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Cushing's syndrome

Synonyms :  Cushing's Disease

Clinical features, Diagnosis, Management, Prognosis, Nutrition, Herbs,

    Cushing’s syndrome 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: 

    1. ACTH-dependent

           Bilateral adrenal hyperplasia due to overproduction of ACTH usually from a pituitary adenoma (Cushing’s disease)

           Ectopic ACTH syndrome (benign or malignant non-endocrine tumour producing ACTH-like proteins) 

    2. Non-ACTH-dependent

           Iatrogenic (long-term corticosteroid therapy)

           Adrenal adenoma

           Adrenal carcinoma 

    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 toothpicks?.

           These characteristic patterns of fat deposition have been described as ‘truncal obesity? ‘pendulous abdomen? ‘moon face?and ‘buffalo hump?

           Glucocorticoid 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.

           Minor trauma produces gaping skin wounds which heal poorly due to the negative effect of glucocorticoids on collagen synthesis.

           The 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.

           In bone 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.

           Glucocorticoids 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).

           Increased 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.

           Suppression of the immune system with increased susceptibility to infections (e.g., fungal skin infections) is also found.

           Glucocorticoids increase vascular sensitivity to noradrenaline and adrenaline, which leads to hypertension.

           Some 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 >

           Various 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.

           Insulin-induced hypoglycaemia stimulates a rise in plasma cortisol in normal subjects but not in patients with Cushing’s syndrome.

           Measurement 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 ACTH.

           Response 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).

           Plain 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.

           If 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 >

             Treatment of choice depends on the cause but it is essential as untreated Cushing’s syndrome has a 50% five-year mortality.

             Adrenal 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.

             Adrenal carcinomas should also be resected if possible, an then treated with radiotherapy.

             Synthesis of glucocorticoids can be blocked by drugs like aminoglutethimide [Cytadren], metyrapone [Metopirone] or mitotane [Lysodren].

             Trans-sphenoidal surgery 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.

             If the diagnosis is not certain then bilateral adrenalectomy may be the correct treatment.

             In 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

    are 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 :-
C

Herbs < BACK TO TOP >

Herbs that alleviate or prevent Cushing's syndrome :-
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