cushing's final output
TRANSCRIPT
CUSHING’S SYNDROME
DEFINITION
Cushing’s disease is a condition in which the pituitary gland releases too
much adrenocorticotropic hormone (ATCH). ACTH stimulates the
production and release of cortisol, a stress hormone. Too much ACTH
means too much cortisol. The pituitary gland is an organ of the endocrine
system.
It is the hyperactivity of the adrenal cortex that results in excessive
secretion of glucocorticoids (cortisol), mineralocorticoids (aldosterone) and
androgen (male sex hormone).
Cortisol is normally released during stressful situations. It controls the
body's use of carbohydrates, fats, and proteins and also helps reduce the
immune system's response to swelling (inflammation).
It may be caused by taking too much corticosteroid medications, such as
prednisone and prednisolone. These drugs are used to treat conditions
such as asthma and rheumatoid arthritis.
This pathology was described by Harvey Cushing in 1932. The syndrome is
also called Itsenko-Cushing syndrome, hyperadrenocorticism or
hypercorticism)
Cushing's syndrome is not confined to humans and is also a relatively
common condition in domestic dogs and horses.
Harvey Williams Cushing, M.D.
(April 8, 1869 - October 7, 1939) was an American neurosurgeon and a
pioneer of brain surgery, and the first to describeCushing's syndrome. He is
often called the "father of modern neurosurgery".
Cushing's Syndrome was also the first autoimmune disease identified in
humans
The incidence of pituitary tumors may be relatively high, as much as one in
five people.
CAUSE
Exogenous vs. endogenous
Hormones that come from outside the body are called exogenous;
hormones that come from within the body are called endogenous.
The most common cause of Cushing's syndrome
is exogenous administration of glucocorticoids prescribed by a health care
practitioner to treat other diseases (called iatrogenic Cushing's syndrome).
This can be an effect of steroid treatment of a variety of disorders such
as asthma and rheumatoid arthritis, or in immunosuppression after an
organ transplant. Administration of synthetic ACTH is also possible, but
ACTH is less often prescribed due to cost and lesser utility.
Although rare, Cushing's syndrome can also be due to the use of
medroxyprogesterone.
Endogenous Cushing's syndrome results from some derangement of the
body's own system of secreting cortisol. Normally, ACTH is released from
the pituitary gland when necessary to stimulate the release of cortisol from
the adrenal glands.
In pituitary Cushing's, a benign pituitary adenoma secretes ACTH.
This is also known as Cushing's disease and is responsible for 70% of
endogenous Cushing's syndrome.
In adrenal Cushing's, excess cortisol is produced by adrenal gland
tumors, hyperplastic adrenal glands, or adrenal glands with nodular
adrenal hyperplasia.
Finally, tumors outside the normal pituitary-adrenal system can
produce ACTH that affects the adrenal glands. This final etiology is
called ectopic or paraneoplastic Cushing's syndrome and is seen in
diseases like small cell lung cancer.
PATHOPHYSIOLOGY
Cortisol excess result in anti-inflammatory effect and excessive catabolism
of protein and peripheral fat to support hepatic glucose production.
The mechanism may be ACTH- dependent, in which elevated plasma
ACTH level stimulate the adrenal cortex to produce excess cortisol, or
ACTH- independent, in which excess cortisol is produced by the adrenal
cortex or exogenously administered. This suppresses the hypothalamic-
pituitary-adrenal axis, also present in ectopic ACTH- secreting tumors.
SIGNS AND SYMPTOMS
Glucocorticiod
Mood change
Skinny arms and leg
Thin skin
Muscle weakness
Poor wound healing
Bruising
Ketonuria
Buffalo hump
Truncal obesity
Pink/purple stretch mark on
the breast, abdomen, thighs
Risk for infection
Hyper glycemia
Glycosuria
Osteoporosis
Mineralocorticoid
Fluid volume
Hypertension
Hypokalemia
Sodium imbalance
Muscle weakness
Androgens
Voice deepening
Hirsutism (female)
Menstrual irregularities
Thinning hair
Decreased libido
NURSING DIAGNOSIS
• Risk for injury related to weakness
• Risk for infection related to altered protein metabolism and inflammatory
response
• Self-care deficit related to weakness, fatigue, muscle wasting, and altered
sleep patterns
• Impaired skin integrity related to edema, impaired healing, and thin and
fragile skin
• Disturbed body image related to altered physical appearance, impaired
sexual functioning, and decreased activity level
• Disturbed thought process related to mood swings, irritability, and
depression
NURSING INTERVENTION
• Decreasing Risk of injury
-establishing a protective environment
-Foods high in protein, calcium and vitamin D are
recommended
• Decreasing Risk of Infection
-patient should avoid unnecessary exposure to others w/
infection
• Preparing the Patient for Surgery
-patient is prepared for adrenalectomy,if indicated, and the
postoperative course
-transspenoidal hypophysectomy
• Encouraging Rest and Activity
-Encourage moderate activity
-help patient to plan or make schedule for his/her rest
periods throughout the day
• Promoting Skin Integrity
-Meticulous skin care
-use of adhesive tapes is avoided
-encourage and assists patient to change position frequently
• Improving Body Image
-provide discussion of the effect the changes that had on
his/her self-concept and relationship with others.
• Improving Thought Processes
-Explanations to the patient and family members about the
cause of emotional instability are important
-Psychotic behavior may occur in few patients and should be
reported.
MEDICAL MANAGEMENT
Agents that inhibit steroidogenesis, such as mitotane, ketoconazole,
metyrapone, aminoglutethimide, trilostane, and etomidate, have been
used to cause medical adrenalectomy. These medications are used
rarely and often are toxic at the doses required to reduce cortisol
secretion. Thus, medical treatment should be initiated cautiously and,
ideally, in conjunction with a specialist. Efficacy of these medical
interventions can be assessed with serial measurements of 24-hour
urinary free cortisol.
Patients receiving these medications may require glucocorticoid
replacement to avoid adrenal insufficiency. Patients should be
counseled on the signs and symptoms of adrenal insufficiency when
starting these drugs.
Metyrapone and trilostane are agents that competitively inhibit a
single steroidogenic enzyme. Ketoconazole and aminoglutethimide
act at several sites. In ACTH-dependent Cushing syndrome, ACTH
secretion continues to stimulate steroidogenesis, which counters the
actions of these medications.
Ketoconazole is probably the most popular and effective of these
agents for long-term use and usually is the agent of choice. It acts on
several of the P450 enzymes, including the first step in cortisol
synthesis, cholesterol side-chain cleavage, and conversion of 11-
deoxycortisol to cortisol.
o A daily dose of 600-800 mg often decreases cortisol production.
If this agent is ineffective at controlling hypercortisolism, the
dose may be maintained while another steroid enzyme inhibitor,
typically metyrapone, is initiated.
o Adverse effects of ketoconazole include headache, sedation,
nausea, irregular menses, decreased libido, impotence,
gynecomastia, and elevated liver function tests. The drug is
contraindicated during pregnancy.
o Ketoconazole is less effective in patients on H2 blockers or
proton-pump inhibitors because gastric acidity is required for
metabolism.
Metyrapone blocks 11-beta-hydroxylase activity, the final step in
cortisol synthesis. Therapy is begun at 1 g/d divided into 4 doses and
increased to a maximum dose of 4.5 g/d. Adverse effects are from
increases in androgen and mineralocorticoid precursors, including
hypertension, acne, and hirsutism.
Aminoglutethimide is an anticonvulsant agent that blocks cholesterol
side-chain cleavage to pregnenolone. It is a relatively weak adrenal
enzyme inhibitor at doses that patients can tolerate.
Aminoglutethimide is typically initiated at 250 mg twice daily, and
doses of 1-2 g daily are often used.
o Adverse effects of aminoglutethimide include somnolence,
headache, a generalized pruritic rash, hypothyroidism, and
goiter.
o In rare cases, it may cause bone marrow suppression.
o Aminoglutethimide increases the metabolism of
dexamethasone but not cortisol.
Mitotane is an adrenolytic agent that acts by inhibiting 11-beta
hydroxylase and cholesterol side-chain cleavage enzymes. This drug
also leads to mitochondrial destruction and necrosis of adrenocortical
cells in the zona fasciculata and reticularis. For this reason, it is used
in treatment of adrenal cancer at doses of 2-4 g daily. Its survival
benefit is unclear. It can be used in addition to radiation therapy for
treatment of Cushing disease and in combination with metyrapone or
aminoglutethimide for treatment of ectopic ACTH secretion.
o Unfortunately, mitotane is expensive, and its utility is limited by
adverse gastrointestinal and neurologic effects, including
nausea, diarrhea, dizziness, and ataxia. Other adverse effects
include rash, arthralgias, and leukopenia.
o It is taken up by adipose tissues and persists in the circulation
long after discontinuation.
o It is a potential teratogen and can cause abortion; therefore, it is
relatively contraindicated in women interested in remaining
fertile.
SURGICAL MANAGEMENT
When Cushing's syndrome results from an ACTH-producing tumor of the
pituitary gland (Cushing's disease), treatment may include surgery,
radiation, or medication to lower cortisol levels.
Surgery
Surgical removal of a small, well-defined pituitary adenoma is called
transsphenoidal adenomectomy. The pituitary is located at the base of the
brain. It is possible to access this area through the gums above the upper
front teeth or the nose.
Using special instruments, the surgeon makes an incision in one of these
areas. The incision is extended through the sphenoid sinus, allowing the
surgeon to see and remove the adenoma with an endoscope (a thin,
lighted tube with a camera).
This type of surgery permanently cures Cushing's syndrome in 60 to 70
percent of people.
Sometimes a tumor cannot be identified; in these cases, half of the pituitary
gland may be removed (hemihypophysectomy) or 85 to 90 percent of the
pituitary gland may be removed (subtotal hypophysectomy) to be certain
that the tumor has been removed.
Surgical removal of half or more of the pituitary gland can reduce pituitary
function and interfere with ovulation (in women) and sperm production (in
men). Lifelong hormone replacement is often necessary after surgery.
Radiation
Radiation can be a useful treatment when pituitary tumors cannot be
completely removed by surgery. Radiation of pituitary tumors reduces
cortisol levels in about half of adults and most children with Cushing's
disease.
Because this cortisol-lowering effect takes time (3 to 12 months),
medications that lower adrenal cortisol production may be given while
waiting for the effects of radiation.
These medications include ketoconazole, metyrapone, and
aminoglutethimide.
Adrenalectomy
Surgical removal of the adrenal glands (adrenalectomy) is a final measure
that may be recommended if other treatments are not successful.
Adrenalectomy stops excess cortisol production but requires that you
begin lifelong daily glucocorticoid and mineralocorticoid replacement
therapy.
MEDICATION
Metyrapone (Metopirone)
- blocks cortisol synthesis by inhibiting steroid 11β-hydroxylase.
- Metyrapone 30mg/kg, maximum dose 3000 mg, is administered at
midnight usually with a snack.
- Metyrapone is used to test if your pituitary gland is sending the proper
Ketoconazole(Nizoral)
- probably the most popular and effective of these agents for long-term use
and usually is the agent of choice.
-suppression of glucocorticoid synthesis
- It is usually taken once a day.
- Adverse effects of ketoconazole include headache, sedation, nausea,
irregular menses, decreased libido, impotence, gynecomastia, and
elevated liver function tests. The drug is contraindicated during pregnancy.
signals to your adrenal glands.
- SIDE EFFECTS: Nausea, upset stomach, headache, dizziness, or
drowsiness may occur.
Mitotane (LYSODREN®)
- works by killing or slowing the growth of adrenal gland cells and also
reverses the side effects caused by too much hormone production.
- Tablets 500 mg
- Take this medication by mouth with or without food, usually 3 or 4 times
daily or as directed by your doctor.
- SIDE EFFECTS: Dizziness, drowsiness, nausea, diarrhea, loss of
appetite,headache, or unusual weakness may occur.
Aminoglutethimide(Cytadren)
- Aminoglutethimide is indicated in conjunction with other drugs for the
suppression ofadrenal function in patients with Cushing's syndrome.
- Take this medication by mouth with or without food, usually 4 times
a day (every 6 hours) or as directed by your doctor.
- SIDE EFFECTS: Drowsiness, dizziness, headache, nausea, vomiting, or
loss of appetite may occur.
DIAGNOSTIC TESTS
• 24-hour urinary free cortisol level. In this test, a person’s urine is
collected several times over a 24-hour period and tested for cortisol.
Levels higher than 50 to 100 micrograms a day for an adult
suggest Cushing’s syndrome.
• Midnight plasma cortisol and late-night salivary cortisol
measurements. The midnight plasma cortisol test measures cortisol
concentrations in the blood.
Cortisol production is normally suppressed at night, but in Cushing’s
syndrome, this suppression doesn’t occur. If the cortisol level is more than
50 nanomoles per liter (nmol/L), Cushing’s syndrome is suspected.
The test generally requires a 48-hour hospital stay to avoid falsely elevated
cortisol levels due to stress.
• Low-dose dexamethasone suppression test (LDDST). In the LDDST, a
person is given a low dose of dexamethasone, a synthetic glucocorticoid,
by mouth every 6 hours for 2 days. Urine is collected before
dexamethasone is administered and several times on each day of the test.
A modified LDDST uses a onetime overnight dose.Cortisol and other
glucocorticoids signal the pituitary to release less ACTH, so the normal
response after taking dexamethasone is a drop in blood and urine cortisol
levels. If cortisol levels do not drop, Cushing’s syndrome is suspected.
• Dexamethasone-corticotropin-releasing hormone (CRH) test. Some
people have high cortisol levels but do not develop the progressive effects
of Cushing’s syndrome, such as muscle weakness, fractures, and thinning
of the skin.
These people may have pseudo-Cushing’s syndrome, a condition
sometimes found in people who have depression or anxiety disorders, drink
excess alcohol, have poorly controlled diabetes, or are severely obese.
Pseudo-Cushing’s does not have the same long-term effects on health as
Cushing’s syndrome and does not require treatment directed at the
endocrine glands.
The dexamethasone-CRH test rapidly distinguishes pseudo-Cushing’s from
mild cases of Cushing’s. This test combines the LDDST and a CRH
stimulation test. In the CRH stimulation test, an injection of CRH causes the
pituitary to secrete ACTH.
Pretreatment with dexamethasone prevents CRH from causing an increase
in cortisol in people with pseudo-Cushing’s. Elevations of cortisol during
this test suggest Cushing’s syndrome.
MNEMONIC
C - Central obesity, Cervical fat pads, Collagen fibre
weakness, Comedones (acne)
U - Urinary free cortisol and glucose increase
S - Striae, Suppressed immunity
H - Hypercortisolism, Hypertension, Hyperglycaemia, Hirsutism
I - Iatrogenic (Increased administration of corticosteroids)
N - Noniatrogenic (Neoplasms)
G - Glucose intolerance, Growth retardation
REFERENCES
http://emedicine.medscape.com/article/117365-treatment
http://www.uptodate.com/contents/patient-information-cushings-syndrome-
treatment
Suzzane C. Smeltzer, et.al.Medical-Surgical Nursing, 12th ed.Lippincott
Williams and Wilkins.2010.pp1281-1286
Cushing’s syndrome
And
Addison’s disease
Submitted by:
Arnel John Marcera
Eloisa Dajes
Johayrah Macadato
Zoren Kier Sabellina
Joy Cheryl Pabololot
Rolin Theresa Sabio
Lorry Calisagan
Submitted to:
Ms. Dolly Banluta,RN