Secondary adrenal insufficiency laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].

OR

Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

OR

[Test] is usually normal among patients with [disease name].

OR

Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].

OR

There are no diagnostic laboratory findings associated with [disease name].

Laboratory Findings

Source of pathology CRH ACTH DHEA DHEA-S cortisol aldosterone renin Na K Causes5
hypothalamus
(tertiary)1
low low low low low3 low low low low tumor of the hypothalamus (adenoma), antibodies, environment (i.e. toxins), head injury
pituitary
(secondary)
high2 low low low low3 low low low low tumor of the pituitary (adenoma), antibodies, environment, head injury,
surgical removal6, Sheehan's syndrome
adrenal glands
(primary)7
high high high high low4 low high low high tumor of the adrenal (adenoma), stress, antibodies, environment, Addison's Disease, trauma, surgical removal (resection), miliary tuberculosis of the adrenal
1 Automatically includes diagnosis of secondary (hypopituitarism)
2 Only if CRH production in the hypothalamus is intact
3 Value doubles or more in stimulation
4 Value less than doubles in stimulation
5 Most common, does not include all possible causes
6 Usually because of very large tumor (macroadenoma)
7 Includes Addison's disease

Routine Investigations

Hormone Test Procedure Normal response
Growth hormone Insulin tolerance
  • Glucose should drop <40 mg/dL, (2.2 mmol/L)
  • GH should be >3–5 μg/L
  • Cut-offs for GH response are BMI related 
GHRH + arginine  
  • Administer GHRH, 1 μg/kg (max 100 μg) iv followed by an arginine infusion 0.5 g/kg (max 35 g) over 30 min
  • Sample blood at 0, 30, 45, 60, 75, 90, 105, and 120 min for GH
  • GH >4 μg/L, but cutoffs for GH response should be correlated to BMI (obesity may blunt GH response to stimulation)
Glucagon
  • Administer glucagon, 1 mg (1.5 mg if weight >90 kg) IM
  • Sample blood at 0, 30, 60, 90, 120, 150, 180, 210, and 240 min for GH and glucose
  • GH >3 μg/L, but cutoffs for GH response should be correlated to BMI (Obesity may blunt GH response to stimulation)
ACTH Insulin tolerance
  • Glucose should drop <40 mg/dL (2.2 mmol/L)
  • Peak cortisol should be >500–550 nmol/L (>18.1–20 μg/dL) depending on assay
Corticotropin standard dose (250 μg)
  • Sample blood at 0, 30, and 60 min for cortisol
  • Cortisol should be at 30 or 60 min >500–550 nmol/L (>18.1–20 μg/dL) depending on assay
Corticotropin low dose (1 μg)
  • Cortisol should be at 30 min >500 nmol/L (18.1 μg/dL) depending on assay
ADH Water deprivation test 
  • Initiate fluid deprivation for 8h (starting from 8 AM)
  • Weigh patient at beginning of testing, then measure weight and urine volume hourly during the test
  • At 4 PM administer DDAVP 2 μg im and allow patient to drink freely
Diabetes insipidus (DI): Plasma osmolality >295 mOsm/L with inappropriately hypotonic urine (urine osmolality/plasma osmolality ratio <2) during the fluid deprivation confirms DI (test is discontinued)

Partial/primary polydipsia: With partial DI or primary polydipsia, urine concentrates partially during the water deprivation test (300–800 mOsm/kg), and further investigation is required including a prolonged water deprivation test or DDAVP therapeutic trial

References

  1. Burke CW (1985). "Adrenocortical insufficiency". Clin Endocrinol Metab. 14 (4): 947–76. PMID 3002680.
  2. Todd GR, Acerini CL, Ross-Russell R, Zahra S, Warner JT, McCance D (2002). "Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom". Arch. Dis. Child. 87 (6): 457–61. PMC 1755820. PMID 12456538.
  3. Stacpoole PW, Interlandi JW, Nicholson WE, Rabin D (1982). "Isolated ACTH deficiency: a heterogeneous disorder. Critical review and report of four new cases". Medicine (Baltimore). 61 (1): 13–24. PMID 6276646.
  4. Cuesta M, Garrahy A, Slattery D, Gupta S, Hannon AM, Forde H, McGurren K, Sherlock M, Tormey W, Thompson CJ (2016). "The contribution of undiagnosed adrenal insufficiency to euvolaemic hyponatraemia: results of a large prospective single-centre study". Clin. Endocrinol. (Oxf). 85 (6): 836–844. doi:10.1111/cen.13128. PMID 27271953.

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