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• Alternatives to the short synacthen test
  oscar,m jolobe
  Published on: 8 December 2019

• Published on: 8 December 2019

  Alternatives to the short synacthen test

  • oscar,m jolobe, retired geriatrician manchester medical society

  Even when one takes into account the possibility that measurement of plasma cortisol after 60 min administration of synthetic ACTH might be a sufficient screening test for adrenal insufficiency(AI)(1), it is important to recognise that there are risk-free alternatives to the short synacthen test(SST) for validating the diagnosis of AI(2)(3)(4).
  According to a retrospective study which evaluated, not only the 30 min and the 60 min cortisol levels, but also the pre-synacthen cortisol levels, a pre-synacthen serum cortisol level of 100 nmol/L or less(obtained during the median time period 08.20 h) is associated with a positive predictive value of 93.2% for the diagnosis of AI, when the gold standard for the latter is a failed SST. In that study of 330 subjects with suspected AI tested with the 250 mcg dose of tetracoscatrin , the subgroup with an eventual diagnosis of AI were tested at the median time of 08.20h(interquatrile range 07.55-09.26). The subjects who passed their SST were tested during the median time of 08.33(interquatrile range 08.01h-09.55h). Conversely. a pre-synacthen serum cortisol of 450 nmol/L or more generated a 98.7% negative predictive value to rule out AI(2). These observations were largely corroborated by a retrospective study of 231 subjects with suspected AI in whom AI was validated by an SST which incorporated 30 min as well as 60 min serum cortisol levels. In that study some patients(unspecified number) were tested at 08.00h...

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  Even when one takes into account the possibility that measurement of plasma cortisol after 60 min administration of synthetic ACTH might be a sufficient screening test for adrenal insufficiency(AI)(1), it is important to recognise that there are risk-free alternatives to the short synacthen test(SST) for validating the diagnosis of AI(2)(3)(4).
  According to a retrospective study which evaluated, not only the 30 min and the 60 min cortisol levels, but also the pre-synacthen cortisol levels, a pre-synacthen serum cortisol level of 100 nmol/L or less(obtained during the median time period 08.20 h) is associated with a positive predictive value of 93.2% for the diagnosis of AI, when the gold standard for the latter is a failed SST. In that study of 330 subjects with suspected AI tested with the 250 mcg dose of tetracoscatrin , the subgroup with an eventual diagnosis of AI were tested at the median time of 08.20h(interquatrile range 07.55-09.26). The subjects who passed their SST were tested during the median time of 08.33(interquatrile range 08.01h-09.55h). Conversely. a pre-synacthen serum cortisol of 450 nmol/L or more generated a 98.7% negative predictive value to rule out AI(2). These observations were largely corroborated by a retrospective study of 231 subjects with suspected AI in whom AI was validated by an SST which incorporated 30 min as well as 60 min serum cortisol levels. In that study some patients(unspecified number) were tested at 08.00h(morning cortisol subgroup), and the rest were tested at 09.00h-13.00h(basal cortisol subgroup). A basal cortisol level of < 85 nmol/L was associated with a specificity of 99.7% and a sensitivity of 24.7% for the diagnosis of AI when the gold standard for AI was a failed SST. for ruling out AI, a serum cortisol of 350 nmol/L or more was associated with a sensitivity of 98.9% and a specificity of 32.2%(3). In that study the receiver operating curve generated a significantly higher area under the curve for basal cortisol than for morning cortisol in predicting a failed SST.
  In the specific context of hypoglycaemia, regardless of the time of day, a single measurement of serum cortisol can unequivocally establish the diagnosis of AI. The rationale is that hypoglycemia is a stressor that activates the entire hypothalamic-pituitary-adrenal axis , thereby exceeding the stressor potential of the SST. All that it needs is for clinicians to be alert to opportunities to utilise the stressor potential of hypoglycaemia. A missed opportunity to do so was exemplified by the cautionary tale of a 19 year old man with type 1 insulin-treated diabetes and autoimmune hypothyroidism, both being the components of the autoimmune polyglandular syndrome. When he was admitted to hospital with hypoglycaemic coma the opportunity was not taken to explore fully the underlying cause of that complication . After his discharge he experienced recurring episodes of hypoglycaemia despite reducing his insulin dose. Eventually, 5 months post discharge, a SST was performed and it showed that he had AI. That diagnosis could have been established with a single measurement of serum cortisol during the episode of hypoglycaemia necessitating his hospital admission.
  The additional advantage of a single measurement of serum cortisol that validates AI is that it obviates the need for a subsequent SST , and its attendant risk(albeit rare) of potentially fatal allergic reaction to exogenous tetracosactrin(5).
  Finally, robust prospective studies are still needed to validate the hypotheses enunciated in (1)(2)(3)
  I have no funding and no conflict of interest
  References
  (1) Kumar R., Carr P., Moore K et al
  Do we need 30 min cortisol measurement in the short synacthen test: a retrospective study
  Postgrad Med J 2019;1doi.org/10.1136/postgradmedj 2019
  (2)struja T., Briner L., Meier A et al
  Daignostic accuracy of basal cortisol level to predict adrenal insufficiency in consyntropin testing results from an observational cohort study with 804 patients
  Endocrine Pract 2017;23: 949-961
  (3) Mansrol W., Phimphllal M., Khorana J., Atthakolol P
  Diagnostic performance of basal cortisol level at 09.00-13.00h in adrenal insufficiency
  PLOS ONE 2019;doi.org/10.1371/journal.pone.0225255 November 18, 2019
  (4) McAulay V., Frier BM
  Addisons's disease in type 1 diabetes presents with recurrent hypoglycaemia
  Postgrad Med J 2000;76:230-232
  (5) Anonymous
  Today's drugs
  Tetracosactrin
  BMJ 10.1136/bmj.2.5545.160 on 15th April 1967

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  Conflict of Interest:
  None declared.

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