persistence of severe auxopathy). We studied the same data considering GH peak threshold both at 8 ng/mL (Italian GHD cut-off) and at 10 ng/mL (international cut-off). Based on stimulation tests, patients were divided into two groups: GHD and no-GHD short children. We described the results in the whole population and then clustering for gender and pubertal stage. We termed as index the test stopped at 90 min. The GH peak after L-DOPA mostly occurred at 60 min. The sensitivity of the index test was the highest, while the specificity was slightly higher using the 8 ng/mL threshold (specificity = 0.68; 95% CI 0.60-0.76) then using the 10 ng/mL threshold (specificity = 0.56; 95% CI 0.47-0.65) at 90 min. The two ROC curves showed moderate performance of the test at 90 min. While the negative predictive value was 100% in both tests, the positive predictive value was slightly better with 10 ng/mL cut-off. Considering the two groups established by GHD definition and placing a GH threshold at 10 ng/mL, stopping L-DOPA test time at 90 min would have changed the test result and subsequentially patient's classification in 3/267 of the analysed tests (1.1%), while with the Italian GH threshold value at 8 ng/mL in 7/267 of the tests (2.6%). Our research shows that omitting 120-min time reduces L-DOPA test specificity, especially with GHD cut-off at 10 ng/mL.

Eje hipotálamo-hipofisario. Regulación neurohormonal, implicaciones patológicas, pruebas funcionales hipofisarias, indicaciones e interpretación

The hypothalamic-pituitary axis is a crucial system for maintaining homeostasis by integrating hormonal and neuronal inputs and outputs. Almost all bodily functions are regulated directly or indirectly by this axis. The hypothalamus, a small but vital brain region, monitors various inputs and maintains physiological set points through hormonal secretion, coordinating with the pituitary gland. This regulation involves multiple feedback mechanisms and interactions with other brain areas.The hypothalamus is anatomically divided into several regions and nuclei, each with specific functions. It produces a variety of hormones, including growth hormone-releasing hormone, corticotropin-releasing hormone, thyrotropin-releasing hormone, and gonadotropin-releasing hormone. These hormones regulate the secretion of corresponding hormones from the anterior pituitary gland, which control several physiological processes, including growth, metabolism, reproduction, and stress response.Pathological implications of hypothalamic-pituitary axis dysfunctions include endocrine disorders such as hyperprolactinemia, growth hormone deficiency, and hypogonadism. In addition, hypothalamic damage can lead to neurological and behavioral problems such as sleep disturbances and thermoregulation.