Incidence Of Adrenal Insufficiency Research Articles

Abstract #1403717: Thyro-Adrenal Insufficiency in Severe Hypothyroidism – A Clinical Mirage? A Cross-Sectional, Propensity-Matched Case-Control Study from a Tertiary Care Centre Kalaburgi, Kalyana Karnataka

Assessment of 8:00 AM cortisol levels and predict risk of adrenal insufficiency in treatment naïve severe hypothyroidism. A cross-sectional, observational, case-control study was conducted at tertiary care teaching hospital in Kalaburagi, Kalyana Karnataka, South India between January 2017 and March 2020. We included 71 consecutive adult individuals in the age group of 18-50 years of either gender, referred to the Division of Diabetes and Endocrinology, Department of Internal Medicine. All the cases were treatment naïve, diagnosed with severe hypothyroidism defined as TSH levels > 100 μIU/ml. We excluded patients with a past history of Grave’s disease, those who had ever used anti-thyroid drugs, those who had taken radioactive iodine, received steroids for any reasons, patients with a history of thyroidectomy, pre-existing pituitary or adrenal disorders, pregnancy, patients on oral contraceptives and patients with any underlying malignancies. The control population included individuals without any known thyroid disorder or any other comorbid conditions that are known to affect the function of hypothalmo-pituitary-adrenal axis. The controls were age and gender-matched. We used SAS 9.4 version software to analyze the data. T3, T4, and cortisol have been categorized and summarized descriptively with the actual collected values. Continuous variables are presented with mean and standard deviation. Categorical parameters are summarized with counts and percentages. Correlation coefficients among the T3, T4, and cortisol were generated for the overall population. Seventy-one cases of severe hypothyroidism (TSH >100 mIU/L) were compared with age and gender-matched controls (n=40). The mean age of the patients was 30.0±9.0 years and 88.7% were females. Serum cortisol levels were significantly lower in cases than in controls (8.6±4.2 vs. 16.0±2.22 μg/dl respectively, p<0.0001). Six (8.5%) cases were identified with adrenal insufficiency. After propensity matching, T3 (20.32±16.94 vs. 39.33±38.92 ng/dl, p=0.018) and T4 (0.81±0.55 vs. 1.93±1.17 μg/dl, p=0.005) levels were comparatively lower in adrenal insufficiency cases than those without adrenal insufficiency. Serum T3 (r = -0.243, p=0.041) but not T4 (r = -0.103, p=0.391) had a significant negative correlation with serum cortisol levels. Transient adrenal insufficiency can be seen in treatment naïve severe hypothyroidism. In our cohort, the incidence of adrenal insufficiency was 8.5%. An apt clinical vigilance is needed to identify adrenal insufficiency in such patients. Further studies are needed to understand the implications of severe hypothyroidism with adrenal insufficiency. A short synaecthien test may be needed in with low cortisol at diagnosis of severe hypothyroidism.

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.

Severity of traumatic adrenal injury does not meaningfully affect clinical outcomes.

There are limited data comparing the severity of traumatic adrenal injury (TAI) and the need for interventions, such as transfusions, hospitalization, or incidence of adrenal insufficiency (AI) and other clinical outcomes. The aim of this study was to analyze the relationship between the grade of TAI and the need for subsequent intervention and clinical outcomes following the injury. After obtaining Institutional Review Board approval, our trauma registry was queried for patients with TAI between 2009 and 2017. Contrast-enhanced computed tomography (CT) examinations of the abdomen and pelvis were evaluated by a board-certified radiologist with subspecialty expertise in abdominal and trauma imaging, and adrenal injuries were classified as either low grade (American Association for the Surgery of Trauma (AAST) grade I-III) or high grade (AAST grade IV-V). Patients without initial contrast-enhanced CT imaging and those with indeterminate imaging findings on initial CT were excluded. A total of 129 patients with 149 TAI were included. Eight-six patients demonstrated low-grade injuries and 43 high grade. Age, gender, and Injury Severity Score (ISS) were not statistically different between the groups. There was an increased number of major vascular injuries in the low-grade vs. high-grade group (23% vs. 5%, p < 0.01). No patient required transfusions or laparotomy for control of adrenal hemorrhage. There was no statistical difference in hospital length of stay (LOS), ventilator days, or mortality. Low-grade adrenal injuries were, however, associated with shorter ICU LOS (10days vs. 16days, p = 0.03). The need for interventions and clinical outcomes between the low-grade and high-grade groups was similar. These results suggest that, regardless of the TAI grade, treatment should be based on a holistic clinical assessment and less focused on specific interventions directed at addressing the adrenal injury.

Evaluation of a perioperative steroid coverage after pituitary surgery

IntroductionSerum cortisol levels within the first days after pituitary surgery have been shown to be a predictor of post-surgical adrenal insufficiency. However, the indication of empirical glucocorticoids to avoid this complication remains controversial.The objective is to assess the role of cortisol in the early postoperative period as a predictor of long-term corticotropic function according to the pituitary perisurgical protocol with corticosteroid replacement followed in our center. MethodsOne hundred eighteen patients who underwent surgery in a single center between December 2012 and January 2020 for a pituitary adenoma were included. Of these, 54 patients with previous adrenal insufficiency (AI), Cushing's disease, or tumors that required treatment with high-dose glucocorticoids (GC) were excluded. A treatment protocol with glucocorticoids was established, consisting of its empirical administration at rapidly decreasing doses, and serum cortisol was determined on the third day after surgery. Subsequent adrenal status was assessed through follow-up biochemical and clinical evaluations. ResultsOut of the 64 patients treated, there were 56 macroadenomas and 8 microadenomas. The incidence of adrenal insufficiency after pituitary surgery was 4.7%. The optimal cut-off value that predicted an adequate corticotropic reserve, taking into account the best relationship of specificity and sensitivity, was ≥4.1 μg/dl for serum cortisol on the third day (sensitivity 95.1%, specificity 100%). ConclusionSerum cortisol on the third day predicts the development of adrenal insufficiency. We suggest a cortisol cut-off point of ≥4.1 μg/dl on postoperative on the third day after surgery as a predictor of the adrenal reserve in the long-term.

Abstract P5-18-08: The relative risk of various endocrinopathies associated with neoadjuvant chemoimmunotherapy use in early-stage triple-negative breast cancer: A systematic review and meta-analysis

Abstract Background: Immune checkpoint inhibitors (ICIs) are known to cause various irreversible endocrinopathies. Lately, multiple clinical trials have demonstrated that the addition of ICI to the standard neoadjuvant chemotherapy improves pathological complete response (pCR) rate in high-risk early-stage triple-negative breast cancer (TNBC). The pCR has long been regarded as a surrogate marker of favorable outcomes in early-stage TNBC. This systematic review and meta-analysis attempt to determine the risks of various endocrinopathies associated with neoadjuvant chemoimmunotherapy use in early-stage TNBC. Methods: We conducted a systematic search in the PUBMED, MEDLINE, EMBASE, American Society of Clinical Oncology, and San Antonio Breast Cancer Symposium meeting abstracts as per PRISMA guidelines from inception through May 30th, 2021. Published phase 2 and 3 randomized control trials (RCTs) using neoadjuvant ICI plus chemotherapy (ICI+C) in the intervention arm for early-stage TNBC and reporting the number of events for various endocrinopathies were included in the analyses. We used the Mantel-Haenszel method and random-effects model to calculate the estimated pooled risk ratio (RR) with a 95% confidence interval (CI). Heterogeneity was tested with the I2 value and Cochran’s Q-test. Results: Two phase 3 RCTs (IMpassion031 and KEYNOTE-522) and Two phase 2 RCTs (GeparNuevo and I-SPY2) were included in the final analysis. These RCTs randomized 1,106 patients in the ICI+C arm and 819 patients in the placebo plus chemotherapy (P+C) arm. Some essential characteristics of these trials are included in table 1. The incidence of any grade hypothyroidism was 12.84% in the ICI+C arm versus 3.17% in the P+C arm. The pooled RR of any grade hypothyroidism was 3.63 (95% CI: 1.78-7.43, p = 0.0004, I2 = 28%), which was statistically significant. The incidence of any grade hyperthyroidism was 5.24% in the ICI+C arm versus 0.98% in the P+C arm. The pooled RR of any grade hyperthyroidism was 4.08 (95% CI: 1.94-8.59, p = 0.0002, I2 = 3%), which was statistically significant. The incidence of any grade adrenal insufficiency was 2.66% in the ICI+C arm versus 0.14% in the P+C arm. The pooled RR of any grade adrenal insufficiency was 6.84 (95% CI: 0.43-108.95, p = 0.17, I2 = 62%), which was not significant. The incidence of any grade hypophysitis was 1.45% in the ICI+C arm versus 0.16% in the P+C arm. The pooled RR of any grade hypophysitis was 5.29 (95% CI: 0.96-29.25, p = 0.06, I2 = 0%), which was not significant. The incidence of any grade diabetes mellitus was 0.42% in the ICI+C arm versus 0.18% in the P+C arm. The pooled RR of any grade diabetes mellitus 1.81 (95% CI: 0.24-13.63, p = 0.57, I2 = 0%), which was not statistically significant. Conclusions: The addition of immune checkpoint inhibitors (ICIs) to the standard neoadjuvant chemotherapy significantly increases the risk of any grade hypothyroidism and hyperthyroidism. Although the incidences of adrenal insufficiency, hypophysitis, and diabetes mellitus were numerically higher in the ICI+C arm than the P+C arm, they have not achieved statistical significance, possibly due to the rarity of these events. Careful endocrine functions monitoring and appropriate early interventions are crucial in reducing endocrine-related morbidities and mortalities in these patients. Table 1.Characteristics of the studies included in the meta-analysisStudyPhaseICI usedC usedNo. of patients (ICI+C)No. of patients (P+C)GaperNuevo2DurvalumabNab-paclitaxel + EC9282I-SPY22PembrolizumabPaclitaxel + AC69181IMpassion0313AtezolizumabNab-paclitaxel + AC164167KEYNOTE-5223PembrolizumabPaclitaxel + carboplatin + AC/EC781389AC: doxorubicin + cyclophosphamide; C: chemotherapy; EC: epirubicin + cyclophosphamide; ICI: immune checkpoint inhibitor; P: placebo Citation Format: Nusrat Jahan, Shabnam Rehman, Lukman Tijani. The relative risk of various endocrinopathies associated with neoadjuvant chemoimmunotherapy use in early-stage triple-negative breast cancer: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-08.

Differentiated approach to surgical treatment of adrenal glands tumors

Objective – to improve the results of treatment of adrenal tumors by optimizing a differentiated approach based on the analysis of the results of various surgical invasions. The paper analyzed the results of treatment of 145 patients with various adrenal tumors, which were divided into 2 groups: І (n=71) - patients after adrenalectomies, II (n=74) – after adrenal resections. Organ-preserving invasions showed better results during the early and long-term postoperative period in patients with corticosteromas, pheochromocytomas and incidentalomas by reducing the severity of fluctuations in hemodynamic parameters and the frequency of adrenal insufficiency. Due to the introduction of the treatment algorithm, the number of adrenal resections increased by 26.6% in patients with neoplasms more than 4,0 cm in diameter (p=0.0001). The choice of surgical invasion should be individualized, taking into account the clinical features of the disease, hormone indicator parameters, the size of tumors, the comprehensiveness of the adrenal gland lesion and the ratio of the latter to nearby organs and structures. Adrenal insufficiency was detected 14.2% more often after adrenalectomies (р=0.044) compared to adrenal resections. Treatment according to the developed algorithm reduced the incidence of adrenal insufficiency by 5.8% (p=0.028). In the long-term postoperative period, contralateral gland tumors occurred with the same frequency (4.8%) among patients after adrenalectomies and resections. Relapse of the neoplasm after resections was detected in 3 (7.1%), as a result of which 2.4% underwent repeated operations with the final removal of the gland. An increase in the size of a single adrenal gland was more common by 21.4% after adrenalectomies.

Evaluación de protocolo de manejo periquirúrgico con glucocorticoides tras cirugía hipofisaria

IntroductionSerum cortisol levels within the first days after pituitary surgery have been shown to be a predictor of post-surgical adrenal insufficiency. However, the indication of empirical glucocorticoids to avoid this complication remains controversial.The objective is to assess the role of cortisol in the early postoperative period as a predictor of long-term corticotropic function according to the pituitary perisurgical protocol with corticosteroid replacement followed in our center. MethodsOne hundred eighteen patients who underwent surgery in a single center between December 2012 and January 2020 for a pituitary adenoma were included. Of these, 54 patients with previous adrenal insufficiency (AI), Cushing's disease, or tumors that required treatment with high-dose glucocorticoids (GC) were excluded. A treatment protocol with glucocorticoids was established, consisting of its empirical administration at rapidly decreasing doses, and serum cortisol was determined on the third day after surgery. Subsequent adrenal status was assessed through follow-up biochemical and clinical evaluations. ResultsOut of the 64 patients treated, there were 56 macroadenomas and 8 microadenomas. The incidence of adrenal insufficiency after pituitary surgery was 4.7%. The optimal cut-off value that predicted an adequate corticotropic reserve, taking into account the best relationship of specificity and sensitivity, was ≥4.1μg/dl for serum cortisol on the third day (sensitivity 95.1%, specificity 100%). ConclusionSerum cortisol on the third day predicts the development of adrenal insufficiency. We suggest a cortisol cut-off point of ≥4.1μg/dl on postoperative on the third day after surgery as a predictor of the adrenal reserve in the long-term.

The Quality of Life of Thalassemic Patients: The Role of Endocrine Defect Compensation.

The improvement of beta thalassaemia treatments has led to an increase in life expectancy. This implies the emergence of new comorbidities. Amongst others, endocrine glands are extremely sensitive to iron overload. We aimed to understand the impact of the endocrine conditions on the patient's quality of life (QOL). Hypogonadism may present with lack or delay of pubertal development, sexual dysfunctions and impaired fertility, which impact QOL in both sexes. Early recognition and treatment, as well as choosing the most appropriate therapy, according to patient's needs (fertility, pubertal development, psychological concerns, comorbidities), are advisable. Osteoporosis affects QOL irrespective of symptoms. Growth hormone deficiency may occur both in childhood and in adulthood, and it affects different aspects of QOL. In adults, it could be difficult to examine if the symptoms are due to GHD, and a trial of GH replacement could be useful to identify benefits and needs. Glucose metabolism impairment is common in thalassaemic patients and early recognition is mandatory because long-term complications can have a detrimental impact on QOL (as blindness or dialysis). Although the incidence of adrenal insufficiency seems to be rare in thalassaemic patients, when it occurs, it has a severe impact on QOL. Limited data is available on QOL in thalassaemic patients, and is even less related to endocrinopathies. We can speculate that endocrinopathies have an impact on everyday life. More studies are needed to allow our patients to achieve not just a longer life but also a better quality of life.

Relationship Between Epidural Steroid Dose and Suppression of Hypothalamus-Pituitary-Adrenal Axis

Background: The suppression of hypothalamic-pituitary-adrenal (HPA) axis is a common complication associated with epidural steroid injections (ESIs). However, the effect of different doses is unknown. Objectives: The primary objective was to compare the differences in the duration of HPA suppression following treatment with different doses of ESI; triamcinolone acetate (TA) 40 mg and TA 20 mg. The secondary objectives were to compare the extent of salivary cortisol (SC) reduction, the incidence of adrenal insufficiency (AI), and the differences in a numeric rating scale (NRS) depending on the varying levels of TA dose used for ESI. Study Design: A double-blind, parallel-group, randomized controlled trial. Setting: Pain clinics in a university hospital. Methods: The patients were treated with TA epidurally and divided into 2 groups (T20 and T40) depending on the dose of TA (20 mg and 40 mg). The SC concentration was measured before and after ESI to calculate the duration of HPA axis suppression, the extent of SC concentration reduction, and the SC recovery rate. Additionally, NRS and adrenocorticotropic hormone stimulation tests were used. Results: Thirty patients were analyzed. The T40 group showed longer HPA suppression (19.7 ± 3.1 days) compared with that of the T20 group (8.0 ± 2.4 days). The recovery rate of the T40 group was lower than that of the T20 group (P &lt; 0.015). However, there was no difference in the extent of reduction in SC concentration after ESI, the occurrence of AI, and pain reduction. Limitations: There were selection bias and no placebo control. Conclusions: Although the difference in pain relief according to the ESI dose is not significant, the HPA suppression is prolonged with a higher dose than a lower dose, and the recovery is slower. Therefore, the time interval between consecutive ESIs should be adjusted depending on the steroid dose to ameliorate the adverse effects of steroids. Key words: Adrenal insufficiency, adverse effects, cushing’s syndrome, epidural injections, glucocorticoids, optimal dosage, pituitary-adrenal system, salivary cortisol

The Incidence of Long-Term Adrenal Insufficiency Following Unilateral Adrenalectomy is Low: Case Series and Review of Literature

Introduction: Acquired adrenal insufficiency is a known risk of unilateral adrenalectomy. However, the rates of early and prolonged adrenal insufficiency following unilateral adrenalectomy are not well defined in the literature. Patients and Methods: We reviewed a case series of 184 consecutive patients to determine the likelihood of steroid supplementation at 30 days and 1 year following adrenalectomy. 109 lesions were non-functional and 75 (41%) demonstrated functionality, including 33 pheochromocytomas, 20 cortisol-producing adenomas, 19 aldosteronomas, and 3 cases of cortisol-secreting hyperplasia. No patients with a nonfunctional lesion, pheochromocytoma, or aldosteronoma required steroid supplementation following surgery. Eleven of 23 patients (48%) with primary adrenal Cushing syndrome required cortisol supplementation at 30 days, and only 1 patient (4%) necessitated supplementation one year following surgery. Discussion: Approximately 50% of patients with cortisol-producing lesions in the adrenal gland will require supplementation 30-days following surgery. Only 4% will require persistent exogenous steroids at 1-year. Conversely, less than 1% of patients with different types of functional or non-functional tumors required supplementation after surgery. Conclusion: The incidence of adrenal insufficiency following unilateral adrenalectomy is low. A large majority of patients requiring steroid supplementation 30 days following surgery are able to wean off this requirement by 1 year. With this information, we can better counsel our patients and set clearer expectations for the potential need of cortisol supplementation following adrenalectomy

Adrenal Insufficiency in Cardiogenic Shock: Incidence and Prognostic Implication

Introduction: Functional integrity of the hypothalamic pituitary axis is disrupted during severe infection or stress. The observed blunted response to corticotropin was interpreted as impaired secretory reserve of the adrenal glands and was termed as relative adrenocortical insufficiency. Aim of the work: To study the incidence of adrenal insufficiency in patients developed cardiogenic shock complicating ST segment elevation myocardial infarction. Materials and methods: Prospective cohort study was done for 90 patients admitted to Algalaa Hospital for whom basal cortisol and ACTH level were measured immediately before a standard-dose (250 μg) ACTH stimulation test (SST) and 60 minutes after SST Δmax is defined as the difference between the maximal value after the test and basal level of serum cortisol. Results: Baseline ACTH and total cortisol showed positive correlation to clinical severity scores (APACHE II and Lactate), LVEF as well as vasoactive inotrope score, all with significant p value (0.000). The higher baseline cortisol level was co-related to increased mortality (Baseline serum cortisol level was significantly lower in survivors (30.6 ± 6.1 vs 45.0 ± 16.3) p value: 0.000) while the better response of the adrenal gland to short stimulation test was co-related more to survival as detected by Δmax TC (difference of cortisol level before and after SST) (13.8 ±3.8 in survivors vs 8.5 ± 4.42 in non survivors) p value 0.000. Conclusion: A high baseline plasma TC was associated with increased mortality in patients with cardiogenic shock post acute myocardial infarction. Patients with lower baseline TC, but with a better adrenal response, appeared to have a survival benefit.

The Role of IL-1, IL-6, TNF-α and MIF in Relative Adrenal Insufficiency in Septic Shock: A Study in Piglet Model

Introduction: Incidence of adrenal insufficiency is high. This study aimed to identify the role of IL-6, IL-1, TNF-α and MIF in septic shock with relative adrenal insufficiency (RAI) in order to develop guidelines for biomarker. Methods: Experimental study conducted in Veterinary Medicine for 6 months. Piglet models aged 6-8 weeks and 5-10 kg. Consecutive sampling was used with total 20 piglets. Piglet were given 50 ug/kg endotoxin (Escherichia coli; Sigma chemical, USA) and were monitored using PiCCO monitor. Blood sample was collected every 15 minutes until septic shock occurred. Corticotropine stimulation test and immunohistochemistry examination were performed. Result: From 19 study subjects had septic shock in 60 minutes. The level of IL-6 at 45 minutes had a significant different compared to the group without RAI ( p = 0.008). The level of IL-1 during septic shock were not significantly different. The level of TNF-α in RAI group had significant different at 15 minutes ( p = 0.002) and at 30 minutes ( p = 0.007) The level of MIF in RAI group during septic shock had a significant different (p = 0.003). Immunohistochemistry staining observed only in the hypothalamus glands of the RAI group. Conclusion: TNF-α increased in earlier minutes, then IL-6 increased and MIF increased in septic shock condition. IL=1 level had no difference for both group. Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. Declaration of Interest: The authors declares that they have no competing interests Ethical Approval: The study was conducted for 6 months (April – September 2015) and was started after obtaining ethical review approval from Medical/Health Research Ethics Committee of the Faculty of Medicine, University of Indonesia/RSUPN Dr. Cipto Mangunkusumo (No. 939/UN2.F1/ETIK/X/2015) and an approval from the Animal Ethics Committee of the Veterinary Faculty, Bogor Agricultural Institute (No. 026/KEH/SKE/IV/2015).

Study of adrenal function in patients with tuberculosis

Although subclinical adrenal insufficiency has been documented in tuberculosis but it has been neglected in mainstream management of TB due to inconclusive data on its prevalence in TB. The fact that adrenal insufficiency may result not only in poor general condition of the patient but also sudden death due to adrenal crisis, makes it all the more important to address this issue seriously. In this non-randomized interventional study comprising of 100 cases of TB, our aim was to assess the adreno-cortical functions in patients with pulmonary TB (50 cases) and extra-pulmonary TB (50 cases) in an attempt to determine if there is any compromise of adrenal function. In this study, 100 cases of active TB were investigated for adrenal insufficiency by measuring morning fasting basal serum cortisol levels, followed by low dose ACTH stimulation test using 1μg synacthen (synthetic ACTH analog). The post-stimulation serum cortisol levels were estimated. Basal serum cortisol levels<220nmol/L or post-stimulation test serum cortisol level increment<200nmol/L or post-stimulation serum cortisol levels<500nmol/L were suggestive of adrenal insufficiency. Basal serum cortisol level was low in 16% cases and after low dose ACTH stimulation test, cortisol response was subnormal in 76% cases. Incidence of adrenal insufficiency in pulmonary TB (74%) and extra-pulmonary TB (78%) were comparable. The number of females having adrenal insufficiency in both the groups was higher than the males (67.3% males and 83.3% females) but the difference was statistically significant only in extra-pulmonary TB group (p=0.011). On analysing the data, the sensitivity of basal serum cortisol level estimation in diagnosing adrenal insufficiency was observed to be 21.05% and its specificity was 100%. Positive predictive value was 100% and negative predictive value was 28.57%. Diagnostic accuracy of basal serum cortisol level estimation was observed to be 40%. The incidence of subclinical adrenal insufficiency in TB cases attending chest department at a tertiary care hospital was significantly high but comparable in both pulmonary and extra-pulmonary type of TB. Females in general and particularly those with extra-pulmonary TB were observed to be at increased risk of adrenal insufficiency. The low dose ACTH stimulation test was able to identify cases with adrenal insufficiency which had normal basal serum cortisol levels. Screening all TB cases for adrenal insufficiency by measuring both morning basal serum cortisol levels and low dose ACTH stimulation test can help identify cases at risk of fatal adrenal crisis and institute timely management, thus improving disease prognosis.

Insuficiencia suprarrenal crónica primaria de etiología autoinmune. Revisión de la literatura a propósito de un caso

La incidencia de la Insuficiencia Suprarrenal es de 1:100 000. Las causas primarias son más raras, apenas constituyen el 40% y se vinculan frecuentemente a enfermedades infecciosas o de etiología autoinmune. El objetivo es describir la presentación de un caso de Insuficiencia suprarrenal crónica primaria de etiología autoinmune diagnosticado en el Hospital General de Cienfuegos. Paciente de 25 años, acude por dolor abdominal. Durante la pesquisa refirió cambio de coloración de la piel y episodios de hipoglicemias. Se constata hipotenso. Los complementarios arrojaron hiponatremia ligera. Posterior estudio mostró ACTH elevado y Cortisol bajo. Resto de los exámenes de sangre e imagenológicos sin alteración. El paciente se encuentra bajo medicación y en seguimiento por consulta. Sin complicaciones.

An analysis of the relationship between serum cortisol and serum sodium in routine clinical patients

ObjectivesAdrenal insufficiency is an uncommon cause of hyponatraemia that should not be overlooked due to the severe consequences of an Addisonian crisis. Using the laboratory database of a large teaching hospital, we have explored the relationship between serum sodium and serum cortisol, and have estimated the frequency of hypoadrenalism in severely hyponatraemic patients. Design and methodsData were gathered over a 23 month period from the Laboratory Information Management System at the Leeds Teaching Hospitals NHS Trust for instances where serum sodium and cortisol had been measured on a single sample. Data were also gathered over the same time period for all patients with severe hyponatraemia (serum sodium ≤120mmol/L) in order to determine the frequency of cortisol requesting and the incidence of adrenal insufficiency. ResultsAnalysis of the data (n=3268 patients) revealed a trend showing higher cortisol concentrations in patients who were severely hypo- or hypernatraemic. The median cortisol concentration for patients with sodium ≤110mmol/L was 856nmol/L, and there was a gradual decrease in cortisol over the sodium range ≤110–150mmol/L (Rs =−0.323, p<0.0001). Patients with sodium ≥151mmol/L had a median cortisol of 725nmol/L. 42% of the 978 patients with serum sodium ≤120mmol/L had serum cortisol measured within two weeks, of whom 1.7% were diagnosed with adrenal insufficiency. ConclusionsThis dataset shows rising cortisol in response to hypo- or hypernatraemia, in keeping with the stress response to illness. The data show that adrenal insufficiency is a rare cause of hyponatraemia which may be overlooked.

The Incidence of Adrenal Insufficiency in Myeloma Patients Receiving Pulse-Dose Dexamethasone

Introduction: Glucocorticoids (GC's) are major drugs in the treatment of multiple myeloma (MM). Chronic administration of supra-physiological doses of GC's suppresses the hypothalamus-pituitary-adrenal (HPA) axis and is associated with secondary adrenal insufficiency (AI). In MM, GC's are usually administered in weekly high dose pulses. Due to long GC-free periods in such therapy, GC-induced AI is not usually considered to be a consequence of GC therapy in MM (Krasner, AS. JAMA, 1999. 282(7): p. 671-6). Here we report on the incidence of AI in MM patients treated at our center with pulse-dose GC.Methods: This is a retrospective cross-sectional study of patients with MM treated with GC-based regimens. Patients were required to have at least a random serum cortisol or a standard 250 mcg ACTH stimulation test result available in their medical record during dexamethasone-based chemotherapy. Patients were excluded if they were on dexamethasone more than 1 day a week, were lost to follow-up, had prior use of synthetic progestational agents such as megestrol or had been on oral glucocorticoids for any other medical indication. Diagnosis of AI was established by a frankly low AM serum cortisol level (<3 ug/dL) or an inadequate cortisol response to ACTH stimulation test (Salvatori, R. JAMA, 2005. 294(19): p. 2481-8).Results: A total of 45 patients were included in this study with median age of 62 (range, 49-89). Fifteen (33.3%) of patients were diagnosed with AI. The median random cortisol level in AI group was 2.3 ug/dL (range, 0.3-7.4 ug/dL) compared to 9.9 ug/dL (range, 1.0-21.2 ug/dL) in the non-AI group. The median time between the last dexamethasone dose and the serum cortisol assay was 5 days (range, 1-21). The median number of GC-based chemotherapy cycles taken before diagnosis of AI was 15 (range, 2-60). The median cumulative dexamethasone consumption was 1280 mg (range, 180-5220 mg). There was no correlation between developing AI and dose or duration of dexamethasone treatment. We observed clinical trend between cumulative doses of ≥1500 mg (P= 0.055) or use of clarithromycin (P=0.079) and developing AI, without reaching a statistically significant difference.Conclusion: The rate of AI was 33% among patients with MM on weekly pulse-dose dexamethasone. As such, patients should be periodically evaluated for this to enable early detection and proper management. DisclosuresBorrello:BMS: Honoraria, Research Funding; WindMIL Therapeutics: Equity Ownership, Patents & Royalties, Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau.

The contribution of undiagnosed adrenal insufficiency to euvolaemic hyponatraemia: results of a large prospective single-centre study.

The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia. Data on SIAD are mainly derived from retrospective studies, often with poor ascertainment of the minimum criteria for the correct diagnosis. Reliable data on the incidence of adrenal failure in SIAD are therefore unavailable. The aim of the study was to describe the aetiology of SIAD and in particular to define the prevalence of undiagnosed adrenal insufficiency. Prospective, single centre, noninterventional, observational study of patients admitted to Beaumont Hospital with euvolaemic hyponatraemia (plasma sodium≤130mmol/l) between January 1st and October 1st 2015. A total of 1323 admissions with hyponatraemia were prospectively evaluated; 576 had euvolaemic hyponatraemia, with 573 (43·4%) initially classified as SIAD. (i) Aetiology of SIAD, defined by diagnostic criteria; (ii) Incidence of adrenal insufficiency. Central nervous system diseases were the commonest cause of SIAD (n=148, 26%) followed by pulmonary diseases (n=111, 19%), malignancy (n=105, 18%) and drugs (n=47, 8%). A total of 22 patients (3·8%), initially diagnosed as SIAD, were reclassified as secondary adrenal insufficiency on the basis of cortisol measurements and clinical presentation; 9/22 cases had undiagnosed hypopituitarism; 13/22 patients had secondary adrenal insufficiency due to exogenous steroid administration. In a large, prospective and well-defined cohort of euvolaemic hyponatraemia, undiagnosed secondary adrenal insufficiency co-occurred in 3·8% of cases initially diagnosed as SIAD. Undiagnosed pituitary disease was responsible for 1·5% of cases presenting as euvolaemic hyponatraemia.

Assessment of Adrenal Function and Health-Related Quality of Life in Advanced Gastric Cancer Patients Who Received First-Line Chemotherapy

Objective: We performed this prospective study to identify both the incidence of adrenal insufficiency (AI) and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients who were treated with the S-1 plus cisplatin (SP) regimen as a first-line palliative chemotherapy. Methods: We assessed adverse events (AEs) observed in 52 patients who received the SP regimen for AGC between January 2009 and June 2010 using the Common Toxicity Criteria Adverse Events (CTCAE) version 3.0. Adrenal function was assessed at baseline and 12 weeks after chemotherapy using the low-dose adrenocorticotropic hormone stimulation test. HRQOL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 (EORTC-QLQ C30). Results: The incidence of AI was 30.8% (n = 16) and of AE observed 55% (n = 29) among 52 patients after 12 weeks of chemotherapy. Of 29 patients with AE, 34.4% (n = 10) were diagnosed with AI, and of 23 patients without AE, 26.1% (n = 6) were diagnosed with AI. Conclusion: The incidence of secondary AI in AGC patients was not rare and was not correlated with the presence of nonspecific AEs. Although patients diagnosed with AI did not show any related symptoms, they are at risk of potentially life-threatening consequences. Thus, the evaluation of AI could be suggested for patients who received chemotherapy.

Incidence of adrenal insufficiency and its relation to mortality in patients with septic shock

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

Incidence of Adrenal Insufficiency in Patients with Multiple Myeloma during High Dose Chemotherapy and Autologous Stem Cell Transplant

s / Biol Blood Marrow Transplant 21 (2015) S127eS146 S142 Conclusions: More than half of patients with int-risk AML in CR1 achieved sustained remissions using autoSCT. Of those who relapse, nearly 50% proceed to alloSCT and 31% are long-term disease-free survivors. Relapse-free survival has likely decreased in the most recent era due to changes in patient selection. AutoSCT remains a reasonable option for int-risk patients with AML in CR1, with outcomes rivaling those currently achieved with alternative donor alloSCT.