Adrenal Insufficiency Diagnosis Algorithm
Clinical features:
- Weight loss, anorexia, Weakness, fatigue, GI distress
- Hypotension, shock, orthostasis
- Hyperpigmented skin (due to high ACTH stimulating melanocytes, only seen in PRIMARY adrenal insufficiency)
- Unexplained hypoglycemia, Hyponatremia, hyperkalemia, eosinophilia
Diagnostic findings (see algorithm):
- AM serum cortisol (around 6-8AM) – if value is < 3, strongly suggestive of adrenal insufficiency; if > 18, adrenal insufficiency unlikely
- If serum cortisol borderline/inconclusive (3-18), proceed with cosyntropin stimulation test:
Steroids that DO not interact with stim test
- dexamethasone
- fludrocortisone
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Adrenal Insufficiency - Diagnosis and Management Summary
Primary Adrenal Insufficiency:
Most Common Cause in the US: Autoimmune Adrenalitis
Other causes: TB, fungal infection, HIV, adrenoleukodystrophy, check point inhibitors, bilateral hemorrhage or metastatic disease (rare), and drugs (ketoconazole, etomidate)
Symptoms and Exam Findings:
Fatigue (85-100%), weight loss (65-75%) w/ anorexia, abdominal pain w/ N/V (60-90%), Muscle/joint pain (10-40%), hyperpigmentation (95%), orthostatic or frank hypotension
In secondary AI, hyponatremia may still be present due to increased ADH. Hyperkalemia is absent because aldosterone levels are unaffected. Hyperpigmentation is absent (low ACTH).
Causes of Secondary Adrenal Insufficiency: Long-term steroid use (most common), pan-hypopituitarism including: pituitary tumor, TB and histoplasmosis, infiltrative diseases, check point inhibitors, lymphocytic hypophysitis, Sheehan's syndrome.
PEARLS:
1. A STIM test can be performed at any time of the day.
2. A baseline 8am cortisol <3 is diagnostic of AI and a cortisol level of at least 18 excludes AI.
ACTH STIM TEST:
1. Obtain baseline cortisol and ACTH
2. Give 250 mcg of cosyntropin
3. Measure cortisol at 30 and 60 minutes
Cortisol level of less than 18 is diagnostic of AI
- Dr. Ann Marie Kumfer @AnnKumfer
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Adrenal Insufficiency Differential Diagnosis Algorithm
Clinical suspicion: Weakness, fatigue, nausea, musculoskeletal pain, dizziness, volume depletion, abdominal pain, hypotension, hyponatremia, hyperkalemia, hyperpigmentation, hypoglycemia
Testing:
• Adrenocorticotropic hormone (ACTH) stimulation test AND
• Baseline plasma ACTH
Low Cortisol Response - Adrenal insufficiency likely:
• High baseline ACTH - Primary adrenal insufficiency
• Low or normal baseline ACTH - Secondary adrenal insufficiency
ARUPConsult @ARUPLabs
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Primary Adrenal Insufficiency:
• ACTH stimulation test - Synthetic ACTH does not stimulate cortisol secretion because the dysfunctional adrenal cortex is already maximally stimulated by endogenous ACTH
• Serum cortisol measured between 8 and 9 AM - Low
• Plasma ACTH - Elevated, because feedback inhibition by adrenal cortisol is absent
• Plasma aldosterone - Low in cases in which injury to the adrenal gland impacts both cortisol and aldosterone production
• CRH stimulation test - Not necessary
• Adrenal autoantibody tests - Serum tests that detect titers of adrenal autoantibodies are available for the confirmation of autoimmune-mediated primary adrenal insufficiency. The most commonly ordered is the 21-hydroxylase antibody test
Secondary Adrenal Insufficiency:
• ACTH stimulation test - If the secondary adrenal insufficiency is mild or of recent onset, there is an increase in cortisol secretion; in chronic secondary adrenal insufficiency plasma cortisol is minimally increased after administration of ACTH because the adrenal cortex is atrophied from a long-term lack of stimulation by ACTH
• Serum cortisol measured between 8 and 9 AM - Low
• Plasma ACTH - Low, because the origin of the disorder is in the hypothalamus or pituitary
• Plasma aldosterone - Often normal, although it may be depressed if there is significant atrophy of the adrenal glands as a result of chronic lack of stimulation by ACTH
• CRH stimulation test - This test can distinguish between ACTH deficiency (from the pituitary) and deficiency of CRH (from the hypothalamus); plasma ACTH and cortisol are measured after administration of CRH; if secondary adrenal insufficiency is the result of a hypothalamic disorder, the CRH will produce an increase in plasma ACTH and cortisol
• Adrenal autoantibody tests - Not necessary
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Primary Adrenal Insufficiency
Addison's Disease - Damage of the adrenal glands with lack of cortisol, androgens and aldosterone
Causes of Adrenal Insufficiency:
Most Common Causes:
• Autoimmune > Tuberculosis
Infiltrative Disorders:
• Infection (tuberculosis, fungal infections)
- Tuberculosis: can cause adrenal calcification and enlargement
• Sarcoidosis
• Lymphoma
Metastatic Disease -> Adrenals:
• Lung cancer
• Renal cell carcinoma, and melanoma
Bilateral Adrenal Hemorrhage:
• Consider if unexpected hypotension develops
• Risk factors for BAH include protein C deficiency, anticoagulation, DIC and sepsis
- (Neisseria meningitidis, H Flu, pneumococci, pseudomonas)
Autoimmune: + 21-Hydroxylase Antibodies:
• 50% will develop another autoimmune endocrine disorder
- Primary hypothyroidism
- Primary ovarian insufficiency
- Celiac disease,
- Hypoparathyroidism
- Type 1 diabetes mellitus
Aldosterone Deficiency:
Symptoms:
• Salt craving
• Dizziness
• Nausea/vomiting
• Fatigue
Signs:
• Orthostasis
• Hypotension
Labs:
• ↑ PRA
• ↓ Serum sodium
• ↑ Serum potassium
• ↑ H+ (NAGMA from RTA type IV)
Cortisol Deficiency:
Symptoms:
• Fatigue
• Weakness
• Low-grade fever
• Weight loss
• Anorexia
• Nausea/vomiting
• Abdominal pain
• Back pain
• Arthralgia
• Myalgia
Cortisol Deficiency: Signs
• Hyperpigmentation ("bronzing")
- Palmar creases
- Extensor surfaces
- Buccal mucosa
- *Not present in approximately 5% patients
• ↓ BP
• ↓ Serum cortisol
• ↑ Plasma ACTH
• ↓ Serum sodium
• ↓ Plasma glucose
• ↑ Eosinophils (Not always present)
↓ DHEA/Androgens:
• Symptoms: Reduced libido
• Signs: Decreased axillary or pubic hair
• Labs: ↓ Serum DHEAS
Diagnosis:
• History and physical:
- Symptoms/physical exam.
- Dark patches on the skin might be a clue
• Blood tests:
- Check sodium, potassium, AM cortisol and ACTH
- + 21-hydroxylase antibodies are found in approximately 90% of autoimmune adrenalitis cases
- Serum cortisol < 3 ug/dL -> Primary AI present
- ACTH stimulation test: Administer 250 mcg ACTH. Measure at 0, 30, and 60 mins.
- Check Serum Cortisol. IF < 18 ug/dL Primary AI present
- ACTH test is not affected by use of DEXAMETHASONE
- ACTH test is affected by HYDROCORTISONE
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