Cushing's syndrome is also called Hypercortisolism. Cushing's syndrome occurs due to high cortisol levels for a prolonged duration in the human body. However, the two terms namely Cushing's syndrome and Cushing's disease are not similar.
Cushing's disease is one cause of Cushing's syndrome characterized by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. Causes various physiological alterations in human systems. Affects an estimated 10-15 million people per year. Cushing’s syndrome most commonly affects adults aged 20-50 years and is more prevalent in females than males. Treatment of Cushing’s syndrome depends on the underlying cause of excess cortisol, the use of cortisol-inhibiting drugs but may include surgery, radiation, and chemotherapy.
2. CUSHING'S SYNDROME-is defined signs and symptoms
associated with corticosteroid excess for long duration.
CUSHING'S DISEASE-is corticosteroid excess due
to pituitary dependent bilateral adrenal hyperplasia.
• Basically , it is cushing's syndrome of pituitary
origin.
• More common in females.
3. NORMAL PHYSIOLOGY
Explained by hypothalamus-pituitary-adrenal axis(HPA)
-responsible for neuroendocrine adaptation component for
stress response.
STIMULUS- stress, physical activity, illness, serum cortisol
levels, circadian rhythm
HYPOTHALAMUS-neuroendocrine neurons in
paraventricular nucleus release corticotropin releasing
hormone(CRH)
ANTERIOR PITUITARY-releases adrenocorticotropic
hormone(ACTH) or corticotropin from corticotrope cells.
ADRENAL CORTEX- produces glucocorticoids mainly
cortisol in humans.
6. CLINICAL FEATURES
PROTEIN METABOLISM
1) Negative nitrogen balance and growth retardation
2)Thinning of skin and subcutaneous tissues; becomes paper like and transparent
3)Steroid myopathy-muscle wasting associated with hypokalemia produces
muscular weakness
4) Hair becomes thin and rough.
5) poor wound healing and minor injuries produces bruises
6)Muscle breakdown increases creatine excretion
7) Reduction in lymphoid tissue and dissolution of lymphocytes increases uric acid
excretion
CARBOHYDRATE METABOLISM
1) Hyperglycemia
2)Glycosuria (due to hyperglycemia and increased GFR)
3)Increased resistance to insulin causing Steroid (Adrenal) Diabetes.
7. 4) Increase in liver glycogen.
FAT METABOLISM –CENTRIPETAL FAT DISTRIBUTION
1)Extremities are thin
2) Deposition of fat
A) Over abdominal wall leads to 'pendular abdomen'-"LEMON ON MATCH STICK"
Causes rupture of thin skin due to stretching
PURPLISH STRIAE -seen over abdomen, buttocks
(due to increased RBC count) thighs.
B) MOON LIKE FACE- with narrow eye slit and fish like mouth (because GC's have
mild mineralocorticoid activity.
C) on upper back BUFFALO HUMP.
3) Increase in FFA level, blood lipids and cholesterol leads to atherosclerosis.
ELECTROLYTE AND WATER IMBALANCE AND VASCULAR REACTIVITY.
Leading to:-
8. 1) Edema.
2) Hypertension ( Increase in Plasma volume and Na+ retention)
BONE METABOLISM- Osteoporosis, vertebral compression # and may precipitate
Tetany.
BLOOD - Eosinopenia, Lymphopenia, basopenia, Neutrophilia, polycythemia,
Increase platelet count and Hypercoagulability
CNS- Euphoria, restlessness and excitability etc.
GIT- Peptic ulcer formation.
ANTI- INFLAMMATORY ACTION- Increased susceptibility to infection.
SEXUAL CHANGES-
1) HIRSUTISM- Increased facial hair and Increased secretion of adrenal
androgen.
2) Impotency and hypogonadism in males and Amenorrhea , Oligomenorrhea in
females { due to gonadal dysfunction }.
10. INVESTIGATIONS
HORMONAL STUDIES- aimed at diagnosis of cushing's syndrome and establishing
the cause.
TEST FOR ESTABLISHING THE PRESENCE OF CUSHING'S SYNDROME
1) PLASMA CORTISOL LEVEL- Normal at 8am(rise) and 12 midnight(lowest level.
In cushing's syndrome- this circadian rhythm is lost and cortisol remains same
throughout.
2)24- HOUR URINARY CORTISOL EXCRETION-
In cushing's -is raised( normal value < 90 microgram/24hour)
In psuedo-cushing's states- like chronic anxiety, depression ,polycystic ovary and
alcoholism milder elevation is seen.
3)OVERNIGHT DEXAMETHASONE SUPPRESSION TEST-
Patient takes dexamethasone at 11pm and plasma cortisol is measured at 8am
following day
11. Normal value < 1.8 microgram/dL ( previous value was <5microgram/dL but reduction
to 1.8microgram/dL. In cushing's cortisol levels are not suppressed
Test may be +ve in obese and alcoholics.
4) LOW DOSE DEXAMETHASONE SUPPRESSION TEST- not performed routinely
- If urinary- free cortisol or overnight dexamethasone suppression tests are
borderline, then this test is performed.
- patient administered with 0.5mg dexamethasone 6hourly for 2 days.
From 2nd day-24 hour urine is collected.
From 3rd day-plasma is collected for cortisol.
CONCLUSION- If urinary free cortisol falls below 10microgram/24hours
OR
Plasma cortisol is below 1.8microgram/dL.
Excludes diagnosis of cushing's syndrome.
12. 5) LATE NIGHT SALIVARY CORTISOL-
Promising for screening of cushings syndrome.
Basis- cortisol concentration in saliva is highly correlated with free plasma cortisol.
TESTS ESTABLISHING THE CAUSE OF CUSHING'S SYNDROME
1)PLASMA ACTH LEVEL AT 8AM-
A) Normal levels(10-80ng/L)- suggest a pituitary source.
B) Intermediate values (80-300ng/L) suggest either pituitary dependent disease or
ectopic ACTH syndrome.
C) Very high levels (>300ng/L)-suggest ectopic ACTH syndrome.
D) Low ACTH(<10ng/L)- suggest adrenal tumors, macronodular adrenal hyperplasia or
exogenous steroid administration.
2)HIGH DOSE DEXAMETHASONE SUPPRESSION TEST
Procedure similar to low dose dexamethasone test only 2mg dexamethasone is
administered.
13. Conclusion- If urinary -free cortisol falls below 10microgram/24 hour
OR
Plasma cortisol below 1.8microgram/dL
Indicates suppression of HPA axis and test is +ve-in cushings disease
-ve in Ectopic ACTH syndrome and
Adrenal tumors.
3)PLASMA K+ LEVELS-
Normal in pituitary dependent diseases and adrenal tumors.
Low(<3.5mmol/L) in ectopic ACTH syndrome.
4)ACTH/ CORTSOL RESPONSE TO CRF-
- Increased levels in pituitary dependent diseases.
-Unchanged in ectopic ACTH syndrome and adrenal tumors.
14. OTHER INVESTIGATIONS-
1) Blood sugar, cholesterol and LDL levels elevated.
2) Plain radiograph of skull.
3) CT/MRI of head.
4) Radiograph of chest to detect bronchogenic carcinoma.
5) MRI abdomen.
6) CT Scan of anterior mediastinum and upper abdomen including pancreas to rule out
tumors.
MANAGEMENT
ADRENAL TUMORS-
- Metyrapone or aminoglutethimide- reduce cortisol overproduction by blocking its
production.
-Adrenal adenoma or carcinoma removed surgically and tumor bed irradiated.
15. CUSHING'S DISEASE-
-Metyrapone or ketoconazole- given during preparation for surgery to reduce C/E
of hypercortisolism.
-tumor if present is surgically removed.
-if no tumor is found radical hypophysectomy done.
-Radiotherapy for treatment of recurrent or residual ACTH-secreting tumors.
-If diagnosis is uncertain B/L ADRENALECTOMY done followed by pituitary
irradiation to prevent NELSON'S DISEASE.
Enlargement of pituitary and presence of aggressive locally invasive pituitary
tumors with very high levels of ACTH in blood and hyperpigmentation of skin.
ECTOPIC ACTH SYNDROME-
-Benign tumors like bronchial carcinoid should be removed.
-Malignant tumors treated with radiotherapy and chemotherapy.