THREE ENDOCRINE MYSTERIES
Three real cases • three diagnostic pivots • thirty minutes
01
Labs, masses, and a biopsy that did not answer the question
02
A lean adult whose diabetes refused to fit the usual categories
03
A four-month spiral of vomiting, anorexia, and weight loss
Chitharanjan Duvoor, MD
ADEEF Symposium • September 19, 2026
2
Three cases. Three mismatches.
The pattern that does not fit is often the clue.
01
The physiology was urgent
The patient looked terminal. One endocrine test changed what we did that afternoon.
02
The phenotype was misleading
Lean. Antibody-negative. C-peptide preserved. Yet a tiny insulin dose changed the CGM.
03
The medication was already stopped
The drug was gone for months — but its endocrine effect was not.
ADEEF Symposium 2026
3
CASE 1
A patient who looked like he was running out of time
58-year-old man • immunosuppressed • 60-lb weight loss • progressive decline
The story before endocrine was called
Night sweats and rigors
Poor appetite and marked weight loss
Confusion / slowed cognition
AKI with no prior advanced CKD
New bilateral adrenal masses
Prior ERCP Bx X 2 non diagnostic ,adrenal biopsy: necrosis / “ghost cells”
Primary team had already discussed goals of care; hospice was consulted, Oncology ,Nephrology on case.
Four numbers that should make you pause
SODIUM
121
mmol/L
POTASSIUM
5.5
mmol/L
CREATININE
2.7
mg/dL
HEART RATE
126
bpm
AUDIENCE QUESTION
What single endocrine process could unify the electrolyte pattern, weight loss, and deterioration?
Case details are de-identified and derived from the clinical record supplied for this presentation.
ADEEF Symposium 2026
4
CASE 1
One test changed the urgency
The question was no longer “what is the mass?” — it became “what must we treat right now?”
COSYNTROPIN STIMULATION
Peak cortisol
~6 µg/dL
Poor response
Na 121 + K 5.5
This physiology could not wait for every send-out test.
AUDIENCE QUESTION
Would you wait for ACTH / antibodies / pathology — or treat now?
Treatment started immediately
Hydrocortisone
50 mg IV q8h
+
Fludrocortisone
0.1 mg/day
REVEAL
Primary adrenal insufficiency
Endocrine Society guidance recommends immediate stress-dose IV hydrocortisone when adrenal crisis is suspected.
ADEEF Symposium 2026
CASE 1 • CT AT PRESENTATION
At presentation: bilateral adrenal enlargement.
Two CT views during active disease — bilateral enlargement was the imaging clue.
Active disease • axial CT
Active disease • coronal CT
6
CASE 1
Then he sat up.
Steroid replacement changed the bedside picture — but it did not explain the bilateral masses.
BEFORE
Progressive decline
Confused / slowed
Barely eating
Severe weight loss
AKI + profound hyponatremia
AFTER HYDROCORTISONE
Sitting up
Walking
Talking normally
Eating
Drinking
ADEEF Symposium 2026
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CASE 1
What was destroying both adrenal glands?
Now the exposure history mattered more than the incidentaloma algorithm.
A
Malignancy / infiltration
Weight loss + bilateral masses + prior nondiagnostic biopsy
B
Tuberculosis / atypical mycobacteria
Could involve both adrenals; prior T-Spot was negative
C
Fungal infection
Immunosuppression + Arkansas/Missouri + farm exposure
D
Autoimmune Addison disease
Explains adrenal failure, but not the new bilateral masses
THE CLUES
•
Humira / methotrexate exposure
•
Cattle + chickens
•
Endemic region
•
Night sweats / rigors
•
New bilateral adrenal masses
•
Existing tissue already available
Would you repeat the biopsy — or ask pathology to go back to the tissue you already have?
ADEEF Symposium 2026
CASE 1 • PATHOLOGY
The biopsy was not the end of the story.
Initial adrenal biopsy: extensive necrosis / necrotic “ghost” cells. The morphology was not yet diagnostic.
H&E — necrotizing granulomatous pattern.
CASE 1 • FINAL REVEAL
Now the pieces fit.
GMS staining of the adrenal biopsy demonstrated numerous fungal organisms.
Disseminated histoplasmosis
with bilateral adrenal involvement
Primary adrenal insufficiency was the endocrine manifestation of bilateral adrenal destruction.
GMS stain → organism identified → treatment redirected.
GMS stain
Numerous small budding yeast forms.
CASE 1 • FOLLOW-UP
Follow-up: the adrenals shrank.
Same plane, different phase: active adrenal enlargement versus interval shrinkage after treatment.
BEFORE • active disease
AFTER • recovery
TEACHING PEARL
Radiographic improvement does not guarantee adrenal recovery.
The glands can involute while adrenal insufficiency persists.
CASE 2
She came to me with an A1c of 10.4% after pregnancy
34-year-old woman • ~140 lb • no strong family history of diabetes
DURING PREGNANCY
A1c 8.5%
Strict diabetic diet
Metformin + glipizide
Glycemia still above goal
POST-PREGNANCY
A1c 10.4%
A1c rose despite continued treatment
Lean phenotype
No classic hyperglycemic symptoms
WHEN SHE SAW ME
Persistent hyperglycemia
Metformin + glipizide
Ozempic 0.5 mg weekly trial
Jardiance → yeast infection; stopped
AUDIENCE QUESTION
What type of diabetes is this — and what would you test next?
ADEEF Symposium 2026
CASE 2
The workup made the classification harder
Autoimmunity was negative. Endogenous insulin secretion was preserved. Genetics did not give us the answer.
DIABETES CLASSIFICATION WORKUP
GAD65 antibody
Negative
Islet-cell antibody (ICA)
Negative
ZnT8 antibody
Negative
Insulin antibody
Negative
Fasting C-peptide
2.4 ng/mL
Preserved endogenous secretion
MODY genetic panel
Negative
SO WHAT IS IT?
Type 1?
Antibodies repeatedly negative
CT Abd normal pancreas.
No family h/o CF
Type 2?
Lean phenotype
no obvious severe insulin resistance. Dexamethasone suppression test neg.
MODY?
Extended Genetic panel negative
Nothing fit cleanly.
IA-2 antibody
Negative
ADEEF Symposium 2026
ADEEF Symposium 2026
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CASE 2
Now what do we call it?
The physiology is clear. The classification is not.
Seronegative type 1?
Possible — negative antibodies do not completely exclude type 1 diabetes.
Lean type 2 / β-cell dysfunction?
Possible — lean phenotype does not rule out type 2 diabetes.
Monogenic diabetes?
Reasonable to investigate — but the tested MODY panel was negative.
Atypical / unclassified?
Sometimes the most honest label while longitudinal data accumulate.
Treat the physiology now. Revisit the label later.
Serial C-peptide with concurrent glucose may become more informative over time.
ADA Standards of Care in Diabetes—2026: C-peptide ≥1.8 ng/mL indicates substantial endogenous secretion in an insulin-treated adult; 5–10% of type 1 diabetes may be antibody-negative.
ADEEF Symposium 2026
CASE 3
Three months. Forty pounds. Still no diagnosis.
Hospitalized with persistent nausea, vomiting, progressive weight loss, and loss of function.
THE DECLINE
240 lb → 200 lb
40-lb loss in ~3 months
Accountant → unable to work by admission
KNOWN HISTORY
Endometrial cancer
On letrozole
No obvious explanation yet for the GI symptoms and weight loss.
THE INPATIENT WORKUP
CT abdomen / pelvis
Imaging
EGD
Colonoscopy
HIDA scan
Extensive testing — still no unifying diagnosis.
THEN SOMEONE CHECKED CORTISOL.
Endocrinology was consulted.
After all of that testing, what history would you reopen?
CASE 3
Endocrine consultation changed the direction of the case
First the cortisol clue. Then the medication history connected the timeline.
1 THE CORTISOL CLUE
CORTISOL
9.6
µg/dL • indeterminate
DHEA-S
13.7
low
ELECTROLYTES
Normal
mineralocorticoid function preserved
BLOOD PRESSURE
Preserved
does not exclude central AI
2 THEN I TOOK THE MEDICATION HISTORY
Endometrial cancer treatment
Letrozole + prior megestrol acetate (Megace)
Megace was used as hormonal therapy for the cancer — not for appetite stimulation.
ON MEGACE
Chronic exposure
~4 MONTHS AGO
Megace stopped
AFTER STOPPING
Decline began
Nausea • vomiting • poor appetite • 40-lb weight loss • functional decline
DIAGNOSTIC PIVOT
Symptoms began after Megace was stopped.
Megestrol has glucocorticoid activity → HPA-axis suppression can persist after withdrawal.
ADEEF Symposium 2026
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CASE 3
Hydrocortisone changed the story
The treatment response matched the suspected physiology.
Nausea
Resolved
Vomiting
Resolved
Appetite
Improved
Overall function
Improved
Dose evolution
Discharge
15 mg AM + 10 mg noon
Insomnia → dose reduced
Current
10 mg AM + 5 mg noon
FINAL DIAGNOSIS
Secondary adrenal insufficiency
from megestrol-induced HPA-axis suppression
Next: reassess HPA-axis recovery over time and use the lowest effective physiologic replacement dose.
ADEEF Symposium 2026
Three cases. Three diagnostic pivots.
The pattern that did not fit was the clue.
01
LOOK AGAIN
A “nondiagnostic” biopsy may deserve a new question — not immediately a new procedure.
02
TRUST THE PHYSIOLOGY
When classification is uncertain, treat the biology you can actually measure.
03
RE-OPEN THE MEDICATION HISTORY
A drug that was stopped months ago can still explain today’s endocrine symptoms.
Treat the physiology first. Keep asking why.
Thank you