Synacthen test

Synacthen test: ACTH promotes secretion from adrenal cortex. Synthetic ACTH is used in synacthen test. this help to identify problem in cortisol deficiency due to adrenal cause or due to central ACTH secretion. Short synacthen test detect problem in cortisol secretion due to adrenal gland defect or ACTH deficiency. Long synacthen test differentiate between them.

Short Synacthen test 

Principle::

Administration of tetracosactrin [synthetic adrenocorticotrophic hormone (ACTH) or ‘synACTHen’] allows the acute adrenal response to ACTH to be assessed. In addition to promoting cortisol secretion, it also increases the production of other ACTH-dependent steroids (eg androgens) in the biosynthetic pathway and hence can be used to exacerbate the enzyme block in differing types of congenital adrenal hyperplasia (CAH) thereby helping to confirm/exclude the diagnosis in patients with equivocal basal values.

Indications •

1.Diagnosis of primary (and secondary) adrenal insufficiency.

2.Diagnosis of CAH (especially non-classical).

Contraindications:

Known allergy to Synacthen; poorly controlled asthma.

Practical details:

Before investigation : In patients

already on hydrocortisone replacement, the morning dose on the day of the test should be withheld until the test has been completed. Some centres also omit the evening dose on the day before the investigation. In subjects taking supraphysiological glucocorticoid therapy (>30 mg hydrocortisone or >7.5 mg prednisolone per day), Synacthen testing should, where possible, be deferred until the dose has been weaned to a more physiological level.

The investigation :: 

1. 9 a.m. Take blood for serum cortisol and plasma ACTH; give Synacthen 250 µg im (or iv).

2. 9.30 a.m. Take blood for serum cortisol.

3. 10 a.m. Take blood for serum cortisol. However, not all centres routinely measure a 60-minute response.

(a) ACTH samples should be taken on ice to the laboratory for immediate processing.

(b) Low-dose Synacthen (1 µg) is advocated by some as a more sensitive test of adrenocortical function, especially if the short Synacthen test is being used to screen for secondary adrenal insufficiency. However, there remain problems with accurate dosing (currently the 250-µg vial must be diluted), and the validity of the test remains to be proven.

(c) For suspected CAH, measurement of 17αhydroxyprogesterone (17-OHP) is also required.

After investigation: interpretation Adrenal insufficiency There is variation between laboratories as to the exact cut-off for a normal response. However, a serum cortisol level of >550 nmol/L at 30 minutes is generally taken to exclude primary adrenal failure.

A subnormal response following Synacthen suggests either: 1 • primary adrenal pathology or 2 • secondary adrenal insufficiency (eg ACTH deficiency or exogenous steroid therapy) with consequent atrophy of the zonae fasciculata and reticularis.

Paired basal serum cortisol and plasma ACTH levels may help to distinguish between these two possibilities (eg low cortisol with elevated ACTH in primary adrenal failure; low cortisol with inappropriately low/normal ACTH in secondary hypoadrenalism). Alternatively, a long (‘depot’) Synacthen test can be performed to confirm the persistent lack of responsiveness in primary adrenal failure, which contrasts with a delayed but detectable rise in cortisol in secondary adrenal insufficiency.

Source: medical masterclass, 2nd edition.