janet a. schlechte, m.d
DESCRIPTION
Cushing’s, Adrenal Insufficiency and Other Glucocorticoid Related Issues Family Practice Residency Program Waterloo, IA September 11, 2013 Janet A. Schlechte, M.D. Disclosure of Financial Relationships. Janet A. Schlechte, M.D. - PowerPoint PPT PresentationTRANSCRIPT
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Cushing’s, Adrenal Insufficiency and Other Glucocorticoid Related Issues
Family Practice Residency Program
Waterloo, IASeptember 11, 2013
Janet A. Schlechte, M.D.
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Janet A. Schlechte, M.D.
has no relationships with any proprietary entity producing
health care goods or services consumed by or
used on patients.
Disclosure of Financial Relationships
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Objectives• Approach to glucocorticoid
excess
• Management of adrenal insufficiency
• Peri-op management of glucocorticoids
• Steroid taper
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Cushing’s Syndrome Causes
• ACTH secreting pituitary tumor
• Adrenal adenoma/carcinoma
• Ectopic ACTH production
• Exogenous glucocorticoid
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Classic Features of Cushing’s
• Centripetal obesity
• Violaceous striae
• Proximal muscle weakness
• Amenorrhea
• Thin skin
• Bruising
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Other Features of Cushing’s
• Hypertension
• Glucose intolerance
• Diabetes
• Hypokalemia
• Bone loss
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Causes of Cushing’s Syndrome
• ACTH secreting pituitary tumor
• Adrenal adenoma/carcinoma
• Ectopic ACTH production
• Exogenous glucocorticoid
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Pituitary versus Adrenal Cushing’s
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Ectopic ACTH Secretion
• Severe hypokalemia• Metabolic alkalosis• Muscle weakness• Few of the classic stigmata• Hyperpigmentation
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Cushing’s Syndrome
• Rare disorder
• How often will it present in the primary care setting?
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• Many people complain of weight gain and bruising but few have Cushing’s
• Even astute clinicians should screen for glucocorticoid excess
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Screening Tests
• 24 hour urine cortisol
• 1 mg dex test
• 11 p.m. salivary cortisol
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• Inconvenient but most sensitive
• May need to do more than one unless results are 2-3x normal
• Occasional false positives
24 Hour Urine Cortisol
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Diurnal Variation of Cortisol
Time
Co
rtis
ol
Pre-Dex
Post-Dex
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1 mg Dex Test
• 1 mg dexamethasone at 11 p.m. and measure 8 a.m. cortisol the next day
• Healthy subjects will have cortisol <2 µg/dl
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• false positives
- dilantin - obesity - estrogen - stress
- depression
1 mg Dex Test
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A 30 y.o. woman has gained 20 pounds over the last six months. She has also noted leg swelling and her blood pressure is harder to control. She takes HCTZ and a BCP.
B/P 140/100, BMI 35, bruises on legs, buffalo hump, pale pink striae.
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• She has read about Cushing’s syndrome and is worried about a pituitary tumor
• Potassium 3.8, A1C 5.6%, CBC nl
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• She takes 1 mg of dex at 11 p.m. and an 8 a.m. cortisol the next day is 10 µg/dl.
• Does she have Cushing’s?
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• She collects a 24 hour UFC and the result is 53 µg/dl (<50)
• Does she have Cushing’s?
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A 40 y.o. man has poorly controlled hypertension. His weight has increased by 50 lb in the last year. He has bright purple striae and significant muscle weakness. A 1 mg DST shows a cortisol of 20 so screening test is positive.
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• To rule out a false positive do confirmatory test
• He collects a 24 hour UFC and the value is 350 µg/dl (<50)
• Test is positive – he has Cushing’s
• Now what?
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When cortisol excess is confirmed draw
ACTH ACTH
Pituitary tumor Adrenal tumor
Ectopic
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Screening Test
Confirm Test
Normal
StopGet ACTH
Undetectable
Adrenal
Elevated
Ectopic
Do DST to differentiate
Pituitary
Stop
AbnormalNormal
Glucocorticoid Excess
Abnormal
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ACTH Cortisol
PituitaryHyperfunction
ACTH Cortisol
AdrenalTumor
ACTH Cortisol
EctopicProduction
baseline
2 mg
8 mg
ACTH
300 µg
180
40
989 µg
991
990
undet.
4034 µg
4000
3989
Urinary free cortisol
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A 41 y.o. collapsed on the golf course in August. For 6 months he has been tired with intermittent nausea, abdominal pain and deterioration of his golf game. In the ER his BP was 60/- with a pulse of 130. He has a deep tan, pigmented buccal mucosa, a small thyroid and a normal neuro exam.
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In The ER
• Sodium 125• Potassium 6.4• Chloride 98
• CO2 18
• Creatinine 1.4• Glucose 75
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Features of Primary AI
• Hyperpigmentation• Fatigue and weakness• Hypotension• Postural dizziness• Abdominal pain• Weight loss
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Causes of Primary Adrenal Insufficiency
• Autoimmune
• Adrenal hemorrhage
• Granulomatous disease
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• Your working diagnosis is primary adrenal insufficiency.
• How do you confirm your suspicion?
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• Cortrosyn stimulation test
- Measure plasma cortisol before and 1 hour after IM injection of 250 µg ACTH (cortrosyn)
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8
0
16
24
32
28
20
12
4
Pre Post PostPre
Cortisol
Normal 1° AI
Short Cortrosyn Stimulation Test
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• After cortrosyn stimulation test begin steroid replacement.
• Little practical reason to start dexamethasone before cortrosyn.
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After the cortrosyn test the IV saline is continued and you give the 100 mg of hydrocortisone. One hour later the lab calls with the cortisol results.
• Basal cortisol 0.1 µg/dl
• Stimulated cortisol 0.1 µg/dl
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What if the results were
• Basal cortisol 9 µg/dl
• Stimulated cortisol 25 µg/dl
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Classical Glucocorticoid Equivalents
Daily Replacement Doses
5 mg Prednisone20-25 mg Hydrocortisone
0.75 mg Dexamethasone
37.5 mg Cortisone acetate
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More Physiologic Equivalents
Daily Replacement Doses
5 mg Prednisone
10-15 mg Hydrocortisone
0.75 mg Dexamethasone
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Treatment Guidelines
• Monitor therapy clinically and with electrolytes.
• Can’t use ACTH or cortisol to monitor therapy.
• Consider other autoimmune disease.
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Long-Term Therapy
• Hydrocortisone (10-15 mg/day)
• Start with hydrocortisone and add florinef as needed.
• Florinef (0.05-0.1 mg/day)
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• Educate patient about use of steroid during “stress”
• Yearly follow-up
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Stress dose?
• Pulling wisdom teeth
• Colonoscopy
• Endometrial biopsy
• Flu with aches and pains
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Stress dose?
• CABG
• Hip replacement
• Final exams
• Death in the family
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A 45 y.o. woman with RA has been treated with 10 mg of prednisone for 3 years. She will undergo laparoscopic surgery in 2 days. Her surgeon wants you to write pre-op orders.
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• Pituitary adrenal axis is suppressed
ACTH due to exogenous glucocorticoid
• Stopping glucocorticoid and/or stress of surgery could lead to adrenal crisis
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• Minor surgical stress- usual dose day of procedure
• Moderate surgical stress- 50 mg HC day of procedure then resume usual dose
Peri-Operative Corticosteroid Coverage
Ann Surg 219:416, 1994
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• Major surgical stress- 100 mg HC on day of procedure- 50 mg HC on post-op day 1
• Resume usual dose unless clinical condition deteriorates
Peri-Operative Corticosteroid Coverage
Ann Surg 219:416, 1994
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• Avoid too much glucocorticoid
• After a stress dose rapidly resume the replacement dose
• Don’t use cortisol or ACTH to try to monitor therapy
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A 60 y.o. man has taken 60 mg of prednisone daily for 6 months for anterior ischemic optic neuropathy. His ophthalmologist has seen no improvement and wants to stop the steroid.
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• Stopping the drug will lead to secondary adrenal insufficiency
• He has muscle weakness and weight gain and his T score is -2.9. The glucocorticoid needs to be stopped as rapidly as possible
The Dilemma
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TaperOption # 1
January 1
January 15
January 30
February 1
February 15
March 1
60 mg
40 mg
20 mg
10 mg
5 mg
Off
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TaperOption # 2
January 1
January 15
February 1
March 1
April 1
60 mg
60 mg q.o.d.
30 mg q.o.d.
10 mg q.o.d.
Off
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TaperOption # 3
January 1
January 2
February 1
March 1
April 1
May 1
etc. until off
60 mg
10 mg
9 mg
8 mg
7 mg
6 mg
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Questions to Ask
• What is the reason for the taper?
• Is it to avoid recurrence of disease?
• Is it to avoid adrenal crisis?
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RR 95% CI p
0<HC<20 1.3 0.7-2.6 ns
20<HC<25 1.4 0.6-3.3 ns
25<HC<30 1.6 1.1-2.4 .014
HC>30 2.9 1.4-5.9 .003
Effect of Dose of Hydrocortisone on Mortality
JCEM 94:4216, 2009
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• Remember glucocorticoid equivalencies
• Use stress doses sparingly
• When HPA axis is suppressed, taper slowly beginning at a maintenance dose
Take Home Points
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A 42 y.o. with a history of chronic back pain has severe fatigue and the lab pages you because his cortisol is 1.0 and his TSH is 1.4.
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One of your patients takes 5 mg of prednisone daily after an organ transplant. She is having her wisdom teeth pulled tomorrow morning and calls to find out what to do about her prednisone since she will be NPO.