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Between 2% and 60% of patients with cured acromegaly may eventually develop growth hormone deficiency. In adults, growth hormone deficiency is associated with abnormal body composition, decreased exercise capacity and quality of life, dyslipidemia, insulin resistance and increased cardiovascular risk. Similar to patients with other sellar lesions, the diagnosis of growth hormone deficiency in adults with cured acromegaly generally requires stimulation testing, with the exception of patients with very low serum insulin-like growth factor I levels and multiple additional pituitary hormone deficiencies. In adults with cured acromegaly, growth hormone replacement may have beneficial effects on body adiposity, muscle endurance, serum lipids and quality of life. Growth hormone replacement is generally well-tolerated. Arthralgias, edema, carpal tunnel syndrome and hyperglycemia may occur in patients with cured acromegaly, as is true of patients with growth hormone deficiency of other etiologies. However, there is evidence of increased cardiovascular risk in some studies of growth hormone replacement in adults with cured acromegaly. More studies are needed to fully establish the beneficial effects and elucidate the risks of growth hormone replacement in adults with cured acromegaly. Until then, growth hormone replacement can be considered in these patients on a case-by-case basis., Competing Interests: Declaration of Competing Interest The author has received occasional consulting fees from Alnylam Pharmaceuticals, Inc and Pfizer, Inc., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Growth hormone is among the most common hormones to be deficient in pituitary insult. It can occur either in isolation or combined with other hormone deficiencies. Growth hormone deficiency in adults (AGHD) can be due to causes acquired in adulthood or have a childhood-onset etiology, but the former is about three times more common. Usual causes of AGHD include mass effects due to a pituitary tumour, and/or its treatment (surgery, medical therapy, or radiotherapy), or radiotherapy to the head and neck region for non-pituitary lesions. The unusual or lesser-known causes of AGHD, are usually due to non-tumoral etiology and range from vascular and infective to inflammatory and miscellaneous causes. These not only expand the spectrum of AGHD but may also contribute to increased morbidity, adverse metabolic consequences, and mortality due to the primary condition, if unrecognised. The review features these lesser-known and rare causes of AGHD and highlights their clinical and diagnostic implications., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder that is characterized by a segmental dermatomal facial port-wine stain birthmark and is frequently accompanied by ipsilateral brain and eye abnormalities. We present a case of a patient with SWS who exhibited hypogonadotropic hypogonadism, growth hormone (GH) deficiency, and central hypothyroidism at the age of 20 despite the absence of radiographic findings in the pituitary and hypothalamus., Case Presentation: A 20-year-old male with SWS with epilepsy and Klippel-Trenaunay syndrome presents with delayed pubertal development, short stature, and obesity. Upon further examination, he was found to have biochemical and clinical evidence of hypogonadism, hypothyroidism, and GH deficiency. A pituitary MRI displayed no abnormalities of the pituitary or hypothalamus. Treatment with testosterone cypionate and levothyroxine was initiated. Despite successful pubertal induction, IGF-1 levels have remained low and treatment with recombinant human growth hormone (rhGH) is now being considered for metabolic benefits., Conclusions: This case emphasizes the importance of endocrine evaluation and treatment of hormonal deficiencies in patients with SWS despite the absence of radiographic findings., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Growth hormone deficiency (GHD) is a common complication in survivors of cancer and patients with tumors of the pituitary region. Growth hormone replacement therapy (GHT) has proven beneficial effects, including increased growth velocity, positive effects on body composition and skeletal integrity, and increased quality of life. However, due to known pro-proliferative, angiogenic, and anti-apoptotic properties of growth hormone, there are still some concerns about the safety of GHT in survivors. This narrative review aims to provide an overview of the long-term sequelae, and subsequently long-term safety, of GHT in survivors of (childhood) cancer and patients with tumors of the pituitary region. We identified predominantly reassuring results regarding the safety of survivors with GHT, although we must take into account the shortcomings of some studies and limited information on adult cancer survivors. Besides the already increased risk for second neoplasms, recurrences, or mortality in survivors due to host-, disease-, and treatment-related factors, we could not identify an increased risk due to GHT in particular. Therefore, we support the consensus that GHT can be considered in survivors after careful individual risk/benefit analysis and in open discussion with the patients and their families, taking into account the known morbidity of untreated GHD in cancer survivors and the positive effects of GHT.

Often transfusions red blood cells in patients with hereditary anemias lead to iron overload, that can cause endocrine complications, such as growth retardation, hypothyroidism, hypogonadism, and disorders of carbohydrate metabolism.Clinical case 1. A boy with transfusion-dependent (TD) Diamond-Blackfan anemia at 16.3 years presented with impaired fasting glucose, growth hormone (GH) deficiency, hypogonadotropic hypogonadism; GH therapy was initiated. At the age of 16.8 years old secondary hypothyroidism, secondary hypocorticism and diabetes mellitus were diagnosed. At 17.2 years continuous glucose monitoring (CGM) detected glucose elevations up to 11.7 mmol/l. Therapy with GH and testosterone ethers was continued; levothyroxine and cortef were stopped by patient. At 17.9 years height was 163 cm; no data supporting hypothyroidism nor hypocorticism; glycaemia within goal range.Clinical case 2. A girl with TD beta-thalassemia major at the age of 11.5 years presented with GH deficiency; GH therapy has been conducted from 12.8 to 15.3 years of age. At 13.8 years retardation of pubertal development was diagnosed. At 15.0 hyperglycemia 7.2 mmol/l was detected; normal results of oral glucose tolerance test (OGTT) were observed; glycemia elevations were up to 9.5 mmol/l according to CGM data. At 16.0 height was 152 cm; because of pubertal development arrest hormone replacement therapy was prescribed.CONCLUSION. Growth, pubertal and carbohydrate metabolism disorders were diagnosed in patients with TD hereditary anemias, that confirms the necessity of regularly endocrine investigation. To detect impairment of carbohydrate metabolism investigation of fasting blood glucose, OGTT, and CGM is recommended; glycated hemoglobin measurement is not considered reasonable.

Objectives: Growth hormone deficiency (GHD) in adults is associated with an increased risk of cardiovascular morbidity and mortality. Although children with GHD are also believed to have a similar cardiovascular disease (CVD) risk beginning at an early age, the available data in children is scarce. We aimed to determine the various CVD risk parameters in children with isolated GHD (IGHD)., Methods: A cross-sectional case-control study was conducted at a tertiary care centre in North India comparing various auxological, biochemical, and echocardiographic parameters between 20 IGHD children aged 5-15 years and their age and sex-matched healthy controls., Results: The mean age of children with IGHD and controls was similar (10.5 ± 2.6 yr vs. 9.9 ± 2.7 yr, p=0.48). Children with IGHD had significantly higher waist-hip-ratio (p=0.01), total cholesterol (p=0.02), non-high-density lipoprotein-cholesterol (p=0.02), serum homocysteine (p<0.001), C-reactive protein (CRP) (p=0.01) and pro-brain natriuretic peptide (pro-BNP) (p=0.04) levels as compared to healthy controls. Left ventricular mass (LVM) and interventricular septal thickness were significantly lower (p=0.04; p=0.02) in IGHD children. Correlation analysis showed that pro-BNP and CRP levels had negative correlation (p<0.001, r=-0.70; and p=0.04, r=-0.44, respectively) and LVM had a positive correlation (p=0.02, r=0.53) with height SDS among IGHD children., Conclusions: Children with IGHD showed abnormalities in several biochemical and cardiac parameters that may be associated with an increased CVD risk in later life. More extensive studies, including younger children with IGHD, are needed to determine the lower ages at which the CVD risk is detectable., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Context: Data on long-term safety of growth hormone (GH) replacement in adults with GH deficiency (GHD) are needed., Objective: We aimed to evaluate the safety of GH in the full KIMS (Pfizer International Metabolic Database) cohort., Methods: The worldwide, observational KIMS study included adults and adolescents with confirmed GHD. Patients were treated with GH (Genotropin [somatropin]; Pfizer, NY) and followed through routine clinical practice. Adverse events (AEs) and clinical characteristics (eg, lipid profile, glucose) were collected., Results: A cohort of 15 809 GH-treated patients were analyzed (mean follow-up of 5.3 years). AEs were reported in 51.2% of patients (treatment-related in 18.8%). Crude AE rate was higher in patients who were older, had GHD due to pituitary/hypothalamic tumors, or adult-onset GHD. AE rate analysis adjusted for age, gender, etiology, and follow-up time showed no correlation with GH dose. A total of 606 deaths (3.8%) were reported (146 by neoplasms, 71 by cardiac/vascular disorders, 48 by cerebrovascular disorders). Overall, de novo cancer incidence was comparable to that in the general population (standard incidence ratio 0.92; 95% CI, 0.83-1.01). De novo cancer risk was significantly lower in patients with idiopathic/congenital GHD (0.64; 0.43-0.91), but similar in those with pituitary/hypothalamic tumors or other etiologies versus the general population. Neither adult-onset nor childhood-onset GHD was associated with increased de novo cancer risks. Neutral effects were observed in lipids/fasting blood glucose levels., Conclusion: These final KIMS cohort data support the safety of long-term GH replacement in adults with GHD as prescribed in routine clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

49,XXXXY is an X and Y chromosome variation that occurs in 1:85,000 to 1:100,000 live male births. Previous case studies have described boys with this disorder to be shorter than average when compared with boys with only one extra chromosome and with the mean stature in a small cohort reported to range from the seventh to 33rd percentile. The origin behind the possible differences in height between boys with 47,XXY and 49,XXXXY is currently unknown, however one study hypothesized that it was due to a difference in the expression of the SHOX gene. This study reports on the anthropometric measurements of 84 boys with 49,XXXXY. Forty-five percent of children with 49,XXXXY were found to be below the third percentile in height at the time of evaluation. In addition, 7.14% of the cohort were diagnosed and given treatment for growth hormone deficiency (GHD). The analysis of this cohort demonstrates that the below average heights seen throughout childhood in this population potentially begins prenatally and suggests that boys with 49,XXXXY may be at a higher risk for intrauterine growth restriction (IUGR) and GHD. Future research is needed to investigate the etiology of the poor growth in boys with 49,XXXXY and evaluate the incidence of GHD and IUGR in this population., (© 2020 Wiley Periodicals LLC.)

Objectives: Childhood growth influences their social and psychological behavior, and abnormal growth may reflect underlying pathological etiologies. It is important to diagnose children with short stature as early as possible to be able to manage treatable causes. We aim to study etiologies and characteristics of short stature in children in Jordan., Methods: This is a cross-sectional retrospective review of the medical records of children diagnosed with short stature at a referral university hospital. Clinical characteristics, auxological, laboratory, and radiological investigations were collected and analyzed., Results: Among a total of 551 children diagnosed with short stature, the number of boys was significantly higher than girls, 304 (55.2%) and 247 (44.8%), respectively with a p-value of 0.015. Average age at presentation for all patients was 10.24 ± 3.23, with no significant difference between boys and girls. Pathological etiology was higher than normal variants 55.7 and 44.3%, respectively with p=0.007. Constitutional delay of growth and puberty (CDGP) was the most frequent cause in the normal variant group, 59.8%. Among the pathological group, the most common etiology was growth hormone deficiency (32.2%) with mean age of presentation of 9.40 years and was not significantly different from the age in other etiological groups, 9.44 years and p=0.931., Conclusions: Growth monitoring of children should start at an early age for boys and girls. Referral to the pediatric endocrine clinic should be considered when growth problems are suspected for accurate diagnosis and etiology profiling., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The prevalence of childhood-onset growth hormone (GH) deficiency (GHD) is estimated to be approximately 1 in 5000 or more, with the cause unknown in most cases (idiopathic isolated GHD). However, additional disorders of secretion of other pituitary hormones reportedly develop over time, with a frequency of 2-94% (median, 16%). Furthermore, median times to development of other anterior pituitary hormone deficiencies have been reported to be 6.4-9.4 years. On the other hand, adult patients affected by childhood-onset GHD reportedly develop impaired ventilation function due to reduced lung volumes and respiratory pressures, probably due to reductions in respiratory muscle strength. In addition, GH is known to play a role in stimulating the glomerular filtration rate (GFR), and the estimated GFR (eGFR) is decreased in patients with GHD., Case Presentation: This case involved a 65-year-old woman. Her short stature had been identified at around 3 years of age, but no effective treatments had been provided. The patient was mostly amenorrheic, and hair loss became apparent in her late 30s. She developed hyperuricemia, dyslipidemia, and hypertension at 45 years of age. In addition, the patient was diagnosed with hypothyroidism at 50 years of age. At 58 years of age, endocrinological examination showed impaired secretion of thyroid-stimulating hormone, luteinizing hormone/follicle-stimulating hormone, and growth hormone, and magnetic resonance imaging showed an empty sella turcica. However, secretion ability of adrenocorticotropic hormone was retained. At 63 years of age, respiratory function tests confirmed a markedly restricted ventilation disorder (vital capacity, 0.54 L; percentage predicted vital capacity, 26.9%). Renal function had also decreased (eGFR, 25.0 mL/min/1.73 m 2 ). Furthermore, she was diagnosed with hypothalamic secondary hypoadrenocorticism. The patient developed CO 2 narcosis at 65 years of age, and noninvasive positive pressure ventilation was started., Conclusions: The rare case of a 65-year-old woman with childhood-onset GHD with panhypopituitarism, including late-onset secondary hypoadrenocorticism in her 60s, associated with severely impaired respiratory function and renal dysfunction, was reported. In GHD patients with risk factors for progression from isolated GHD to combined pituitary hormone deficiency, such as empty sella turcica, lifelong endocrinological monitoring may be important.

Nodding syndrome (NS) is a progressive encephalopathy of children and adolescents characterized by seizures, including periodic vertical head nodding. Epidemic NS, which has affected parts of East Africa, appears to have clinical overlap with sub-Saharan Nakalanga syndrome (NLS), a brain disorder associated with pituitary dwarfism that appears to have a patchy distribution across sub-Sahara. Clinical stages of NS include inattention and blank stares, vertical head nodding, convulsive seizures, multiple impairments, and severe cognitive and motorsystem disability, including features suggesting parkinsonism. Head nodding episodes occur in clusters with an electrographic correlate of diffuse high-amplitude slow waves followed by an electrodecremental pattern with superimposed diffuse fast activity. Brain imaging reveals differing degrees of cerebral cortical and cerebellar atrophy. Brains of NS-affected children with mild frontotemporal cortical atrophy display neurofibrillary pathology and dystrophic neurites immunopositive for tau, consistent with a progressive neurodegenerative disorder. The etiology of NS and NLS appears to be dominated by environmental factors, including malnutrition, displacement, and nematode infection, but the specific cause is unknown., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: GH deficiency (GHD) is characterized by a cluster of cardiovascular risk factors and subtle inflammation. We aimed to demonstrate, through a proteomic approach, molecules directly modulated by GHD and involved in the inflammatory state., Methods: Ten children with isolated GHD were studied before and after 1 year of treatment with rhGH and compared with 14 matched controls. A two-dimensional electrophoresis plasma proteomics analysis was performed at baseline and after GH treatment to identify the top molecules modulated by GH. In vitro studies on human hepatoma (HepG2) cells were performed to validate the data., Results: Twelve of 20 proteomic spots were predicted to be isoforms α and β of haptoglobin (Hp) and confirmed by liquid chromatography tandem mass spectrometry and Western immunoblot analyses. Hp levels were higher in patients with GHD than controls at baseline (P < 0.001) and were reduced following GH treatment (P < 0.01). In HepG2 cells, both GH and IGF-1 were able to downregulate IL-6-induced Hp secretion. Moreover, Hp secretion was restored in pegvisomant-treated HepG2 cells., Conclusions: Hp is a molecule acting in the inflammatory state of GHD and a possible biomarker for GH treatment. Nevertheless, the contribution of other factors and the molecular pathways involved in the GH downregulation of Hp remain to be clearly defined., (Copyright © 2019 Endocrine Society.)

Objectives: Voice is produced by the vibration of the vocal folds expressed by its fundamental frequency (Hz), whereas the formants (F) are fundamental frequency multiples, indicating amplification zones of the vowels in the vocal tract. We have shown that lifetime isolated growth hormone deficiency (IGHD) causes high pitch voice, with higher values of most formant frequencies, maintaining a prepuberal acoustic prediction. The objectives of this work were to verify the effects of the therapy with a semi-occluded vocal tract (SOVTT) and choir training on voice in these subjects with IGHD. We speculated that acoustic vocal parameters can be improved by SOVTT or choir training., Study Design: This is a prospective longitudinal study without control group., Methods: Acoustic analysis of isolated vowels was performed in 17 adults with IGHD before and after SOVTT (pre-SOVTT and post-SOVTT) and after choir training (post training), in a 30-day period., Results: The first formant was higher in post training compared with the pre-SOVTT (P = 0.009). The second formant was higher in post-SOVTT than in pre-SOVTT (P = 0.045). There was a trend of reduction in shimmer in post-choir training in comparison with pre-SOVTT (P = 0.051), and a reduction in post-choir training in comparison with post-SOVTT (P = 0.047)., Conclusions: SOVTT was relevant to the second formant, whereas choir training improved first formant and shimmer. Therefore, this speech therapy approach was able to improve acoustic parameters of the voice of individuals with congenital, untreated IGHD. This seems particularly important in a scenario in which few patients are submitted to growth hormone replacement therapy., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Hypoglycaemia in infants and children is caused by a number of endocrine and metabolic defects, some of which are unique to this age group. Growth hormone deficiency (GHD) has been rarely reported as a cause of recurrent fasting hypoglycaemia in children. An 18-month-old male child presented to us for evaluation of neuroglycopenic symptoms caused by recurrent episodes of fasting hypoglycaemia. Laboratory evaluation revealed ketotic hypoinsulinaemic hypoglycaemia. The child was diagnosed to have GHD on the basis of two failed stimulation tests. A detailed work-up for metabolic and other hormonal causes of hypoglycaemia was negative. We present the case for its rarity and to highlight the importance of a detailed metabolic and hormonal assessment in evaluation of childhood hypoglycaemia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Available evidence suggests that the fertility of growth hormone deficient female patients could be decreased, although the responsible mechanisms are unknown. Taking into account the multiple effects of growth hormone on reproduction suggested by experimental and clinical studies in women without growth hormone deficiency, the growth hormone deficit by itself could contribute to infertility in these patients. However, the necessity of growth hormone administration and the profile of the infertile patients with growth hormone deficiency who would benefit from treatment are largely unknown. Growth hormone effects on oocyte quality is one of the possible mechanisms through which growth hormone could be involved in fertility of these patients. However, this hypothesis was not tested in patients with adequately diagnosed growth hormone deficiency. We present the case of a 29-year-old female patient with growth hormone deficiency and tubal infertility who was referred for in vitro fertilization treatment. The couple underwent two conventional in vitro fertilization procedures: the first one, without growth hormone treatment and, because no pregnancy was achieved, the second one after growth hormone (somatropinum) administration for 3 months. Although the number of the retrieved oocytes was the same, the quality of the oocytes was improved and their ability to evolve into good quality embryos after fertilization was increased after growth hormone administration. Consequently, the pregnancy was obtained after the second in vitro fertilization treatment and patient gave birth to a healthy boy. In conclusion, our case report suggests that adequate levels of growth hormone are essential for an adequate competence of the oocytes in infertile patients with growth hormone deficiency. Therefore, growth hormone administration should be taken into consideration for patients with this deficiency in order to optimize the results of infertility treatment. Abbreviations: GH: growth hormone; GHD: growth hormone deficiency; HCG: human chorionic gonadotropin; IVF: in vitro fertilization; IGF: insulin like growth factor.

Biological functions of immunoglobulin-free light chains (FLCs), other than in chronic inflammatory diseases, are still poorly defined; the field of insulin resistance (IR) has not been investigated, despite the strict relationships with oxidative stress (OS) and inflammation. Therefore, we evaluated FLCs levels and their relationships with metabolic parameters in adult growth hormone deficiency (GHD) and metabolic syndrome (MetS), both characterized by IR. One hundred subjects were enrolled: group A, patients with GHD [n =31, 24-69 years, mean ± SEM body mass index (BMI) 26.8 ± 1.5 kg/m 2 ]; group B, patients with MetS (n = 29, 21-70 years, BMI 31.9 ± 1.3); group C, controls (N = 40, 21-62 years, BMI 21.6 ± 1.1). Groups were matched by age range and, for patients, by BMI. Morning blood sample was collected for metabolic parameters and FLCs, assessed by turbidimetric assay. GHD patients show levels of FLCs significantly higher than MetS and controls (mean ± SEM κ 37.21 ± 6.97, 15.27 ± 0.86, 12.34 ± 0.85 mg/l; λ 19.44 ± 2.61, 11.78 ± 0.72 and 11.67 ± 0.77 mg/l; κ/λ ratio 1.77 ± 0.13, 1.38 ± 0.09; and 1.10 ± 0.06, respectively); only κ were higher in MetS versus controls. Therefore, the ratio showed progressive declining values in GHD versus MetS versus controls. Our data show increased FLCs levels in GHD and MetS, with the highest values in the former. Both conditions show OS, but with different molecular patterns. FLCs may contribute to chronic inflammation, leading to OS, and cardiovascular complications of GHD. Prognostic and therapeutic implications require further investigation. © 2018 BioFactors, 44(5):480-484, 2018., (© 2018 International Union of Biochemistry and Molecular Biology.)

Growth hormone (GH) and the insulin-like growth factor I (IGF-I) have cell proliferative and differentiation properties. Whether these hormones have a role in mutagenesis is unknown. Nevertheless, severe IGF-I deficiency seems to confer protection against the development of neoplasms. Here, we report five cases of adult patients with severe and congenital isolated GH deficiency (IGHD) due to the c.57+1G>A mutation in the GHRH receptor gene, who developed tumors. Four GH-naïve subjects presented skin tumors: a 42-year-old man with a fibroepithelial polyp, a 53-year-old woman and two men (59 and 56 years old) with epidermoid skin cancers. One of these died from it after three surgeries and radiotherapy. The fifth patient was a 25-year-old woman, who had intermittently received GH replacement therapy (GHRT) from age 11 to 18, who developed an ependymoma extending from the fourth ventricle to the end of the thoracic spine. She underwent three surgical procedures, without obvious evidence of tumor recurrence during the six years follow up. These observations suggest that severe IGHD does not protect completely from development of tumors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Studies on pulmonary function tests (PFTs) in Growth Hormone Deficiency (GHD) children are lacking. The aims of this study were: (i) to investigate PFTs in GHD pre-pubertal children with respect to Controls, before starting Growth Hormone Therapy (GHT) (T0); (ii) to evaluate changes of PFTs in GHD vs Controls, after 1-year GHT (T1). For both aims the mediation analysis (MA) was applied to evaluate the extent to which the relationship between GHD and PFTs could be ascribed to a height-mediated (indirect) or a GH direct effect., Methods: 47 pre-pubertal GHD children (aged 5-14 years) underwent PFTs at T0 and T1. At T0, 47 healthy children matched for age and sex were enrolled as Controls. A MA was performed to assess the relationship between GHD and PFTs and height. Statistical analyses were performed using the statistical software R (https://cran.r-project.org/mirrors.html). A p-value <0.05 was considered significant., Measurements and Main Results: At T0, PFTs indices were significantly lower in GHD than in Controls. From T0 to T1 a significant improvement was found in PFTs. The percentages of the mediated effect on FVC, FEV 1 , FEF 25-75% and TLC were <50% at T0, suggesting that the direct effect was prevalent. At T1, the percentages of the mediated effect for spirometry indices were ≥50%, indicating that the indirect (height-mediated) effect was the most relevant., Conclusions: The study shows that pre-pubertal children with GHD have an impairment of lung function not exclusively attributable to the indirect (height-mediated) effect, but also to the direct GH action which is mitigated after 1-year of GHT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Approximately 30% of children with idiopathic growth hormone deficiency (IGHD) also suffer from other pituitary hormone deficien-cies. Of children with IGHD, approximately 10% are unable to generate appropriate ACTH levels in response to stress. This study was prospectively designed to test the integrity of the adrenal axis in patients with an established diagnosis of IGHD using the glucagon stimulation test (GST). The study population comprised 39 patients with established childhood-onset IGHD. The diagnosis of GHD was established on the basis of failure of GH to increase over 10 ng/ml after two stimulation tests. The GST was performed by intra-muscular injection of 1 mg glucagon. The criteria followed to define adrenal deficiency was cortisol less than 167 ng/l in response to GST. The mean peak blood glucose level was 8.64 ±1.71 mmol/l. Analysing the cohort using the cut-off of 167 ng/ml to define adrenal insufficiency under GST, there were 25.64% of children diagnosed: 20% among males and 35.7% among females. Subjects with GH and ACTH deficiency had a mean peak GH of 2.07 ±1.79 ng/ml - significantly lower than GH peak of children with IGHD alone (p < 0,001). The frequency of children with combined somatotroph and corticotroph deficiencies with a GH peak < 3 ng/ml was 21% (p < 0,001). The current study identified a prevalence of adrenal insufficiency of 25.64%, which could predict greater risk for children if untreated, especially because a substantial proportion of patients do not present clinical symptoms.

Background: Short stature is one of the common disorders referred for investigation of an endocrine disorder. The etiologies of short stature vary and are commonly grouped into pathological and non-pathological disorders. The objective of the study was to determine the etiologies and describe the characteristics of short stature patients who attended the Pediatric Endocrinology Clinic and to compare factors between normal variant short stature (NVSS) and growth hormone deficiency (GHD)., Methods: This was a retrospective review of 572 patients referred for evaluation of short stature between January 2004 and December 2015. Short stature was defined as height below -2 standard deviation score (SDS) by gender and age based on population data of Thai children., Results: In total, 521 patients were identified as having short stature. NVSS was the most common etiology (44.9%) and pathological short stature was found in 35.3% of the cases, of which 21.2% had GHD. The median age at presentation of NVSS patients was 8.6 years while that of pathological short stature patients was 2.1 years (p<0.001). Patients with NVSS had significantly higher median height SDS (HSDS) than patients with pathological diseases. The common etiologies in severe short patients, defined by HSDS ≤-3, were syndromic short stature (16.2%) and GHD (14.1%). In the moderate short stature group (HSDS between -2 and -3), constitutional delay of growth and puberty (CDGP) was the most common etiology (34.1%)., Conclusions: NVSS was the most common etiology of short stature, followed by syndromic short stature and GHD. Physical examination is crucial to identify GHD from syndromic short patients.

Objective: Although insulin-like growth factor 1 (IGF-1) has been shown to be important for inner-ear development in animal models, little is known about the otologic and audiologic findings of children with growth hormone deficiency (GHD). The goal of this study is to evaluate the prevalence, type, and severity of hearing impairment in children with GHD., Methods: Audiologic, otologic, and demographic data were recorded for children with a diagnosis of GHD in the AudGen database. Data for each patient were selected based on the first encounter with available complete audiometric data or the first encounter with a type of hearing loss documented. The patients were then stratified by type and severity of hearing loss, and otologic issues were documented. A separate cohort comprised of children with GHD without hearing loss was compared as a control., Results: 209 children with GHD met inclusion criteria. 173 (83%) of these patients had hearing loss. 79% of losses were bilateral and 21% were unilateral (309 total ears with hearing loss). 293 of the 309 ears with hearing loss had audiograms with ear-specific thresholds; 47 had conductive, 24 had sensorineural, 65 had mixed and 157 had undefined hearing loss with incomplete audiograms. Pure-tone averages (PTA) were higher among patients with mixed hearing loss compared to patients with all other loss types., Conclusion: Hearing loss is prevalent in children with GHD with a predisposition to be bilateral. These findings suggest the need for increased awareness and routine hearing screening for patients with GHD. Further studies may elucidate the etiology of the hearing impairment in children with GHD to better aid pediatricians, endocrinologists, otolaryngologists and audiologists when assessing and managing these children., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We describe the anaesthetic management for caesarean section in a 32-year-old patient with pituitary dwarfism. In addition to supportive treatment, we offered a postoperative epidural analgesia pump. The patient recovered well without any complications., (Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Growth hormone is important for the development and function of the immune system, but there is controversy on whether growth hormone deficiency is associated to immune disorders. A model of isolated growth hormone deficiency may clarify if the lack of growth hormone is associated with increased susceptibility to infections, or with an altered responsiveness of the immune system. We have studied the frequency of infectious diseases and the immune function in adults with congenital, untreated isolated growth hormone deficiency. In a cross-sectional study, 35 adults with isolated growth hormone deficiency due to a homozygous mutation in the growth hormone releasing hormone receptor gene and 31 controls were submitted to a clinical questionnaire, physical examination serology for tripanosomiasis, leishmaniasis, HIV, tetanus, hepatitis B and C, and serum total immunoglobulin G, M, E and A measurement. The immune response was evaluated in a subset of these subjects by skin tests and response to vaccination for hepatitis B, tetanus, and bacillus Calmette-Guérin. There was no difference between the groups in history of infectious diseases and baseline serology. Isolated growth hormone deficiency subjects had lower total IgG, but within normal range. There was no difference in the response to any of the vaccinations or in the positivity to protein Purified Derived, streptokinase or candidin. Adult untreated isolated growth hormone deficiency does not cause an increased frequency of infectious diseases, and does not alter serologic tests, but is associated with lower total IgG levels, without detectable clinical impact.

The aim of this study was to evaluate the ability of the growth hormone-releasing peptide-2 (GHRP-2) test to clinically diagnose hypothalamo-pituitary-adrenal (HPA) axis failure. We performed an insulin tolerance test (ITT), CRH stimulation test, and GHRP-2 test on 47 patients suspected of having a hypothalamo-pituitary disorder. Patients with pituitary disorders had significantly lower ACTH responses to the GHRP-2 test compared to patients with hypothalamic disorders and the control group. In contrast, peak cortisol levels in response to the GHRP-2 test were significantly lower in both hypothalamic and pituitary disorder cases compared with the control group. Assignment of a cut-off value of 11.6 μg/dL for the peak serum cortisol level demonstrated that the GHRP-2 test was able to predict secondary hypoadrenalism with 88.9% specificity and 89.7% sensitivity. The responses of ACTH and cortisol to the GHRP-2 test had no correlation to the CRH test, suggesting the involvement of a different mechanism of ACTH secretion. These results indicate that the GHRP-2 test may induce ACTH secretion from the pituitary gland through direct stimulation. Although the GHRP-2 test does not have the same predictive value as the insulin tolerance test (ITT), it has similar diagnostic potential as the CRH stimulation test for evaluating HPA axis failure.

Background: Agenesis of the internal carotid artery (ICA) is a rare congenital abnormality, sporadically reported to be associated with a combined congenital hypopituitarism. Nevertheless, only a few cases have been extensively described, and none of these have been characterized by an isolated growth hormone (GH) deficiency., Case Presentation: Here, we describe a 17-year old boy referred to our hospital for fatigue, decreased muscle strength and severe headache reported after the cessation of rhGH treatment for a GH deficiency diagnosed at the age of 2 years and 3 months. Magnetic resonance imaging (MRI) showed an adenohypophyseal hypoplasia with a lack of posterior pituitary hyperintensity, whereas MRI angiography indicated the absence of a normal flow void in the left ICA. Endocrinological tests confirmed the GH deficiency (GH peak after growth-hormone-releasing hormone (GHRH) + arginine: 2.42 ng/mL) with a very low IGF-I value (31 ng/mL) and normal function of other pituitary axes., Conclusion: To the best of our knowledge this is the first confirmed case of an isolated GH deficiency in a patient with ICA agenesis. The presence of an isolated pituitary deficit is unlike to be considered only as an effect of hemodynamic mechanism, suggesting a role for genetic factor(s) as a common cause of these two rare birth defects. Further studies could clarify this issue and the underlying mechanisms to better understand the etiopathogenetic characteristics of this disorder.

Introduction: Mitochondrial respiratory chain (MRC) disorders, defined as primary diseases of the oxidative phosphorylation system, are a protean group of metabolic disorders, difficult to diagnose and classify. The diagnosis is complex and requires the integration of information obtained by clinical, laboratory testing, imaging and muscle biopsy. They may be associated with endocrine disorders, including hypothyroidism, diabetes mellitus, hyperinsulinemia and growth hormone (GH) deficiency., Case Report: We describe a case of five years old male with polymalformative syndrome with a systemic involvement. At 6 months of age, he was sent to metabolic consultation because of facial dysmorphy and short stature. During the investigation it was diagnosed at the boy a growth hormone deficiency and because of his multisystemic involvement, muscle biopsy was carried out and showed reduced activity of complex II (38%) of the mitochondrial respiratory chain. Currently, the boy is under GH therapy with growth in the 5th percentile and coenzime Q10., Discussion: Mitochondrial biology is one of the fastest growing areas in genetics and medicine. Disturbances in mitochondrial metabolism are now known to play a role not only in rare childhood diseases, but also in many common diseases of aging. In mitochondrial disorders, short stature is a common symptom, but its underlying lesion, growth hormone deficiency, is rarely investigated.

Perrault syndrome is a rare genetically heterogeneous autosomal recessive group of disorders described in 1951 by Perrault as gonadal dysgenesis with deafness. Here we present a rare case of sporadic Perrault syndrome with short stature and growth hormone deficiency (GHD). Although there was a report on partial GHD in Perrault, our case is a first of its kind with documented GHD (Nishi Y, Hamamoto K, Kajiyama M, Kawamura I. The Perrault syndrome: clinical report and review. Am J Med Genet 1988;31:623-9). We report this case because of the rarity of keeping this condition as a differential diagnosis while evaluating for short stature with amenorrhea.

Purpose: The purpose of this study was to assess the occlusal characteristics of individuals with growth hormone deficiency (GHD), idiopathic short stature (ISS), and Russell-Silver syndrome (RSS), and compare them to the means of a normal population., Methods: Data about the stage of dentition, diastema, maxillary transverse deficiency, overjet, overbite, molar classification, and maxillary and mandibular crowding were obtained from orthodontic screening notes and standardized clinical exams of children with growth disorders seen at screening events. The prevalence of these occlusal characteristics was calculated and compared to the pooled mean of a normal population as determined by the National Health and Nutrition Examination Survey studies., Results: Twenty RSS subjects and 16 subjects with GHD or ISS were studied. The RSS cohort presented statistically significant greater mean overbite as well as mandibular and maxillary crowding compared to the general population. Descriptive statistics were performed for the GHD and ISS group., Conclusion: Occlusal abnormalities are prevalent in children with growth disorders.

Background: Growth hormone deficiency (GHD) in adults is associated with increased cardiovascular events, but detailed assessment of cardiac and vascular function is lacking. Thus we assessed cardiac, arterial, and endothelial functions, using conventional and speckle-tracking echocardiography, in adults with GHD compared with controls with similar cardiovascular risk., Methods: Fifty-two patients with GHD (47 ± 16 years; 34 men) and no cardiovascular disease or diabetes were enrolled prospectively and compared with 50 age- and sex-matched controls. Comprehensive echocardiography was performed in all participants. Regional left ventricular (LV) function was assessed from global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS), whereas LV torsion (LVtor) was calculated from basal (RotB) and apical (RotA) rotations. Arterial function was assessed from intima-media thickening, local wave speed, and beta index of stiffness, whereas endothelial function was assessed from flow-mediated dilation. Levels of pro-brain natriuretic peptide (proBNP) were measured., Results: GLS and GCS were decreased more in patients with GHD than in controls (-17.2% ± 2.7% vs. -19.3% ± 3.3% and -15.9% ± 5.4% vs. -18.8% ± 3.5%; both P < 0.01), whereas GRS was similar. RotB and LVtor were also decreased in patients with GHD (-4.8° ± 2.6° vs. -6.2° ± 2.1°/cm and 1.8° ± 0.6° vs. 2.3° ± 1.1°/cm; both P < 0.05). ProBNP was increased in patients with GHD (61.0 ± 74 pg/dL vs. 24.7 ± 21 pg/dL; P = 0.002). Arterial and endothelial functions were similar between groups., Conclusions: In conclusion, adults with GHD had LV longitudinal dysfunction and increased proBNP levels compared with controls, suggesting intrinsic myocardial disease. Further studies are needed to assess if this cardiac impairment in adults with GHD is reversible after GH replacement., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Hyperglycaemic hyperosmolar state (HHS) is a life-threatening condition rarely seen in paediatrics. It is becoming increasingly recognised with the growing incidence of childhood type 2 diabetes mellitus (T2DM). We present a 16-year-old boy with Bardet-Biedl syndrome, with comorbidities including chronic renal impairment requiring renal transplant, isolated growth hormone (GH) deficiency and obesity, who presented on routine follow-up with new onset T2DM and in HHS. Investigations revealed hyperglycaemia (45.7 mmol/L), ketones of 0.1 mmol/L, pH 7.38 and osmolarity 311 mOsmol/kg. After acute management with fluid resuscitation and intravenous insulin, he is now stable on metformin. He has lost weight, renal function is stable and he has stopped GH therapy. We discuss the dilemmas encountered in his long-term management due to his renal transplant and comorbidities, and whether or not, given his significant T2DM risk, this case was preventable or predictable., (2015 BMJ Publishing Group Ltd.)

Objectives: Growth hormone deficiency (GHD) is a major problem among children with short stature. In this study, the role of brain magnetic resonance imaging (MRI) in defining the underlying defects among short children with GHD is evaluated., Methods: In a cross-sectional study, data of 158 children were evaluated. Growth hormone (GH) levels were measured using stimulating tests and brain MRI with gadolinium contrast was applied, as well., Results: Some 25.3% of patients had GHD with a mean age of 8.01±3.40 years. MRI results showed 35 as normal, four with pituitary hypoplasia, and one with microadenoma. The MRI results were significantly associated with GH levels and presence of other endocrine disorders. There was a significant association between prenatal disorders and patients' bone age delay., Conclusions: In patients with severe GHD and patients with multiple pituitary hormone deficiencies, MRI is more likely to be abnormal, and bone age is much delayed in patients with history of prenatal disorders.

Objective: SOX3 is located on the long arm of the X chromosome (Xq27.1) and both the under- and over-expression of this gene have been reported in cases of hypopituitarism with or without intellectual disabilities. Nevertheless, only a few cases have as yet been extensively described., Design: A 3-year 11 month-old male was brought in for growth failure (height -2.4 SDS). The patient was born at term of a second uneventful pregnancy by caesarean section for podalic presentation: the birth weight (0.1 SDS), length (0.4 SDS), and head circumference (-0.3SDS) were normal. Neurodevelopmental delays and ocular motor dyspraxia had been noted since 6 months of age. The endocrinological evaluation showed a very low IGF-I concentration (44 μg/L). The thyroid hormone level was normal and coeliac disease markers were negative. Bone age was considerably delayed. Target height was normal (0.5 SDS)., Results: Growth hormone stimulation tests were compatible with a classic GHD, while a brain MRI disclosed a pituitary hypoplasia with ectopic neurohypophysis. rhGH treatment was then begun and the auxological follow-up showed a good response. At the age of 9 yrs, the height was 0.3 SDS, the weight was 0.1 SDS, and the pubertal evaluation was PH1 AH1 T2 ml bilaterally. Due to the presence of neuromotor delays and MRI abnormalities, a genetic evaluation was conducted and an array-CGH of the patient's DNA discovered an Xq26.3-27.3 duplication comprising the SOX3 gene., Conclusions: SOX3 involvement should be considered in a male with short stature due to GH deficiency associated with intellectual disability.

Objectives: The Quality of Life in Short Stature Youth (QoLISSY) questionnaire was recently developed in five European countries to assess health-related quality of life in children and adolescents with idiopathic short stature or growth hormone deficiency from child and parent perspectives. In addition to the existing French version, a Flemish version is needed for use of QoLISSY in the Flemish speaking part of Belgium., Methods: Children (8-18 years) and their parents recruited from two Belgian paediatric endocrinology clinics completed the QoLISSY in a cross-sectional study. Cronbach's Alpha and test-retest reliability was assessed. Validity was examined by correlation with the generic KIDSCREEN questionnaire as well as by group comparisons according to diagnostic and treatment status., Results: The QoLISSY scales had an acceptable internal consistency with Cronbach's Alpha ranging from 0·80 to 0·94 (child version) and from 0·77 to 0·92 (parent version). Test-retest reliability correlation coefficients ranged from r = 0·75 to 0·89 in the child version and from r = 0·58 to 0·85 in the parent version. Moderate correlations with the generic KIDSCREEN questionnaire suggested construct validity. Differences between child groups according to child age, underlying diagnosis, and degree of height deficit were found. Correlations with the European QoLISSY were significant for all scales., Discussion: The Flemish QoLISSY instrument is a psychometrically sound, reliable, and valid short stature specific questionnaire measuring health-related quality of life. It is expected to be of great use in upcoming clinical research on growth disorders and growth hormone treatment in Belgium and Europe.

Objective: To evaluate the hearing status of growth hormone (GH)-naive adults with isolated GH deficiency (IGHD) belonging to an extended Brazilian kindred with a homozygous mutation in the GH-releasing hormone receptor gene., Study Design: Cross-sectional., Setting: Divisions of Endocrinology and Otorhinolaryngology of the Federal University of Sergipe., Subjects and Methods: Twenty-six individuals with IGHD (age, 47.6 ± 15.1 years; 13 women) and 25 controls (age, 46.3 ± 14.3 years; 15 women) were administered a questionnaire on hearing complaints and hearing health history. We performed pure-tone audiometry, logoaudiometry, electroacoustic immittance, and stapedial reflex. To assess outer hair cell function in the cochlea, we completed transient evoked otoacoustic emissions (TEOAEs). To assess the auditory nerve and auditory brainstem, we obtained auditory brainstem responses (ABRs)., Results: Misophonia and dizziness complaints were more frequent in those with IGHD than in controls (P = .011). Patients with IGHD had higher thresholds at 250 Hz (P = .005), 500 Hz (P = .006), 3 KHz (P = .008), 4 KHz (P = .038), 6 KHz (P = .008), and 8 KHz (P = .048) and mild high-tones hearing loss (P = .029). Stapedial reflex (P < .001) and TEOAEs (P = .025) were more frequent in controls. There were no differences in ABR latencies. Hearing loss in patients with IGHD occurred earlier than in controls (P < .001)., Conclusion: Compared with controls of the same area, subjects with untreated, congenital lifetime IGHD report more misophonia and dizziness, have predominance of mild high-tones sensorineural hearing loss, and have an absence of stapedial reflex and TEOAEs.

We present the case of a young boy with Dent's disease, identified as having a mutation in the kidney-specific chloride-proton antitransporter CLCN5 during investigation for nephrotic-range proteinuria. He went on to develop growth hormone deficiency and was treated with recombinant growth hormone. He later presented acutely with hepatorenal failure and thrombotic occlusion of the middle and right hepatic veins consistent with a diagnosis of Budd-Chiari syndrome, which required a prolonged period of intensive care. The diagnosis of Dent's disease should be considered early in boys with nephrotic-range proteinuria in the absence of clinical oedema and hypoalbuminaemia to allow for the timely introduction of strategies, such as a high-citrate diet, to preserve renal function. The measurement of urinary β-2 microglobulin has been shown by this case to be a more reliable and specific marker of tubular dysfunction than the urinary retinol-binding protein.

Objective: To determine differences between parents and children in ratings of child health-related quality of life (HRQL) prior to growth hormone treatment., Method: HRQL measures were collected from 144 children and their caregivers. Inclusion criteria were aged between 10 and 16 years, diagnosed with Turner's syndrome, acquired or idiopathic growth hormone deficiency (AGHD or IGHD) and eligible to begin human GH treatment (GHT), or non-growth hormone deficient (GHD) short stature., Results: Parents rated children to have poorer physical and psychosocial HRQL than children rated themselves. Differences depended on the measure used. Parents rated children with IGHD and non-GHD short stature better than children rated themselves, but they rated children with AGHD or Turner's much worse than children rated themselves in terms of physical but not psychosocial functioning., Conclusions: Decisions to prescribe GHT should include children's perspectives of HRQL whenever possible. Differences between parents and children are most likely in conditions that involve more complex medical needs (AGHD and Turner's). Generic and disease-specific HRQL measures may vary in sensitivity to HRQL differences between groups. More work is required to evaluate HRQL among younger children., (© 2013 John Wiley & Sons Ltd.)

This review paper provides a summary of the current state of knowledge regarding GHD provides recommendations for the diagnosis and treatment of GHD in adult patients with thalassaemia major (TM). The reported prevalence of adult GHD and /or IGF-I deficiency in TM patients varies from 8% to 44 % in different centers. Because GH treatment requires analysis of many factors, including the effect of treatment on cardiac functions, metabolic parameters and psychosocial functioning, along with safety, ethical considerations, financial cost and other burdens of therapy, stringent diagnostic criteria are needed. The authors report the diagnostic recommendations of the International Study Group of Endocrine Complications in Thalassemia (I-CET) for adult TM patients.The pros and cons of GH treatment must be discussed with each patient, after which GH doses should be individualized and titrated to maximum efficacy with minimal side effects. Prospective studies to monitor potential benefits versus possible side-effects will enable endocrinologists to define recommendations on dosage and the long term effects, particularly on cardiovascular and bone status of GH therapy in adult TM patients.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease spanning from simple benign steatosis to steatohepatitis with fibrosis and scarring that can eventually lead to cirrhosis. Its prevalence is rising rapidly and is developing into the leading indication for liver transplantation worldwide. Abnormalities in endocrine axes have been associated with NALFD, including hypogonadism, hypothyroidism, GH deficiency and hypercortisolaemia. In some instances, correction of the endocrine defects has been shown to have a beneficial impact. While in patients with type 2 diabetes the association with NAFLD is well established and recognised, there is a more limited appreciation of the condition among common endocrine diseases presenting with hormonal excess or deficiency. In this review, we examine the published data that have suggested a mechanistic link between endocrine abnormalities and NAFLD and summarise the clinical data endorsing these observations.

A 7 year old male with a history of congenital neutropenia and growth hormone deficiency presented with abdominal pain, fevers, and diarrhea. Imaging and endoscopy revealed significant inflammation of the ascending colon with stenosis at the level of the hepatic flexure. A right hemicolectomy was performed, and pathologic findings were consistent with diffuse intestinal ganglioneuromatosis. Due to recurrent mass effect at the intestinal anastomotic site detected radiologically, a second intestinal resection was performed 7 months later. Genetic testing was negative for mutations in the RET protooncogene, NF1 and PTEN tumor suppressor genes. We report a case of diffuse intestinal ganglioneuromatosis in a child with congenital neutropenia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Aim: Growth Hormone Deficiency (GHD) is characterized by increased visceral fat accumulation. Echocardiographic epicardial fat thickness is a new marker of visceral adiposity. Aim of the present study was to evaluate whether epicardial fat thickness can significantly change and therefore serve as a marker of visceral fat reduction after short-term rhGH replacement therapy in patients with adult-onset GHD., Methods and Results: Echocardiographic epicardial fat thickness was measured in 18 patients (10 M, 8 F, age 48 ± 11.8 yrs, BMI 29 ± 5.9 kg/m(2)) with adult-onset GHD, at baseline and after 6 and 12 months of rhGH therapy and in 18 healthy matched controls, at baseline. Echocardiographic epicardial fat thickness, conventional anthropometric and metabolic parameters, body fat percentage and quality of life were also evaluated. Epicardial fat thickness in adult GHD patients was higher than in controls (9.8 ± 2.8 vs 8 ± 3 mm, p < 0.05). Epicardial fat thickness significantly decreased after 6-months of rhGH replacement therapy (from 9.8 ± 2.8 to 7.0 ± 2.3 mm, P < 0.01, i.e. -29% from baseline). After 12 months of rhGH replacement therapy, epicardial fat thickness showed a further significant decrease (from 7.0 ± 2.3 to 5.9 ± 3.1 mm, P < 0.01, i.e. -40% from baseline). No significant changes in BMI or waist circumference after 6 or 12 months of rhGH therapy were observed., Conclusions: Echocardiographic epicardial fat thickness may represent a valuable and easy marker of visceral fat and visceral fat changes during rhGH replacement treatment in patients with adult-onset growth hormone deficiency., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: To report a novel clinical and genetic presentation of a patient with 4H syndrome, which is a recently described leukodystrophy syndrome characterized by ataxia, hypomyelination, hypodontia, and hypogonadotropic hypogonadism., Design: Case report., Setting: University teaching hospital., Patient: A 20-year-old male patient with 4H syndrome., Results: The patient was found to have delayed tooth eruption and a late-onset growth hormone deficiency without overt growth failure. He was a compound heterozygote for the novel missense mutations R1005H and A1331T of POLR3A, which codes for the largest subunit of RNA polymerase III., Conclusion: This is the first report of this type of leukodystrophy from southeastern Europe, which suggests that POLR3A mutations should be suspected in patients with hypomyelination and various central nervous system–based endocrine abnormalities.

The availability of growth hormone (GH)-deficient dwarf rats with otherwise normal pituitary function provides a powerful tool to examine the relative role of hyperglycaemia and the reordering of hormonal factors in the hypertrophy-hyperfunction of the adrenal gland that is seen in experimental diabetes. Here, we examine the effects of long-term (6 months) experimental diabetes on the growth of the adrenal glands; their content of phosphoribosyl pyrophosphate (PRPP); and the activity of the PRPP synthetase, G6P dehydrogenase and 6PG dehydrogenase enzymes in GH-deficient dwarf rats compared to heterozygous controls. These parameters were selected in view of the known role of PRPP in both de novo and salvage pathways of purine and pyrimidine synthesis and in the formation of NAD, and in view of the role of the oxidative enzymes of the pentose phosphate pathway in both R5P formation and the generation of the NADPH that is required in reductive synthetic reactions. This study shows that GH deficiency prevents the increase in adrenal gland weight, PRPP synthetase, PRPP content and G6P dehydrogenase and 6PG dehydrogenase. This contrasts sharply with the heterozygous group that showed the expected increase in these parameters. The blood glucose levels of the groups of long-term diabetic rats, both GH-deficient and heterozygous, remained at an elevated level throughout the experiment. These results are fully in accord with earlier evidence from studies with somatostatin analogues which showed that the GH-insulin-like growth factor I (IGF-I)-axis plays a key role in the adrenal diabetic hypertrophy-hyperfunction syndrome., (© 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.)