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Cushing's Syndrome

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by

Adrian Aguilar

on 17 November 2013

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Transcript of Cushing's Syndrome

Other symptoms appear in the skin, which becomes fragile and thin. It bruises easily and heals poorly. Purplish pink stretch marks may appear on the abdomen, thighs, buttocks, arms and breasts. The bones are weakened, and routine activities such as bending, lifting or rising from a chair may lead to backaches, rib and spinal column fractures.
Symptoms
Symptoms vary, but most people have upper body obesity, rounded face, increased fat around the neck, and thinning arms and legs. Children tend to be obese with slowed growth rates.
Treatments
What is Cushing's Syndrome?
Cushing's syndrome is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. Sometimes called "hypercortisolism," it is relatively rare and most commonly affects adults aged 20 to 50. An estimated 10 to 15 of every million people are affected each year.
Medical Therapy
Used in order to :
Normalize circulating cortisol
Doubt on source of ACTH
After an unsuccessful surgery
Waiting for radiotherapy results
Presence of psychiatric complications
Reduce likelihood of death
Target is normal cortisol prod. rate.
Metyraprone
Fast acting
Cortisol synthesis inhibitor
Blocks 11-Deoxycortisol from being converted to cortisol.
Ketoconazole
Slower acting than metyraprone
Anti-fungal agent
Antiadregenic features +Females -Males
Variety of formulations
Blocks cholesterol cleavage
Mitotane
Etomidate
Originally a anesthetic agent
Induces hypoadrenalism
Can correct hypercortisolemia in seriously ill patients with ectopic ACTH production.
Needs to be given intravenously
Mifepristone (RU486)
Used in treatment of adrenocortical carcinoma
Blocks side-chain cleavage of cholesterol
Slow sustained effects
Cushing's syndrome
By: Adrian Aguilar
Carlos Olvera
David Alonzo

24- hour Urinary Free Cortisol
Late night salivary cortisol
Sleeping midnight serum cortisol
Overnight Dexamethasone Suppression (ODS)
Standard 2-day low-dose suppression (LDDS)
LDDS-Corticotropin-releasing hormone (CRH)
Chemotherapy
Tumors located on the pituitary
gland will cause hypercortisolism.

Chemotherapy would be used to kill
the tumor cells
Cortisol synthesis Inhibitor
Leads to hypoadrenalism, Hirsutism and
elevated levels of 11-Deoxycortisol

Cortisol synthesis Inhibitor
Hypoadrenalism, skin rashes, liver
enzyme dysfunction in up to 10% of
cases
Reduced Total cholesterol and LDL
cholesterol
Adverse: Nausea & diarrhea with neurological effects at higher doses. Also known to cause Hypecholesterolemia, hyperuricemeia and is a teratogen
Normal Physiology
Cortisol synthesis Inhibitor
Antagonist to glucocorticoid and progesterone repceptors.
Blocks cortisol action.
Also known as and abortion pill
Successfully able to treat small number of patients
Problem: Induces ACTH production through negative feedback. Makes it difficult to monitor therapy.
Dopamine Agonists
Used for treatment of hyperprolactinaemia and acromegaly.
Caused a fall in 50% of patients with Cushing's Disease
Non lasting effects
Adverse effects: Nausea, postural hypotension, headaches and hallucinations..
In a study of 20 patients:
Normalized UFC in 7
8 exhibited a response
After wards 8 out of the 20 were fully controlled
Others had adverse effects to lead to possible risk of cardiac valve fibrosis.
Surgery
Negative feedback
Pasireotide
Fisher, Conrad. "Cushing's Syndrome."
Medical-Institution
. 25 March 2013. Web. 14 November 2013.http://www.medical-institution.com/cushings-syndrome/
Has a high affinity to somatostatin receptors.
Study of 162 patients:
Median UFC fell by 50%
UFC normalization in 15% at 600microgram/day.
UFC normalization in 26% at 1200microgram/day.
Inhibits ACTH secretion
Adverse Effects: Similar to hypergycemia-related adverse effects.
Bilateral laparoscopic adrenalectomy
Used for both Pituitary-dependent CD and Ectopic ACTH syndrome.
Was preceded by open adrenalectomy
Widely accepted since its description in 1992.
Reduction in length of or recovery and hospitalization with less complications.
Hypertrichosis over forehead is a clinical clue.
The Endocrine Society guidelines of circumstances for screening:
Patients with multiple, progressive, discriminatory findings for CS
Cases with unusual features like hypertension or osteoporosis at young age.
Adrenal incidentalomas
Children with a decreasing height percentile and increasing weight.
Study of 171 patients:
out of 31 who exhibited signs
3 had elevated 24 hour UFC.
1 true CS
Best approach is to test multiple times and utilizing other tests.
Two samples obtained and refrigerated
False Positives:
Come from Carbamazepine and fenofibrate
Excess water intake
False Negative:
Renal impairment and mild CS
Two samples between 11pm and 12am
Either by passive drooling or salivette method
False Positive:
Oral licorice
Tobacco
Gels containing steriods
Altered day and night cycle
Stress
Risk Factors
Taken at 12am while sleeping or 5 min of awaking.
Need to be indoors 24-48 hrs and precannulation
False Positive:
Stress
Altered day and night cycle
collection procedure prerequisites no met
Diabetes
Enlargement of pituitary tumor
Fractures due to osteoporosis
High blood pressure
Kidney stones
Serious infections
Oral dexamethasone taken at 11pm
Serum collected next morning 8am next morning
False Positive:
Phenytoin or rifampicin
Pregnancy
Oral dexamethasone taken every 6 hours for 2 days
Serum collection at 6 hour of last dose
False Positive:
Can vary in absorption and metabolism of dexamethasone can influence test
Used in patients with high index of clinical suspicion or negative initial test results.
2 hours after last dose CRH is given and serum levels tested 15 min later.
Cortisol
http://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/causes.aspx
Causes
Medications
Exogenous
Cortisol-like steroid drugs/ glucocorticoids.
Some medications used to treat:
Allergies
Asthma
Autoimmune diseases
Organ transplantation
Cancerous (Malignant)
Adrenal Cancer
Cancer in lungs, pancreas, thyroid, thymus or any place other than pituitary or adrenal glands.
Noncancerous (Benign)
Pituitary adenoma
Adrenal Adenoma
Adrenal micronodular
Adenomas
Tumors
Endogenous
Bromocriptin
Cabergoline
Diagnostic Procedures
National Cushing's Syndrome Awareness day - April 8th
Questions
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