Early Basal Cortisol Level as a Predictor of Hypothalamic-Pituitary-Adrenal (HPA) Axis Function After Pituitary Tumor Surgery

Abstract Purpose The purpose of this study was to evaluate the clinical relevance of the early postoperative basal cortisol level in assessing the postoperative hypothalamic-pituitary-adrenal (HPA) axis function after pituitary tumor surgery. Methods We performed a prospective observational study that enrolled 83 patients operated for pituitary adenoma or other sellar lesions at the University Hospital Center Zagreb between December 2013 and April 2017 (44 nonfunctioning pituitary adenomas, 28 somatotropinomas, 5 craniopharyngiomas, 2 prolactinomas resistant to medical therapy and 4 other lesions - Rathke's cleft cyst, arachnoid cyst, chondroma and gangliocytoma). Exclusion criteria were Cushing's disease, chronic therapy with glucocorticoids prior to surgery and preoperative adrenal insufficiency. Early postoperative basal cortisol levels (measured on the second postoperative day) and the Synacthen stimulation test (performed 3 months after the surgery with the peak cortisol level of>500 nmol/L considered as a normal response) were analyzed to assess HPA axis function during follow-up. Results ROC analysis showed a cut-off of the basal cortisol level of ≥300 nmol/L measured on the second postoperative day to predict normal postoperative HPA axis function with the sensitivity of 92.31%, specificity of 87.14% and positive predictive value of 57.14%. Conclusion The basal cortisol level on the second postoperative day is a valuable tool to predict integrity of the HPA axis after pituitary tumor surgery. Our data suggest that the cortisol level of ≥300 nmol/L accurately predicts adrenal sufficiency and that in these patients glucocorticoid therapy can be withdrawn.

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Early postoperative basal cortisol level as good predictor of hypothalamic-pituitary-adrenal axis function after transsphenoidal surgery for pituitary tumours

Endocrine Abstracts ◽

10.1530/endoabs.37.ep827 ◽

2015 ◽

Author(s):

Tanja Skoric Polovina ◽

Mirsala Solak ◽

Ivana Kraljevic ◽

Tina Dusek ◽

Maja Baretic ◽

...

Keyword(s):

Cortisol Level ◽

Good Predictor ◽

Transsphenoidal Surgery ◽

Hypothalamic Pituitary Adrenal Axis ◽

Pituitary Tumours ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Basal Cortisol ◽

Basal Cortisol Level ◽

Pituitary Adrenal Axis

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Elevated basal cortisol level predicts lower hippocampal volume and cognitive decline in Alzheimer’s disease

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2008.12.026 ◽

2009 ◽

Vol 16 (10) ◽

pp. 1283-1286 ◽

Cited By ~ 73

Author(s):

Chi-Wei Huang ◽

Chun-Chung Lui ◽

Weng-Neng Chang ◽

Cheng-Hsien Lu ◽

Ya-Ling Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Cortisol Level ◽

Hippocampal Volume ◽

Basal Cortisol ◽

Basal Cortisol Level

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One microgram is the lowest ACTH dose to cause a maximal cortisol response. There is no diurnal variation of cortisol response to submaximal ACTH stimulation

Acta Endocrinologica ◽

10.1530/eje.0.1370172 ◽

1997 ◽

pp. 172-175 ◽

Cited By ~ 57

Author(s):

G Dickstein ◽

D Spigel ◽

E Arad ◽

C Shechner

Keyword(s):

Diurnal Variation ◽

Cortisol Level ◽

Low Dose ◽

Cortisol Response ◽

Acth Stimulation ◽

Baseline Cortisol ◽

Maximal Stimulation ◽

Basal Cortisol ◽

Basal Cortisol Level ◽

Cortisol Responses

There are many suggestions in the literature that the adrenal gland is more sensitive to ACTH in the evening than in the morning. However, all these studies in humans were conducted when the basal cortisol level was not suppressed, and were based on the observation that, after stimulation, the increases in cortisol differed, though the peak values were the same. To examine this, we established the lowest ACTH dose that caused a maximal cortisol stimulation even when the basal cortisol was suppressed, and used a smaller dose of ACTH for morning and evening stimulation. The lowest ACTH dose to achieve maximal stimulation was found to be 1.0 microgram, with which dose cortisol concentration increased to 607.2 +/- 182 nmol/l, compared with 612.7 +/- 140.8 nmol/l with the 250 micrograms test (P > 0.3). The use of smaller doses of ACTH (0.8 and 0.6 microgram) achieved significantly lower cortisol responses (312 +/- 179.4 and 323 +/- 157.3 nmol/l respectively; both P < 0.01 compared with the 1 microgram test). When a submaximal ACTH dose (0.6 microgram) was used to stimulate the adrenal at 0800 and 1600 h, after pretreatment with dexamethasone, no difference in response was noted at either 15 min (372.6 +/- 116 compared with 394.7 +/- 129.7 nmol/l) or 30 min (397.4 +/- 176.6 compared with 403 +/- 226.3 nmol/l; P > 0.3 for both times). These results show that 1.0 microgram ACTH, used latterly as a low-dose test, is very potent in stimulating the adrenal, even when baseline cortisol is suppressed; smaller doses cause reduction of this potency. Our data show that there is probably no diurnal variation in the response of the adrenal to ACTH, if one eliminates the influence of the basal cortisol level and uses physiologic rather than superphysiologic stimuli.

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Consistent Reduction of ACTH responses to stimulation with CRH, Vasopressin and Hypoglycaemia in Patients with Major Depression

The British Journal of Psychiatry ◽

10.1192/bjp.155.4.468 ◽

1989 ◽

Vol 155 (4) ◽

pp. 468-478 ◽

Cited By ~ 48

Author(s):

Roger G. Kathol ◽

Richard S. Jaeckle ◽

Juan F. Lopez ◽

William H. Meller

Keyword(s):

Major Depression ◽

Hpa Axis ◽

Negative Correlation ◽

Arginine Vasopressin ◽

Corticotropin Releasing Hormone ◽

Hypothalamic Pituitary Adrenal ◽

Releasing Hormone ◽

Control Subjects ◽

Basal Cortisol ◽

Cortisol Responses

Eleven patients with major depression and 12 control subjects were administered corticotropin-releasing hormone (CRH), aqueous arginine vasopressin (AVP), and insulin hypoglycaemia (IH) to test for differences in hypothalamic–pituitary–adrenal (HPA) axis function. Patients with major depression demonstrated lower ACTH responses to CRH when compared with controls, and a trend toward such after administration of AVP. Despite lower ACTH responses in patients with depression, there were no differences in Cortisol responses to these stimuli. In the CRH and AVP tests, there was no correlation between the basal Cortisol and ACTH responses in either controls or patients, but in the IH test there was a negative correlation between these responses for both groups. The ACTH responses to CRH and AVP were positively correlated in controls and patients. Cortisol responses to all three provocative stimuli were positively correlated in both subject groups. These findings are consistent with the hypothesis that hypothalamic or supra-hypothalamic overactivity may be involved in the development of HPA-axis abnormalities in patients with depression.

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Reproducibility of the cortisol response to stimulation with a low dose of ACTH(1–24): the effect of basal cortisol levels and comparison of low-dose with high-dose secretory dynamics

Journal of Endocrinology ◽

10.1677/joe.0.1360167 ◽

1993 ◽

Vol 136 (1) ◽

pp. 167-172 ◽

Cited By ~ 61

Author(s):

S. Crowley ◽

P. C. Hindmarsh ◽

J. W. Honour ◽

C. G. D. Brook

Keyword(s):

Cortisol Level ◽

Low Dose ◽

Standard Dose ◽

Serum Cortisol ◽

Cortisol Concentration ◽

Acth Stimulation ◽

Basal Cortisol ◽

Basal Cortisol Level ◽

Adrenal Response ◽

Serum Cortisol Concentration

ABSTRACT We compared the reproducibility and repeatability of the acute adrenal response to low doses (90 and 500 ng/1·73 m2) of Synacthen (ACTH(1–24)) with that of the standard dose (250 μg/1·73 m2). We also examined the effect of basal cortisol levels on peak values achieved after stimulation with a low dose. ACTH(1–24) was given to six male volunteers: 90 ng/1·73 m2 twice at 90-min intervals on day 1, and 90 and 500 ng/1·73 m2 once on day 2 and 250 μg/1·73 m2 once on day 3. The rise in serum cortisol concentration with repeated low doses of ACTH was not attenuated (161 ± 49 (s.d.) nmol/l on initial vs 150 ± 41 nmol/l on repeat stimulation; P = 0·5) and this was reproducible (161 ± 49 nmol/l on day 1 vs 148 ± 15 nmol/l on day 2; P = 0·6). A dose of 500 ng ACTH(1–24)/1·73 m2 produced a maximal adrenal response in that the rise in serum cortisol concentration at 20 min was identical with that produced at the same time by the standard dose of 250 μg/1·73 m2. There was a strong positive correlation between the basal cortisol level and peak cortisol concentration after low-dose ACTH stimulation (r = 0·93, P < 0·001) but not between the basal cortisol level and the incremental rise (r= −0·1, P = 0·69). These results suggest that the cortisol response to low-dose ACTH stimulation is reproducible and not attenuated by repeat stimulation at 90-min intervals. The incremental rise in serum cortisol concentration after ACTH stimulation appears constant in these situations and is not influenced by the basal cortisol level. When there is concern that the standard dose may be excessive and mask subtle but important changes in adrenal function, the low dose (500 ng) of ACTH should be used. Journal of Endocrinology (1993) 136, 167–172

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Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder

The British Journal of Psychiatry ◽

10.1192/bjp.184.6.496 ◽

2004 ◽

Vol 184 (6) ◽

pp. 496-502 ◽

Cited By ~ 227

Author(s):

Stuart Watson ◽

Peter Gallagher ◽

James C. Ritchie ◽

I. Nicol Ferrier ◽

Allan H. Young

Keyword(s):

Bipolar Disorder ◽

Hpa Axis ◽

Cortisol Response ◽

Hypothalamic Pituitary Adrenal ◽

The Core ◽

Basal Cortisol ◽

Suppression Test ◽

Cortisol Levels ◽

Dexamethasone Suppression ◽

Pituitary Adrenal Axis

BackgroundHypothalamic-pituitary-adrenal (HPA) axis function, as variously measured by the responses to the combined dexamethasone/ corticotrophin-releasing hormone (dex/ CRH) test, the dexamethasone suppression test (DST) and basal cortisol levels, has been reported to be abnormal in bipolar disorder.AimsTo test the hypothesis that HPA axis dysfunction persists in patients in remission from bipolar disorder.MethodSalivary cortisol levels and the plasma cortisol response to the DST and dex/CRH test were examined in 53 patients with bipolar disorder, 27 of whom fulfilled stringent criteria for remission, and in 28 healthy controls. Serum dexamethasone levels were measured.ResultsPatients with bipolar disorder demonstrated an enhanced cortisol response to the dex/CRH test compared with controls (P=0.001). This response did not differ significantly between remitted and non-remitted patients. These findings were present after the potentially confounding effects of dexamethasone levels were accounted for.ConclusionsThe dex/CRH test is abnormal in both remitted and non-remitted patients with bipolar disorder. Thismeasure of HP Aaxis dysfunction is a potential trait marker in bipolar disorder and thus possibly indicative of the core pathophysiological process in this illness.

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Diagnostic performance of basal cortisol level at 0900-1300h in adrenal insufficiency

PLoS ONE ◽

10.1371/journal.pone.0225255 ◽

2019 ◽

Vol 14 (11) ◽

pp. e0225255 ◽

Cited By ~ 3

Author(s):

Worapaka Manosroi ◽

Mattabhorn Phimphilai ◽

Jiraporn Khorana ◽

Pichitchai Atthakomol

Keyword(s):

Adrenal Insufficiency ◽

Cortisol Level ◽

Diagnostic Performance ◽

Basal Cortisol ◽

Basal Cortisol Level

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Effect of Arginine on the Hypothalamic–Pituitary–Adrenal Axis in Individuals With and Without Vasopressin Deficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa157 ◽

2020 ◽

Vol 105 (7) ◽

pp. e2327-e2336

Author(s):

Katja Bologna ◽

Nicole Cesana-Nigro ◽

Julie Refardt ◽

Cornelia Imber ◽

Deborah R Vogt ◽

...

Keyword(s):

Diabetes Insipidus ◽

Hpa Axis ◽

Pituitary Hormones ◽

University Hospital ◽

Healthy Controls ◽

Arginine Infusion ◽

Hypothalamic Pituitary Adrenal ◽

Primary Polydipsia ◽

Patients With Diabetes ◽

Different Response

Abstract Context Arginine stimulates pituitary hormones, like growth hormone and vasopressin, but its effect on the hypothalamic–pituitary–adrenal (HPA) axis is unknown. Arginine may also stimulate the HPA axis, possibly through a mechanism involving vasopressin. Objective To investigate the effect of arginine on adrenocorticotropic hormone (ACTH) and cortisol in subjects with and without vasopressin deficiency. Design Prospective study, University Hospital Basel. Participants 38 patients with central diabetes insipidus, 58 patients with primary polydipsia, and 50 healthy controls. Intervention Arginine infusion with measurement of ACTH, cortisol and copeptin at baseline and 30, 45, 60, 90, and 120 minutes. Results We found different response patterns to arginine: in patients with diabetes insipidus (and low stimulated copeptin levels) median (interquartile range [IQR]) ACTH and cortisol increased from 22.9 (16.8, 38.7) to 36.6 (26.2, 52.1) ng/L and from 385 (266, 463) to 467 (349, 533) nmol/L, respectively. In contrast, median (IQR) ACTH and cortisol levels decreased in patients with primary polydipsia (despite high stimulated copeptin levels): ACTH from 17.3 (12.3, 23) to 14.8 (10.9, 19.8) ng/L and cortisol from 343 (262, 429) to 272 (220.8, 360.3) nmol/L; likewise, in healthy controls: ACTH from 26.5 (17.6, 35.7) to 14.8 (12.1, 22.7) ng/L and cortisol from 471 (393.3, 581.8) to 301.5 (206.5, 377.8) nmol/L. Conclusion Diabetes insipidus is associated with increased responsiveness of ACTH/cortisol to arginine. In contrast, arginine does not stimulate the HPA axis in healthy controls or in primary polydipsia.

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