scholarly journals Subnormal Serum Insulin-Like Growth Factor-I Levels in Young Adults with Childhood-Onset Nonacquired Growth Hormone (GH) Deficiency Who Recover Normal GH Secretion May Indicate Less Severe but Persistent Pituitary Failure

2007 ◽  
Vol 92 (10) ◽  
pp. 3788-3795 ◽  
Author(s):  
Georges Gelwane ◽  
Catherine Garel ◽  
Didier Chevenne ◽  
Priscilla Armoogum ◽  
Dominique Simon ◽  
...  
Keyword(s):  
Young Adults ◽  
Anterior Pituitary ◽  
Gh Deficiency ◽  
Childhood Onset ◽  
Mri Findings ◽  
Gh Secretion ◽  
Structural Abnormalities ◽  
Igf I ◽  
Ectopic Neurohypophysis

Abstract Context: The unexpected observation of a normal GH peak in 22% of young adults with childhood-onset GH deficiency (GHD) and ectopic neurohypophysis has raised questions about the criteria defining GHD in young adults and whether patients with subsequent increases in GH secretion nonetheless have a subtle form of GHD. Objective: Our objective was to determine the characteristics of patients with childhood-onset nonacquired GHD who recover normal peak GH secretion when adult height has been achieved. Design and Setting: We conducted a university hospital-based observational follow-up study. Participants: Sixty-two patients with ectopic neurohypophysis (n = 24), isolated hypoplastic anterior pituitary (n = 14), or normal hypothalamic pituitary area (n = 24) on magnetic resonance imaging (MRI) at the time of GHD diagnosis underwent reevaluation of the GH-IGF-I axis at a mean age of 16.8 ± 1.6 yr. Main Outcome Measures: Outcome measures included clinical and MRI findings and serum IGF-I and peak GH levels. Results: On retesting, peak GH exceeded 10 μg/liter in 31 patients (50%): six (20%) patients with ectopic neurohypophysis, 10 (32%) patients with initially isolated hypoplastic anterior pituitary, and 15 (48%) patients with normal MRI findings. Among these patients, serum IGF-I levels were significantly lower in patients with ectopic neurohypophysis than in those without structural abnormalities of the hypothalamic pituitary axis (n = 25), but patients without structural abnormalities also had significantly lower serum IGF-I levels than control subjects, after controlling for age, sex, and body mass index (mean serum IGF-I levels of 374 ± 83 vs. 446 ± 108 μg/liter; β-coefficient = −72; P = 0.003). Conclusions: The severity of the disease seems to have decreased over time in these patients, who may nonetheless present persistent pituitary failure. The natural history and clinical implications of these findings remain to be clarified. The possibility of a deterioration in the secretion of GH and other pituitary hormones later in life in a subset of these patients warrants the careful long-term follow-up of this population.

scholarly journals 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

2007 ◽  
Vol 92 (10) ◽  
pp. 3875-3884 ◽  
Author(s):  
Natascia di Iorgi ◽  
Andrea Secco ◽  
Flavia Napoli ◽  
Carmine Tinelli ◽  
Annalisa Calcagno ◽  
...  
Keyword(s):  
Young Adults ◽  
Waist Circumference ◽  
Anterior Pituitary ◽  
Pituitary Function ◽  
Posterior Pituitary ◽  
Childhood Onset ◽  
Gh Secretion ◽  
Igf I ◽  
Anterior Pituitary Function

Abstract Context: The current criteria for definition of partial GHD in young adults are still a subject of debate. Objectives: 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. Design and Setting: This was a prospective explorative study conducted in a university research hospital. Patients and Methods: Thirteen subjects with a mean age of 17.2 ± 0.7 yr and a peak GH after insulin tolerance test (ITT) higher than 5 μg/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. Results: 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 μg/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). Conclusions: 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.

scholarly journals Do All Patients with Childhood-Onset Growth Hormone Deficiency (GHD) and Ectopic Neurohypophysis Have Persistent GHD in Adulthood?

2005 ◽  
Vol 90 (2) ◽  
pp. 650-656 ◽  
Author(s):  
Juliane Léger ◽  
Stéphanie Danner ◽  
Dominique Simon ◽  
Catherine Garel ◽  
Paul Czernichow
Keyword(s):  
Anterior Pituitary ◽  
Adult Height ◽  
Pituitary Stalk ◽  
Childhood Onset ◽  
Gh Therapy ◽  
Group Iii ◽  
Gh Secretion ◽  
Group I ◽  
Height Gain ◽  
Ectopic Neurohypophysis

Cerebral magnetic resonance imaging findings are of great value for the diagnosis of nonacquired GH deficiency (GHD), and ectopic posterior pituitary hyperintense signal (EPPHS) is a sensitive and specific indicator of hypopituitarism. It has been suggested that patients with childhood-onset GHD and EPPHS do not require additional investigation of GH secretion and should not be retested when adult height is achieved. This recommendation has never been validated through a systematic study. This study aimed to characterize the anterior pituitary function status of patients with EPPHS treated for GHD during childhood after completion of GH therapy when adult height had been achieved. Patients (n = 18; 15 males and three females) with childhood-onset GHD associated with ectopic neurohypophysis were treated with hGH (0.20 ± 0.05 mg/kg·wk) for 9.9 ± 4.0 yr (from 6.8 ± 4.7 to 17.7 ± 1.3 yr of age) with a mean height gain of 2.6 ± 1.4 sd score. GH secretion was reevaluated by arginine insulin (n = 15) or propanolol glucagon (n = 3) test after 0.5 ± 0.6 yr of GH withdrawal. At reevaluation, peak GH was more than 10 μg/liter in four patients (22%; range, 11.7–19.5 μg/liter; group I), between 5 and 10 μg/liter in three patients (17%; range, 7.3–9 μg/liter; group II), and less than 5 μg/liter in 11 patients (61%; range, 0–4.7 μg/liter; group III). A positive correlation was found between serum IGF-I and peak GH levels after attainment of adult height (P = 0.007). Only one of the seven patients who showed increased GH secretion ability in adulthood (groups I and II) demonstrated other hormonal deficiencies (gonadotropin and adrenal insufficiencies). Among the 11 patients with persistent severe GHD (group III), 10 (91%) of the 11 subjects were shown to have multiple pituitary hormone deficits after attainment of adult height. The structure of the hypothalamo-pituitary axis differs among groups [i.e. patients who showed increased GH secretion ability in adulthood (groups I and II) vs. those who remained severely GHD (group III)]. The location of the EPPHS was significantly different among groups (P < 0.003). The EPPHS was found at the median eminence in all but one of group III patients and along the pituitary stalk (proximal stalk) in all but one of group I and II patients. The pituitary stalk was visible and described as normal (n = 1) or thin (n = 6) in all group I and II patients, whereas the pituitary stalk was not visible even after enhancement in seven of the 11 group III patients (P < 0.02). The prevalence of anterior pituitary hypoplasia and the mean height gain sd score were similar in each group. In conclusion, only 61% of patients with childhood-onset GHD and EPPHS remained severely GHD, and thus suitable for GH therapy, in adulthood. Although the pathogenesis of anterior pituitary dysfunction remains unclear in patients with ectopic neurohypophysis, isolated GHD, location of EPPHS along the stalk, and visibility of the pituitary stalk on magnetic resonance imaging findings clearly represent important markers to predict a less severe form of the disease.

scholarly journals Retesting Young Adults with Childhood-Onset Growth Hormone (GH) Deficiency with GH-Releasing-Hormone-Plus-Arginine Test1

2000 ◽  
Vol 85 (10) ◽  
pp. 3693-3699
Author(s):  
G. Aimaretti ◽  
C. Baffoni ◽  
S. Bellone ◽  
L. Di Vito ◽  
G. Corneli ◽  
...  
Keyword(s):  
Young Adults ◽  
Gh Deficiency ◽  
Statistical Significance ◽  
Young Patients ◽  
Normal Subjects ◽  
Childhood Onset ◽  
Gh Treatment ◽  
Provocative Test ◽  
Gh Secretion ◽  
The Mean

Within an appropriate clinical context, severe GH deficiency (GHD) in adults has to be defined biochemically by provocative testing of GH secretion. Patients with childhood-onset GHD need retesting in late adolescence or young adulthood to verify whether they have to continue recombinant human GH treatment. GHRH + arginine (GHRH+ARG) is the most reliable alternative to the insulin-induced hypoglycemia test (ITT) as a provocative test for the diagnosis of GHD in adulthood, provided that appropriate cut-off limits are assumed (normal limits, 16.5 μg/L as 3rd and 9.0 μg/L as 1st centile). We studied the GH response to a single GHRH (1 μg/kg iv) + ARG (0.5 g/kg iv) test in 62 young patients who had undergone GH replacement in childhood, based on the following diagnosis: 1) organic hypopituitarism with GHD (oGHD)[ n = 18: 15 male (M), 3 female (F); age, 26.8 ± 2.2 yr; GH peak < 10 μg/L after two classical tests]; 2) idiopathic isolated GHD (iGHD) [n = 23 (15 M, 8 F); age, 23.0 ± 1.5 yr; GH peak < 10 μg/L after two classical tests]; and 3) GH neurosecretory dysfunction (GHNSD) [n = 21 (10 M, 11 F); age, 25.1 ± 1.6 yr; GH peak > 10 μg/L after classical test but mGHc < 3 μg/L]. The GH responses to GHRH+ARG in these groups were also compared with that recorded in a group of age-matched normal subjects (NS) [n = 48 (20 M, 28 F); age, 27.7 ± 0.8 yr]. Insulin-like growth factor I levels in oGHD subjects (61.5 ± 13.7μ g/L) were lower (P < 0.001) than those in iGHD subjects (117.2 ± 13.1 μg/L); the latter were lower than those in GHNSD subjects (210.2 ± 12.9 μg/L), which, in turn, were similar to those in NS (220.9 ± 7.1 μg/L). The mean GH peak after GHRH+ARG in oGHD (2.8 ± 0.8 μg/L) was lower (P < 0.001) than that in iGHD (18.6 ± 4.7μ g/L), which, in turn, was clearly lower (P < 0.001) than that in GHNSD (31.3 ± 1.6 μg/L). The GH response in GHNSD was lower than that in NS (65.9 ± 5.5 μg/L), but this difference did not attain statistical significance. With respect to the 3rd centile limit of GH response in young adults (i.e. 16.5 μg/L), retesting confirmed GHD in all oGHD, in 65.2% of iGHD, and in none of the GHNSD subjects. With respect to the 1st centile limit of GH response (i.e. 9.0 μg/L), retesting demonstrated severe GHD in 94% oGHD and in 52.1% of iGHD. All oGHD and iGHD with GH peak after GHRH+ARG lower than 9 μg/L had also GH peak lower than 3 μg/L after ITT. In the patients in whom GHD was confirmed by retesting, the mean GH peak after GHRH+ARG was higher than that after ITT (3.4 ± 0.5 vs. 1.9 ± 0.4). In conclusion, given appropriate cut-off limits, GHRH+ARG is as reliable as ITT for retesting patients who had undergone GH treatment in childhood. Among these patients, severe GHD in adulthood is generally confirmed in oGHD, is frequent in iGHD, but never occurs in GHNSD.

scholarly journals Phenotype and Genetic Analysis of a Syndrome Caused by an Inactivating Mutation in the Growth Hormone-Releasing Hormone Receptor: Dwarfism of Sindh1

1998 ◽  
Vol 83 (11) ◽  
pp. 4065-4074
Author(s):  
Hiralal G. Maheshwari ◽  
Bernard L. Silverman ◽  
Josée Dupuis ◽  
Gerhard Baumann
Keyword(s):  
Gh Deficiency ◽  
Postnatal Growth ◽  
N Gene ◽  
Molecular Characteristics ◽  
Clinical Genetic ◽  
Gh Treatment ◽  
Gh Secretion ◽  
Absolute Requirement ◽  
Igf I ◽  
Igf Binding

We report, in detail, a new form of familial dwarfism, including its phenotypic features, hormonal profile, and molecular basis. Following a newspaper report of severe dwarfism in two villages in the province of Sindh, Pakistan, we organized an expedition to study its clinical, genetic, and molecular characteristics. We identified 18 dwarfs (15 male, 3 female), all members of a consanguineous kindred, ranging in age from newborn to 28 yr. Mean height was 7.2 sd below the norm, with mean adult heights of 130 cm for males and 113.5 cm for females. Body proportions and habitus were normal; but head circumference was 4.1 sd, and blood pressure approximately 3 sd below the norm. There was no dysmorphism, no microphallus, and no history of hypoglycemia. Serum GH did not respond to provocative stimuli (GHRH, l-dopa, or clonidine). Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were low (5.2 ± 2.0 ng/mL and 0.42 ± 0.13 μg/mL, respectively; mean ± sd) but rose normally with GH treatment. One affected, dwarfed couple had a son, demonstrating fertility in both sexes. Clinical and endocrinological evidence suggested isolated GH deficiency with a recessive inheritance pattern. The GH-N gene was found to be intact. Linkage analysis of microsatellite chromosomal markers near other candidate genes yielded a high LOD score (6.26) for the GHRH receptor (GHRH-R) locus. DNA sequencing revealed a nonsense mutation (Glu50→Stop) in the extracellular domain of the GHRH-R. This mutation predicts a severely truncated GHRH-R; it is identical to that recently reported in four patients from two other families. Inheritance is autosomal recessive (chromosome 7p) with a high degree of penetrance. Relatives heterozygous for the mutation had moderately decreased IGF-I levels and slightly blunted GH responses to GHRH and l-dopa, but they showed only minimal or no height deficit. This syndrome represents the human homologue of the little (lit/lit) mouse and closely resembles its phenotype. It demonstrates the absolute requirement of GHRH signaling for pituitary GH secretion and postnatal growth in humans, and its relatively minor (but discernible) biological importance in extrapituitary sites. The syndrome is distinct from other forms of GH deficiency with respect to microcephaly, asymptomatic hypotension, and absence of features such as facial dysplasia, significant truncal obesity, microphallus, or hypoglycemia. Its discovery raises the possibility of milder mutations in the GHRH-R gene as potential causes for partial GH insufficiency and idiopathic short stature.

scholarly journals Ghrelin test for the assessment of GH status in successfully treated patients with acromegaly

2006 ◽  
Vol 154 (5) ◽  
pp. 659-666 ◽  
Author(s):  
S Pekic ◽  
M Doknic ◽  
D Miljic ◽  
M Joksimovic ◽  
J Glodic ◽  
...  
Keyword(s):  
Gh Deficiency ◽  
Provocation Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Provocative Test ◽  
Gh Secretion ◽  
Control Subjects ◽  
Igf I ◽  
Secretory Capacity ◽  
Igfbp 3

Objective: Posttreatment assessment of disease activity and definition of cure of acromegaly, using measurement of GH secretion, remains problematic. Furthermore, with our efforts to achieve tight biochemical control of the disease it is foreseeable that a proportion of patients may be rendered GH deficient, thus requiring testing for GH deficiency. The aim of our study was to evaluate residual GH secretion in cured patients with acromegaly. Design and methods: At baseline, circulating GH, IGF-I, IGFBP-3, leptin and lipid (cholesterol and tri-glycerides) levels were measured in 33 acromegalic patients nine years after treatment with surgery of whom 6 were additionally irradiated. Two tests were performed: the GH suppression test - oral glucose tolerance test (OGTT) and the GH provocation test - ghrelin test (1 μg/kg i.v. bolus) and the results were compared with 11 age- and sex-matched control subjects. Results: According to the consensus criteria (normal IGF-I levels and post-OGTT GH nadir <1 μg/l), 21 treated acromegalic patients were cured, 6 had discordant IGF-I and GH nadir values during OGTT, while 6 had persistent acromegaly. After the GH provocative test with ghrelin (cut-off for severe GH deficiency is GH <3 μg/l), we detected 9 severely GH deficient patients (GHD) among 21 cured acromegalic patients. Mean GH peak (±s.e.m.) response to the ghrelin test in GHD acromegalics was significantly lower compared with acromegalics with sufficient GH secretory capacity and control subjects (1.2 ± 0.2 μg/l vs 20.1 ± 2.4 μg/l vs 31.1 ± 2.5 μg/l respectively, P<0.0001). Mean IGF-I and IGFBP-3 levels were not different between GHD and GH-sufficient cured acromegalics. Leptin levels and body mass index (BMI) were significantly higher in GHD male acromegalics compared with GH-sufficient male acromegalics. GHD female acromegalics tended to have higher BMIs while leptin levels were not different. Conclusions: The assessment of residual GH secretory capacity by the GH provocation test is necessary in the long-term follow-up of successfully treated acromegalics since a large proportion of these patients are rendered GH deficient.

scholarly journals Growth Hormone (GH) Secretion in Patients with Childhood-Onset GH Deficiency: Retesting after One Year of Therapy and at Final Height

2003 ◽  
Vol 59 (1) ◽  
pp. 7-15 ◽  
Author(s):  
M. Thomas ◽  
G. Massa ◽  
M. Maes ◽  
D. Beckers ◽  
M. Craen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Final Height ◽  
Childhood Onset ◽  
Gh Secretion ◽  
One Year

scholarly journals Cut-off limits of the peak GH response to stimulation tests for the diagnosis of GH deficiency in children and adolescents: study in patients with organic GHD

2016 ◽  
Vol 175 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Chiara Guzzetti ◽  
Anastasia Ibba ◽  
Sabrina Pilia ◽  
Nadia Beltrami ◽  
Natascia Di Iorgi ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Children And Adolescents ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Gh Secretion ◽  
Insulin Tolerance ◽  
Igf I ◽  
Stimulation Tests

ObjectiveThe diagnosis of GH deficiency (GHD) in children and adolescents is established when GH concentrations fail to reach an arbitrary cut-off level after at least two provocative tests. The objective of the study was to define the optimal GH cut-offs to provocative tests in children and adolescents.DesignRetrospective study in 372 subjects who underwent evaluation of GH secretion. GH and IGF-I were measured by chemiluminescence assay in all samples. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal GH cut-offs and the diagnostic accuracy of provocative tests.MethodsSeventy four patients with organic GHD (GH peak <10μg/L after two provocative tests) and 298 control subjects (GH response >10μg/L to at least one test) were included in the study. The provocative tests used were arginine, insulin tolerance test (ITT) and clonidine. Diagnostic criteria based on cut-offs identified by ROC analysis (best pair of values for sensitivity and specificity) were evaluated for each test individually and for each test combined with IGF-I SDS.ResultsThe optimal GH cut-off for arginine resulted 6.5μg/L, 5.1μg/L for ITT and 6.8μg/L for clonidine. IGF-I SDS has low accuracy in diagnosing GHD (AUC=0.85). The combination of the results of provocative tests with IGF-I concentrations increased the specificity.ConclusionsThe results of the ROC analysis showed that the cut-off limits which discriminate between normal and GHD are lower than those commonly employed. IGF-I is characterized by low diagnostic accuracy.

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