Diagnosis of growth-hormone deficiency in adults

Hoffman, David; O’Sullivan, Anthony J; Ho, Ken K. Y.; Baxter, Robert C.

doi:10.1016/s0140-6736(94)90181-3

Cited by 448 publications

(323 citation statements)

References 17 publications

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“…The value of the study of spontaneous GH secretion for the diagnosis of adult GHD is therefore low even if it is performed after fasting. 28 The lack of GH response to fasting in obesity could reflect impairment of neuroendocrine reaction to starvation. Hypothalamic somatostatin hyperactivity seems unlikely, 5 but there is evidence for reduced activity of GHRH-secreting neurons, 5 although short-term treatment with GHRH does not restore the GH response to GHRH itself.…”

Section: Discussionmentioning

confidence: 99%

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

et al. 2001

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OBJECTIVE: Reduction of growth hormone (GH) secretion in obesity probably reflects neuroendocrine and metabolic abnormalities. Even short-term fasting stimulates GH secretion and distinguishes normal from hypopituitary subjects with growth hormone deficiency (GHD). Marked weight loss improves GH secretion in obesity but the effect of fasting is controversial. We studied the effects of a 36 h fasting on the GH=IGF-I axis and metabolic parameters in obesity. SUBJECTS: We studied nine obese patients (OB; three male and six female; age, 29.2 AE 4.8; range, 18 -59 y; body mass index (BMI), 43.4 AE 2.7 kg=m 2 ; WHR, 0.9 AE 0.1). Fifteen normal subjects (NS; eight male and seven female 28.9 AE 0.6, 25 -35 y; 21.6 AE 0.4 kg=m 2 ) and 10 adult hypopituitary patients with severe GH deficiency (GHD; seven male and three female; 37.6 AE 2.3, 29 -50 y; 24.5 AE 1.0 kg=m 2 ; GH peak < 3mg=l after ITT and=or < 9mg=l after GHRH þ arginine) served as control groups. STUDY DESIGN: We studied the effects of 36 h fasting on 8 h diurnal mean GH, insulin and glucose concentrations (mGHc, mINSc and mGLUc; assay every 30 min from 8.00 am to 4.00 pm) as well as on IGF-I, IGFBP-3, ALS, IGFBP-1, GHBP and free fatty acid (FFA) levels. RESULTS: Before fasting, basal IGF-I and ALS levels in OB were similar to those in NS and both were higher (P < 0.001) than those in GHD. IGFBP-3 levels in OB were lower (P < 0.01) than in NS but higher (P < 0.02) than in GHD. GHBP levels in OB and GHD were similar and both were higher (P < 0.01) than in NS. Glucose levels were similar in all groups. FFA levels in OB were higher (P < 0.01) than in NS but similar to those in GHD. IGFBP-1 in OB were lower (P < 0.05) than in NS and GHD which, in turn, were similar. On the other hand, mINSc in OB was higher (P < 0.01) than that in NS and GHD which, in turn, were similar. The mGHc in OB was similar to that in NS but only the latter was higher (P < 0.05) than in GHD. The individual mGHc in the three groups overlapped. After fasting, IGF-I levels in GHD were unchanged while they decreased in OB (P ¼ NS) as well as in NS (P < 0.01). IGFBP-3 and ALS levels did not change. GHBP levels in OB and GHD were unchanged while they increased in NS (P < 0.01). Glucose and FFA levels were reduced and increased, respectively, in all groups (P < 0.02 and P < 0.01). IGFBP-1 increased while mINSc decreased in all groups (P < 0.02 and P < 0.01); in OB they persisted lower and higher (P < 0.01) respectively, than in NS and GHD. Fasting significantly increased mGHc in NS (P < 0.001) but not in OB as well as in GHD. Individual mGHc in OB showed persistent overlap with GHD. CONCLUSIONS: Short-term fasting does not increase GH secretion in obesity and does not distinguish somatotroph function in obese from that in severe GHD adults. Short-term fasting in obesity has attenuated effects on insulin and IGFBP-1 secretion while it normally increases free fatty acids in spite of any change in GH secretion.

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Section: Discussionmentioning

confidence: 99%

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

et al. 2001

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“…25,26 In fact, in this latter condition IGF-I and IGFBP-3 assays as well as the study of spontaneous GH secretion are not reliable diagnostic tools 25±27 while insulin-induced hypoglycemia has been proposed as the golden standard test. 26 More recently, testing with GHRH combined with arginine, which likely acts via inhibition of hypothalamic somatostatin release and potentiates the GH response to the neurohormone, 28,29 has been proposed as the best way to explore the maximal secretory capacity of somatotrope cells and to distinguish between normal subjects and GH de®cient patients. 30 At present, there is consensus about the fact that rhGH replacement therapy is allowed only for GHD patients presenting with GH peak response lower than 3 mg/l after provocative stimulation.…”

Section: Introductionmentioning

confidence: 99%

Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

et al. 1997

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OBJECTIVE: To evaluate the maximal secretory capacity of somatotrope cells in obesity and to compare it with that in hypopituitaric patients with GH de®ciency. DESIGN: Stimulation with GHRH. (1 mg/kg iv) combined with arginine (ARG, 0.5 g/kg iv), which strongly potentiates the GH response to the neurohormone, likely inhibiting hypothalamic somatostatin. The reproducibility of the GH response to GHRH ARG was evaluated in a second session. SUBJECTS: Forty-®ve patients with simple obesity (OB 11 male and 34 female, age 40.5 AE AE 1.8 y, BMI 38.8 AE AE 1.1 kg/m 2 ), 49 patients with hypopituitarism (GHD, 23 male and 26 female, 43.6 AE AE 2.4 y, 24.7 AE AE 0.7 kg/m 2 ) and 44 normal young volunteers (NS, 25 male and 19 female, 33.8 AE AE 1.0 y, 21.6 AE AE 0.3 kg/m 2 ) were studied. MEASUREMENTS: GH levels were assayed by IRMA method, basally at 7 60 and 0 min, and than every 15 min up to 120 min. Basal IGF±I levels were assayed by RIA method, after acid-ethanol extraction. RESULTS: IGF±I levels in OB were lower (P`0.005) than those in NS but higher (P`0.005) than those in GHD. Mean peak GH response to GHRH ARG in OB was clearly lower than that in NS (P`0.005) and higher (P`0.005) than that in GHD. Sixty±percent OB and 100% GHD showed peak GH responses lower than the minimum normal limit in NS (16.5 mg/l) while 4% OB and only 53% GHD with GH responses lower than 3 mg/l, the limit under which GH replacement therapy of severe de®ciency is allowed. Good intraindividual reproducibility of the GH response to GHRH arginine test was present in all groups (OB: r 0.78, P`0.0001; GHD: r 0.57, P`0.003; NS: r 0.74, P`0.0001;. CONCLUSIONS: The maximal secretory capacity of somatotrope cells is clearly less than normal in the obese but still more than is seen in GHD subjects. However, in about 50% of obese patients, the pituitary GH releasable pool overlaps with that of hypopituitaric patients with GH de®ciency. Thus, even when the maximal secretory capacity of somatotrope cells is evaluated by a potent and reproducible provocative tests such as GHRH arginine, overweight has to be taken in a great account as the cause of severely impaired GH response in patients with suspected GH de®ciency.

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“…2008a), and GH‐deficient individuals often exhibit impaired insulin sensitivity (Hoffman et al. 1994). Our results show that in isolated muscle, GH acutely stimulates STAT5, but does not increase the phosphorylation of AKT, which is consistent with previous findings, some of which indicate GH‐induced reductions in AKT activity (Takano et al.…”

Section: Discussionmentioning

confidence: 99%

Acylated and unacylated ghrelin do not directly stimulate glucose transport in isolated rodent skeletal muscle

Cervone

Dyck

2017

Physiol Rep

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Emerging evidence implicates ghrelin, a gut‐derived, orexigenic hormone, as a potential mediator of insulin‐responsive peripheral tissue metabolism. However, in vitro and in vivo studies assessing ghrelin's direct influence on metabolism have been controversial, particularly due to confounding factors such as the secondary rise in growth hormone (GH) after ghrelin injection. Skeletal muscle is important in the insulin‐stimulated clearance of glucose, and ghrelin's exponential rise prior to a meal could potentially facilitate this. This study was aimed at elucidating any direct stimulatory action that ghrelin may have on glucose transport and insulin signaling in isolated rat skeletal muscle, in the absence of confounding secondary factors. Oxidative soleus and glycolytic extensor digitorum longus skeletal muscles were isolated from male Sprague Dawley rats in the fed state and incubated with various concentrations of acylated and unacylated ghrelin in the presence or absence of insulin. Ghrelin did not stimulate glucose transport in either muscle type, with or without insulin. Moreover, GH had no acute, direct stimulatory effect on either basal or insulin‐stimulated muscle glucose transport. In agreement with the lack of observed effect on glucose transport, ghrelin and GH also had no stimulatory effect on Ser473 AKT or Thr172 AMPK phosphorylation, two key signaling proteins involved in glucose transport. Furthermore, to our knowledge, we are among the first to show that ghrelin can act independent of its receptor and cause an increase in calmodulin‐dependent protein kinase 2 (CaMKII) phosphorylation in glycolytic muscle, although this was not associated with an increase in glucose transport. We conclude that both acylated and unacylated ghrelin have no direct, acute influence on skeletal muscle glucose transport. Furthermore, the immediate rise in GH in response to ghrelin also does not appear to directly stimulate glucose transport in muscle.

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Diagnosis of growth-hormone deficiency in adults

Cited by 448 publications

References 17 publications

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

Acylated and unacylated ghrelin do not directly stimulate glucose transport in isolated rodent skeletal muscle

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