The Glucocorticoid axisReem Alyahya

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.

Learning objectives:

• Which additional radiological investigations do you recommend?

• Which treatment would you propose?

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.

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.

Radiological investigations

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-rayRadiolabelled

octreotide(Scintigraphy)

Adrenal CT or MRI:

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

Pituitary MRI

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

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).

Radiolabelled octreotide(Scintigraphy)

• involves injection of a radioactive substance followed by an imaging scan.

• Occasionally used in locating ectopic ACTH tumors.

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.

pharmacotherapy

Surgery Radiotherapy

Depending on the cause.

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.

• Metyrapone750 mg – 4 g daily , in 3-4 divided doses.

• Ketoconazole :200 mg three times daily

Surgery and radiotherapy (Cushing’s disease)

Trans-sphenoidal removal of the

tumor.

Bilateral adrenalectomy

Pituitary irradiation

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.

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.

Radiotherapy (pituitary irrdiation).

• Alone is slow acting.

• Only effective in 50-60% even after prolonged follow up

• Used mainly after failed pituitary surgery.

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.

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.

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.

Thank you for listening.Any question?