Cushing’s, Adrenal Insufficiency and Other Glucocorticoid Related Issues

Family Practice Residency Program

Waterloo, IASeptember 11, 2013

Janet A. Schlechte, M.D.

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

Objectives• Approach to glucocorticoid

excess

• Management of adrenal insufficiency

• Peri-op management of glucocorticoids

• Steroid taper

Cushing’s Syndrome Causes

• ACTH secreting pituitary tumor

• Adrenal adenoma/carcinoma

• Ectopic ACTH production

• Exogenous glucocorticoid

Classic Features of Cushing’s

• Centripetal obesity

• Violaceous striae

• Proximal muscle weakness

• Amenorrhea

• Thin skin

• Bruising

Other Features of Cushing’s

• Hypertension

• Glucose intolerance

• Diabetes

• Hypokalemia

• Bone loss

Causes of Cushing’s Syndrome

• ACTH secreting pituitary tumor

• Adrenal adenoma/carcinoma

• Ectopic ACTH production

• Exogenous glucocorticoid

Pituitary versus Adrenal Cushing’s

Ectopic ACTH Secretion

• Severe hypokalemia• Metabolic alkalosis• Muscle weakness• Few of the classic stigmata• Hyperpigmentation

Cushing’s Syndrome

• Rare disorder

• How often will it present in the primary care setting?

• Many people complain of weight gain and bruising but few have Cushing’s

• Even astute clinicians should screen for glucocorticoid excess

Screening Tests

• 24 hour urine cortisol

• 1 mg dex test

• 11 p.m. salivary cortisol

• Inconvenient but most sensitive

• May need to do more than one unless results are 2-3x normal

• Occasional false positives

24 Hour Urine Cortisol

Diurnal Variation of Cortisol

Time

Co

rtis

ol

Pre-Dex

Post-Dex

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

• false positives

- dilantin - obesity - estrogen - stress

- depression

1 mg Dex Test

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.

• She has read about Cushing’s syndrome and is worried about a pituitary tumor

• Potassium 3.8, A1C 5.6%, CBC nl

• 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?

• She collects a 24 hour UFC and the result is 53 µg/dl (<50)

• Does she have Cushing’s?

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.

• 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?

When cortisol excess is confirmed draw

ACTH ACTH

Pituitary tumor Adrenal tumor

Ectopic

Screening Test

Confirm Test

Normal

StopGet ACTH

Undetectable

Adrenal

Elevated

Ectopic

Do DST to differentiate

Pituitary

Stop

AbnormalNormal

Glucocorticoid Excess

Abnormal

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

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.

In The ER

• Sodium 125• Potassium 6.4• Chloride 98

• CO2 18

• Creatinine 1.4• Glucose 75

Features of Primary AI

• Hyperpigmentation• Fatigue and weakness• Hypotension• Postural dizziness• Abdominal pain• Weight loss

Causes of Primary Adrenal Insufficiency

• Autoimmune

• Adrenal hemorrhage

• Granulomatous disease

• Your working diagnosis is primary adrenal insufficiency.

• How do you confirm your suspicion?

• Cortrosyn stimulation test

- Measure plasma cortisol before and 1 hour after IM injection of 250 µg ACTH (cortrosyn)

8

0

16

24

32

28

20

12

4

Pre Post PostPre

Cortisol

Normal 1° AI

Short Cortrosyn Stimulation Test

• After cortrosyn stimulation test begin steroid replacement.

• Little practical reason to start dexamethasone before cortrosyn.

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

What if the results were

• Basal cortisol 9 µg/dl

• Stimulated cortisol 25 µg/dl

Classical Glucocorticoid Equivalents

Daily Replacement Doses

5 mg Prednisone20-25 mg Hydrocortisone

0.75 mg Dexamethasone

37.5 mg Cortisone acetate

More Physiologic Equivalents

Daily Replacement Doses

5 mg Prednisone

10-15 mg Hydrocortisone

0.75 mg Dexamethasone

Treatment Guidelines

• Monitor therapy clinically and with electrolytes.

• Can’t use ACTH or cortisol to monitor therapy.

• Consider other autoimmune disease.

Long-Term Therapy

• Hydrocortisone (10-15 mg/day)

• Start with hydrocortisone and add florinef as needed.

• Florinef (0.05-0.1 mg/day)

• Educate patient about use of steroid during “stress”

• Yearly follow-up

Stress dose?

• Pulling wisdom teeth

• Colonoscopy

• Endometrial biopsy

• Flu with aches and pains

Stress dose?

• CABG

• Hip replacement

• Final exams

• Death in the family

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.

• Pituitary adrenal axis is suppressed

ACTH due to exogenous glucocorticoid

• Stopping glucocorticoid and/or stress of surgery could lead to adrenal crisis

• 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

• 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

• Avoid too much glucocorticoid

• After a stress dose rapidly resume the replacement dose

• Don’t use cortisol or ACTH to try to monitor therapy

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.

• 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

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

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

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

Questions to Ask

• What is the reason for the taper?

• Is it to avoid recurrence of disease?

• Is it to avoid adrenal crisis?

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

• Remember glucocorticoid equivalencies

• Use stress doses sparingly

• When HPA axis is suppressed, taper slowly beginning at a maintenance dose

Take Home Points

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.

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.