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group_5_presentation_1_-_glucocorticoid_hyperfunction_cushing_s_syndrome [2017/10/01 12:21] mohamesb [Signs and Symptoms of Cushing's] |
group_5_presentation_1_-_glucocorticoid_hyperfunction_cushing_s_syndrome [2018/01/25 15:18] (current) |
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| {{youtube>J6-KRmqimIQ?medium}} | {{youtube>J6-KRmqimIQ?medium}} | ||
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| + | ==== Adrenal Glucocorticoid Hyperfunction: Cushing's Syndrome PowerPoint ==== | ||
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| + | {{:cushing_s_presentation.pptx|}} | ||
| ===== Introduction ===== | ===== Introduction ===== | ||
| - | <box 34% round left | > {{ :hpa_.jpg?nolink&400 |}} </box| Figure 1: The HPA (stress response) Axis > | + | <box 32% round right | > {{ ::screen_shot_2017-10-01_at_12.42.47_pm.png?345 |}} </box| Figure 1: The HPA (stress response) Axis > |
| - | Cushing’s syndrome results from excessive, long-term exposure to endogenous or exogenous forms of glucocorticoids (Orth, 1995). Glucocorticoids are a class of steroids, with cortisol being the most important. Glucocorticoids are particularly important in mediating the stress response of the body, and they are also involved in anti-inflammatory actions (Marshall, Bangert & Lapsley, 2012). Normally, the hypothalamic-pituitary-adrenal axis (HPA Axis) releases cortisol from the adrenal glands in response to a stressor (Figure 1). The hypothalamus releases corticotropin-releasing hormone (CRH), stimulating the pituitary gland to release adrenocorticotropic hormone (ACTH), which acts on the adrenal glands to release cortisol. | + | Cushing’s syndrome results from excessive, long-term exposure to endogenous or exogenous forms of glucocorticoids (Orth, 1995). Glucocorticoids are a class of steroids, with cortisol being the most important. Glucocorticoids are particularly important in mediating the stress response of the body, and they are also involved in anti-inflammatory actions (Marshall, Bangert & Lapsley, 2012). Normally, the hypothalamic-pituitary-adrenal axis (HPA Axis) releases cortisol from the adrenal glands in response to a stressor (Figure 1). Activation of the HPA axis initiates a cortisol cascade. Various stressors will result in the secretion of corticotropin-releasing hormone (CRH) from the hypothalamus, which then stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH). Circulating ACTH acts on the adrenal cortex to release cortisol and exert negative feedback control to restore homeostasis. |
| - | However, in Cushing's Disease (the most prevalent endogenous subtype of this syndrome), a tumour in the pituitary causes excessive release of ACTH, therefore acting on the adrenal glands to produce abnormally high levels of cortisol(Orth, 1995). Other endogenous causes of Cushing’s syndrome include an adrenal adenoma over-secreting glucocorticoids, or an ectopic non-pituitary ACTH-producing tumour. Potential sources of an ectopic tumour include the lungs, pancreas, or thymus (Marshall, Bangert & Lapsley, 2012). | + | However, in Cushing's Disease (the most prevalent endogenous subtype of this syndrome), a tumour in the pituitary causes excessive release of ACTH, therefore acting on the adrenal cortex to produce abnormally high levels of cortisol (Orth, 1995). The excess release of glucocorticoids present life-threatening conditions and a host of clinical manifestations. Other endogenous causes of Cushing’s syndrome include a tumour of the adrenal cortex over-secreting cortisol, an ectopic non-pituitary ACTH-secreting tumour, or a tumour of the hypothalamus secreting excessive CRH leading to activation of the cortisol cascade. Potential sources of an ectopic tumour include the lungs, pancreas, or thymus (Marshall, Bangert & Lapsley, 2012). |
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| * Ectopic (a non-pituitary ACTH secreting tumour) | * Ectopic (a non-pituitary ACTH secreting tumour) | ||
| - | Regardless of the class of diagnosis, patients with Cushing’s syndrome exhibit a multitude of similar symptoms with some sex specific. | + | Regardless of the class of diagnosis, patients with Cushing’s exhibit a multitude of similar symptoms with some sex specific. |
| Most Common Symptoms: | Most Common Symptoms: | ||
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| - Eosinophils and lymphocytes are decreased because excess cortisol weakens the immune system. T-cells respond to cytokine molecules (called interleukins)via a signalling pathway. Cortisol blocks the proliferation of T-cells by preventing them from recognizing interleukin signals. More specifically some individuals with Cushings' may also be needed to be treated for severe parasitic infections, since eosinophils are responsible for clearing parasitic infections, declined levels leave affected individuals more susceptible to parasites. | - Eosinophils and lymphocytes are decreased because excess cortisol weakens the immune system. T-cells respond to cytokine molecules (called interleukins)via a signalling pathway. Cortisol blocks the proliferation of T-cells by preventing them from recognizing interleukin signals. More specifically some individuals with Cushings' may also be needed to be treated for severe parasitic infections, since eosinophils are responsible for clearing parasitic infections, declined levels leave affected individuals more susceptible to parasites. | ||
| - | ===== Diagnosis of Adrenal Hyperfunction ===== | + | ===== Diagnosis of Adrenal Hyperfunction: Glucocorticoids ===== |
| One of the goals of diagnosis is to distinguish Cushing’s disease from Cushing’s syndrome, as the disease is a variation of Cushing's syndrome. Secondary adrenal hyperfunction results from a pituitary tumour leading to excessive production of ACTH. Elevated ACTH stimulates the adrenal cortex to produce high levels of cortisol giving rise to the disease state. Testing for Cushing's is outlined below and random plasma cortisol levels are unacceptable due to the variations of cortisol levels throughout the day. | One of the goals of diagnosis is to distinguish Cushing’s disease from Cushing’s syndrome, as the disease is a variation of Cushing's syndrome. Secondary adrenal hyperfunction results from a pituitary tumour leading to excessive production of ACTH. Elevated ACTH stimulates the adrenal cortex to produce high levels of cortisol giving rise to the disease state. Testing for Cushing's is outlined below and random plasma cortisol levels are unacceptable due to the variations of cortisol levels throughout the day. | ||
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| **Figure 2:** Suspected Cushing's syndrome algorithm to determine the origin of excess glucocorticoids in the blood (Marshall, Bangert & Lapsley, 2012) | **Figure 2:** Suspected Cushing's syndrome algorithm to determine the origin of excess glucocorticoids in the blood (Marshall, Bangert & Lapsley, 2012) | ||
| - | === 24-Hour Urinary Cortisol Excretion === | + | === 24 Hour Urine Free Cortisol Excretion === |
| The best screening test for Cushing's is 24 hour urinary free cortisol, as urine cortisol levels are representative of blood cortisol levels. A 24 hour urine collection test is done to collect urine over a full daily cycle of the patient. 24 hour urinary cortisol excretion have normal levels of less than 300 nmol/24 hours (Marshall, Bangert & Lapsley, 2012). Values exceeding the normal range are characteristic of Cushing's. | The best screening test for Cushing's is 24 hour urinary free cortisol, as urine cortisol levels are representative of blood cortisol levels. A 24 hour urine collection test is done to collect urine over a full daily cycle of the patient. 24 hour urinary cortisol excretion have normal levels of less than 300 nmol/24 hours (Marshall, Bangert & Lapsley, 2012). Values exceeding the normal range are characteristic of Cushing's. | ||
| - | === Low-Dose Dexamethansone Suppression Test === | + | === Low Dose Dexamethasone Suppression Test === |
| Dexamethasone is a synthetic glucocorticoid that binds to cortisol receptors in the pituitary and suppresses ACTH release. This ultimately suppresses the secretion of cortisol by the adrenal gland in normal, healthy individuals (Marshall, Bangert & Lapsley, 2012). A 1mg dosage is given at night and blood is drawn for measurement of cortisol the next morning. In healthy individuals this level should be less than 50 nmol/L. (Marshall, Bangert & Lapsley, 2012). Failure to suppress ACTH levels are suggestive of Cushing’s. | Dexamethasone is a synthetic glucocorticoid that binds to cortisol receptors in the pituitary and suppresses ACTH release. This ultimately suppresses the secretion of cortisol by the adrenal gland in normal, healthy individuals (Marshall, Bangert & Lapsley, 2012). A 1mg dosage is given at night and blood is drawn for measurement of cortisol the next morning. In healthy individuals this level should be less than 50 nmol/L. (Marshall, Bangert & Lapsley, 2012). Failure to suppress ACTH levels are suggestive of Cushing’s. | ||
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| ====Pasireotide (Signifor)==== | ====Pasireotide (Signifor)==== | ||
| - | Pasireotide acts as an analog to somatostatin, which is known as a growth hormone-inhibiting hormone. The drug inhibits corticotropin secretion from the hypothalamus, a hormone that leads to the secretion of ACTH and eventually the secretion of cortisol (McKeage, 2013). | + | Pasireotide acts as an analog to somatostatin, which is known as a growth hormone-inhibiting hormone. The drug inhibits adrenocorticotropin (ACTH) secretion from the pituitary gland, a hormone that eventually leads to the secretion of cortisol (McKeage, 2013). |
| A study done by researchers looked at patients with Cushing’s disease and prescribed them with pasireotide for 6 months. At the end of the trials, 25% of all patients have normalized UFC levels and a significant decrease in the mean UFC levels of all patients. Patients that saw a reduction in their UFC levels also saw improvements in clinical symptoms as well, such as blood pressure and body weight. The drug, however, has shown to cause hyperglycemia in patients and is still under further testing (McKeage, 2013). | A study done by researchers looked at patients with Cushing’s disease and prescribed them with pasireotide for 6 months. At the end of the trials, 25% of all patients have normalized UFC levels and a significant decrease in the mean UFC levels of all patients. Patients that saw a reduction in their UFC levels also saw improvements in clinical symptoms as well, such as blood pressure and body weight. The drug, however, has shown to cause hyperglycemia in patients and is still under further testing (McKeage, 2013). | ||
