EXPLAINING OF CUSHING SYNDROME

EXPLAINING OF CUSHING SYNDROME

Definition 

Cushing syndrome or hypercortisolism it is an endocrine or hormonal disorders which characterized by excessive or increased production of glucocorticoids or cortisol in the circulating blood which due to various causes such as iatrogenic steroids uses when the increased in the glucocorticoids is due to a pituitary tumor it is called cushing disease the cushing syndrome is more common in women than men

Causes of cushing syndrome

There are many causes which can be divided into

Causes related to adrenal gland and

 Causes not related to the adrenal gland

Causes related to adrenal gland

The adrenal gland is a small gland which lies above the kidney and there are two glands in the body one on each side above the kidney and  each gland consists of two parts outer cortex and inner medulla

The cortex of the adrenal gland responsible for production of the glucocorticoids or cortisol into the circulating blood these hormones are not stored in the adrenal cortex but they are released on demand which their secretion under negative feedback control as follow

Any stimulation such as stress fever or exercise to hypothalamus which is a part from the brain lead to release of corticotrophin releasing hormone (ACH) which stimulate the pituitary gland to release adrencorticotrophic hormone ACTH this hormone stimulate the zona fasiculata of the adrenal cortex which release cortisol into the blood so

 Causes of adrenal gland such as

•  Adrenal gland carcinoma which most common causes in children
• Adrenal gland adenoma
• Adrenal gland hyperplasia

Causes not related to the adrenal gland such as

• Iatrogenic causes by prolonged used of steroids drugs like predinsolone and predinsone for a long time such in cases of some chronic diseases like bronchial asthma collagen disease such as rheumatoid arthritis systemic lupus erythromatosis
•  Pituitary gland adenoma see here causing ACTH hypersecretion it is called cushing disease it is most common causes after an iatrogenic causes
• Ectopic ACTH  secretion in these cases there are tumors either benign or malignant away from the pituitary gland which secreted ACTH which in turn stimulate the adrenal gland to release cortisol such as

• Small cell or oat cell carcinoma of the lung
• Bronchial carcinoma
• Bronchial adenoma
• Thymic gland tumors
• Islt cell tumor of the pancrease
•  Medullary carcinoma of the thyroid gland

Familial cushing syndrome causes

Normally the cushing syndrome is not inherited disease but in rare case in some individual there is may inherited condition such as in multiple endocrine neoplasm MEN which has two known types

MEN type I( Werner syndrome) and MEN type II which has two types MEN IIa (Sipple syndrome ) and MEN II b

In MEN I syndrome  or Werner sundrome there are

• Parathyroid hyperplasia
• Pituitary adenoma which secreted ACTH
• Thyroid adenoma
• Adrenal adenoma or carcinoma
• Pancreatic and duodenal endocrine tumors
• For gut or mid gut carcinoid tumors
• Lipoma

What are the patient complaining in cushing syndrome or

Symptoms and signs and complications of cushing syndrome

Can be divided into the following items

General characters

• Truncal obesity in such case the patient suffer from obesity above the waste upper body obesity with thin legs and arms
• Buffalo hump increased fat deposition between the shoulder region
• Muscle wasting and weakness due to increased protein catabolsim
• Retarted growth rate in children
• Moon face the patient face become rounded red and full face
• Easy fatigue

Skin characters

• thin skin with easy bruising due to loss of collagen in capillary walls
• Skin striae or stretched or purple marks in the abdomen thigh and breast
• Acni and skin infection
• Skin pigmentation due to elevated ACTH levels stimulate melanocyte stimulating hormone which in turn stimulate melanin pigment release
• Poor wound healing cortisol inhibits fibroblasts and it is immunosuppressive agent

Effect on the bone

• Easy bone fractures like ribs and spine pathological fractures due to osteoporosis because cortisol inhibit the action of vitamin D which reduced calcium absorption from the intestine
• Back  and bone pain and tenderness
• Kyphosis due to osteoporosis

Effect on other hormones

• Diabetes melluites the cortisol has inhibitory effect on insulin also increased protein catabolism to glucose patient suffer from excessive urination and thirsty and dry tongue
• Hirsutism presence or hair distribution in abnormal site in women such as male as in chin face abdomen chest
• Amenorrhoea or menstrual cycle disturbances as the cortisol suppresses the pituitary gland gonadotrophin
• Imoptance in male and decreased libido or has no desire for sex
• Hypertension due to retention of sodium and water patient suffer from headache
• Edema or swelling of the lower legs due to retention of sodium and water

Effect on the brain

• Depression cortisol causes psychological disturbance
• Anxiety and behavior changes

Diagnosis and investigations of cushing syndrome

From symptoms and signs as above may helpful

Laboratory

Plasma cotisol measurements

Measured at morning and night the cortisol level become raised with loss of diurnal variation

Dexamethasone suppression test

In normal patient who taken 2 mg oral dexamethasone at midnight and plasma cortisol levels are measured at 8 AM at morning this inhibit ACTH production from pituitary gland and hence cortisol levels but in patient with cushing syndrome there is no decreased in the morning cortisol level is seen

False negative results may be seen in patients with mild disease 

False positive results also can be seen in patients  with chronic renal failure depression patients take medications like phenytoin drug 

The 24 hour urinary cortisol collection

Is very sensitive and specific test urinary free cortisol excretion of less than 100 ug|dl rules out hypercortisolism cortisol level elevated

Plasma ACTH levels

Checked to assess corticotrophin function levels of plasma ACTH by immunoradiometric assay  will be undetectable in primary adrenal tumors and the level will be suppressed after administration of CRH in cushing disease as in pituitary adenoma but not in an ectopic source

Salivary cortisol measurements

Using special kits highly sensitive test but they do not used as a routine

Radiological studies

CT and MRI scanning of the abdomen

They can be identified the adrenal tumors and also can help to distinguishing adrenal adenoma from cacinoma In which adrenal adenoma appear darker than the liver

And allowing for  assessment of vascular anatomy

CT and MRI scanning of the brain

To showing and assess the pituitary gland and if there is any tumors but CT and MRI scanning may not showing small microdenoma

Inferior petrosal sinus sampling for ACTH

Very effective to showing small microadenoma of pituitary gland

In this approach a catheter are placed in both internal jugular veins and peripheral veins and the ratio of petrosal to peripheral vein ACTH  level greater than 2 in the basal state and greater than 3 after CRH stimulation is diagnostic of pituitary tumor

CT and  MRI scanning of the chest and anterior mediastinum 

In case of ectopic tumors secreted ACTH ectopic ACTH  such as lung cancer bronchial cancer or adenoma

   

Radioscinitigraphic imaging of the adrenals gland

Using NP-59 to distinguish adrenal adenoma from adrenal hyperplasia  in adrenal adenoma show increased uptake on NP-59 with suppression of uptake in the contralateral or opposite gland  but the hyperplastic glands showing bilateral uptake

Bone density

   

Measured by dual X rays absorptiometery DEXAshowing bone osteoporosis

Treatment of cushing syndrome

Treatment of cushing syndrome depend on the causes such as

Cushing syndrome due to iatrogenic or prolonged  used of steroids

Steroid drugs should be gradually withdrawal or stopped by decreasing the dose of the steroids on several days in divided dose until completely stopped

But if the patient can not stopped it due to it is associated disease so these patients need for monitoring  their  blood sugar for glucose or diabetes and cholesterol level and bone density

Cushing syndrome due to adrenal tumors

Treated by removal of the tumors either by surgical or laparoscopic removal  by operation called adrenalectomy  which may be unilateral as in case of adrenal adenoma or bilateral adrenalectomy in case of bilateral adrenal hyperplasia

Cushing syndrome due to pituitary tumors

Pituitary adenoma is treated by transsphenoidal excision

Pituitary irradiation in case of persistent or recurrent disease after surgery

but it is has high rate of panhypopituitarism and some patients developed visual deficits

Sterotatic radiosurgery

Which uses CT guidance to deliver high doses of radiotherapy to the pituitary tumors to avoid the surgical complications as above

Medical treatment

Medical treatment are indicated in patient who fail to respond to other treatment

These treatment include the following drugs ketocoazole which it is antifungal drugs  also acts by inhibition of the adrenal gland secretion  metyrapone or aminoglutethimide drugs also inhibit adrenal gland secretion they acts as medical adrenalectomy

Cushing syndrome due to ectopic ACTH production

Treated by treatment the primary tumors like cancer lung bronchogenic carcinoma or adenoma cancer pancreas etc

Medical adrenalectomy by medical drugs such as metyrapone aminoglutethimide and mitotane

Bilateral surgical or laparoscopic adrenalectomy as palliative treatment and for unresectable tumors or for recurrent or persistent cushing disease also if the ectopic ACTH secreting tumor cannot be localized

 

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