Evaluation of GH deficiency and central adrenal insufficiency in patients following craniospinal irradiation in young ages: comparison between the glucagon stimulation test and the insulin tolerance test

Abstract Introduction: Low or borderline cortisol concentrations and impaired response to dynamic testing have been reported in patients with fibromyalgia, potentially related to hypothalamus-pituitary dysfunction.1,2 Superimposed adrenal insufficiency (AI) may contribute to some fibromyalgia symptoms or delay improvement in patients enrolled in fibromyalgia treatment programs. We hypothesized that a subset of patients with fibromyalgia have: 1) partial secondary AI and concomitant growth hormone (GH) deficiency 2) a discordance in Cosyntropin stimulation test and 3) improvement in fibromyalgia symptoms with initiation of glucocorticoid and/or GH replacement. Design: This was a retrospective study of patients with fibromyalgia diagnosed with partial secondary AI based on abnormal insulin tolerance test (peak cortisol < 18 mcg/dL) at our institution from June 2002 to August 2019. Patients were excluded if they had other reasons for adrenal insufficiency, including steroid exposure and opioid use. Results: We identified 22 patients (18 women, 82%) diagnosed with partial AI at a median age of 38 years (range 19-65). The fibromyalgia symptoms included fatigue (n=22, 100%), pain (n=22, 100%), sleep disturbance (n=15, 68%), and bowel changes (n=13, 59%). The median morning cortisol concentration was 8.6 mcg/dL (range 1.1-11); 9 patients (41%) had a morning cortisol concentration below the normal range (7 mcg/dL). The median ACTH level was 15.5 pg/mL (range 7.7-54). Nineteen patients had baseline IGF1 levels, with a median z-score of -0.94 (range -1.96 to 1.70). MRI pituitary imaging was performed in 20 patients and showed no significant pituitary pathology. All patients achieved hypoglycemia <=40 mg/dL during the insulin tolerance test. Peak median cortisol level was 11 mcg/dL (range 5.4-17). Nineteen patients (86%) also had partial GH deficiency (defined as a peak GH < 4 ng/mL) with a median GH level of 0.36 ng/mL (range 0.03-3.83). Cosyntropin stimulation test was performed in 13 patients (59%) with a 1 mcg dose in 2 patients and 250 mcg dose in 11 patients. The peak cortisol was >=18 mcg/dL in 10 (77%) patients. All patients were started on physiologic glucocorticoid replacement, and 12 patients were started on GH replacement. Endocrinology follow-up information was available for 13 patients, and 8 (62%) reported symptom improvement after starting treatment. Conclusions: Patients with fibromyalgia can have co-existing partial secondary AI and GH deficiency as defined by insulin-induced hypoglycemia. Cosyntropin stimulation test can be used in patients with fibromyalgia, but a normal test does not rule out partial secondary AI. Replacing the underlying deficiency improved symptoms in some patients demonstrating certain fibromyalgia symptoms may overlap with AI and GH deficiency. 1Gur et al. Ann Rheum Dis. 2004. 63(11):1504-1506. 2Kirnap et al. Clin Endocrinol (Oxf). 2001. 55(4):455-459.

Download Full-text

Prospective comparison of the glucagon stimulation test (GST) with the insulin tolerance test (ITT) in patients following pituitary surgery

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0028-1096360 ◽

2008 ◽

Vol 116 (09) ◽

Author(s):

C Berg ◽

T Meinel ◽

A Yüce ◽

H Lahner ◽

K Mann ◽

...

Keyword(s):

Pituitary Surgery ◽

Tolerance Test ◽

Insulin Tolerance Test ◽

Stimulation Test ◽

Glucagon Stimulation Test ◽

Insulin Tolerance ◽

Prospective Comparison

Download Full-text

Different cut-off values of the insulin tolerance test, the high-dose short Synacthen test (250 μg) and the low-dose short Synacthen test (1 μg) in assessing central adrenal insufficiency

Clinical Endocrinology ◽

10.1111/cen.12397 ◽

2014 ◽

Vol 81 (1) ◽

pp. 77-84 ◽

Cited By ~ 27

Author(s):

Hwa Y. Cho ◽

Jung H. Kim ◽

Sang W. Kim ◽

Chan S. Shin ◽

Kyong S. Park ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Low Dose ◽

Tolerance Test ◽

Insulin Tolerance Test ◽

High Dose ◽

Insulin Tolerance ◽

Synacthen Test ◽

Central Adrenal Insufficiency ◽

Short Synacthen Test

Download Full-text

Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery

Acta Endocrinologica ◽

10.1530/eje-09-0824 ◽

2010 ◽

Vol 162 (3) ◽

pp. 477-482 ◽

Cited By ~ 55

Author(s):

Christian Berg ◽

Timo Meinel ◽

Harald Lahner ◽

Ali Yuece ◽

Klaus Mann ◽

...

Keyword(s):

Roc Analysis ◽

Pituitary Surgery ◽

Tolerance Test ◽

Insulin Tolerance Test ◽

Stimulation Test ◽

Diagnostic Utility ◽

Glucagon Stimulation Test ◽

Gh Secretion ◽

Insulin Tolerance ◽

Potential Alternative

ObjectiveThe glucagon stimulation test (GST) like the insulin tolerance test (ITT) stimulates both ACTH and GH secretion. However, there are limited data with modern assays on sensitivity and specificity for GST in comparison to ITT. The aim of this study was to evaluate the diagnostic utility of the GST for GH deficiency (GHD) and adrenal insufficiency (AI) in patients following pituitary surgery.Design and patientsITT and GST were performed within 7 days in 49 patients at least 3 months after transsphenoidal surgery. Serum GH and cortisol were measured by Immulite 2000 assay (Siemens AG). Receiver-operating characteristic (ROC) analysis was performed to identify the thresholds for GST.ResultsIn ITT, 18/49 cases were classified as AI. ROC analysis revealed a peak cortisol value >599 nmol/l in GST for adrenal sufficiency with 100% specificity and 32% sensitivity, and a peak cortisol <277 nmol/l with >95% specificity and 72% sensitivity for AI. Of the 49 subjects, 25 (51%) demonstrated levels between these cut-offs and could not be diagnosed by GST alone with sufficient accuracy. Regarding GHD, 21/49 cases were classified as insufficient by ITT. ROC analysis revealed a cut-off of 2.5 ng/ml with 95% sensitivity and 79% specificity. Of the 49 cases, seven (14%) were discordant in terms of defining GHD, with six subjects being treated for GHD according to GST although being sufficient in ITT.ConclusionIn our prospective series of patients with pituitary disease, GST is a potential alternative test for the assessment of GH reserve, but is a poor test for ACTH reserve. Test-specific cut-offs should be applied to avoid misinterpretation.

Download Full-text

P-38 Prospective comparison of the Glucagon Stimulation Test (GST) with the Insulin Tolerance Test (ITT) in patients following pituitary surgery

Growth Hormone & IGF Research ◽

10.1016/s1096-6374(08)70123-0 ◽

2008 ◽

Vol 18 ◽

pp. S38

Author(s):

C. Berg ◽

T. Meinel ◽

A. Yüce ◽

H. Lahner ◽

K. Mann ◽

...

Keyword(s):

Pituitary Surgery ◽

Tolerance Test ◽

Insulin Tolerance Test ◽

Stimulation Test ◽

Glucagon Stimulation Test ◽

Insulin Tolerance ◽

Prospective Comparison

Download Full-text

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.

Download Full-text

Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test

Acta Endocrinologica ◽

10.1530/eje.0.1330305 ◽

1995 ◽

Vol 133 (3) ◽

pp. 305-312 ◽

Cited By ~ 78

Author(s):

Hans C Hoeck ◽

Peter Vestergaard ◽

Poul E Jakobsen ◽

Peter Laurberg

Keyword(s):

Growth Hormone ◽

Gh Deficiency ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Tolerance Test ◽

Insulin Tolerance Test ◽

Repeated Testing ◽

Provocative Test ◽

Insulin Tolerance ◽

Gh Deficiency In Adults

Hoeck HC, Vestergaard P, Jakobsen PE, Laurberg P, Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test. Eur J Endocrinol 1995;133:305–12. ISSN 0804–4643 The insulin tolerance test (ITT) is regarded as the most reliable provocative test in the diagnosis of growth hormone (GH) deficiency in adults. In the present study the test was evaluated by investigating the range of GH responses in normal adult males and females and the intra-individual reproducibility of the test. Sixteen healthy non-obese adults, eight males (median age 31.5 years) and eight females (median age 31.8 years) were tested twice with the ITT, with a minimum of 72 h between each test. The females were tested between day 3 and day 10 of their menstrual cycles. Adequate hypoglycemia was achieved in all cases with a median nadir blood glucose of 1.3 mmol/l (range 0.8–2.0). Growth hormone in serum was measured by immunoradiometric assay and low values were confirmed by a different assay. Median peak GH concentration responses to the ITT were: in males 27.9 μg/l, range 5.0–71.1 (test 1) and 30.5 μg/l, range 7.9–69.5 (test 2); and in females 9.0 μg/l, range 4.1–17.9 (test 1) and 8.4 μg/l, range 0.09–42.4 (test 2). The rise in GH concentration during the ITT was higher in males than in females. In the males, all stimulated GH values were ≥5.0 μg/l. In the females, four out of 16 tests gave values below 5.0 μg/l and in one test the GH value was around the detection limit of the assays. There was poor reproducibility during repeated testing, with no correlation between the results of the two tests. The results did not correlate to the magnitude of the hypoglycemia. The results of this study illustrate the complexity of the regulation of GH secretion and indicate that the ITT is less useful for diagnosing GH deficiency in adults than previously anticipated. The diagnosis of GH deficiency in adults and especially in adult females should not be based on the results of a single ITT alone. Hans C Hoeck, Department of Endocrinology, Aalborg Regional Hospital, Reberbansgade, DK-9000 Aalborg, Denmark

Download Full-text