A 50-year-old Scottish male tourist presents with a three-day history of nausea, vomiting, general lethargy and dizziness. He had similar symptoms one year previously while on holiday in Cyprus and has had multiple presentations to his GP since then with general lethargy and weight loss.
The results of his investigations are as follows:

Parameter

Patient Value

Normal Adult Range

FiO2

0.3

pH

7.29*

7.35 – 7.45

pCO2

22 mmHg (2.9 kPa)

35 – 45 (4.6 – 6.0)

PO2

108 mmHg

SaO2

99%

Bicarbonate

11 mmol/L*

22 – 26

Base Excess

-14 mmol/L*

-2 – +2

Lactate

0.8 mmol/L

< 2.0

Sodium

116 mmol/L*

135 – 150

Potassium

4.7 mmol/L

3.4 – 5.0

Chloride

89 mmol/L*

100 – 110

Urea

1.3 mmol/L*

3.0 – 8.0

Creatinine

40 mmol/L*

50 – 120

Glucose

4.8 mmol/L

3.0 – 5.4

Albumin

39 G/L

35 – 50

Calcium (corrected)

2.08 mmol/L*

2.15 – 2.64

 

a) What is the likely diagnosis?
b) What investigation would you order to confirm your diagnosis?

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College Answer

a)  Hypoadrenalism or Addisonian crisis.

b)  Random cortisol.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high; 78.4mmHg
    PAO2 = (0.3 × 713) - (22 x 1.25) = 186.4
    Thus, A-a = (186.4 - 108) = 78.4mmHg.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -14, suggesting a severe metabolic acidosis
  5. The respiratory compensation is adequate - the expected PaCO2(11 x 1.5) + 8 = 24.5mmHg, and the measured 22mmHg is close enough for government work.
  6. The anion gap is raised:
    (116) - (89  + 11) = 16, or 20.7 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (16 - 12) / (24 - 11) = 0.3
    This suggests that there is a normal anion gap metabolic acidosis here, with just a hint of HAGMA.
  7. Urinary pH or electrolytes are not available.

There is a severe mixed metabolic acidosis with severe hyponatremia and moderate hypocalcemia, in the presence of a normal lactate and normal renal function. Hyperglycaemia is not to blame - the BSL is 4.8

If the patient had a higher serum potassium, the diagnosis of Addisonian crisis would be easier to conjure. Addison's disease is discussed briefly in the chapter on adrenal insufficiency; it causes a Type 4 renal tubular acidosis by interfering with the actions of aldosterone at the cortical collecting duct.

As for the anion gap? I cannot explain that. Nor can I explain why this patient had to be a Scotsman, or the involvement of Cyprus.

And yes, to confirm hypoadrenalism, one would ask for a random cortisol, as well as a short synacthen test.

References

References

Corey, Howard E., Alfredo Vallo, and Juan Rodríguez-Soriano. "An analysis of renal tubular acidosis by the Stewart method." Pediatric Nephrology 21.2 (2006): 206-211.

Soriano, Juan Rodríguez. "Renal tubular acidosis: the clinical entity." Journal of the American Society of Nephrology 13.8 (2002): 2160-2170.

Karet, Fiona E. "Mechanisms in hyperkalemic renal tubular acidosis." Journal of the American Society of Nephrology 20.2 (2009): 251-254.