Morning Serum Cortisol Level Predicts Central Adrenal Insufficiency Diagnosed by Insulin Tolerance Test

Gasco, Valentina; Bima, Chiara; Geranzani, Alice; Giannelli, Jacopo; Marinelli, Lorenzo; Bona, Chiara; Cambria, Valeria; Berton, Alessandro Maria; Prencipe, Nunzia; Ghigo, Ezio; Maccario, Mauro; Grottoli, Silvia

doi:10.1159/000514216

Cited by 9 publications

(9 citation statements)

References 37 publications

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“…The ITT is especially preferred when damage to the hypothalamus is suspected. 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 ].…”

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

Yeoh

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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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

Yeoh

Dwyer

Anghel

et al. 2022

International Journal of Endocrinology

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“…Furthermore, Gasco et al . [ 19 ] reported that the cut-off of morning serum cortisol concentration that best predicted a deficient response to ITT was ≤126.4 nmol/L, while the cut-off of morning serum cortisol concentration that best predicted a normal response to ITT was >444.7 nmol/L [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Recalibration of thinking about adrenocortical function assessment: how the ‘random’ cortisol relates to the short synacthen test results

Michaelidou

Yadegarfar

Morris

et al. 2021

Cardiovascular Endocrinology &Amp; Metabolism

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Background The short synacthen test (SST) is the most commonly performed investigation to assess adrenal function. Appropriate criteria for when an SST is performed are subject to debate. We investigated how random serum cortisol levels relate to SST response. Methods We examined random cortisol measurements taken between 04.40–23.55 p.m. results of SST baseline and 30-/60-min cortisol performed over 12 months (225 SSTs) at Salford Royal Hospital. Serum cortisol was measured on the Siemens Centaur Analyser. A 30–60-min cortisol concentration of ≥450 nmol/L defined a pass; 350–449 nmol/L defined borderline. Results Patients only proceeded to SST if random cortisol was <400 nmol/L. For those not on corticosteroids for at least 2 weeks, 42/43 (97.7%) cases with random cortisol concentration of ≥200 nmol/L had an SST ‘pass’. The relation was less clear with corticosteroid treatment (19/35 cases; 54%). For those not taking glucocorticoid treatment (including inhaled/topical corticosteroids) in the previous 2 weeks, 91.8% of SSTs were pass/2.7% borderline/5.5% fail. For those on steroids, 51.9% of SSTs were a pass/11.4% were borderline. In relation to the postsynacthen cortisol pass cut-off of ≥450 nmol/L, in 15/207 (7.2%) of cases, the 60-min cortisol was ≥450 nmol/L (adequate adrenocortical function), but 30-min cortisol was below this. In all cases where the 30-min cortisol did indicate a pass (i.e. was ≥450 nmol/L) the 60-min cortisol was also ≥450 nmol/L. Conclusion Our findings suggest that if the random cortisol level is ≥200 nmol/L, regardless of the time of day and the person was not taking corticosteroid treatment in the previous 2 weeks, SST may not be needed. Our data also suggests that 60-min cortisol retains utility.

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“…According to the results of this study, if the cortisol evaluation is made with immunoassays using monoclonal antibodies, the grey range of 2016 guidelines potentially tighten even more allowing to identify of a narrower population to test [ 13 ]. In this context, the most recent studies stressed the importance of selecting patients to test according to the pretest probability of SAI that should be quantified by evaluating the patients’ clinical background and the morning cortisol levels [ 14 , 15 ]. Bioletto et al proposed an integrated score for the prediction of SAI when morning cortisol is in the grey zone based on morning cortisol levels, sex, and the presence of at least three other pituitary deficits, trying to narrow even more the patients that need to be tested [ 16 ].…”

Section: Patients To Be Tested and Timing For Testingmentioning

confidence: 99%

ACTH Stimulation Test for the Diagnosis of Secondary Adrenal Insufficiency: Light and Shadow

et al. 2023

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Secondary Adrenal Insufficiency (SAI) is a condition characterized by inappropriately low ACTH secretion due to a disease or injury to the hypothalamus or the pituitary. The evaluation when suspected is often challenging for the non-specific symptoms, the rarity of the disease, and the pitfalls associated with laboratory tests. A prompt and correct diagnosis of SAI is essential because although an adequate hormonal replacement therapy could be lifesaving, inappropriate life-long therapy with steroids can be harmful. The gold standard test for assessing the hypothalamus-pituitary-adrenal axis (HPA) is the insulin tolerance test (ITT), but due to safety issues is not widely used. Conversely, the ACTH stimulation test is a safer and well-tolerated tool for SAI diagnosis. However, data about its diagnostic accuracy show great variability due to both technical and interpretative aspects, such as dose, route of administration, the timing of the test, and assay used for cortisol measurements. Consequently, the clinical background of the patient and the pretest probability of HPA axis impairment become of paramount importance. We aimed to summarize the recent literature evidence in the conduction and interpretation of the ACTH stimulation test for the diagnosis of SAI to provide updated insights on its correct use in clinical practice.

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Morning Serum Cortisol Level Predicts Central Adrenal Insufficiency Diagnosed by Insulin Tolerance Test

Cited by 9 publications

References 37 publications

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

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

Recalibration of thinking about adrenocortical function assessment: how the ‘random’ cortisol relates to the short synacthen test results

ACTH Stimulation Test for the Diagnosis of Secondary Adrenal Insufficiency: Light and Shadow

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