Prediction of the transsphenoidal endoscopic adenomectomy results in patients with cushing’s disease

Introduction. Transsphenoidal adenomectomy (TSA) is the method of choice in the treatment of Cushing’s disease (CD), but remission of hypercorticism cannot be achieved in all patients. The search for predictors of CD remission after TSA remains to be an important challenge in the endocrinology today.Aim. To study the preoperative and postoperative data of patients with CD to identify the predictors of hypercorticism remission after TSA.Materials and methods. 101 patients with confirmed CD after TSA were included. One year after operation all patients were examined for the presence of hypercorticism remission and divided into two groups: with CD remission and its absence. In both groups’ preoperative pituitary magnetic resonance imaging (MRI) data, the results of preoperative high dose dexamethasone suppression test (HDDST) and the results of serum cortisol collected in the morning 2–3 days after surgery were compared.Results. One year after TSA, CD remission was confirmed in 63 patients (62.4%), whereas in 38 patients (37.6%) hypercortisolism persisted. Favorable predictors of CD remission were: the adenoma size > 3 mm without the invasive growth according to pituitary MRI (specificity 82.4%, sensitivity 82.8%), serum cortisol suppression ≥ 74% in preoperative HDDST (specificity 81.5%, sensitivity 86.3%), morning serum cortisol level in 2–3 days after surgery ≤ 388 nmol/l (specificity 79.3%, sensitivity 97.4%).Conclusions. Pituitary MRI data, the results of preoperative HDDST and morning serum cortisol in the 2–3 days after surgery can be used as predictors of CD remission.

Morning Serum Cortisol as a Predictor for the HPA Axis Recovery in Cushing’s Disease

Background. The suppressed hypothalamic-pituitary-adrenal (HPA) axis after successful surgery for Cushing’s disease (CD) will recover in almost all patients. We aimed to identify the predictive factors for HPA axis recovery in CD patients with postoperative remission. Design and Methods. This observational retrospective cross-sectional study enrolled 69 CD patients with postoperative remission in Huashan Hospital from 2015 to 2019. All subjects had a detailed clinical evaluation. The low-dose ACTH stimulation test (LDT) was conducted as the gold standard for assessing the HPA axis function. Results. Peak cortisol in LDT was found only to be positively correlative with morning serum cortisol (MSC) ( ρ = 0.451 , p < 0.001 ). The MSC was higher ( p < 0.001 ), and the median postoperative course was significantly longer ( p = 0.025 ) in the patients with the recovered HPA axis function compared with unrecovered patients. The AUC value of MSC for predicting the recovery of the HPA axis was 0.701, and the optimal cutoff was 6.25 μg/dl (sensitivity 85.19% and specificity 47.62%). Other useful cutoff values were 10.74 μg/dl (specificity 100%) and 4.18 μg/dl (sensitivity 100%). Besides, combined with the postoperative course, the AUC values were higher than MSC alone (0.935 vs. 0.701, p < 0.001 ). Conclusions. MSC is a viable first-step diagnostic predictor for HPA axis recovery in CD patients with postoperative remission. For the patients with cortisol levels between 4.18 and 10.74 μg/dl, a confirmatory test should be conducted. When the MSC level was 10.74 μg/dl or greater, the replacement therapy could be discontinued.

Morning Serum Cortisol May Be Less Accurate for Diagnosing Adrenal Insufficiency in Hospitalized Patients, Particularly Those on Opioids

Introduction: The positive predictive value of a low morning serum cortisol to diagnose adrenal insufficiency (AI) is reported to be &gt;90%, which is the basis for guidelines recommending morning cortisol as the first-line test for central AI. A level &lt;3 µg/dL is considered diagnostic. However, studies that established this cut-off were conducted primarily in outpatients, not hospitalized patients in whom diurnal variation may be disrupted. Studies suggest that opioids suppress cortisol levels acutely, may disrupt diurnal cortisol rhythm, and cause adrenal insufficiency in 8–50% of chronically-exposed patients. The impact of hospitalization, particularly in the setting of opioid use, on the accuracy of diagnostics for AI is unknown. We hypothesized that low morning cortisol values in hospitalized patients, especially those prescribed opioids, do not accurately diagnose adrenal insufficiency, as determined by corticotropin stimulation test (CST) peak cortisol &lt;18 µg/dL. Methods: We performed a retrospective analysis of CSTs in hospitalized patients in the Mass General Brigham health system from 5/2015 to 9/2020. Opioid-exposed adults who underwent CST were included if they had a morning cortisol (5–9 AM) result. Control patients were matched by age, gender and race and had no opioid prescriptions within 30 days of testing. Patients were excluded if tested in the outpatient or ICU setting, had a history of cirrhosis or pituitary disease, had an elevated ACTH, were prescribed oral estrogen, or received oral, IV or intraarticular glucocorticoids within 30 days. Results: The analysis included 124 opioid-exposed and 322 control patients, mean (±SD) age 60.8±14.4 and 63.8±15.3y, and 55.6% and 45.0% female, respectively. Twenty-two (17.7%) opioid-exposed and 33 (10.2%) control patients were diagnosed with AI by CST (p=0.031). Nineteen opioid-exposed (15.3%) and 22 control (6.8%) patients had morning cortisol of &lt;3 µg/dL (p=0.005). A morning cortisol &lt;3 µg/dL had a positive predictive value of 36.8% (CI 19.1–59.0%) for AI in opioid-exposed and 50.0% (CI 30.7–69.3%) in control patients. In opioid-exposed patients with low morning cortisol levels, mean daily morphine milligram equivalent and duration of opioid exposure did not differ between those with AI confirmed by CST and those with normal CST (p=0.13 and 0.38, respectively). Conclusion: Among hospitalized patients with suspected AI, those prescribed opioids have a higher prevalence of central AI than controls. Serum morning cortisol &lt;3 µg/dL is not an accurate test for AI in hospitalized patients, including those prescribed opioids in whom low morning cortisol is more prevalent than in controls. Given the risks associated with misdiagnosis of AI, caution should be exercised in relying on morning cortisol values for the diagnosis of AI in hospitalized patients.

Ambient air pollutants are associated with morning serum cortisol in overweight and obese Latino youth in Los Angeles

Background Hypothalamic-pituitary-adrenal (HPA)-axis dysfunction has been associated with a variety of mental health and cardio-metabolic disorders. While causal models of HPA-axis dysregulation have been largely focused on either pre-existing health conditions or psychosocial stress factors, recent evidence suggests a possible role for central nervous system activation via air pollutants, such as nitrogen dioxide (NO2), ozone (O3) and particulate matter (PM). Therefore, in an observational study of Latino youth, we investigated if monthly ambient NO2, O3, and PM with aerodynamic diameter ≤ 2.5 (PM2.5) exposure were associated with morning serum cortisol levels. Methods In this cross-sectional study, morning serum cortisol level was assessed after a supervised overnight fast in 203 overweight and obese Latino children and adolescents (female/male: 88/115; mean age: 11.1 ± 1.7 years; pre-pubertal/pubertal/post-pubertal: 85/101/17; BMI z-score: 2.1 ± 0.4). Cumulative concentrations of NO2, O3 and PM2.5 were spatially interpolated at the residential addresses based on measurements from community monitors up to 12 months prior to testing. Single and multi-pollutant linear effects models were used to test the cumulative monthly lag effects of NO2, O3, and PM2.5 on morning serum cortisol levels after adjusting for age, sex, seasonality, social position, pubertal status, and body fat percent by DEXA. Results Single and multi-pollutant models showed that higher O3 exposure (derived from maximum 8-h exposure windows) in the prior 1–7 months was associated with higher serum morning cortisol (p < 0.05) and longer term PM2.5 exposure (4–10 months) was associated with lower serum morning cortisol levels (p < 0.05). Stratification by pubertal status showed associations in pre-pubertal children compared to pubertal and post-pubertal children. Single, but not multi-pollutant, models showed that higher NO2 over the 4–10 month exposure period associated with lower morning serum cortisol (p < 0.05). Conclusions Chronic ambient NO2, O3 and PM2.5 differentially associate with HPA-axis dysfunction, a mechanism that may serve as an explanatory pathway in the relationship between ambient air pollution and metabolic health of youth living in polluted urban environments. Further research that uncovers how ambient air pollutants may differentially contribute to HPA-axis dysfunction are warranted.

DIAGNOSTIC AND MANAGEMENT OF PATIENT WITH ADRENOCORTICAL CARCINOMA

Endogenous Cushing’s syndrome is a rare case, and about 8% is due to adrenocortical carcinoma. We report a case of a 31-year-old womanwith complaints of weight gain, round face, brown lines, menstrual disorders, and limb weakness. On physical examination, there werehypertension, moon face, central obesity, and stroke. On laboratory examination, there were morning serum cortisol levels were 46.87 andACTH levels 5. On CT scan. It was found that the right adrenal gland solid mass enhancement was +/- 6.6x4.9x7.3 cm, with suspicion ofadrenal carcinoma. On histopathological examination, adrenocortical carcinoma was obtained, and capsule invasion was obtained. Patients underwent surgery to remove the tumor, radiotherapy and chemotherapy. The patient was alive and had no residual mass at the surgical bed.

MORNING SERUM CORTISOL LEVEL PREDICTS CENTRAL ADRENAL INSUFFICIENCY DIAGNOSED BY INSULIN TOLERANCE TEST

Introduction According to guidelines, a morning serum cortisol level <83 nmol/L is diagnostic for central adrenal insufficiency (CAI), a value >414 nmol/L excludes CAI, while values between 83 and 414 nmol/L require stimulation tests. However, there are no currently reliable data on morning serum cortisol for prediction of cortisol response to insulin tolerance test (ITT). Objective Using the receiver operating characteristic curve analysis, the purpose of this study was to detect the morning serum cortisol cut-off with a specificity (SP) or a sensitivity (SE) above 95% that identify those patients who should not be tested with ITT. Methods We included 141 adult patients (83 males) aged 42.7+/-12.3 (mean +/- SD) years old. Based on serum cortisol response to ITT, patients have been divided in two groups: subjects with CAI (peak serum cortisol <500 nmol/L; 65 patients) and subjects with preserved adrenocortical function (peak cortisol >500 nmol/L; 76 patients). Results The best morning cortisol cut-off, in terms of SE (87.7%) and SP (46.1%), was ≤323.3 nmol/L. The cut-off of morning serum cortisol concentration that best predicted a deficient response to ITT was ≤126.4 nmol/L (SE 13.8%, SP 98.7%). The cut-off of morning serum cortisol concentration that best predicted a normal response to ITT was >444.7 nmol/L (SE 96.9%, SP 14.5%). Conclusions This is the first study that identifies a morning serum cortisol cut-off that best predict the response to ITT in order to simplify the diagnostic process in patients with suspected CAI. A new diagnostic flow chart for CAI is proposed.

Steroid-Induced Iatrogenic Adrenal Insufficiency in Children: A Literature Review

The present review focuses on steroid-induced adrenal insufficiency (SIAI) in children and discusses the latest findings by surveying recent studies. SIAI is a condition involving adrenocorticotropic hormone (ACTH) and cortisol suppression due to high doses or prolonged administration of glucocorticoids. While its chronic symptoms, such as fatigue and loss of appetite, are nonspecific, exposure to physical stressors, such as infection and surgery, increases the risk of adrenal crisis development accompanied by hypoglycemia, hypotension, or shock. The low-dose ACTH stimulation test is generally used for diagnosis, and the early morning serum cortisol level has also been shown to be useful in screening for the condition. Medical management includes gradually reducing the amount of steroid treatment, continuing administration of hydrocortisone corresponding to the physiological range, and increasing the dosage when physical stressors are present.