Download What is the sensitivity and specificity of the cosyntropin (ACTH

What is the sensitivity and specificity
of the cosyntropin (ACTH) stimulation test
for adrenal insufficiency?
Evidence-Based Answer
Standard-dose, 250-mcg cosyntropin (ACTH) stimulation
testing is 97.5% sensitive and 95% specific for the diagnosis of primary adrenal insufficiency. For the diagnosis of
secondary adrenal insufficiency, the testing is less sensitive. With specificity set to 95%, the 250-mcg test has
a sensitivity of 57% and the 1-mcg test has a sensitivity of 61%. No demonstrable difference has been found
between the standard-dose and low-dose tests in diagnosing secondary adrenal insufficiency. (SOR A, based on systematic review of consistent level 1 studies.)
A 2003 systematic review of the diagnosis of primary and secondary adrenal insufficiency compiled data
from 1966 to 2002 from MEDLINE.1 A total of 122
cases of previously diagnosed primary adrenal insufficiency were included from 8 cohort studies. Additionally, 347 cases of suspected or confirmed secondary
adrenal insufficiency were included from 20 cohort
studies. Either insulin tolerance tests or metyrapone
tests were used as gold-standard diagnostics.
Sensitivity and specificity data were extracted and
compiled to create summary receiver-operator characteristics (ROC) curves. ROC curves were compared
using area under the curve (AUC) methods. Cortisol
cutoff limits were selected to obtain a specificity of 95%
in an attempt to minimize the number of false-positive
results. The authors asserted that this strategy was
important, as often patients with abnormal cosyntropin
testing will not undergo further confirmatory testing.1
In the case of primary adrenal insufficiency, a
serum cortisol cutoff of 415 nmol/L was chosen. Levels were measured 30 to 60 minutes after the administration of 250 mcg cosyntropin. Aggregate sensitivity,
positive likelihood ratio (LR+), and negative likelihood ratio (LR–) were 97.5% (95% confidence interval [CI], 95%–100%), 19.5 (95% CI, 19.0–20.0), and
0.026 (95% CI, 0.0–0.6), respectively, with specificity
set to 95%.1
For the diagnosis of secondary adrenal insufficiency, a serum cortisol cutoff of 500 nmol/L was chosen.
In the case of the 250-mcg test (standard), the aggregate sensitivity, LR+, and LR– were 57% (95% CI,
44%–71%), 11.5 (95% CI, 8.7–14.2), and 0.45 (95%
CI, 0.3–0.6), respectively, with specificity set to 95%.
In the case of the 1-mcg test (low dose), the aggregate sensitivity, LR+, and LR– were 61.4% (95% CI,
45%–78%), 12.3 (95% CI, 9.0–15.5), and 0.41 (95%
CI, 0.24–0.58), respectively, again with specificity set
to 95%.1
The 1-mcg and 250-mcg tests were compared
via AUC analysis of the ROC curves. No statistically significant differences were observed between the
low-dose and standard-dose cosyntropin tests for secondary adrenal insufficiency at either 30 or 60 minutes after cosyntropin administration (P=.18 and .50,
respectively).1
Kimberly Johnson, MD
Joshua Merok, MD
UIC/Illinois Masonic FMR
Chicago, IL
1. Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med. 2003;
139(3):194–204. [LOE 1a]
What is the risk of breast cancer in women who
take oral contraceptives?
Evidence-Based Answer
In older studies, oral contraceptive (OC) use in women
was associated with a small increase in the relative
risk of breast cancer during use and in the first 10
years after stopping. Newer studies of patients using
lower dose OCs have not found such an association.
(SOR B, based on heterogeneous cohort studies)
It is estimated that since the introduction of OCs in the
1960s, more than 300 million women have used them.1
The assessment of teratogenic risk from their use has
evolved over time.
In 1996, the Collaborative Group on Hormonal Factors in Breast Cancer analyzed data from 54
studies of various types, conducted in 25 countries,
examining 53,297 women with breast cancer and
100,239 women without breast cancer.2 In women
taking OCs, there was a small but definite increase
of having breast cancer (relative risk 1.24; 95% confidence interval [CI], 1.15–1.33), but no significant
excess risk 10 or more years after stopping. The
study also found that the cancers diagnosed in
women using combined OCs were less clinically advanced, and the pattern of risk and exposure
Evidence-Based Practice / Vol. 12, No. 8
9
seemed incompatible with a genotoxic effect (damaging to DNA and thereby capable of causing mutations or cancer).2
Similarly, the International Agency for Research
in Cancer concluded in 2005 that there was a small
but increased risk of breast cancer among OC users.3
The report also concluded that OCs provide a protective effect against endometrial and ovarian cancers.
The authors recommended that the small excess risk
of breast cancer be put into perspective with overall risks versus benefits when counseling women on
OC use.
Conversely, the largest modern study, published
in 2002, was a population-based, case-control study
focusing on the risk of breast cancer among current and
former users of OCs.4 More than 9,000 women (4,575
with breast cancer and 4,682 controls) between 35 and
64 years of age were interviewed. The relative risk of
breast cancer was 1.0 for women currently using OCs
and 0.9 for women who had previously used OCs.4
These results were similar for both black and white
women, and were not found to increase consistently
with longer periods of use or higher doses of estrogen.4
Thus, among the defined age group, neither current
nor former OC use was associated with a significantly
increased risk of breast cancer.4
In 2007, a UK cohort study was published that
tracked 45,950 women for an average of 24 years,
beginning in 1968. Incident data were used to examine the absolute risks or benefits of cancer associated
with OCs.1 This study also concluded that OCs were
not associated with an overall increased risk of cancer.
Women who had ever used OCs actually had a 12%
reduction in the risk of any cancer compared with
women who had never used OCs (adjusted relative risk
0.88; 95% CI, 0.83–0.94).1
Deepa Sharma, DO
Amy D. Gruber, MD
Overlook Family Practice
Summit, NJ
1. Hannaford PC, Selvaraj S, Elliot AM, Angus V, Iversen L, Lee AJ. Cancer risk among users
of oral contraceptives: cohort data from the Royal College of General Practitioner’s oral
contraception study. BMJ. 2007; 335(7621):651. [LOE 2b]
2. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal
contraceptives: collaborative reanalysis of individual data on 53 297 women with breast
cancer and 100 239 women without breast cancer from 54 epidemiological studies.
Lancet. 1996; 347(9017):1713-1727. [LOE 2a]
3. Casey PM, Cerhan JR, Pruthi S. Oral contraceptive use and risk of breast cancer. Mayo
Clin Proc. 2008; 83(1):86–90. [LOE 2a]
4. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast
cancer. N Engl J Med. 2002; 346(26):2025–2032. [LOE 3b]
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Evidence-Based Practice / August 2009
What is the best treatment for pseudogout?
Evidence-Based Answer
Intramuscular steroid injections are an effective option
for patients with acute pseudogout. (SOR B, based on
a case series.) Nonsteroidal anti-inflammatory drugs
(NSAIDs) and intraarticular steroids are also recommended for acute pseudogout. (SOR C, based on expert
opinion.) Colchicine and hydroxychloroquine are effective in treating chronic pseudogout with recurrent
attacks. (SOR B, based on small clinical trials.)
Pseudogout is a painful, inflammatory arthritis resulting
from the deposition of calcium pyrophosphate dehydrate
crystals within the joint space. Pseudogout is classified
based on the number of joints involved and frequency
of attacks into the following categories: monoarticular,
polyarticular, acute, or chronic. There are no good clinical trials evaluating the best treatment for pseudogout
and most recommendations come from expert opinion
or small case series that are extrapolated from studies
on gout.
NSAIDs are widely used for treatment of acute
mono- and polyarticular pseudogout.1 A literature
review showed effectiveness with NSAIDs in the
treatment of gout, but no clinical trials focused on
pseudogout.1
In 1997, a small case series demonstrated subjective improvement in all 14 patients with crystal-proven
pseudogout who were prospectively treated with 60 mg
daily intramuscular triamcinolone over a 30-day period.2 Intraarticular steroids have benefit in gout and are
assumed to help with pseudogout.1
Colchicine is commonly used in the treatment
of acute pseudogout similar to its use for acute gout
attacks. In 1986, a small, prospective, self-controlled
clinical trial compared colchicine prophylaxis in 10
male patients with recurrent attacks of crystal proven
pseudogout.3 In the year before starting 0.6 mg BID
colchicine, 32 acute pseudogout attacks were recorded
compared with only 10 attacks during the year after
initiation of therapy (P<.001).3
In 1997, hydroxychloroquine was evaluated
in a small but well-designed prospective, parallel
group, double-blind, randomized control trial of 36
patients with radiologic-proven chronic pseudogout.4
Hydroxychloroquine reduced the number of affected joints by 4.8±2.7 compared with a reduction of