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Mehul T. Dattani - One of the best experts on this subject based on the ideXlab platform.

  • Progression from isolated growth Hormone Deficiency to combined pituitary Hormone Deficiency
    CHURCHILL LIVINGSTONE, 2017
    Co-Authors: Cerbone M, Mehul T. Dattani
    Abstract:

    Growth Hormone Deficiency (GHD) can present at any time of life from the neonatal period to adulthood, as a result of congenital or acquired insults. It can present as an isolated problem (IGHD) or in combination with other pituitary Hormone deficiencies (CPHD). Pituitary deficits can evolve at any time from GHD diagnosis. The number, severity and timing of occurrence of additional endocrinopathies are highly variable. The risk of progression from IGHD to CPHD in children varies depending on the etiology (idiopathic vs organic). The highest risk is displayed by children with abnormalities in the Hypothalamo-Pituitary (H-P) region. Heterogeneous data have been reported on the type and timing of onset of additional pituitary Hormone deficits, with TSH Deficiency being most frequent and Diabetes Insipidus the least frequent additional deficit in the majority, but not all, of the studies. ACTH Deficiency may gradually evolve at any time during follow-up in children or adults with childhood onset IGHD, particularly (but not only) in presence of H-P abnormalities and/or TSH Deficiency. Hence there is a need in these patients for lifelong monitoring for ACTH Deficiency. GH treatment unmasks central hypothyroidism mainly in patients with organic GHD, but all patients starting GH should have their thyroid function monitored closely. Main risk factors for development of CPHD include organic etiology, H-P abnormalities (in particular pituitary stalk abnormalities, empty sella and ectopic posterior pituitary), midline brain (corpus callosum) and optic nerves abnormalities, genetic defects and longer duration of follow-up. The current available evidence supports longstanding recommendations for the need, in all patients diagnosed with IGHD, of a careful and indefinite follow-up for additional pituitary Hormone deficiencies

  • effect of growth Hormone Deficiency on brain structure motor function and cognition
    Brain, 2012
    Co-Authors: Emma A Webb, Michelle A Oreilly, Jonathan D Clayden, Kiran K Seunarine, W K Chong, Naomi Dale, Alison Salt, Chris A Clark, Mehul T. Dattani
    Abstract:

    The growth Hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth Hormone Deficiency on brain structure. Children with isolated growth Hormone Deficiency (peak growth Hormone 10 µg/l) underwent cognitive assessment, diffusion tensor imaging and volumetric magnetic resonance imaging prior to commencing growth Hormone treatment. Total brain, corpus callosal, hippocampal, thalamic and basal ganglia volumes were determined using Freesurfer. Fractional anisotropy (a marker of white matter structural integrity) images were aligned and tract-based spatial statistics performed. Fifteen children (mean 8.8 years of age) with isolated growth Hormone Deficiency [peak growth Hormone 10 µg/l (mean 15 µg/l) and normal growth rate] were recruited. Compared with controls, children with isolated growth Hormone Deficiency had lower Full-Scale IQ (P < 0.01), Verbal Comprehension Index (P < 0.01), Processing Speed Index (P < 0.05) and Movement-Assessment Battery for Children (P < 0.008) scores. Verbal Comprehension Index scores correlated significantly with insulin-like growth factor-1 (P < 0.03) and insulin-like growth factor binding protein-3 (P < 0.02) standard deviation scores in isolated growth Hormone Deficiency. The splenium of the corpus callosum, left globus pallidum, thalamus and hippocampus (P < 0.01) were significantly smaller; and corticospinal tract (bilaterally; P < 0.045, P < 0.05) and corpus callosum (P < 0.05) fractional anisotropy were significantly lower in the isolated growth Hormone Deficiency group. Basal ganglia volumes and bilateral corticospinal tract fractional anisotropy correlated significantly with Movement-Assessment Battery for Children scores, and corpus callosum fractional anisotropy with Full-Scale IQ and Processing Speed Index. In patients with isolated growth Hormone Deficiency, white matter abnormalities in the corpus callosum and corticospinal tract, and reduced thalamic and globus pallidum volumes relate to deficits in cognitive function and motor performance. Follow-up studies that investigate the course of the structural and cognitive deficits on growth Hormone treatment are now required to confirm that growth Hormone Deficiency impacts significantly on brain structure, cognitive function and motor performance.

  • genetic causes and treatment of isolated growth Hormone Deficiency an update
    Nature Reviews Endocrinology, 2010
    Co-Authors: Kyriaki S. Alatzoglou, Mehul T. Dattani
    Abstract:

    Isolated growth Hormone Deficiency is the most common pituitary Hormone Deficiency and can result from congenital or acquired causes, although the majority of cases are idiopathic with no identifiable etiology. Known genes involved in the genetic etiology of isolated growth Hormone Deficiency include those that encode growth Hormone (GH1), growth-Hormone-releasing Hormone receptor (GHRHR) and transcription factor SOX3. However, mutations are identified in a relatively small percentage of patients, which suggests that other, yet unidentified, genetic factors are involved. Among the known factors, heterozygous mutations in GH1 remain the most frequent cause of isolated growth Hormone Deficiency. The identification of mutations has clinical implications for the management of patients with this condition, as individuals with heterozygous GH1 mutations vary in phenotype and can, in some cases, develop additional pituitary Hormone deficiencies. Lifelong follow-up of these patients is, therefore, recommended. Further studies in the genetic etiology of isolated growth Hormone Deficiency will help to elucidate mechanisms implicated in the control of growth and may influence future treatment options. Advances in pharmacogenomics will also optimize the treatment of isolated growth Hormone Deficiency and other conditions associated with short stature, for which recombinant human growth Hormone is a licensed therapy.

  • Molecular analysis of novel PROP1 mutations associated with combined pituitary Hormone Deficiency (CPHD).
    Clinical endocrinology, 2008
    Co-Authors: Daniel Kelberman, S J Rhodes, James P. G. Turton, Kathryn S. Woods, Ameeta Mehta, M. Al-khawari, James Greening, P. G F Swift, Timo Otonkoski, Mehul T. Dattani
    Abstract:

    Summary Objective  Homozygous mutations in the gene encoding the pituitary transcription factor PROP1 are associated with combined pituitary Hormone Deficiency (CPHD) in both mice and humans with a highly variable phenotype with respect to the severity and time of initiation of pituitary Hormone Deficiency. We have ascertained three pedigrees with PROP1 mutations from a large cohort of patients with variable degrees of CPHD who were screened for mutations in PROP1. Results  Affected individuals from all three pedigrees were found to harbour novel PROP1 mutations. We have identified two siblings in one family who were homozygous for an intronic mutation (c.343–11C > G) that disrupts correct splicing resulting in the loss of exon 3 from the PROP1 transcript. Two siblings from a second, unrelated family are compound heterozygotes for two point mutations in the coding region, a missense mutation (p.R125W) that leads to impaired transcriptional activation, and a deletion of a single nucleotide (c.310delC) resulting in a frameshift and nonfunctional mutant protein. Additionally, we identified a homozygous deletion of the PROP1 locus in two patients born to consanguineous parents. Conclusion  Mutations in PROP1 are a frequent cause of familial CPHD. We have described four novel mutations in PROP1 in 3 pedigrees, all resulting in PROP1 Deficiency by different mechanisms. The phenotypic variation observed in association with PROP1 mutations both within and between families, together with the evolving nature of Hormone deficiencies and sometimes changing pituitary morphology indicates a need for continual monitoring of these patients.

  • growth Hormone Deficiency and related disorders insights into causation diagnosis and treatment
    The Lancet, 2004
    Co-Authors: Mehul T. Dattani, M A Preece
    Abstract:

    Advances in molecular biology have led to the identification of mutations within several novel genes associated with the phenotype of isolated growth Hormone Deficiency, combined pituitary Hormone Deficiency, and syndromes such as septo-optic dysplasia. Progress has also been made in terms of the optimum diagnosis of disorders of stature and their treatment. The use of growth Hormone for the treatment of adults with growth Hormone Deficiency and conditions such as Turner's syndrome, Prader-Willi syndrome, intrauterine growth restriction, and chronic renal failure has changed the practice of endocrinology, although cost-benefit implications remain to be established.

Nicholas A Tritos - One of the best experts on this subject based on the ideXlab platform.

  • growth Hormone Deficiency in adults with cushing s disease
    Best Practice & Research Clinical Endocrinology & Metabolism, 2020
    Co-Authors: Nicholas A Tritos
    Abstract:

    Growth Hormone Deficiency (GHD) generally occurs in patients with Cushing's disease (CD) as a consequence of cortisol excess. Mass effect may contribute to the development of GHD in the minority of patients with CD due to corticotroph macroadenomas. Patients with CD in remission are at considerable risk of GH Deficiency as a consequence of pituitary surgery or radiation therapy. The purpose of the present review is to summarize data on GH Deficiency in adults with CD. Untreated GH Deficiency is associated with increased visceral adiposity, decreased lean mass, bone mass, and exercise capacity, impaired linear growth (in children), dyslipidemia, insulin resistance and impaired quality of life. Evaluation and treatment of GHD should be considered in patients with CD in remission. Serum insulin-like growth factor I (IGF-I) can be helpful in the diagnosis of GHD among patients with multiple additional pituitary Hormone deficiencies. The diagnosis of GHD generally requires dynamic testing, including insulin, glucagon or macimorelin stimulation. Growth Hormone replacement may improve body composition, bone density, linear growth (in children), exercise capacity, dyslipidemia and quality of life. While generally safe, GH replacement requires careful monitoring to assure effectiveness and tolerance in treated patients.

  • effects of growth Hormone therapy on bone density and fracture risk in age related osteoporosis in the absence of growth Hormone Deficiency a systematic review and meta analysis
    Endocrine, 2018
    Co-Authors: Maya Barake, Anne Klibanski, Asma Arabi, Nancy Nakhoul, Ghada Elhajj Fuleihan, Sarah El Ghandour, Nicholas A Tritos
    Abstract:

    Purpose In adults, growth Hormone Deficiency (GHD) has been associated with low bone mineral density (BMD), an effect counteracted by growth Hormone (GH) replacement. Whether GH is beneficial in adults with age-related bone loss and without hypopituitarism is unclear.

  • focus on growth Hormone Deficiency and bone in adults
    Best Practice & Research Clinical Endocrinology & Metabolism, 2017
    Co-Authors: Nicholas A Tritos
    Abstract:

    Growth Hormone (GH) exerts several effects on the skeleton, mediated either directly or indirectly, leading to increased bone formation and resorption rates. Patients with growth Hormone Deficiency (GHD) of adult onset have decreased bone mineral density (BMD) and increased fracture risk. Some, but not all, studies have found that adults with childhood onset GHD also have lower BMD than healthy controls. Adults with GHD of childhood onset have smaller bone dimensions, leading to possible underestimation of areal BMD (measured by dual energy X-ray absorptiometry), thus potentially confounding the interpretation of densitometric data. Available data suggest that patients with childhood onset GHD are at increased fracture risk. Prospective studies and some clinical trials found that GH replacement for at least 18–24 months leads to increased BMD. Retrospective and prospective data suggest that GH replacement is associated with decreased fracture risk in adults. However, data from randomized clinical trials are lacking.

János Sólyom - One of the best experts on this subject based on the ideXlab platform.

  • High prevalence of PROP1 gene mutations in hungarian patients with childhood-onset combined anterior pituitary Hormone Deficiency
    Endocrine, 2006
    Co-Authors: Zita Halász, Judit Tőke, Attila Patócs, Rita Bertalan, Zsófia Tömböl, Ágnes Sallai, Éva Hosszú, Ágota Muzsnai, László Kovács, János Sólyom
    Abstract:

    Combined pituitary Hormone Deficiency is characterized by the impaired production of pituitary Hormones, commonly including growth Hormone. The pathomechanism of the childhood-onset form of this disorder may involve germline mutations of genes encoding pituitary transcription factors, of which PROP1 gene mutations have been studied most extensively. However, controversy exists about the significance of PROP1 gene mutations, as both low and high frequencies have been reported in these patients. Because the different results may be related to differences in patient populations and/or the variability of clinical phenotypes, we performed the present study to examine the prevalence and spectrum of PROP1 gene mutations in 35 patients with non-acquired childhood-onset growth Hormone Deficiency combined with at least one other anterior pituitary Hormone Deficiency. Genetic testing indicated the presence of disease-causing mutations in exons 2 and 3 of the PROP1 gene in 15 patients (43% of all patients; homozygous mutations in 10 patients and compound heterozygous mutations in 5 patients). Comparison of clinical data of patients with and without PROP1 gene mutations failed to show significant differences, except an earlier growth retardation detected in patients with PROP1 gene mutations. In one patient with PROP1 gene mutation, radiologic imaging showed an enlargement of the anterior lobe of the pituitary, whereas the other patients had hypoplastic or normal pituitary gland. All patients with PROP1 gene mutations had normal posterior pituitary lobe by radiologic imaging. These results indicate that using our inclusion criteria for genetic testing, PROP1 gene mutations can be detected in a high proportion of Hungarian patients with non-acquired childhood-onset growth Hormone Deficiency combined with at least one other anterior pituitary Hormone defect.

Peter E Clayton - One of the best experts on this subject based on the ideXlab platform.

  • associations with multiple pituitary Hormone Deficiency in patients with an ectopic posterior pituitary gland
    Clinical Endocrinology, 2008
    Co-Authors: Philip G Murray, Leena Patel, Neville B Wright, Catherine M Hall, C Hague, O Fafoula, Andreas Raabe, C Cusick, Rakesh Amin, Peter E Clayton
    Abstract:

    INTRODUCTION: The presence of an ectopic posterior pituitary gland (EPP) on magnetic resonance imaging (MRI) is associated with hypopituitarism with one or more Hormone deficiencies. We aimed to identify risk factors for having multiple pituitary Hormone Deficiency (MPHD) compared to isolated growth Hormone Deficiency (IGHD) in patients with an EPP. METHODS: In 67 patients (45 male) with an EPP on MRI, the site (hypothalamic vs. stalk) and surface area (SA) [ x (maximum diameter/2) x (maximum height/2), mm(2)] of the EPP were recorded and compared in patients with IGHD and MPHD in relation to clinical characteristics. RESULTS: In MPHD (n = 32) compared to IGHD (n = 35) patients: age of presentation was younger (1.4 [0.1-10.7]vs. 4.0 [0.1-11.3] years, P = 0.005), major incidents during pregnancy were increased (47%vs. 20%, P = 0.02) as were admissions to a neonatal intensive care unit (NICU) (60%vs. 26%, P = 0.04), whilst EPP SA was lower (12.3 [2.4-34.6]vs. 25.7 [6.9-48.2] mm(2), P < 0.001). In patients with a hypothalamic (n = 56) compared to a stalk sited EPP (n = 11): prevalence of MPHD was greater (55%vs. 9%,P = 0.05) and EPP surface area was smaller (17.3 [2.4-48.2]vs. 25.3 [11.8-38.5] mm(2), P < 0.001). In regression analysis, after adjusting for age, presence of MPHD was associated with: major incidents during pregnancy (RR 6.8 [95%CI 1.2-37.7]), hypothalamic EPP site (RR 10.9 [1.0-123.9]) and small EPP SA (RR 2.5 [1.0-5.0] for tertiles of SA). CONCLUSION: In patients with an EPP, adverse antenatal events, size (small) and position (hypothalamic) of the posterior pituitary gland on MRI were associated with MPHD. These findings suggest that adverse factors during pregnancy may be important for the development of an EPP.

  • optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia multiple pituitary Hormone Deficiency isolated growth Hormone Deficiency and idiopathic short stature
    The Journal of Pediatrics, 2004
    Co-Authors: Niels H Birkebaek, Leena Patel, Neville B Wright, John R Grigg, Smeeta Sinha, Catherine M Hall, David Price, Ian Christopher Lloyd, Peter E Clayton
    Abstract:

    Objective To objectively define criteria for intracranial optic nerve (ON) size in ON hypoplasia (ONH) on magnetic resonance imaging (MRI) scans. Study design Intracranial ON sizes from MRI were compared between 46 children with ONH diagnosed by ophthalmoscopy (group 1, isolated ONH, 8 children; and group 2, ONH associated with abnormalities of the hypothalamic-pituitary axis and septum pellucidum, 38 children) and children with multiple pituitary Hormone Deficiency (group 3, multiple pituitary Hormone Deficiency, 14 children), isolated growth Hormone Deficiency (group 4, isolated growth Hormone Deficiency, 15 children), and idiopathic short stature (group 5, idiopathic short stature, 10 children). Intracranial ON size was determined by the cross-sectional area, calculated as [π × ½ height × ½ width]. Results Groups 1 and 2 had lower intracranial ON size than did groups 3, 4, and 5 ( P 2 . Visual acuity correlated significantly with ON size ( P Conclusions Magnetic resonance imaging of the ONs with cross-sectional area 2 in a short child more than 12 months of age, with or without hypothalamic-pituitary axis abnormalities, confirms the clinical diagnosis of ONH.

Anne Klibanski - One of the best experts on this subject based on the ideXlab platform.