Adrenal Crisis Research Articles

Primary adrenal insufficiency in adults: When to suspect, how to diagnose and manage.

Primary adrenal insufficiency is rare but serious; it puts patients at risk of acute decompensation and adrenal crisis due to insufficient cortisol and aldosterone production. Further, its diagnosis is often delayed, or it is mistaken for secondary adrenal insufficiency, which can have life-threatening consequences. Early recognition and appropriate treatment can greatly improve patient outcomes and quality of life.

Addisonian Pigmentation – The Great Mimicker – A Review

Abstract Skin colour usually depends upon melanin, haemoglobin, and carotenoids. Pigmentary disorders indicate an increased amount of melanin, leading to a darker colour of the skin, called hypermelanosis. Addison’s disease is a rare endocrinal disorder with severe oral and systemic manifestations. Any form of diffuse skin hyper-pigmentation which is more pronounced on sun-exposed areas mimics Addison’s disease and is called Addisonian pigmentation. Pigmentation often precedes other manifestations by months to years and hence can lead to early diagnosis and can prevent life-threatening adrenal crisis. The most common cause of adrenal insufficiency in developing countries is tuberculosis. A similar pattern of pigmentation has been reported in Cushing’s syndrome, ectopic ACTH-producing tumours, vitamin B12 deficiency, and thyrotoxicosis. Addisonian pigmentation can be a manifestation of multiple systemic diseases; hence, an inter-disciplinary approach is needed with extensive clinical and laboratory evaluation. It is not merely a cosmetic concern. Not much data are available in the literature regarding this entity. This brief review serves as an important source for clinicians to stay up-to-date regarding the history, clinical presentation, differential diagnosis, and management of this entity.

Does secondary adrenal insufficiency require supplementation prior to oral surgery procedures? An update

Adrenal insufficiency (AI) is linked to a rare medical emergency, acute AI, or adrenal crisis (AC), which can occur following stressful events, like infection or surgery. A commonly overlooked form of secondary AI occurs when individuals take exogenous glucocorticoids for extended periods of time, resulting in hypoactivity of the adrenal glands. Many patients take glucocorticoids to treat conditions like asthma, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, or dermatitis. These patients may be prone to secondary AI, which may go undetected, increasing their risk of facing a medical emergency. Our aim is to review the literature on current guidelines for corticosteroid supplementation for patients at risk of AC; and assess the risk of developing AI in patients taking exogenous glucocorticoids and whether the current supplementation guidelines require modifications. Current recommendations from the Addison’s disease self-help group and Miller suggest steroid supplementation for dental procedures only for patients with primary AI. However, they do not recommend supplementation for patients with secondary or tertiary adrenal insufficiency. The drawbacks of short-term supplementation of glucocorticoids in patients at risk of secondary AI, for stressful dental procedures is negligible. Adverse effects of glucocorticoid use are typically seen after prolonged usage. Thus, steroid supplementation before dental procedures should be considered, customized based on identified risk factors and the stress associated with the procedure, as a pragmatic and preemptive approach to reduce the risk of AC. Moreover, this review highlights the need for updated guidance on supplementing patients at risk of secondary AI

Temporal Trends in Acute Adrenal Insufficiency Events in Children With Congenital Adrenal Hyperplasia During 2019-2022.

It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDEs) and hospitalization rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events. Study temporal trends of AI related AE in the I-CAH Registry. In 2022, data on the occurrence of AI-related AE in children aged <18 years with 21-hydroxylase deficiency CAH were compared to data collected in 2019. In 2022, a total of 513 children from 38 centers in 21 countries with a median of 8 children (range 1-58) per center had 2470 visits evaluated over a 3-year period (2019-2022). The median SDE per patient year in 2022 was 0 (0-2.5) compared to 0.3 (0-6) in 2019 (P = .01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the 2 cohorts. Of the 38 centers in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%), and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalization compared to 299 of 1099 SDEs (27%) in the 2019 cohort (P = .02). The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring.

Approach to the child and adolescent with Adrenal Insufficiency.

The management of adrenal insufficiency is challenging, and the overall goals of treatment are to prevent life-threatening adrenal crises, to optimize linear growth, to control androgen levels without overdosing in subjects with congenital adrenal hyperplasia (CAH) and to improve quality of life in affected individuals. Standard glucocorticoid formulations fail to replicate the circadian rhythm of cortisol and control the adrenal androgen production driven by adrenocorticotropic hormone. In order to personalize and tailor glucocorticoid therapy and to improve patient outcomes, new pharmacological strategies have been developed that best mimic physiological cortisol secretion. Novel therapeutic approaches in the management of adrenal insufficiency include new ways to deliver circadian cortisol replacement as well as various adjunctive therapies to reduce androgen production and/or androgen action/effects. Preclinical studies are exploring the role of restorative cell-based therapies, and a first recombinant adeno-associated virus-based gene therapy is also being developed in humans with CAH. In this article, we present three illustrative cases of adrenal insufficiency with different underlying etiologies and times of presentation. Diagnostic and management processes are discussed with emphasis on treatment and outcomes. We have also provided the most up-to-date evidence for the tailored management of children and adolescents with adrenal insufficiency.

Asymptomatic Empty Sella Syndrome: A "New" Hypothalamic Pathology or Paraphysiological Variant.

The term empty sella refers to a shrunken or displaced (by a subarachnoid diverticulum) pituitary gland. It can be primary (genetically determined) or secondary (due to trauma/surgery/radiation). It has been reported that 50% of patients are asymptomatic, and others experience symptoms, such as headache, hypertension, or visual field defects. Few cases have an empty sella syndrome, i.e., lacking functional pituitary hormones. Diagnosis is made through NMR or CT. If asymptomatic, this condition requires no treatment; otherwise, empty sella syndrome needs hormonal replacement therapy. We examined the case of asymptomatic empty sella syndrome. A 67-year-old female patient was admitted for dilatative cardiomyopathy. She had a past medical history of arterial hypertension and right ICA endovascular repair. Blood tests demonstrated hypothyroidism, hypoadrenalism, and GH deficiency, without any signs or symptoms. NRM confirmed an empty sella, hence replacement therapy with levothyroxine and cortisone acetate was started. During a follow-up evaluation, we discovered that this biochemical profile of the patient had been known for more than a decade and never treated. Despite being exposed to stress conditions, vascular surgery and angiography, she never developed an adrenal crisis, nor has she ever been symptomatic for severe hypothyroidism. Hormonal replacement therapy was performed. The described clinical scenario is rare, as usually, empty sella syndrome presents with signs of hormone deficiency, even if asymptomatic cases have been described. Some authors suggest considering it as a hypothalamic dysfunction requiring treatment; others identify it as a paraphysiological variant. However, more cases are needed to establish a correct therapeutic strategy for these patients.

Long-term Sequelae: Sheehan’s Syndrome Unveiled 12 Years Postpartum Haemorrhage Complicated by Pulmonary Tuberculosis – A Clinical Case Report

Sheehan’s syndrome, a rare but significant endocrinopathy, often emerges in the backdrop of severe postpartum haemorrhage and can remain undiagnosed for years. Primary care physicians play a crucial role in suspecting and diagnosing this condition, especially in women presenting with a history of puerperal haemorrhage, lactation failure and amenorrhea. The syndrome’s potential to cause life-threatening adrenal crises during episodes of acute illness, such as infections or pulmonary tuberculosis, underscores the need for vigilance and prompt intervention in affected individuals. This report highlights the case of a 35-year-old female who was diagnosed with Sheehan’s syndrome a notable 12 years after experiencing a severe postpartum haemorrhage. Her condition was eventually unmasked following her affliction with pulmonary tuberculosis, emphasising the complexity and delayed presentation of this syndrome. This case underscores the critical need for heightened awareness among healthcare professionals for early identification and management of Sheehan’s syndrome to prevent serious complications.

Pituitary-adrenal axis dysfunction induced by tislelizumab immunotherapy for non-small cell lung cancer: a case series and literature review

BackgroundAdverse events of secondary adrenal insufficiency caused by anti-PD-1 immune agents are relatively rare in clinical practice, so in this article, we retrospectively analyzed three patients who suffered secondary adrenal cortex dysfunction caused by tislelizumab immunotherapy for Non-Small Cell Lung Cancer (NSCLC)and reviewed the literature. This rare immune-related adverse event was investigated by summarizing the clinical features of the patients.Case presentationWe reported three NSCLC patients who suffered secondary adrenal cortex dysfunction induced by tislelizumab immunotherapy at our hospital from July 2021 to October 2023. We analyzed and summarized the clinical characteristic, laboratory examination, pathological staging, etc. We also reviewed related literature of pituitary inflammation and adrenal cortex dysfunction caused by immunotherapy.ResultsThe median age of the three patients was 56 years. All the patients had a history of smoking. After receiving tislelizumab treatment (median cycle: 7), laboratory examination showed a decrease in morning cortisol and adrenocorticotropic hormone (ACTH), both were diagnosed with secondary adrenal insufficiency. Only one patient had symptoms of fatigue, vomiting, and weight loss. One of these patients also had simultaneous subclinical hypothyroidism. All three patients discontinued immunotherapy and received replacement therapy with glucocorticoids. At the last follow-up, none of the three patients restarted immunotherapy, because cortisol did not return to normal. This is similar to that of previous reports.ConclusionBased on previous reports and our three cases, when laboratory tests of NSCLC patients receiving immunotherapy showed a decrease in morning cortisol and ACTH levels, especially when clinical symptoms were obvious, the possibility of immunotherapy-related pituitary inflammation causing secondary adrenal cortex dysfunction should be considered. Prompt monitoring and hormone replacement therapy should be provided to prevent adrenal crises.

Late diagnosis of partial 3β-hydroxysteroid dehydrogenase type 2 deficiency - characterization of a new genetic variant.

Congenital adrenal hyperplasia (CAH) is one of the most common inherited rare endocrine disorders. This case report presents two female siblings with delayed diagnosis of non-classical CAH 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2D/HSD3B2) despite early hospital admission and apparent CAH manifestations such as infections, hirsutism, menstrual disturbances, and PCOS phenotype. Initially, sister 1 was misdiagnosed with PCOS and then 11-hydroxylase deficiency (CYP11B1), based on ultrasound, biochemical findings, and negative genetic testing for 21-hydroxylase deficiency (CYP21A2). Additional diagnostic workup was performed when sister 2also presented with symptoms of androgen excess. Genetic testing for CAH/steroid disorders finally revealed that both siblings were compound heterozygous for two variants in the HSD3B2 gene: a frameshift variant, c.558dup, p.(Thr187Hisfs*17) and a novel missense variant, c.65T>C, p.(Leu22Ser). A Synacthen test showed an insufficient cortisol increase. In vitro studies of the variants in a cell model revealed loss of function for the p.(Thr187Hisfs*17) and partial activity for p.(Leu22Ser) confirming non-classic CAH. Overlapping symptomatology and lack of specialized knowledge on steroid biosynthesis and associated rarest forms of CAH may explain the delayed diagnosis. However, with newer diagnostic methods comprising a less biased approach, very rare forms of non-classical CAH may no longer be overlooked in the future. Non-classic 3βHSD2 is likely underdiagnosed. Late diagnosis of mild non-classic 3βHSD2 does occur and one should be aware of this diagnosis. Early diagnosis of NCCAH may prevent many consequences such as severe hirsutism, prolonged menstrual irregularities, infertility, or even adrenal crisis with severe infections. Comprehensive steroid profiling and genetic testing should be used earlier, especially when in doubt about a diagnosis.

The Glucocorticoid Taper: A Primer for the Clinicians.

Glucocorticoid (GC) therapy can ameliorate debilitating and life-threatening symptoms in several inflammatory/immunological disorders. However, it can also cause significant side effects, especially with higher doses and longer duration of use. Therefore, GCs should be used at the lowest effective dose for the shortest possible time to minimise adverse effects. GC therapy may cause suppression of the endogenous hypothalamic-pituitary-adrenal (HPA) axis and abrupt discontinuation predisposes patients to features of GC-induced adrenal insufficiency. The practice of tapering GC therapy allows for recovery of the HPA axis while minimising the risk of a disease flare-up or symptoms of AI. Moderate-to-high dose GC therapy may be tapered rapidly to near-physiological doses while watching for features of disease reactivation. Once close to the physiological dose, tapering is slower and at longer intervals to allow for recovery of the HPA axis. It is important to use short- or intermediate-acting GC preparations such as hydrocortisone or prednisolone in physiological doses, administered in the morning to mimic the endogenous cortisol rhythm. A general principle to follow is that HPA axis recovery takes longer if the period of suppression has been long. In such cases, tapering should be slower over a few months to even a year. In select cases at high risk of AI or if symptoms appear during tapering, the decision to further taper and discontinue steroids may be based on testing of HPA axis function using basal and/or stimulated serum cortisol. All patients on exogenous steroids should be advised about the need for an appropriate increase in GC doses during acute medical or surgical illness and should carry a steroid alert card to avoid adrenal crisis.

Appendicitis Hidden under the Facade of Addison’s Crisis: A Case Report

The clinical picture of Addison’s crisis closely simulatesthat of Acute abdominal Inflammatory diseases. Hence, a differential diagnosis between Addisonian Crisis and Acute Abdominal Inflammation can be confusing and difficult. This is not to say both cannot present in a patient at the same time which can complicate reaching an accurate diagnosis even more. Below is one such case.

SG15 A topical matter: iatrogenic adrenal crisis following excessive prescription corticosteroid use

SG15 A topical matter: iatrogenic adrenal crisis following excessive prescription corticosteroid use

Hyponatremia as acute adrenal insufficiency in patients with type 1 diabetes mellitus and kidney transplantation cause end-stage chronic kidney disease

Diabetes mellitus type 1 (DM1) and chronic adrenal insufficiency (CAF) are among the most common autoimmune endocrine diseases that develop both isolated and in combination with each other and with other diseases of autoimmune origin, as part of various syndromes. At the same time, type 1 diabetes is quite often the first component of a systemic autoimmune lesion and acts as a predictor of the development of congenital disorder, which, in turn, against the background of type 1 diabetes, acquires a mild, sometimes atypical course, which complicates the diagnosis and prescription of therapy. The clinical case describes a patient with type 1 diabetes and end-stage chronic kidney disease (CKD), kidney allotransplantation (ART), who was on triple immunosuppressive therapy, who developed CHN, which was manifested by severe hyponatremia and the occurrence of frequent hypoglycemic conditions.

Comparison of modified-release hydrocortisone capsules versus prednisolone in the treatment of congenital adrenal hyperplasia.

Prednisolone and prednisone are recommended treatment options for adults with congenital adrenal hyperplasia (CAH); however, there is no randomised comparison of prednis(ol)one with hydrocortisone. Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study was the design of the study. The method of the study was hydrocortisone dose equivalent and 09:00-h 17-hydroxyprogesterone (17OHP) from 48 patients taking prednis(ol)one at baseline. At baseline, the median hydrocortisone dose equivalent was 30 mg/day and 17OHP was < 36 nmol/L (3× upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to modified-release hydrocortisone capsule (MRHC) at the same hydrocortisone-equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP < 36 nmol/L. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg/day and 82% had 17OHP < 36 nmol/L. The per cent of patients with 17OHP < 36 nmol/L on a hydrocortisone dose equivalent ≤ 25 mg/day was greater at 18 months in the extension study on MRHC than while on prednis(ol)one at baseline: 57% vs 27%, P = 0.04. In the randomised study, no patients had an adrenal crisis on MRHC and one on prednisolone. In the extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years). MRHC reduces 17OHP at 09:00 h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.

Adrenal Insufficiency Presenting as Pulseless Ventricular Tachycardia

Adrenal insufficiency (AI) is a severe sickness induced by adrenal gland or hypothalamic-pituitary-adrenal (HPA) axis dysfunction. It can induce a variety of symptoms, the most serious of which are potentially fatal adrenal crises. This case report describes a clinical scenario involving a 42-year-old male patient who had previously had brain tumor surgery. The patient had presented with fever and gastrointestinal symptoms. He developed pulseless ventricular tachycardia on day two of admission. Patient was promptly treated with electrical cardioversion. Workup revealed QT prolongation on ECG and adrenal insufficiency. Both the patient’s arrhythmias and QT prolongation on ECG responded to intravenous hydrocortisone.

Hormonal Changes During Acute Stress Response

In today’s environment, people constantly find themselves confronted with a wide range of upsetting situations. It is possible for stress to cause changes in the levels of a wide variety of hormones that are found in the serum, including glucocorticoids, catecholamines, growth hormone, and thyroid hormones. The “fight or flight” response requires certain adjustments to be made in order to ensure the individual’s safety. There is a possibility that certain stress-related responses can lead to endocrine illnesses such as Graves’ disease, gonadal dysfunction, psychosexual dwarfism, and obesity. Furthermore, stress has the potential to alter the clinical status of a wide variety of preexisting endocrine illnesses, such as contributing to the onset of adrenal crisis and thyroid storm. Significant consequences of stress include changes in behavior and systemic alterations, as well as changes in cellular mechanisms, hormonal , and brain stimulation. These changes can be observed at all levels, including cellular mechanisms, hormonal changes, and brain stimulation. An entirely new field of research has lately revealed the impacts of stress on human behavior, social cognition, and health. This is in spite of the fact that the influence of stress on health has been the subject of substantial research for a considerable amount of time

A case of tuberculosis of adrenal gland presenting as acute adrenal insufficiency following initiation of anti-tubercular therapy

Adrenal tuberculosis is one important cause of acute or chronic adrenal insufficiency in developing countries like India. There are many random cases in literature describing various clinical situations of adrenal tuberculosis presenting with adrenal insufficiency, especially after initiation of anti-tubercular therapy. A 43-year-old male recently diagnosed patient with pulmonary tuberculosis and chronic coronary syndrome was admitted for acute decompensated heart failure with pulmonary edema. He was taking fixed dose combination anti-tubercular therapy. During admission, he had hyponatremia (serum sodium 96 mEq/L) and during treatment, he developed hypotension and shock, which were appropriately treated. Due to ischemic hepatitis, anti-tubercular treatment (ATT) was modified to streptomycin, ethambutol, and ofloxacin regimen to avoid further hepatotoxicity. Hyponatremia and shock recovered. Rifampicin and isoniazid were restarted. He again developed easy fatigability, nausea, vomiting, and hypotension. Suspecting adrenal insufficiency, fasting serum cortisol, and adrenocorticotropic hormone (ACTH) were done, which revealed a low serum fasting cortisol and high ACTH. Computed tomography abdomen showed enlarged left adrenal gland with calcifications. He was started on prednisolone 2 mg/kg/day with full dose fixed dose ATT, following which his symptoms resolved.

Insuficiencia suprarrenal

Adrenal insufficiency is an endocrine disorder with a low prevalence, but it can potentially be fatal if not treated. It is caused by a deficit in cortisol production by the adrenal glands, a deficit in pituitary ACTH production, or can occur after abrupt suppression of glucocorticoid intake. Hemodynamic collapse is the usual clinical presentation in an acute adrenal crisis. The diagnosis entails demonstrating a cortisol deficiency, for which dynamic tests are available to evaluate the adrenal reserve. Knowing the method used in the biochemical determination of cortisol is of interest in order to establish appropriate reference ranges. Restoration of volemia and the use of intravenous glucocorticoids constitute the initial management of an acute crisis and must never be delayed when there is clinical suspicion. In chronic forms, oral glucocorticoid treatment at physiological doses is started. Mineralocorticoid treatment is indicated only for the primary etiology.

Tratamiento de la insuficiencia suprarrenal

Adrenal insufficiency is an endocrine disorder with a low prevalence, though it can potentially be severe if not treated. Hemodynamic collapse and refractory hypotension characterize an acute adrenal crisis. Treatment must never be delayed while awaiting biochemical results in these cases. Hydrocortisone, the pharmacological name for cortisol, is the drug of choice, as it has greater mineralocorticoid activity than other synthetic glucocorticoids. During an acute crisis, clearly supraphysiological doses should be used together with aggressive fluid replacement until hemodynamic stabilization is achieved. In patients with chronic manifestations, the maintenance dose is 15 to 25mg, accompanied by mineralocorticoid replacement if the origin of the AI is primary. Clinical response is the best indicator of treatment response. Patient education is fundamental and should be aimed at recognizing an acute crisis and how to act in stressful situations in order to prevent them.

Secondary Adrenal Insufficiency : A Case Report

Introduction: Insufficient pituitary hormone output is referred to as hypopituitarism. Individuals experiencing lethargy, dizziness, orthostatic hypotension, hypoglycemia, nausea, vomiting, or generalized abdominal pain may be diagnosed with acute adrenocorticotropic hormone (ACTH) insufficiency. This report detailed a unique instance of hypopituitarism in a patient who complained of nausea, vomiting, hypotension, hypoglycemia, and overall abdominal pain and soreness. Case presentation: A 65-year-old male presented to the outpatient department with complaints of a cough of 1-day duration on August 9/03/21 associated with 4 to 5 episodes of vomiting and pain in the abdomen, in addition to that whole body darkening, fatigue, and appetite loss of 6 months. weight loss intermittent sweating, and eyebrow and axillary hair loss. SOB with mild activity and also bilateral breast pain but no mass. Discussion: The diagnosis of hypothyroidism and inexplicable fatigue made us believe that there was an adrenal deficiency, which might be treated with cortisol around eight o’clock. Even though the patient with a high stress level the cortisol was immeasurable; so the diagnosis, of adrenal insufficiency, could be made. Other tests including ACTH and Imaging are usually needed to discover the subtype of insufficiency. The follow-up after 1 month showed no signs or symptoms left and a much better condition. Conclusion: When treating individuals who have fatigue that cannot be attributed to anything else, especially when weight loss and muscle weakness are present, adrenal insufficiency should be taken into consideration. A secondary adrenal insufficiency may exist even in the absence of skin pigmentation, which frequently triggers anxieties and ideas about Addison’s disease. If it is not identified promptly, it may potentially result in an adrenal crisis in situations with high-stress levels. Our patient presented with vague and largely mild symptoms related to early secondary adrenal insufficiency. These included nausea and vomiting, as well as fatigue. Laboratory studies indicated new hyponatremia and urine studies showed inappropriately normal urine sodium and osmolality. His morning serum cortisol was low, with borderline low ACTH, consistent with a secondary cause.