Hyponatremia due to secondary adrenal insufficiency

Thanks to Jess for presenting the fascinating case of a middle-aged woman with family history of autoimmune disease who presented with acute onset of fatigue and abdominal pain, found to have vitiligo on exam.  Work up revealed hyponatremia due to a secondary adrenal insufficiency, pancytopenia, and panhypopituitarism possibly due to a yet to be diagnosed autoimmune disorder!

Clinical pearls

  • Remember that hyponatremia is a problem of water regulation that can be compounded by low solute intake.
  • Primary adrenal insufficiency is disorder at the level of the adrenal glands and manifests with low sodium and high serum potassium levels.
  • Secondary adrenal insufficiency is disorder at the level of the pituitary and manifests with low/normal sodium and normal potassium levels (because low cortisol leads to high ADH levels and hyponatremia).
    • Make sure to do work up to rule out panhypopituitarism.  Keep in mind that the most sensitive test for HPA access integrity is LH/FSH.
  • Tertiary adrenal insufficiency is disorder at the level of the hypothalamus and presents similarly to secondary AI.
  • Test for adrenal insufficiency with a cort-stim test and/or AM cortisol and ACTH levels.


Remember these three steps to working up hyponatremia:

  1. Is there a sodium problem? check serum osm
  2. Are the kidneys responding appropriately? check urine osm
  3. Is ADH revved up for a hemodynamic reason? check urine Na 


Adrenal insufficiency

Adrenal insufficiency
Source: NIDDK.gov

Primary AI:

  • Failure of adrenal glands
  • Causes: Addison’s (most common in the US), infiltrative processes (TB, sarcoid), hemorrhage, toxins
  • Labs would show ↓Na and ↑potassium (b/c aldosterone is gone)

Secondary AI:

  • Failure of pituitary (low ACTH)
  • Causes: pituitary lesions, surgeries, TBI, drugs
  • Clinically may present with loss of other anterior pituitary hormones
  • Labs would show ↓Na (because low cortisol leads to high ADH levels) but normal potassium levels (b/c aldosterone is active)

Tertiary AI:

  • Failure of hypothalamus (low CRH)
  • Causes: more commonly iatrogenic (cessation of high dose glucocorticoid therapy without taper) or post surgical interventions.




  • Inflammation of the pituitary
  • Four categories based on histologic findings:
    • Lymphocytic
      • Most common form
      • Seen in late pregnancy and post-partum period
      • Also associated with CTLA4 inhibitors like ipilimumab
    • Granulomatous
      • Idiopathic or secondary to GPA, sarcoid, TB
    • Plasmacytic (IgG4-related)
    • Xanthomatous (most rare)
  • Clinical presentation
    • Headache out of proportion to exam findings
    • Preferential decrease in ACTH and TSH ⇒ adrenal insufficiency and hypothyroidism
  • Prognosis:
    • Pituitary size eventually normalizes but pituitary loss of function is often permanent.


Angioedema and hyperkalemia management

Thanks to Audris for presenting the case of a middle-aged man with vasculopathy on ACEi who presented with angioedema requiring intubation!  We discussed the  diagnostic work up and management of angioedema as well as hyperkalemia!

Clinical Pearls

  • First order of business when suspecting angioedema is the ABCs!
  • Treat angioedema in the acute setting with H1 blockers and steroids, even if you are suspicious of a non-histaminergic pathway.
  • Always assess for concurrent anaphylaxis (hypotension or bronchospasm in addition to hives or angioedema).  If anaphylaxis is present, then treatment involves IM 0.3-0.5 mg of 1:1000 dilution epinephrine (1mg/mL), repeat every 20 minutes until symptoms resolve (max 3 doses)
  • If you have access to a functioning kidney, favor loop diuretics over cation exchange binders (i.e. kayexalate) to lower serum potassium!
  • Patiramer is much better tolerated than kayexalate and has a more favorable side effect profile.
  • Calcium gluconate has a role in the treatment of hyperkalemia when EKG changes are present. Give a dose and repeat the EKG.  If no improvement, repeat to a maximum of 3 doses until EKG has normalized.


  • 3 pathophysiologic subtypes:
    • Mast cell/histamine mediated
      • Etiologies:
        • Allergic reactions: food/insect stings, latex, drugs. Can also be idiopathic. IgE type 1 hypersensitivity
        • Direct mast cell release: drugs (opiates, contrast). IgE is not involved.
        • ASA/NSAIDs: via IgE or direct mast cell release
        • Chronic urticaria w/w/o angioedema
      • S/sx affecting organ systems other than the skin? Suspicious for anaphylaxis ⇒ give epi
      • Treatment: H1 blockers, glucocorticoids. 
    • Bradykinin mediated
      • Inhibition of enzymes involved in the degradation of bradykinin, or deficiency/dysfunction of complement C1 inh
      • More prolonged time course, develops over 24-46 hours and resolves within 2-4 days
      • Relationship between trigger and onset of symptom is not as apparent
      • Not associated with other s/sx. More common to have abdominal pain due to bowel wall involvement.
      • Treatment: bradykinin pathway mediators (ecallantide, icatibant), C1 inhibitor concentrate, or plasma replacement.
    • Unknown mechanism
      • Idiopathic angioedema
      • Infections (in children)
      • CCBs
      • Other drugs: sirolimus, everolimus, amiodarone, metoprolol, risperidone, paroxetine, and etanercept, inhaled cocaine.
      • Herbal meds
      • Urticarial vasculitis
      • Hypereosinophilic syndrome and Gleich syndrome




Agents that reduce serum potassium via transient intracellular shift:

  • Insulin: give with D50 if normoglycemic to avoid hypoglycemia and be sure to check FSG hourly for 4 hours after to ensure no hypoglycemia develops
  • Albuterol (10-20 mg) nebs: this is significantly higher than the dose we give in COPD (2.5 mg) and is equal to ~8 treatments! So make sure to continue the nebs when the patient arrives on the floor from the ER if they are still hyperkalemic.
  • NaHCO3: best for management of chronic hyperkalemia in the outpatient setting.  In the acute management of hyperkalemia, alkalinization of serum with a large bicarb load can lead to a reduction in serum calcium levels.  Lower serum calcium can lead to more cardiac membrane instability and fatal arrhythmias!

Agents that eliminate potassium from the body:

  • Loop diuretics: first choice if a functioning kidney is available!
  • Cation exchange binders: preferred when kidneys are not available
    • Patiramer (available at VMC), much more tolerable than kayexalate and highly effective at lowering serum potassium.  Like kayexalate, it works over hours to days.
    • Sodium zirconium: similar to patiramer but not currently available
    • Kayexalate: not pleasant to take orally. Also carries with it the slight risk of colonic ischemia especially in post renal transplant patients and those with baseline colonic dysfunction (due to infection or inflammation).
  • Dialysis

Indication for using calcium gluconate: when EKG changes are noted.  Repeat doses (maximum 3) until EKG changes have resolved.

Lupus Nephritis

Shout out to Paige for admitting the interesting young woman with no medical history who presented with blurry vision, found to be in hypertensive emergency and nephrotic syndrome.  Her work up revealed diffuse proliferative lupus nephritis (class IV) without any other clinical features of lupus!

Clinical Pearls

  • Proteinuria is primarily caused by three processes: 1) overflow (due to elevated paraprotein levels), 2) glomerular disease, 3) tubular disease (rarely reaches nephrotic range)
  • Renal involvement is noted in ~50% of patients with SLE and can present as nephrotic and/or nephritic syndromes.
  • The most common and severe form is diffuse proliferative lupus nephritis (class IV)
  • Keep in mind that SLE flare is associated with a normal/low WBC, normal/low CRP, and absence of fever.  Infection, which can instigate a lupus nephritis flare, would cause an elevated WBC, elevated CRP, and fever.
  • Lab findings suggestive of SLE flare also include an elevated anti-dsDNA (correlates with disease activity), low complement levels (especially C3), worsening proteinuria, and elevated creatinine.
  • Treatment involves an induction phase with cytoxan or MMF plus solumedrol followed by a maintenance phase with the goal of reducing urine protein excretion to <0.33 g/day.

Hypertension urgency/emergency:

  • Urgency: BP>180/120 without end organ damage
    • Manage with orals, goal to lower (not necessarily correct) over 24-48 hours
  • Emergency: elevated BP + end organ damage (brain, eye, heart, kidney)
    • Manage with IV meds, reduce DBP by 10-15% over the first hour, then by 25% over the next 6-12 hours.
    • Special situations:
      • Lower rapidly in acute aortic dissection (goal SBP <110 ASAP)
      • Recent ischemic stroke: do not lower BP unless > 220/120 (> 185/110 if received reperfusion therapy)


  • Female to male prevalence is 9:1
  • Diagnose using Systemic Lupus International Collaborating Clinics (SLICC) criteria.  Must have > 4 (at least 1 clinical and 1 laboratory) OR biopsy proven lupus nephritis with a positive ANA or dsDNA
  • Autoantibodies:
    • dsDNA is 50% sensitive but 97% specific –> can monitor disease activity
    • Smith is 10-20% sensitive but >90% specific
  • Work up of presumed flare:
    • Important to distinguish flare from acute infection but keep in mind that infection can trigger flare
    • SLE flare:
      • Low WBC and normal CRP (except when serositis is present)
      • Fever is unusual
    • Infection:
      • High WBC and high CRP
      • Fever is common 
  • Treatment:
    • Plaquenil for all unless contraindicated
    • Mild/mod:
      • plaquenil, NSAIDs, low dose steroids (pred 5 daily)
    • Severe
      • Acute: high dose steroids
      • Chronic: Immunosuppressive agents (MTX, cyclosporine, cyclophosphamide, azathioprine, mycophenolate, belimumab)
  • Prognosis
    • Worse with pediatric onset, ethnic minority, renal involvement, increased number of diagnostic criteria, low complement, e/o end organ damage
    • High association of CVD and SLE

SLE and renal disease

  • Renal involvement is common and eventually occurs in ~50% of SLE patients
  • 10% progress to ESRD
  • High mortality compared to SLE without nephritis
  • More common and severe in African Americans, Hispanics, Asians
  • Classifications of GN: can evolve from one to another
    • Minimal mesangial lupus nephritis (class I)
      • Earliest and mildest form
      • Rarely diagnosed b/c pts have a normal U/A, no or  minimal proteinuria, and normal Cr
    • Mesangial proliferative lupus nephritis (class II)
      • Microscopic hematuria and/or proteinuria
      • Light microscopy would show mesangial hypercellularity or mesangial matrix expansion
    • Focal lupus nephritis (class III)
      • Hematuria, proteinuria, some HTN, decreased GFR
      • Less than 50% glomeruli affected by light microscopy
      • Segmental glomerulonephritis
        • A: active lesions –> focal proliferative
        • A/C: active and chronic lesions –> focal proliferative and sclerosing
        • C: chronic inactive lesions and scarring –> sclerosing
    • Diffuse lupus nephritis (class IV)
      • Most common and most severe
      • Hematuria, proteinuria, nephrotic syndrome, HTN, reduced GFR
      • Hypocomplementemia (esp C3) and elevated anti-dsDNA during active disease
      • >50% of glomeruli are affected
    • Lupus membranous nephropathy (class V)
      • nephrotic syndrome, Cr normal or slightly elevated
      • Diffuse thickening of the glomerular capillary wall and subepithelial deposits
      • Can present without any other clinical or serologic manifestations of SLE
    • Advanced sclerosing lupus nephritis (class VI)
      • Slow, progressive renal dysfunction with proteinuria and relatively bland urine sediment
      • Global sclerosis >90% of glomeruli
      • Active GN no longer observed
  • Treatment:
    • Best to initiate early
    • Aimed at proliferative lupus nephritis
    • Induction
      • 3 – 12 months: goal is to obtain renal response.
      • Cytoxan or MMF PLUS solumedrol 250-1 g/day x 3 days (former takes 10-14 days to have an effect so the latter is much faster) or prednisone 60 mg/day
    • Maintenance
    • Response:
      • substantial reduction in urine protein excretion to <0.33 g/day
      • improvement or stabilization of serum creatinine
      • improvement of urinary sediment

Approach to glomerular disease:

* can be nephritic or nephrotic

Hot Topics of 2018!

Today, we reviewed some of the hottest and potentially practice changing articles of 2018.  This is by no means an exhaustive list and meant to encourage debate and tickle your fancy for more!

1. Aspirin for primary prevention of cardiovascular disease?

Bottom line: no net benefit in primary prevention of cardiovascular disease.

  • ARRIVE: 12000 middle aged (mean age 64), non-diabetic participants with moderate ASCVD risk (>20%) randomized to receive aspirin 100 mg or placebo for primary prevention and followed for 5 years. Found that ASA showed no reduction in major adverse cardiovascular events or mortality, but a 2-fold higher risk of bleeding.
  • ASCEND (aspirin): 15000 middle aged (mean age 63) diabetic participants randomized to aspirin 100 mg vs placebo for primary prevention of CVD and followed for 7 years. Authors found a 12% reduction in major adverse cardiovascular events with ASA but a 29% higher risk of bleeding.
  • ASPREE: 19000 older patients (median age, 74) regardless of other risk factors randomized to ASA 100 mg or placebo and followed for 5 years.  Study found that patients who received ASA had a 14% higher all cause mortality, no decrease in the rate of adverse CVD, and no change in disability-free survival.

2. Omega-3 for primary prevention of cardiovascular disease?

Bottom line: potentially beneficial at really high doses in patients with CV risk factors

  • VITAL: 26000 middle aged (mean age, 67) people without CV disease were randomized to receive fish oil (1g) or placebo and followed for ~5 years. Study found similar rates of primary endpoint (nonfatal MI, stroke, or CV-related death) and all cause mortality in the two groups and a small but significant decrease in the incidence of MI in the fish oil group (1.1% vs 1.5%).
  • ASCEND (fish oil): same study population as ASCEND for aspirin, also looked at using 1g fish oil or placebo and followed patients for ~7 years and found no difference in the risk of major adverse cardiac events.
  • REDUCE-IT: 8000 participants with controlled LDL but elevated triglycerides, randomized to receive 2g of a different fish oil (icosapent ethyl as opposed to the eicosapentaenoic acid plus docosahexaenoic acid used in the previous two trials) vs placebo and followed for 5 years.  Study found a 25% reduction in risk of major cardiovascular events. Caveat is high dose used at this formulation is very expensive and the study was funded by Amarin Pharma.

3. VTE prophylaxis in hospitalized patients

Bottom line: High rates of inappropriate use of pharmacologic VTE prophylaxis.  Use padua score before prescribing VTE prophylaxis.

  • Grant et al. JAMA Intern Med 2018: retrospective study of 45000 non-ICU patients hospitalized for > 2 days found that prophylaxis (pharmacologic or mechanical) was prescribed for 78% of low-risk patients. 27% of high risk patients with contraindications to pharmacologic prophylaxis still received it, and 22% of high risk patients did not receive prophylaxis.

4. Is there such a thing as too much oxygen?

Bottom line: higher rates of mortality associated with liberal use of oxygen in hospitalized patients.

  • Chu et al. Lancet 2018: Meta-analysis of 25 randomized trials on 16000 hospitalized patients treated with liberal (median FiO2 0.52) vs conservative (median FiO2 0.21) supplemental oxygenation found that at 30 days, the relative risk of death was significantly higher in the liberal oxygenation group.

5. Plavix + ASA for TIA or minor stroke?

Bottom line: Starting DAPT within 12 hours of symptom onset (likely for 30 days) in patients with high risk TIA or minor ischemic stroke reduces 90 day stroke incidence but increases bleeding rates.

  • POINT:  Followed the earlier CHANCE trial in a Chinese population that showed DAPT for 21 days after TIA or minor stroke reduced stroke recurrence at 90 days without a difference in bleeding rates.  POINT randomized ~5000 patients to DAPT for 90 days vs ASA alone in a primarily white patient population and found lower rates of recurrent stroke but higher rates of bleeding. Majority of stroke reduction occurred during the first 7 days after stroke and extended for 30 days whereas the bleeding rates were stable throughout the 90 day follow up period.

6. Steroids in septic shock?

Bottom line: Steroids might be beneficial in high risk patients with refractory septic shock.

  • Rochwerg B et al. Crit Care Med 2018: Meta-analysis of 42 randomized trials with >10000 patients receiving steroids vs none in septic shock found a 2% relative reduction in 30-day mortality with steroids which was not statistically significant, and a similar reduction in mortality at 60 days to 1 year which reached significance (NNT 50). Reversal of shock at 7 days occurred more frequently in the steroid group (NNT 10) but mild-to-moderate adverse events also occurred more frequently in this group (hyperglycemia, hypernatremia, and neuromuscular disease).

7. Is it safe to discharge to home from the ICU?

Bottom line: patients admitted to the ICU for substance-related disorders, seizures, or metabolic derangements may be ok to go home from the ICU.

  • Stelfox et al. JAMA 2018: retrospective cohort study of 6700 adult patients admitted to ICUs in Canada, 14% of whom were discharged to home, found that 30 day hospital readmissions and ED visits and 1 year mortality rates were similar in those discharged from the ICU vs wards.  Those discharged home were typically younger and more likely to have been admitted due to overdose, seizure, substance withdrawal, or metabolic derangements.

8. NS vs LR?

Bottom line: balanced crystalloids (like LR) are associated with fewer adverse events than normal saline in hospitalized patients.

  • SMART: 16000 patients admitted to the ICU were randomized to NS or a balanced crystalloid (majority received LR). Study found that more patients in the NS group reached the composite outcome of major adverse kidney events (death, renal replacement therapy, or doubling of creatinine at discharge) vs those who received balanced crystalloids.
  • SALT-ED: 13000 patients admitted from the ED to non-ICU beds were randomized to NS vs a balanced crystalloid (majority received LR).  Study found similar rates of primary outcome of hospital-free days but a higher rate of adverse kidney events within 30 days than the NS group.

Nephrotic Syndrome Secondary to Minimal Change Disease (12/3/2018)

Narges presented a case today with a middle age woman with uncontrolled insulin dependent diabetes Type 2, multiple malignancies s/p resection, presenting with acute anasarca and shortness of breath developed over a few days. She was anasarcic up to the mid back on presentation, with an albumin of 0.9 (baseline of 3.8 a month ago). Her UA had 3+ protein and a urine protein/Cr ratio of 23. If you’re thinking nephrotic syndrome, that’s right! Biopsy revealed the diagnosis of minimal change disease (MCD) with concurrent ATN!

Nephrotic Syndrome

Some definitions

  • Nephrotic range proteinuria: > 3.5g proteinuria per day or spot urine protein/cr ratio of > 3.5
  • Nephrotic syndrome: Above + symptoms (edema, HLD, hypoalbuminemia, lipiduria, etc)


  • Most common primary cause of nephrotic syndrome in adults in the US is FSGS
  • Most common secondary cause of nephrotic syndrome in adults in the US is Diabetic Nephropathy


  • AKI (underlying glomerulonephritis vs hypovolemia vs sepsis vs ATN)
  • Hypercoagulability (loss of anticoagulant proteins namely antithrombin III, C, S)
  • Hyperlipidemia (reactive hepatic synthesis of proteins due to hypoproteinuria)
  • Malnutrition (gut edema, dec body weight, edema) leading to anemia, osteomalacia, vitamin D deficiency
  • Immunocompromise (inc risk for infection due to hypoimmunogammopathy)
  • Edema (low oncotic pressure due to hypoalbuminemia)


  • 24 urine protein > 3.5g is diagnostic
  • Spot urine protein/cr ratio > 3.5 is also diagnostic
  • Exactly cause will require additional work up, to be discussed below in differential

General Management Strategies

  • Proteinuria control (ACEi, ARB)
  • BP Control
  • Volume Control (Diuretics, low salt)
  • HLD: usually resolves with disease control, can use statins
  • Immunosuppresion for primary causes
  • Treat underlying secondary causes

Differential Diagnosis


Source: Grepmed

The three most commonly encountered causes, besides diabetic nephropathy, are:


Minimal Change Disease

As seen in this patient, is typically seen in pediatric population and it is the most common cause of nephrotic syndrome in kids < 8-10 years old. It only accounts for 10% of cases of nephrotic syndrome in adults.


  • Acute onset edema
  • Higher incidences of thrombotic events in adults
  • AKI common, at higher risk for ATN


  • Biopsy, electron microscopy with podocyte effacement


  • Corticosteroids: initial course of 6-8 weeks in adults, 1.5mg/kg/day
  • Cyclosporine for non-responders
  • Other options: mycophenolate (Cellcept), azathioprine (but pt is already on this, Imuran!)


  • 80-90% of patients respond to initial corticosteroid therapy
  • Up to 50% can recur

Focal Segmental Glomerulosclerosis (FSGS)


  • Higher incidence among African Americans (5 times more likely than White)
  • Associated with HIV (collapsing variant), heroin (30x risk)


  • Biopsy: focal and segmental hyalinization of the glomeruli, often with immunostaining showing IgM and complement (C3) deposits in a nodular and coarse granular patter


  • Primary: Immunosuppression, corticosteroids +/- cyclosporine, tacrolimus + plasma exchange
  • Secondary: Treat underlying cause

Prognosis: Poor

  • > 50% develop renal failure within 10 years of diagnosis, and 20% develop ESRD within 2 years despite treatment
  • May recur after kidney transplantation.
  • Heroin addicts with FSGS: can experience complete remission if they STOP EARLY.

Membranous Nephropathy


  • Associated with malignancy i.e. lymphoma, colon cancer, lung cancer
  • Most cases are idiopathic


  • Biopsy
  • Microscopy: Thickened capillary loops
  • Immunoassay: Granular IgG & C3 depositions in the subepithelial layer


  • Immunosuppression similar to above, treat any secondary causes


  • Generally pretty god, 30-40% treated go into complete remission, 30-50% go into partial remission. Treatment can be prolonged.
  • Treating secondary causes also can induce remission.

Note that there are some other causes that can present with both nephrotic and nephritc features, i.e. membranoproliferative glomerulonephritis. Complement levels are NORMAL in MCD, FSGS, and MN, while complement levels are low in MPGN.

Primary anticoagulation for patients with nephrotic syndrome can be considered in some cases but not routinely done. Please refer to this article for reference.


GPA – 10/1/18

Yours truly presented a case of a middle-aged woman with a recent history of otitis, sore throat, conjunctivitis, photophobia, and arthralgias who presented with chronic and progressive decline in functional status and AMS, found to be uremic with work up revealing c-ANCA associated ESRD.

Clinical Pearls

  • Remember that oval fat bodies are specific for glomerular pathology (more commonly nephrotic syndrome but can be seen in nephritic disease as well).
  • ANCA-associated vasculitides include GPA, MPA, eGPA (and renal-limited vasculitis).
  • All have similar features on renal histology (focal necrotizing, crescentic, pauci-immune glomerulonephritis).
  • They can affect multiple organ systems (see breakdown below) which makes their clinical diagnosis challenging apart from the following differences:
    • c-ANCA is associated with GPA, p-ANCA is seen in MPA and eGPA
    • Granulomas are seen in GPA and eGPA
    • Eosinophilia and asthma are associated with eGPA

ANCA-associated vasculitides


Chart above adapted from this paper by Koldingsnes et al.

Granulomatosis with polyangiitis (GPA)

Diagnostic criteria (two or more has 88% sensitivity and 92% specificity):

  • Nasal or oral inflammation (painful/painless oral ulcers, or purulent or bloody nasal discharge)
  • Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities
  • Abnormal urinary sediment (microscopic hematuria w/w/o red cell casts)
  • Granulomatous inflammation on bx of artery or perivascular area

Clinical presentation:

  • Most commonly in older adults, M=F
  • More common among white individuals (~89%)
  • S/s
    • Fatigue, fever, weight loss, arthralgias, rhinosinusitis, cough, dyspnea, urinary abnormalities, purpura, and neurologic dysfunction.
    • ENT
      • 90% of GPA cases, only 35% of MPA
      • Nasal crusting, sinusitis, otitis media, earache, polychondritis, ulcers, discharge
      • Conductive and/or sensorineural hearing loss
      • Saddle nose deformity
    • Tracheal and pulmonary disease
      • Airways or parenchyma
    • Renal
      • ~18% at presentation but subsequently develops in 77-85% of patients within the first 2 years of disease onset
      • High risk of progression to ESRD
      • Asymptomatic hematuria
      • Subnephrotic range proteinuria
      • Rapidly progressive GN
    • Cutaneous
      • ~50% of patients
      • Leukocytoclastic angiitis is most common which causes purpura of lower extremities
      • Other findings: urticarial, livedo reticularis, nodules, erythema nodosum, pyoderma gangrenosum, and Sweet syndrome
    • Ophthalmic/orbital
      • Conjunctivitis, corneal ulcers, episcleritis/scleritis, optic neuropathy, retinal vasculitis, and uveitis.
    • Other organs
      • CNS: neuropathy, CN abnormalities, mass lesions, hearing loss, granulomatous inflammation of the CNS
      • GI tract, heart, lower GU, parotids, thyroid, liver, or breast
      • High incidence of DVT (unclear mechanism)
    • Can progress slowly over months or explosively over days
    • Relapses can manifest differently than original presentation

Diagnosis requires biopsy!


  • Prompt initiation of therapy can be life and organ sparing
  • Induction therapy: Steroids +-Cyclophosphamide +-Rituximab
  • Maintenance therapy: multiple options-Azathioprine, MTX, Rituximab, Leflunomide

Hyponatremia – 9/18/18

Thanks to Joe for presenting the case of a young man with no known medical history who presented with acute onset of generalized weakness, found to have symptomatic hyponatremia to 120 resulting from psychogenic polydipsia!

Clinical Pearls

  • Hyponatremia is largely a problem of too much free water (sometimes compounded by too little solute) and defined as a Na <135
  • Pick a systematic approach to solving the underlying diagnosis for any patient with hyponatremia (see below for one possible outline).
  • The term “pseudohyponatremia” refers to the presence of substances that interfere with laboratory measurement of sodium concentration in the blood, specifically high triglycerides and paraproteins.
    • Hyperglycemia does NOT fall into this category because glucose is osmotically active and pulls water into the intravascular space, resulting in a dilutional and true hyponatremia.
  • Chronic hyponatremia (>72 hours) must be corrected slowly to avoid osmotic demyelinating syndrome (ODS).  Acute hyponatremia (<48 hours) can be corrected more rapidly.  That said, we rarely have a Na value within 48 hours prior to patient presentation to determine acuity.  As a result, and given the neurologic risks, most patients are treated as if they have chronic hyponatremia.
  • ADH leads to increased uric acid excretion through the kidneys so low serum uric acid levels have been associated with SIADH.  But this test is not very specific.
  • Osmolarity of normal saline is 308 compared to human serum which is normally 280-295.  In a hyponatremic patient, NS infusion becomes a relatively hypertonic (rather than isotonic) solution!


For more detailed information, refer to this prior post and this review article.