Adrenal Insufficiency

Adrenal Axis Insufficiency After Endoscopic Transsphenoidal Resection of Pituitary Adenomas.

PD23-11 IMMUNE CHECKPOINT INHIBITORS FOR KIDNEY AND BLADDER CANCER: ADRENOTOXIC CONSEQUENCES

Chronic fatigue syndrome and Addison's disease

BackgroundAntiphospholipid syndrome causes systemic arterial and venous thromboses due to the presence of antiphospholipid antibodies. Adrenal insufficiency is a rare complication of antiphospholipid syndrome that may result in fatal outcomes if left untreated. Therefore, we report adrenal insufficiency as a rare complication of bilateral adrenal infarction associated with antiphospholipid syndrome and trauma surgery.Case presentationA 64-year-old male patient underwent surgery for a left traumatic hemothorax. He concurrently had antiphospholipid syndrome and was receiving warfarin. Postoperatively, the patient complained of severe lumbar back pain despite resuming anticoagulation therapy, and he experienced paralytic ileus and shock. Abdominal contrast-enhanced computed tomography revealed adrenal swelling and increased surrounding retroperitoneal adipose tissue density. Diffusion-weighted abdominal magnetic resonance imaging showed high-intensity areas in the bilateral adrenal glands. Cortisol and adrenocorticotropic hormone levels were 3.30 μg/dL and 185.1 pg/dL, respectively. Subsequently, the patient was diagnosed with bilateral adrenal infarction and acute adrenal insufficiency, and hydrocortisone was immediately administered. Adrenal insufficiency improved gradually, and the patient was discharged after initiating steroid replacement therapy.ConclusionsThe timing of postoperative anticoagulant therapy initiation remains controversial. Therefore, adrenal insufficiency due to adrenal infarction should be monitored while anticoagulant therapy is discontinued in patients with antiphospholipid syndrome.

We report a patient with combined pulmonary arterial hypertension (PAH) and autoimmune polyglandular syndrome (APS) type 2. A 41 y/o woman with hypothyroidism presented for right heart (RHC) in the work up of PAH. Pt had a medical history of PAH diagnosed by transthoracic echocardiogram (TTE) and hypothyroidism. She reported symptoms of fatigue, shortness of breath with increased pigmentation of her skin progressive for several years. Preadmission lab found hyponatremia of 126 and potassium of 6.6. She was admitted and treated with IV insulin with D50, kayexalate, IV fluids. A random 11 AM cortisol was 0.57 mcg/dl N: AM: 6. 0–30. 0 mcg/dl; PM: 3. 0–16. 0 mcg/dl. Acosyntropin test was ordered. Pt failed the stimulation test (baseline 0.39, 30 min 0.49, 60 min 0.50, with an ACTH at baseline of 1423 pg/ml N: 7.2-63.3). Pt was started on hydrocortisone 20 mg AM/10 mg PM with fludrocortisone 0.1mg. On follow up at 2 weeks, her energy, mood, appetite and breathing tolerance had improved. Follow up RHC in 4 weeks found normalization of right heart pressures. APS is a collection of autoimmune diseases. Type I APS, caused by a defect in the autoimmune regulator (AIRE) gene, is diagnosed with two of three conditions, chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal cortical insufficiency. Type II APS (formally "Schmidt's Syndrome"), associated with HLA haplotypes DR3 (DQB*0201) and DR4 (DQB1*0302), is diagnosed with chronic autoimmune adrenal insufficiency with either Type 1 DM or chronic autoimmune thyroid disease (commonly Hashimotos but can be Graves). It typically presents later in life compared to APS I, age 30-40s. The association between PAH is rare but has been noted in several case studies. It has been associated with APS I in Korniszewski et al. and Bhansali et al. For APS II, the first association was reported by Barrou et al. of a patient with hypothyroidism, hypogonadism, and adrenal insufficiency who later developed PAH. Two cases reported by García-Hernández et al found PAH with positive adrenal antibodies without adrenal insufficiency. In 2009 Walid R. et al. reported a case of severe adrenal insufficiency (hypotension, hypokalemia) with PAH. She improved with steroids, but her PAH was present on TTE four years after treatment started. Pt in that case declined RHC. The patient in this case study proceeded with a RHC which did show normalization of right heart pressures, the first reported case to document normalization of PAH with replacement steroid treatment. Presentation: No date and time listed

Disclosure: V. Rao: None. J. Turella: None. A.D. Rao: None.Introduction: Secondary/tertiary adrenal insufficiency (AI) is a relatively rare condition that affects approximately 300 individuals per million worldwide. Although treatment with steroid replacement is well established, complications of treatment, especially with regards to bone health, are less clear. Men are an under diagnosed and under treated population with regards to osteoporosis. Few studies have examined bone health in men with AI. Methods: We utilized a retrospective case control study design to compare osteoporosis and fracture risk in men with and without secondary/tertiary AI who were seen at Temple University Hospital between January 1, 2014-December 31, 2023. We included men age >=50 with an ICD-10 diagnosis of secondary or tertiary AI who were receiving steroid replacement therapy as cases. Controls were derived from the same population and included men who were incorrectly coded as AI, i.e. men age >=50 without laboratory evidence of AI and without steroid replacement or long-term steroid treatment. We excluded individuals >89 and with an ICD-10 diagnosis of any cancer, primary adrenal insufficiency, or other disorders established to have high risk of secondary osteoporosis. Comparisons between groups were performed with Fisher’s exact test, unpaired t-test, and linear regression. Results: In total, our study included 28 men with AI (46.4% secondary to steroids) and 33 men without AI. We found that 39.3% of men with AI had an osteoporotic fracture, which was significantly higher than men without AI (p=0.0185). Using body surface area to determine the appropriate hydrocortisone replacement dose (BSA*14.7), 39.3% of men received higher doses than recommended. Although those who received excess steroids had a higher osteoporotic fracture rate, it was not significant (p=0.0527). Further, 46.4% of men with AI had evidence of osteoporosis, of which 30.8% were prescribed an anti-resorptive or anabolic agent, 61.5% calcium, and 100% vitamin D. DEXA scans were ordered in less than half of men with AI. Conclusions: These data indicate that the high osteoporotic fracture rate in men with AI, who do not have confounding secondary risk factors, is likely related to over treatment. They also highlight the need for preemptive screening and possibly treatment to prevent fractures.Presentation: Sunday, July 13, 2025

Adrenal insufficiency causes Addison's disease, a chronic endocrine disease that needs to be managed by hormone replacement therapy for the rest of one's life. Alternative and complementary methods for reducing symptoms and improving patient quality of life have been studied recently. Using secondary plant metabolites, bioactive substances are generated by plants that can alter a variety of physiological processes. Alkaloids, flavonoids, terpenoids, and phenolic compounds are examples of secondary plant metabolites that display a variety of pharmacological activities, including immunomodulatory, antioxidant, and anti-inflammatory properties. The various symptoms of Addison's disease, which include immunological dysfunction, persistent fatigue, and muscle weakness, may be better managed with these qualities. Multiple pathways contribute to the therapeutic potential of secondary plant metabolites in the management of Addison's disease. Flavonoids, which are anti-inflammatory substances, can help reduce systemic inflammation, a common issue in patients with Addison's disease. By reducing oxidative stress, antioxidants such as phenolic acids can protect adrenal tissue from further damage. Moreover, considering that Addison's patients have reduced cortisol production, adaptogenic herbs containing terpenoids help to support the body's stress response. Certain plant extracts, such as those from Glycyrrhiza glabra (Licorice) and Withania somnifera (Ashwagandha), have been shown in studies to have the ability to modify adrenal function and promote hormone synthesis. For example, glycyrrhizin, found in Glycyrrhiza glabra, can act as a corticosteroid substitute and help alleviate specific symptoms of adrenal insufficiency. Withania somnifera is recognized for its adaptogenic properties, which have been demonstrated to enhance the body's ability to withstand stress and may benefit the overall health of patients with Addison's disease. Including secondary plant metabolites in the treatment of Addison's disease provides an alternative strategy that may reduce reliance on synthetic corticosteroids and minimize related adverse effects. To determine the effectiveness, ideal doses, and safety profiles of these substances in the context of Addison's disease, further clinical trials are needed. This Chapter advocates for integrative approaches that utilize the medicinal capabilities of substances produced from plants by highlighting the potential of secondary plant metabolites as an adjunct therapy in the management of Addison's disease. Patients with this challenging endocrine condition may experience improved patient outcomes and a higher quality of life by leveraging secondary plant metabolism. An overview of the possible management of Addison's disease by secondary plant metabolites is given in this abstract, with a focus on the pharmacological characteristics of these compounds and the need for additional study to confirm their therapeutic utility.

Background. The insulin tolerance test (ITT) is the “gold standard” of the secondary adrenal insufficiency (SAI) diagnosis but it is rather difficult to carry out, has some contraindications and requires patient’s hospitalization. The availability of a reliable screening method could reduce the necessity of using ITT.Aim: to compare different methods of screening with ITT and to work out an optimal diagnostic algorithm of SAI.Methods. 40 patients (20 women) after craniospinal (CSI) irradiation in a doze 35 Gy were examined. The average age at the time of the observation was 19,5±3 years, at the time of treatment 12,5±3,5 years. Patient’s blood samples were collected for basal cortisol (BC), DHEA-S. ITT was performed for all patients, glucagon stimulation test (GST) was for 27 persons. Patients were divided into groups: SAI and without SAI (W-SAI) after ITT. ROC- analysis was conducted to identify the thresholds for BC, DHEA-S and GST. Cut-off points for BC and DHEA-S levels corresponding to 100% sensitivity (Se) for SAI group and 100% specificity (Sp) for W-SAI patients were estimated to select a group of patients which do not require stimulative tests. Linear regression was used to construct a predictive model (PM) of SAI occurrence after CSI.Results. 22/40 subjects failed ITT, 13/27 passed GST. 3 patients failed ITT but passed GST. Their level of neutrophils and monocytes was higher than the other patients'. SAI-patients had BC and DHEA-S lower than W-SAI (321±102 vs 516± 183; p=0,003 and 2,6±1,4 vs 5,1±2,1, p=0,003). ROC-analysis showed area under curve (AUC) for GST=0,91 with optimal cut-off for cortisol=489 which corresponds to 100% Sp and 62% Se. AUC was 0,83 for BC and 0,84 for DHEA-S.In 70% patients' BC was in a “grey zone” (32% of them passed ITT), 8% had BC lower than 200 (which corresponds to 100% Se) and 22% more than 499 (100% Sp). 50% of patients were in a “grey zone” for DHEA-S (50% of them had SAI), 18% had DHEA-S level below 2,0 and 32% above 4,7. A combination of BC and DHEA-S in the PM of SAI (0,592+0,001*BC+0,11*DHEA-S) had AUC 94%. This PM didn’t give the prognosis of SAI for 32% (CI: 18-49%) of patients. The addition of maximal cortisol (MC) level during GST (0,53+0,01*BC+0,066*DHEA-S+0,001*MC) increased AUC to 99% and didn’t allow to predict SAI in 8% (3,2% - 24,9%) of patients only.Conclusions. When the screening methods were used separately, they showed comparable accuracy and it was not high. The PM may be used as optimal screening method for SAI and may allow to use ITT more rarely. But further studies are required to validate the PM proposed in this study.

Primary adrenal insufficiency (PAI) is a rare pathology with a prevalence of 100 to 140 cases per one million. X-linked adrenoleukodystrophy (X-ALD) and X-linked congenital adrenal hypoplasia (X-CAH) are the leading pathologies among boys (after congenital cortical dysfunction adrenal glands) and account for 3.1% and 2.0% of all PAI, respectively. Establishing the PAI etiology is necessary to predict the course of the disease and adhere to special protocols for examining patients. The purpose of this research was to compare the PAI course in diseases with an X-linked type of inheritance. Materials and methods used: a single-center, one-stage observational comparative retrospective study was conducted in 25 male patients with genetically confirmed diagnoses of X-ALD, X-CAH and who had PAI as a component of the disease. The study was conducted at the Pediatric Endocrinology Institute with the Endocrinology Research Centre of the Ministry of Healthcare of Russia (Moscow, Russia) in 2019-2022 as well as based on the patients’ medical records that have been forwarded for a genetic search for the causes of adrenal insufficiency under the “Alfa-Endo” Charity Program for children with endocrine diseases in the same period of time. Results: X-ALD was detected in 11/25 (44%) patients, median age of manifestation was 6.2 [4.5; 7.2] y/o and 2 y/o was the earliest. A single patient with X-ALD was found to have TARTs (testicular adrenal rest tumors). X-CAH was diagnosed in the remaining 14/25 (56%) patients, median age of manifestation was 1.9 [0.04; 3.9] y/o, p=0.015. The oldest age of manifestation was 14 y/o. A single patient was found to have hypogonadotropic hypogonadism (HH) and another one had bilateral cryptorchidism. There were no statistically significant differences in symptoms, adrenocorticotropic hormone (ACTH), cortisol levels during the manifestation of PAI and doses of replacement therapy (p=0.756 for ACTH, p=0.591 for cortisol, p=0.825 for hydrocortisone and p=0.148 for fludrocortisone). Conclusion: it is necessary to exclude X-ALD and X-CAH when diagnosing PAI in boys regardless of the age of the disease manifestation. It is highly recommended to conduct a genetic study of a panel of genes responsible for the development of PAI in order to establish the PAI etiology, and regardless of the established PAI etiology it is necessary to perform an ultrasonic study of the testicles with the purpose of excluding the space-occupying formations. It is necessary to evaluate ACTH levels in patients with testicular masses for timely diagnosis of PAI and optimal treatment.

Autoimmune Addison's disease and premature ovarian failure are characterized by the presence of organ-specific autoantibodies. The main adrenal and gonadal autoantigens have been identified and cloned, and the relationship between the autoantibodies detected by immunofluorescence techniques and those detected by the new assays using recombinant autoantigens needed to be investigated. We studied 165 patients with Addison's disease: 143 patients had different forms of autoimmune Addison's disease (13 with idiopathic premature ovarian failure) and 22 had nonautoimmune Addison's disease. Adrenal-cortex autoantibodies and steroid-producing cell autoantibodies were measured by the immunofluorescence techniques. Autoantibodies to steroid 21-hydroxylase, 17alpha-hydroxylase, and P450 side chain cleavage enzyme were measured by immunoprecipitation assay using 35S-labeled recombinant proteins. Adrenal-cortex autoantibodies and autoantibodies to 21-hydroxylase were found in 81% of the patients with autoimmune Addison's disease. None of the patients with nonautoimmune Addison's disease had adrenal-cortex autoantibodies or autoantibodies to 21-hydroxylase. A high association between these two markers in patients with different forms of autoimmune Addison's disease and in those with short- or long-standing disease was found. Steroid-producing cells autoantibodies were found in 26% of the patients with autoimmune Addison's disease, and autoantibodies to 17alpha-hydroxylase and/or P450 side chain cleavage enzyme in 36% of the patients. Steroid-producing cells autoantibodies were found in 11/13 (85%) of patients with idiopathic premature ovarian failure associated with autoimmune Addison's disease, and autoantibodies to 17alpha-hydroxylase and/or P450 side chain cleavage were found 12/13 (92%) of patients; the only case negative for all these three markers suffered from Turner's syndrome. Provided that a high standard of immunofluorescence technique is maintained, measurement of adrenal cortex autoantibodies or steroid-producing cells autoantibodies by either immunofluorescence or immunoprecipitation assay is essentially equivalent.

Adrenal suppression is a potential side effect of glucocorticoid (GC) therapy. Timely diagnosis and management can significantly reduce morbidity and mortality from adrenal crisis. There is a need for pediatric-specific guidelines to provide non-endocrinologist GC prescribers with diagnostic and management tools to keep children and youth safe. To assess the adrenal suppression screening and management practices amongst surveyed pediatric endocrinology members of the Pediatric Endocrinology Society (PES), to support the need for national pediatric adrenal suppression guidelines. A survey (19 questions, implied consent model), developed by members of the PES Adrenal Special Interest Group and the PES Drugs and Therapeutics Committee, was distributed to PES members. Among 154 survey respondents, 90.9% were pediatric endocrinology attendings, predominantly working in the US (91.6%) in an academic setting (86.4%). A majority (70.1%) have seen adrenal crisis due to adrenal suppression. Only 48.1% participants follow any pediatric adrenal suppression guidelines (within which 32.5% used a local guideline); 27.9% use adult guidelines. While 52.6% reported that adrenal suppression cases are managed by both endocrinologists and non-endocrinologists, only 38.3% of respondents provide resources to non-endocrinologists. Most screen for adrenal suppression with early morning cortisol (88.3%) or a low-dose ACTH stimulation test (55.8%). Notably, 8.4% of respondents believe that use of inhaled corticosteroids is not associated with a risk of adrenal suppression. Nearly all respondents (99.4%) agree that an official PES guideline on adrenal suppression would reduce morbidity and mortality by raising awareness and standardizing management. Adrenal crisis due to adrenal suppression remains a preventable yet persistent threat. Screening and management practices vary widely among North American pediatric endocrinologists, underscoring the need for pediatric-specific guidelines. Establishing such guidelines would fill a critical care gap and promote a standardized approach to diagnosis and management across clinicians.

Hypothalamic Pituitary Adrenal Suppression

Background: Topical corticosteroids are a mainstay of therapy for inflammatory skin disorders. Hypothalamic–pituitary–adrenal (HPA) axis suppression is a potential systemic risk of topical steroid use. Our aim was to review available data on the risk of HPA axis suppression associated with long-term topical steroid use and to distinguish between pathologic and physiologic adrenal suppression.Methods: We performed a PubMed search for literature that evaluated the risk of HPA axis suppression associated with topical steroid use.Results: Fifteen of sixteen clinical trials reviewed did not report any pathologic adrenal suppression. In the single clinical trial that reported pathologic adrenal suppression, the patients used twice the maximum recommended amount of clobetasol propionate continuously for as long as 18 months. Physiologic adrenal suppression was seen as early as 1–2 weeks after treatment with class I–IV topical corticosteroids. In about half of these patients, cortisol levels spontaneously returned to normal within a few weeks, despite continuous therapy.Conclusion: Even when adrenal suppression occurs, topical corticosteroids are unlikely to be associated with clinical signs or symptoms of HPA axis suppression and are extremely safe as long as they are used within the current safety guidelines.

ContextThe COVID-19 pandemic has impacted healthcare environment.ObjectiveTo determine the impact of the pandemic on self-reported outcomes in patients with adrenal insufficiency (AI).Design and settingProspective longitudinal survey study at 2 tertiary centers.ParticipantsPatients with AI.InterventionPatient-centered questionnaire.Main outcome measuresDepression Anxiety Stress Scales-21, Short Form-36, and AI self-management.ResultsOf 342 patients, 157 (46%) had primary AI, 109 (32%) had secondary AI, and 76 (22%) had glucocorticoid-induced AI. When compared to prepandemic, daily glucocorticoid dose and number of adrenal crises did not change. However, patients reported a higher financial impact from AI (34% vs 23%, P = 0.006) and difficulty accessing medical care (31% vs 7%, P < 0.0001) during the pandemic. A third of patients reported difficulty managing AI during the pandemic. After adjusting for duration and subtypes of AI, younger patients [odds ratio (OR) 2.3, CI 95% 1.3-4.1], women (OR 3.7, CI 95% 1.9-7.1), poor healthcare access(OR 4.2, CI 95% 2.3-7.7), lack of good insurance support (OR 2.8, CI 95% 1.3-5.9), and those with a higher financial impact (OR 2.3, CI 95% 1.3-4.3) reported greater difficulties managing AI. Patients were more likely to report a higher anxiety score (≥8) if they found managing AI challenging during the pandemic (OR 3.0, CI 95% 1.3-6.9), and had lower Physical Component Summary (OR 4.9, CI 95% 2.2-11.0) and Mental Component Summary (OR 4.1, CI 95% 1.8-9.5) scores prior to the pandemic.ConclusionsA third of patients with AI reported difficulties with management of AI during the pandemic, particularly in younger patients, women, and those with poor healthcare access.

Although two studies have shown that Addison's disease (AD) is still a potentially lethal condition for cardiovascular, malignant, and infectious diseases, a recent retrospective study showed a normal overall mortality rate. Differently from secondary hypoadrenalism, scanty data exist on the role of conventional glucocorticoid replacement on metabolic and cardiovascular outcome in AD. In 38 AD under conventional glucocorticoid replacement (hydrocortisone 30 mg/day or cortisone 37.5 mg/day) ACTH, plasma renin activity (PRA), DHEAS, fasting glucose and insulin, 2-h glucose after oral glucose tolerance test, serum lipids, 24-h blood pressure and intima-media thickness (IMT) were evaluated and compared with 38 age-, sex- and body mass index (BMI)-matched controls (CS). AD had ACTH and PRA higher and DHEAS lower (p<0.0005) than CS. Mean waist was higher (p<0.05) in AD than in CS. Although no differences were found for mean gluco-lipids levels, a higher percentage of AD compared to CS were IGT (8 vs 0%), hypercholesterolemic (18 vs 8%), and hypertriglyceridemic (18 vs 8%); none of the AD and CS showed either HDL<40 mg/dl or LDL>190 mg/dl. At the multiple regression analysis, in both AD and CS, BMI was the best predictor of 2-h glucose and age of total and LDL cholesterol; in AD, no significant correlation was found between the above mentioned metabolic parameters and either hormone levels or disease duration. In both AD and CS 24-h blood pressure and IMT were normal. Our study shows a higher prevalence of central adiposity, impaired glucose tolerance and dyslipidemia in AD patients.