GH deficiency in patients after cure of acromegaly by surgery alone

ObjectiveThe aim of this study was to determine the frequency and characteristics of severe GH deficiency (sGHD) in patients after treatment of acromegaly by surgery alone.Design and methodsOne hundred and eighty-six patients fulfilling the criteria for cure of acromegaly were examined by GH-releasing peptide-2 stimulation test or arginine stimulation test as well as oral glucose tolerance test (GTT). In addition, the Japanese adult hypopituitarism questionnaire was completed to determine the quality of life (QoL).ResultssGHD was found in 17 patients (9.1%; the GH-deficient group), and not found in 169 patients (90.9%; the GH-sufficient group). There were no significant differences in preoperative serum GH levels, IGF1 levels, incidence of hyperprolactinemia, tumor volumes, or incidence of microadenoma between the two groups. Upon follow-up examination, IGF1 levels and Z-scores of IGF1 levels were significantly lower in the GH-deficient group than in the GH-sufficient group, whereas neither basal GH levels nor nadir GH levels during 75 g GTT were significantly different between the two groups. Moreover, sGHD patients had a substantially higher incidence of multiple pituitary failures (17.6 vs 2.4%) and dyslipidemia (60 vs 16.2%). sGHD patients had a substantially poorer condition-related QoL.ConclusionsThis is the first large-scale, single-center, clinical study to evaluate sGHD in patients after cure of acromegaly by surgery alone. This study found that sGHD occurred in ∼9% of patients and assessment of GHD by stimulation tests is critical after successful treatment of acromegaly by surgery.

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Prevalence of GH deficiency in cured acromegalic patients: impact of different previous treatments

Acta Endocrinologica ◽

10.1530/eje-09-0222 ◽

2009 ◽

Vol 161 (1) ◽

pp. 37-42 ◽

Cited By ~ 21

Author(s):

C L Ronchi ◽

C Giavoli ◽

E Ferrante ◽

E Verrua ◽

S Bergamaschi ◽

...

Keyword(s):

Gh Deficiency ◽

Previous Treatment ◽

Tolerance Test ◽

Oral Glucose ◽

Fat Percentage ◽

Treatment Groups ◽

Gh Secretion ◽

Group 2 ◽

Design And Methods ◽

Group 1

ObjectiveRadiotherapy (RT) for pituitary adenomas, including GH-secreting ones, frequently leads to GH deficiency (GHD). Data on the effects of surgery alone (S) on dynamic GH secretion are limited. The aim of the study was to investigate the occurrence of GHD in acromegalic patients treated with different therapeutic options.Design and methodsFifty-six patients in remission from acromegaly, (33 F & 23 M, age: 54±13 years, body mass index (BMI): 28.4±4.1 kg/m2, 21 with adequately substituted pituitary deficiencies) treated by S alone (n=33, group 1) or followed by RT (n=23, group 2), were investigated for GHD by GHRH plus arginine testing, using BMI-adjusted cut-offs. Several metabolic and cardiovascular parameters (waist circumference, body fat percentage, blood pressure, fasting and post-oral glucose tolerance test glucose, HbA1c, insulin resistance and lipid profile) were evaluated in all the patients and 28 control subjects with known diagnosis of GHD.ResultsSerum GH peak after challenge was 8.0±9.7 μg/l, without any correlation with post-glucose GH nadir and IGF-1 levels. The GH response indicated severe GHD in 34 patients (61%) and partial GHD in 15 patients (27%). IGF-1 were below the normal range in 14 patients (25%). The frequency of GHD was similar in the two treatment groups (54% in group 1 and 70% in group 2). No significant differences in metabolic parameters were observed between acromegalic patients and controls with GHD.ConclusionsSevere GHD may occur in about 60% of patients treated for acromegaly, even when cured after S alone. Thus, a stimulation test (i.e. GHRH plus arginine) is recommended in all cured acromegalic patients, independently from previous treatment.

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

Frontiers in Endocrinology ◽

10.3389/fendo.2021.737947 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fabio Bioletto ◽

Mirko Parasiliti-Caprino ◽

Alessandro Maria Berton ◽

Nunzia Prencipe ◽

Valeria Cambria ◽

...

Keyword(s):

Gh Deficiency ◽

Quantitative Estimation ◽

Tolerance Test ◽

Stimulation Test ◽

Internal Validation ◽

Risk Class ◽

Insulin Tolerance ◽

Adult Gh Deficiency ◽

Igf I ◽

Stimulation Tests

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

Acta Endocrinologica ◽

10.1530/eje.1.02148 ◽

2006 ◽

Vol 154 (5) ◽

pp. 659-666 ◽

Cited By ~ 9

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.

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Importance of Intestinal Environment and Cellular Plasticity of Islets in the Development of Postpancreatectomy Diabetes

10.2337/figshare.13626788 ◽

2021 ◽

Author(s):

Tatsuya Fukuda ◽

Ryotaro Bouchi ◽

Takato Takeuchi ◽

Kikuko Amo-Shiinoki ◽

Atsushi Kudo ◽

...

Keyword(s):

Insulin Resistance ◽

Short Chain Fatty Acids ◽

Tolerance Test ◽

Oral Glucose ◽

Cellular Plasticity ◽

Β Cell ◽

Microbiome Composition ◽

Significant Difference ◽

Histological Characteristics ◽

Design And Methods

OBJECTIVE To elucidate the pathogenesis of post-pancreatectomy diabetes (PPDM). RESEARCH DESIGN AND METHODS Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) (n = 20) or distal pancreatectomy (DP) (n = 28) were included. 75-g oral glucose tolerance test was performed every 6 months. Microbiome composition and short-chain fatty acids in feces were examined before and 6 months after surgery. The association of histological characteristics of the resected pancreas with PPDM were examined. RESULTS During follow-up (median, 3.19 years), 2 out of 20 PD patients and 16 out of 28 DP patients developed PPDM. Proteobacteria relative abundance, plasma GLP-1, and fecal butyrate levels increased only after PD. Postsurgical butyrate levels were correlated with postsurgical GLP-1 levels. With no significant difference in the volume of the resected pancreas between the surgical procedures, both β-cell and α-cell areas in the resected pancreas were significantly higher in DP patients than in PD patients. In DP patients, the progressors to diabetes showed pre-existing insulin resistance compared with non-progressors, and both increased α- and β-cell areas were predictors of PPDM. Furthermore, in DP patients, α-cell and β-cell areas were associated with ALDH1A3 expression in islets. CONCLUSIONS We postulate that a greater removal of β-cells contributes to the development of PPDM after DP. Islet expansion along with pre-existing insulin resistance is associated with high cellular-plasticity, which may predict the development of PPDM after DP. In contrast, PD is associated with alterations of gut microbiome and increases in SCFA production and GLP-1 secretion, possibly protecting against PPDM development.

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Influence of Body Mass Index and Gender on Growth Hormone (GH) Responses to GH-Releasing Hormone Plus Arginine and Insulin Tolerance Tests

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1450 ◽

2005 ◽

Vol 90 (3) ◽

pp. 1563-1569 ◽

Cited By ~ 60

Author(s):

Xiao-Dan Qu ◽

Irene T. Gaw Gonzalo ◽

Mohammed Y. Al Sayed ◽

Pejman Cohan ◽

Peter D. Christenson ◽

...

Keyword(s):

Body Mass Index ◽

Gender Differences ◽

Body Mass ◽

Healthy Subjects ◽

Gh Deficiency ◽

Tolerance Test ◽

Insulin Tolerance Test ◽

Insulin Tolerance ◽

Stimulation Tests ◽

And Gender

The aim of this study is to assess whether gender and body mass index (BMI) should be considered in developing thresholds to define GH deficiency, using GH responses to GHRH + arginine (ARG) stimulation and insulin tolerance test (ITT). Thirty-nine healthy subjects (19 males, 20 females; ages 21–50 yr) underwent GHRH + ARG, and another 27 subjects (19 males, 8 females; ages 20–49 yr) underwent ITT. Peak GH response was significantly higher (P = 0.005) after GHRH + ARG than with ITT, and this difference could not be explained by age, gender, or BMI. Peak GH response was negatively correlated with BMI in both tests (GHRH + ARG, r = −0.76; and ITT, r = −0.65). Peak GH response to GHRH + ARG was higher in females than males (P = 0.004; ratio = 2.4), but it was attenuated after eliminating the influence of BMI (P = 0.13; ratio = 1.6). No significant gender differences were found in peak GH responses to ITT, which could be due to the smaller number of female subjects studied. GH response to GHRH + ARG and ITT stimulation is sensitive to BMI differences and less so to gender differences. A higher BMI is associated with a depressed GH response to both stimulation tests. BMI should therefore be considered as a factor when defining the diagnostic cut-off points in the assessment of GH deficiency, whereas whether gender should be likewise used is inconclusive from this study.

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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

Acta Endocrinologica ◽

10.1530/eje-16-0105 ◽

2016 ◽

Vol 175 (1) ◽

pp. 41-47 ◽

Cited By ~ 16

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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Association of postprandial and fasting triglycerides with traits of the metabolic syndrome in the Metabolic Intervention Cohort Kiel

Acta Endocrinologica ◽

10.1530/eje-09-0446 ◽

2010 ◽

Vol 162 (4) ◽

pp. 719-727 ◽

Cited By ~ 10

Author(s):

Diana Rubin ◽

Ulf Helwig ◽

Michael Nothnagel ◽

Ulrich R Fölsch ◽

Stefan Schreiber ◽

...

Keyword(s):

Metabolic Syndrome ◽

Lipid Metabolism ◽

Cell Function ◽

International Diabetes Federation ◽

Tolerance Test ◽

Oral Glucose ◽

Middle Aged ◽

The Metabolic Syndrome ◽

Β Cell Function ◽

Design And Methods

ObjectivePostprandial (pp) lipid metabolism is associated with insulin resistance and type 2 diabetes. In young men, pp triglycerides (TGs) are more strongly associated with traits of metabolic syndrome (MS) than fasting TGs. We established a cohort of middle-aged men selected for traits of MS and pp lipid metabolism to determine if fasting TGs or pp TGs are more closely related to MS.Research design and methodsA total of 1558 men were characterized for MS. A total of 755 men underwent an oral metabolic tolerance test consisting of a standardized high-fat meal and an oral glucose tolerance test. Blood samples were drawn in the fasting state and hourly until 9 h to determine pp TGs and free fatty acids. Glucose and insulin were analyzed until 5 h pp.ResultsIn the overall cohort, 329 subjects (21.1%) had a complete MS based on the Adult Treatment Panel III criteria, and 650 subjects (41.7%) had a complete MS based on the International Diabetes Federation criteria. The association of pp TGs with MS parameters was not stronger than the association of fasting TGs with them. Pp TGs were independently associated with β-cell function.ConclusionsPp TGs did not show a higher correlation with MS traits than fasting TGs. This finding is probably due to the high incidence of overweight subjects in this middle-aged cohort.

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Update on the diagnosis of GH deficiency in adults

Acta Endocrinologica ◽

10.1530/eje.0.148s003 ◽

2003 ◽

pp. S3-S8 ◽

Cited By ~ 18

Author(s):

R Abs

Keyword(s):

Gh Deficiency ◽

Tolerance Test ◽

Cranial Irradiation ◽

Pituitary Hormone ◽

Childhood Onset ◽

Gh Secretion ◽

Insulin Tolerance ◽

Stimulation Tests ◽

History Of ◽

Considerable Morbidity

GH deficiency (GHD) in adults is associated with considerable morbidity and mortality. The diagnosis of GHD is generally straightforward in children as growth retardation is present; however, in adults, diagnosis of GHD is often challenging. Other markers are therefore needed to identify adults who have GHD and could potentially benefit from GH replacement therapy. Consensus guidelines for the diagnosis and treatment of adult GHD recommend provocative testing of GH secretion for patients who have evidence of hypothalamic-pituitary disease, patients with childhood-onset GHD, and patients who have undergone cranial irradiation or have a history of head trauma. Suspicion of GHD is also heightened in the presence of other pituitary hormone deficits. Tests for GHD include measurement of the hormone in urine or serum or measurement of stimulated GH levels after administration of various provocative agents. The results of several studies indicate that non-stimulated serum or urine measurements of GH levels cannot reliably predict deficiency in adults. Although glucagon and arginine tests produce a pronounced GH response with few false positives, the insulin tolerance test (ITT) is currently considered to be the gold standard of the GH stimulation tests available. Unfortunately, the ITT has some disadvantages and questionable reproducibility, which have prompted the development of several new tests for GHD that are based on pharmacological stimuli. Of these, GH-releasing hormone (GHRH) plus arginine and GHRH plus GH-releasing peptide (GHRP) appear to be reliable and practical. Thus, in cases where ITT is contraindicated or inconclusive, the combination of arginine and GHRH is an effective alternative. As experience with this test as well as with GHRH/GHRP-6 accumulates, they may supplant ITT as the diagnostic test of choice.

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Endocrine investigations and laboratory reference ranges

10.1093/med/9780199232222.003.0101 ◽

2011 ◽

Author(s):

Gary Butler ◽

Jeremy Kirk

Keyword(s):

Glucose Tolerance Test ◽

Tolerance Test ◽

Stimulation Test ◽

Oral Glucose ◽

Reference Ranges ◽

Trh Test ◽

Gh Secretion ◽

Provocation Tests ◽

Laboratory Reference ◽

Generation Test

General guidelines 330GH provocation tests 331Tests for GH secretion 332IGF-1 generation test 334Oral glucose tolerance test for investigating excess GH secretion 335TRH test 336LHRH/GnRH (gonadotropin-releasing hormone) stimulation test 337Triple pituitary stimulation test 338Water deprivation test (WDT) 340...

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Ghrelin and Peptide YY in Youth: Are There Race-Related Differences?

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-2448 ◽

2006 ◽

Vol 91 (8) ◽

pp. 3117-3122 ◽

Cited By ~ 23

Author(s):

Fida Bacha ◽

Silva A. Arslanian

Keyword(s):

Insulin Sensitivity ◽

Racial Differences ◽

Peptide Yy ◽

Tolerance Test ◽

Oral Glucose ◽

Obesity Prevalence ◽

Satiety Hormone ◽

Design And Methods ◽

Relationship Of ◽

The Relationship

Abstract Objective: Obesity prevalence is higher in African-American (AA) vs. American white (AW) youth. Ghrelin is a “hunger” peptide that is high preprandially and decreases postprandially, and peptide YY (PYY) is a “satiety” hormone increasing after meals. Impaired regulation of ghrelin/PYY may be conducive to obesity. We hypothesized that racial differences in childhood obesity could partly be explained by differences in ghrelin/PYY dynamics. Research Design and Methods: We investigated: 1) ghrelin suppression/PYY elevation in response to an oral glucose tolerance test (OGTT) in AA vs. AW, and 2) the relationship of ghrelin and PYY dynamics to insulin sensitivity. Thirty-three AA and 54 AW prepubertal children underwent an OGTT measuring ghrelin, PYY, glucose, and insulin. Fasting glucose to insulin ratio (GF/IF) was used to assess the relationship of insulin sensitivity to fasting and post-OGTT ghrelin and PYY levels. Results: OGTT-induced suppression in ghrelin (Δ ghrelin) was lower in AA youth. Δ ghrelin correlated with GF/IF (r = 0.47, P < 0.001) and Δ insulin at 30 min (r = −0.47, P < 0.001). In multiple regression analysis, race (P = 0.013) and GF/IF (P = 0.004) contributed independently to the variance in Δ ghrelin (R2 = 0.28, P < 0.001). Fasting and post-OGTT PYY levels were lower in AAs and were not related to insulin sensitivity. Conclusion: The lower suppression of ghrelin in AA, but not the lower PYY levels, correlates with insulinemia and insulin resistance. Less ghrelin suppression and PYY elevation after a meal in black youth could be a potential mechanism of race-related differences in hunger/satiety predisposing to risk of obesity.

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