Definition Of Growth Hormone Deficiency Research Articles

Accuracy of Glucagon Testing Across Transition in Young Adults with Childhood-Onset Growth Hormone Deficiency.

The 2019 AACE guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 µg/L and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase. Aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement. Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies-HDs) and 18 severe organic GHD (≥3 HDs). Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis-ROC- identified 7.3 μg/L as the optimal GH peak cutoff to GST (95% CI 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value-PPV-88.0%, negative predictive value-NPV-95.7%), able to correctly classify 91.8% of the entire cohort while 5.8 μg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3HDs showed a GH peak <5μg/L at ITT and <5.8μg/L at GST but one. The optimal cutoff for IGF1 was -1.4 SDS (95% CI -1.94-0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population. A GH peak to GST <5.8 μg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pre-test probability of permanent GHD.

Diagnosing Growth Hormone Deficiency After Aneurysmal Subarachnoid Hemorrhage

To the Editor: We read with interest the article by Dimopoulou1 on hypopituitarism after aneurysmal subarachnoid hemorrhage (SAH). Although this topic deserves the attention of the neurological community treating these patients, especially those readers who, from the scope of the journal cannot be expected to be familiar with diagnostic criteria for endocrine disorders, deserve to be assured about the soundness of the proposed definitions of neuroendocrine dysfunction and the conclusions derived thereof. In the case of the authors’ definition of growth hormone deficiency (GHD) in SAH patients, this should be questioned for several reasons. The authors assume inadequate growth hormone secretion indicative of GHD in their patients if IGF-I levels are <2 standard deviations for the appropriate age range, quoting an article by Aimaretti et al.2 However, insulin-like growth factor (IGF)-I levels do not only reflect growth hormone (GH) secretory status but also are influenced by several other factors. Therefore, low IGF-I levels can only be considered a parameter of impaired GH secretion if malnutrition, liver failure, poorly controlled diabetes mellitus, and uremia are ruled out.3 It is well-known that the IGF-I levels observed in hypopituitary patients and the normal range of IGF-I levels progressively overlap with advancing age of the patients. Along these …

Assessment of growth hormone (GH) secretion in men with adult-onset GH deficiency compared with that in normal men--a clinical research center study.

It is not known how patients who acquire GH deficiency (GHD) in adulthood differ in measures of GH secretion from normal adults. To characterize measures of GH secretion in such patients compared to those in normal subjects, we studied 23 men (median age, 51 yr; range, 32-62 yr) with adult-onset pituitary disease, defined as GH-deficient based on having no detectable GH response to two pharmacological agents, and 17 normal men. Patients less than 50 yr old received insulin (0.1 U/kg, i.v.) and clonidine (0.15 mg, orally), whereas those 50 yr of age or older as well as normal controls received arginine (30 g, i.v.) and clonidine. Patients were compared to normal men by investigating GH sampling every 10 min for 24 h and serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein 2 (IGFBP-2), IGFBP-3, and GH-binding protein. Frequent venous sampling of GH was analyzed in terms of mean 24-h levels, pooled 24-h GH, mean levels over the 12 h between 2000-0800 h (mean overnight GH level), and pulse analysis (pulses per 24 h and pulse amplitude) by the Pulsar computer program. Although there were significant differences between the two groups for almost all measures of GH secretion, overlap between the groups was always present. GH levels measured using a highly sensitive chemiluminescence assay on 24-h pools derived from frequent sampling displayed the least overlap between the two groups, as only 2 of 17 normal controls overlapped with the GHD patients. The pooled 24-h GH level using this technique was significantly lower in patients with GHD than in controls (0.117 +/- 0.021 vs. 0.861 +/- 0.098 micrograms/L; P < 0.0001). In the analysis of frequent GH sampling using a standard immunoradiometric assay, mean overnight GH levels provided the best separation between the two groups, as all 23 patients had values of 0.6 microgram/L or less, and 13 of 17 normal controls had values greater than 0.6 microgram/L. The mean overnight GH level in patients was 0.6 +/- 0.0 microgram/L compared to 1.0 +/- 0.1 microgram/L in controls (P < 0.0001). The mean 24-h GH level in patients was 0.5 +/- 0.0 microgram/L compared to 0.8 +/- 0.1 microgram/L in normal controls (P < 0.0001). GH pulse frequency and pulse amplitude were also reduced in patients with GHD compared to those in normal controls [1.7 +/- 0.5 vs. 5.1 +/- 0.5 pulses/24 h (P < 0.0001) and 0.6 +/- 0.1 vs. 2.8 +/- 0.4 microgram/L (P < 0.0001), respectively]. The mean serum IGF-I level was significantly lower in patients with GHD than in normal controls (106.7 +/- 8.0 vs. 218.7 +/- 16.7 microgram/L; P < 0.0001). Three of 23 patients overlapped with control values. Mean serum levels of IGFBP-3 and the serum IGF-I/IGFBP-2 ratio were also significantly lower in patients than in controls, but values overlapped substantially. We conclude that overlap occurs on measures of GH secretion between normal men and men identified as GH deficient despite a stringent definition of GHD. The best separation was obtained using pooled 24-h GH levels determined by a highly sensitive chemiluminescence assay.

The severity of growth hormone deficiency in adults with pituitary disease is related to the degree of hypopituitarism

A number of studies of the effect of GH replacement therapy in adult patients with GH deficiency have been published, but the definition of GH deficiency has varied considerably. In order to define severe GH deficiency more critically we have determined GH status in the context of gonadotrophin, ACTH and TSH secretion in adult patients with pituitary disease. Analysis of peak GH response to an insulin tolerance test performed during comprehensive assessment of pituitary function. One hundred and ninety non-acromegalic patients (96 male) with pituitary disease whose ages ranged from 16 to 72 (mean 39.4) years. The patients were divided into four groups according to the number of anterior pituitary hormone deficiencies demonstrated; isolated GH deficiency (GHD0), or GH deficiency plus an additional one, two or three pituitary hormone deficits (GHD1, GHD2, GHD3). The four groups were matched for age and blood glucose nadir during the ITT. The median (interquartile range) GH peaks were GHD0, 10.0 (5.4-16); GHD1, 4.0 (2.7-7.7); GHD2, 2.0 (1-2.9); GHD3, 1.8 (1-3.2) mU/l. There was a significant downward trend in the medians (P < 0.0001). The differences between GHD0 and GHD1, and GHD1 and GHD2, were highly significant (P < 0.0001); however, there was no difference between GHD2 and GHD3. Ninety-one per cent of patients in combined groups GHD2 and GHD3, 55% in GHD1 and 24% in GHD0 had a peak GH < 5 mU/l. Our study has shown that GH deficiency is variable according to the degree of hypopituitarism present and that the greater the number of pituitary hormone deficits the more severe the GH deficiency. These observations will help to clarify the diagnosis of GH deficiency in adult life.

Use of Growth Hormone in the Treatment of Short Stature: Boon or Abuse?

Growth hormone (GH) was isolated approximately 30 years ago. Since then, we have witnessed major advances in understanding the regulation and pattern of GH secretion and its many metabolic actions.1 With the advent of recombinant DNA-generated growth hormone (rhGH) in 1985, the opportunities to treat children who have organic or idiopathic GH deficiencies are now, for the first time, unlimited. DEFINITION OF GROWTH HORMONE DEFICIENCY Although a role for GH in the treatment of certain children deficient in GH is established, the definition of GH deficiency remains controversial. The controversy surrounding the diagnosis of GH deficiency was highlighted recently when it was shown that, among the many commercial assay kits available, the same serum sample yielded GH concentrations that differed by as much as 100% for the same sample. Using different GH assay kits, a child who has short stature could be determined to be deficient in GH in the view of one endocrinologist but to have sufficient GH (ie, to be normal) by another endocrinologist.2,3 Despite these obvious limitations, GH testing has an important role in the clinical evaluation of the child who is short. When a child fails a simple screening test (ie, serum GH level of

Use of Growth Hormone in the Treatment of Short Stature: Boon or Abuse?

Growth hormone (GH) was isolated approximately 30 years ago. Since then, we have witnessed major advances in understanding the regulation and pattern of GH secretion and its many metabolic actions.1 With the advent of recombinant DNA-generated growth hormone (rhGH) in 1985, the opportunities to treat children who have organic or idiopathic GH deficiencies are now, for the first time, unlimited. DEFINITION OF GROWTH HORMONE DEFICIENCY Although a role for GH in the treatment of certain children deficient in GH is established, the definition of GH deficiency remains controversial. The controversy surrounding the diagnosis of GH deficiency was highlighted recently when it was shown that, among the many commercial assay kits available, the same serum sample yielded GH concentrations that differed by as much as 100% for the same sample. Using different GH assay kits, a child who has short stature could be determined to be deficient in GH in the view of one endocrinologist but to have sufficient GH (ie, to be normal) by another endocrinologist.2,3 Despite these obvious limitations, GH testing has an important role in the clinical evaluation of the child who is short. When a child fails a simple screening test (ie, serum GH level of &amp;lt;10 ng/mL following vigorous exercise, such as running for 20 minutes), more definitive GH testing is the next step.

Diagnosis of Growth Hormone Deficiency and the Treatment of Short Stature-Reply

In Reply. — We tried to summarize the complexity of current controversies about the diagnosis of growth hormone deficiency and the treatment of non-growth hormone—deficient short stature. The points raised by Dr Rotenstein further illustrate this complexity, and we welcome the opportunity to clarify these issues. Dr Rotenstein raises the question of growth hormone response to growth hormone releasing factor in the diagnosis of growth hormone deficiency. However, the classic definition of growth hormone deficiency does not involve assessment of the growth hormone secretory response to growth hormone releasing factor. The rise in growth hormone levels in some growth hormone—deficient children following administration of growth hormone releasing factor is a separate issue and suggests that the etiology of growth hormone deficiency in many children is actually deficiency of growth hormone releasing factor. We agree that the question of growth hormone treatment for very short non—growth hormone—deficient children who have marginal