Confirmation of Feasibility of Selective Glucocorticoid Replacement Following Unilateral Adrenalectomy for Hypercortisolism and Primary Aldosteronism

Abstract Background: Secondary adrenal insufficiency (AI) can develop following unilateral adrenalectomy (UA) foradrenal-dependent hypercortisolism (HC) and has been reported after UA for primaryaldosteronism (PA). An institutional study previously demonstrated that cosyntropin stimulationtesting on postoperative day 1 (POD1-CST) successfully identified patients who requiredglucocorticoid replacement (GR) following UA; 50% of HC patients required GR and no PApatients required GR. The aim of this study was to reevaluate the need for GR following UA forpatients with HC and PA in a larger cohort of patients. Methods We reviewed 108 patients from a prospectively maintained adrenal database who underwent UAfor HC (n=74), PA (n=22), and concurrent HC/PA (n=12) from 9/2014-10/2020. PA patientswithout preoperative evaluation for HC were excluded. Patients with 1mg dexamethasonesuppression test (DST) cortisol >1.8 (µg/dL) were defined as having mild HC, with ³5 defined asovert Cushing’s Syndrome (CS). All patients underwent our institutional POD1-CST protocoland GR was initiated for patients with basal cortisol £5 or stimulated cortisol £14 (<18 prior to4/2017). Results: Overall, 51 (47%) patients had an abnormal POD1-CST and were discharged on GR (44 HC, 1PA, and 6 HC/PA). Two (2%) patients with CS had a normal POD1-CST but developed AIrequiring GR at 8 and 12 weeks post UA. Of the 74 patients with HC, 44 (59%) had an abnormalPOD1-CST and were discharged on GR, including 19/28 (68%) with CS and 25/46 (54%) withmild HC. Preoperative DST cortisol was higher in HC patients who required GR compared topatients with a normal POD1-CST (4.1 vs 3.6; p=0.007). Median cortisol levels for HC patientswith an abnormal POD1-CST vs those with a normal test were: basal: 3.8 vs 15.6 (p=0.027); 30-minute: 10.1 vs 20.1 (p=0.403); and 60-minute 11.4 vs 22.2 (p=0.260). Of the 22 PA patients, 19(86%) had a normal POD1-CST. Median cortisol levels for PA patients with an abnormal POD1-CST vs those with a normal test were: basal: 0.4 vs 12.1; 30-minute: 8.8 vs 24.6; and 60-minute:12.2 vs 28.9. Of the 3 (14%) PA patients with an abnormal POD1-CST, 1 was dischargedwith GR and began tapering after 2 weeks; the other 2 did not require GR and did not developAI. Of the 12 patients with combined PA/HC, 6 (50%) were discharged on GR based on POD1-CST. GR was required by 30 (59%) patients for <3 months and 82% for <12 months; 7/9 whorequired GR >12 months had CS. Conclusions: Using a standard protocol for POD1-CST in patients who underwent unilateral adrenalectomyfor HC, PA, or combined PA/HC, this study demonstrated that routine GR is not required in 32%of patients with CS and 46% of patients with mild HC. POD1-CST safely identifies patients whowill require GR with no immediate concern for adrenal insufficiency. These data also suggestthat routine evaluation for AI in postoperative PA patients is not needed if cortisol excess hasbeen excluded preoperatively.

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Selective Glucocorticoid Replacement Following Unilateral Adrenalectomy for Hypercortisolism and Primary Aldosteronism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab698 ◽

2021 ◽

Author(s):

Olivia M DeLozier ◽

Sophie Y Dream ◽

James W Findling ◽

Ty B Carroll ◽

Douglas B Evans ◽

...

Keyword(s):

At Risk ◽

Primary Aldosteronism ◽

Preoperative Evaluation ◽

Unilateral Adrenalectomy ◽

Basal Cortisol ◽

Patients At Risk ◽

Life Threatening ◽

Suppression Test ◽

Dexamethasone Suppression ◽

Prospective Database

Abstract Background An institutional study previously demonstrated that cosyntropin stimulation testing on postoperative day 1 (POD1-CST) identified patients at risk for adrenal insufficiency (AI) following unilateral adrenalectomy (UA) for adrenal-dependent hypercortisolism (HC) and primary aldosteronism (PA), allowing for selective glucocorticoid replacement (GR). This study reevaluates the need for GR following UA for patients with HC and PA in a larger cohort. Methods A prospective database identified 108 patients who underwent UA for mild autonomous cortisol excess (MACE) (n=47), overt hypercortisolism (OH) (n=27), PA (n=22), and concurrent PA/HC (n=12) from 9/2014-10/2020; all underwent preoperative evaluation for HC. MACE was defined as 1mg dexamethasone suppression test (DST) cortisol >1.8 (μg/dL), with ≥5 defined as OH. GR was initiated for basal cortisol ≤5 or stimulated cortisol ≤14 (≤18 prior to 4/2017) on POD1-CST. Results Fifty-one (47%) patients had an abnormal POD1-CST; 54 (50%) were discharged on GR (27 MACE, 20 OH, 1 PA, 6 PA/HC). Median duration of GR was OH: 6.0 months, MACE: 2.1 months, PA: 1 month, PA/HC: 0.8 months. Overall, 26% (n=7) of OH patients and 43% (n=20) of MACE patients did not require GR. Two (2%) OH patients had normal POD1-CST but developed AI several weeks postoperatively requiring GR. None experienced life-threatening AI. Conclusion POD1-CST identifies HC patients at risk for AI after UA, allowing for selective GR. One-quarter of OH patients and nearly half of MACE patients can forego GR after UA. PA patients do not require evaluation for AI if concurrent HC has been excluded preoperatively.

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Adrenal Insufficiency After Unilateral Adrenalectomy in Primary Aldosteronism: Long-Term Outcome and Clinical Impact

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00996 ◽

2019 ◽

Vol 104 (11) ◽

pp. 5658-5664 ◽

Cited By ~ 4

Author(s):

Daniel A Heinrich ◽

Christian Adolf ◽

Finn Holler ◽

Benjamin Lechner ◽

Holger Schneider ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Primary Aldosteronism ◽

Serum Cortisol ◽

Adrenal Crisis ◽

Acth Stimulation ◽

Term Outcome ◽

Unilateral Adrenalectomy ◽

Long Term Outcome ◽

Cortisol Levels

Abstract Context Primary aldosteronism (PA) represents a secondary form of arterial hypertension that can be cured by surgery. Evidence of adrenal insufficiency (AI) was recently found in patients with PA who had undergone unilateral adrenalectomy (uADX). Objective To study the incidence and long-term outcome of postoperative AI after uADX for PA. Design Prospective registry study (August 2014 until the end of 2018). Setting Tertiary referral center. Patients One hundred consecutive patients undergoing uADX for PA were included. All patients underwent postoperative ACTH stimulation testing. Intervention Postoperative ACTH stimulation testing to identify patients with AI. Main Outcome Measures Incidence of patients with postoperative AI and definition of long-term outcome. Results Twenty-seven percent of patients developed postoperative AI. Of these, 48% had postoperative ACTH stimulation serum cortisol levels ≤13.5 µg/dL (severe AI); 52% were classified into the group with moderate AI (stimulated serum cortisol levels: 13.5 to 17 µg/dL). Patients with severe AI required significantly longer hydrocortisone replacement therapy than the moderate group (median [25th, 75th percentiles]: 353 [294, 476] days; 95% CI: 284 to 322 days; vs 74 [32, 293] days; 95% CI: 11 to 137 days; P = 0.016). One patient with severe AI was hospitalized for an acute adrenal crisis. With a cumulative follow-up of 14.5 years, this produced an incidence rate of 6.9 adrenal crises per 100 patient-years. Conclusion We suggest performing postoperative ACTH stimulation tests in all patients who undergo uADX for PA.

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Comparative study of glucagon and insulin tests for diagnostics of secondary adrenal insufficiency and growth hormone deficiency in children and adolescents

Problems of Endocrinology ◽

10.14341/probl12528 ◽

2021 ◽

Vol 66 (6) ◽

pp. 50-58

Author(s):

A. V. Vitebskaya ◽

E. A. Pisareva ◽

A. V. Popovich

Keyword(s):

Growth Hormone ◽

Children And Adolescents ◽

Growth Hormone Deficiency ◽

Adrenal Insufficiency ◽

Early Morning ◽

Hormone Deficiency ◽

Secondary Adrenal Insufficiency ◽

Glucagon Test ◽

Cortisol Levels ◽

Glucagon And Insulin

BACKGROUND: Diagnostics of growth hormone deficiency (GHD) and secondary adrenal insufficiency (SAI) is based on estimation of peak GH and cortisol concentrations in provocation tests. Russian consensus on diagnostics and treatment of hypopituitarism in children and adolescences recommends to measure GH and cortisol concentrations in every time-point of insulin test (IT). Glucagon test (GT) is discussed in literature as alternative to IT.AIMS: To estimate the possibility to use provocation GT for diagnostics of SAI and GHD in children and adolescents.MATERIALS AND METHODS: We investigated blood and urine cortisol levels, IT, and GT in 20 patients 6.5–17.8 years (Me 13.0 (10.4; 15.3)) after surgery and/or radiology and/or chemical therapy of head and neck tumors; remission for 0.4–7.5 years (Ме 2.1 (1.5; 5.2)).RESULTS: With cut-off point 550 nmol/L sensitivity and specifity of IT was 100% and 60%, GT — 100% and 53% respectively. Minimal cortisol cut-off level for GT with sensitivity 100% was 500 nmol/L, maximal with specifity 100% — 400 nmol/L.Early morning cortisol levels did not exceed 250 nmol/l in 2 patients with SAI; and were above 500 nmol/l in 8 patients without SAI while primary or repeated examination.GHD was reviled by IT in all patients. Maximal GH concentrations in GT and IT did not differ significantly (p>0.05) but GT results of 4 patients exceeded or met cut-off for this test (7 ng/ml).GT was characterized by less severity compared with IT.CONCLUSIONS: For diagnostics of SAI by GT we can advise cut-off points of cortisol level 500 (sensitivity 100%, specifty 53%) and 400 nmol/L (sensitivity 80%, specifity 100%). Measuring of cortisol levels in 2–3 early morning blood samples allows to exclude or to suspect SAI in half of patients before tests. GH peaks in GT can exceed similarly data in IT that needs future investigation.

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Salivary cortisol levels during Ramadan fasting in hydrocortisone-treated secondary adrenal insufficiency patients

Endocrine ◽

10.1007/s12020-020-02452-9 ◽

2020 ◽

Vol 70 (2) ◽

pp. 404-411

Author(s):

Melika Chihaoui ◽

Wiem Madhi ◽

Meriem Yazidi ◽

Bessem Hammami ◽

Ibtissem Oueslati ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Salivary Cortisol ◽

Secondary Adrenal Insufficiency ◽

Ramadan Fasting ◽

Cortisol Levels

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Mifepristone Accelerates HPA Axis Recovery in Secondary Adrenal Insufficiency

Case Reports in Endocrinology ◽

10.1155/2016/4709597 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Pejman Cohan

Keyword(s):

Adrenal Insufficiency ◽

Hpa Axis ◽

Adrenal Adenoma ◽

Serum Cortisol ◽

Pharmacological Therapy ◽

Secondary Adrenal Insufficiency ◽

Unilateral Adrenalectomy ◽

Undetectable Serum ◽

Biochemical Testing ◽

Acth Secreting

Context. Transient secondary adrenal insufficiency (SAI) is an expected complication following successful adenomectomy of ACTH-secreting pituitary adenomas or unilateral adrenalectomy for cortisol-secreting adrenal adenomas. To date, no pharmacological therapy has been shown to hasten recovery of the hypothalamic-pituitary-adrenal (HPA) axis in this clinical scenario.Case Description. A 33-year-old woman underwent uncomplicated unilateral adrenalectomy for a 3.7 cm cortisol-secreting adrenal adenoma. Postoperatively, she developed SAI and was placed on hydrocortisone 15 mg/day, given in divided doses. In the ensuing six years, the patient’s HPA axis failed to recover and she remained corticosteroid-dependent. Quarterly biochemical testing (after withholding hydrocortisone for 18 hours) consistently yielded undetectable serum cortisol and subnormal plasma ACTH levels. While she was on hydrocortisone 15 mg/day, mifepristone was initiated and gradually titrated to a maintenance dose of 600 mg/day after 5 months. Rapid recovery of the HPA axis was subsequently noted with ACTH rising into the supranormal range at 4 months followed by a subsequent rise in cortisol levels into the normal range. After 6 months, the dose of hydrocortisone and mifepristone was lowered and both were ultimately stopped after 8 months. The HPA axis remains normal after an additional 16 months of follow-up.Conclusion. Mifepristone successfully restored the HPA axis in a woman with prolonged secondary adrenal insufficiency (SAI) after adrenalectomy for Cushing’s syndrome (CS).

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SUN-311 Adrenal Reserve Testing with the Glucagon Stimulation Test (GST) and Cosyntropin Stimulation Test (CST) in Deployed Veterans with Mild Traumatic Brain Injury

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.604 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Rama Priyanka Nagireddi ◽

Htet Htet Win ◽

Sarah Wagstaff ◽

Moira Neal ◽

Kathryn Friedman ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Adrenal Insufficiency ◽

Mild Traumatic Brain Injury ◽

Stimulation Test ◽

Pituitary Hormone ◽

Secondary Adrenal Insufficiency ◽

Glucagon Stimulation Test ◽

Cortisol Levels ◽

Cosyntropin Stimulation Test

Abstract Introduction: Mild Traumatic Brain Injury (mTBI) is associated with anterior pituitary hormone dysfunction. The potential long-term effect of this injury on pituitary function in Veterans is not clear. We reviewed the utility of the fixed dose Glucagon Stimulation Test (GST) compared with the high dose Cosyntropin Stimulation test (CST) for hypothalamic-pituitary-adrenal (HPA) reserve over time in these patients with mTBI. Methods: We present an interim report of our 4-year longitudinal prospective pilot study of pituitary function in Veterans diagnosed with mTBI. Of the 34 mTBI Veterans enrolled, we have tested 28 of them (4 female, 24 male; age and BMI, 31.5±7.0 years and 30.4±6.2, mean±SD, respectively) for baseline pituitary hormone levels and cortisol response to the CST. In 22 subjects growth hormone and cortisol responses to GST were tested at baseline (Year 0). Follow-up testing was done for 18 mTBI subjects in Year 1, 13 subjects in Year 2, 10 subjects in Year 3 and 5 subjects in Year 4. The same baseline data were obtained for 14 age-, sex-, deployment- and BMI-matched control subjects without mTBI (2 female,12 male; age and BMI 34.4±6.8 years and 30.5±4.9, mean±SD, respectively). Cortisol cutoffs of <18 mcg/dL with the CST and <9.0 mcg/dL with the GST were used for the diagnosis of adrenal insufficiency. Results: Secondary adrenal insufficiency (AI), likely partial, was identified during this study on 6 occasions: 3/22 subjects at Year 0, 1/18 at Year 1, 0/13 at Year 2, 1/10 at Year 3 and 1/5 at Year 4. Two baseline subjects with AI reverted to normal in Years 1-3, one relapsed in Year 4 and a third had no further testing. Correlations of the cortisol levels from GST vs the 60-minute cortisol from CST were significant at Year 0 (n=22, r=0.553, p=0.008) and at Year 1 (n=18, r=0.802, p<0.0001). Due to decreased numbers, there were no significant correlations at Years 2 through 4. Similar correlations were obtained using the 30-minute CST values. However, the CST cortisol value predicted the low GST value in only 2/6 subjects. The mean GST cortisol levels and 60-minute CST cortisol levels for subjects at each year were not significantly different over Years 0 through 4 based on ANOVA analyses (CST: F=1.519, p= 0.206; GST: F= 0.796, p=0.532). Conclusions: Secondary adrenal insufficiency, likely partial, related to mTBI was detected by GST on 6 occasions (twice in one patient) over 4 years of observation. GST can provide useful information about HPA axis reserve, and appears to be more reliable than CST. Identification of potential secondary adrenal insufficiency using the GST in Veterans with mTBI can provide a beneficial combined test for these patients when other testing is not feasible.

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Glucocorticoid Replacement Affects Serum Adiponectin Levels and HDL-C in Patients With Secondary Adrenal Insufficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00420 ◽

2019 ◽

Vol 104 (12) ◽

pp. 5814-5822

Author(s):

Reiko Hayashi ◽

Daisuke Tamada ◽

Masahiko Murata ◽

Tetsuhiro Kitamura ◽

Kosuke Mukai ◽

...

Keyword(s):

Lipid Profile ◽

Adrenal Insufficiency ◽

Replacement Therapy ◽

Serum Levels ◽

Adrenal Function ◽

Serum Adiponectin ◽

Secondary Adrenal Insufficiency ◽

Glucocorticoid Replacement Therapy ◽

Cortisol Levels ◽

The Relationship

Abstract Context Low serum adiponectin and high-density lipoprotein–cholesterol (HDL-C) levels are risk factors for cardiovascular disease. Patients with primary adrenal insufficiency are at higher risk of cardiovascular complications compared with healthy subjects. However, there is no information on the relationship between adiponectin and glucocorticoid replacement therapy in patients with secondary adrenal insufficiency (SAI). Objective To determine the effects of intrinsic adrenal function and glucocorticoid replacement therapy on serum adiponectin levels and lipid profile in patients with SAI. Design Part 1: a cross-sectional study. Part 2: a randomized, double-blind, crossover study. Setting Osaka University Hospital, Osaka, Japan. Patients Part 1: 58 patients diagnosed with nonfunctioning pituitary adenoma who underwent insulin tolerance test (ITT) for assessment of adrenal function. Part 2: 12 SAI patients randomly received hydrocortisone replacement therapy at a dose of 10, 20, or 30 mg/d for 4 weeks per term for three terms. Outcome Measurements Part 1: we analyzed the relationship between serum cortisol levels during ITT and serum adiponectin levels and the lipid profile. Part 2: serum adiponectin levels and lipid profile were measured every 4 weeks. Results Serum levels of adiponectin and HDL-C correlated significantly with peak cortisol levels after ITT. Serum adiponectin and HDL-C levels were significantly lower in patients with SAI than non-SAI. Serum levels of adiponectin and HDL-C increased in a hydrocortisone dose-dependent manner. Conclusions Glucocorticoid replacement therapy increased serum levels of adiponectin, an adipose-derived anti-atherogenic factor, and HDL-C in patients with SAI.

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Clinical features and diagnosis of secondary adrenal insufficiency followed complex treatment nonpituitary brain tumors

Problems of Endocrinology ◽

10.14341/probl10246 ◽

2019 ◽

Vol 65 (5) ◽

pp. 330-340

Author(s):

Alla E. Yudina ◽

Maria G. Pavlova ◽

Vladimir M. Sotnikov ◽

Alla E. Yudina ◽

Yulia P. Sych ◽

...

Keyword(s):

Brain Tumors ◽

Adrenal Insufficiency ◽

Maximum Level ◽

Tolerance Test ◽

Cross Sectional Study ◽

Screening Tests ◽

Complex Treatment ◽

Secondary Adrenal Insufficiency ◽

Cross Sectional ◽

Basal Cortisol

BACKGROUND: The most of the current studies include patients who are different by the etiology of secondary adrenal insufficiency (SAI), or investigate SAI among other late effects of the radiation therapy. AIMS: To describe the features of SAI and to select the best method of screening SAI in adult patients followed complex treatment of nonpituitary brain tumors in childhood. MATERIALS AND METHODS: It was the retrospective cross-sectional study. 31 patients after the complex treatment of nonpituitary brain tumors in childhood and 20 healthy volunteers were examined. Age and sex ratio were comparable between the groups. Biochemical and clinical blood tests, levels of cortisol, ACTH, DHEA-C were evaluated. The insulin tolerance test (ITT) was performed for all patients and 11 volunteers. RESULTS: The prevalence of SAI by ITT was 45.2%. The levels of basal cortisol (BC) were significantly higher in patients without SAI in comparison with the SAI group and volunteers (505 [340; 650] vs 323 [233; 382] and 372 [263; 489] nmol / l; pSAI- without_SAI=0.001; pwihtout_SAI-healthy = 0.04). The SAI group had DHEA-C significantly lower than in other groups one (3.1 [1.8; 3.4] vs 5.1 [2.5; 6.4] and 6.8 [4.1; 8.9]; рSAI- without_SAI = 0.036; pSAI-healthy = 0.001). ROC analysis showed that BC and DHEA-S can be used as high-quality screening tests for SAI (AUC = 89.3% and 88.3%). The maximum level of cortisol (656 [608-686] vs 634 [548-677]; p = 1) and the time of its increase (45 and 60 min) did not differ during ITT in patients without SAI and volunteers. Side effects: delayed hypoglycemia occurred in 4/14 patients of the SAI group 4090 minutes late of injection 60-80 ml of 40% glucose solution for stopping hypoglycemia in the test. CONCLUSIONS: 45.2% of patients followed craniospinal irradiation had SAI that is characterized by a decrease in DHEA-C levels. A highly normal level of basal cortisol was observed in 45% of patients without SAI. DHEA-C and blood cortisol can be used for SAI screening.

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