Cushing Disease: Highlighting the Importance of Early Diagosis for Both de Novo and Recurrent Disease in Light of Evolving Treatment Patterns

ObjectiveTo highlight and summarize current literature on Cushing disease (CD)-related morbidity and mortality, focusing on residual complications after “cure” and the changing role of pharmacologic therapy in CD.MethodsCurrent journal articles on the consequences of untreated or undertreated CD, CD recurrence, and recent trends in CD treatment were collected from PubMed searches and analyzed in combination in view of the authors’ clinical experience.ResultsTimely recognition and treatment of de novo and recurrent CD remains a singular clinical challenge. Chronic excess cortisol exposure leads to potentially irreversible sequelae and death, stressing the importance of early diagnosis and treatment. Disease relapse after primary pituitary adenomectomy is prevalent and recurrence may manifest decades after initial surgery. Increased risk for mortality and hypercortisolism-related complications in postsurgical CD patients may indicate persistent subclinical disease and further underscores the need for cautious, ongoing observation and testing. Potential long-term pharmacologic treatment options (e.g., pasireotide, mifepristone) have recently emerged that may provide biochemical and symptomatic remission for those with refractory CD, or those for whom surgery is contraindicated.ConclusionDelays in CD diagnosis, management, and follow-up are common and lead to increased adverse metabolic complications and mortality. Rapid recognition and treatment as well as vigilant monitoring are therefore essential. After surgical treatment, some patients may suffer from persistent subclinical CD that remains difficult to detect with routine testing. Although long-term pharmacologic treatment has historically been limited by adverse reactions or escape from response, new treatments may offer more options for patients with refractory disease. (Endocr Pract. 2014;20:945-955)     

Mifepristone Treatment for Mild Autonomous Cortisol Secretion Due to Adrenal Adenomas: A Pilot Study

Objective: Adrenal incidentalomas are increasingly detected with the widespread use of thoracic and abdominal imaging. The most common secretory syndrome in adrenal nodules is autonomous cortisol secretion (ACS). Recent data show that even mild cortisol excess is associated with adverse outcomes. The glucocorticoid receptor antagonist mifepristone has been used in patients with overt Cushing syndrome and hyperglycemia. The purpose of our study was to determine the effect of mifepristone on metabolic parameters in patients with ACS and concomitant prediabetes or diabetes.Methods: Eight patients with either unilateral or bilateral adrenal nodules with ACS were included in the study. Fasting laboratory tests including glucose and insulin levels to calculate homeostatic model assessment for insulin resistance (HOMA-IR) were performed at baseline and again after either 3 months (3 patients) or 6 months (5 patients) on mifepristone 300 mg daily treatment. Patients also completed several validated surveys on mood and quality of life at baseline and follow-up.Results: There were significant reductions in fasting glucose measurements and insulin resistance as measured by HOMA-IR in the 6 of 8 study patients in whom these measurements were available (P = .03).Conclusion: This pilot study demonstrates that mifepristone treatment of ACS is associated with a significant decrease in fasting glucose and insulin resistance as measured by HOMA-IR scores. Mifepristone treatment of ACS may be considered as a medical option for patients with ACS due to adrenal adenomas with concomitant abnormal glucose parameters in whom surgical removal is not being considered.Abbreviations: ACS = autonomous cortisol secretion; ACTH = adrenocorticotropic hormone; AI = adrenal incidentaloma; DHEAS = dehydroepiandrosterone sulfate; GR = glucocorticoid receptor; HbA1c = hemoglobin A1c; HOMA-IR = homeostatic model assessment for insulin resistance; ODT = overnight dexamethasone suppression test; QoL = quality of life; STAI = state trait anxiety inventory; TSH = thyroid stimulating hormone; UFC = urinary free cortisol     

A New Therapeutic Approach in the Medical Treatment of Cushing’S SYNDROME: GLUCOCORTICOID RECEPTOR BLOCKADE WITH MIFEPRISTONE

ObjectiveCushing’s syndrome (CS) is a serious endocrine disorder caused by prolonged exposure to high cortisol levels. Initial treatment of this condition is dependent upon the cause, but is generally surgical. For patients whose hypercortisolism is not cured by surgery, medical therapy is often required. Drugs that have typically been used for CS medical therapy act by decreasing cortisol levels. Mifepristone is a glucocorticoid receptor antagonist now available for use in patients with CS. Unlike other agents, mifepristone does not decrease cortisol levels, but directly antagonizes its effects. Our objective is to review the pharmacology and clinical use of this novel agent and to discuss detailed guidance on the management of CS patients treated with mifepristone.MethodsWe review the literature regarding mifepris-tone use in CS and recently published clinical trial data. Detailed information related to clinical assessment of mifepristone use, potential drug interactions, drug initiation and dose titration, and monitoring of drug tolerability are provided.ResultsClinical trial data have shown that mifepris-tone improves glycemic control and blood pressure, causes weight loss and a decrease in waist circumference, lessens depression, and improves overall wellbeing. However, adverse effects include adrenal insufficiency, hypokalemia, and endometrial thickening with vaginal bleeding. These findings are supported by the earlier literature case reports.ConclusionThis article provides a review of the pharmacology and clinical use of mifepristone in Cushing’s syndrome, as well as detailed guidance on the management of patients treated with this novel agent. (Endocr Pract. 2013;19:313-326)     

Successful Long-Term Treatment of Cushing Disease with Mifepristone (RU486)

ObjectiveWe describe a girl with Cushing disease for whom surgery and radiation treatments failed and the sub- sequent clinical course with mifepristone therapy.MethodsWe present the patient’s clinical, biochemi- cal, and imaging findings.ResultsA 16-year-old girl presented with classic Cushing disease. After transsphenoidal surgery, Cyberknife radiosurgery, ketoconazole, and metyrapone did not control her disease, and she was prescribed mifepristone, which was titrated to a maximal dosage of 1200 mg daily with subsequent symptom improvement. Mifepristone (RU486) is a high-affinity, nonselective antagonist of the glucocor- ticoid receptor. There is limited literature on its use as an off-label medication to treat refractory Cushing disease. Over her 8-year treatment with mifepristone, her therapy was complicated by hypertension and hypokalemia requir- ing spironolactone and potassium chloride. She received a 2-month drug holiday every 4 to 6 months to allow for withdrawal menstrual bleeding with medroxyprogester- one acetate. Urinary cortisol, serum cortisol, and cortico- tropin levels remained elevated during mifepristone drug holidays. While on mifepristone, her signs and symptoms of Cushing disease resolved. Repeated magnetic resonance imaging demonstrated stable appearance of the residual pituitary mass. Bilateral adrenalectomy was performed, and mifepristone was discontinued after 95 months of medical therapy.ConclusionsWe describe the longest duration of mifepristone therapy thus reported for the treatment of refractory Cushing disease. Mifepristone effectively controlled all signs and symptoms of hypercortisolism. Menstruating women who take the drug on a long-term basis should receive periodic drug holidays to allow for menses. The lack of reliable serum biomarkers to monitor the success of mifepristone therapy requires careful clini- cal judgment and may make its use difficult in Cushing disease. (Endocr Pract. 2012;18:e114-e120)     

Effective Long-Term Treatment of Cushing’s Disease with Pasireotide: A Case Report

ObjectiveCushing’s disease is a rare, devastating condition associated with high morbidity and increased mortality. Primary treatment for Cushing’s disease is transsphenoidal surgery to remove the pituitary adenoma; however, recurrence can occur in up to 25% of patients. Second-line medical therapies do not directly target the pituitary tumor. Thus, normalization of adrenocorticotropic hormone (ACTH) and inhibition of tumor growth is not usually achieved.MethodsIn this case report, we present a de novo patient with a pituitary macroadenoma who was randomized to receive treatment with subcutaneous twice-daily injections of pasireotide 900 μg as part of the double-blind, Phase III CSOM230B2305 clinical trial.ResultsAround one month after treatment initiation, the patient’s urinary free cortisol (UFC) level showed a dramatic reduction (from 151.1 to 7.4 μg/24h) necessitating a dose reduction to 600 μg to relieve the symptoms of corticosteroid withdrawal. One month after dose reduction, the patient’s UFC levels remained stable and were associated with improvements in clinical signs and symptoms. These improvements continued into the 12-month extension phase following a dose increase to 900 μg and were accompanied by a significant reduction in tumor volume (from 0.797 cm³ at baseline to 0.359 and 0.365 cm³ at months 18 and 24, respectively). UFC remained normalized throughout the extension period. During the study, the patient developed hyperglycemia, which was effectively controlled with diet and then medication.ConclusionIn this case study, long-term pasireotide treatment as first-line therapy led to normalization of UFC, reduction of tumor volume and significant improvement in the clinical signs and symptoms of Cushing’s disease. (Endocr. Pract. 2013;19:e92-e96)     

Association Between Mifepristone Dose,Efficacy, and Tolerability in Patients With Cushing Syndrome

Objective: To examine the relationship between dose, clinical response (based on independent evaluation of metabolic, physical, neurologic, and social assessments), and safety of mifepristone treatment in patients with endogenous Cushing syndrome (CS).Methods: This post hoc analysis included 40 clinical responders and 50 participants who received a dose of mifepristone (safety population) in the 24-week phase 3 SEISMIC (Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing Syndrome) trial. The dose of mifepristone at the initial clinical response was analyzed, and the rate of serious adverse events (SAEs) and AEs reported in ≥20% of patients were compared to average mifepristone doses over time.Results: Among the clinical responders, 85% and 35% had their initial clinical responses at mifepristone doses ≥600 and ≥900 mg/day, respectively. The SAE rate did not increase with a higher dose over time. The AE rates for fatigue, headache, nausea, and peripheral edema declined significantly at weeks 16 to 24 (all P<.05 vs. weeks 1–2) as the study progressed and mifepristone doses were increased. Other AEs such as hypokalemia, vomiting, and decreased appetite did not significantly increase from weeks 1 to 2 as mifepristone doses were increased.Conclusions: The majority of clinical responders in the SEISMIC trial received mifepristone doses ≥600 mg/day suggesting that higher doses were required to achieve optimal clinical benefit in patients with endogenous CS. Notably, mifepristone dose escalations did not result in any significant or concordant increase in the rates of SAEs and common AEs.Abbreviations:ACTH = adrenocorticotropic hormoneAE = adverse eventCD = Cushing diseaseCS = Cushing syndromeSAE = serious adverse event     

Postsurgical Recurrent Cushing Disease: Clinical Benefit of Early Intervention in Patients with Normal Urinary Free Cortisol

Objective: To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC).Methods: The design was a single-center, retrospective chart review. Patients treated by the authors from 2008–2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST).Results: We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had ≥1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements.Conclusion: LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker.Abbreviations:ACTH = adrenocorticotropic hormoneCD = Cushing diseaseCS = Cushing syndromeCV = coefficient of variationDST = dexamethasone suppression testIPSS = inferior petrosal sinus samplingLNSC = late-night salivary cortisolQoL = quality of lifeTSS = transsphenoidal adenoma resectionUFC = urinary free cortisol     

Adrenocorticotropic Hormone Independent Macronodular Adrenal Hyperplasia due to Aberrant Receptor Expression: Is Medical Treatment Always an Option?

ObjectiveTo investigate the efficacy of medical treatment as an alternative option to bilateral adrenalectomy in patients with cortisol excess due to adrenocorticotropic hormone (ACTH) independent macronodular adrenal hyperplasia (AIMAH).MethodsWe focused on the efficacy of somatostatin analogues in a patient with food-dependent AIMAH and of leuprolide acetate in a patient with AIMAH due to aberrant LH/hCG receptor expression.ResultsTwo female patients with bilateral macronodular adrenal hyperplasia and cortisol excess were evaluated for the presence of aberrant cortisol responses. One patient demonstrated an aberrant response to mixed meal and the other, a menopausal female, to luteinizing hormonereleasing hormone (LHRH) and human chorionic gonadotropin (hCG) administration. In the first patient, subcutaneous octreotide was administered prior to mixed meal and completely abolished food-induced cortisol secretion. Thus, the patient was treated with the long-acting somatostatin analogue octreotide long-acting release (LAR) for 3 months. There was no control of cortisol excess upon reevaluation and acute subcutaneous octreotide administration prior to meal was no longer effective in blocking food-induced cortisol secretion. The second patient successfully responded to leuprolide acetate and, for 40 months, her cortisol excess remains in long-term control.ConclusionA luteinizing hormone/human chorionic gonadotropin (LH/hCG) responsive patient with AIMAH sustained long-term control of cortisol excess on leuprolide acetate. In contrast, in a meal-responsive patient with apparent gastric inhibitory polypeptide (GIP) dependent AIMAH, did not achieve remission under somatostatin analogues. (Endocr Pract. 2013;19:e77-e82)     

The Rationale for Prandial Glycemic Control in Diabetes Mellitus

Background:Diabetes mellitus (DM) is of epidemic proportions worldwide, and its microvascular and macrovascular complications have been well described. Achieving glycemic control has been demonstrated to reduce patients' risk of developing these complications.Objective:The objective of this article was to examine how prandial hyperglycemia-especially postprandial hyperglycemia (PPHG)-affects overall glycemic control and the complications of DM and to discuss the pharmacologic agents available to reduce PPHG.Methods:Materials used for this article were identified through a MEDLINE search of the literature (1975–2006). English-language randomized, controlled, prospective, cohort, and observational studies were chosen using the search terms postprandial hyperglycemia, oxidative stress, cardiovascular disease, macrovascular disease, microvascular disease, lipidemia, and coagulation.Results:Data show that controlling prandial hyperglycemia reduces the risk of cardiovascular disease (CVD) andmicrovascular complications, lowers glycosylated hemoglobin levels, causes less oxidative stress, and leads to a more favorable coagulation and postprandial lipidemia profile. Guidelines for targeting PPHG are becoming standard, and various pharmacologic agents (eg, a-glucosidase inhibitors, amylin analogues, incretin mimetics, rapid-acting insulins and insulin analogues, meglitinide analogues) that target PPHG may also improve overall glycemic control and reduce CVD risk.Conclusions:Although the level of hyperglycemia that leads to microvascular and macrovascular complications inpatients with DM remains to be elucidated, it appears prudent to address prandial hyperglycemia, especially PPHG, rather than focus solely on fasting glucose levels. Clinicians should consider incorporating agents that lower PPHG in their treatment of patients with DM.     

Adrenocorticotropic Hormone Stimulation Test During High-Dose Glucocorticoid Therapy

ObjectiveTo define the effective time frame of adequate serum cortisol response to the short standard 250-μg adrenocorticotropic hormone stimulation test (ACTH-ST) after initiation of high-dose glucocorticoid therapy in order to assist in the diagnosis of adrenal insufficiency.MethodsWe performed an ACTH-ST at 4 different times in hospitalized patients, who had a documented intact hypothalamic-pituitary-adrenal axis and were receiving high-dose dexamethasone therapy for nonendocrine diseases, to determine the time until the serum cortisol response is compromised. The ACTH-ST was performed at the following time intervals after initiation of dexamethasone therapy—24, 48, 72, and 96 hours. The outcome measures were cortisol levels measured at 0, 30, and 60 minutes after administration of 250 μg of cosyntropin.ResultsOf the overall group of 11 study patients, all those (n = 8) tested within the first 72 hours after initiation of dexamethasone therapy had an adequate response (serum cortisol level at 60 minutes, ≥ 18 μg/dL). Two of the 3 patients tested at 96 hours after initiation of dexamethasone therapy had a suppressed cortisol response at 60 minutes. At 30 minutes, all cortisol levels except 1 were inadequate (< 18 μg/dL).ConclusionThis study suggests indirectly that the ACTH-ST may be used for the diagnosis of suspected adrenal insufficiency within the first 3 days after initiation of empiric glucocorticoid therapy. An inadequate response of serum cortisol at 60 minutes to the ACTH-ST may be indicative of adrenal insufficiency in this setting. Additional studies with more patients in each therapy time point are needed to confirm these initial results. (Endocr Pract. 2009;15:122-127)     

Nuevas perspectivas en el tratamiento farmacológico de la enfermedad de Cushing

Hypercortisolism induced by Cushing disease causes high morbidity and mortality.The treatment of choice is pituitary surgery, but it often fails to achieve cure, and other treatment modalities (radiotherapy, bilateral adrenalectomy) may therefore be required. If these treatments are not effective or while waiting for their results, hypercortisolism should be controlled with drugs.The classical drug treatments are those that act by inhibiting cortisol secretion by the adrenal gland (ketoconazole, metyrapone, mitotane, etomidate).The preliminary results of a new drug (LCI699) which is a potent enzyme inhibitor of cortisol secretion have been reported.A clinical trial of the safety and efficacy of mifepristone, a glucocorticoid receptor antagonist, has just been published.The drugs deserving more attention today are those with a direct action on the tumor by inhibiting ACTH secretion: somatostatin analogues (pasireotide), dopamine agonists (cabergoline), PPAR-γ, and retinoic acid.A special review is made of the available clinical trials with pasireotide and cabergoline.     

Predicting Recovery Of The Hypothalamic-Pituitary-Adrenal Axis After Prolonged Glucocorticoid Use

Objective: Prolonged exposure to glucocorticoids lead to hypothalamic-pituitary-adrenal (HPA) axis suppression that recovers after cessation of treatment. We aimed to identify the predictive factors for HPA axis recovery after prolonged glucocorticoid use.Methods: Retrospective review of patients who had undergone first short Synacthen test (SST) to assess HPA axis recovery after prolonged use of glucocorticoids.Results: A total of 61% (20/33) of patients had adequate SST response at a median time of 2 years after diagnosis of adrenal insufficiency. Those who had adequate response during SST had higher ambulatory early morning cortisol (P<.01), shorter duration of exposure to glucocorticoids (P = .01), and lower final cumulative hydrocortisone replacement dose (P = .03). Age, gender, body mass index, indications for glucocorticoid use, and basal adrenocorticotropic hormone levels were not predictive of HPA axis recovery. On multivariate analysis, ambulatory early morning cortisol was the only independent predictor of adequate SST response (odds ratio, 1.02; 95% confidence interval, 1.01 to 1.04; P = .02). Using receiver operating characteristic curve analysis, ambulatory early morning cortisol of 8.8 μg/dL predicted a positive SST response with a sensitivity of 70% and specificity of 93%.Conclusion: Early morning ambulatory cortisol could be used to decide on timely SST in order to prevent complications from unnecessary replacement with glucocorticoids.Abbreviations: ACTH = adrenocorticotropic hormone; BMI = body mass index; CV = coefficient of variation; HPA = hypothalamic-pituitary-adrenal; SST = short Synacthen test     

Pituitary Mri Findings in Patients With Pituitary and Ectopic Acth-Dependent Cushing Syndrome: Does A 6-Mm Pituitary Tumor Size Cut-Off Value Exclude Ectopic Acth Syndrome?

Objective: Expert opinion and a consensus statement on Cushing syndrome (CS) indicate that in a patient with a clinical presentation and biochemical studies consistent with a pituitary etiology, the presence of a pituitary tumor ≥6 mm is highly suggestive of Cushing disease (CD). The purpose of the present study was to determine the optimal pituitary tumor size that can differentiate between patients with CD and ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS) and obviate the need for inferior petrosal sinus sampling (IPSS).Methods: We performed a retrospective study of 130 patients seen between 2000 and 2012 including 104 patients with CD and 26 patients with EAS.Results: A pituitary lesion was reported in 6/26 (23%) patients with EAS and 71/104 (68.3%) patients with CD, with median (range) sizes of 5 mm (3–14) and 8 mm (2–31), respectively. All tumors in the EAS group measured ≤6 mm except for 1 that measured 14 mm. The presence of a pituitary tumor >6 mm in size had 40% sensitivity and 96% specificity for the diagnosis of CD. ACTH levels >209 pg/mL and serum potassium <2.7 mmol/L were found in patients with EAS. All patients with EAS had a 24-hour urine free cortisol (UFC) >3.4 times the upper limit of normal (×ULN)Conclusion: Pituitary incidentalomas as large as 14 mm in size can be seen in patients with EAS. However, the 6-mm tumor size cut-off value provided 96% specificity and may be a reasonable threshold to proceed with surgery without the need for IPSS when the biochemical data support a pituitary etiology.Abbreviations: ACTH = adrenocorticotropic hormone CD = Cushing disease CRH = corticotropin-releasing hormone CS = Cushing syndrome EAS = ectopic ACTH secretion IPSS = inferior petrosal sinus sampling HDDST = high-dose dexamethasone suppression test LDDST = low-dose dexamethasone suppression test MRI = magnetic resonance imaging UFC = urine free cortisol ULN = upper limit of normal     

苍砂白芥汤联合平消胶囊对子宫肌瘤患者T淋巴细胞亚群、性激素水平和子宫动脉血流指数的影响

目的:探讨苍砂白芥汤联合平消胶囊治疗子宫肌瘤的临床疗效及对患者T淋巴细胞亚群、性激素水平和子宫动脉血流指数的影响。方法:选择2018年12月～2019年12月我院收治的子宫肌瘤患者90例为研究对象,采用随机数字表法及随机余数分组法分为对照组(30例,给予米非司酮片治疗)、观察1组(30例,给予米非司酮片+平消胶囊治疗)和观察2组(30例,给予米非司酮片+平消胶囊+苍砂白芥汤治疗),治疗3个月后比较三组中医临床疗效、肌瘤体积、T淋巴细胞亚群、性激素水平、子宫动脉血流指数和不良反应。结果:临床总有效率观察2组为96.67%,观察1组为86.67%,对照组为70.00%,三组比较差异有统计学意义(P0.05);治疗3个月后,三组卵泡刺激素(FSH)、孕酮(P)、雌二醇(E_2)水平较治疗前降低,且治疗3个月后观察2组低于观察1组,观察1组低于对照组,观察2组肌瘤体积、子宫动脉阻力指数(RI)、子宫动脉搏动指数(PI)低于观察1组和对照组(P0.05);治疗3个月后三组CD3~+、CD4~+及CD4~+/CD8~+水平较治疗前明显升高,CD8~+水平较治疗前明显降低,观察1组、观察2组CD3~+、CD4~+及CD4~+/CD8~+水平高于对照组,CD8~+水平低于对照组(P0.05)。三组不良反应的发生率比较差异无统计学意义(P0.05)。结论:苍砂白芥汤联合平消胶囊可提高子宫肌瘤患者的治疗效果,改善患者的T淋巴细胞亚群、性激素水平和子宫动脉血流指数,且并未增加药物不良反应。     

Random Postoperative Day-3 Cortisol Concentration as a Predictor of Hypothalamic-Pituitary-Adrenal Axis Integrity after Transsphenoidal Surgery

ObjectiveTo determine whether a random postoperative day-3 cortisol value of 10 μg/dL or greater is predictive of adrenal sufficiency 3 to 10 weeks after transsphenoidal surgery (TSS) and during long-term clinical follow-up.MethodsWe retrospectively reviewed the case records of patients who underwent TSS at our institution between 1991 and 2008. Inclusion criteria were as follows: random cortisol measured on the morning of postoperative day 3, adrenal dynamic testing performed 3 to 10 weeks after TSS, and clinical assessment of the hypothalamicpituitary-adrenal (HPA) axis at least 6 months after TSS.ResultsA total of 466 patients underwent TSS at our institution during the study period. Eighty-three patients met study inclusion criteria. Sensitivity of a random postoperative day-3 serum cortisol value of 10 μg/dL or greater for the prediction of adrenal sufficiency at a median follow-up of 42 days was 64.81% (95% confidence interval, 50.6%-77.32%), with an odds ratio of 3.1 (95% confidence interval, 1.08-8.58). Specificity was 62.1% (95% confidence interval, 42.3%-79.3%). At a median follow-up of 500 days, only 2 patients with a postoperative day-3 cortisol value of 10 μg/dL or greater required hydrocortisone replacement, both of whom had multiple anterior pituitary hormone deficiencies and evidence of pituitary dysfunction during the perioperative period.ConclusionsIn the appropriate clinical context, a postoperative day-3 cortisol value of 10 μg/dL or greater accurately predicts the integrity of the HPA axis. The final decision regarding corticosteroid replacement should be personalized, considering the postoperative day-3 cortisol level, the clinical context in which the measurement was obtained, and any evidence of concomitant pituitary dysfunction in the perioperative period. (Endocr Pract. 2011;17:717-726)     

Atypical Hypocortisolism

ObjectiveTo report a patient who had developed reversible hypocortisolism during the use of quetiapine.MethodsEarly morning cortisol levels were measured on two separate days. In addition, the patient underwent testing with intravenous synthetic adrenocorticotropic hormone (1 mcg tetracosactide) before and after tapering of quetiapine. Pituitary function was assessed and magnetic resonance imaging (MRI) was performed.ResultsThe patient had low early morning cortisol levels at presentation when using quetiapine. Tetracosactide testing indicated hypocortisolism. A MRI of the pituitary was unremarkable. The patient was treated temporarily with hydrocortisone and quetiapine was tapered. After quetiapine had been discontinued, the patient’s cortisol production had returned to normal.ConclusionAlthough lowering cortisol levels has been previously reported, this is the first report of hypocortisolism associated with the use of quetiapine. It is possible symptoms of malaise in patients who use quetiapine could be attributed to quetiapine-related hypocortisolism. (Endocr. Pract. 2013;19:e112-e114)