Tag: curbsiders

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Some addenda to my Curbsiders podcast on NAGMA

In my discussion on The Curbsiders I talked about the urine anion gap as a way to estimate urine ammonium. Here are the figures I would have shown for the urine anion gap, if the Curbsiders was a television show rather than a podcast:

The urine anion gap is wildly inaccurate at estimating urine ammonium. In this study of 1,044 people with chronic kidney disease, the urine anion gap was 42, while the urine ammonium was only 21:

Would you trust a technique to measure serum sodium if it was twice the actual serum sodium?

There is a second way to estimate the urine ammonium, the urine osmolar gap. The urine osmolar gap was devised to escape a different weakness in the urine anion gap, the problem with large amounts of urine anions, like ketones or hippurate.

The osmolar gap assumes that the difference between the measured and calculated osmolality will largely be made up by ammonium salts.

Here is a tweetorial about this, if that is your thing:

Part One: Don’t trust equations:

Part Two: But you need to understand the equations so you can use them properly, the urine anion and osmolar gap:

The other mistake I made was an over simplification on how NH4+ is made. I said NH3 was made in the proximal tubule but it is more complicated than that. A lot more complicated. From David Goldfarb:

The proximal tubule makes 2 molecules of NH4+ via Glutaminase which also produces a  1 alpha-ketaglutamate (AKG). The AKG generates 2 molecules of HCO3 which is added to the blood. The NH4 gets tossed into the tubular fluid. So for every NH4+ created in the proximal tubule, one bicarb gets added to the blood.

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Curbsiders #104: Renal Tubular Acidosis

This is the back half of my Acid-Base talk, a detailed dive into non-anion gap metabolic acidosis with an examination of renal tubular acidosis. This one turned out pretty good.

Here is a link to the Curbsiders page for this episode.

This is the sequel to #88 Acid base, boy bands, and grandfather clocks with Joel Topf MD

Before that I did episode #67 and #69 on chronic kidney disease

Before that was #48 Hyponatremia Deconstructed

And I started my Curbsiders career with #31 Diuretics, leg cramps and resistant hypertension.

So non-anion gap metabolic acidosis is my fifth or sixth appearance on the Curbsiders. Thanks guys.

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Adrenal insufficiency and hyponatremia

Every intern knows that the evaluation of hyponatremia includes a TSH and a cortisol level to rule out hypothyroidism and adrenal insufficiency as occult causes of euvolemic hyponatremia.

The mechanism of adrenal insufficiency is a bit confusing with some sources stating that these patients are volume depleted while others are euvolemic.

In some patients without aldosterone, the patients develop severe salt wasting, become hypotensive and get a non-osmotic release of ADH resulting in hyponatremia. These patients will respond to saline. Treat the hypovolemia and the sodium will go up.

Hyponatremia is a common manifestation of adrenal insufficiency even in cases without adrenal crisis. Giving saline to these patients is not effective at correcting the hyponatremia. Giving cortisol, however, results in a brisk water diuresis and rapid correction of the serum sodium (Oelkers, NEJM, 1989).

In addition to being resistant to saline, ADH antagonists (think tolvaptan) protect against this type of adrenal insufficiency-induced hyponatremia.

This means cortisol corrects an abnormality that is due to excess ADH. 

Here is the explanation from the late 90’s from The Fluid, Electrolyte and Acid-Base Companion. 

Bartter and Schwartz original definition of SIADH required a normal cortisol specifically to exclude patients with hypopituitism and primary adrenal insufficiency. In primary adrenal insufficiency, in addition to loss of cortisol there is an aldosterone deficiency which can result in sodium wasting, volume depletion and a non-osmotic (decreased perfusion in this case) stimulates for the release of ADH. In this scenario, the patient should appear salt/volume depleted and would not be considered euvolemic.

A nice review of secondary adrenal insufficiency and hyponatremia was done by Sven Diederich.

Remember:

  • Primary adrenal insufficiency: destruction of the adrenal glands leads to loss of endogenous cortisol. These patients typically also have aldosterone deficiency, so they will be salt wasters, resulting in hypovolemia. They will also have hyperkalemia.
  • Secondary adrenal insufficiency: decreased ACTH (from pituitary or hypothalamic disease, or from pharmacologic steroids) prevents secretion of cortisol

In Diederich’s review they pulled 139 cases of hyponatremia that were referred to endocrinology. (Clearly this study suffers from profound selection bias. Here is a a cleaner study on the epidemiology of hyponatremia by Schrier, from back in the day.) They found 28 cases of hypopituitism leading to hyponatremia. Patients tended to be older (average age 68) and more female (75%). In 25 cases the hypopituitism had not previous been diagnosed and 12 patients had previously been admitted (between 1 and 4 times) for severe hyponatremia without an adequate diagnosis.

Basal cortisol levels were as follows:

  • Below 100 nmol/L (3.6 mcg/dL) in 7
  • Below 200 nmol/L (7.2 mcg/dL) in 21
  • The mean level was 157 nmol/L (5.7 mcg/dL)
  • The highest basal level was 439 nmol/L (16 mcg/dL)

Imaging results:

  • Twelve patients had an ‘empty sella’
  • Six patients had pituitary tumors

  • One had secondary adrenal insufficiency due to chronic treatment with prednisolone because of ankylosing spondylitis

Don’t be the doctor that corrects the hyponatremia but fils to diagnose adrenal insufficiency and discharges and sends the patient home only to redevelop hyponatremia another day. Turn over every stone, especially in patients with SIADH of undetermined etiology.