The Cut-off Limits of Growth Hormone Response to the Insulin Tolerance Test Related to Body Mass Index for the Diagnosis of Adult Growth Hormone Deficiency

Gasco, Valentina; Ferrero, Alberto; Bisceglia, Alessandro; Prencipe, Nunzia; Cambria, Valeria; Bioletto, Fabio; Ghigo, Ezio; Maccario, Mauro; Grottoli, Silvia

doi:10.1159/000508103

Cited by 12 publications

(17 citation statements)

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“…The GH response to GHRH + ARG test was defined as normal when GH > 11.0 mg/l for lean subjects, when GH > 8.0 mg/l for overweight subjects and when GH > 4.0 mg/l for obese subjects (1,21). The GH response to ITT was defined as normal when GH > 3.5 mg/l for lean subjects and when GH > 1.3 mg/l for overweight or obese subjects, in agreement with a recent paper that has identified these as the best BMI-related GH cutoffs for the diagnosis of GHD at ITT (28). Patients with a concordantly normal response to both tests were considered as having a normal function of the somatotroph axis.…”

Section: Data Collectionsupporting

confidence: 79%

Development and Internal Validation of a Predictive Model for Adult GH Deficiency Prior to Stimulation Tests

et al. 2021

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BackgroundThe diagnosis of adult GH deficiency (GHD) relies on a reduced GH response to provocative tests. Their diagnostic accuracy, however, is not perfect, and a reliable estimation of pre-test GHD probability could be helpful for a better interpretation of their results.MethodsEighty patients showing concordant GH response to two provocative tests, i.e. the insulin tolerance test and the GHRH + arginine test, were enrolled. Data on IGF-I values and on the presence/absence of other pituitary deficits were collected and integrated for the estimation of GHD probability prior to stimulation tests.ResultsAn independent statistically significant association with the diagnosis of GHD was found both for IGF-I SDS (OR 0.34, 95%-CI 0.18-0.65, p=0.001) and for the presence of other pituitary deficits (OR 6.55, 95%-CI 2.06-20.83, p=0.001). A low (<25%) pre-test GHD probability could be predicted when IGF-I SDS > +0.91 in the presence of other pituitary deficits or IGF-I SDS > -0.52 in the absence of other pituitary deficits. A high (>75%) pre-test GHD probability could be predicted when IGF-I SDS < -0.82 in the presence of other pituitary deficits or IGF-I SDS < -2.26 in the absence of other pituitary deficits.ConclusionThis is the first study that proposes a quantitative estimation of GHD probability prior to stimulation tests. Our risk class stratification represents a simple tool that could be adopted for a Bayesian interpretation of stimulation test results, selecting patients who may benefit from a second stimulation test and possibly reducing the risk of wrong GHD diagnosis.

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Section: Data Collectionsupporting

confidence: 79%

Development and Internal Validation of a Predictive Model for Adult GH Deficiency Prior to Stimulation Tests

et al. 2021

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“…The GHRH + ARG test has been shown to distinguish adult patients with GHD from normal subjects with a sensitivity comparable to the ITT, considering appropriate BMI-related cutoffs [69, 75]. Indeed, the GH response to GHRH + ARG is negatively associated with BMI (Table 1), as also recently demonstrated for the ITT [76]. Thus, the GHRH + ARG test could be the first choice in the elderly for its safety profile and the lack of significant contraindications, except for chronic renal failure [77].…”

Section: Gh Deficiencymentioning

confidence: 75%

Dynamic Tests in Pituitary Endocrinology: Pitfalls in Interpretation during Aging

et al. 2021

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Aging and age-related diseases represent hot topics of current research. Progressive damage in morphology and function of cells and tissue characterizes the normal process of aging, that is influenced by both genetic and environmental factors. The ability of each individual to adapt to these stressors defines the type of aging and the onset of age-related diseases (i.e. metabolic syndrome, inflammatory disorders, cancer and neurodegenerative diseases). The endocrine system plays a critical role in this process, because of its complex relationships with brain, immune system, and skeletal muscle; thus, alterations in hormonal networks occur during aging to maintain homeostasis, with consequent under- or overactivity of specific hypothalamic-pituitary-peripheral hormone axes. On the other hand, the increase in life expectancy has led to increasing incidence of age-related diseases, including endocrine disorders, which may prompt assessment of endocrine function in aging individuals. In this context, there is growing awareness that natural changes of endocrine physiology and physiopathology occurring with increasing age may necessitate age-driven diagnostic cut-offs requiring validation in the elderly. This review aims to analyse the available literature on the hormone response to the most important dynamic tests currently used in the clinical practice for the screening of anterior pituitary-related diseases, to underline pitfalls in interpretation during aging.

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“…A BMI-adjusted GH response to GHRH-arginine (BMI <25: peak <11 μ g/L, BMI 25–30: peak <8 μ g/L, BMI >30: <4 μ g/L) is a strong indicator of GHD, although a normal response does not exclude GHD. To examine the well-known negative association between GH response to stimulation tests and BMI, Gasco and colleagues studied 106 patients who underwent GHRH + arginine stimulation as well as an ITT, enabling investigators to establish BMI cut-offs for diagnosing adult GHD [ 23 ]. The ITT is especially preferred when damage to the hypothalamus is suspected.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies have compared the ITT with alternative tests including morning cortisol [ 24 , 25 ], ACTH stimulation test [ 26 , 27 ], GHRH + arginine [ 28 ], and glucagon [ 29 ]. A recent study demonstrated that with appropriate BMI cut-off limits, the ITT is a reliable test to diagnose adult GHD [ 23 ]. However, the ITT (with adequate hypoglycaemia) is superior to other endocrine tests of combined GH responsivity [ 4 ] and HPA axis integrity.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of the Blood Glucose, Growth Hormone, and Cortisol Responses to Two Doses of Insulin (0.15 U/kg vs. 0.10 U/kg) in the Insulin Tolerance Test: A Single-Centre Audit of 174 Cases

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Dwyer

Anghel

et al. 2022

International Journal of Endocrinology

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Objective. The insulin tolerance test (ITT) is the gold standard endocrine test used to assess the integrity of the growth hormone (GH) and cortisol axes. The ITT has potential risks, and severe hypoglycaemia may necessitate intravenous glucose rescue. There is no clear consensus as to the optimal insulin dose for the ITT. Therefore, we sought to compare the standard dose (0.15 U/kg) and a low-dose ITT (0.1 U/kg). Design. Single-centre audit of ITT data (2012–2021). Patients and Measurements. Patients who underwent an ITT to assess possible GH deficiency/adrenal insufficiency were included. Glucose, GH, and cortisol were measured at baseline and 30, 45, 60, 90, and 120 minutes following I.V. insulin bolus (0.15 U/kg or 0.10 U/kg). Results. Of the ITTs performed, only 3/177 (1.7%) did not achieve adequate hypoglycaemia (≤2.2 mmol/L) with a single insulin dose. In total, 174 patients (43.5 ± 12.1 yrs, mean ± standard deviation) were included for analysis (0.15 U/kg: n = 113, 0.10 U/kg: n = 61). All 174 subjects had adequate hypoglycaemia regardless of baseline fasting blood glucose level or insulin dose. Neither nadir glucose nor glucose delta (i.e., baseline minus nadir) differed between insulin doses. Trends in both cortisol and GH responses over time were similar between groups, and a greater proportion of patients receiving the standard dose had an adequate cortisol response (77/106 (72.6%) vs. 32/60 (53.3%), p = 0.01 ). The rates of glucose rescue did not differ in a subset of 79 patients, with on-demand glucose rescue in 4/35 (11%) for the standard dose and 2/44 (5%) for the low dose ( p = 0.25 ). Conclusions. Our results suggest that the low-dose ITT produces comparable glucose, cortisol, and GH responses to the higher dose. Given the risks associated with hypoglycaemia, the low dose appears to be preferable to the standard dose ITT in most circumstances.

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The Cut-off Limits of Growth Hormone Response to the Insulin Tolerance Test Related to Body Mass Index for the Diagnosis of Adult Growth Hormone Deficiency

Cited by 12 publications

References 45 publications

Development and Internal Validation of a Predictive Model for Adult GH Deficiency Prior to Stimulation Tests

Development and Internal Validation of a Predictive Model for Adult GH Deficiency Prior to Stimulation Tests

Dynamic Tests in Pituitary Endocrinology: Pitfalls in Interpretation during Aging

A Comparison of the Blood Glucose, Growth Hormone, and Cortisol Responses to Two Doses of Insulin (0.15 U/kg vs. 0.10 U/kg) in the Insulin Tolerance Test: A Single-Centre Audit of 174 Cases

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