HPA Tests

Question 1

Discuss the Short Synacthen Test

Answer 1

Used to diagnose primary Adrenal Failure / Addisons disease
* The patient should be resting quietly but not fasting. It is recommended that the test is done in the morning.

• Resuscitation facilities should be available in case of an allergic reaction.
• Blood is taken for basal cortisol assay. Synacthen
  250 µg is given by intramuscular or intravenous injection.
• Blood is taken for cortisol assay at baseline, 30 and 60 min.

The current trend is to assay ACTH itself which will be high when Cortisol is low

Question 2

What drugs should be discontinued in SST?

Answer 2

Done only after discontinuation of interfering drugs (steroids other than dexamethasome/betamethasone) for minimum 12hrs before sample collection). Stop Hydrocort for 24hrs before SST

Question 3

Interpretation of SST

Answer 3

Interpretation

• Normally the plasma cortisol concentration increases by at
  least 200 nmol/L, to a concentration >550 nmol/L.
• The peak is usually at 30 min, although a steady increase at 60 min may imply secondary hypoadrenalism due to
  pituitary or hypothalamic disease.
• ACTH may be normal in mild 2ndry Adrenal Failure
• Adrenocortical Antibodies should be measured in confirmed cases

*Insulin Tolerance Test (cortisol response to hypoglycaemia)
Parenteral ACTH is given to diagnose Adrenal Insufficiency/CAH to distinguish between CAH (the heterozygous State) from the homozygous AI and Premature Adrenache.

Question 4

Discuss the Low dose SST

Answer 4

Modified version of Standard dose Test

• Uses physiologic rather than Pharmacologic dose of ACTH when SDST fails to detect mild impairments of adrenal function
• LDST is by far more sensitive & safe
  LDST is performed in Children with normal response to SDST
• Clinical cases missed using the standard dose are easily picked with the LDST.
  LDST is more Sensitive than SDST

Question 5

Discuss ITT
What are some meausures to consider?

Answer 5

• Measures Cortisol response to stress induced by hypoglycaemia

ITT not reliable within 4 weeks of Pituitary surgery. Not long enough to cause adrenal atrophy
Severe allergic reactions to have been reported in some children

Patient should rest for minimum 30mins after Canula insertion before sampling

Steroid therapy to be restored immediately after sampling.

This test is potentially dangerous and must be done under direct medical supervision.

Question 6

Indications of the insulin stimulation test may include:

Answer 6

● assessment of GH in growth deficiency,
● assessment of ACTH/cortisol reserve (although the development of plasma ACTH assays has made such testing less necessary),
● differentiation of Cushing’s syndrome from pseudoCushing’s syndrome, for example depression or alcohol excess.

Question 7

ITT Protocol

Answer 7

• Commence test by 9.00am ideally
  Give ACTH (i.v) slowly over 2 minutes OR
  Give i/m as follows; (36µg/Kg ≤ 6month; 125µg/Kg 6-24Months, & 250Kg in Children > 2yrs)
• Measure serum Cortisol at: 0, +30 & +60mins after stimulation
• Measure also ACTH at the start of the test if PAI (Personalized Activity Intelligence) is suspected
• If 21∝𝑂𝐻lase def. is suspected add; i. 17-OH Progesterone (at 0, +30, and +60 mins) to the tests ii. Testosterone, Androstenedione, DHEA & DHEAS at 0 minute, and Urinary Steroid analysis

Question 7

What drugs should be discontinued in ITT?

Answer 7

Hydrocortisone to be discontinued at least 12 hrs prior to test

Prednisolone and others discontinued at least 3 days prior to prevent error due to interference with ACTH

Question 8

Interpretation of ITT

Answer 8

Plasma Cortisol at 30 minutes Should be >550 nmol/l (20mcg/l) OR rise above basal level >200nm/l)

Question 9

Discuss the Dexamethasone Suppression Test

Answer 9

A synthetic analogue of Cortisol that suppresses ACTH secretion by negative feedback inhibition at the hypothalamic & Pituitary levels to suppress Cortisol secretion

Patients with Cushing’s Syndrome lose this feedback inhibition and fail to suppress

Overnight DST (Indications)
Used as a Screening Test (an Outpatient Proceedure) with good sensitivity but poor specificity. Hence, Patients who fail to suppress will require Formal Low dose Dexamethasone Suppression Test

Question 10

Discuss LDDST

Answer 10

PRECAUTION!!! Ensure Patient is not on Steroid Therapy

Give Oral Dexamethasone 0.3mg per Square Metre given at midnight;

8:00hr following morning, take blood sample for Cortisol, ACTH, DHEAS, Androstenedione & Testosterone (if an androgen Secreting Tumour is Suspected

Determine Serum dexamethasone in the 08:00hr to ensure adherence to Rx

Question 11

Interpretation of LDDST

Answer 11

In normal subjects 8:00am Cortisol Concentration (˂ 50nmol/l or 1.815µg/dl) is expected
Patients with Cushing’s Syndrome fail to suppress adequately
In that case a 48-hr LDDST should be performed
Failure of suppression is observed in Androgen Secreting Tumours

Question 12

What test is used to differentiate Cushing’s Syndrome from simple Obesity?

Answer 12

48hr DDST
The 48-h lowdose dexamethasone suppression test may be useful as
it gives fewer false-positives than the overnight low-dose dexamethasone test:

0.5 mg dexamethasone is given orally at 6-h intervals from 09.00 h on day 1 for eight doses, and then plasma cortisol is measured after 48 h at 09.00 h.

Plasma cortisol should normally suppress to less than 50 nmol/L, but not in Cushing’s syndrome