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Cushing’s Syndrome

Title

Ñ    Cushing’s Syndrome

Definition

Ñ    Cushing’s syndrome

Is a condition caused by:

Ñ    Increased free circulating glucocorticoid

Pathogenesis

Causes

ACTH dependent

Ñ    Pituitary dependent (Cushing’s disease):

·          Pituitary adenoma

·          Pituitary carcinoma

·          CRH secreting tumour:

Hypothalamic, ectopic

Ñ    Ectopic ACTH producing tumours:

Small cell carcinoma of lung

Bronchial carcinoid

Medullary thyroid carcinoma

Pancreatic carcinoma

Phaeochromocytoma

Non-ACTH dependent

Ñ    Adrenal adenoma

Ñ    Adrenal carcinoma

Ñ    Exogenous steroid

Pathophysiology

Ñ    Increased physiological effects of cortisol

Clinical Features

History:

E&M

Ñ    Weight gain

Ñ    Growth arrest:

In children

KUS

Ñ    Polyuria

Ñ    Polydypsia

RAG

Ñ    Loss of libido

Ñ    Amenorrhoea, oligomenorrhoea

CNS

Ñ    Insomnia

Ñ    Depression

Ñ    Psychosis

Ñ    Muscular weakness

LMS

Ñ    Backache

Examination

E&M

Ñ    Central obesity

Ñ    Moon face

Ñ    Buffalo hump

IS

Ñ    Hirsutism

Ñ    Frontal balding

Ñ    Acne

Ñ    Pigmentation:

ACTH excess

Ñ    Thin skin

Ñ    Skin infections

Ñ    Poor wound healing

Ñ    Striae

Ñ    Bruising

Ñ    Plethora

CVS

Ñ    Hypertension

Ñ    Venous thrombosis

Ñ    Oedema

CNS

Ñ    Proximal muscle weakness

LMS

Ñ    Osteoporosis

Ñ    Fractures:

Vertebrae

Ribs

Investigations

Confirm Cushing’s

Fluids

Ñ    24 hour urinary free cortisol

Ñ    Loss of circadian rhythm of cortisol secretion

Ñ    48 hour low dose dexamethasone suppression test (0.5 mg 6 hourly for 48 hours):

Failure to suppress cortisol

Determine Cause

Imaging

Ñ    Adrenal CT or MRI

Ñ    Pituitary MRI

Ñ    Chest x-ray

Fluids

Ñ    High dose dexamethasone suppression test (2 mg 6 hourly for 48 hours):

Failure to suppress cortisol suggests ectopic source or adrenal tumour

Pituitary dependent disease suppresses

Ñ    Plasma ACTH levels

Ñ    CRH test:

Exaggerated ACTH or cortisol response suggests pituitary dependent disease

Ectopic sources do not respond

Management

Control

Drugs

Ñ    Metyrapone

Ñ    Ketoconazole:

Synergistic with metyrapone

Ñ    Aminoglutethimide

Ñ    Trilostane

Ñ    Mitotane:

Palliation of adrenal carcinoma

Ñ    Chemotherapy:

ACTH secreting tumours

Surgery

Pituitary Dependent

Ñ    Trans-sphenoidal removal of pituitary tumour

Ñ    Bilateral adrenalectomy:

·          Cushing’s disease, as a last resort:

With pituitary irradiation to prevent Nelson’s syndrome

Adrenal adenoma

Ñ    Resection

Adrenal carcinoma

Ñ    Resection or debulking

ACTH secreting tumours

Ñ    Resection if possible

Radiotherapy

Ñ    Pituitary irradiation

Ñ    Irradiation of ACTH secreting tumours

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