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CPE-008 · version 1.0.0
Adrenal Insufficiency Pattern Engine: when to test, how to read cortisol and ACTH, and what is an emergency
Morning cortisol bands, ACTH and stimulation results, glucocorticoid exposure and the adrenal-crisis situations that cannot wait.
Adrenal insufficiency hides behind fatigue, weight loss and a low sodium. The Adrenal Insufficiency Pattern Engine separates the features that justify testing from the ones that do not, reads a morning cortisol against the Endocrine Society bands, and uses ACTH to place the problem in the adrenal gland or above it.
It also holds the situations that matter most in practice: glucocorticoid exposure by any route, immune checkpoint inhibitors, central hypothyroidism before levothyroxine, and a suspected adrenal crisis, where it says to treat first and wait for nothing. It names no dose, not even in an emergency.
Playground
Load a synthetic case or type your own values. The result recomputes as you type, and every rule links to its page.
Cortisol testing
- <5 very likely
- 5–14.9 indeterminate
- ≥15 unlikely
46 pg/mL is assumed when empty.
Chemistry and vitals
Symptoms and signs
Exposures, history and context
What it does
- Reads an 8 am cortisol as very likely (<5 µg/dL), indeterminate (5 to <15) or unlikely (≥15), and the cosyntropin peak against 18 µg/dL.
- Uses ACTH to label a primary or a secondary/tertiary pattern, and prompts the cause work-up for each.
- Flags results that may mislead: late sampling, estrogen or pregnancy, low binding-protein states, recent glucocorticoid.
- Recognizes glucocorticoid-induced risk by any route, megestrol and opioids, and checkpoint-inhibitor symptoms.
- Escalates suspected adrenal crisis, severe hyperkalemia or hypoglycemia with adrenal clues, and a central hypothyroid pattern before levothyroxine.
What it never does
- Diagnose adrenal insufficiency, or call hyperpigmentation or salt craving pathognomonic.
- Name a glucocorticoid dose or taper.
- Delay an emergency for laboratory confirmation.
- Treat fatigue alone as a reason to test.
Safety gates
These gates run before the pattern is shown, and urgent findings are displayed first.
- Hypotension with a recognized adrenal risk raises an emergency alert: treat first, do not wait for results.
- Potassium ≥6.0 or glucose <54 with other adrenal features raises an urgent alert.
- A central hypothyroid pattern raises a priority alert to assess the adrenal axis before levothyroxine.
- Known insufficiency with fever, vomiting, trauma or surgery raises a sick-day-rules alert.
Inputs
- 8 am cortisol, ACTH, cosyntropin-stimulated peak
- Sodium, potassium, glucose, eosinophils, systolic blood pressure
- Symptoms and signs including hyperpigmentation and salt craving
- Glucocorticoid exposure, checkpoint inhibitors, known insufficiency
- Pituitary context and central hypothyroid pattern
Scope
In scope
- Adults aged 18 and over
Routed out
- Patients under 18
The full rule catalog
19 active rules. Each has its own page with conditions, outputs and evidence. 19 of 19 active rules are exercised by at least one synthetic case.
Screening
Classification
Safety
Missing data
Synthetic cases
Every case is synthetic. Open one to see the inputs, the full result and the rule trace; then change the values.
ADR-FX-01
Low sodium, high potassium, weight loss and nausea
A 44-year-old with hyperpigmented scars.
ADR-FX-02
Hyperpigmentation and fatigue
No labs yet.
ADR-FX-03
Salt craving and dizziness on standing
Low sodium.
ADR-FX-04
Cortisol 2.1 with ACTH 180
Low cortisol and high ACTH: a primary pattern.
ADR-FX-05
Morning cortisol 9 µg/dL
Indeterminate.
ADR-FX-06
Morning cortisol 17 µg/dL
Unlikely.
ADR-FX-07
Stimulated peak cortisol of 11 µg/dL
Insufficient response.
ADR-FX-08
Cortisol 3.0 with ACTH 5, after head trauma
A secondary pattern.
ADR-FX-09
Prednisone 10 mg for eight weeks, now tired
Glucocorticoid exposure.
ADR-FX-10
Repeated joint injections and high-dose inhaled steroid
Non-oral routes count.
ADR-FX-11
Checkpoint inhibitor, headache and sodium 129
An immune-related adverse event to look for.
ADR-FX-12
Blood pressure 78/40, known adrenal insufficiency, vomiting
A possible adrenal crisis.
ADR-FX-13
Hypotension after stopping long-term prednisone
Chronic glucocorticoid exposure and sodium 124.
ADR-FX-14
Known adrenal insufficiency with fever
Sick-day rules.
ADR-FX-15
Low free T4 with low TSH
Assess the adrenal axis before levothyroxine.
ADR-FX-16
Cortisol 8 µg/dL drawn at 2 pm
Afternoon sample.
ADR-FX-17
Cortisol 14 on an oral contraceptive
Binding globulin raises total cortisol.
ADR-FX-18
Cortisol 3.5, ACTH missing
The axis cannot be classified.
ADR-FX-19
Potassium 6.4, sodium 126 and hyperpigmentation
Severe metabolic derangement.
ADR-FX-20
A 15-year-old is outside the adult pathway
Pediatric patient.
ADR-FX-21
Fatigue alone
One non-specific symptom does not justify testing.
ADR-FX-22
Primary pattern, antibodies already done
The cause work-up continues.
ADR-FX-23
Megestrol use and fatigue
Megestrol has glucocorticoid activity.
ADR-FX-24
Normal stimulation test
Peak cortisol 22 µg/dL.
Evidence
Guidelines and references the rules cite. Each rule page lists the ones that support it.
EV-ES-PAI-2016Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-389.
Supports: Morning cortisol and ACTH as first tests; ACTH stimulation with 250 µg cosyntropin; peak cortisol below 18 µg/dL as insufficient Suspected adrenal crisis must be treated without waiting for tests
EV-HUSEBYE-2014Husebye 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;275(2):104-115.
Supports: Morning cortisol below about 5 µg/dL makes insufficiency very likely, above about 15 µg/dL unlikely
EV-ES-HYPOPIT-2016Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(11):3888-3921.
Supports: Assess the adrenal axis before thyroid replacement in central hypothyroidism Secondary adrenal insufficiency testing
EV-ES-GCAI-2024Beuschlein F, Else T, Bancos I, et al. European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency. J Clin Endocrinol Metab. 2024;109(7):1657-1683.
Supports: Glucocorticoid exposure by any route can suppress the axis; do not stop abruptly; cross-reactivity of prednisolone in cortisol assays
EV-ASCO-IRAE-2021Schneider BJ, Naidoo J, Santomasso BD, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol. 2021;39(36):4073-4126.
Supports: Endocrine immune-related adverse events: hypophysitis and adrenal insufficiency
EV-RUSHWORTH-2019Rushworth RL, Torpy DJ, Falhammar H. Adrenal Crisis. N Engl J Med. 2019;381(9):852-861.
Supports: Recognition of adrenal crisis and its precipitants
Frequently asked questions
What cortisol values does the engine use?
For an 8 am total cortisol: below 5 µg/dL makes adrenal insufficiency very likely, 5 to under 15 is indeterminate and needs a stimulation test, and 15 or above makes it unlikely. A stimulated peak below 18 µg/dL is an insufficient response. These follow the Endocrine Society guideline and the primary-insufficiency consensus statement, and assays differ.
How does it tell primary from secondary adrenal insufficiency?
With ACTH. Low cortisol with ACTH above the laboratory upper limit points to the adrenal gland (primary); low cortisol with ACTH not raised points to the pituitary or hypothalamus, or to suppression by exogenous glucocorticoid. Without ACTH the engine says the axis cannot be classified.
What does it do in a suspected adrenal crisis?
It raises an emergency alert: hypotension in a patient with known insufficiency, glucocorticoid exposure, hyponatremia, hyperkalemia or hypoglycemia. The text says to treat first per protocol and not wait for test results. It names no dose.
Why does steroid exposure by an inhaled or injected route count?
The 2024 ESE/Endocrine Society guideline on glucocorticoid-induced adrenal insufficiency includes exposure by any route at or above about 5 mg a day of prednisone equivalent for 3 to 4 weeks, including high-dose inhaled, injected and topical glucocorticoids.
Why does a central hypothyroid pattern trigger an adrenal alert?
Because low free T4 with a low or normal TSH raises the possibility of pituitary disease, and starting levothyroxine in unrecognized adrenal insufficiency can precipitate a crisis. The thyroid engine raises the same alert from its side.
Specification status: Executable specification v1.0.0, authored by Biod from the narrative CPE-008 specification and current guidelines. Reviewed by Dr. Vinicius Amaral, D.O. Not for clinical production use.
Clinical review: Dr. Vinicius Amaral, D.O., Medical reviewer, 2026-10-03.
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Game
Pattern challenge
Guess what the engine will report.
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