The biggest trigger for adrenal crisis is
gastrointestinal illness.[10] The physiological mechanisms underlying an adrenal crisis involve the loss of endogenous
glucocorticoids' typical inhibitory effect on inflammatory
cytokines.[9]
A tailored prescription, as well as a strategy for administering additional
glucocorticoids for physiological stress, are critical preventative measures. When an adult experiences an adrenal crisis, they require immediate parenteral
hydrocortisone.[13]
About 6 to 8% of patients with
adrenal insufficiency experience an adrenal crisis at some point each year.[7] The mortality rate linked to adrenal crises is up to 6%.[6]
There is a greater risk for adrenal suppression with longer durations, greater doses, and oral and
intraarticular preparations. Nonetheless, no amount, time frame, or mode of administration can reliably predict
adrenal insufficiency.[30]
Patients with
adrenal insufficiency have a 50% lifetime risk of experiencing an adrenal crisis,[5] and those who have experienced an adrenal crisis in the past seem to be more susceptible to another episode.[6]
Triggers
A known precipitating event can be found in over 90% of episodes of adrenal crisis.[5] The most common cause of adrenal crisis is
gastrointestinal illness. This is probably because it has a direct impact on how well oral
glucocorticoids are absorbed through the
intestines.[6] Stress from surgery is another common cause.[32]
Loss of
cortisol suppresses nuclear factor
κB (NF-κB) and
activator protein 1 (AP-1) at the cellular level, which allows genes that generate inflammatory proteins to be activated without restriction. This is because cortisol normally inhibits NF-κB's binding to the
glucocorticoid receptor.[9] Additionally, through
potassium retention and
sodium and water loss,
mineralocorticoid deficiency—which is common in primary but not in secondary
adrenal insufficiency—is likely to aggravate adrenal crises.[31]
Diagnosis
When a patient with
adrenal insufficiency is known to be exhibiting symptoms of an adrenal crisis, treatment needs to start right away. When a patient is deemed medically unstable, treatment shouldn't be postponed in even when diagnosis is still pending.[11]
A customized prescription as well as a plan for the administration of additional
glucocorticoids for physiological stress are important preventative measures. If oral
glucocorticoids are not an option, parenteral
hydrocortisone should be used, preferably at home. Devices like
MedicAlert bracelets and necklaces can alert caregivers to the possibility of adrenal crisis in patients who are unable to communicate verbally.[9]
Although the exact dosage has been debated, it is generally agreed upon that all patients with proven adrenal insufficiency should receive
glucocorticoid replacement during stressful times. The recommended amounts of glucocorticoid replacement are dependent on the anticipated stress, and the current guidelines depend on expert opinion.[39] Though there may be variations in specific regimens, most agree that stress doses for simple surgery should be quickly tapered and should not last longer than three days. This is because unneeded steroid excess can lead to infections, poor wound healing, and
hyperglycemia.[5]
In those who are unable to tolerate oral medication or do not respond to stress doses, a low threshold to initiate parenteral
hydrocortisone management should be used to guarantee adequate systemic absorption, since
gastroenteritis frequently precedes an adrenal crisis[6] and a rise in oral
glucocorticoids may not always avoid an adrenal crisis.[40]
Patients experiencing vomiting, chronic
diarrhea, or an imminent adrenal crisis should receive
intramuscular hydrocortisone. Patients must be prepared to administer it themselves because they can rapidly deteriorate.[39] A lot of patients may own a
hydrocortisone ampoule,[41] but not all have practiced the injection, and most will depend on medical professionals to give it to them in the event of an adrenal crisis episode.[32] Patients may experience significant physical as well as
cognitive impairment during their illness, which may impair their capacity to make wise decisions or administer medicine.[42] Therefore, patients should receive training on intramuscular
hydrocortisone use and education on how to recognize an adrenal crisis, as well as assistance from a close family member or friend.[39]
In case an individual suffering from
adrenal insufficiency loses consciousness, they must receive the necessary medical attention. Reminding patients to always wear or keep a
MedicAlert bracelet or just an emergency card is important.[43] A survey of 46 patients revealed that some medical professionals are reluctant to medicate the condition even when it is brought to their attention, which is a serious cause for concern. Only 54% of patients got
glucocorticoid administration within 30 minutes of arrival, even though 86% of patients were promptly attended to by a medical professional within forty-five minutes of a distress call.[44] In situations when doctors are unsure about a patient's need for additional
hydrocortisone, it is wise to listen to patients and their loved ones as they frequently have the most knowledge about this rare disorder.[45]
Treatment
The two foundations of treatment for adrenal crisis are steroid replacement and
fluid resuscitation.[5] When adrenal crisis treatment is started as soon as possible, it can be effective in preventing irreversible effects from prolonged
hypotension.[9] Treatment shouldn't be postponed while doing diagnostic tests. If there is reason to suspect something, a blood sample could be taken right away for
ACTH and serum
cortisol testing; however, treatment needs to begin right away, regardless of the results of the assay. Once a patient has recovered clinically, it is safe to confirm the diagnosis in an acutely ill patient.[46]
In cases of emergency, parenteral
hydrocortisone can be given as soon as possible by
intramuscular (IM) injection while IV access is being established, or as a
bolus injection of 100 mg of intravenous (IV)
hydrocortisone. After this bolus, 200 mg of
hydrocortisone should be administered every 24 hours, either continuously by IV infusion or, if that is not possible, in doses of 50 mg of
hydrocortisone per IV/IM injection every 6 hours.[47] A constant infusion of
hydrocortisone results in a
cortisol concentration insert at a steady state.[48]
Patients with
hypoadrenalism are more likely to die from adrenal crises; the death rate from adrenal crises can amount to 6% of crisis events.[6] "Adrenal failure" accounted for 15% of deaths in a study conducted in
Norway involving 130
Addison's disease patients, making it the second most common cause of death.[51] While symptoms may have gone unnoticed prior to the fatal episode, fatal adrenal crises have happened in patients who had never been diagnosed with
hypoadrenalism.[52]
Epidemiology
An adrenal crisis occurs in roughly 6–8% of those with
adrenal insufficiency annually.[7] Patients with
primary hypoadrenalism experience adrenal crises somewhat more frequently compared to those with
secondary adrenal insufficiency.[31] This is likely due to the fact that patients with primary hypoadrenalism lack
mineralocorticoid secretion and some secondary adrenal insufficiency patients retain some
cortisol secretion.[53] Despite varying degrees of consequent adrenal suppression, patients with
hypoadrenalism from long-term
glucocorticoid therapy rarely experience adrenal crises.[54]
The treatment of
pituitary tumors and the widespread use of
opioids for both malignant and increasingly non-malignant pain, as well as exogenous
glucocorticoid therapy for the numerous inflammatory as well as malignant conditions that become more common in people over 60, are the main causes of a new diagnosis of
adrenal insufficiency in older adults.[57][54] Adrenal crisis is more likely to occur in older people.[58]Urinary tract infections, particularly in older women, are often linked to an adrenal crisis, as is
pneumonia as well as a flare-up of
chronic respiratory disease.[59]Cellulitis is linked to adrenal crises within this age range and may be more prevalent in patients with fragile skin who have been exposed to higher doses of
glucocorticoids.[60] Older adults frequently experience falls and
fractures, which may be linked to
postural hypotension, especially in those who have
primary adrenal insufficiency.[61]
Older patients have a higher mortality rate from adrenal crisis, at least in part due to the existence of
comorbidities that make treatment more difficult.[62]
While studies on the prevalence of adrenal crisis in older adults are scarce, one population-based investigation into hospital admissions for adrenal crisis found that the incidence increased with age in older patients, going from 24·3 (60–69 years) to 35·2 (70–79 years) and 45·8 (80+ years) per million per year. This is significantly higher compared to the general adult admission rate, which is 15·0 per million annually in the same population.[60]
Untreated adrenal crisis can cause severe morbidity in both the mother and the fetus, such as inadequate wound healing, infection,
venous thromboembolism, extended hospital stays, preterm birth,
fetal intrauterine growth restriction, and an increased risk of
cesarean delivery.[65] The occurrence of adrenal crisis during pregnancy is uncommon, even in patients who have a documented history of adrenal insufficiency. In one study, pregnancy was identified as a trigger for adrenal crisis in 0.2% of the 423 patients. In a different study only 1.1% of the 93 patients in the study who had a known insufficiency experienced an adrenal crisis during pregnancy.[66]
Studies have demonstrated that younger children with
congenital adrenal hyperplasia experience adrenal crisis events more frequently than older children and adolescents.[71] Furthermore, research on
congenital adrenal hyperplasia in children shows that individuals with more severe salt-wasting types have a higher chance of needing to be hospitalized.[72] There are differences in the incidence of adrenal crises between the sexes, and these differences change with age.[73] Psychosocial factors have the potential to alter the baseline adrenal crisis risk as well, especially as patients transition from parental treatment oversight to self-management in adolescence.[74] Management in this age group is further complicated by changes in cortisol
pharmacokinetics, resulting in an increased clearance as well as volume without a change to the
cortisol half-life that has been shown during the pubertal period.[75]
There is still a significant morbidity and death associated with
adrenal insufficiency in newborns and early children. It has been estimated that 5–10 episodes of adrenal crisis occur for every 100 patient years in children with adrenal insufficiency; incidences may be higher in specific countries. Adrenal crisis among kids results in death in about 1/200 cases.[13]
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