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Pituitary Oct 2023To analyze the clinical, hormonal, and radiological characteristics of Pituitary stalk interruption syndrome (PSIS) in children with growth hormone deficiency (GHD).
PURPOSE
To analyze the clinical, hormonal, and radiological characteristics of Pituitary stalk interruption syndrome (PSIS) in children with growth hormone deficiency (GHD).
METHODS
This is a prospective cross-sectional study, conducted over a period of three years in a short stature clinic of tertiary care referral hospital. 57 severe short stature children with proven GHD were included in the study.
RESULTS
Among 57 children with GHD, 14 (24%) were diagnosed as PSIS. The mean age at diagnosis was 11.8 ± 2.6years. The male to female ratio was 2.5:1. Nine (64%) children had multiple pituitary hormone deficiency (MPHD) and 5 (36%) had isolated growth hormone deficiency (IGHD). In spite of absent or ectopic posterior pituitary (EPP)in Magnetic Resonance Imaging (MRI) of PSIS cohorts, only one had Arginine vasopressin (AVP) deficiency. EPP was seen near median eminence in 6 (44%), elsewhere in 4 (28%), and absent in 4 (28%)children. The height gain following growth hormone therapy was better in PSIS cohorts as compared to non-PSIS.
CONCLUSION
Male gender, breech presentation, external congenital anomalies like cryptorchidism, midline defects and nystagmus were more common in children with PSIS. MPHD were more frequently seen in PSIS whereas IGHD in non-PSIS cohort. AVP deficiency is very rare in PSIS despite of absent or ectopic posterior pituitary in MRI. High index of clinical suspicion in all severe short stature may lead to early diagnosis and prompt initiation of growth hormone treatment for better outcome.
Topics: Adolescent; Child; Female; Humans; Male; Cross-Sectional Studies; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism; Magnetic Resonance Imaging; Pituitary Gland; Pituitary Hormones; Prospective Studies
PubMed: 37695468
DOI: 10.1007/s11102-023-01351-2 -
Best Practice & Research. Clinical... Dec 2023In recent years, mild traumatic brain injury (mTBI) has been recognized as a cause of acquired growth hormone deficiency (AGHD) and is likely much more prevalent than... (Review)
Review
In recent years, mild traumatic brain injury (mTBI) has been recognized as a cause of acquired growth hormone deficiency (AGHD) and is likely much more prevalent than previous estimates. There is great overlap between persistent symptoms following mTBI and those of AGHD and it is possible that these persistent symptoms of mTBI are, at least in part, due to or aggravated by AGHD. This article reviews the current literature of AGHD following mTBI, and proposes practice recommendations for the screening, diagnosis, and management of patients with AGHD following mTBI.
Topics: Adult; Humans; Brain Concussion; Dwarfism, Pituitary; Growth Hormone
PubMed: 37666680
DOI: 10.1016/j.beem.2023.101818 -
Endocrine Practice : Official Journal... Nov 2023Bioinactive growth hormone (BGH) is a structurally abnormal, biologically inactive, but immunoreactive form of growth hormone encoded by pathogenic growth hormone 1 gene... (Review)
Review
OBJECTIVE
Bioinactive growth hormone (BGH) is a structurally abnormal, biologically inactive, but immunoreactive form of growth hormone encoded by pathogenic growth hormone 1 gene variants. The underlying cause of the defective physiology is decreased BGH binding affinity to both growth hormone binding proteins and growth hormone receptors (GHRs). GHR cannot dimerize when it is in a quiescent state because BGH cannot activate it. Nondimerized GHR is unable to activate intracytoplasmic signaling pathway molecules such as Janus kinase 2 and signal transducer and activator of transcription, which initiate insulin-like growth factor-1 (IGF-1) transcription. IGF-1 cannot therefore be synthesized and IGF-1 levels in the circulation decrease. In contrast to children with growth hormone insensitivity, children with short stature due to BGH, known as Kowarski syndrome, exhibit an outstanding linear growth response to recombinant growth hormone therapy. For a number of reasons, differential diagnosis presents some difficulties. Similar diseases caused by genetic abnormalities that cause short stature range in severity from minor to severe clinical spectrum. Furthermore, some patients with Kowarski syndrome have previously been diagnosed with familial short stature, constitutional delayed puberty, and idiopathic short stature. This paper aims to review the particular clinical and laboratory findings of BGH.
METHODS
This study collected clinical and laboratory data from KS cases reported in the literature.
RESULTS
This review reports that KS cases have lower SDSs for height and IGF-1 compared to growth hormone deficiency.
CONCLUSION
The diversity of genetic defects underlying Kowarski syndrome (KS) will provide new insights into growth hormone insensitivity. As the availability of genetic analysis, including functional investigations expands, researchers will identify new underlying genetic pathways.
Topics: Child; Humans; Growth Hormone; Insulin-Like Growth Factor I; Dwarfism, Pituitary; Human Growth Hormone
PubMed: 37657628
DOI: 10.1016/j.eprac.2023.08.013 -
Best Practice & Research. Clinical... Dec 2023Daily injections of recombinant human growth hormone (rhGH) have been used in clinical practice for almost four decades as a replacement therapy in adult patients with... (Review)
Review
Daily injections of recombinant human growth hormone (rhGH) have been used in clinical practice for almost four decades as a replacement therapy in adult patients with GH deficiency (GHD). Long-term adherence to daily injections of rhGH is a clinical concern that may result in reduced therapeutic efficacy, and long-acting GH (LAGH) formulations have been developed in an attempt of overcoming this problem. Long-term safety issues of rhGH are the other side of the coin that has been carefully monitored over the years, particularly related to the proliferative actions of GH that could increase the risk of tumor recurrence or induce the development of new benign and malignant tumors. In this review, we present what is currently known about the cancer risk in GHD adults treated with daily rhGH injections and we discuss the major concerns and responses needed from future surveillance studies regarding the safety of LAGH preparations.
Topics: Adult; Humans; Growth Hormone; Human Growth Hormone; Dwarfism, Pituitary; Hormone Replacement Therapy; Recombinant Proteins; Neoplasms
PubMed: 37643936
DOI: 10.1016/j.beem.2023.101817 -
Best Practice & Research. Clinical... Dec 2023Growth hormone (GH) plays an essential role not only in promoting growth in children, but also in many important metabolic processes in adults. One of the major... (Review)
Review
Growth hormone (GH) plays an essential role not only in promoting growth in children, but also in many important metabolic processes in adults. One of the major metabolic functions of GH is its stimulatory effects on the liver in generating approximately 80% of circulating insulin-like growth factor 1 (IGF-1). Adult growth hormone deficiency (GHD) is an established clinical entity defined as a defect in endogenous GH secretion that is frequently associated with central obesity, loss of muscle mass, decreased bone mass, and impaired quality of life. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are conditions that are often under-recognized in adults with GHD, and accordingly some studies have shown that GH and IGF-1 levels are decreased in patients with NAFLD. Furthermore, it has been reported that it can progress to end-stage liver cirrhosis in some adults and children with GHD. Due to their underlying mechanisms of action, GH and IGF-1 can act on hepatocytes, macrophages, and hepatic stellate cells to mitigate progression to steatosis and fibrosis. It is, thus, important to recognize NAFLD/NASH as important complications in adult and childhood GHD. Therefore, careful and thorough evaluation of NAFLD/NASH in adults with GHD and the consideration for GH replacement therapy is crucial in these patients, together with management of other metabolic risk factors, such as obesity and dyslipidemia. This review will focus on recent reports on the role of GH and IGF-1 in the liver and its clinical significance in the regulation of hepatic function.
Topics: Adult; Child; Humans; Non-alcoholic Fatty Liver Disease; Insulin-Like Growth Factor I; Quality of Life; Growth Hormone; Human Growth Hormone; Dwarfism, Pituitary; Obesity
PubMed: 37643935
DOI: 10.1016/j.beem.2023.101816 -
Children (Basel, Switzerland) Aug 2023Growth hormone (GH) deficiency (GHD) is a rare disorder. The diagnosis of GHD requires a combination of two provocative GH tests. This study aimed to find agreement...
Reliability of Agreement between Insulin, Clonidine, and Glucagon Stimulation Tests for the Diagnosis of Growth Hormone Deficiency in Children: A Retrospective Cohort Study.
Growth hormone (GH) deficiency (GHD) is a rare disorder. The diagnosis of GHD requires a combination of two provocative GH tests. This study aimed to find agreement between commonly used medications to determine which combined tests have high reliability of agreement. This retrospective cohort included 201 children who underwent GH provocation testing from January 2012 to December 2022. The insulin tolerance test (ITT) with the clonidine stimulation test (CST) or glucagon stimulation test (GST) with the CST were performed. We calculated Cohen's kappa to determine the agreement between the test medications by considering the post-stimulation peak GH level with a cut-off value of 10 ng/mL as the primary outcome. A total of 151 patients underwent the two provocative tests and were included in the analysis. Of these patients, 119 underwent the ITT and CST and 54 (45.3%) were diagnosed with GHD. However, 32 patients underwent the GST and CST and 18 (56.2%) were diagnosed with GHD. The kappa value for ITT and CST was 0.258 (25.8%), indicating fair agreement between clonidine and insulin ( = 0.005). However, the kappa value for CST and GST was 0.178 (17.8%), representing slight agreement. The correlation coefficient revealed a very strong relationship between ITT and CST. Clonidine has fair agreement and a very strong correlation coefficient with ITT when used to diagnose GHD in children. Among the commonly used pharmacological tests for GH provocation in our unit, the CST was considered the best pharmacological test in terms of safety and reduced parental anxiety.
PubMed: 37628380
DOI: 10.3390/children10081381 -
The EPMA Journal Sep 2023Human growth hormone (GH) is the indispensable hormone for the maintenance of normal physiological functions of the human body, including the growth, development,... (Review)
Review
Human growth hormone (GH) is the indispensable hormone for the maintenance of normal physiological functions of the human body, including the growth, development, metabolism, and even immunoregulation. The GH is synthesized, secreted, and stored by somatotroph cells in adenohypophysis. Abnormal GH is associated with various GH-related diseases, such as acromegaly, dwarfism, diabetes, and cancer. Currently, some studies found there are dozens or even hundreds of GH proteoforms in tissue and serum as well as a series of GH-binding protein (GHBP) proteoforms and GH receptor (GHR) proteoforms were also identified. The structure-function relationship of protein hormone proteoforms is significantly important to reveal their overall physiological and pathophysiological mechanisms. We propose the use of proteoformics to study the relationship between every GH proteoform and different physiological/pathophysiological states to clarify the pathogenic mechanism of GH-related disease such as pituitary neuroendocrine tumor and conduct precise molecular classification to promote predictive preventive personalized medicine (PPPM / 3P medicine). This article reviews GH proteoformics in GH-related disease such as pituitary neuroendocrine tumor, which has the potential role to provide novel insight into pathogenic mechanism, discover novel therapeutic targets, identify effective GH proteoform biomarker for patient stratification, predictive diagnosis, and prognostic assessment, improve therapy method, and further accelerate the development of 3P medicine.
PubMed: 37605654
DOI: 10.1007/s13167-023-00329-1 -
Growth Hormone & IGF Research :... Aug 2023Late night spontaneous growth hormone (GH) pulses may influence the pituitary GH response to provocation tests. We evaluated GH response during...
OBJECTIVE
Late night spontaneous growth hormone (GH) pulses may influence the pituitary GH response to provocation tests. We evaluated GH response during arginine-insulin-tolerance test (AITT) after a GH peak during a short spontaneous nocturnal profile (SSNP) in children with short stature or low growth velocity.
DESIGN
Using SSNP and subsequent AITT, we examined 257 children 4-18 years old (138 (53.7%) males) recruited from three hospitals. Medical records were reviewed retrospectively. Refractory children were defined as a GH peak ≥7 μg/L during SSNP but no GH peak ≥7 μg/L during AITT.
RESULTS
In total, 201/257 children had a GH peak ≥7 μg/L at SSNP and/or AITT. Of these, 21.9% were refractory. The proportion of males (p = 0.033) and body mass index (BMI) standard deviation score (SDS) (p = 0.037) were higher in the refractory group than in children with a GH peak ≥7 μg/L during AITT. The median period between last GH peak ≥7 μg/L during SSNP and GH at AITT was 210 (30-390) minutes. The GH at AITT occurred 30 min earlier for children without a peak ≥7 μg/L during the SSNP (p = 0.004). The number of refractoriness differed somewhat between the hospitals (p = 0.025).
CONCLUSIONS
Many children with short stature were refractory at testing; among them we found few clinical characteristics. Refractoriness might be influenced by some differences in procedure, but needs to be considered when evaluating GH response in children.
Topics: Male; Humans; Child; Child, Preschool; Adolescent; Female; Retrospective Studies; Prevalence; Insulin-Like Growth Factor I; Growth Hormone; Human Growth Hormone; Insulin; Dwarfism; Arginine; Growth Disorders
PubMed: 37562165
DOI: 10.1016/j.ghir.2023.101549 -
Journal of Pediatric Endocrinology &... Sep 2023The aim of our study was the longitudinal assessment of bone health index (BHI) in short-statured children during growth hormone (GH) treatment to estimate changes in...
OBJECTIVES
The aim of our study was the longitudinal assessment of bone health index (BHI) in short-statured children during growth hormone (GH) treatment to estimate changes in their bone health.
METHODS
256 short-statured children (isolated GH deficiency (IGHD) n=121, multiple pituitary hormone deficiency (MPHD) n=49, intrauterine growth retardation (small for gestational age (SGA)) n=52, SHOX (short stature homeobox gene) deficiency n=9, Ullrich Turner syndrome (UTS) n=25) who started with GH between 2010 and 2018 were included. Annual bone ages (Greulich and Pyle, GP) and BHI were, retrospectively, analysed in consecutive radiographs of the left hand (BoneXpert software) from GH therapy start (T0) up to 10 years (T10) thereafter, with T max indicating the individual time point of the last available radiograph. The results are presented as the median (25 %/75 % interquartile ranges, IQR) and statistical analyses were performed using non-parametric tests as appropriate.
RESULTS
The BHI standard deviation scores (SDS) were reduced (-0.97, -1.8/-0.3) as bone ages were retarded (-1.6 years, -2.31/-0.97) in all patients before start of GH and were significantly lower in patients with growth hormone deficiency (GHD) (-1.04, -1.85/-0.56; n=170) compared to non-GHD patients (-0.79, -1.56/-0.01; n=86; p=0.022). BHI SDS increased to -0.17 (-1/0.58) after 1 year of GH (T1, 0.5-1.49, p<0.001) and to -0.20 (-1/-0.50, p<0.001) after 5.3 years (T max, 3.45/7.25).
CONCLUSIONS
BHI SDS are reduced in treatment-naive short-statured children regardless of their GH status, increase initially with GH treatment while plateauing thereafter, suggesting sustained improved bone health.
Topics: Humans; Child; Growth Hormone; Human Growth Hormone; Retrospective Studies; Bone Density; Hypopituitarism; Dwarfism, Pituitary; Body Height; Growth Disorders; Short Stature Homeobox Protein
PubMed: 37531076
DOI: 10.1515/jpem-2023-0084 -
The Journal of Clinical Endocrinology... Jan 2024The success of growth hormone (GH) replacement in children with classical GH deficiency has led to excitement that other causes of short stature may benefit similarly.... (Review)
Review
The success of growth hormone (GH) replacement in children with classical GH deficiency has led to excitement that other causes of short stature may benefit similarly. However, clinical experience has shown less consistent and generally less dramatic effects on adult height, perhaps not surprising in light of increased understanding of GH and growth plate biology. Nonetheless, clinical demand for GH treatment continues to grow. Upon the 20th anniversary of the US Food and Drug Administration's approval of GH treatment for idiopathic short stature, this review will consider the factors underlying the expansion of GH treatment, the biological mechanisms of GH action, the non-GH-deficient uses of GH as a height-promoting agent, biological constraints to GH action, and future directions.
Topics: Child; Adult; Humans; Growth Hormone; Human Growth Hormone; Dwarfism, Pituitary; Biology; Body Height; Growth Disorders
PubMed: 37450564
DOI: 10.1210/clinem/dgad417