Normal Growth Hormone Response Research Articles

Is Gadolinium Contrast Necessary for Pituitary MRI in the Evaluation of Pediatric Short Stature and Growth Hormone Deficiency?

Introduction: Short stature is a common concern that necessitates pediatric endocrinology evaluation. Growth hormone deficiency (GHD) is a commonly considered etiology. Brain and pituitary magnetic resonance imaging (MRI) with gadolinium-based contrast agents (GBCAs) is the most widely used imaging in assessing patients with GHD. Given the significant strides made in MRI technology, the need for contrast material should be reassessed. Method: We performed a retrospective review of healthy patients with short stature and/or GHD who underwent brain and pituitary MRI with and without contrast to assess the added value of contrast administration. Results: 227/318 identified patients underwent growth hormone (GH) stimulation testing; 28 (12.3%) with normal GH response and 62 (27.3%) with severe GHD. We found a low incidence of sellar and suprasellar pathologies. When comparing noncontrast and contrast MRI, we found perfect agreement in detecting abnormal posterior pituitary bright spots (kappa:1.0) and substantial agreement in detecting pars intermedia cysts and posterior superior sellar cysts (kappa: 0.74 and 0.71, respectively). Initially, only moderate agreement was found in detecting infundibular abnormalities (kappa: 0.51), although a revised noncontrast MRI protocol with high-resolution 3D images enabled visualization of the infundibulum. Conclusion: The MRI evaluation of healthy patients with short stature and/or isolated GHD may be completed without the use of GBCAs. The slight overestimation of pituitary stalk interruption by noncontrast images can be overcome by adding newer high-resolution sequences.

195-LB: Metabolomic Characterization of Laron and Guevara-Rosenbloom Syndromes Using UHPLC-HRMS

Laron syndrome (LS) is a rare autosomal recessive growth hormone (GH) insensitivity condition due to GH receptor mutation, and with phenotypic features likened to GH deficiency. The incidence of LS in Ecuador is very high and has gained worldwide attention due to its low incidence of cancer and diabetes mellitus. A more recently described population is affected with “Guevara-Rosenbloom syndrome” (GRS). While both groups exhibit severe short stature (-4 to -12 SDS), GRS subjects have normal GH signaling and responses and, unlike LS, have intrauterine growth retardation and early onset type 2 diabetes (T2DM). Since both groups have diminished insulin secretion, there is a unique opportunity to investigate their metabolome under each specific disease. Levels of certain amino acids in insulin-resistant (IR) states such as T2DM are distinct and special attention has been given to the predicting power of branched chain and aromatic amino acids, carnitines, and free fatty acids for IR and T2DM risk assessment. Our aim was to understand the metabolic differences between LS and GRS, which both have diminished insulin secretion but different GH counter-regulation as well as to compare these groups to normal controls. The metabolome of these 3 cohorts was assessed at the following instances: a) At the fasting state, and b) After an oral challenge of 1.5 mg/kg of glucose per kilogram of body weight, administered immediately after the fasting sample was drawn (samples were taken every 30 minutes for 5 hours [5h]). Preliminary results (by ANOVA) show a strong correlation, in the fasting state, between the control and the LS groups with clear discrimination from the GRS cohort, as determined by a heatmap of the top 100 features. Furthermore, the analysis of the 5h profile after the glucose challenge in the 3 groups revealed significant correlations in the levels of amino-acids that have been related to the genesis of IR and T2DM. This work represents the first deep-metabolome analysis in this unique study group. Disclosure V. Rubio: None. C.A. Chamberlain: None. C. Wasserfall: None. J. Guevara-Aguirre: None. A. Guevara: None. A.L. Rosenbloom: None. M.A. Atkinson: None. R.A. Yost: None. T.J. Garrett: None. Funding National Institutes of Health (U24DK097209)

Growth hormone transgenesis in coho salmon disrupts muscle immune function impacting cross-talk with growth systems.

Suppression of growth during infection may aid resource allocation towards effective immune function. Past work supporting this hypothesis in salmonid fish revealed an immune-responsive regulation of the insulin-like growth factor (IGF) system - an endocrine pathway downstream of growth hormone (GH). Skeletal muscle is the main target for growth and energetic storage in fish, yet little is known about how its growth is regulated during an immune response. We addressed this knowledge gap by characterising muscle immune responses in size-matched coho salmon (Oncorhynchus kisutch) achieving different growth rates. We compared a wild-type strain with two GH transgenic groups from the same genetic background achieving either maximal or suppressed growth - a design separating GH's direct effects from its influence on growth rate and nutritional state. Fish were sampled 30 h post-injection with phosphate-buffered saline (control) or mimics of bacterial or viral infection. We quantified mRNA expression levels for genes from the GH, GH receptor, IGF hormone, IGF1 receptor and IGF-binding protein families, along with immune genes involved in inflammatory or antiviral responses and muscle growth status marker genes. We demonstrate dampened immune function in GH transgenics compared with wild-type. The muscle of GH transgenics achieving rapid growth showed no detectable antiviral response, coupled with evidence of a constitutive inflammatory state. GH and IGF system gene expression was strongly altered by GH transgenesis and fast growth, both for baseline expression and responses to immune stimulation. Thus, GH transgenesis strongly disrupts muscle immune status and normal GH and IGF system expression responses to immune stimulation.

Updates in Diagnosis and Treatment of Acromegaly.

Acromegaly is a rare disease, caused largely by a growth hormone (GH) pituitary adenoma. Incidence is higher than previously thought. Due to increased morbidity and mortality, if not appropriately treated, early diagnosis efforts are essential. Screening is recommended for all patients with clinical features of GH excess. There is increased knowledge that classical diagnostic criteria no longer apply to all, and some patients can have GH excess with normal GH response to glucose. Treatment is multifactorial and personalised therapy is advised.

Clinical and laboratory parameters predicting a requirement for the reevaluation of growth hormone status during growth hormone treatment: Retesting early in the course of GH treatment

ObjectiveWe aimed to define the predictive criteria, in the form of specific clinical, hormonal and radiological parameters, for children with growth hormone deficiency (GHD) who may benefit from the reevaluation of GH status early in the course of growth hormone (GH) treatment. Design and MethodsTwo hundred sixty-five children with growth hormone deficiency were retested by GH stimulation at the end of the first year of GH treatment. The initial clinical and laboratory characteristics of those with a normal (GH≥10ng/ml) response and those with a subnormal (GH<10ng/ml) response were compared to predict a normal GH status during reassessment. ResultsSixty-nine patients (40.6%) out of the 170 patients with isolated growth hormone deficiency (IGHD) had a peak GH of ≥10ng/ml during the retest. None of the patients with multiple pituitary hormone deficiency (MPHD) had a peak GH of ≥10ng/ml. Puberty and sex steroid priming in peripubertal cases increased the probability of a normal GH response. Only one patient with IGHD who had an ectopic posterior pituitary without stalk interruption on MRI analysis showed a normal GH response during the retest. Patients with a peak GH between 5 and 10ng/ml, an age at diagnosis of ≥9years or a height gain below 0.61 SDS during the first year of treatment had an increased probability of having a normal GH response at the retest. ConclusionEarly reassessment of GH status during GH treatment is unnecessary in patients who have MPHD with at least 3 hormone deficiencies. Retesting at the end of the first year of therapy is recommended for patients with IGHD who have a height gain of <0.61 SDS in the first year of treatment, especially those with a normal or ‘hypoplastic’ pituitary on imaging. Priming can increase the likelihood of a normal response in patients in the pubertal age group who do not show overt signs of pubertal development.

High Frequency of Normal Response during GH Stimulation Tests in Patients with Ectopic Posterior Pituitary Gland: A Source of False-Negative Diagnosis of Pituitary Insufficiency

Aims: To report false-negative normal growth hormone (GH) peak response in patients with ectopic posterior pituitary gland (EPP) identified with a simplified magnetic resonance imaging (FAST1-MRI). Methods: We analyzed 75 EPP patients with short stature and reduced growth velocity. Sagittal-T1 imaging (thickness: 2 mm and gap: 0.2 mm) without gadolinium administration was used. A GH peak of ≥5 ng/ml after clonidine or insulin stimulation was considered normal. Results: Normal GH response was observed in 15 of 75 (20%) patients [mean (SDS) peak = 8.2 (4.1) ng/ml]. Age at diagnosis [6.5 (3.0) years vs. 7.8 (4.1) years], gender (10 males/5 females vs. 44 males/16 females), pubertal stage (14 prepubertal/1 pubertal vs. 51 prepubertal/7 pubertal), and target height [-0.4 (0.6) vs. -0.4 (0.9)] were recorded. The perinatal history did not differ between responsive and nonresponsive patients. There was a trend to more frequent multiple hormone deficiency in nonresponsive when compared with responsive patients [3/15 (20%) and 31/60 (51.7%), respectively (p = 0.055)]. Height at diagnosis was lower in nonresponsive patients (p = 0.042). No significant difference in the IGF1 levels (p = 0.598) was observed between the groups. Conclusion: Normal GH values after stimulation tests do not exclude EPP-associated GH deficiency. A simplified fast acquisition sagittal-T1 MRI protocol investigation included at the initial diagnostic approach is able to prevent misdiagnosis of GH deficiency in patients with short stature.

Severe growth hormone deficiency and empty sella in obesity: a cross-sectional study.

Obesity is associated with blunted growth hormone (GH) secretion. In some individuals, hypothalamic-pituitary (HP) structural lesions may contribute to GH deficiency (GHD). We explored pituitary morphology in obese patients with suspected GHD and its association with cardiovascular risk factors, body composition, and cardiac morphology. One hundred and eighty-four adults obese patients with symptoms and signs of GHD (147 females and 37 males; mean age 46.31 ± 12.11 years), out of 906 consecutive white obese outpatients, were evaluated. The main measures were anthropometric data, blood pressure, lipid profile, glycemic parameters, pituitary hormones, and insulin-like growth factor-1 values, echocardiography, magnetic resonance imaging (MRI) of the HP region, body composition, and growth hormone-releasing hormone plus arginine test. Seventy patients had GHD (GH peak values <4.2 μg/mL). GHD patients showed significantly higher body mass index and fat mass, lower lumbar bone mineral density, increased left ventricular mass index, and epicardial fat thickness. The MRI of the HP region showed empty sella (ES) in 69 and normal pituitary in one of the 70 GHD patients; the 114 patients with normal GH response had ES (n = 62, 54 %), normal pituitary (n = 37, 32 %), microadenomas (n = 10, 8 %), and other pituitary abnormalities (n = 5, 4 %). ES was a significant independent predictor of GH secretory capacity as determined by multiple regression analysis. The close relationship between ES and GH secretory capacity points out to the possibility of the organic nature of GHD in a portion of obese individuals and opens a new scenario with regard to the potential of GH treatment on metabolic consequences of obesity.

Constitutional delay influences the auxological response to growth hormone treatment in children with short stature and growth hormone sufficiency.

In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age. In the first year, GH was associated with marked increase in HtSDS (+0.46 (0.19, 0.76), p < 0.001) and GV-SDS (from −1.9 (−3.6, −0.7) to +2.7 (0.45, 4.2), p < 0.001). The increase in HtSDS but not in GV-SDS was greatest with younger patients and greater bone age delay, with no effect of sex, BMI-SDS or baseline HtSDS. PAH-SDS increased with treatment (+0.94 (0.18, 1.5)); increased PAH-SDS was associated with less bone age delay and greater initial increase in HtSDS. This study shows that greater bone age delay was associated with greater initial improvement in height but less improvement in predicted adult heights, suggesting that children with very delayed bone ages may show accelerated maturation during GH treatment.

Does priming with sex steroids improve the diagnosis of normal growth hormone secretion in short children?

Introduction:There is still controversy for priming with sex steroid before growth hormone (GH) testing.Objective:We studied GH response to stimulation in 92 children >9 years with idiopathic short stature (height standard deviation score [HtSDS]-2). They were divided randomly into two groups. Children in Group 1 (n = 50) were primed with premarin in girls and testosterone in boys and those in Group 2 were not primed (n = 42). All children were tested using standard clonidine test and their serum insulin-like growth factor-I concentration (IGF-I). Additionally the growth and GH-IGF-I data of the two groups of children were compared with those for 32 short children (HtSDS <−2) below the age 9 years who were non-primed before GH testing (Group 3).Results:Neither GH peak response to provocation nor IGF-I concentrations differed between the two groups with and without priming.Discussion:Taking a cut-level of 7 ng/ml for normal GH response to clonidine, priming with sex steroids did not significantly increase the percentage of patients with normal GH response (52%) versus nonpriming (47%). IGF-I level did not show any significant difference among the two studied groups >9 years. The peak GH response to clonidine provocation test did not differ before (n = 42) versus after 9 years (n = 32) of age.Conclusions:In this randomized study priming with sex steroids before GH testing did not significantly increase the yield of diagnosing short patients with normal GH secretion. In addition, GH response to provocation did not vary significantly between young (<9 years) and old (>9 years) short children.

Subcutaneous rhIGF-1 Significantly Increases Circulating IGF-1 Concentrations in Children With Crohn's Disease Induced Growth Failure

Introduction Faltering growth is a complication of paediatric Crohn9s disease, affecting up to a third of patients. There is no recognised treatment targeted at improving linear growth. These children have low circulating insulin-like growth factor-1 (IGF-1), a hormone essential for linear growth and the primary mediator of growth hormone (GH) action. Low IGF-1 concentrations occur despite normal GH response to stimulation testing – the children thus having a functional GH insensitivity. Injections with recombinant human IGF-1 (rhIGF-1) have been reported to improve growth in animal models of colitis and in children with genetic GH insensitivity syndrome using doses of 80–120 μg/kg bd. rhIGF-I therapy has never previously been used in children with Crohn9s disease. We hypothesised that subcutaneous injections of rhIGF-1 would significantly increase circulating IGF-1 concentrations in children with Crohn9s disease induced growth failure, and that twice daily injections would maintain these concentrations. Methods Eight children with active Crohn9s disease and growth failure were recruited for an open-label pharmacokinetics study of rhIGF-1 (Increlex). A subcutaneous injection of rhIGF-1 (dose 120 μg/kg) was given, and levels were measured over 24 h. Children were also studied over a second period (5 days) of repeated doses. Blood sugar levels were monitored as hypoglycaemia is a potential adverse effect. Protein losing enteropathy was measured by stool α1-antitrypsin and related to IGF-1 levels attained. Results The median age(range) of the children was 12 years(10–14). 4 were female, 4 male, mean (SD) Paediatric Crohn9s Disease Activity Index (PCDAI) was 31.25(14.08). All the children had poor growth (mean growth velocity standard deviation score(SDS) −3.34 (SD 1.13)). All the subjects completed the study. The rhIGF-1 was well tolerated, with only one patient having an (asymptomatic) hypoglycaemic episode. All patients except for one had low baseline IGF-1 levels (mean SDS -1.78 (SD 1.37)) and all showed an increase in 3-h circulating IGF-1 levels following administration of rhIGF-1 (mean SDS 2.70 (SD 3.06)). This increase was significant(p = 0.007). IGF-1 levels were maintained above 0.0 SDS by twice daily injections. This occurred without any change in PCDAI over the 5-day trial period (p = 0.77) Protein-losing enteropathy did not inhibit this response. Conclusion Subcutaneous administration of rhIGF-1 significantly increased circulating concentrations of IGF-1 in children with Crohn9s disease-related growth retardation. These results support the initiation of trials to assess the impact of long-term rhIGF replacement therapy on linear growth.

Subcutaneous rhIGF-1 significantly increases circulating IGF-1 concentrations in children with Crohn's disease induced growth failure

IntroductionFaltering growth is a complication of paediatric Crohn's disease, affecting up to a third of patients. There is no recognised treatment targeted at improving linear growth. These children have low...

Effects of ghrelin, growth hormone–releasing peptide–6, and growth hormone–releasing hormone on growth hormone, adrenocorticotropic hormone, and cortisol release in type 1 diabetes mellitus

In type 1 diabetes mellitus (T1DM), growth hormone (GH) responses to provocative stimuli are normal or exaggerated, whereas the hypothalamic-pituitary-adrenal axis has been less studied. Ghrelin is a GH secretagogue that also increases adrenocorticotropic hormone (ACTH) and cortisol levels, similarly to GH-releasing peptide–6 (GHRP-6). Ghrelin's effects in patients with T1DM have not been evaluated. We therefore studied GH, ACTH, and cortisol responses to ghrelin and GHRP-6 in 9 patients with T1DM and 9 control subjects. The GH-releasing hormone (GHRH)–induced GH release was also evaluated. Mean fasting GH levels (micrograms per liter) were higher in T1DM (3.5 ± 1.2) than in controls (0.6 ± 0.3). In both groups, ghrelin-induced GH release was higher than that after GHRP-6 and GHRH. When analyzing Δ area under the curve (ΔAUC) GH values after ghrelin, GHRP-6, and GHRH, no significant differences were observed in T1DM compared with controls. There was a trend ( P = .055) to higher mean basal cortisol values (micrograms per deciliter) in T1DM (11.7 ± 1.5) compared with controls (8.2 ± 0.8). No significant differences were seen in ΔAUC cortisol values in both groups after ghrelin and GHRP-6. Mean fasting ACTH values were similar in T1DM and controls. No differences were seen in ΔAUC ACTH levels in both groups after ghrelin and GHRP-6. In summary, patients with T1DM have normal GH responsiveness to ghrelin, GHRP-6, and GHRH. The ACTH and cortisol release after ghrelin and GHRP-6 is also similar to controls. Our results suggest that chronic hyperglycemia of T1DM does not interfere with GH-, ACTH-, and cortisol-releasing mechanisms stimulated by these peptides.

Preliminary Evidence of Increased Pain and Elevated Cytokines in Fibromyalgia Patients with Defective Growth Hormone Response to Exercise

Mounting evidence suggests fibromyalgia (FM) symptoms are influenced by dysfunction of the hypothalamic-pituitary-hormonal axes (HPHA) and the immune response system. The predominant FM symptoms of widespread pain, fatigue, sleep disturbance, depression, stiffness and exercise intolerance are related to abnormal levels of growth hormone (GH) and are reminiscent of "sickness behavior"; a syndrome initiated by the production of pro-inflammatory cytokines in response to various stressors. Cognizant of the reciprocal relationship between HPHA activity and the immune response system, we hypothesized that serum cytokine levels and FM symptom severity would be higher in FM patients with defective growth hormone response to exhaustive exercise compared to those without. Outpatients with FM (n = 165) underwent a Modified Balke Treadmill Protocol and GH response to exhaustive exercise was measured in peripheral blood samples. Levels of IL-1α, IL-1β, IL-1RA, IL-6, IL-8, IL-10, and TNF-α were measured from stored serum on a subset of 24 participants (12 with and 12 without normal GH response to exhaustive exercise). FM symptom severity was assessed using the Fibromyalgia Impact Questionnaire (FIQ), number of tender points and cumulative myalgic scores. GH dysfunction was associated with increased pain scores on the FIQ (p = 0.024), a greater number of tender points (p = 0.014), higher myalgic scores (p = 0.001) and higher pre-exercise levels of inflammatory cytokines IL-1α (p = 0.021), IL-6 (p = 0.012), and IL-8 (p = 0.004). These results suggest that a defective growth hormone response to exercise may be associated with increased levels of blood cytokines and pain severity in FM patients.

Relationship Between Growth Hormone/Insulin-Like Growth Factor-1 Axis Integrity and Voluntary Weight Loss After Gastric Banding Surgery for Severe Obesity

The aim of this observational study was to determine, in a retrospective analysis, whether growth hormone (GH) and insulin-like growth factor-1 (IGF-1) at baseline or changes in the GH/IGF-1 axis after laparoscopic adjustable gastric banding (LAGB) is associated with weight loss and body composition changes in severely obese nondiabetic patients. Weight loss (expressed as percent excess weight loss [EWL%]), anthropometry, body composition by bioelectrical impedance analysis (BIA), serum IGF-1, and GH peak after GH-releasing hormone (GHRH) plus arginine (ARG) test were measured and expressed as standard deviation scores (SDS) of reference values in 104 women and 36 men, age (mean +/- SD) 34 +/- 11 and 30.2 +/- 11 years, and BMI 44 +/- 5.7 and 39 +/- 3.2, respectively, before and 6 months after LAGB. After LAGB, 25% of women and 22.5% of men had GH deficiency, while 30.8% of women and 33.3% of men had IGF-1 deficiency or insufficiency. The median EWL was 36.8% in women and 40.0% in men. In both genders, percent decrease of waist circumference, EWL, and fat mass (FM) and percent increase of fat-free mass (FFM) was greater in patients with normal GH secretion and IGF-1 levels. The GH peak after GHRH + ARG, IGF-1 levels, and IGF-1 SDS were inversely correlated with EWL% (r = -0.50, r = -0.53, and r = -0.42, respectively; p < 0.0001) and percent FM (r = -0.41, r = -0.36, and r = -0.35, respectively; p < 0.0001). In stepwise linear regression analysis, the GH peak after GHRH + ARG was the major determinant of EWL% (p < 0.0001) and FM (p = 0.001). The efficacy of LAGB was greater in the patients with a normal GH response to GHRH + ARG and with normal IGF-1 levels. The percent of FM, FFM, and EWL were significantly correlated with the GH response to GHRH + ARG and with IGF-1 levels.

Growth and Factors Affecting it in Thalassemia Major

In our thalassemic (T) cohort, 45% of them had height standard deviation score (HtSDS) less than −2 and 56% of them had growth velocity standard deviation score (GVSDS) less than −1. Their mid-arm circumference and triceps skin-fold thickness were decreased versus normal controls. Their circulating insulin-like growth factor-I (IGF-I) concentrations were significantly lower than normal children. Growth hormone (GH) response to provocation with clonidine and glucagon was defective in half of the short T children (peak GH < 7 ng/dL). Some of the short T children, with normal GH response to provocation, had defective spontaneous nocturnal GH secretion. IGF-I generation after one GH injection was reduced in T children than those with GH deficiency (GHD) and constitutional delay of growth and puberty (CDGP). GH therapy for a year significantly increased IGF-I concentrations, GV, and HtSDS in T children but to a lower level compared to those with GHD or CDGP, suggesting partial GH insensitivity. Pubertal induction with human chorionic gonadotropin in T adolescents was associated with increased IGF-I concentrations, GV, and HtSDS.

Growth responses to growth hormone therapy in children with attenuated growth who showed normal growth hormone response to stimulation tests

* , Seoul National University Bundang Hospital, Seong-Nam, Korea Purpose: The aim was to investigate the clinical characteristics and responses to growth hormone (GH) therapy in children with attenuated growth who showed normal GH responses to GH stimulation tests (GHST). Methods: The study included 39 patients with height velocity (HV) of less than 4 cm/yr and normal GHST results. Clinical characteristics of patients were analyzed retrospectively. Results: Eleven were born as small for gestational age (SGA) and 28 as appropriate for age (AGA). In the SGA group, the standard deviation score (SDS) of age and height measured at their first visit was significantly low. Sixteen patients were treated with GH and six of 23 without GH therapy were followed for 1 year after GHST. The mean (range) of HV was 7.7 (4.9 to 11.1) cm/yr in patients with GH therapy and 3.7 (2.7 to 4.5) cm/yr in those without GH therapy, which was statistically significant (P<0.001). In the GH-treated group, HV and difference in height SDS during the treatment increased significantly (P<0.001; P< 0.001, respectively). HV increased after 1 year of GH therapy in the SGA and AGA groups (SGA, P=0.043; AGA, P=0.003). The level of Insulin-like growth factor-I was significantly lower in GH-treated patients with height SDS <-3 than those with ≥3 (P=0.023). Conclusion: In children with growth failure and normal GHST, HV increases significantly by short-term GH therapy. The assessment of long-term effects of GH therapy is necessary. Moreover, further studies should be considered to evaluate the GH-IGF-I axis due to the possibility of GH insensitivity syndrome. (Korean J Pediatr 2009;52:922-929)

Pituitary hypoplasia and growth hormone deficiency in a woman with glycogen storage disease type Ia: a case report

IntroductionGrowth retardation is one of the cardinal manifestations of glycogen storage disease type Ia. It is unclear which component of the growth hormone and/or insulin-like growth factor axis is primarily disrupted, and management of growth impairment in these patients remains controversial. Here we report the first case in the literature where glycogen storage disease type Ia is associated with pituitary hypoplasia and growth hormone deficiency.Case presentationA 20-year-old woman with glycogen storage disease type Ia was admitted to our endocrinology department because of growth retardation. Basal and overnight growth hormone sampling at 2-hour intervals demonstrated low levels; however, provocative testing revealed a relatively normal growth hormone response. A hypoplastic anterior pituitary with preserved growth hormone response to provocative testing suggested the possibility of growth hormone neurosecretory dysfunction and/or primary pituitary involvement.ConclusionPituitary hypoplasia may result from growth hormone-releasing hormone deficiency, a condition generally known as growth hormone neurosecretory dysfunction. It is an abnormality with a spontaneous and pulsatile secretion pattern, characterized by short stature, growth retardation and normal serum growth hormone response to provocative testing. However, in the case described in this report, a normal although relatively low growth hormone response during insulin tolerance testing and pituitary hypoplasia suggested that primary pituitary involvement or growth hormone neurosecretory dysfunction may occur in glycogen storage disease type Ia. This is a potential cause of growth failure associated with a lower somatotroph mass, and may explain the variable responsiveness to growth hormone replacement therapy in people with glycogen storage disease.

Spondylocarpotarsal synostosis: Long‐term follow‐up of a case due to FLNB mutations

Spondylocarpotarsal synostosis: Long‐term follow‐up of a case due to <i>FLNB</i> mutations

Final Heights of Boys with Normal Growth Hormone Responses to Provocative Tests Following Priming

Priming with sex steroids prior to growth hormone (GH) stimulation tests for the diagnosis of GH deficiency is still debatable. We analyzed the auxological data of boys with growth retardation who had normal GH responses to stimulation tests only after priming to establish the validity of priming in the diagnosis of GH deficiency. We also analyzed the effect of different protocols for priming and their efficiency in the diagnosis of GH deficiency. Fifty boys with growth retardation who failed to respond to unprimed GH stimulation tests but responded normally to primed tests were included in the study. Thirty-one of 50 boys responded to GH stimulation tests after single low dose testosterone, 11/50 boys after single conventional dose, and 8/50 boys with multiple-dose testosterone. The study group was followed till final height; height velocity, final height and height SDS were compared to parental and mid-parental heights to determine whether or not the children achieved their height potential. Mean final height SDS of the study group (-1.27 +/- 0.72 SDS) was similar to mid-parental (-1.38 +/- 0.72 SDS) (p = 0.249) and maternal height SDS (-1.26 +/- 1.05 SDS) (p = 0.941), whereas it was greater than the paternal height SDS (-1.7 +/- 0.86) (p = 0.001). The final height SDS of the study group was correlated to maternal, paternal and mid-parental height SDS. Height velocity after the test was greater than the previous height velocity. Final height SDS of the boys who responded to the GH stimulation tests with different priming protocols were compared and found to be similar. Normal responders in primed GH tests grow normally to their target height, suggesting that priming might be a valuable method in the assessment of GH status. Use of priming in the GH stimulation tests of peripubertal boys with decreased growth rate may help avoid unnecessary GH therapy. Multiple-dose testing might exclude GHD in a patient population who failed to respond to a single dose of testosterone. This finding suggests that multiple-dose testosterone might be a more valuable method for priming in the differentiation of normal from abnormal GH secretion.

Deterioration of Growth Hormone (GH) Response and Anterior Pituitary Function in Young Adults with Childhood-Onset GH Deficiency and Ectopic Posterior Pituitary: A Two-Year Prospective Follow-Up Study

The current criteria for definition of partial GHD in young adults are still a subject of debate. The objective of the study was to reinvestigate anterior pituitary function in young adults with congenital childhood-onset GHD associated with structural hypothalamic-pituitary abnormalities and normal GH response at the time of first reassessment of GH secretion. This was a prospective explorative study conducted in a university research hospital. Thirteen subjects with a mean age of 17.2 +/- 0.7 yr and a peak GH after insulin tolerance test (ITT) higher than 5 microg/liter were recruited from a cohort of 42 patients with childhood-onset GHD and ectopic posterior pituitary at magnetic resonance imaging. GH secretion after ITT and GHRH plus arginine, IGF-I concentration, and body mass index, waist circumference, blood pressure, total cholesterol, and fibrinogen were evaluated at baseline and at 2-yr follow-up. At mean age of 19.2 +/- 0.7 yr, the mean peak GH response decreased significantly after ITT (P = 0.00001) and GHRH plus arginine (P = 0.0001). GH peak values after ITT and GHRH plus arginine were less than 5 and 9 microg/liter in 10 and eight patients, respectively. Additional pituitary defects were documented in eight patients. Significant changes were found in the values of IGF-I sd score (P = 0.0026), waist circumference (P = 0.00001), serum total cholesterol (P = 0.00001), and serum fibrinogen (P = 0.0004). The results of this study underline the importance of further reassessment of pituitary function in young adults with GHD of childhood-onset and poststimulation GH responses suggestive of partial GHD.