Case of the Month 21

tedsegarra · July 21, 2017 at 5:54 pm

Whooooo boy! Well, Rithvik, you better get ready yourself for some serious pontificating (complete with zebras!)..

Diagnosis
The differential diagnosis for the patient is initially large and should include a wide range of disorders including common intra-abdominal pathologies (cholecystitis, appy, pancreatitis, SBO), sepsis (TB recurrence, primary HIV, pyelonephritis, appendicitis), drug related etiologies (esp RIPE induced hepatitis, pancreatitis), hematologic disorders (leukemia/lymphoma), and endocrine/metabolic disorders (DKA/HHS, DM gastroparesis, SIADH, adrenal insufficiency). Given her extensive organomegaly, we can also consider infiltrative/deposition diseases like amyloidosis.

However, our labs and imaging help us narrow down the scope by ruling out DKA (bicarb >18, no acetone), pancreatitis, hepatitis, cholecystitis, appy, and SBO. We are left with a patient who is hypotensive, tachycardic, with bilateral CVAT and abdominal ttp, with significant leukocytosis (46, and bandemia 11%), anemia, thrombocytopenia, and diffuse electrolyte abnormalities. Our patient has hyponatremia (116, corrected 126), elevated potassium (5.2), mildly low bicarb (20), an elevated anion gap w/o overt acidosis (AG 17, corrected 20; VpH 7.37), AKI/CKD, and hyperglycemia (526). UA reveals sterile pyuria and glucosuria. Imaging reveals ascites and diffuse organomegaly, with a clear CXR.

When we think about hyponatremia, it’s helpful to classify by volume status into hyper, hypo, and euvolemic hyponatremia. Euvolemic hyponatremia is most commonly caused by SIADH, cortisol deficiency (seen in both primary and secondary adrenal insufficiency), and hypothyroidism; while hypovolemic hyponatremia is usually caused by diuretics and salt wasting (renal salt wasting 2/2 primary adrenal insufficiency with associated hypoaldosteronism; and cerebral salt wasting). However, clinical assessment of fluid status is only about 49% accurate, and so urine studies are often needed to differentiate between mild hypovolemia and euvolemia. Urine sodium and chloride are helpful in distinguishing between these, but in patients with AKI and reduced GFR (ie: this patient), the FeNa is even better at determining volume status. As a result, this patient would benefit from further studies, including a serum osm, urine osm, urine lytes, urine creatinine (with calculation of FeNa), cortisol, and TSH.

Our patient presents with hypotension, dry mucous membranes, and tachycardia, combined with an AKI with a pre-renal ratio (88/3.23, ratio 27:1), thus painting a clinical picture of hypotension (hypovolemic hyponatremia). In combination with her hyponatremia, hyperkalemia, and borderline metabolic acidosis, the available data is highly suggestive of primary adrenal insufficiency (low cortisol, low aldosterone). Hyponatremia in this setting is primarily due to inappropriately high ADH caused by low cortisol (patients are unable to excrete free water). Hyperkalemia and mild metabolic acidosis are caused by aldosterone deficiency (similar to a Type IV RTA, hypoaldosterone state). In this patient, the relatively normal pH is likely due to a combined metabolic acidosis (adrenal insufficiency) and metabolic alkalosis (contraction from GI losses and polyuria).

In this particular patient with a history of prior TB, we must consider the possibility of primary adrenal insufficiency secondary to miliary TB, which frequently spreads hematogenously to blood rich organs (such as those indicated as having organomegaly on her CT scan – kidneys, liver, uterus), and which often causes ascites, hepatomegaly, and weight loss. In addition, miliary TB is frequently associated with sterile pyuria, normocytic anemia, and thrombocytopenia, and can also present with significant leukocytosis suggestive of a leukemoid reaction.

Despite completion of a 6 month TB regimen, we know nothing about the resistance pattern of her isolates, and so it’s possible that this patient may have been resistant to her initial therapy, resulting in inadequate clearance and persistence of her infection. So in addition to basic labs and cultures, and the above-mentioned tests for hyponatremia, she would additionally benefit from AFB stains and mycobacterial cultures of her blood, urine, sputum, and possibly from a mycobacterial liver biopsy/culture depending on her initial response to therapy. She would also likely benefit from diagnostic paracentesis for r/o SBP and for AFB stain/cultures. In addition, an HIV test should be sent to rule out concomitant HIV infection, as this can predispose to TB/MAC treatment failure or to direct HIV adrenalitis. Another point to consider is that patients taking Rifampin may present with secondary adrenal insufficiency (cortisol deficiency) due to increased metabolism of cortisol.

Treatment
In regards to treatment, she should receive coverage for gram negative organisms and anaerobes (coverage for SBP, bacterial pyelonephritis, and other intra-abdominal sources) with ceftriaxone (or levofloxacin) PLUS flagyl (better choice than Zosin given the patient’s AKI) or Zosin. She doesn’t require Vanco as she has no evidence of soft tissue infxn, line infection, or HCAP. Depending on her initial AFB smears and other culture data, she can also be re-started on RIPE after consultation with ID.

Careful correction of her hyponatremia is required in order to prevent both hyponatremic seizure and Osmotic Demyelination Syndrome (ODS, previously Central Pontine Myelinolysis) from rapid overcorrection. Initial treatment with normal saline was appropriate, as her hypovolemic hyponatremia may simply have been the result of renal losses. However, her worsening hyponatremia with normal saline supports inappropriate ADH secretion, and given the severity (Na <110) and associated symptoms of nausea/vomiting, she requires treatment with hypertonic saline rather than just free water restriction. Correction should be aimed at 4-6 mEq/L over 24 hours (this amount can be achieved within first 6 hours, with maintenance of that level over the next 18 hours) in order to avoid ODS. This can be given as a bolus of 50 mL 3% NS, followed by slow infusion at 15-30 cc/hr, and should be stopped once her sodium reaches 113 mEq (can correct by another 4-6 mEq the following day). Although we don’t know her Ideal Body Weight, if we assume she is 60 kg, with 60% TBW, we can calculate that she will need about 540 cc of 3% NS (containing 513 mEq/L Na) to reach a goal of 113 mEq/L(from her current 107 mEq/L) in the first 24 hours.

Although she likely has adrenal insufficiency, this patient is currently HD stable and so does not require emergent administration of hydrocortisone (best steroid choice for treatment in primary adrenal insufficiency, as it has both glucocorticoid and mineralocorticoid activity, 1:1 activity ratio). However, if her labs show significantly reduced activity, or if she becomes HD unstable, she will likely require replacement therapy, generally dosed at Hydrocortisone 100mg IV q6 hrs.

Dispo
As the patient has no clinical symptoms of active pulmonary TB she shouldn't require isolation. However, she will likely require admission to the MICU given her increased risk of seizures and the need for central line administration of hypertonic saline. Once her hyponatremia has resolved, if she remains HD stable, she could be downgraded to the medicine floors.