Postoperative Adrenal Insufficiency Research Articles

7859 Primary Hyperaldosteronism And Mild Autonomous Cortisol Secretion (MACS) In Adrenal Incidentaloma

Abstract Disclosure: K. Chanturishvili: None. Q. Gvazava: None. N. Zavrashvili: None. An adrenal incidentaloma is a mass lesion greater than 1 cm in diameter, discovered by radiologic examination, performed for another reason. Widespread use of imaging studies in everyday clinical practice has led to the increased rates of adrenal incidentalomas. Two main questions arise after discovering adrenal mass: is it malignant or benign, and is the mass hormonally active?We present a case of a 55 years old male, with a history of obesity (BMI 35).He had no significant past medical history and was not taking any medications.He presented to our clinic with an upper respiratory tract infection and shortness of breath. Chest CT was done to evaluate for possible pneumonia, where 46 x 30 cm adrenal incidentaloma with -5 HU was discovered.He was referred to our department for endocrine evaluation.Initial assessment revealed previously unknown hypertension with left ventricular hypertrophy. Laboratory workup revealed high aldosterone, suppressed renin, low normal ACTH and DHEA-S, positive 1-mg overnight dexamethasone suppression test (DST- 2.66 ug/dL) and 8-mg DST (2.26 ug/dL).Additionally, the metabolic panel showed prediabetes and hyperlipidemia.Diagnosis of adrenal macroadenoma with cortisol and aldosterone co-secretion was made.Unilateral adrenalectomy was planned. Possible postoperative adrenal insufficiency has been established. Recommendation for proper glucocorticoid coverage was given.In conclusion, evaluation of the functional status of adrenal tumors is essential to uncover hidden medical issues, as s well as to properly guide the patient for intra and postoperative management, avoiding the risks of adrenal insufficiency with proper glucocorticoid coverage. Surgical management of hormonally active adrenal incidentalomas, especially larger >2.4 cm, has potential benefit of improving and preventing metabolic abnormalities: hyperglycemia, dyslipidemia as well as comorbidities such as obesity, hypertension and osteoporosis. Presentation: 6/1/2024

7829 Hydrocortisone Vs Prednisone During Recovery Following Surgical Cure For Endogenous Hypercortisolism: A Longitudinal Observational Study

Abstract Disclosure: R. Sandooja: None. J. Saini: None. R. Gregg garcia: None. C. Zhang: None. S. Achenbach: None. E. Atkinson: None. J. Van Gompel: None. W.F. Young: None. I. Bancos: None. Hydrocortisone vs Prednisone During Recovery Following Surgical Cure for Endogenous Hypercortisolism: A Longitudinal Observational Study Introduction: Glucocorticoid withdrawal syndrome (GWS) is a constellation of symptoms that occurs after successful surgery for endogenous hypercortisolism. The objective of this study is to compare hydrocortisone versus prednisone on GWS symptoms. Methods: Study design: Single-center prospective longitudinal cohort study, 2019-2023. Participants: Adults with Cushing syndrome (CS) and mild autonomous cortisol secretion (MACS) with post-operative adrenal insufficiency treated with either hydrocortisone or prednisone for glucocorticoid replacement. Measurements: Clinical and biochemical severity scores for hypercortisolism were calculated. Quality of life (QOL) was assessed using Short Form-36 (SF-36) and Cushing QOL surveys. GWS was assessed using weekly AddiQoL surveys for the first 12 weeks after surgery. Results: Of 131 patients, 91 (69%) patients were treated with hydrocortisone and 40 (31%) with prednisone. No differences in age (median age 51 vs 53 years, P=0.62), sex (84 vs 85% women, P=0.83), etiology of hypercortisolism (ACTH-dependent: 44% vs 48%, P=0.26), clinical severity of hypercortisolism (median score 13 vs 12, P=0.97), or biochemical severity of hypercortisolism (median score of 6 in both, P=0.31) were noted between groups. When assessed at 4-, 8-, and 12-weeks post-surgery, the prevalence and trajectory of symptoms (fatigue, myalgias/arthralgias, sleep, headaches, nausea, weakness) were similar in patients treated with hydrocortisone and prednisone (P>0.05 for all). However, patients treated with prednisone were less likely to report mood changes (8.5% vs 20.9%, P= 0.004) compared to those treated with hydrocortisone. When compared to the presurgical baseline, the overall Cushing QOL score 12 weeks post-surgery improved in both groups (mean delta 8.9 vs 13.0, P=0.21). No differences in the hydrocortisone vs prednisone treatment were found in the SF-36 physical component score (mean delta of -1.7 vs 0.3, P=0.23) and SF-36 mental component score (mean delta 2.3 vs 5.0, P=0.22). Using multivariable analysis, age (estimate 0.22, P= 0.005), clinical severity score (estimate -0.73, P<0.001), female sex (estimate -5.45, P= 0.046) but not glucocorticoid type (estimate -0.06, P=0.98) were associated with the overall GWS symptom burden at 12 weeks. Conclusion: Use of prednisone after curative surgery for hypercortisolism was associated with lower mood symptoms, but did not impact the overall severity or trajectory of other symptoms associated with GWS. Baseline clinical severity of hypercortisolism, age, and female sex were associated with GWS burden. Presentation: 6/1/2024

6917 Multiple Red Herrings Complicating the Diagnosis of Cyclic Cushing’s Syndrome

Abstract Disclosure: A. Grover: None. R. McGlotten: None. L.K. Nieman: None. Introduction: Cyclic Cushing’s syndrome (CCS) is a rare disorder characterized by intermittent hypercortisolemia. It may be caused by pituitary tumor (Cushing disease), ectopic ACTH tumor secretion (EAS), or primary adrenal disease. We present a case of CCS with multiple red herrings complicating the diagnosis. Case: A 57-year-old Cushingoid appearing woman presented elsewhere with weight gain, brain fog, weakness, hypertension, worsening diabetes, and OSA. Screening tests showed more than three episodes of hypercortisolism with interval eucortisolism: salivary and 24-urine cortisol (UFC) ranged from 0.06-0.34 µg/dL (reference range, RR, ≤0.09 µg/dL) and 59.7-137.1 µg/24 h (RR 4-50 µg/24 h) respectively. The patient was symptomatic throughout. Differential diagnosis was CCS vs a physiologic non-neoplastic condition. As she had no clear etiology for the latter, further testing was performed. ACTH was indeterminate (23-27 pg/mL, RR <46). Pituitary MRI showed a left 7 mm lesion. Inferior petrosal sinus sampling (IPSS) with Corticotropin Releasing Hormone (CRH) administration showed peripheral baseline ACTH levels of 9.0 and 10.0 pg/mL, suggesting that she had cycled out of a hypercortisolemic phase. The left petrosal baseline values were low (9 pg/mL,16 pg/mL), suggesting poor catheterization, which was confirmed by a low prolactin-normalized ACTH ratio. The petrosal levels were lower than expected (maximum 767 pg/ml), due to suppression of normal corticotropes vs poor tumor response. However, a central:peripheral step-up was consistent with Cushing's disease (CD) or pseudo-CS. She was referred to us for re-evaluation. A low FSH, LH, low normal TSH, and UFC of 160 µg/24h supported a diagnosis of CS. ACTH was 14.6 pg/mL. Pituitary MRI showed a 1.3 cm x 0.8 cm mass extending into the left cavernous sinus. She did not suppress cortisol during a dexamethasone suppression test (DST). After CRH administration ACTH levels doubled. Based on the macroadenoma and CRH response, CD was established; IPSS was not repeated. After transsphenoidal hypophysectomy, pathology revealed ACTH positive adenoma. Post-operative adrenal insufficiency required hydrocortisone replacement. Conclusion: CCS can pose a diagnostic challenge due to unpredictable duration and frequency of hypercortisolism. Intermittently elevated cortisol levels with CS symptoms should raise suspicion for CCS. In our case, low peripheral ACTH levels further suggested this possibility. DST may give spurious results in CCS owing to spontaneous falls or rises in cortisol at the time of testing. Prolonged hypercortisolism is required in all patients to ensure suppression of normal corticotropes, which if not complete, may confound results in patients with EAS. Finally, inadequate catheterization may affect accuracy of lateralization in any patient with CS and is ideally evaluated both by venography and prolactin measurement. Presentation: 6/1/2024

8412 Resolution of Central Hypothyroidism shortly after Transsphenoidal Surgery For Cushing’s Disease

Abstract Disclosure: L. Esper: None. A. Ibrahim: None. N. El Asmar: None. Background: Cushing's disease is a rare endocrine disorder characterized by excessive cortisol production, resulting in various metabolic disturbances. Hypercortisolism is known to cause central hypothyroidism. The mechanism is complex and involves hypercortisolism mediated decreased TRH and TSH secretion in addition to inhibition of peripheral deiodination. This case details the successful management and recovery of a patient with Cushing's disease and reversal of central hypothyroidism after pituitary surgery.Case:A 43-year-old man was evaluated for central hypogonadism, 20 pound weight gain with central weight distribution, and the development of purple abdominal striae for the past year. He had a normal thyroid exam and appeared euthyroid. He was alsodiagnosed with hypertension and prediabetes in the past yearrequiring medical therapy.A low dose dexamethasone suppression test (DST) resulted in AM cortisol of 12.9 mcg/dl. Two adequate 24hr Urinary cortisol measurements showed elevated cortisol excretion at 458 and 378mcg/24. Lab evaluation revealed elevated cortisol levels along with elevated adrenocorticotropic hormone (ACTH) levels(ACTH of 172 pg/ml with a cortisol level of 23.9 mcg/dl). A high dose DST demonstrated suppression of cortisol to 3.4 mcg/dl. MRI pituitary was performed which showed a clearright sided 7mm pituitary adenoma.Thyroid function tests performed were consistent with central hypothyroidism, with low levels of free thyroxine (FT4) at 0.67ng/dl along with an inappropriately low normal thyroidstimulating hormone (TSH) at 0.596 uIU/ml. Total T4 was low at 4 ug/dl in addition to a low total T3 of 66 ng/dl. Remaining labs revealed central hypogonadism along with slightly elevated prolactin of 16 ng/ml. He was not started on thyroid hormone.He then underwent transsphenoidal surgery for tumor removal. He developed post-operative adrenal insufficiency (cortisol 2.12 mcg/dl) 16 hours post-op after which he was started on hydrocortisone replacement, indicating remission. 12 hours post-op, his TSH was 0.656 uIU/ml with a free t4 of 0.79 ng/dl, both in the normal range. 36 hours post-op, TSH was 0.524 uIU/ml and free t4 was 1.15 ng/dl. Histopathological examination confirmed the diagnosis of an ACTH-secreting pituitary adenoma.At 4 weeks post-op, thyroid labs showed normal FT4 (1.07ng/dl) and TSH (2.06uIU/ml). Conclusion: Hypercortisolism causes a global inhibition of the thyroid axis, with decreased levels of TSH, T4, and T3 (1). Previous studies suggest the monitoring of thyroid function at 6 and 12 months after surgical cure of hypercortisolism. Our case suggests that the resolution of hypothyroidism occurs shortly after surgery for Cushing’s disease and the need for earlier monitoring. Presentation: 6/3/2024

8219 Biochemical Disease Severity Score For Hypercortisolism Can Predict Adrenal Insufficiency After Adrenalectomy For Mild Autonomous Cortisol Secretion

Abstract Disclosure: O. Hamidi: Advisory Board Member; Self; Corcept, Neurocrine Biosciences, Amryt Pharma, Recordati Rare Diseases, Lantheus, Xeris. B.H. Salama: None. P. Dogra: None. A.P. Dackiw: None. F. Nwariaku: None. A. Islam: None. A. Mehta: None. S.C. Oltmann: None. S. Mirfakhraee: None. T. McKenzie: None. T.R. Foster: None. M. Lyden: None. B.M. Dy: None. I. Bancos: None. Introduction: Patients with mild autonomous cortisol secretion (MACS) are at risk for adrenal insufficiency (AI) after unilateral adrenalectomy. We aimed to determine the prevalence, predictors, and duration of AI after unilateral adrenalectomy for MACS, and to compare baseline and peak cortisol post cosyntropin stimulation test (CST) in diagnosing AI. Methods: We conducted a dual-center retrospective cohort study of patients with MACS who underwent unilateral adrenalectomy and were evaluated with postoperative cosyntropin stimulation test (CST). AI was diagnosed when postoperative morning cortisol was <10μg/dL and/or CST peak cortisol was <18μg/dL. Baseline and CST peak cortisol levels were considered concordant when both met corresponding cut-offs. Biochemical (BSS) and clinical (CSS) severity scores for hypercortisolism were calculated. Results: In 100 adults with MACS (77% women, median age 56 years, interquartile range [IQR] 48-63), median adenoma size was 2.8 cm (IQR, 2.2-3.7), and 25 (25%) had bilateral nodules. Median BSS was 3 (IQR, 2-5) and median CSS was 4 (IQR, 2-8). After adrenalectomy, AI was diagnosed in 56 (56%) patients. AI was associated with higher BSS, larger tumor size, but not age, sex, BMI, tumor laterality. Baseline and CST peak cortisol levels were concordant in 76% of cases. In 14% of cases morning cortisol was <10μg/dL but CST peak cortisol was ≥18μg/dL, and in 10% of cases morning cortisol was ≥10μg/dL, but CST peak cortisol was <18μg/dL. On a multivariable analysis that included age, sex, BMI, BSS, laterality, and tumor size, only higher BSS (odd ratio [OR] = 1.6 per 1 point) was associated with postoperative baseline cortisol <10μg/dL (P<0.05 for all). Independent predictors of CST peak cortisol <18μg/dL were BSS (OR 1.5 per 1 point) and unilateral adenoma (OR 3.7). During a median postoperative follow up of 13 months, 33 (59%) patients recovered from AI. Median time to recovery was 6.0 months, with AI recovery in 28% of patients by 2 months, 42% by 3 months, 53% by 6 months, and 64% by 12 months. Conclusions: Prevalence of postoperative AI in MACS was 56%. Only 76% of patients had concordant baseline and CST peak cortisol, with peak CST cortisol being more commonly abnormal in patients treated for unilateral MACS. Patients with larger adenomas and higher BSS were at higher risk for AI. Patients with MACS should be counseled about the risk and duration of AI after adrenalectomy. Presentation: 6/3/2024

Challenges in the postsurgical recovery of cushing syndrome: glucocorticoid withdrawal syndrome.

Glucocorticoid withdrawal syndrome is a challenging clinical phenomenon that can complicate the postsurgical recovery of Cushing syndrome. It is characterized by physical tolerance and dependence to supraphysiologic glucocorticoid exposure during active Cushing syndrome followed by the abrupt decline in cortisol levels after surgical treatment. The symptoms of glucocorticoid withdrawal often overlap with those of postoperative adrenal insufficiency and can be difficult for patients to cope with and for clinicians to treat. This mini review will discuss the clinical characteristics, pathophysiology, and management of glucocorticoid withdrawal syndrome while highlighting recent data in the field.

Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study.

Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. Retrospective matched cohort analysis. Academic medical center/pituitary center. Patients with CD with surgical remission and surgically treated NFPA. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). The small sample of patients with autoimmune disease limited identification of independent risk factors. Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. Recordati Rare Diseases Inc.

Adrenal insufficiency (hypocorticism) on the background of adrenalectomy for corticosteroma

Adrenal insufficiency (AI) occurs after adrenalectomy for adrenal corticosteroma due to inhibition of the hypothalamicpituitary-adrenal axis and decreased function of the contralateral adrenal gland. Treatment of postoperative AI is based on glucocorticoid replacement therapy and is generally required in all patients with adrenalectomy for Cushing’s syndrome, but dosage and duration of treatment may vary. It is important to educate patients for self-adjustment of substitution therapy dosages and prevention of AI decompensation, it is especially important in this pathology. The article presents a clinical case of a patient with acute adrenal insufficiency that developed against the background of adrenalectomy for corticosteroma of the left adrenal gland.

FRI184 Impact Of Adrenalectomy On Cognition In Patients With Mild Autonomous Cortisol Secretion

Abstract Disclosure: J. Saini: None. R. Nathani: None. C. Zhang: None. M. Suresh: None. K. Thangamuthu: None. S. Singh: None. V. Fell: None. E.J. Atkinson: None. S. Achenbach: None. N.H. Stricker: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have impaired cognition compared to patients with non-functioning adrenal adenomas. However, the impact of adrenalectomy on cognitive function in patients with MACS is unclear. Objective: To determine the impact of adrenalectomy on cognitive function in patients with MACS. Methods: Single-center prospective longitudinal study of adults with MACS. MACS was defined as serum cortisol >1.8 mcg/dL after the 1 mg dexamethasone suppression test (DST) in patients with adrenal adenomas without any overt features of hypercortisolism. Patients underwent cognitive evaluation using the standardized National Institute of Health (NIH) Toolbox Cognition Battery (7 tests of attention, episodic and working memory, language, executive function, cognitive flexibility, and processing speed) prior to adrenalectomy and at follow-up at least 10 months post-surgery. Fully corrected T-scores for age, sex, education, and race were compared using a paired t-test before and after adrenalectomy. A T-score of 50 is average performance (SD of 10). Total cognition is composite of fluid cognition (executive function, episodic memory, cognitive flexibility, working memory and processing speed) and crystallized cognition (language and vocabulary). Results: A total of 27 patients with MACS (median age 59.7 years, IQR 51.4-66.9, 17, 63% women) underwent cognitive evaluation prior to and at a median of 1.5 years (IQR, 1.1- 2.0) after adrenalectomy. Before surgery, median post-DST cortisol was 3.8 mcg/dL (IQR, 2.7-6.4) mcg/dL. Of the 27 patients, 21 (78%) patients developed post-operative adrenal insufficiency with 6 (21%) patients still requiring still requiring glucocorticoid replacement at the time of the last follow-up. At baseline, the mean total composite T-score was 50.7 (9.3), with fluid composite T-score of 49.9 (9.4) and crystallized composite T-score of 51.3 (8.7). Following adrenalectomy, all three composite T-scores improved compared to baseline. The crystallized composite T-score (composed of language and vocabulary) increased by a mean of 3.7 (5.5), P=0.001, the fluid composite T-score (composed of episodic, executive, working memory, cognitive flexibility, and processing speed) increased by a mean of 3.1 (8.3), P=0.068, and the total composite T-score improved by a mean of 3.9 (6.2), P=0.004. Conclusion: We showed that adrenalectomy in patients with MACS is associated with improvement in cognition. However, as test results may improve with practice (i.e., improvement due to taking the test the second time), to determine whether the improvements observed represent a reliable change in cognition, the next step is to evaluate for cognition score changes in referent subjects. Presentation: Friday, June 16, 2023

Partial adrenalectomy: evaluation and management—a clinical practice review

: Since the initial description of adrenalectomy, surgical management of adrenal masses has continued to evolve. In this article, the clinical evaluation, indications for partial adrenalectomy, surgical approaches and technical aspects of partial adrenalectomy, and outcomes are reviewed. The advantages and disadvantages of different operative approaches are discussed in the context of performance of pADX, including anterior, posterior, laparoendoscopic single site (LESS) surgery and robot-assisted approaches. Finally, post-operative management and outcomes are reviewed. The published literature (English language) was reviewed by searching PubMed between the years January 1, 1990 to December 31, 2021. Expert consensus and personal experiences were included to highlight nuances in planning and management. Partial adrenalectomy, in specific situations, is preferred to bilateral total adrenalectomy to avoid the need for long-term steroid supplementation, as steroid dependence is associated with decreased quality of life and increased morbidity and mortality. Various types of adrenal pathology may involve both adrenal glands, either concurrently or sequentially, especially in those with hereditary syndromes. Advancements in understanding the underlying disease processes, indications and contraindications to pADX, and minimally invasive surgery, including robotic assistance and other intraoperative adjuncts, have allowed for more widespread offering of pADX to appropriate patients. Partial adrenalectomy is a safe and effective operation in patients who otherwise would be relegated to bilateral adrenalectomy, permanent postoperative adrenal insufficiency and the need for lifelong steroid supplementation. Preoperative planning and intraoperative conduct of the operation are key to selecting appropriate patients and managing patients over the long-term, especially for those expected to have disease recurrence due to genetic mutations.

Safety of Withholding Perioperative Hydrocortisone for Patients With Pituitary Adenomas With an Intact Hypothalamus-Pituitary-Adrenal Axis

Pituitary adenoma is the second most common primary brain tumor. Perioperative hydrocortisone has been used for decades to avoid postoperative adrenal insufficiency. Recent studies suggest that withholding perioperative hydrocortisone may be safe for patients with an intact hypothalamus-pituitary-adrenal (HPA) axis. To assess the safety of withholding hydrocortisone during the perioperative period of pituitary adenoma surgery for patients with an intact HPA axis. A parallel-group, triple-masked, noninferiority randomized clinical trial was conducted at Peking Union Medical College Hospital from November 1, 2020, to January 31, 2022, among 436 patients aged 18 to 70 years with an intact HPA axis undergoing surgery for pituitary adenomas. Hydrocortisone supplementation protocol (intravenous and subsequent oral hydrocortisone, using a taper program) or no-hydrocortisone protocol. The primary outcome was the incidence of new-onset adrenal insufficiency (morning cortisol level, <5 μg/dL with adrenal insufficiency-related symptoms) during the perioperative period (on the day of operation and the following 2 days). The secondary outcome was the incidence of adrenal insufficiency in postoperative month 3. Analysis was on an intention-to-treat basis. Of the 436 eligible patients, 218 were randomly assigned to the hydrocortisone group (136 women [62.4%]; mean [SD] age, 45.4 [13.0] years) and 218 to the no-hydrocortisone group (128 women [58.7%]; mean [SD] age, 44.5 [13.8] years). All patients completed 3-month postoperative follow-up. The incidence of new-onset adrenal insufficiency during the perioperative period was 11.0% (24 of 218; 95% CI, 6.9%-15.2%) in the no-hydrocortisone group and 6.4% (14 of 218; 95% CI, 3.2%-9.7%) in the hydrocortisone group, with a difference of 4.6% (95% CI, -0.7% to 9.9%), meeting the prespecified noninferiority margin of 10 percentage points. The incidence of adrenal insufficiency at the 3-month follow-up was 3.7% (8 of 218) in the no-hydrocortisone group and 3.2% (7 of 218) in the hydrocortisone group (difference, 0.5%; 95% CI, -3.0% to 3.9%). Incidences of new-onset diabetes mellitus (1 of 218 [0.5%] vs 9 of 218 [4.1%]), hypernatremia (9 of 218 [4.1%] vs 21 of 218 [9.6%]), hypokalemia (23 of 218 [10.6%] vs 34 of 218 [15.6%]), and hypocalcemia (6 of 218 [2.8%] vs 19 of 218 [8.7%]) were lower in the no-hydrocortisone group than in the hydrocortisone group. Lower preoperative morning cortisol levels were associated with higher risks of the primary event (<9.3 µg/dL; odds ratio, 3.0; 95% CI, 1.5-5.9) and the secondary event (<8.8 µg/dL; odds ratio, 7.8; 95% CI, 2.6-23.4) events. This study found that withholding hydrocortisone was safe and demonstrated noninferiority to the conventional hydrocortisone supplementation regimen regarding the incidence of new-onset adrenal insufficiency among patients with an intact HPA axis undergoing pituitary adenomectomy. ClinicalTrials.gov Identifier: NCT04621565.

ODP639 The Occurrence and Predictors of Postoperative Adrenal Insufficiency for Patients With Subclinical Cushing's Syndrome

Abstract Objective To identify the occurrence and predictive factors of postoperative adrenal insufficiency in patients with subclinical Cushing's syndrome (SCS), and try to provide evidence for decision-making in SCS management. Methods The present retrospective analysis included 77 patients who underwent unilateral laparoscopic adrenalectomy for SCS between December 2011 and April 2021. Among them, 59 patients with complete follow-up data were included. We compared clinical characteristics of patients with and without postoperative adrenal insufficiency. The logistic regression model was used to find the potential risk factors in predicting the occurrence of postoperative adrenal insufficiency. The receiver operating characteristic (ROC) curve was used to evaluate the predictive values. Results We included 59 patients, of whom the incidence of postoperative adrenal insufficiency is 42.37%. The circadian rhythms of adrenocorticotropic hormone (ACTH) and cortisol disappeared in both two groups. Compared patients without postoperative adrenal insufficiency, patients with postoperative adrenal insufficiency were characterized by suppressed plasma ACTH level [1.11(1.11, 1.83) pmol/L vs 2.56(1.16, 4.63) pmol/L], elevated midnight cortisol level [268. 00(164. 00, 347.50) nmol/L vs 181.50(156.32, 227. 00) nmol/L] and increased cortisol level after 1 mg overnight dexamethasone suppression test (DST) [281. 00(241. 00, 396.64) nmol/L vs 172.50(144. 05, 215.25) nmol/L] (all P &amp;lt; 0. 05). Multivariate logistic regression analysis showed that the serum cortisol after a 1 mg-DST was the only independent predictive factor for the occurrence of postoperative adrenal insufficiency. The ROC curve showed that the best cut-off value of the serum cortisol after a 1 mg-DST was 233 nmol/L, with a sensitivity of 80. 00% and a specificity of 82.35%. The combination of the serum cortisol after a 1 mg-DST, plasma ACTH and midnight cortisol had the highest predictive accuracy (83. 05%). Conclusion Patients who underwent unilateral laparoscopic adrenalectomy for SCS had a risk of postoperative adrenal insufficiency. The pre-surgical assessment of the serum cortisol after a 1 mg-DST plus elevated midnight cortisol and suppressed plasma ACTH had predictive value for the occurrence of postoperative adrenal insufficiency. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.

Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?

Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing’s disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Methods: Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. Results: The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, p = NS) and Cushingoid features (27.5% vs. 20.0%, p = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2 × ULN vs. 1.3 ± 0.8 × ULN, respectively, p = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. Conclusions: While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study.

Perioperative Management of a Patient With Cushing Disease.

Patients with Cushing disease (CD) may present with both chronic and acute perioperative complications that necessitate multidisciplinary care. This review highlights several objectives for these patients before and after transsphenoidal surgery. Preoperative management includes treatment of electrolyte disturbances, cardiovascular comorbidities, prediabetes/diabetes, as well as prophylactic consideration(s) for thromboembolism and infection(s). Preoperative medical therapy (PMT) could prove beneficial in patients with severe hypercortisolism or in cases of delayed surgery. Some centers use PMT routinely, although the clinical benefit for all patients is controversial. In this setting, steroidogenesis inhibitors are preferred because of rapid and potent inhibition of cortisol secretion. If glucocorticoids (GCs) are not used perioperatively, an immediate remission assessment postoperatively is possible. However, perioperative GC replacement is sometimes necessary for clinically unstable or medically pretreated patients and for those patients with surgical complications. A nadir serum cortisol of less than 2 to 5µg/dL during 24 to 74 hours postoperatively is generally accepted as remission; higher values suggest nonremission, while a few patients may display delayed remission. If remission is not achieved, additional treatments are pursued. The early postoperative period necessitates multidisciplinary awareness for early diagnosis of adrenal insufficiency (AI) to avoid adrenal crisis, which may also be potentiated by acute postoperative complications. Preferred GC replacement is hydrocortisone, if available. Assessment of recovery from postoperative AI should be undertaken periodically. Other postoperative targets include decreasing antihypertensive/diabetic therapy if in remission, thromboprophylaxis, infection prevention/treatment, and management of electrolyte disturbances and/or potential pituitary deficiencies. Evaluation of recovery of thyroid, gonadal, and growth hormone deficiencies should also be performed during the following months postoperatively.

Adrenal surgery amid COVID-19 pandemic

COVID-19 pandemic affected every aspect of medical life, including the field of adrenal glands (AG). Our purpose is to overview the literature concerning AG domain, especially adrenal surgery amid COVID-19 pandemic. The approach of adrenal tumors (AT) is reflected by two aspects: what happens to a patient known with an adrenal mass if COVID-19 infection is positive and the other is related to restrictions amid pandemic daily practice that involve AT surgery. Patients with AT underling active hormonal over-production are at higher risk of COVID-19 infection or at increased risk of developing a more severe form of coronavirus infection, for instance, via diabetes mellitus, high blood pressure, and obesity. During the first year of pandemic, especially if considering the periods with severe restrictions and lockdown, there was a massive reduction of adrenalectomies, when compare to the same months of the previous year. Several systems of deciding the timing of intervention were used; they is still an insufficient statistical validation of these scores until now. The reduction of surgery volume was less expressive during the second year of pandemic. The rate of peri-operatory infections is relatively low, but it depends on center. Post-operative adrenal insufficiency exposes the patient to a higher risk of infections, including coronavirus infection. Peri-operative management can be handle via telemedicine in most of cases.

Postoperative adrenal insufficiency in Conn's syndrome-does it occur frequently?

Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Recently, frequent clinically significant adrenal insufficiency after adrenalectomy in subjects with PA has been reported, which may make the early postsurgical management difficult. We retrospectively searched for possible adrenal insufficiency in subjects who underwent adrenalectomy for PA and have measured cortisol in the early postoperative course. We included subjects with confirmed diagnosis of PA who underwent either posture testing (blood draw at 06:00 and 08:00) and/or adrenal venous sampling (AVS) (blood draw between 08:00 and 09:00) and have also measured cortisol after surgery (cortisol measured approximately at 07:00). Cortisol was measured by immunoassay. In this study, we identified 150 subjects (age 48.5 ± 10.3 years) with available cortisol values in the early postoperative course (median [25th percentile, 75th percentile]) 6 [5,6] days. Postoperative cortisol values (551 ± 148 nmol/l) were normal and significantly higher, compared to preoperative standing cortisol values (404 ± 150 nmol/l; (P < 0.001) and AVS cortisol values (493 ± 198 nmol/l; P = 0.009), and did not significantly differ from preoperative supine cortisol values. Postsurgical cortisol values were not different among subjects with or without abnormal dexamethasone suppression test or elevated urinary free cortisol pre-surgery, and were significantly higher in subjects with abnormal diurnal cortisol variability compared with subjects with normal diurnal variability. No patient presented with adrenocortical crisis in the later follow-up. In conclusion, postoperative cortisol values did not indicate any suspicion of possible adrenal insufficiency. To exclude possible adrenal insufficiency, it may be sufficient to measure morning cortisol in the early postoperative course.

Синдром Нельсона: питання та відповіді (клінічний випадок)

Даний клінічний випадок відображає варіабельність перебігу хронічної наднирникової недостатності після проведеної двобічної адреналектомії з приводу хвороби Іценка — Кушинга, розвиток і ріст аденоми гіпофіза, що може призвести до геморагічного інсульту в самій рецидивуючій пухлині гіпофіза. Метою патогенетичних методів лікування є зниження секреції адренокортикотропного гормону, відновлення нормальної секреції тропних гормонів гіпофіза, а також запобігання подальшому росту пухлини гіпофіза й адекватна компенсація наднирникової недостатності. Випадок показує лабільний перебіг післяопераційної наднирникової недостатності та, відповідно, різні підходи до діагностики і потреби у замісній терапії на різних етапах захворювання.

Pituitary function after transsphenoidal surgery including measurement of basal morning cortisol as predictor of adrenal insufficiency.

IntroductionPatients with pituitary adenomas undergoing transsphenoidal surgery require pre- and post-surgery examination of pituitary hormones. There is currently no consensus on how to evaluate the adrenal axis post-surgery. The aims of this study were to investigate factors that may predict postoperative adrenal insufficiency (AI) and to investigate the overall effect of transsphenoidal surgery on pituitary function.MethodsOne hundred and forty-three consecutive patients who had undergone transsphenoidal surgery for pituitary adenomas were included. Data on tumour size, pituitary function pre-surgery, plasma basal cortisol measured within 48 h post-surgery and pituitary function 6 months post-surgery were collected. Patients with AI prior to surgery, perioperative glucocorticoid treatment, Cushing’s disease and no re-evaluation after 1 month were excluded (n = 93) in the basal cortisol analysis.ResultsLow plasma basal cortisol post-surgery, tumour size and previous pituitary surgery were predictors of AI (all P < 0.05). A basal cortisol cut-off concentration of 300 nmol/L predicted AI 6 months post-surgery with sensitivity and negative predictive value of 100%, specificity of 81% and positive predictive value of 25%. New gonadal, thyroid and adrenal axis insufficiencies accounted for 2, 10 and 10%, respectively. The corresponding recovery rates were 17, 7 and 24%, respectivelyConclusionTranssphenoidal surgery had an overall beneficial effect on pituitary endocrine function. Low basal plasma cortisol measured within 48 h after surgery, tumour size and previous surgery were identified as risk factors for AI. Measurement of basal cortisol post-surgery may help to identify patients at risk of developing AI.

Characteristics of preoperative steroid profiles and glucose metabolism in patients with primary aldosteronism developing adrenal insufficiency after adrenalectomy

Treatment of choice in patients with unilateral aldosterone producing adenoma (APA) is adrenalectomy. Following surgery, most patients retain normal adrenal function, while some develop adrenal insufficiency (AI). To facilitate early detection and treatment of AI, we aimed to identify variables measured pre-operatively that are associated with post-operative AI. Variables obtained from 66 patients before and after surgery included anthropometrical data, clinical chemistry, endocrine work-up. LC–MS/MS steroid hormone profiles from tests before surgery (ACTH-stimulation, saline infusion, dexamethasone suppression) were obtained. Based on 78 variables, machine-learning methods were used in model fitting for classification and regression to predict ACTH-stimulated cortisol after surgery. Among the 78 variables, insulin concentration during pre-operative oral glucose tolerance test (OGTT) correlated positively, and dexamethasone suppressed glucocorticoids correlated negatively with ACTH-stimulated cortisol after surgery. Inclusion of LC–MS/MS measurements allowed construction of better models associated with the occurrence of AI in the training data, but did not allow reliable prediction in cross-validation. Our results suggest that glucocorticoid co-secretion (low insulin during pre-operative OGTT and insufficient suppression of glucocorticoids following dexamethasone) are correlated with the development of post-operative AI. Addition of steroid profiles improved the accuracy of prediction, but cross validation revealed lack of reliability in the prediction of AI.

Pre-operative hypercortisolism and post-operative adrenal insufficiency in pheochromocytomas: a single center retrospective analysis of 168 patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)