1. The Glucocorticoid axis
Reem Alyahya

2. Introduction
• A 46 y/o man present with fever, red
tender area on his right leg, consistent
with erysipelas.
• His recent medical history reveals
fatigue, easy bruising and wt. gain in the
past 6 months.
• His family history is negative for DM and
HT.
• physical examination shows central
obesity (BMI 32.5 kg/m2, waist
circumference 115 cm)
• BP 160/104
• Moon face appearance, a dorsal fat pad
in the neck and abdominal purple striae.

3. Learning objectives:
• Which additional radiological investigations do you recommend?
• Which treatment would you propose?

4. What is Cushing’s syndrome?
• Cushing syndrome is caused by prolonged exposure to elevated levels of
either endogenous glucocorticoids or exogenous glucocorticoids.
endogenous
• glucocorticoid
overproduction
or
hypercortisolism
• Due to primary
adrenocortical
neoplasm
exogenous
• Following the
therapeutic
adminstrition of
synthetic
steroids of
ACTH.

5. Cushing’s syndrome VS Cushing’s disease ?
• Cushing’s syndrome :
- clinical state of increased free
circulating glucocorticoid
- Spontaneous Cushing’s
syndrome rare
• Cushing’s Disease:
- ACTH dependent
hypercorticism , pituitary
dependant.
- it is the most common cause of
Cushing's.

6. Radiological investigations

7. Radiological investigations
 It should be performed after the biochemical laboratory evaluation has
been done.
 It’s used to determine the cause or complications.
Adrenal CT or
MRI
Pituitary MRI Chest X-ray
Radiolabelled
octreotide
(Scintigraphy)

8. Adrenal CT or MRI:
• Adrenal adenomas and
carcinomas are relatively large
and can be detected by CT scan
imaging.

9. Pituitary MRI
• A pituitary adenoma can be seen
but it is often small and not
visible in a significant proportion
of cases.

10. Chest X-ray
• It is used in patients with
suspected ectopic ACTH
production.
• The ACTH-secreting tumors are
often oat-cell carcinomas of the
lung (bronchus carcinoma).

11. Radiolabelled octreotide
(Scintigraphy)
• involves injection of a radioactive
substance followed by an imaging
scan.
• Occasionally used in locating
ectopic ACTH tumors.

12. Treatment
• Successful treatment of Cushing’s syndrome should lead to reversal of the
presenting clinical features.
• However, untreated Cushing’s syndrome has a very bad prognosis, with
death from: hypertension, MI, infection and heart failure.
• Whatever the underlying cause, cortisol hypersecretion should be
controlled prior to surgery or radiotherapy.

13. pharmacotherapy
SurgeryRadiotherapy
Depending
on the
cause.

14. Pharmacotherapy (Cushing’s syndrome)
• The goal of pharmacotherapy is to reduce morbidity and prevent
complications.
Somatostatin
Analogs
• bind and activate human
somatostatin receptors
resulting in inhibition of
ACTH secretion, which
leads to decreased
cortisol secretion.
• pasireotide
0.6-0.9 twice daily
Adrenal steroid
inhibitors
• These agents either
inhibit the synthesis of
mineralocorticoids and
glucocorticoids, or
competitively bind
glucocorticoid receptors.
• Metyrapone
750 mg – 4 g daily , in 3-4
divided doses.
• Ketoconazole :200 mg
three times daily

15. Surgery and radiotherapy (Cushing’s disease)
Trans-sphenoidal
removal of the
tumor.
Bilateral
adrenalectomy
Pituitary
irradiation

16. Trans-sphenoidal removal of the tumor
• Is the treatment of choice.
• Result in remission of 75-80% of
the cases.
• But the results vary considerably.
• Experienced surgeon is essential.

17. Bilateral adrenalectomy
• It’s an effective last resort if other
measures fail to control the
disease.
• The patient will need
hydrocortisone (cortisol)
replacement therapy after
surgery, and possibly continued
throughout life.

18. Radiotherapy (pituitary irrdiation).
• Alone is slow acting.
• Only effective in 50-60% even
after prolonged follow up
• Used mainly after failed pituitary
surgery.

19. Cushing’s syndrome due to other causes.
 Adrenal adenomas:
- should be resected after
achievement of clinical remission
with metyrapone.
 Adrenal carcinoma:
- are highly aggressive and has
poor prognosis.
- if there’s no widespread
metastases, tumor bulk should be
removed surgically.
- adrenolytic drug mitotane may
inhibit the growth of the tumor
and prolonged survival.
- radiotherapy can be used.

20. conclusion
• A 46 y/o man present with fatigue, easy bruising and wt. gain
• The patient had moon face appearance, a dorsal fat pad in the neck and
abdominal purple striae.
• The diagnostic tests reveals that the patient has Cushing's syndrome.
• The patient will initially manage the cortisol levels by taking metyrapone
4 gm/ 3 daily, Ketoconazole, 200 mg /3 daily
• Further treatment decided based on the specific etiology.

21. References
• Kumar & Clarks, Clinical Medicine ,
eighth edition (2012).
• Up to date : Cushing's syndrome.
• Up to date : Cushing's syndrome
treatment (Beyond the Basics)
• Emedicine : medscape: Cushing’s
syndrome.

22. Thank you for listening.
Any question?