how to do cortisol stimulation test in office?

[Guest guest]

Hello fellow IMP's,Does anyone do cortisol stimulation tests in their office?

UpToDate recommends IV bolus (see below).  I don't think labs will do this.  How do you guys get these done, or don't you? 

(I haven't put in an IV in quite awhile, although I probably should ).  If I do the high dose version (see below), which apparently can be IM, what do I order (or does anyone have one dose I can buy?)  I seem to remember looking at this years ago and it was super expensive and sold in a pack.

Thanks,Sharon

From UpToDate:

 ACTH STIMULATION TESTS — Several protocols have been used to assess the response to exogenous ACTH. The agent used is synthetic ACTH(1-24) (cosyntropin), which has the full biologic potency of native ACTH(1-39). Short (one hour or less) tests involve administration of a single-dose in a " low " or " high " concentration and can be performed on an outpatient basis. Both tests result in supraphysiological plasma ACTH concentrations: about 60,000 pg/mL (1320 pmol/L) after the standard high-dose ACTH test and about 1900 pg/mL (41.8 pmol/L) after the low-dose test [4]. There are no untoward side effects. Allergic reactions are almost unheard of with cosyntropin. Prolonged ACTH stimulation tests are seldom performed because measurements of plasma ACTH in conjunction with the low-dose ACTH test provide the necessary information.

Standard high-dose ACTH stimulation test — This test consists of measuring serum cortisol immediately before and 30 and 60 minutes after intravenous injection of 250 mcg (85 nmol, or 40 international units) of cosyntropin, which represents the entire contents of the vial. This dose of cosyntropin results in pharmacological plasma ACTH concentrations for the 60-minute duration of the test.

The advantage of the high-dose test is that the cosyntropin can be injected intramuscularly (IM), because pharmacologic plasma ACTH concentrations are still achieved [5]. The low-dose test has not been evaluated after IM injection and may not provide valid results by this route.

Low-dose ACTH stimulation test — A test involving more physiological plasma concentrations of ACTH theoretically provides a more sensitive index of adrenocortical responsiveness. The low-dose ACTH test is performed by measuring serum cortisol immediately before and 30 minutes after intravenous injection of cosyntropin (synthetic ACTH(1-24)) in a dose either of 1 mcg (160 milli-international units) [6] or of 0.5 mcg (80 milli-international units) per 1.73 m2 [7].

The 0.5 mcg per 1.73 m2 dose has the advantage of compensating for plasma volume, but it is about one-half the 1 mcg dose in most patients and may not result in the same peak serum cortisol concentrations at 30 minutes because the peak tends to be reached earlier and is 30 percent lower than after insulin-induced hypoglycemia [7-9]. Furthermore, doses of 0.6 mcg and 0.8 mcg resulted in significantly lower responses than 1 mcg [10].

Because a dose of 1 mcg/1.73 m2 has not been studied in patients whose surface area varied significantly from 1.73 m2, it should be used with caution in such patients. Because it may lead to lower peak cortisol values, a normal result can be interpreted with confidence. By contrast a subnormal response may result if the ACTH dose is insufficient.

Plasma ACTH can also be measured in the basal sample, as in all ACTH stimulation tests. In healthy individuals, cortisol responses are greatest in the morning, but in patients with adrenal insufficiency, the response to cosyntropin is the same in the morning and afternoon [11]. Thus, we recommend that the test be done in the morning to minimize the risk of misdiagnosis in a normal individual. This dose stimulates maximal adrenocortical secretion up to 30 minutes post-injection and in normal subjects results in a peak plasma ACTH concentration about twice that of insulin-induced hypoglycemia [9].

There is no commercially available preparation of " low dose " cosyntropin. One prepares the low-dose solution of cosyntropin locally; the vials of cosyntropin currently available contain 250 mcg and come with sterile normal saline solution to be used as diluent. Instructions are as follows:

Inject 1 mL of the diluent into the vial of cosyntropin to produce a 250 mcg/mL solution and shake thoroughly.

Using a 1 mL tuberculin syringe, withdraw 0.2 mL (ie, 50 mcg cosyntropin) and inject it into a vial containing 24.8 mL of sterile normal saline solution to produce a 2 mcg/mL solution.

After shaking thoroughly, again using a 1 mL syringe, withdraw 0.5 mL (1 mcg cosyntropin) or the appropriate volume for the patient's surface area, and inject the entire volume immediately intravenously.

Eight-hour ACTH stimulation test — The eight-hour test, which is now rarely performed, consists of infusing 250 mcg (40 international units) of cosyntropin continuously over eight hours in 500 mL of isotonic saline. A 24-hour urine specimen is collected the day before and the day of the infusion for cortisol or 17-hydroxycorticoid (17-OHCS) and creatinine determination, and serum cortisol is determined at the end of the infusion. Plasma ACTH concentrations are supraphysiologic throughout the infusion.

The infusion solution must contain isotonic saline (154 meq/L NaCl) because patients with adrenal insufficiency, who may already be hyponatremic and lack aldosterone, can become severely hyponatremic if given hypotonic solutions. (See  " Hyponatremia and hyperkalemia in adrenal insufficiency " .)

Two-day ACTH infusion test — The two-day ACTH infusion test is similar to the eight-hour infusion test, except that the same dose of ACTH is infused for eight hours on two consecutive days [12]. Daily 1 mg intramuscular injections of long-acting ACTH(1-18)-NH2 can be used outside the United States.

This test may be helpful in distinguishing secondary from tertiary adrenal insufficiency (see below). The one-day eight-hour test is too short for this purpose, while longer tests add little further useful information.

Sharon McCoy MDRenaissance Family Medicine10 McClintock Court; Irvine, CA  92617PH: (949)387-5504   Fax: (949)281-2197  Toll free phone/fax:  www.SharonMD.com

[Guest guest]

I found Henry Schein offers the Amphastar Pharmaceuticals brand Cortrosyn 0.25 mg for $158.

Anyone ever tried writing a prescription for this and having patient pick up at pharmacy?  Or gotten reimbursed for it from insurance?

Thanks again,Sharon

Hello fellow IMP's,

Does anyone do cortisol stimulation tests in their office?

UpToDate recommends IV bolus (see below).  I don't think labs will do this.  How do you guys get these done, or don't you? 

(I haven't put in an IV in quite awhile, although I probably should ).  If I do the high dose version (see below), which apparently can be IM, what do I order (or does anyone have one dose I can buy?)  I seem to remember looking at this years ago and it was super expensive and sold in a pack.

Thanks,Sharon

From UpToDate:

 ACTH STIMULATION TESTS — Several protocols have been used to assess the response to exogenous ACTH. The agent used is synthetic ACTH(1-24) (cosyntropin), which has the full biologic potency of native ACTH(1-39). Short (one hour or less) tests involve administration of a single-dose in a " low " or " high " concentration and can be performed on an outpatient basis. Both tests result in supraphysiological plasma ACTH concentrations: about 60,000 pg/mL (1320 pmol/L) after the standard high-dose ACTH test and about 1900 pg/mL (41.8 pmol/L) after the low-dose test [4]. There are no untoward side effects. Allergic reactions are almost unheard of with cosyntropin. Prolonged ACTH stimulation tests are seldom performed because measurements of plasma ACTH in conjunction with the low-dose ACTH test provide the necessary information.

Standard high-dose ACTH stimulation test — This test consists of measuring serum cortisol immediately before and 30 and 60 minutes after intravenous injection of 250 mcg (85 nmol, or 40 international units) of cosyntropin, which represents the entire contents of the vial. This dose of cosyntropin results in pharmacological plasma ACTH concentrations for the 60-minute duration of the test.

The advantage of the high-dose test is that the cosyntropin can be injected intramuscularly (IM), because pharmacologic plasma ACTH concentrations are still achieved [5]. The low-dose test has not been evaluated after IM injection and may not provide valid results by this route.

Low-dose ACTH stimulation test — A test involving more physiological plasma concentrations of ACTH theoretically provides a more sensitive index of adrenocortical responsiveness. The low-dose ACTH test is performed by measuring serum cortisol immediately before and 30 minutes after intravenous injection of cosyntropin (synthetic ACTH(1-24)) in a dose either of 1 mcg (160 milli-international units) [6] or of 0.5 mcg (80 milli-international units) per 1.73 m2 [7].

The 0.5 mcg per 1.73 m2 dose has the advantage of compensating for plasma volume, but it is about one-half the 1 mcg dose in most patients and may not result in the same peak serum cortisol concentrations at 30 minutes because the peak tends to be reached earlier and is 30 percent lower than after insulin-induced hypoglycemia [7-9]. Furthermore, doses of 0.6 mcg and 0.8 mcg resulted in significantly lower responses than 1 mcg [10].

Because a dose of 1 mcg/1.73 m2 has not been studied in patients whose surface area varied significantly from 1.73 m2, it should be used with caution in such patients. Because it may lead to lower peak cortisol values, a normal result can be interpreted with confidence. By contrast a subnormal response may result if the ACTH dose is insufficient.

Plasma ACTH can also be measured in the basal sample, as in all ACTH stimulation tests. In healthy individuals, cortisol responses are greatest in the morning, but in patients with adrenal insufficiency, the response to cosyntropin is the same in the morning and afternoon [11]. Thus, we recommend that the test be done in the morning to minimize the risk of misdiagnosis in a normal individual. This dose stimulates maximal adrenocortical secretion up to 30 minutes post-injection and in normal subjects results in a peak plasma ACTH concentration about twice that of insulin-induced hypoglycemia [9].

There is no commercially available preparation of " low dose " cosyntropin. One prepares the low-dose solution of cosyntropin locally; the vials of cosyntropin currently available contain 250 mcg and come with sterile normal saline solution to be used as diluent. Instructions are as follows:

Inject 1 mL of the diluent into the vial of cosyntropin to produce a 250 mcg/mL solution and shake thoroughly.

Using a 1 mL tuberculin syringe, withdraw 0.2 mL (ie, 50 mcg cosyntropin) and inject it into a vial containing 24.8 mL of sterile normal saline solution to produce a 2 mcg/mL solution.

After shaking thoroughly, again using a 1 mL syringe, withdraw 0.5 mL (1 mcg cosyntropin) or the appropriate volume for the patient's surface area, and inject the entire volume immediately intravenously.

Eight-hour ACTH stimulation test — The eight-hour test, which is now rarely performed, consists of infusing 250 mcg (40 international units) of cosyntropin continuously over eight hours in 500 mL of isotonic saline. A 24-hour urine specimen is collected the day before and the day of the infusion for cortisol or 17-hydroxycorticoid (17-OHCS) and creatinine determination, and serum cortisol is determined at the end of the infusion. Plasma ACTH concentrations are supraphysiologic throughout the infusion.

The infusion solution must contain isotonic saline (154 meq/L NaCl) because patients with adrenal insufficiency, who may already be hyponatremic and lack aldosterone, can become severely hyponatremic if given hypotonic solutions. (See  " Hyponatremia and hyperkalemia in adrenal insufficiency " .)

Two-day ACTH infusion test — The two-day ACTH infusion test is similar to the eight-hour infusion test, except that the same dose of ACTH is infused for eight hours on two consecutive days [12]. Daily 1 mg intramuscular injections of long-acting ACTH(1-18)-NH2 can be used outside the United States.

This test may be helpful in distinguishing secondary from tertiary adrenal insufficiency (see below). The one-day eight-hour test is too short for this purpose, while longer tests add little further useful information.

Sharon McCoy MDRenaissance Family Medicine10 McClintock Court; Irvine, CA  92617PH: (949)387-5504   Fax: (949)281-2197  Toll free phone/fax: 

www.SharonMD.com