When therapy fails (Proceedings)


Dysautonomia is a neuropathy of unknown etiology that affects all aspects of the autonomic nervous system.


Dysautonomia is a neuropathy of unknown etiology that affects all aspects of the autonomic nervous system. It was originally described as a disease of cats in the United Kingdom, but has subsequently been reported in dogs in the United States, with Kansas appearing to be an "epi-center"! Traditionally it appears to be a "seasonal" disease affecting mostly young dogs from rural settings. Although this would appear to narrow the search towards particular causes (environmental exposure, toxin ingestion, etc.), as of yet no culprit has been identified. To complicate matters, at CSU we are seeing the disease in dogs somewhat outside the norm; older animals and some breeds hardly known for their rugged rural lifestyle.

Clinical signs consistent with a diagnosis of dysautonomia include poor body condition, lethargy, constipation and/or diarrhea (rarely to the point of fecal incontinence), regurgitation and/or vomiting, and anorexia. Signs of urinary dysfunction (i.e. incontinence) can also occur. In addition to overall poor body condition (although at CSU we've also seen dogs that look quite healthy on the outside) physical examination often reveals dry mucus membranes, dilated pupils and raised 3rd eyelids, slow or absent papillary light reflexes, an inappropriately low heart rate, and poor anal tone.

The initial diagnostic pathway often hinges on whether vomiting or regurgitation is determined to be the presenting or most prominent problem. Baseline blood work shows non-specific changes consistent with vomiting, malnutrition, or muscle wasting. Plain thoracic films will often reveal megaesophagus, or fluoroscopy/barium contrast shows esophageal hypomotility. Abdominal films can be particularly striking. The bladder is often large (and flaccid) and the stomach maybe chalked full of food hours after the last meal. The appearance of the intestinal track is frequently interpreted as consistent with a GI obstruction, or in their most extreme state, a mesenteric torsion. This explains why one of the more frequent "diagnostic tests" in cases of dysautonomia is a negative abdominal exploratory surgery. Often the degree and extent of intestinal distention is actually an important clue – if there is an obstruction, where would it be to cause this pattern?!

It requires a high index of suspicion and an attentive history and physical examination to support a clinical diagnosis of dysautomonia. But once dysautonomia makes it on to the list of differentials there are a number of ancillary diagnostics to perform while resisting the urge to open the animal's abdomen. A Shirmer tear test may reveal "dry eyes", the dog's bradycardia is minimally responsive to atropine, intradermal histamine (compared to saline control) fails to elicit a wheal or flare, and dilute pilocarpine (compared to the non-dysautonomic dog in the next cage) leads to an extremely mitotic pupil (denervation hypersensitivity). The simplistic nature of this battery of tests makes us uncomfortable, but if we're lucky, the combination of bizarre results makes us confident in our diagnosis, there just aren't many other conditions that fit. The problem arises if we fail to consider dysautonomia in the first place, or the diagnostics come back inconclusive.

Supportive care (e.g., artificial tears, elevated feedings, expressing the urinary bladder, antibiotics, etc.) is the basis of therapy, as well as parasympathomimetic drugs such as bethanechol and metoclopramide. A low-profile gastrostomy feeding tube can be placed to help the owner provide adequate nutritional support if the patient's megaesophagus precludes effective oral intake. The prognosis for dysautonomic pets is grave and the owner must be committed to providing extensive nursing and supportive care. Even with partial recovery of some faculties, complete recovery is highly unlikely.

Typical hypoadrenocorticism

Typical or Primary Hypoadrenocorticism represents a lack of production of both glucocorticoids and mineralocorticoids following the immune-mediated destruction of the adrenal cortex. Atypical Addison's refers to cases where there is only a glucocorticoid deficiency (destruction of only the Zona Fasciculata of the adrenal cortex?); mineralocorticoid production is normal. It is unclear whether or not Atypical Addison's progresses to Typical Addison's, with destruction of the Zona Glomerulosa (that part of the adrenal cortex responsible for production of mineralocorticoids).


  • Signalment: Young female dogs (Breed predisposition: Leonbergers, standard poodle)

  • Chief Complaint: Lethargy (95%), anorexia (90%), vomiting (75%), weight loss (50%), Diarrhea (40%), PU/PD (25%)

  • History: Waxing and Waning course, intermittent GI signs, previous response to treatment

  • Physical Examination: Weak (75%), dehydration (45%), hypothermia (35%), slow CRT (30%), weak pulses (20%), bradycardia (18%), melena (15%)

  • Minimum Data Base:

  • HyperK+ (95%), azotemia (85%), hyperPO4- (85%), hypoNa+ (80%), hypoCl- (40%), metabolic acidosis (40%), elevated liver enzymes (30%), hyperCa++ (30%), anemia (25%), elevated t. bili (20%), hypoglycemia (17%), eosinophilia (13%), lymphocytosis (10%), dilute urine specific gravity, hypoalbuminemia, metabolic acidosis

  • ECG: bradycardia, prolonged QRS complexes, decreased R wave amplitude, increased "spiked" T wave amplitude, prolonged/absent P waves, atrial standstill

  • [adapted from Peterson & Kintzer, JAVMA 1996]

  • Diagnosis: ACTH Response Test (Cosyntropin 0.5 microg/kg IV)

NOTE: Prednisone (but not Dexamethasone SP) interferes with the cortisol assay used for the ACTH stimulation test (if already administered, wait 24 hours prior to testing).

Endogenous ACTH levels: requires special sample handling, confirm with your diagnostic laboratory prior to sample acquisition. Rarely performed in the diagnosis of hypoadrenocorticism at CSU; would help distinguish between Primary disease (adrenal gland destruction, HI endogenous ACTH with loss of negative feedback) and Secondary disease (destruction of the Pituitary Gland and low levels of endogenous ACTH).

  • Treatment

o Mineralocorticoid supplementation (oral)

o Fludrocortisone (Florinef, 15-20 μg/kg/day P0 q 24 hr) or

o Deoxycorticosterone pivalate (DOCP, 2.2 mg/kg q 25 days)

o Glucocorticoid supplementation (0.22 mg/kg)

o must be given with DOCP, needed in ~ 50% of dogs on Fludrocortisone also administered in anticipation of stressful events

NOTE: [From Kintzer & Peterson JVIM 1997] Only ~ 20% of dogs require the recommended dose (2.2 mg/kg q 25 days) of DOCP. Therefore, may consider an initial dose of 1.5 mg/kg q 25d.

"Addisonian crisis"

The Addisonian Crisis (acute manifestation of hypoadrenocorticism) is a life-threatening emergency. The "classic" case is a dog presenting collapsed with acute vomiting, diarrhea and hypovolemic, but with an inappropriately low heart rate, often bradycardic. Hypoglycemic seizures or the appearance of hemorrhagic gastroenteritis are other possible presentations. NOTE: As the catheters are going in the pre-treatment samples are coming out (i.e. collection of CBC, biochemical profile, and urinalysis prior to therapeutic intervention can be particularly important as the rule-out list for this presentation includes Acute Renal Failure).

  • Treatment

o Fluids, electrolytes, glucocorticoids, gastrointestinal signs, mineralocorticoids

o IV Fluids - 0.9% NaCl through a jugular catheter (1/4 shock over 15 minutes, repeat), 5% dextrose added for severe hypoglycemia if necessary

o Electrolytes – Hyperkalemia

o 10% Dextrose (4-10 ml/kg) to stimulate endogenous insulin release

o Regular insulin (0.1 Unit/Kg IV) with Dextrose (4 ml/Unit of 50% dextrose)

o 10% calcium gluconate (0.5-1.0 mg/kg IV over 10-20 minutes)

o Glucocorticoids - Dexamethasone sodium phosphate (0.5-1 mg/kg IV BID)

o Gastrointestinal tract – Sucralfate (PO drug, difficult in vomiting animal), H2 blocker (Famotidine IV) blood transfusion

o Mineralocorticoid supplementation - Fludrocortisone acetate (Florinef)

o Metabolic acidosis - if severe and minimally responsive to fluids (persistent pH < 7.1) consider sodium bicarbonate (controversial, approach with caution) [0.4 x BW(kg) x base deficit] 25% of this calculated dose IV

o Hypoglycemia – if symptomatic, slow IV bolus of 50% dextrose (0.5-1.0 ml/kg).

"Atypical" Addisons

Hypoadrenocorticism typically involves the destruction of both mineralocorticoid and glucocorticoid producing cells. Atypical Addisons is seen when only glucocorticoids are lost, mineralocorticoids are still present. Therefore, patient has a normal Na/K ratio, but often has similar symptoms (GI signs) and a lack of a stress leukogram.

Compiled from Thompson et al. JAVMA 2007, Lifton et al. JAVMA 1996, Sadek et al. JAAHA 1996, Rogers et al. JAVMA 1981.

  • Signalment

o 55-78% female, < 7 years old, > 20kg; Great Dane, WHW terrier, Lab, Pointers, Setters, Terriers, Great Pyrenees [older than Typical]

  • Chief Complaint

o Lethargy, weakness, anorexia, vomiting [less than Typical], weight loss, tremors, seizures

  • History

o Lethargy, anorexia, vomiting, weight loss, diarrhea, PU/PD, Regurgitation w/ megaesophagus [duration of clinical signs longer than Typical]

  • Physical Examination

o Variable; from shock-like [rare compared to Typical] to relatively normal

  • Minimum Data Base

o Normal Na/K ratio (by definition), hypoCl-, non-regenerative anemia [more common than Typical], hypoglycemia, hypoalbuminemia, lack of a stress leukogram [although neutrophilia maybe present, lymphs, monocytes and eosinophils were WNL], hypocholesterolemic [more common than Typical], less likely to be azotemic, acidotic, or hypercalcemic.

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