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8/7/2019 Addisonian Crisis
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Manish K
Medical Officer
IGMH
Addisonian Crisis
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y Addisonian Crisis is an acute exacerbation of symptoms in
someone withAddisons disease (namely adrenal
insufficiency)
y Addisons disease is seen in someone with a deficiency in
corticosteroids.
y Whereas Cushings syndrome is seen in patients with excesscorticosteroids,
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INTRODUCTIONINTRODUCTION
y Addison disease is adrenocortical insufficiency
y due to the destruction or dysfunction of the entireadrenal cortex.
y affects both glucocorticoid and mineralocorticoidfunction.
y The onset of disease usually occurs 90% of bothadrenal cortices are dysfunctional or destroyed.
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y Much like Thyroid disease,Addisons disease is failure ofsome aspect the complex system of hormones and feedbackloops
y Also, like Thyroid disease, there may be dysfunction as thesehormones and messengers interact with the hypothalamus,pituitary and the site of hormone release (in this case the
adrenal glands)
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Connecting the dots
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Adrenal Gland
y Description
y AKA
y Suprarenal gland
y Location
y On top of each kidney
y Composed of:
y Adrenal cortex
y Adrenal Medulla
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yAdrenal Cortex
yZona Glomerulosa
mineralocorticoid production,aldosterone
yZona Fasciculataglucocorticoid production, cortisol
y
Zona Reticularisandrogen production, includingtestosterone
yMedullacatecholamines epinephrine andnorepinephrine
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Hormone & Function
y Adrenal Cortex
y Mineralocortioids
y Aldosterone
y Function
y Regulates electrolyte & fluid
homeostasis
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Hormone & Function
y Adrenal Cortex
y Glucocorticoidsy
Cortisoly Hydrocortisone
y Functiony Stim. gluconeogenesis & K
blood glucosey Anti-inflammatory
y Anti-immunity
y Anti- allergy
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Hormone & Function
y Adrenal Cortex
y Androgen
y Sex hormones
y Function
y Female
y Stim. Sex drive
y Men
y Negligible
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Hormone & Function
y Adrenal Medulla
y Epinephrine
y Adrenaline
y Functiony Prolong & K SNS
(sympathetic nervous
system) response to stress
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Hormone & Function
y Adrenal Medulla
y Norepinephrine
y Function
y Prolong & K SNS
(sympathetic nervous
system) response to stress
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Effects ofEpinephrine & Norepinephrine
a. K cardiac output
b. K metabolic rate
c. Vasoconstriction
d. K respiratory rate
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Learning Tip
SALT, SUGAR& SEX
y Aldosterone = promotes salt retention
y Cortisol= sugar
y Androgens = sex hormones
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y Race: no association.
y Gender: Idiopathic autoimmune Addison diseasetends to be more common in and children.
y Age: The most common 30-50 years, but maypresent earlier in patients with:
y polyglandular autoimmune syndromes,
y congenital adrenal hyperplasia (CAH), or
y
if onset is due to a disorder of long-chain fatty acidmetabolism.
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Mortality and morbidity.Mortality and morbidity.
y Usually are due to
y failure or delay in making the diagnosis or
y failure to institute adequate glucocorticoid andmineralocorticoid replacement.
y If not treated promptly, acute addisonian crisismay result in death.
y May be either de novo, such as by adrenal
hemorrhage, or
y In the setting of an acute event superimposed onchronic or
y Inadequately treated adrenocortical insufficiency.
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Causes:Causes:
y Idiopathic autoimmune adrenocorticalinsufficiency:
- The most common cause.
- Accounts for more than 80% of cases.
Due to -y autoimmune atrophy,y fibrosis, andy
lymphocytic infiltration of the adrenal cortex, usuallywith sparing of the adrenal medulla.
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y Idiopathic autoimmune Addison disease may occur inisolation or in association with other autoimmunephenomena such as:
Schmidt syndrome:
The association of Addison disease and Hashimotothyroiditis.
Polyglandular autoimmune syndrome type 1:The association of Addison disease with
hypoparathyroidism and mucocutaneous candidiasis.
It may have an autosomal recessive mode ofinheritance. It has no human leukocyte antigen (HLA)associations.
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Polyglandular autoimmune syndrome type2:
The association of Addison disease with type 1diabetes mellitus and Hashimoto thyroiditis or Gravesdisease. It may be associated with HLA-B8 and DR-3.
Chronicgranulomatous diseases:
TB, sarcoidosis, histoplasmosis, blastomycosis, and
cryptococcosis could involve the adrenal glands.
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Malignancies:Malignant infiltration of the adrenal cortices, as with
Hodgkin and non-Hodgkin lymphoma and leukemia,may cause Addison disease.
Metastatic malignant disease: Bilateral involvement ofthe adrenal glands could occur in the setting ofmetastatic cancer of the lung, breast, or colon or renalcell carcinoma.
Infiltrative metabolic disorders :
Amyloidosis and hemochromatosis could involve theadrenal glands and lead to primary adrenocorticalinsufficiency.
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y Acquired immunodeficiencysyndrome:as a result of invasion of CMV, Mycobacteriumavium intracellulare, cryptococci, or Kaposisarcoma.
y Allgrove syndrome:congenital adrenocortical unresponsiveness toACTH typically presents in childhood with failure
to thrive, features of adrenocortical insufficiencyand hypoglycemia.
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y Drug-related causes:-Ketoconazole inhibits the adrenal
cytochrome P450 steroidogenic enzymes.
-Aminoglutethimide blocks the earlyconversion of cholesterol to pregnenolone byinhibiting the 20,22-desmolase enzyme.
-Busulphan, etomidate, and trilostane inhibit
or interfere with adrenal steroid biosynthesis.
AbdominalIrradiation.
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Clinical presentation:Clinical presentation:y The onset of symptoms most often is insidious and
nonspecific.- Hyperpigmentation of the skin and mucous membranes
often precedes all other symptoms by months toyears.y Due to stimulant effect of excess (ACTH) on the
melanocytes to produce melanin.y Seen on the sun-exposed areas of the skin, extensor
surfaces, knuckles, elbows and knees in addition tomucous membranes; dentogingival margins and buccalareas.
- Vitiligo:y common in autoimmune Addison disease as a result of
melanocytes destruction.
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Physical examination:Physical examination:y Female patients may show an
y absence of axillary and pubic hair
y decreased body hair.
y
Due to loss of the adrenal androgens, a major source ofandrogens in women.
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y Dizziness with orthostasisy due to hypotension occasionally may lead to syncope.y due to the combined effects ofvolume depletion, loss of
the mineralocorticoid effect of aldosterone, and loss of thepermissive effect of cortisol in enhancing the vasopressor
effect of the catecholamines.
y Myalgias and flaccid muscle paralysisy may occur due to hyperkalemia.
y Progressive weakness, fatigue, poor appetite,andweight loss.
y Gastrointestinal symptomsy may include nausea, vomiting, and occasional diarrhea.
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Diagnosis:
Review of patientss history + skin tanning
Biochemical tests (insufficient cortisol) X-ray (calcium deposit: TB)
Synthetic ACTH ( 250 mg i.v.)
30-60 min
Blood/Urine Cortisol (T0, 30,60)
I. Rapid ACTH test
ACTH stimulation test: most specific
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y In acute adrenal crisis,y a blood sample for a random plasma cortisol level
should be drawn prior to starting hydrocortisonereplacement.
y A random plasma cortisol value of 25 mcg/dLeffectively excludes adrenal insufficiency of any
kind.
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y Interpreting Rapid ACTH stimulation test:
y -Two criteria are necessary for diagnosis:y (1) in the baseline cortisol value of 7 mcg/dL
y (2) the value must rise 20 mcg/dL in 30 - 60 mins,establishing normal adrenal glucocorticoid function.
y In patients with Addison disease, both cortisol andaldosterone show minimal or no change in responseto ACTH.
y When the results of the rapid ACTH do not meet the2 criteria mentioned above, further testing might berequired to distinguish Addison disease fromsecondary adrenocortical insufficiency.
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II. Long ACTH stimulation test:
synthetic ACTH (i.v or i.m)
48-72 hr
Blood / urine cortisol (T 0, 48, 72)
Interpretation: - primary adrenal insufficiency: no response
- secondary adrenal insufficiency: adequate response
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(Normal: glucose fall, cortisol rise)
Insulin-induced hypoglycemia
Blood glucose, cortisol at T0
Fast-acting insulin injection
Blood glucose, cortisol at T 30,45,90 min
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y Urea and electrolyte:
- Na, K, and a mild nonanion-gap metabolicacidosis due toy the loss of the Na-retaining & K + H ion-secreting action of
aldosterone.
- BUN and creatinine due toy
hypovolemia, GFR, and renal plasma flow.
- Hypoglycemia may be present in fasted patients,or it may occur spontaneously
y caused by the peripheral utilization of glucose and insulinsensitivity.
y more prominent in children and in patients with secondaryadrenocortical insufficiency.
- Urinary and sweat Na also may be .
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y CBC:- may reveal a normocytic normochromic anemia.
Thyroid-stimulating hormone:- TSH,y with or without thyroxine,y with or without associated thyroid autoantibodies,y with or without symptoms of hypothyroidism,
y may occur in patients with Addison disease and inpatients with secondary adrenocorticalinsufficiency due to isolated ACTH deficiency.
y These findings may be slowly reversible withcortisol replacement.
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ManagementManagement -- ImagingImaging::
y Chest x-ray:- normaly except in evidence of TB or fungal infection that
initially cause Addison disease.
y CTscan:- Abdominal CT scan may be normal but- May show bilateral enlargementof the Adrenal
glands in patients with Addison diseasey TB, fungal infections, adrenal hemorrhage, orinfiltrating diseases involving the adrenal glands.
- In idiopathic autoimmune Addison disease, theadrenal glands usually are atrophic.
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Histological finding:Histological finding:
y In cases due to idiopathic autoimmuneadrenocortical atrophy, the adrenal glands usuallyare atrophic, with marked lymphocytic infiltrationand fibrosis of the adrenal capsule. The adrenal
medulla is spared.
y In cases due to TB, the adrenal glands may beenlarged and contain caseating granulomas.Diffuse calcification may be evident, and the
adrenal medulla usually is involved.
y In patients with AIDS, the adrenal glands mayshow necrotizing inflammation, hemorrhage, andinfarction.
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y Histology
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Medical treatment: inpatient careMedical treatment: inpatient care
y In case of adrenal crisis:
- IV access should be established urgently.
-IV NS to restore volume deficit & correct hypotension.
- Some patients may require glucose supplementation.
- Find and Correct precipitating cause
- Hydrocort 100 mg IV bolus stat
- Administer 100 mg of hydrocortisone in 100 cc of NSby continuous IV infusion @10-12 cc/h.
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y Clinical improvement, especially BP response, shouldbe evident within 4-6 hours of hydrocort infusion.
y After 2-3 days, the stress hydrocortisone doseshould be to 100-150 mg, infused over a 24-hourperiod, irrespective of the patient's clinical status.y To avoid stress gastrointestinal bleeding.
y As the patient improves and as the clinical situationallows,y the hydrocortisone infusion can be gradually tapered
over the next 4-5 days to daily replacement doses ofapproximately 3 mg/h (72-75 mg over 24 h)
y and eventually to daily oral replacement doses, whenoral intake is possible.
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y As long as the patient is receiving 100 mgHydrocort in 24 hours,y
no mineralocorticoid replacement is necessary.y The mineralocorticoid activity of hydrocortisone in
this dosage is sufficient.
y Thereafter, as the hydrocort dose is weaned,y
mineralocorticoid replacement should be instituted indoses equivalent to the daily adrenal glandaldosterone output of 0.05-0.20 mg every 24 hours.
y The usual mineralocorticoid used for this purposeis 9-alpha-fludrocortisone, usually in doses of0.05-0.10 mg per day or q other day.
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Management: outpatientManagement: outpatient
y Closely monitor Pts on steroid replacementtherapy fory any signs of inadequate replacement (e.g., morning
headaches, weakness, and dizziness) andy any signs of over-replacement (e.g., cushingoid
features).y A periodic bone dual-energy x-ray absorptiometry
(DEXA) detecting early osteoporosis in patients whoare over-replaced with maintenance steroids.
y
Patients should be instructed to 2x / 3x tripletheir steroid replacement doses in stressfulsituations such as a common cold or toothextraction.
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SpecialSpecial concernconcern -- Intra OpIntra Op
y Continuous IV infusion of 10mg per hourhydrocortisone or an intermittent IV bolus injectionevery 6-8 hours may be used.
y After the procedure, the hydrocortisone may berapidly tapered within 24-36 hours to the usualreplacement doses, or as gradually as the clinicalsituation dictates.
y Mineralocorticoid replacement usually can bewithheld until the patient resumes dailyreplacement steroids.
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Summary
Hypofunction Hyperfunction
Disorder Addisonsdisease
Cushing syndrome
S&S Na+ & H20 loss
Hypotension
Hypoglycemia
Fatigue
Hyperkalemia
Na+ & H20 retention
Wt. gain
Hyperglycemia
Buffalo humpMoon face
Hypokalemia
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Summary
Hypofunction Hyperfunction
Usual tx Glucocorticoids
Meneralocorticoid
Restore fluid
Alter steroid Rx
Surgery
Nrs Dx Fluid volume deficit Fluid volumeexcess
Glucose intolerance
Diet K Na+L K+
L Na+
K K+
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