454: DANTROLENE AS TREATMENT FOR HYPERPYREXIA AND RHABDOMYOLYSIS DUE TO LIFE-THREATENING ADRENAL CRISIS

Abstract Introduction Adrenal insufficiency (AI) is an uncommon, life-threatening disorder requiring lifelong treatment with steroid therapy and special attention to prevent adrenal crisis. Little is known about the prevalence of AI in Canada or healthcare utilization rates by these patients. Objective We aimed to assess the prevalence and healthcare burden of AI in Alberta, Canada. Methods This study used a population-based, retrospective administrative health data approach to identify patients with a diagnosis of AI over a 5-year period and evaluated emergency and outpatient healthcare utilization rates, steroid dispense records and visit reasons. Results The period prevalence of AI was 839 per million adults. Patients made an average of 2.3 and 17.8 visits per year in the emergency department and outpatient settings, respectively. This was 3-4 times as frequent as the average Albertan and only 5% were coded as visits for AI. The majority of patients were dispensed glucocorticoid medications only. Conclusion The prevalence of AI in Alberta is higher than published data in other locations. The frequency of visits suggests a significant healthcare burden and emphasizes the need for a strong understanding of this condition across all clinical settings. Our most concerning finding is that 94.3% of visits were not labelled with AI, even though many of the top presenting complaints were consistent with adrenal crisis. Several data limitations were discovered that suggest improvements in the standardization of data submission and coding can expand the yield of future studies using this method.

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The incidence of adrenal crisis in the postoperative period of HPA axis insufficiency after surgical treatment for Cushing’s syndrome

Acta Endocrinologica ◽

10.1530/eje-19-0202 ◽

2019 ◽

Vol 181 (2) ◽

pp. 201-210 ◽

Cited By ~ 1

Author(s):

Leonie H A Broersen ◽

Femke M van Haalen ◽

Tina Kienitz ◽

Olaf M Dekkers ◽

Christian J Strasburger ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Hpa Axis ◽

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Adrenal Crisis ◽

Pituitary Hormone ◽

Increased Risk ◽

Potential Risk Factors ◽

Life Threatening ◽

Glucocorticoid Deficiency

Background Adrenal crisis, the most feared complication of adrenal insufficiency, is a potentially life-threatening state of acute glucocorticoid deficiency. After successful surgery for Cushing’s syndrome, many patients develop (transient) adrenal insufficiency. The incidence of adrenal crisis in patients treated for hypercortisolism is unknown. Methods Cohort study included consecutive patients with Cushing’s syndrome with adrenal insufficiency after surgery from Leiden and Berlin from 2000 to 2015. We summarized the incidence of adrenal crisis, compared patients with and without adrenal crisis regarding potential risk factors for its occurrence and assessed the effect of better education in time on incidence of adrenal crisis. Results We included 106 patients, of whom 19 patients had a total of 41 adrenal crises. There were 9.0 crises per 100 patient-years at risk (95% confidence interval (CI): 6.7–12.0). All crises occurred while on hydrocortisone replacement. The risk ratio for a recurrent crisis was 2.3 (95% CI: 1.2–4.6). No clear change in incidence of adrenal crisis due to better education in time was observed. There was no difference in recurrence rate between patients with, and without any crisis, but patients with adrenal crisis had more often pituitary deficiencies. Conclusions The incidence of adrenal crises after treatment for Cushing’s syndrome is substantial, and patients who suffered from an adrenal crisis have higher risk for recurrent crisis. Adrenal crisis tends to present early after remission of Cushing’s syndrome, which is probably the period of severest HPA axis suppression, despite in general higher hydrocortisone replacement doses for withdrawal complaints in this period. Additional pituitary hormone deficiencies may be a risk marker for increased risk of adrenal crisis. However, further risk factor analysis is needed to identify risks for a first crisis. Effective education methods to prevent adrenal crises should be identified and implemented, including stress instructions by trained nursing staff before hospital discharge.

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Frequently Asked Questions in Patients With Adrenal Insufficiency in the Time of COVID-19

Frontiers in Endocrinology ◽

10.3389/fendo.2021.805647 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chiara Sabbadin ◽

Corrado Betterle ◽

Carla Scaroni ◽

Filippo Ceccato

Keyword(s):

Adrenal Insufficiency ◽

Short Review ◽

Acute Illness ◽

Self Management ◽

Vaccine Hesitancy ◽

Adrenal Crisis ◽

Risk Of Infection ◽

Telemedicine Consultation ◽

Life Threatening ◽

Cortisol Deficiency

Adrenal insufficiency (AI) is a life-threatening disorder, with increased morbidity and mortality, especially in case of an acute illness that can increase the requirement of cortisol. A novel infectious disease, termed Coronavirus Disease 2019 (COVID-19), appeared in 2020. Therefore, AI patients are experiencing a novel challenge: the risk of infection. In our experience, a prompt contact to the Endocrine center (with a telemedicine consultation) and a full awareness of diseases (cortisol deficiency, COVID-19 and the self-management of an adrenal crisis) are important to motivate patients. Vaccine is an effective treatment to prevent hospitalization and aggressive course of COVID-19. Some patients manifest challenges due to inequitable access and vaccine hesitancy, resulting in a delay in the acceptance of vaccines despite the availability of vaccination services. Therefore, an effort of all physicians must be conducted in order to advise patients with AI. In this short review, we try to answer some frequently asked questions regarding the management of patients with AI.

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Hyperglycaemia, diabetes, and other endocrine emergencies

10.1093/med/9780199687039.003.0069 ◽

2015 ◽

Author(s):

Yves Debaveye ◽

Dieter Mesotten ◽

Greet Van den Berghe

Keyword(s):

Intensive Care ◽

Diabetic Ketoacidosis ◽

Specific Treatment ◽

Blood Glucose Monitoring ◽

Thyroid Storm ◽

Adrenal Crisis ◽

Complex Disorders ◽

State Management ◽

Electrolyte Disturbances ◽

Life Threatening

Although endocrine pathology is usually treated in outpatient clinic, intensive care may be required when endocrinopathies are associated with other medical illnesses or reach a state of decompensation. Although endocrine emergencies are quite rare, they are potentially life-threatening, if not recognized promptly and managed effectively. Therefore, every clinician should always be attentive to a possible diagnosis of these complex disorders. The three major diabetic emergencies comprise diabetic ketoacidosis, hyperglycaemic hyperosmolar state, and prolonged hypoglycaemia. Hyperglycaemic crises are characterized by hypovolaemia, electrolyte disturbances, and potentially life-threatening triggers. Hence, airway-breathing-circulation securement, diagnosis and treatment of the underlying condition, and fluid resuscitation are the cornerstones of acute diabetic ketoacidosis/hyperglycaemic hyperosmolar state management. Subsequently, monitoring and correction of electrolyte disturbances and insulin treatment are initiated. Profound hypoglycaemia should be suspected in every coma patient with an indistinct history or treated with insulin or sulfonylurea/meglitinide. This condition warrants an immediate and a sufficiently long administration of glucose, under blood glucose monitoring. Alternatively, glucagon may be injected subcutaneously, or preferably intramuscularly. Hyperglycaemia in intensive care unit patients is associated with adverse outcome which can be prevented via the implementation of glucose control with intravenous insulin. One should hereby target glucose levels to be as close to normal as possible, without evoking unacceptable glucose fluctuations and hypoglycaemia. The classical non-diabetic endocrine emergencies comprise thyroid storm, myxoedema coma, acute adrenal crisis, and phaeochromocytoma. They all pose diagnostic and therapeutic challenges and require specific treatment such as endocrine replacement or blockage therapy. It is important to note that they are occasionally the presenting manifestation in undiagnosed patients. This chapter also briefly discusses amiodarone-induced thyroid dysfunction.

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THERAPY OF ENDOCRINE DISEASE: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe

Acta Endocrinologica ◽

10.1530/eje-13-0450 ◽

2013 ◽

Vol 169 (6) ◽

pp. R165-R175 ◽

Cited By ~ 67

Author(s):

Ashley Grossman ◽

Gudmundur Johannsson ◽

Marcus Quinkler ◽

Pierre Zelissen

Keyword(s):

Adrenal Insufficiency ◽

Clinical Signs ◽

Adrenal Crisis ◽

Dose Selection ◽

Endocrine Disease ◽

Once Daily ◽

Mortality And Morbidity ◽

Medical Need ◽

Life Threatening

BackgroundConventional glucocorticoid (GC) replacement for patients with adrenal insufficiency (AI) is inadequate. Patients with AI continue to have increased mortality and morbidity and compromised quality of life despite treatment and monitoring.Objectivesi) To review current management of AI and the unmet medical need based on literature and treatment experience and ii) to offer practical advice for managing AI in specific clinical situations.MethodsThe review considers the most urgent questions endocrinologists face in managing AI and presents generalised patient cases with suggested strategies for treatment.ResultsOptimisation and individualisation of GC replacement remain a challenge because available therapies do not mimic physiological cortisol patterns. While increased mortality and morbidity appear related to inadequate GC replacement, there are no objective measures to guide dose selection and optimisation. Physicians must rely on experience to recognise the clinical signs, which are not unique to AI, of inadequate treatment. The increased demand for corticosteroids during periods of stress can result in a life-threatening adrenal crisis (AC) in a patient with AI. Education is paramount for patients and their caregivers to anticipate, recognise and provide proper early treatment to prevent or reduce the occurrence of ACs.ConclusionsThis review highlights and offers suggestions to address the challenges endocrinologists encounter in treating patients with AI. New preparations are being developed to better mimic normal physiological cortisol levels with convenient, once-daily dosing which may improve treatment outcomes.

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Stress hyperglycaemia and endocrine emergencies

The ESC Textbook of Intensive and Acute Cardiovascular Care ◽

10.1093/med/9780198849346.003.0068 ◽

2021 ◽

pp. 912-925

Author(s):

Jan Gunst ◽

Yves Debaveye ◽

Greet Van den Berghe

Keyword(s):

Blood Glucose ◽

Critically Ill ◽

Critically Ill Patients ◽

Glucose Monitoring ◽

Specific Treatment ◽

Thyroid Storm ◽

Adrenal Crisis ◽

Electrolyte Disturbances ◽

Life Threatening ◽

Unclear Etiology

Although endocrine pathology is usually treated in an outpatient clinic, intensive care may be required when endocrinopathies are associated with other medical illnesses or reach a state of decompensation. Although endocrine emergencies are quite rare, they are potentially life-threatening if not recognised promptly and managed effectively. Therefore, every clinician should always be attentive to a possible diagnosis of these complex disorders. The three major diabetic emergencies comprise diabetic ketoacidosis, hyperglycaemic hyperosmolar state, and prolonged hypoglycaemia. Hyperglycaemic crises are characterised by hypovolaemia and electrolyte disturbances, and may be triggered by potentially life-threatening conditions. Hence, airway-breathing-circulation securement, early fluid resuscitation, and adequate diagnosis and treatment of the underlying condition are the cornerstones of acute management. Subsequently, monitoring and correction of electrolyte disturbances and insulin treatment are initiated. Profound hypoglycaemia should be suspected in every patient with coma of unclear etiology, especially if the patient has an indistinct history or was treated with insulin or sulfonylurea/meglitinide. This condition warrants an immediate administration of glucose, followed by regular blood glucose monitoring. Alternatively, glucagon may be injected subcutaneously, or preferably intramuscularly. Hyperglycaemia in critically ill patients is associated with adverse outcome. The optimal blood glucose target for critically ill patients remains unclear, however. In any case, clinicians should prevent severe hyperglycaemia, hypoglycaemia and large glucose fluctuations. The classical non-diabetic endocrine emergencies comprise thyroid storm, myxoedema coma, acute adrenal crisis, and phaeochromocytoma. They all pose diagnostic and therapeutic challenges and require specific treatment such as endocrine replacement or blockage therapy, apart from supportive care and treatment of the inciting event. It is important to note that such conditions are occasionally the first manifestation of an endocrine disorder. This chapter also briefly discusses amiodarone-induced thyroid dysfunction.

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Assessment of autoantibodies against 21-hydroxylase in the diagnosis of primary autoimmune adrenal insufficiency

Problems of Endocrinology ◽

10.14341/probl12106 ◽

2020 ◽

Author(s):

Leila Sozaeva ◽

Nadezhda Makazan ◽

Larisa Nikankina ◽

Natalya Malysheva ◽

Ekaterina Kuvaldina ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Patient Survival ◽

Adrenal Crisis ◽

Primary Adrenal Insufficiency ◽

Adrenal Steroidogenesis ◽

Threatening Condition ◽

Life Threatening ◽

The One

Primary adrenal insufficiency is manifested by a deficiency of adrenal cortex hormones and can lead to a life-threatening condition. Early diagnosis is key to patient survival. Auto-antibodies to one of the adrenal steroidogenesis enzymes, 21-hydroxylase, are an immunological marker of autoimmune adrenal insufficiency. On the one hand, the study of antibodies to 21-hydroxylase is a method that helps establish the etiology of the disease the autoimmune genesis of adrenal gland damage. On the other hand, the determination of autoantibodies to 21-hydroxylase is the only prognostic factor of the risk of adrenal insufficiency, which makes it possible to prevent the development of acute adrenal crisis. The article provides a brief literature review on autoantibodies to 21-hydroxylase and the pathogenesis of autoimmune adrenal insufficiency, and a series of clinical cases that illustrates the significant role of autoantibodies to 21-hydroxylase in diagnosis of adrenal insufficiency.

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Pericardial Effusion as an Initial Presentation of Panhypopituitarism

European Journal of Case Reports in Internal Medicine ◽

10.12890/2020_001478 ◽

2020 ◽

Author(s):

Rosa Alves ◽

Sofia Alegria ◽

Henrique Vara Luiz ◽

Tiago Judas

Keyword(s):

Pericardial Effusion ◽

Incidental Finding ◽

Hormone Replacement ◽

Pericardial Tamponade ◽

Adrenal Crisis ◽

Secondary Hypothyroidism ◽

Rare Manifestation ◽

Initial Work ◽

Life Threatening ◽

Work Up

Pericardial effusion has a broad spectrum of clinical presentation, ranging from an incidental finding on imaging to a potentially fatal emergency such as pericardial tamponade, the most severe presentation. The authors present a case of a middle-aged male hospitalized due to shortness of breath. Initial work-up was positive for massive pericardial effusion with haemodynamic compromise. Additional study revealed panhypopituitarism. The acromegalic phenotype was suggestive of acromegaly secondary to pituitary adenoma, which had probably evolved to apoplexy. Hormone replacement was started with clinical improvement. At the 3-year follow-up, there was no evidence of recurrence of pericardial effusion. Panhypopituitarism is a relatively rare entity, but can lead to life-threatening complications such as adrenal crisis, coma and myxoedema-associated cardiac failure. Pericardial effusion is an extremely rare manifestation of secondary hypothyroidism.

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MON-256 A Late-Onset Case of Sheehan’s Syndrome Presenting as Life Threatening Adrenal Insufficiency

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1392 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Salman Zahoor Bhat ◽

Itivrita Goyal ◽

Manav Batra

Keyword(s):

Cortisol Level ◽

Postpartum Hemorrhage ◽

Late Onset ◽

Adrenal Crisis ◽

High Dose ◽

Sheehan’S Syndrome ◽

Number Of Patients ◽

Patient Reported ◽

Life Threatening ◽

Sheehan's Syndrome

Abstract OBJECTIVE Sheehan’s syndrome or postpartum pituitary necrosis, is an important but rare cause of hypopituitarism, caused due to severe postpartum hemorrhage. Seen more commonly in the developing world, it is less common in developed countries due to advanced obstetric practices. It can present acutely but more frequently has an insidious course (onset 10-20 years later) with variable hormonal deficiencies. Here, we report a late-onset case of Sheehan’s syndrome, 24 years after the incident event, presenting as life threatening adrenal failure. CASE PRESENTATION A 48-year-old female with no significant past medical history was admitted to the hospital after being found unresponsive at home. She had not seen a physician for many years. She complained of weakness and lethargy for a week and recently established care with a primary care physician. The patient was severely hypotensive in the emergency department and had an elevated temperature of 101°F. Physical examination showed no significant abnormalities. CBC and metabolic panel were not significantly altered. CSF analysis and CSF/blood cultures were negative for any infection. TSH was 4.29 mIU/mL (0.27-4.20) but the total and free T4 (fT4) were severely low at 1.1 mcg/mL (4.6-12) and 0.24 ng/dL (0.93-1.70) respectively. On further questioning, patient reported severe postpartum hemorrhage 24 years ago, needing multiple units of blood transfusion. This was followed by inability to lactate and menstruate but was never worked up as she had not seen any physician all these years. Pituitary hormonal panel was obtained, demonstrating multiple hormonal deficiencies with fT4 severely low at 0.24 ng/dL, ACTH of 2.6 pg/mL (7.2-63.3), prolactin (PRL) 1 ng/mL (4.8-23.3) and insulin like growth factor-1 (IGF-1) low at 10 ng/mL (56-194). Cortisol level was elevated in the hospital due to administration of high dose IV steroids but a morning cortisol level obtained 1 week prior by her primary was 1.5 mcg/dL (10-20). Estradiol levels were low with FSH and LH levels inappropriately normal. MRI of the pituitary was obtained which showed an empty sella turcica. Patient was diagnosed as late-onset Sheehan’s syndrome. She was started on hormone replacement with hydrocortisone followed by levothyroxine and had marked improvement in her symptoms. She continues to do well. CONCLUSION Our patient presented late due to lack of medical care and awareness. A great number of patients with Sheehan’s diseasae go undiagnosed due to subtle clinical presentations, thus delaying treatment. It is imperative to diagnose this condition timely with appropriate obstetric/gynecological history and clinical suspicion to avoid late manifestations of the disease, especially adrenal crisis. Patients at risk need long term follow-up. Early treatment is necessary to improve quality of life and reduce morbidity and mortality associated with this condition.

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