Etiology Of Adrenal Insufficiency Research Articles

Fertility and pregnancy in adrenal insufficiency.

Despite the availability of adrenal hormone replacement therapy, patients with adrenal insufficiency can be affected by reduced fertility and parity. Patients with well-managed adrenal insufficiency are expected to have uneventful pregnancies and favourable outcomes, but an increased risk of maternal and neonatal complications has been reported in some cases. Many physiological changes occur to the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy, often making a new diagnosis and management of adrenal insufficiency challenging. The management of adrenal insufficiency also needs to reflect the physiologic changes of pregnancy, often requiring increased doses of glucocorticoid as pregnancy progresses and in some circumstances mineralocorticoid replacement (in primary adrenal insufficiency patients only), especially in the third trimester. To date, there are no prospective data guiding management of adrenal insufficiency in pregnancy. In this review, we focus on the impact of adrenal insufficiency on fertility and parity based on the aetiology of adrenal insufficiency and provide a practical approach to the management of patients with adrenal insufficiency before and during pregnancy.

FRI195 Tuberculosis and Adrenal Glands: The Great Forgotten

Abstract Disclosure: I. Vina: None. R. Sánchez: None. I.C. Fernández: None. C. Vázquez: None. Background: Tuberculous adrenalitis is an extremely rare cause of Addison disease in developed countries. Since more than 80% of the primary adrenal insufficiency cases in the developed world are caused by autoimmune disease, tuberculous adrenalitis often go unnoticed. The aim of this case report is to remember that, even if it is not frequent, TB cannot be overlooked as a cause of longstanding primary adrenal insufficiency, even without evidence of pulmonary or extra glandular TB disease. Herein, we reported a case of bilateral tuberculous adrenalitis, wherein the patient initially presented with gastrointestinal symptoms, hyperpigmentation, bilateral adrenal masses, and no evidence of extra-adrenal tuberculosis. Case report: A 57-year-old woman from Madrid with no medical relevant history, was admitted to our hospital with 4 months of evolution of asthenia, weight loss (-8kg) and nausea that in recent days has been accompanied by fever and anorexia. He also refers progressive hyperpigmentation for the past 3 years. Denies recent travel abroad. On physical examination hypotension (80/53 mmHg) and generalized hyperpigmentation predominantly in the oral mucosa stand out. Blood test: Glu: 41 mg/dL, Na+: 122 mmol/L, K+: 4.8 mmol/L, ACTH: 922 pg/mL, Cortisol: 4.63 ug/dL, Anti-Hydroxylase Ab and Anti-Adrenal glands Ab: negative A computed tomography scan of the abdomen with intravenous contrast revealed bilaterally enlarged adrenal glands with small bilateral calcifications (12-18mm). TB QuantiFERON test: positive. She was initially treated with saline serum and intravenous hydrocortisone causing her symptoms to improve significantly in a few days and was subsequently discharged on hydrocortisone and fludrocortisone and proper treatment for TB Adrenalitis and follow-up in outpatient clinics. Conclusions: Although not frequent, infectious causes should always be kept in mind, such as the etiology of adrenal insufficiency in a patient with long-term compatible symptoms, even though it is a developed country, given world globalization, which makes infectious diseases highly transmissible between countries and continents. Presentation: Friday, June 16, 2023

"A morning cortisol is the most effective clinical predictor of short synacthen test outcome": A tertiary care centre experience.

Increasing referrals to Endocrinology with nonspecific symptoms of suspected adrenal insufficiency (AI)has increased use of the short-synacthen test (SST). Prevailing resource and safety concerns emphasise importance of patient selection criterion to optimise SST use. This study aimed to (1) document the adverse event profile of the SST (2) identify any pretest predictors of SST outcome. Retrospective data analysis of all patients referred for SST in Oxford from 2017 to 2021. Pretest clinical variables (age, sex, BMI, blood pressure and electrolytes), symptoms (fatigue, dizziness, weight loss) and pretest morning cortisol were included in the statistical model with the aim of identifying any variables that could predict SST outcome in Group 1 primary AI, Group 2 central AI and Group 3 glucocorticoid inducedAI. Symptoms and signs during and post SST were also noted with the aim of describing adverse effects to synacthen across a large cohort. A total 1480 SSTs (Males:38%, age 52 [39-66] years) were performed: 505 (34.1%) in Group 1, 838 (57%) in Group 2, and 137 (9.3%) in Group 3. Adverse-effects were recorded in 1.8% of tests, including one episode of anaphylaxis. Pretest morning-cortisol was the only predictor for an "SST pass" (whole cohort: B = 0.015, p < 0.001, Group 1: B = 0.018, p < .001; Group 2: B = 0.010, p < 0.012; Group 3: B = 0.018, p = <.001). A threshold of ≥343 nmol/l (receiver-operating characteristic[ROC] area under the curve [AUC] = 0.725, 95% confidence interval [CI] 0.675-0.775, p < 0.001) for the whole cohort, ≥300 nmol/L (ROC AUC = 0.763, 95%CI 0.675 to 0.850, p < 0.001) for Group 1, ≥340 nmol/L (ROC AUC = 0.688, 95%CI 0.615 to 0.761, p < 0.001) for Group2, and ≥376 nmol/L [baseline cortisol] (ROC AUC = 0.783, 95%CI 0.708 to 0.859, p < 0.001) for Group 3, predicted an 'SST pass' with 100% specificity. Adverse effects to synacthen are rare. Pretest morning cortisol is a reliable predictor for SST outcome and is a helpful tool to rationalise use of the SST. Predictive morning-cortisol thresholds vary according to the aetiology of AI.

RF09 | PSAT83 Diagnosis of Adrenal Insufficiency Based on Peak Stimulated Cortisol Levels Between 14 and 18 mcg/dL on High Dose Cosyntropin Stimulation Testing

Abstract Background Traditionally, stimulated serum cortisol &amp;lt; 18 mcg/dL at 30 or 60 minutes has been used as the cutoff for diagnosis of adrenal insufficiency (AI) during high dose cosyntropin stimulation testing (CST). Recent studies suggest that a cutoff of 14-15 mcg/dL is more accurate when using more specific monoclonal immunoassays (IAs). In February 2017, our institution switched from a polyclonal IA to a monoclonal IA. Despite this change, providers were diagnosing AI based on the 18 mcg/dL cutoff. Long term glucocorticoid use has several unwanted pleiotropic effects such as impaired glucose tolerance or diabetes mellitus (DM), hypertension (HTN), and increased risk of infection. Our study aims to evaluate patients with peak stimulated cortisol levels between 14-18 mcg/dL diagnosed with AI and placed on steroids. Methods We retrospectively reviewed charts of patients with peak cortisol levels 14-18 mcg/dL at 30 or 60 minutes on high dose CST with 250 mcg cosyntropin between February 2017 and August 2021. Cortisol levels were assessed using the monoclonal IA Roche Elecsys Cortisol II. Data regarding type and etiology of AI as well as patient demographics, comorbidities, steroid regimen, and follow up cortisol testing was collected. Worsening HTN and DM were defined as increase in blood pressure and HgbA1c respectively and/or intensification of medications between baseline at time of CST and last follow up while on steroids. Results 41 patients met inclusion criteria. 29 (71%) patients were female and mean age at CST was 52 years (range 21-86). Most patients were diagnosed with secondary (71%) or partial secondary (19%) AI by provider. Most common etiologies were pituitary disease (45%), chronic steroid use (24%), and unilateral adrenalectomy (19%). Mean follow up was 23 months (range 0.5-57). 33 (80%) patients were started or continued on glucocorticoid replacement. Remaining patients who were never started on steroids had a peak cortisol ≥ 15.6 mcg/dL. 21/33 (64%) of patients started on steroids had repeat adrenal function testing a mean of 18 months (range 2-42) after the initial CST. Based on testing or clinical judgement, 19/33 (58%) were taken off steroids. In patients treated with steroids, 64% developed weight gain, 42% worsening HTN, and 6% worsening DM. Additionally, 48% developed an infection, 24% insomnia, and 15% psychiatric illness. Conclusions The majority of patients with peak stimulated cortisol between 14-18 mcg/dL on high dose CST had secondary AI. Over 50% of patients started on steroids were later able to stop. Steroid-related complications were observed, but this may not differ significantly from the general population. This study underscores the importance of interpreting CST results in the context of the cortisol assay used and evaluating patients with secondary AI for recovery of the hypothalamic-pituitary-adrenal axis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:06 p.m. - 1:11 p.m.

What factors have impact on glucocorticoid replacement in adrenal insufficiency: a real-life study

PurposeThe impact of patient’s characteristics on glucocorticoid (GC) replacement therapy in adrenal insufficiency (AI) is poorly evaluated. Aims of this study were to assess the influence of sex and body weight on GC dosing and to describe the choice of GC in AI of different etiologies.MethodsWe retrospectively evaluated hydrocortisone (HC) equivalent total daily dose (HC-TDD) and per-kg-daily dose (HC-KDD) in 203 patients (104 primary AI [pAI], 99 secondary AI [sAI]) followed up for ≥ 12 months. They were treated with HC, modified-release HC (MRHC) or cortisone acetate (CA) and fludrocortisone acetate (FCA) in pAI.ResultsAt baseline, CA was preferred both in pAI and sAI; at last visit, MRHC was most used in pAI (49%) and CA in sAI (73.7%). Comparing the last visit with baseline, in pAI, HC-TDD and HC-KDD were significantly lower (p = 0.04 and p = 0.006, respectively), while FCA doses increased during follow-up (p = 0.02). The reduction of HC-TDD and HC-KDD was particularly relevant for pAI women (p = 0.04 and p = 0.002, respectively). In sAI patients, no change of HC-KDD and HC-TDD was observed, and we found a correlation between weight and HC-TDD in males (r 0.35, p = 0.02).ConclusionsOur real-life study demonstrated the influence of etiology of AI on the type of GC used, a weight-based tailoring in sAI, a likely overdosage of GC treatment in pAI women at the start of treatment and the possibility to successfully increase FCA avoiding GC over-treatment. These observations could inform the usual clinical practice.

OR25-04 Over 14% of Inpatients with Euvolemic Hyponatremia Have Undiagnosed Adrenal Insufficiency

Background- The commonest cause of euvolemic hyponatremia (EvHNa) is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The diagnosis of SIADH requires the exclusion of secondary adrenal insufficiency (AI) and untreated hypothyroidism. Studies have suggested about 4% of unselected patients presenting to the emergency room with EvHNa have undiagnosed SAI.1 Among patients admitted to specialized endocrine units this prevalence maybe as high as 20%.2Objective- To study the prevalence of undiagnosed AI among inpatients with EvHNa admitted to general medical wards. Methods- This was a prospective, single centre observational study conducted among inpatients with EvHNa. EvHNa was defined as patients with a serum sodium (Na) <135 mEq/L, with no clinical evidence of dehydration or fluid excess, and a urine spot Na >30mmol/L. In addition patients with recent vomiting, renal failure, recent diuretic use, uncontrolled hyperglycemia and patients with history of use of oral or parenteral steroids in the last 6 months were excluded. Adrenal functions were assessed by a modified porcine ACTH stimulation test which has been described recently by Nair et al. A cut off cortisol value of <18mg/dl after 60 minutes of ACTH injection was used to diagnose AI.3Results- One hundred and forty one (141) patients were included after informed consent and all underwent a modified ACTH stimulation test. They had a mean age of 58 years and 52.3% (n=74) were males. Modified ACTH stimulation testing suggested 20/141 (14.2%) had undiagnosed AI. The mean age among those with AI was 55.2 years. In only 25% (5/20) AI was suspected based on clinical presentation by the treating physician. Despite excluding patients with documented steroid use, the commonest cause of AI (9/20) was secondary AI due to exogenous steroid use including high potency inhaled steroids (5/9) and the use of undocumented steroids or steroid containing medicaments by alternative practitioners (4/9). Hypopituitarism was diagnosed as the cause of AI in 5 patients, which included unsuspected Sheehan’s syndrome in post menopausal women (3/5), non functioning pituitary adenoma (1/5) and lymphocytic hypophysitis (1/5). Despite primary AI not commonly presenting as EvHNa, 3/20 patients had primary AI and in the remaining 3 patients the aetiology of AI remained unclear. Conclusions- Undiagnosed AI is much more common in our country among inpatients presenting with EvHNa to medical units. This increase is primarily driven by inhaled and undocumented exogenous steroid use and undiagnosed Sheehan’s syndrome. An assessment of the hypothalamic-pituitary-adrenal axis is mandatory before making a diagnosis of SIADH. References -(1) Diederich et al. Eur J Endocrinol 2003; 148: 609-617. (2) Cuesta et al. Clin Endocrinol (Oxf) 2016; 85: 836-844. (3) Nair A et al. Eur J Endocrinol. 2019 Oct 1. pii: EJE-19-0558.R2.

MON-365 Immune Checkpoint Inhibitors: Endocrinopathies and Severe Electrolyte Abnormalities

Background: Immune Checkpoint Inhibitors (ICPi) are promising therapies for advanced malignancies, including melanoma, lung cancer, and renal cancer. However, their use can induce mechanism-based toxicities called as immune-related adverse events (irAE) that can potentially affect various organ tissues, including the endocrine system. We present the case of a patient who developed secondary adrenal insufficiency & thyrotoxicosis within 9 weeks & severe electrolyte abnormalities within 13 weeks of starting therapy with ICPi. Case: A 56-year old woman with metastatic small cell lung cancer received 6 cycles of chemotherapy with carboplatin+etoposide, followed by whole brain radiation for multiple brain metastases. Subsequently, second-line therapy with ICPi was initiated, with a plan to administer four doses of combined ipilimumab (anti-CTLA-4 antibody) + nivolumab (anti-PD-1 antibody), followed by nivolumab alone every 2 weeks. Nine weeks post-initiation of ICPi therapy, she was hospitalized with symptoms of nausea & vomiting, she was hypotensive & an endocrine work-up confirmed adrenal insufficiency (AI). Possibility of immune-mediated AI was considered & she was started on hydrocortisone 30 mg/day & fludrocortisone 0.1 mg daily. However, subsequent evaluation confirmed the etiology of AI as secondary. Work-up during this hospitalization revealed a low TSH & low FT4 (central hypothyroidism vs. euthyroid sick syndrome). She did not have any symptoms or signs suggestive of hypophysitis & MRI brain did not reveal any pituitary pathology. Two months later, she was readmitted with confusion. Her thyroid function tests, this time, revealed severe thyrotoxicosis (with no increased TSI or anti-TPO antibodies); possibility of primary hyperthyroidism vs. destructive thyroiditis was considered, & pending thyroid scan, she was treated with methimazole and propranolol. She returned to the hospital in a week for nausea and vomiting; she had severe hypokalemia, hypocalcemia & hypomagnesemia requiring aggressive IV replacements. She required continued oral electrolyte replacements. At that point, nivolumab was discontinued. She had an endocrine clinic visit 3 weeks post-last hospitalization; she was asymptomatic, euadrenal and euthyroid, & had normal electrolytes. Dose of fludrocortisone was reduced & methimazole was discontinued (with decision to review post-thyroid scan). Conclusion: Novel ICPi can cause immune imbalance & irAE involving the endocrine system. Careful monitoring for & treatment of endocrinopathies is required during ICPi therapy. Nivolumab may likely induce severe electrolyte disturbances as well.

Patients with adrenal insufficiency hate their medication: concerns and stronger beliefs about the necessity of hydrocortisone intake are associated with more negative illness perceptions.

Patients with adrenal insufficiency (AI) require daily and life-long hydrocortisone substitution with risks of under- and overreplacement, the necessity to adjust the dose in stressful situations, and a lack of clinical and biochemical parameters to assess optimal dosing. The spectrum of medication beliefs in patients with AI is currently unknown. The objective of the study was to examine the possible association between illness perceptions and medication beliefs about hydrocortisone (HC) in patients with AI. This was a cross-sectional evaluation of illness perceptions and medication beliefs in 107 patients with primary AI (n = 49), secondary AI after the treatment of Cushing's syndrome (n = 29), or treatment of nonfunctioning pituitary adenoma (n = 29). The Illness Perception Questionnaire-Revised and the Beliefs about Medicines Questionnaire were used for the assessment. Stronger beliefs about the necessity of HC and stronger concerns about the adverse effects of HC were associated with attribution of more symptoms to AI, to the perception of AI being more cyclical, to the perception of more negative consequences of AI, and to the presence of stronger emotional representations (all P < .05). Furthermore, stronger beliefs about the necessity of HC intake were associated with feelings of less personal control over AI (P < .05). Stronger concerns about the adverse effects of HC were associated with lower perceived treatment control and lower illness coherence (both P < .05). In addition, patients with Cushing's syndrome reported stronger beliefs regarding the necessity of taking HC, compared with patients with Addison's disease (P = .039) or nonfunctioning pituitary adenoma (P < .001). Specific beliefs about the necessity of hydrocortisone replacement and concerns about its adverse effects were strongly associated with more negative illness perceptions. These specific beliefs differed, depending on the etiology of AI. These results need to be taken into account in the treatment of patients with AI and may serve to enable the development of psychosocial education/self-management programs aiming at improving quality of life.

Insuficiencia suprarrenal iatrogénica

Adrenal insufficiency is a disease caused by the deficit in production and/or secretion of glucocorticoids. The aetiology of Adrenal Insufficiency (AI) can be classified into primary and secondary, and it should be taken that the incidence and prevalence of the secondary formare much higher than the primary form.One of the main causes of AI is due to prescription of exogenous steroids. It can be taken orally, which is more common, or topically. The latter is more uncommon but it should not be a a reason for ruling it out. We have to be aware when giving a topical treatment and to monitor the frequency our patients ask for the prescription.