scholarly journals Evaluation of pituitary function in the fatigued patient: a review of 59 cases

2006 ◽  
Vol 154 (1) ◽  
pp. 147-157 ◽  
Author(s):  
Jerry R Greenfield ◽  
Katherine Samaras
Keyword(s):  
Autoimmune Disease ◽  
Gastrointestinal Haemorrhage ◽  
Early Morning ◽  
Tolerance Test ◽  
Secondary Adrenal Insufficiency ◽  
Presenting Symptoms ◽  
Insulin Tolerance ◽  
Morning Cortisol ◽  
History Of ◽  
Cortisol Responses

Objective: The aim of this study was to review the results of dynamic pituitary testing in patients presenting with fatigue. Methods: We reviewed clinical histories and insulin tolerance test (ITT) results of 59 patients who presented with fatigue and other symptoms of glucocorticoid insufficiency over a 4-year period. All patients referred for ITT had an early-morning cortisol level of <400 nM and a low or normal ACTH level. Results: Peak cortisol and GH responses following insulin-induced hypoglycaemia were normal in only seven patients (12%). Median age of the remaining 52 patients was 47 years (range, 17–67 years); all but five were female. Common presenting symptoms were neuroglycopaenia (n = 47), depression (n = 37), arthralgia and myalgia (n = 28), weight gain (n = 25), weight loss (n = 9), postural dizziness (n = 15) and headaches (n = 13). Other medical history included autoimmune disease (n = 20; particularly Hashimoto’s thyroiditis, Graves’ disease and coeliac disease), postpartum (n = 8) and gastrointestinal (n = 2) haemorrhage and hyperprolactinaemia (n = 13). 31 subjects had peak cortisol levels of <500 nM (suggestive of ACTH deficiency; 18 of whom had levels < 400 nM) and a further six had indeterminate results (500–550 nM). The remaining 15 subjects had normal cortisol responses (median 654 nM; range, 553–1062 nM) but had low GH levels following hypoglycaemic stimulation (5.9 mU/l; 3–11.6 mU/l). Conclusion: Our results suggest that patients presenting with fatigue and symptoms suggestive of hypocortisolism should be considered for screening for secondary adrenal insufficiency, particularly in the presence of autoimmune disease or a history of postpartum or gastrointestinal haemorrhage. Whether physiological glucocorticoid replacement improves symptoms in this patient group is yet to be established.

scholarly journals Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children

2013 ◽  
Vol 169 (2) ◽  
pp. 139-145 ◽  
Author(s):  
Michael J O'Grady ◽  
Conor Hensey ◽  
Miriam Fallon ◽  
Hilary Hoey ◽  
Nuala Murphy ◽  
...  
Keyword(s):  
Paediatric Population ◽  
Tolerance Test ◽  
Specific Reference ◽  
Cortisol Response ◽  
Reference Ranges ◽  
Factors Affecting ◽  
Insulin Tolerance ◽  
Morning Cortisol ◽  
Systemic Glucocorticoids ◽  
Cortisol Responses

ObjectiveBased on adult data, a peak cortisol response ≥500 nmol/l to insulin-induced hypoglycaemia constitutes a normal. Age-specific reference ranges for basal morning cortisol have been developed for clinical use in the paediatric population. Such reference ranges are not clearly established for peak cortisol responses to insulin-induced hypoglycaemia despite limited data suggesting an effect of age on peak cortisol. The aims of this study were to assess factors affecting the cortisol response to insulin-induced hypoglycaemia in children and to determine whether the peak cortisol response was related to age.DesignThe present study was a retrospective cohort study.MethodsRetrospective analysis of children and adolescents aged ≤18 years undergoing the insulin tolerance test with adequate hypoglycaemia was undertaken. Patients with hypopituitarism or severe hypothalamic–pituitary–adrenal axis impairment (peak cortisol value <400 nmol/l) or using systemic glucocorticoids were excluded.ResultsTwo hundred and twenty-three tests were analysed. Peak cortisol responses ≥500 nmol/l occurred in 183 (82%) tests. Age was negatively associated with peak cortisol responses (r=−0.15, P=0.03). A peak cortisol response <500 nmol/l was significantly less common in patients aged <12 years (9/97 (9%) vs 31/126 (25%); P=0.004). In children aged <12 years, the median (5th–95th centiles) peak cortisol values were 610 (480–806) nmol/l compared with 574 (442–789) nmol/l in children aged ≥12 years (P<0.004). Similarly, median cortisol increment was significantly higher in younger patients (301 nmol/l compared with 226 nmol/l (P=0.0004)).ConclusionsUse of a single peak cortisol threshold in children of all ages is not appropriate and will result in overdiagnosis of adrenal insufficiency in adolescents.

scholarly journals Update on the diagnosis of GH deficiency in adults

2003 ◽  
pp. S3-S8 ◽  
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.

scholarly journals Reduced epinephrine reserve in response to insulin-induced hypoglycemia in patients with pituitary adenoma

2007 ◽  
Vol 157 (3) ◽  
pp. 265-270 ◽  
Author(s):  
Shinya Morita ◽  
Michio Otsuki ◽  
Maki Izumi ◽  
Nobuyuki Asanuma ◽  
Shuichi Izumoto ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Adrenal Insufficiency ◽  
Serum Cortisol ◽  
Tolerance Test ◽  
Secondary Adrenal Insufficiency ◽  
Counterregulatory Hormones ◽  
Insulin Tolerance ◽  
Secondary Hypothyroidism ◽  
Severe Impairment ◽  
Plasma Gh

Objective: Hypoglycemia induces rapid secretion of counterregulatory hormones such as catecholamine, glucagon, cortisol, and GH. Insulin-induced hypoglycemia is used for evaluating GH–IGF-I and ACTH–adrenal axes in patients with pituitary disorders. The aim of this study was to determine whether the response of catecholamine secretion to hypoglycemia is disrupted in patients with pituitary adenoma. Methods: The study population comprised 23 patients with pituitary adenoma (non-functioning adenoma or prolactinoma). An insulin tolerance test was performed and serum catecholamines as well as plasma GH and serum cortisol were measured. Results: The study patients showed diminished response of plasma epinephrine to insulin-induced hypoglycemia. With the cutoff level of peak epinephrine for defining severe impairment set at 400 pg/ml, more patients with secondary adrenal insufficiency showed severe impairment of the epinephrine response than did those without it. Peak epinephrine levels to insulin-induced hypoglycemia were significantly correlated with peak cortisol levels. In patients with secondary hypothyroidism, secondary hypogonadism, GH deficiency, or diabetes insipidus, the prevalence of severe impairment of the epinephrine response was similar to that in patients without these deficiencies. Conclusions: Impaired epinephrine secretion in response to insulin-induced hypoglycemia was frequently observed in patients with pituitary adenoma. This disorder was especially severe in patients with secondary adrenal insufficiency.

scholarly journals A Cross-Sectional Study to Evaluate the Safety and Efficacy of the Insulin Tolerance Test

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A621-A622
Author(s):  
Ahmad Yehia Ghamlouche ◽  
Fouad Alzaroui ◽  
Tamara Altaweel ◽  
Adel Alwakeedi ◽  
Hassan A Khan ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Adverse Effects ◽  
Adverse Events ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Clinical Safety ◽  
Safety And Efficacy ◽  
Insulin Tolerance ◽  
Normal Ranges ◽  
History Of

Abstract Introduction: The insulin tolerance test (ITT) is the current standard for the diagnosis of pituitary diseases such as growth hormone deficiencies (GHD). Previous reports indicated that the ITT as having a high adverse event profile, and the cosyntropin test as being sensitive enough to diagnose GHD in adults. The purpose of this study is to validate the safety and efficacy of the ITT. Design: Over 400 ITT tests were conducted over the course of 3 years from (2017-2020) at our facility. This study is only focused on adult physiology (Cohort Age 16 - 78) and excludes any pediatric tests. An important measure, time spent in critical state (Tc), is done to know the expected time a patient is to remain hypoglycemic, both for patient expectations and clinician logistics. We did not use a CGM, instead drew blood samples on set intervals for glucose measurements. Since the measurements aren’t continuous, a consistent overestimation is done for all subject encounters to capture the maximum time spent in hypoglycemia. Insulin like growth factor one (IGF-1) was measured before the test was conducted and is listed in the spreadsheet. Growth hormone peaks were and the time to reach that peak (Tp) were also measured. This time is calculated from the listed time of the first dosage of insulin to the time of the GH peak. Other measures listed in the spreadsheet include a brief medical history of the patient, their age, weight, gender, and the blood pressure and heart rate measured at test completion. Any immediate interventions such as intravenous fluid injections were listed. Symptoms of hypoglycemia are excluded as a complication of the test. This is due to the inherent nature of the ITT whose goal is to drop one’s blood sugar past normal ranges. Results: Our results show (0.45%) rate of adverse events. 2 patients in the entire cohort suffered from seizures during their hypoglycemic period. Both of them were successfully aborted with Ativan, and patients were monitored until recovery from post ictal state and discharged home with stable vitals and no acute symptoms. It was later discovered these patients had remote history of epilepsy and should’ve been excluded from this trial. Of the remaining 448 subject encounters, (20%) of them required urgent intervention to BP. Zero of those patients suffered any other symptoms or ongoing adverse effects. 5 patients underwent the ITT twice, again, with no adverse effects. Conclusion: No permanent adverse events or hospitalizations were reported. Based on our findings the clinical safety concerns of the ITT test are minimal compared with the benefit of obtaining an accurate diagnosis in this patient cohort, if done within the correct protocol. Using IGF-1 measures as a determinant of GHD is wildly inaccurate as seen in our results. Combining IGF-1 with the Cosyntropin test is not a good enough measure for diagnosing GHD. The ITT test remains the most accurate and reliable test available today.

The Use of the Short Tetracosactrin Test for the Investigation of Suspected Pituitary Hypofunction

1996 ◽  
Vol 33 (2) ◽  
pp. 112-118 ◽  
Author(s):  
T W M Wang ◽  
M S Wong ◽  
J Falconer Smith ◽  
T A Howlett
Keyword(s):  
Hpa Axis ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Cortisol Response ◽  
Established Method ◽  
Time Points ◽  
Routes Of Administration ◽  
Insulin Tolerance ◽  
Significant Difference ◽  
Cortisol Responses

The short Synacthen (tetracosactrin) test (SST) is an established method of assessing adrenocortical reserve, and is increasingly replacing the insulin tolerance test (ITT) for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis. However, there is no consensus on how the test is performed, and various time points and routes of administration are used. The present study was done, first, to determine whether there was any difference in cortisol responses when Synacthen was administered intramuscularly compared with intravenously and, secondly, to compare cortisol responses at 30 and 60 min. We found no significant difference between the two routes of administration. However, cortisol responses at 60 min were significantly higher than at 30 min ( P < 0·05). Previous validations for the use of the SST in place of the ITT have used cortisol responses 30 min after Synacthen. We conclude that where the SST is used to assess the HPA axis, cortisol response at 30 min after intravenous Synacthen should be used.

scholarly journals The Impact of Irradiation on Growth Hormone Responsiveness to Provocative Agents Is Stimulus Dependent: Results in 161 Individuals with Radiation Damage to the Somatotropic Axis1

2001 ◽  
Vol 86 (2) ◽  
pp. 663-668 ◽  
Author(s):  
C. A. Lissett ◽  
S. Saleem ◽  
A. Rahim ◽  
B. M. D. Brennan ◽  
S. M. Shalet
Keyword(s):  
Radiation Damage ◽  
Tolerance Test ◽  
Cranial Irradiation ◽  
Somatotropic Axis ◽  
Provocative Test ◽  
Routine Testing ◽  
Insulin Tolerance ◽  
Stimulation Tests ◽  
History Of ◽  
The Impact

GH provocative tests remain the mainstay for the diagnosis of GH deficiency and at present the insulin tolerance test (ITT) is the gold standard. There are, however, a variety of other stimulation tests used in clinical practice. Each necessitates the use of a specific cut-off derived from normative data, but there remains a widely held view that the implications from a “failed” test are independent of the nature of the stimulus. We sought to examine whether this is the case in individuals with evidence of radiation damage to the somatotropic axis. One hundred and sixty-one nonacromegalic patients were identified who had undergone an arginine stimulation test (AST) and an ITT within a 3-month period as part of routine testing between 1975 and 1999. They were divided into those tested before (n = 81; 48 males) and those tested after (n = 80; 36 males) completion of growth and puberty. Patients were considered for inclusion in the study if they had a history of cranial irradiation and a GH response to one provocative test of less than 8 μg/L, taken as indicating that some damage to the GH axis may have occurred. The patients were compared with 2 control groups. The first comprised 35 adults (18 males) and the second consisted of 16 prepubertal children (10 males). The median peak (range) GH response to the ITT was significantly greater (P &lt; 0.0001) than that to the AST in the adult controls: 24.9 (4.1–76.9) vs. 12.2 (0.88–35.0)μ g/L, respectively. However, in the patients the GH responses were similar (P = 0.28): 2.2 (0.2–25.7) vs. 1.4 (0.2–12.8) μg/L to the ITT and AST, respectively. In contrast to the pattern seen in the adult controls, the response to an ITT in childhood controls was of similar magnitude (P = 0.5) to that to the AST: 17.5 (8.1–40.0) vs. 19.4 (7.3–53.8) μg/L, respectively. However in the patients, the GH response to the AST was greater than that to the ITT (P &lt; 0.0001): 4.3 (0.7–17.2) vs. 3.0 (0.4–18.1) μg/L, respectively. In summary, we have shown that the impact of irradiation on GH responsiveness to provocative agents is stimulus dependent. The GH response to an AST appears to be more resistant to the effects of irradiation than that to the ITT. When investigating the impact of irradiation on GH secretory status, the GH response to an AST may be a less sensitive guide to the functional ability of the GH axis.

scholarly journals Acylated ghrelin as a provocative test for the diagnosis of GH deficiency in adults

2013 ◽  
Vol 168 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Valentina Gasco ◽  
Guglielmo Beccuti ◽  
Chiara Baldini ◽  
Nunzia Prencipe ◽  
Stellina Di Giacomo ◽  
...  
Keyword(s):  
Gh Deficiency ◽  
Characteristic Curve ◽  
Tolerance Test ◽  
Acylated Ghrelin ◽  
Diagnostic Reliability ◽  
Provocative Test ◽  
Insulin Tolerance ◽  
History Of ◽  
The One ◽  
Overweight Subjects

ObjectiveInsulin tolerance test (ITT) is the test of reference for the diagnosis of adult GH deficiency (GHD), although GHRH in combination with arginine (ARG) or GH secretagogues are considered equally reliable tests. Testing with GH secretagogue alone is, anyway, a potent stimulus exploring the integrity of hypothalamic pathways controlling somatotropic function. We therefore aimed to determine the diagnostic reliability of testing with ghrelin, the natural GH secretagogue.MethodsWe studied the GH response (every 15 min from −15 to +120 min) to acylated ghrelin (1 μg/kg i.v. at 0 min) in 78 patients with a history of pituitary disease (49 male, 29 female; age (mean±s.d.): 52.1±18.7 years; BMI: 26.7±5.3 kg/m2). The lack of GH response to GHRH+ARG and/or ITT was considered the gold standard for the diagnosis of GHD. The best GH cut-off to ghrelin test, defined as the one with the best sensitivity (SE) and specificity (SP), was identified using the receiver-operating characteristic curve analysis.ResultsThe best GH cut-off to ghrelin test was 7.3 μg/l in lean subjects (SE 88.2%, SP 90.9%), 2.9 μg/l in overweight subjects (SE 92.6%, SP 100%) and 0.6 μg/l in obese subjects (SE 50%, SP 100%). The diagnostic accuracy was 89.3, 94.1 and 62.5% respectively.ConclusionsOur data show that testing with acylated ghrelin represents a reliable diagnostic tool for the diagnosis of adult GHD, in lean and overweight subjects, if appropriate cut-off limits are assumed. Obesity strongly reduces GH response to ghrelin, GH weight-related cut-off limit and diagnostic reliability of the test.

scholarly journals The choice of the optimal secondary adrenal insufficiency screening method

2016 ◽  
Vol 62 (5) ◽  
pp. 74-75
Author(s):  
Alla E. Yudina ◽  
Tatyana Y. Tselovalnikova ◽  
Maria G. Pavlova ◽  
Nadezhda A. Mazerkina ◽  
Irina A. Arefyeva ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Roc Analysis ◽  
Screening Method ◽  
Diagnostic Algorithm ◽  
Tolerance Test ◽  
Screening Methods ◽  
Grey Zone ◽  
Secondary Adrenal Insufficiency ◽  
Insulin Tolerance ◽  
Optimal Screening

Background. The insulin tolerance test (ITT) is the “gold standard” of the secondary adrenal insufficiency (SAI) diagnosis but it is rather difficult to carry out, has some contraindications and requires patient’s hospitalization. The availability of a reliable screening method could reduce the necessity of using ITT.Aim: to compare different methods of screening with ITT and to work out an optimal diagnostic algorithm of SAI.Methods. 40 patients (20 women) after craniospinal (CSI) irradiation in a doze 35 Gy were examined. The average age at the time of the observation was 19,5±3 years, at the time of treatment 12,5±3,5 years. Patient’s blood samples were collected for basal cortisol (BC), DHEA-S. ITT was performed for all patients, glucagon stimulation test (GST) was for 27 persons. Patients were divided into groups: SAI and without SAI (W-SAI) after ITT. ROC- analysis was conducted to identify the thresholds for BC, DHEA-S and GST. Cut-off points for BC and DHEA-S levels corresponding to 100% sensitivity (Se) for SAI group and 100% specificity (Sp) for W-SAI patients were estimated to select a group of patients which do not require stimulative tests. Linear regression was used to construct a predictive model (PM) of SAI occurrence after CSI.Results. 22/40 subjects failed ITT, 13/27 passed GST. 3 patients failed ITT but passed GST. Their level of neutrophils and monocytes was higher than the other patients'. SAI-patients had BC and DHEA-S lower than W-SAI (321±102 vs 516± 183; p=0,003 and 2,6±1,4 vs 5,1±2,1, p=0,003). ROC-analysis showed area under curve (AUC) for GST=0,91 with optimal cut-off for cortisol=489 which corresponds to 100% Sp and 62% Se. AUC was 0,83 for BC and 0,84 for DHEA-S.In 70% patients' BC was in a “grey zone” (32% of them passed ITT), 8% had BC lower than 200 (which corresponds to 100% Se) and 22% more than 499 (100% Sp). 50% of patients were in a “grey zone” for DHEA-S (50% of them had SAI), 18% had DHEA-S level below 2,0 and 32% above 4,7. A combination of BC and DHEA-S in the PM of SAI (0,592+0,001*BC+0,11*DHEA-S) had AUC 94%. This PM didn’t give the prognosis of SAI for 32% (CI: 18-49%) of patients. The addition of maximal cortisol (MC) level during GST (0,53+0,01*BC+0,066*DHEA-S+0,001*MC) increased AUC to 99% and didn’t allow to predict SAI in 8% (3,2% - 24,9%) of patients only.Conclusions. When the screening methods were used separately, they showed comparable accuracy and it was not high. The PM may be used as optimal screening method for SAI and may allow to use ITT more rarely. But further studies are required to validate the PM proposed in this study.

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