Cosyntropin

A 40-year-old male suspected of having adrenal insufficiency is treated with a synthetic derivative of cosyntropin to assess adrenocortical activity. Which of the following enzymes is activated by cosyntropin ... 

L The answer is a. (Hardman, pp 1460, 14642) Cosyntropin is related to adrenocorticotropin. It corresponds to the first 24 amino acids of adreno-corticotropin. Cosyntropin complexes with a plasma membrane receptor that brings about the activation of adenylyl cyclase. Adenylyl cyclase catalyzes the formation of cAMP from ATP In the cytoplasm, cAMP activates cAMP-dependent protein kinase, which participates in the phosphorylation of specific substrate proteins (e.g., enzymes). The phosphorylated protein eventually induces the particular response on the target cell. 

The short cosyntropin-stimulation test can be used to assess patients with suspected hypocortisolism. An increase to a cortisol level >18 mcg/dL (500 mmol/L) rules out adrenal insufficiency. 

Patients with Addison s disease have an abnormal response to the short cosyntropin-stimulation test. Plasma ACTH levels are usually 400 to 2,000 pg/mL in primary insufficiency versus normal to low (0 to 50 pg/mL) in secondary insufficiency. A normal cosyntropin-stimulation test does not rule out secondary adrenal insufficiency. 

Cosyntropin (Cortwsyn) is a polypeptide that consists solely of the first 24 amino acids of corticotropin. It ap-... 

Corticotropin (adrenocorticotropic hormone, ACTH) regulates the function of the adrenal cortex and has numerous other effects on metabolism. It contains 39 amino acids in the form of a random coil, owing to the presence of several proline residues that prevent helix formation. Species differences are seen in amino acids 25-39 the rest of the ACTH molecule is identical in all animals and humans. The first 24 amino acids are responsible for all of the biological action of ACTH synthetic human ACTHj 24 is known as cosyntropin. 

Clinically, ACTH stimulation of the adrenals is used diagnostically to detect adrenal insufficiency plasma cortisol levels are measured before and 60 minutes following an intravenous injection of cosyntropin. Adrenocortical insufficiency is known as Addison s disease Addison s classic description, in 1855, namely general debility, remarkable feebleness of the heart, irritability of the stomach, and a peculiar change of the colour of the skin , summarizes the clinical features of this disease, which is uniformly fatal if undetected and untreated. Therapeutically, corticotropin therapy has been essentially abandoned in favor of the direct administration of glucocorticoids. However, ACTH is still rarely used in the treatment of the infantile spasm seizure disorder. 

Cosyntropin Chemically synthesized active peptide fragment Diagnosis of adrenal disorders... 

Cosyntropin alpha 1-24 corticotropin (a ACTH subunit) synthetic... 

The effects of budesonide aqueous nasal spray (64 micrograms/day) on adrenal function were studied in a 6-week double-blind, placebo-controlled study in 78 patients with allergic rhinitis aged 2-5 years (39). Adrenal function, evaluated by the mean change in morning plasma cortisol concentration after cosyntropin stimulation, was not suppressed. This dose of budesonide by nasal spray is unlikely to have significant systemic activity. 

Human ACTH is a single peptide chain of 39 amino acids. The amino terminal portion containing amino acids 1-24 is necessary for full biologic activity. The remaining amino acids (25-39) confer species specificity. Synthetic human ACTHi 24 is known as cosyntropin. The amino terminal amino acids 1-13 are identical to melanocyte-stimulating hormone (cr-MSH), which has been found in animals but not in humans. In states of excessive pituitary ACTH secretion (Addison s disease or an ACTH-secreting pituitary tumor), hyperpigmentation—caused by the -MSH activity intrinsic to ACTH—may be noted. 

ACTH stimulation of the adrenals will fail to elicit an appropriate response in states of adrenal insufficiency. A rapid test for ruling out adrenal insufficiency employs cosyntropin (see below). Plasma cortisol levels are measured before and either 30 minutes or 60 minutes following an intramuscular or intravenous injection of 0.25 mg of cosyntropin. A normal plasma cortisol response is a stimulated peak level exceeding 20 g/dL. A subnormal response indicates primary or secondary adrenocortical insufficiency that can be differentiated using endogenous plasma ACTH levels (which are increased in primary adrenal insufficiency and decreased in the secondary form). 

An incremental rise in plasma aldosterone generally occurs in secondary but not primary adrenal insufficiency after cosyntropin stimulation. 

Cosyntropin is the preferred preparation for diagnostic use. The standard diagnostic test dose of 0.25 mg is equivalent to 25 units of porcine corticotropin. ACTH is rarely indicated but is available for use in doses of 10-20 units four times daily. Repository ACTH, 40-80 units, may be administered every 24-72 hours. 

The toxicity of therapeutic doses of ACTH resembles that of the glucocorticoids (see Chapter 39 Adrenocorticosteroids Adrenocortical Antagonists), with the added adverse effect of hyperandrogenism in women. The occasional development of antibodies to animal ACTH or to depot cosyntropin (a preparation not currently available in the USA) has produced anaphylactic reactions or refractoriness to ACTH therapy in a few individuals. Painful swelling occurs at the injection site more often with the zinc hydroxide depot preparation than with the gelatin preparation. Contraindications are similar to those of glucocorticoids. When immediate effects are desired, glucocorticoids are preferable. 

There are virtually no adverse effects from diagnostic doses of cosyntropin. 

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