Question 7.2

Highest mark

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.

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.
There is acidaemia
The PaCO₂ is compensatory
The SBE is -14, suggesting a severe metabolic acidosis
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.
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.
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.

And yes, to confirm hypoadrenalism, one would ask for a random cortisol, as well as a short synacthen test. 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. As a reader had pointed out (thank you Damian), this may be an allusion to the increased risk of a cold-loving northdweller being exposed to the hot sweatiness of a Mediterranean holiday. As Dineen et al (2019) had put it, "In the case of a hot climate or strong perspiration, it is necessary to increase the fludrocortisone dose (0.1–0.2mg/ day) or the salt intake to compensate."

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.

Dineen, Rosemary, Christopher J. Thompson, and Mark Sherlock. "Adrenal crisis: prevention and management in adult patients." Therapeutic advances in endocrinology and metabolism 10 (2019): 2042018819848218.

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