Emergency management of adrenal insufficiency in children: advocating for treatment options in outpatient and field settings

Adrenal insufficiency (AI) remains a significant cause of morbidity and mortality in children with 1 in 200 episodes of adrenal crisis resulting in death. The goal of this working group of the Pediatric Endocrine Society Drug and Therapeutics Committee was to raise awareness on the importance of early recognition of AI, to advocate for the availability of hydrocortisone sodium succinate (HSS) on emergency medical service (EMS) ambulances or allow EMS personnel to administer patient’s HSS home supply to avoid delay in administration of life-saving stress dosing, and to provide guidance on the emergency management of children in adrenal crisis. Currently, hydrocortisone, or an equivalent synthetic glucocorticoid, is not available on most ambulances for emergency stress dose administration by EMS personnel to a child in adrenal crisis. At the same time, many States have regulations preventing the use of patient’s home HSS supply to be used to treat acute adrenal crisis. In children with known AI, parents and care providers must be made familiar with the administration of maintenance and stress dose glucocorticoid therapy to prevent adrenal crises. Patients with known AI and their families should be provided an Adrenal Insufficiency Action Plan, including stress hydrocortisone dose (both oral and intramuscular/intravenous) to be provided immediately to EMS providers and triage personnel in urgent care and emergency departments. Advocacy efforts to increase the availability of stress dose HSS during EMS transport care and add HSS to weight-based dosing tapes are highly encouraged.

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MON-181 Clinical Features of Immune Checkpoint Inhibitor-Related Adrenal Insufficiency: A Retrospective Analysis

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.737 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Qinwen Jenny Zhou ◽

Sandip Patel ◽

Vala Hamidi

Keyword(s):

Adrenal Insufficiency ◽

Health Care Providers ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Immune Checkpoints ◽

Imaging Features ◽

Care Providers ◽

Endocrine Society ◽

Antibody Positivity ◽

Auto Antibody

Abstract Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment over the past decade. Despite their increasing use in clinical practice, there are few established, evidence-based guidelines for the screening and management of immune-related adverse events (irAEs), particularly with regard to autoimmune endocrinopathies. Adrenal insufficiency is an irAE that is poorly characterized due to the nonspecific nature of its presentation and can be life-threatening if not promptly recognized and treated. Our aim is to better define the clinical, biochemical, and imaging features of ICI-related adrenal insufficiency (AI) to mediate earlier recognition and treatment. Methods: We identified a total of 54 patients treated with either nivolumab, pembrolizumab, or ipilimumab combination therapy between January 2010 and August 2018 found to have a random cortisol level less than 2 or morning cortisol less than 5 during or following therapy. Patients who had been on prednisone or dexamethasone at the time of cortisol testing, had a history of adrenalectomy or radiation to the adrenal glands, or had adrenal or pituitary metastasis were excluded. Results: 11 patients met criteria for new onset ICI-related AI based on clinical and biochemical findings. 78% were formally diagnosed with AI, 61% had subsequent workup with ACTH, 17% had dedicated MRI pituitary imaging, 22% had HPA axis testing, 50% were referred to Endocrinology, and 45% were appropriately treated with hydrocortisone. Mean time to onset was 137 days from initiation of ICI. Peripheral eosinophilia was observed in 55% of patients. No anti-21 hydroxylase antibodies were drawn, and no patients had known underlying autoimmune disease or auto-antibody positivity. Six patients (55%) were felt to have secondary AI from ICI-related hypophysitis and one patient (9%) was felt to have ICI-related adrenalitis. Conclusions: As ICIs are being used with increasing frequency, it is crucial for health care providers to recognize the characteristics of immune-mediated adrenal insufficiency and initiate the appropriate workup, treatment, and referrals. Cortisol levels are routinely ordered as part of screening of ICI infusion but often dismissed without proper workup or follow up when levels meet criteria for AI. Our findings suggest that ICI-related AI more frequently manifests as ACTH deficiency in the context of hypophysitis, though primary AI can occur as well. Ultimately, further investigation is necessary to develop a systematic approach to diagnosing and managing ICI-related AI. References: 1. Chang et al. Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Endocr Rev. 2019;40(1):17-65. 2. Castinetti et al. French Endocrine Society Guidance on endocrine side-effects of immunotherapy. Endocr Relat Cancer. 2018;26(2):G1-G8.

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Development and assessment of a low-health-literacy, pictographic adrenal insufficiency action plan

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0541 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Patrick T. Reeves ◽

Ashley C. Packett ◽

Carolyn Sullivan Burklow ◽

Sofia Echelmeyer ◽

Noelle S. Larson

Keyword(s):

Patient Education ◽

Adrenal Insufficiency ◽

Assessment Tool ◽

Action Plan ◽

Consumer Information ◽

Care Plan ◽

Endocrine Society ◽

Readability Score ◽

Suitability Assessment ◽

Individualized Care

Abstract Objectives Adrenal insufficiency (AI) is an overall rare disorder characterized by the chronic need for pharmacotherapy to prevent threat to life. The Pediatric Endocrine Society has recommended the use of clinical action tools to improve patient education and help guide acute management of AI. We aimed to develop and assess an easy-to-use, patient-friendly, evidence-based, personalized pictogram-based adrenal insufficiency action plan (AIAP) to aid in the management of AI in children. Methods Patients/caregivers (P/Cs) responded to surveys which measured the concepts of transparency, translucency, and recall in order to assess the pictograms. Readability was assessed using six formulas to generate a composite readability score. Quality was graded by P/Cs using the Consumer Information Rating Form (CIRF) (>80% rating considered acceptable). Understandability and actionability was assessed by medical librarians using the Patient Education Materials Assessment Tool-Printable (PEMAT-P) (>80% rating was acceptable). Suitability was evaluated by clinicians using the Suitability Assessment of Materials (SAM) instrument (>70% rating considered superior). Results All pictograms met criteria for inclusion in the AIAP. Composite readability score=5.4 was consistent with a fifth-grade level. P/Cs (n=120) judged the AIAP to be of high quality with CIRF rating=85.2%. Three medical librarians rated the AIAP to have 100% understandability and 100% actionability. Thirty-three clinicians completing the SAM generated a suitability rating of 90.0%. Conclusions The AIAP visually highlights individualized care plan components to facilitate optimized preventative and acute AI care. Further investigation will determine if AIAP improves clinical outcomes for patients with AI.

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Diagnosis and treatment of adrenal insufficiency including adrenal crisis: a Japan Endocrine Society clinical practice guideline [Opinion]

Endocrine Journal ◽

10.1507/endocrj.ej16-0242 ◽

2016 ◽

Vol 63 (9) ◽

pp. 765-784 ◽

Cited By ~ 31

Author(s):

Toshihiko Yanase ◽

Toshihiro Tajima ◽

Takuyuki Katabami ◽

Yasumasa Iwasaki ◽

Yusuke Tanahashi ◽

...

Keyword(s):

Clinical Practice ◽

Adrenal Insufficiency ◽

Clinical Practice Guideline ◽

Practice Guideline ◽

Diagnosis And Treatment ◽

Adrenal Crisis ◽

Endocrine Society

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ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of adrenal insufficiency

Acta Endocrinologica ◽

10.1530/eje-20-0361 ◽

2020 ◽

Vol 183 (1) ◽

pp. G25-G32 ◽

Cited By ~ 14

Author(s):

Wiebke Arlt ◽

Stephanie E Baldeweg ◽

Simon H S Pearce ◽

Helen L Simpson

Keyword(s):

Adrenal Insufficiency ◽

Clinical Deterioration ◽

Adrenal Crisis ◽

Modified Release ◽

Risk Of Infection ◽

Course Of Disease ◽

Restricted Access ◽

Increased Risk ◽

Sick Day Rules ◽

Stress Dose

We provide guidance on prevention of adrenal crisis during the global COVID-19 crisis, a time with frequently restricted access to the usual level of healthcare. Patients with adrenal insufficiency are at an increased risk of infection, which may be complicated by developing an adrenal crisis; however, there is currently no evidence that adrenal insufficiency patients are more likely to develop a severe course of disease. We highlight the need for education (sick day rules, stringent social distancing rules), equipment (sufficient glucocorticoid supplies, steroid emergency self-injection kit) and empowerment (steroid emergency card, COVID-19 guidelines) to prevent adrenal crises. In patients with adrenal insufficiency developing an acute COVID-19 infection, which frequently presents with continuous high fever, we suggest oral stress dose cover with 20 mg hydrocortisone every 6 h. We also comment on suggested dosing for patients who usually take modified release hydrocortisone or prednisolone. In patients with adrenal insufficiency showing clinical deterioration during an acute COVID-19 infection, we advise immediate (self-)injection of 100 mg hydrocortisone intramuscularly, followed by continuous i.v. infusion of 200 mg hydrocortisone per 24 h, or until this can be established, and administration of 50 mg hydrocortisone every 6 h. We also advise on doses for infants and children.

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Perioperative Adrenal Crisis

10.1093/med/9780190226459.003.0028 ◽

2017 ◽

Author(s):

Jing Tao ◽

Jeffrey J. Schwartz

Keyword(s):

Adrenal Insufficiency ◽

Adrenal Crisis ◽

Life Saving ◽

Distributive Shock ◽

Threatening Condition ◽

Life Threatening ◽

High Doses ◽

Patient At Risk ◽

Stress Dose ◽

Timely Treatment

Perioperative adrenal insufficiency (AI) (adrenal crisis) is an uncommon life-threatening condition manifested by distributive shock that is poorly responsive to the administration of fluids and vasopressors. Timely treatment with high doses of glucocorticoids can be life saving. The difficulty is in recognizing the patient at risk, suspecting the diagnosis, and distinguishing it from other forms of shock. The incidence of adrenal crisis is rare, in large part, due to the liberal use of perioperative “stress dose” steroids in patients already receiving steroids. In this chapter we review the pathophysiology involved in both primary and secondary AI, and provide step-by-step treatment recommendations for patients as risk for this condition.

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Perioperative glucocorticoid management based on current evidence

Anesthesia and Pain Medicine ◽

10.17085/apm.20089 ◽

2021 ◽

Vol 16 (1) ◽

pp. 8-15

Author(s):

Kwon Hui Seo

Keyword(s):

Adrenal Insufficiency ◽

Surgical Stress ◽

Perioperative Period ◽

Hemodynamic Instability ◽

Current Evidence ◽

Major Surgery ◽

Adrenal Crisis ◽

Number Of Patients ◽

Glucocorticoid Administration ◽

Stress Dose

Glucocorticoid preparations, adreno-cortical steroids, with strong anti-inflammatory and immunosuppressive effects, are widely used for treating various diseases. The number of patients exposed to steroid therapy prior to surgery is increasing. When these patients present for surgery, the anesthesiologist must decide whether to administer perioperative steroid supplementation. Stress-dose glucocorticoid administration is required during the perioperative period because of the possibility of failure of cortisol secretion to cope with the increased cortisol requirement due to surgical stress, adrenal insufficiency, hemodynamic instability, and the possibility of adrenal crisis. Therefore, glucocorticoids should be supplemented at the same level as that of normal physiological response to surgical stress by evaluating the invasiveness of surgery and inhibition of the hypothalamus-pituitary-adrenal axis. Various textbooks and research articles recommend the stress-dose of glucocorticoids during perioperative periods. It has been commonly suggested that glucocorticoids should be administered in an amount equivalent to about 100 mg of cortisol for major surgery because it induces approximately 5 times the normal secretion. However, more studies, with appropriate power, regarding the administration of stress-dose glucocorticoids are still required, and evaluation of patients with possible adrenal insufficiency and appropriate glucocorticoid administration based on surgical stress will help improve the prognosis.

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Addison-Krise – Risiko erkennen und rasch behandeln

DMW - Deutsche Medizinische Wochenschrift ◽

10.1055/s-0043-111729 ◽

2018 ◽

Vol 143 (06) ◽

pp. 392-396 ◽

Cited By ~ 1

Author(s):

Gesine Meyer ◽

Klaus Badenhoop

Keyword(s):

Continuous Infusion ◽

Adrenal Insufficiency ◽

Joint Pain ◽

Early Recognition ◽

Educational Programs ◽

Adrenal Crisis ◽

Stress Symptoms ◽

Risk Of Mortality ◽

Life Threatening ◽

Life Threatening Complication

AbstractAn adrenal crisis (Addisonian crisis) is an acute life-threatening complication of adrenal insufficiency. It occurs when hydrocortisone demand is not met by supplementation in the context of an infection – often gastrointestinal, fever, trauma, acute psychological or physical stress. Symptoms of weakness, nausea, muscle/joint pain and drowsiness may develop out of robust health within few hours. If overlooked, treated too late, with insufficient dose or route of application, there exists a considerable risk of mortality. Treatment consists of immediate parenteral hydrocortisone (100 mg bolus) and subsequent continuous infusion until the underlying precipitating cause is cured and/or when regular supplementation can be continued. Physicians and nurses must not underestimate the condition, since diagnosis and treatment must not be delayed. Patients, relatives and spouses need to be trained in prevention and early recognition through educational programs and emergency cards.

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Corticosteroids Replacement in a Patient With Panhypopituitarism and COVID-19 Infection

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1180 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A578-A579

Author(s):

Gowri Karuppasamy ◽

Zaina Abdelhalim Alamer ◽

Samman Rose ◽

Ibrahim Abdulla Al-Janahi

Keyword(s):

Pituitary Adenoma ◽

Adrenal Insufficiency ◽

Hormone Replacement ◽

Hypogonadotropic Hypogonadism ◽

Adrenal Crisis ◽

High Dose ◽

Pituitary Hormone ◽

Secondary Hypothyroidism ◽

Stress Dose

Abstract Background: Hypopituitarism refers to complete or partial insufficiency of pituitary hormone secretion and patients require lifelong hormone replacement. Those with ACTH deficiency rely on exogenous glucocorticoids and at times of intercurrent illness require stress doses to prevent an adrenal crisis. The benefits and adverse effects of corticosteroids for treatment of COVID-19 pneumonia are currently under investigation. We report our experience in a patient with COVID-19 pneumonia who received high dose corticosteroids for panhypopituitarism. Clinical Case: A 51-year-old man presented with one-week history of fever and generalized weakness. He had been diagnosed with a non-functional pituitary macro-adenoma causing panhypopituitarism 1 year ago when he developed generalized tonic-clonic seizures. He underwent trans-sphenoidal resection of the pituitary adenoma. However, he then discontinued his hormonal therapy and was lost to follow up. He had postural hypotension but was not tachypneic or hypoxemic. He tested positive for COVID-19 and chest x-ray showed prominent bilateral broncho-vascular markings; he was hospitalized as mild COVID-19 pneumonia. Laboratory investigations revealed secondary adrenal insufficiency, secondary hypothyroidism and hypogonadotropic hypogonadism. MRI of the pituitary now showed persistence of the pituitary macroadenoma, measuring 3.5 x 3.7 x 2.4 cm in dimensions, causing sellar obliteration and left cavernous sinus invasion. Treatment with stress dose steroids, Hydrocortisone 50 mg 4 times daily was initiated, followed by thyroid hormone replacement with Levothyroxine 125 mcg daily. He also received antivirals and supportive care for COVID-19, guided by local hospital protocol. After significant clinical improvement, steroids were tapered down and he was discharged on a maintenance dose of 20 mg hydrocortisone per day in divided doses. The patient was stable at outpatient follow up after one month. He was started on testosterone replacement for erectile dysfunction due to hypogonadotropic hypogonadism. He was offered surgery for complete resection of the residual pituitary adenoma, but he declined and preferred to continue medical therapy. Conclusion: Hypopituitarism is associated with significant morbidity and premature mortality, a key risk factor being cortisol deficiency. Adrenal crisis is a life-threatening medical emergency and remains an important cause of death in patients with adrenal insufficiency. These patients are also vulnerable to develop severe complications from COVID-19 infection due to the absence of normal cortisol responses to stress. Despite receiving stress dose corticosteroids, this high-risk patient recovered from COVID-19 pneumonia without complications. These findings support the use of corticosteroids when necessary for treatment of coexisting conditions in patients with COVID-19.

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Hypopituitarism

10.1093/med/9780199764495.003.0048 ◽

2013 ◽

Author(s):

Liana G Hosu ◽

Lori A Aronson

Keyword(s):

Pituitary Gland ◽

Adrenal Insufficiency ◽

Corticosteroid Treatment ◽

Pituitary Hormones ◽

Adrenal Crisis ◽

Dose Corticosteroid ◽

Stress Dose

Hypopituitarism refers to decreased secretion of pituitary hormones, which can result from diseases of the pituitary gland or hypothalamus. Surgery in the presence of untreated panhypopituitarism is rare. It is important to recognize the presence of hypopituitarism and most importantly adrenal insufficiency, a condition that can result in mortality from adrenal crisis without stress-dose corticosteroid treatment.

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