The Nervous System|
Synonyms : Cushing's Disease
is defined as the set of symptoms and signs associated with prolonged and
inappropriate elevation of free glucocorticoid (corticosteroid) levels.
Patients with Cushing’s syndrome can be classified into two groups on the
basis of whether the condition is ACTH-dependent or independent:
adrenal hyperplasia due to overproduction of ACTH usually from a pituitary
adenoma (Cushing’s disease)
ACTH syndrome (benign or malignant non-endocrine tumour producing ACTH-like
(long-term corticosteroid therapy)
Cushing’s syndrome of pituitary origin or associated with an adrenal tumour is four times more common in women than men. In contrast the ectopic ACTH syndrome (often due to a small cell carcinoma of the bronchus) is more common in men. When the iatrogenic and ectopic groups are excluded, pituitary dependent Cushing’s disease is the commonest cause of Cushing’s syndrome, accounting for about 80% of adult cases.
Clinical features: < BACK TO TOP >
Weight gain is the most common feature and results from the accumulation of adipose
tissue in the trunk, facial and cervical areas (like a ‘lemon on
characteristic patterns of fat deposition have been described as ‘truncal
obesity? ‘pendulous abdomen? ‘moon face?and ‘buffalo hump?
excess leads to collagen breakdown
which results in thinning of the skin and blood vessels with resultant
bruising, striae (bluish stretch marks especially over the abdomen, buttocks
and thighs) and skin breaks and ulcerations.
trauma produces gaping skin wounds which heal
poorly due to the negative effect of glucocorticoids on collagen
loss of protein from muscles (amino acids are used for gluconeogenesis) leads
to muscle atrophy (wastage) and weakness presenting as difficulty standing up
from a squatting position.
loss of the protein matrix leads to osteoporosis
presenting with back pain from spontaneous vertebral compression fractures and
in time abnormal body posture and reduced height.
interfere with the action of growth hormone in long bones leading to growth
retardation and short stature in children (a common problem when children are
on prolonged oral corticosteroid therapy as in severe asthma).
gluconeogenesis may lead to impaired glucose tolerance, tendency for hyperglycaemia and in 20% of individuals diabetes mellitus develops due to exhaustion of pancreatic b-cells.
Skin pigmentation (characteristic brownish or bronze colour) is found in
ACTH-dependent Cushing’s syndrome and is caused by the melanocyte
stimulating hormone (MSH) sequence which is a part of the ACTH molecule.
of the immune system with increased susceptibility
to infections (e.g., fungal skin infections) is also found.
increase vascular sensitivity to noradrenaline and adrenaline, which leads to hypertension.
women may experience increased hair growth (especially facial hair), acne,
oligomenorrhoea or amenorrhoea due to associated increased adrenal androgen
secretion, which is usually found in adrenal carcinomas.
Adults frequently present with psychiatric problems ranging from irritability and depression to wide range of psychotic symptoms.
Diagnosis: < BACK TO TOP >
laboratory tests are used in diagnosis, including urinary and plasma cortisol (both elevated).
Dexamethasone suppression test involves administration of synthetic glucocorticoid
dexamethasone [Dexamethasone, Sofradex] and then measurements of plasma
cortisol. In normal individuals dexamethasone causes drop in plasma cortisol
levels through the feedback mechanism involving the pituitary gland (reduced
release of ACTH). In Cushing’s syndrome this effect is missing and no
change in plasma cortisol level is observed.
hypoglycaemia stimulates a rise in plasma cortisol in normal subjects but not
in patients with Cushing’s syndrome.
of plasma ACTH is the key to
establishing the differential diagnosis; elevated levels suggest pituitary or
ectopic ACTH source, adrenal tumour is associated with undetectable plasma
to administered corticotrophin-releasing
factor (CRF) can be then used to distinguish between pituitary and
ectopic ACTH-dependant Cushing’s syndromes (in pituitary disease there is
increase in ACTH level after the administration of CRF; this is missing in
ectopic ACTH production because it is not CRF-dependant).
skull X-rays are usually normal in
patients with pituitary-dependent Cushing’s disease because microadenomas
are usually very small; high resolution CT scanning may be more accurate.
ACTH is undetectable, suggesting an adrenal tumour, then an adrenal
scan using selenium-75-labelled cholesterol is useful in locating an
adrenal adenoma (carcinomas do not usually take up the isotope and therefore
are not readily visualised).
Abdominal CT or MR scanning may be an option for diagnosis of adrenal tumours.
Management < BACK TO TOP >
of choice depends on the cause but it is essential as untreated Cushing’s
syndrome has a 50% five-year mortality.
adenomas should be surgically removed
via a loin approach. It may take several months for the contralateral adrenal
gland and the hypothalamus and pituitary to recover. During this time
replacement therapy in form of hydrocortisone is required.
carcinomas should also be resected
if possible, an then treated with radiotherapy.
of glucocorticoids can be blocked
by drugs like aminoglutethimide [Cytadren], metyrapone [Metopirone] or
through the nose with selective removal of the pituitary adenoma (found in
75% of cases) is the treatment of choice in Cushing’s disease and results
in cure in about 80% of patients. The rest of the pituitary function will
also need to be assessed.
diagnosis is not certain then bilateral adrenalectomy
may be the correct treatment.
ectopic ACTH syndrome benign or malignant tumours causing this syndrome
(usually in the lungs) have to be treated appropriately (surgical removal,
radiotherapy and chemotherapy).
Therapeutic Use of Corticosteroids
The anti-inflammatory actions of corticosteroids have led to their use in a wide variety of clinical conditions (various autoimmune diseases, asthma etc.). With modern corticosteroid drugs it is possible to distinguish between glucocorticoid and mineralocorticoid effects, but not between wanted anti-inflammatory and unwanted metabolic actions. Metabolic effects
identical to those found in Cushing’s syndrome and they are
related to dose and duration of treatment. Some patients experience marked changes
in mood on high-dose glucocorticoid therapy ranging from euphoria to
profound depression. Osteoporosis
is a major problem of long-term, high dose therapy. Glucose intolerance or
frank diabetes mellitus may be produced. Hypertension
is also common, as well as damage to
the stomach mucosa (especially if given together with nonsteroidal
anti-inflammatory drugs) which can lead to acute gastritis and peptic ulcer
(with of without bleeding).
Suppression of hypothalamus-pituitary-adrenal axis is found in long-term treatment and is characterised with very low ACTH secretion. This is the reason why corticosteroids should be withdrawn slowly to prevent the development of adrenal insufficiency. HPA axis suppression can to some extent be avoided if these drugs are given in single morning dose when levels of endogenous glucocorticoid production reaches its peak.
Prognosis < BACK TO TOP >
Nutrition < BACK TO TOP >
Nutrition that alleviate or prevent Cushing's syndrome :-
Herbs < BACK TO TOP >
Herbs that alleviate or prevent Cushing's syndrome :-
(source : -)
7 April 2010
10 December 2004 - International Human Rights Day
World No-Tobacco Day
World Health Day
speaker Mr NgThian Watt the Principal Trainer from
Napoleon Hill Associates MalaysiaDetails
Montaine Gift vouchers