Addisonian Crisis (Adrenal Crisis)

Addisonian crisis is a rare occurrence, characterized by a sudden onset insufficiency in the production of cortisol and aldosterone by the adrenal glands. It may be induced by an acute relapse episode of chronic adrenal insufficiency, usually preceded by infections, surgical procedures or traumatization of the adrenal glands and constitutes a medical emergency, since failure to treat the episode can endanger the life of a patient. Symptoms include fatigue, loss of consciousness, tachycardia, dizziness, tachypnea and a variety of other clinical manifestations.


Presentation

An Addisonian crisis is induced by an acute failure of the adrenal glands to produce aldosterone and cortisol; if left untreated, it can put the patient's life at a great risk [1] [2] [3]. An Addisonian crisis tends to produce a multitude of symptoms, which are non-specific, but do indicate a severe underlying pathology [4] [5] [6]. Patients may be febrile, in a disoriented or comatose state, dizzy and display a tendency towards slow, uncoordinated movement. Nausea, vomiting, headache, and fatigue are also common symptoms alongside profound sweating that is localized on the palmar surface of the hands and face. Symptoms related to the cardiovascular system are also elicited, such as tachycardia and hypotension, while the respiratory rate may also be elevated. Lastly, pain may be experienced in the region of the abdomen or flanks.

With regard to the signs exhibited by a patient affected by Addisonian crisis, localized hyperpigmentation may be evident in areas of the skin that are subjected to prolonged exposure to sunlight.

cardiovascular
Hypotension
  • Classically it presents as severe hypotension refractory to IV fluids and vasopressors. Background Adrenal glands produce mineralocorticoids (aldosterone), glucocorticoids (cortisol) and androgens in the outer cortex.[coreem.net]
  • - confusion - nausea - vomiting - diarrhea - vague abdominal pain Hypotension may lead to shock.[signsandsyndromes.com]
  • , balance the effects of insulin helps maintain bp, water/salt balance secondary to an illness or a stressful event; becomes life threatening acute deficiency in cortisol production and this results in circulatory collapse and electrolyte imbalances hypotension[quizlet.com]
  • The features of acute adrenal crisis include hypotension (particularly postural hypotension), shock, and hyponatraemia in 90% of patients. Hyperkalaemia is also a feature in 65% of patients.[bmj.com]
  • The patient’s vitals are pertinent for significant hypotension (60s/40s) after receiving a 1L NS bolus, tachycardia, and tachypnea.[emdocs.net]
Orthostatic Hypotension
  • hypotension ( G90.3 ) orthostatic hypotension ( I95.1 ) postprocedural shock ( T81.1- ) psychogenic syncope ( F48.8 ) shock NOS ( R57.9 ) shock complicating or following abortion or ectopic or molar pregnancy ( O00 - O07 , O08.3 ) shock complicating[icd10data.com]
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  • gastrointestinal
    Vomiting
    • If you can't keep the medication down because of vomiting, take the medication by injection, as directed by your medical team. Other home care Increase your salt intake if your health care provider advises you to.[mountnittany.org]
    • If unable to retain medication due to vomiting, notify the health care provider.[uclahealth.org]
    • Immediate medical attention is needed when severe infections, vomiting, or diarrhea occur. These conditions can precipitate an addisonian crisis. A patient who is vomiting may require addisonian crisis treatment.[endocrine-system.emedtv.com]
    • But now she feels very weak and seems to be vomiting again. Her blood pressure is 80/40, so she was triaged straight to the resuscitation bay.[emsimcases.com]
    • Has the patient been unwell recently with vomiting or other severe illness? A crisis may be triggered by any severe intercurrent illness.[endobible.com]
    Nausea
    • Patients may experience lightheadedness or dizziness, weakness, sweating, abdominal pain, nausea and vomiting, or even loss of consciousness.[uclahealth.org]
    • […] hypotension (particularly postural) - tachycardia (rapid heart rate) - dehydration - hyponatremia (reduced serum sodium levels) - hyperkalemia (elevated serum potassium levels) - hypoglycemia (low blood sugar levels) - fever - weakness - confusion - nausea[signsandsyndromes.com]
    • The types of emergencies include a range of presentations such as semiconsciousness, unconsciousness, difficulty breathing, weakness, nausea, headache, slurred speech, chest pain, allergic reaction, seizure, and anxiety.[books.google.com]
    • Adrenal crisis can also lead to severe nausea, diarrhea and vomiting, notes MedlinePlus. Patients may also have no appetite, and can experience sudden and unexpected weight loss.[livestrong.com]
    • Weight loss, nausea, dizziness and increased pigmentation are typical features suggesing long standing glucocorticoid deficiency. See Addison's disease pages for full assessment.[endobible.com]
    Abdominal Pain
    • Patients may experience lightheadedness or dizziness, weakness, sweating, abdominal pain, nausea and vomiting, or even loss of consciousness.[uclahealth.org]
    • It is equally important in all persons with chronic abdominal pain for whom surgery is considered necessary FULL TEXT[annals.org]
    • pain Hypotension may lead to shock.[signsandsyndromes.com]
    • Acute adrenal crisis (Addisonian Crisis / Acute Adrenal Insufficiency) Addison's Disease Depression Fatigue Nausea and Vomiting Abdominal pain Hair loss Decreased appetite Headache High-grade fever Rapid heartbeat Low Blood Pressure (Hypotension) Dehydration[mymed.com]
    Loss of Appetite
    • Acute adrenal crisis (Addisonian Crisis / Acute Adrenal Insufficiency) Addison's Disease Depression Fatigue Nausea and Vomiting Abdominal pain Hair loss Decreased appetite Headache High-grade fever Rapid heartbeat Low Blood Pressure (Hypotension) Dehydration[mymed.com]
    • When to seek medical care Call your doctor right away if you have any of the following: Tiredness or weakness Loss of appetite or weight loss Dizziness when you stand up after sitting or lying down Muscle aches Nausea, vomiting, or diarrhea Sharp pain[mountnittany.org]
    • […] of appetite Signs and tests: An ACTH (cortrosyn) stimulation test shows low cortisol.[uclahealth.org]
    • The syndrome usually starts with nausea, vomiting, loss of appetite, and diarrhea with unspecific abdominal cramps. Such gastrointestinal manifestations of an acute Addisonian crisis can be accompanied by fever, chills, and profuse sweating.[news-medical.net]
    • Symptoms include: Abdominal pain Confusion or coma Darkening of the skin Dehydration Dizziness or light-headedness Fatigue Flank pain Headache High fever Joint pain Loss of appetite Loss of consciousness Low blood pressure Nausea Profound weakness Rapid[drugs.com]
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  • Entire body system
    Fever
    • […] hypovolemic shock, profound hypoglycemia, confusion, altered mental status, ventricular dysrhythmias, GI (N/V, diarrhea, anorexia, cramps), hyperpigmentation of the skin pts usually present with non specific symptoms (weakness, fatigue, sometimes a fever[quizlet.com]
    • Stress and the HPA Axis Clinical Presentation Variable and non-specific complaints – weakness, confusion, fever, nausea, vomiting, abdominal pain Shock and fever can be only signs Common precipitants – surgery, infection, burn, sepsis, trauma, metabolic[coreem.net]
    • These include: - hypotension (particularly postural) - tachycardia (rapid heart rate) - dehydration - hyponatremia (reduced serum sodium levels) - hyperkalemia (elevated serum potassium levels) - hypoglycemia (low blood sugar levels) - fever - weakness[signsandsyndromes.com]
    • This includes a high fever and dehydration. The dehydration can cause a dangerous drop in blood volume, leading to severely low blood pressure.[livestrong.com]
    Hypothermia
    • On presentation, the patient will have mild hypothermia, hypoglycemia, and hypotension. The team will have to initiate fluid resuscitation and an initial workup.[emsimcases.com]
    • […] known primary or secondary adrenocortical insufficiency AIDS Invasive or infiltrative disorders Tuberculosis Physical: Unexplained shock, usually refractory to fluid and pressor resuscitation Nausea, vomiting, abdominal or flank pain Hyperthermia or hypothermia[addisons-help.com]
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  • Workup

    In order to evaluate a patient with a suspected Addisonian crisis, various laboratory tests should be performed. A complete blood count, serum electrolyte levels, BUN and creatinine levels, cortisol and adrenocorticotropic hormone (ACTH) levels and calcium levels in the blood should be measured and the thyroid function should also be assessed [7].

    As far as imaging modalities are concerned, computerized tomography (CT) can be employed to identify pathology of the adrenal glands, such as trauma, calcification caused by tuberculosis or malignancy. A CT scan of the head can also detect pituitary abnormalities that may secondarily cause the insufficient production of adrenal hormones and lead to an Addisonian crisis.

    Lastly, the ACTH stimulation test is another useful tool that can help to evaluate the functionality of the adrenal glands by measuring their response to the administration of ACTH. After serum cortisol and ACTH levels have been obtained, 0.25 mg of tetracosactide (cosyntropin) is administered. It is a synthetic ACTH product [8] [9]. The substance is administered intravenously or intramuscularly and serum cortisol levels are tested half an hour and six hours after the administration. Should serum cortisol concentration fail to rise after the administration of synthetic ACTH, adrenal insufficiency is established as the diagnosis, always after the careful evaluation of the other parameters. Treatment should not be at any cost delayed in order for the ACTH stimulation test to be performed, as the reliability of the results is unaffected by the administration of dexamethasone. Cortisol levels can also be measured in the urine over a 24-hour period, but this test is only employed in cases where there is no immediate threat to the patient's life.

    Laboratory

    Serum
    Hyponatremia
    • […] electrolytes, neuro checks (hypoperfusion, hypoglycemia, hyponatremia), daily weights, monitor for fluid overload provide a safe environment, teamwork and communication, minimize stress, nutritional intake (need to add salt!)[quizlet.com]
    • Eventually, they will receive critical VBG results that indicate a mild metabolic acidosis, hyperkalemia, and hyponatremia. The team will need to treat the hyperkalemia and initiate hydrocortisone therapy.[emsimcases.com]
    • An insulin stress test should cause hypoglycemia and a spike in both plasma cortisol and serum growth hormone within 1-2 hours. hypoglycemia hyponatremia, hyperkalemia return to top Differential Diagnosis return to top Treatments Hydrocortisone is the[sharinginhealth.ca]
    • These include: - hypotension (particularly postural) - tachycardia (rapid heart rate) - dehydration - hyponatremia (reduced serum sodium levels) - hyperkalemia (elevated serum potassium levels) - hypoglycemia (low blood sugar levels) - fever - weakness[signsandsyndromes.com]
    • A 22-year-old man was admitted to an intensive care unit with severe hyponatremia, hypotension and somnolence.[nature.com]
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  • Imaging

    X-ray
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  • Treatment

    Prognosis

    Complications

    Paralytic Ileus
    • Adrenal crisis with paralytic ileus was diagnosed. Intravenous hydrocortisone (100mg x3/d) and intravenous fluid commenced.[ispub.com]
    Ileus
    • Adrenal crisis with paralytic ileus was diagnosed. Intravenous hydrocortisone (100mg x3/d) and intravenous fluid commenced.[ispub.com]
    Fever
    • […] hypovolemic shock, profound hypoglycemia, confusion, altered mental status, ventricular dysrhythmias, GI (N/V, diarrhea, anorexia, cramps), hyperpigmentation of the skin pts usually present with non specific symptoms (weakness, fatigue, sometimes a fever[quizlet.com]
    • Stress and the HPA Axis Clinical Presentation Variable and non-specific complaints – weakness, confusion, fever, nausea, vomiting, abdominal pain Shock and fever can be only signs Common precipitants – surgery, infection, burn, sepsis, trauma, metabolic[coreem.net]
    • These include: - hypotension (particularly postural) - tachycardia (rapid heart rate) - dehydration - hyponatremia (reduced serum sodium levels) - hyperkalemia (elevated serum potassium levels) - hypoglycemia (low blood sugar levels) - fever - weakness[signsandsyndromes.com]
    • This includes a high fever and dehydration. The dehydration can cause a dangerous drop in blood volume, leading to severely low blood pressure.[livestrong.com]
    Shock
    • ( R57.0 ) carotid sinus syncope ( G90.01 ) heat syncope ( T67.1 ) neurocirculatory asthenia ( F45.8 ) neurogenic orthostatic hypotension ( G90.3 ) orthostatic hypotension ( I95.1 ) postprocedural shock ( T81.1- ) psychogenic syncope ( F48.8 ) shock NOS[icd10data.com]
    • Medical Emergency - Addisonian crisis is an emergency that needs sorting to prevent death from shock! What is it? An acute episode of adrenal insufficiency. That means the adrenal glands stop producing cortisol .[medrevise.co.uk]
    • In contrast, an acute adrenal crisis can present with vomiting, abdominal pain, and hypovolemic shock.[addisons-help.com]
    • Why it Matters While adrenal crisis is a relatively rare presentation, shock is not.[emsimcases.com]
    • […] water/salt balance secondary to an illness or a stressful event; becomes life threatening acute deficiency in cortisol production and this results in circulatory collapse and electrolyte imbalances hypotension, tachycardia, dehydration, hypovolemic shock[quizlet.com]
    Hypoglycemia
    • Treat severe hyperglycemia with 1-2 gm/kg of D50 Consider infusion of D5NS for continued hypoglycemia Check FS glucose Q1-2 hours to ensure improving hypoglycemia Hypotension IVF bolus of 30 cc/kg Consider using D5NS for resuscitation if the patient[coreem.net]
    • […] balance secondary to an illness or a stressful event; becomes life threatening acute deficiency in cortisol production and this results in circulatory collapse and electrolyte imbalances hypotension, tachycardia, dehydration, hypovolemic shock, profound hypoglycemia[quizlet.com]
    • An insulin stress test should cause hypoglycemia and a spike in both plasma cortisol and serum growth hormone within 1-2 hours. hypoglycemia hyponatremia, hyperkalemia return to top Differential Diagnosis return to top Treatments Hydrocortisone is the[sharinginhealth.ca]
    • On presentation, the patient will have mild hypothermia, hypoglycemia, and hypotension. The team will have to initiate fluid resuscitation and an initial workup.[emsimcases.com]
    • These include: - hypotension (particularly postural) - tachycardia (rapid heart rate) - dehydration - hyponatremia (reduced serum sodium levels) - hyperkalemia (elevated serum potassium levels) - hypoglycemia (low blood sugar levels) - fever - weakness[signsandsyndromes.com]
    Acidosis
    • Eventually, they will receive critical VBG results that indicate a mild metabolic acidosis, hyperkalemia, and hyponatremia. The team will need to treat the hyperkalemia and initiate hydrocortisone therapy.[emsimcases.com]
    • Check pH, electrolytes and glucose frequently Blood gas and BGL hourly x 2 hours; then 2-4 hourly once normoglycaemic and acidosis correcting.[rch.org.au]
    • […] to loss of androgens Crisis: hypotension, shock dehydration fever Excess: edema (excess G) return to top Investigations lab investigations diagnostic imaging Lab Investigations hyponatremia and salt craving (M) hyperkalemia (mild) hypercalcemia mild acidosis[sharinginhealth.ca]
    • Pituitary apoplexy – infarction or hemorrhage of tumor Chronic steroid therapy (suppresses HPA axis) Tumors, granulomas Diagnostic Studies : CBC, BMP, VBG, fingerstick /- EKG Hypoglycemia Hyponatremia ( Hyperkalemia ( 5mEq/L) Non-anion gap metabolic acidosis[coreem.net]
    • Aldosterone deficiency results in sodium loss, hyperkalemia, and acidosis. Hyperkalemia stimulates aldosterone release to improve potassium excretion. Aldosterone is the first-line defense against hyperkalemia.[emedicine.medscape.com]
    Metabolic Acidosis
    • Eventually, they will receive critical VBG results that indicate a mild metabolic acidosis, hyperkalemia, and hyponatremia. The team will need to treat the hyperkalemia and initiate hydrocortisone therapy.[emsimcases.com]
    • acidosis Low bicarbonate (15-20mEq/L) Elevated BUN and creatinine Management Steroid Replacement Initial Dose Hydrocortisone 100mg IV preferred but can be given IM if necessary Stress dose hydrocortisone has mineralocorticoid activity (20mg 0.1mg Florinef[coreem.net]
    • Pathophysiologically, there is significant hyponatremia and hyperkalemia, often associated with metabolic acidosis, hypoglycemia, and (every so often) hypercalcemia.[news-medical.net]
    • Signs and symptoms include low blood pressure, nausea and vomiting, syncope, hypoglycemia, hyponatremia, hyperkalemia, a metabolic acidosis, lethergy, confusion, and convulsions.[openanesthesia.org]
    Hypotension
    • Classically it presents as severe hypotension refractory to IV fluids and vasopressors. Background Adrenal glands produce mineralocorticoids (aldosterone), glucocorticoids (cortisol) and androgens in the outer cortex.[coreem.net]
    • - confusion - nausea - vomiting - diarrhea - vague abdominal pain Hypotension may lead to shock.[signsandsyndromes.com]
    • , balance the effects of insulin helps maintain bp, water/salt balance secondary to an illness or a stressful event; becomes life threatening acute deficiency in cortisol production and this results in circulatory collapse and electrolyte imbalances hypotension[quizlet.com]
    • The features of acute adrenal crisis include hypotension (particularly postural hypotension), shock, and hyponatraemia in 90% of patients. Hyperkalaemia is also a feature in 65% of patients.[bmj.com]
    • The patient’s vitals are pertinent for significant hypotension (60s/40s) after receiving a 1L NS bolus, tachycardia, and tachypnea.[emdocs.net]
    Hyperkalemia
    • Eventually, they will receive critical VBG results that indicate a mild metabolic acidosis, hyperkalemia, and hyponatremia. The team will need to treat the hyperkalemia and initiate hydrocortisone therapy.[emsimcases.com]
    • Usually normalized w/ fluids and steroid replacement Monitor K Q2-3 hours as may fall during initial rehydration See Core EM post on Hyperkalemia for further management Prevention Triple PO steroids if known susceptibility to crisis in setting of physiologic[coreem.net]
    • Aldosterone deficiency results in sodium loss, hyperkalemia, and acidosis. Hyperkalemia stimulates aldosterone release to improve potassium excretion. Aldosterone is the first-line defense against hyperkalemia.[emedicine.medscape.com]
    • , hypercalcemia, azotemia (nitrogen), high creatinine sudden withdrawal of glucocorticoids, extress stress, trauma, sepsis, TB, adrenal hemorrhage, autoimmune watch VS (extreme hypotension), tele monitoring (hyperkalemia, hyponatremia), electrolytes,[quizlet.com]
    • An insulin stress test should cause hypoglycemia and a spike in both plasma cortisol and serum growth hormone within 1-2 hours. hypoglycemia hyponatremia, hyperkalemia return to top Differential Diagnosis return to top Treatments Hydrocortisone is the[sharinginhealth.ca]
    Hyponatremia
    • […] electrolytes, neuro checks (hypoperfusion, hypoglycemia, hyponatremia), daily weights, monitor for fluid overload provide a safe environment, teamwork and communication, minimize stress, nutritional intake (need to add salt!)[quizlet.com]
    • Eventually, they will receive critical VBG results that indicate a mild metabolic acidosis, hyperkalemia, and hyponatremia. The team will need to treat the hyperkalemia and initiate hydrocortisone therapy.[emsimcases.com]
    • An insulin stress test should cause hypoglycemia and a spike in both plasma cortisol and serum growth hormone within 1-2 hours. hypoglycemia hyponatremia, hyperkalemia return to top Differential Diagnosis return to top Treatments Hydrocortisone is the[sharinginhealth.ca]
    • These include: - hypotension (particularly postural) - tachycardia (rapid heart rate) - dehydration - hyponatremia (reduced serum sodium levels) - hyperkalemia (elevated serum potassium levels) - hypoglycemia (low blood sugar levels) - fever - weakness[signsandsyndromes.com]
    • A 22-year-old man was admitted to an intensive care unit with severe hyponatremia, hypotension and somnolence.[nature.com]
    Hypovolemic Shock
    • […] maintain bp, water/salt balance secondary to an illness or a stressful event; becomes life threatening acute deficiency in cortisol production and this results in circulatory collapse and electrolyte imbalances hypotension, tachycardia, dehydration, hypovolemic[quizlet.com]
    • This can cause patients to go into hypovolemic shock, which results in rapid and shallow breathing combined with an extremely fast but weak heart rate. An adrenal crisis can also result in a general feeling of fatigue and shaking chills.[livestrong.com]
    • In contrast, an acute adrenal crisis can present with vomiting, abdominal pain, and hypovolemic shock.[addisons-help.com]
    • This patient with bladder cancer metastatic to adrenal gland presented as acute adrenal insufficiency with hypovolemic shock.[ispub.com]
    Adrenocortical Insufficiency
    • Adrenal Crisis Adrenal Crisis excerpt Synonyms and related keywords: acute adrenal crisis, acute adrenocortical insufficiency, acute adrenal insufficiency, addisonian crisis, adrenal apoplexy, cortisol, aldosterone, primary adrenocortical insufficiency[addisons-help.com]
    • insufficiency E27.2 Addisonian crisis E27.3 Drug-induced adrenocortical insufficiency E27.4 Other and unspecified adrenocortical insufficiency E27.40 Unspecified adrenocortical insufficiency E27.49 Other adrenocortical insufficiency E27.5 Adrenomedullary[icd10data.com]
    • Steroid withdrawal is the most common cause of acute adrenocortical insufficiency and almost exclusively causes a glucocorticoid deficiency.[emedicine.medscape.com]
    • Secondary adrenocortical insufficiency occurs when exogenous steroids have suppressed the hypothalamic-pituitary-adrenal (HPA) axis.[emedicine.medscape.com]
    • Addisonian Crisis occurs primarily in patients with adrenocortical insufficiency, such as those suffering from Addison's disease . It can be triggered by stress (e.g. from infection, trauma, surgery, hemorrhage, or psychological distress).[signsandsyndromes.com]
    Hypothermia
    • On presentation, the patient will have mild hypothermia, hypoglycemia, and hypotension. The team will have to initiate fluid resuscitation and an initial workup.[emsimcases.com]
    • […] known primary or secondary adrenocortical insufficiency AIDS Invasive or infiltrative disorders Tuberculosis Physical: Unexplained shock, usually refractory to fluid and pressor resuscitation Nausea, vomiting, abdominal or flank pain Hyperthermia or hypothermia[addisons-help.com]

    Etiology

    Causes

    Metabolic Acidosis
    • Eventually, they will receive critical VBG results that indicate a mild metabolic acidosis, hyperkalemia, and hyponatremia. The team will need to treat the hyperkalemia and initiate hydrocortisone therapy.[emsimcases.com]
    • acidosis Low bicarbonate (15-20mEq/L) Elevated BUN and creatinine Management Steroid Replacement Initial Dose Hydrocortisone 100mg IV preferred but can be given IM if necessary Stress dose hydrocortisone has mineralocorticoid activity (20mg 0.1mg Florinef[coreem.net]
    • Pathophysiologically, there is significant hyponatremia and hyperkalemia, often associated with metabolic acidosis, hypoglycemia, and (every so often) hypercalcemia.[news-medical.net]
    • Signs and symptoms include low blood pressure, nausea and vomiting, syncope, hypoglycemia, hyponatremia, hyperkalemia, a metabolic acidosis, lethergy, confusion, and convulsions.[openanesthesia.org]

    Epidemiology

    Sex distribution
    Age distribution

    Pathophysiology

    Prevention

    Summary

    Patient Information

    Self-assessment

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    References

    1. Sunil P, A Shrestha, D Maksey, et al. Addisonian Crisis Precipitated By Thyroxine Therapy In A Patient With Type 2 Autoimmune Polyglandular Syndrome.Journal of Chitwan Medical College 2013; 3(4); 54-56.
    2. Husebye ES, Allolio B, Arlt W, et al; Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med. 2014 Feb;275(2):104-15.
    3. Hahner S, Loeffler M, Bleicken B, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency - the need for new prevention strategies. Eur J Endocrinol. 2010 Mar;162(3):597-602.
    4. Husebye ES, Allolio B, Arlt W, et al; Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med. 2014 Feb;275(2):104-15.
    5. Hahner S, Loeffler M, Bleicken B, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010 Mar; 162(3):597-602.
    6. Ahi S, Esmaeilzadeh M, Kayvanpour E, Sedaghat-Hamedani F, Samadanifard SH. A bulking agent may lead to adrenal insufficiency crisis: a case report. Acta Med Iran. 2011; 49(10):688-9.
    7. Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008 Jun; 36(6):1937-49.
    8. Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann. Intern. Med. 2003;139 (3): 194–204.
    9. Oelkers W, Diederich S, Bahr V. Diagnosis and therapy surveillance in Addison's disease: rapid adrenocorticotropin (ACTH) test and measurement of plasma ACTH, renin activity, and aldosterone. J Clin Endocrinol Metab. 1992 Jul; 75(1):259-64.

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