1. Adrenal
Pathology
Kristine Krafts, M.D.

2. Adrenal Path Lecture Outline
Introduction
A disease with too much hormone: Cushing syndrome
A disease with too little hormone: Addison disease
Tumors of the adrenal

3. Adrenal Path Lecture Outline
Introduction

4. Adrenal gland anatomy

5. Adrenal gland histology and hormones
Mineralocorticoids
(e.g., aldosterone)
Hormones:
Zona glomerulosa
Glucocorticoids
(e.g., cortisone)
Capsule
Sex hormones
e.g., dehydroepiandrosterone)
Zona fasiculata
and
Adrenalin
Zona reticularis
Noradrenalin
Medulla
Adrenal gland histology and hormones

6. Adrenal Path Lecture Outline
Introduction
A disease with too much hormone: Cushing syndrome

7. Cushing Syndrome Elevated serum cortisol Clinical features:
Hypertension
Characteristic pattern of weight gain
Hyperglycemia
Thin skin
Depression
Most common cause: exogenous steroids

8. Cushing syndrome: buffalo hump

9. Cushing syndrome: moon facies

10. Causes of Cushing syndrome

11. Adrenal Path Lecture Outline
Introduction
A disease with too much hormone: Cushing syndrome
A disease with too little hormone: Addison disease

12. Addison Disease Also called primary chronic adrenal insufficiency
Decreased serum cortisol and mineralocorticoids
Most common cause: autoimmune attack on adrenal cortex
Eventually fatal if not treated

13. Symptoms of Addison Disease
Early: signs are vague (weakness, fatigue)
Later: skin bronzing/hyperpigmentation
Eventually: serious complications (hypotension, electrolyte imbalances)
Misdiagnosis is not uncommon

14. Why is there hyperpigmentation in Addison disease?
Cortisol
Normal
ACTH
Addison Disease
↓ Cortisol

15. Hyperpigmentation in Addison disease

16. 33 year-old female with no prior medical issues.
Day 1 prior to admission
Headache
Day 2 prior to admission
Very fatigued, vomiting
Day of admission
Husband brought to ER
Vision loss right eye
BP 100/60
Given IV fluids

17. Day 2 post admission
Right-sided paralysis
Oxygen levels dropping
CT: brain swelling
Day 3 post admission
Coma
BP 70/33 despite IV fluids
40 pound weight gain
Day 4 post admission
No brain activity
Acute renal failure
“Nothing else can be done.”

18. Day 5 post admission
Different doctor
IV Na+, hydrocortisone, dextrose
Day 6 post admission
Opened eyes
Day 10 post admission
IV removed

19. In ensuing weeks
Feeding tube removed
Intensive speech, physical,
occupational therapy
Two months later
Back to work
Feeling normal
Must take steroids daily for the rest of her life

20. Adrenal Path Lecture Outline
Introduction
A disease with too much hormone: Cushing syndrome
A disease with too little hormone: Addison disease
Tumors of the adrenal

21. Pheochromocytoma Derived from adrenal medulla cells
Cells produce epinephrine
Patients present with hypertension
Usually benign
Diagnosis: epinephrine breakdown products in urine

22. A couple good pheo mnemonics
Pheo symptoms
The 10% tumor
10% occur outside
the adrenal
10% bilateral
10% familial
10% malignant
Paroxysms of...
Pressure (hypertension)
Perspiration
Palpitations (tachycardia)
Pallor

23. Neuroblastoma Derived from neural crest cells
Relatively common childhood tumor
Prognosis better in:
Children < 18 months
Lower stage/grade
Hyperdiploid tumors
Fewer copies of N-myc

24. MEN Syndromes

25. Brad Pitt vs. John Cleese

34. No contest!

35. MEN Syndromes
Inherited disorders that predispose patients to getting endocrine tumors
MEN-1 and MEN-2 (A and B)
MEN tumors are much more aggressive than sporadic tumors

36. MEN Syndromes Ridiculously Simplified
Thyroid
Not much
Medullary carcinoma
Other Endocrine Organs
Hyperplasia, adenoma, carcinoma

37. MEN Syndromes Ridiculously Simplified
Thyroid
Not much
Medullary carcinoma
Other Endocrine Organs
Hyperplasia, adenoma, carcinoma

38. MEN I Clinical Features
Parathyroid hyperplasia
Pancreatic endocrine tumors
Pituitary adenoma

39. MEN I Genetics MEN1 gene mutation Tumor suppressor gene Encodes menin
Mutation turns off the gene

40. MEN-1
Pitt-uitary adenoma
MEN1 gene
run-of-the-mill
inactive
turn off

41. MEN Syndromes Ridiculously Simplified
Thyroid
Not much
Medullary carcinoma
Other Endocrine Organs
Hyperplasia, adenoma, carcinoma

42. MEN 2A Clinical Features
Medullary thyroid carcinoma
Pheochromocytoma
Parathyroid hyperplasia

43. MEN 2A Genetics RET gene mutation Proto-oncogene
Encodes tyrosine kinase receptor
Mutation turns gene on

44. MEN 2B 2B has most of the features of MEN 2A
Medullary thyroid carcinoma
Pheochromocytoma
RET gene mutation
But it’s slightly different
No parathyroid involvement
Patients are “marfanoid”

45. MEN-2 Cleese-cell hyperplasia bRETon gene one of a kind
always turned on