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Cushing's Syndrome


Cushing's Syndrome overview and Definition

Cushing’s syndrome takes place when the body secrete too much of stress monitoring hormone which is known as Cortisol.  The cortisol also maintains the blood pressure, regulate blood glucose level, reduces the inflammation and turn the food you eat into energy. It is also known as Hypercotisolism.


Structure of Cushing's Syndrome

The kidney is a bean shaped organ. Adrenal gland is a triangular shaped organ which is present  above the kidney adrenal glands are present which aids in the production of cortisol. Adrenal gland consists of adrenal cortex and adrenal medulla. The adrenal cortex consists of zona glomerulosa, zona reticularis, zona fasiculata. Adrenal medulla is present inside the cortex and it is present in the stress hormone including Adrenaline. The adrenal cortex.


Pathophysiology

When  ACTH stimulation occurs it might result in the adrenal gland secretion of cortisol and other steroid hormones. ACTH is produced by the pituitary gland and it is released into the petrosal venous sinus in response to stimulation by the corticotrophin releasing hormone(CRH) from the hypothalamus. ACTH is released n the diurnal pattern independent of the circulating cortisol levels.  Peak release occurs just before awakening and ACTH levels then decline throughout the day. Control of CRH and ACTH release is maintained through the negative feedback by cortisol at the hypothalamic and pituitary levels. Neuronal input at the hypothalamic level can also stimulate the CRH levels.

The tumours of the cushing’s disease secreate excessive amount of adrenocorticotrophic hormones and results in negative feedback responsiveness to high doses of glucocorticoids. Ectopic sources of ACTH occurs in the form of extracranial neoplasms are generally not responsive to negative feedback with high doses of glucocorticoid.  Cushing’s syndrome is classified into ACTH dependent or ACTH independent.

Depression, alcoholism, medications, eating disorders and other conditions can cause mild clinical and laboratory findings, similar to those in Cushing's syndrome, termed “pseudo-Cushing's syndrome.” The laboratory and clinical findings of hypercortisolism disappear if the primary process is successfully treated.

Dexamethasone, an exogenous glucocorticoid, is used to test for Cushing's syndrome. This gluococorticoid does not interfere with cortisol assays but induces similar physiologic responses.


Clinical signs & symptoms

  • Weight gain in face which is known as moon face
  • Weight gain above the collar bone (supraclavicular fat pad)
  • Weight gain on the back of neck also known as buffalo hump
  • Skin changes with easy bruising in the extremities and development of purplish stretch marks called striae particularly over the abdomen or axillary region
  • Red, round face (plethora)
  • Central obesity with weight gain centered over the chest and abdomen with thin arms and legs
  • Excessive hair growth (hirsutism) on face, neck, chest, abdomen and thighs
  • Female balding
  • Generalized weakness and fatigue
  • Blurry vision
  • Vertigo
  • Muscle weakness
  • Menstrual disorders in women known as amenorrhoea
  • Decreased fertility and/or sex drive (libido)
  • Hypertension
  • Diabetes mellitus
  • Poor wound healing
  • Severe depression
  • Extreme mood swings


Differential Diagnosis

  • Blood and urine tests: These tests measure and evaluate the level of adrenal hormones as well as pituitary hormones. They also help assess blood glucose levels and sodium levels.
  • Imaging tests: Ultrasound, CT, MRI and X-ray imaging take pictures of the adrenal gland. They help detect possible tumours, impact on the gland and other signs of disease.
  • For pheochromocytoma, a specialized scan called a meta-iodobenzylguanidine (MIBG) scan.
  • The dexamethasone suppression test (DST) is used to assess adrenal gland function by measuring how cortisol  levels change in response to oral doses or an injection of dexamethasone It is typically used to diagnose cushing’s syndrome.
  • Petrosal sinus sampling. This test can help determine whether the cause of Cushing syndrome is rooted in the pituitary or somewhere else. For the test, blood samples are taken from the veins that drain the pituitary gland (petrosal sinuses).

 

There are several types of DST procedures:

  1. Overnight DST - An oral dose of dexamethasone is given between 11pm and midnight, and the cortisol level is measured at 8 - 9am the next morning
  2. Two-day DST - This involves giving an oral dose of dexamethasone at six-hourly intervals for 2 days, with the cortisol level measured 6 hours after the final dose was given
  3. Intravenous DST
  4. Dexamethasone-CRT test


Prognosis

Most of the people with cushing syndrome shows proper prognosis. Most of them can be cured.


Prevention

Avoid the exposure to corticosteroids