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Volume 7 | Issue 5 | May/June 2015
Clinical Consults
What’s Your Diagnosis?
PATIENT HISTORY
SIGNALMENT: “Autumn”, 17 year old spayed
female domestic longhair, 6 pounds/2.7 kg.
PERTINENT PAST HISTORY: “Autumn” has
generally been a healthy geriatric cat. She
has received regular annual examinations for
the past 3 years and routine preventative
care as recommended by her veterinarian.
During these past 3 years her owner has
reported gradual weight loss despite a good
appetite and one pound of weight loss (from
7 to 6 pounds) had been documented by
her veterinarian. A heart murmur has also
been documented at each annual visit but
no further diagnostics had been pursued.
During this same time period, “Autumn’s”
owner has expressed concerns about her
declining vision.
See Table 1 for “Autumn’s” laboratory
trends and blood pressure measurements
over the past 2 years.
In May 2012, “Autumn’s” veterinarian
documented decreased to absent menace
OU and lack of a direct pupillary light
response (PLR) in her right eye. A fundic
exam revealed a possibly detached retina
with floating fibrin strands. “Autumn’s”
blood pressure was taken at that time and
was within normal limits using an
oscillometric device. Clinical Note:
Oscillometric devices in cats are less
accurate when compared to direct or
Doppler measurements. It is easy to
obtain inaccurate readings if patient
restraint or cuff size and placement are not
correct. Table 2 outlines proper blood
pressure measurement technique and
differences between devices.
CRITICAL THINKING ABOUT
HYPERTENSION AND
HYPOKALEMIA—
Chronic Kidney Disease or something more?
Donna J. Spector, DVM, DACVIM, Internal Medicine
Case materials and images contributed by Dr. Anya Gambino, DVM, DACVECC;
VCA Veterinary Specialty Center of Seattle, Lynnwood, Washington
PERTINENT PAST HISTORY CONTINUED:
“Autumn’s” minimum database was fairly unremarkable but her renal parameters classified her
as IRIS Stage 2 CKD. No further follow up was recommended at this time. Clinical Note: Given
the presence of renal disease and retinal findings, a recheck blood pressure should have been
scheduled (ideally using a Doppler or appropriate cuff and technique) and her bloodwork
should have been rechecked in a minimum of 6 months.
At her annual exam in May 2013, “Autumn” was found to have an absent menace OU and her
left eye had a diminished direct PLR. The fundic exam revealed retinal hemorrhages OU. Her
minimum database was repeated and a mild increase of her azotemia was noted with a creatinine
increase to 2.2 mg/dL. Her blood pressure was measured again using an oscillometric device but
this time she was noted to be hypertensive. Clinical Note: Notice the wide range of blood
pressure readings obtained at this visit. This alludes to the inaccuracy of the oscillometric
device in small cats like “Autumn.” Referral for both cardiology and ophthalmology
consultations was recommended to “Autumn’s” owner in order to further define the status of her
vision abnormalities and to identify the nature of her cardiac disease, however, the owner declined
referral at this time. Clinical Note: Despite the owner’s unwillingness to seek referral, antihypertensive therapy should have been started to address “Autumn’s” marked hypertension at
this time. Thoracic radiographs should have also been performed to obtain general
information about cardiac enlargement and the need for additional therapy. No specific
therapy or follow up was performed.
“Autumn” returned for her annual examination in May 2014 with a history of progressive weight
loss and intermittent vomiting. She lacked both menace and PLRs OU. Her fundic examination
revealed attenuation of her retinal vessels. Her blood pressure was obtained on a Doppler unit
2014 visits. Clinical Note: A reminder system
of doctor and technician follow up calls can
help keep owners on track with their
recommended recheck schedule. Eight
months later “Autumn” presented as an
emergency for evaluation of marked weakness
and ataxia. On examination, she weighed 5.9
pounds (2.7 kg), her temperature was 97.2
degrees F, a III/VI parasternal systolic heart
murmur was noted and blood was detected in
the anterior chamber of her left eye. She had
significant neurologic abnormalities
characterized by marked ventroflexion of the
neck, truncal ataxia, head tilt to the right,
horizontal nystagmus with fast phase to the left,
and right-sided conscious proprioceptive
deficits in both thoracic and pelvic limbs. Her
and she was noted to be markedly
hypertensive with a systolic blood pressure of
approximately 220 mmHg. Although her
serum creatinine concentration was stable at
2.2 mg/dL, she had a progressive decrease of
her urine concentrating ability and her
potassium and magnesium were markedly
decreased (2.7 and 1.0 mEq/L respectively)
which were felt to be consistent with declining
renal function. Clinical Note: Serum
creatinine is a relatively insensitive marker to
monitor progression of early renal disease.
The presence of declining urine specific
gravity and progressive hypokalemia and
hypomagnesemia was thought to be
consistent with primary renal failure with
excess electrolyte losses.
TABLE 1.
“AUTUMN’S” ANNUAL MINIMUM DATABASE TRENDS AND ABNORMALITIES
Clinical Note: Monitoring trends in laboratory work is critically important! Note the following
trends in “Autumn” over 2 years:
• Gradually increasing creatinine and decreasing urine specific gravity (IRIS stage 2)
• Proteinuria as an early indicator of renal disease
• Gradually decreasing potassium and magnesium
• Gradually increasing blood pressure
5/2012
5/2013
5/2014
BUN (ref. range: 14-36 mg/dL)
26
28
34
Creatinine (ref. range: 0.6-2.4 mg/dL)
1.8
2.2
2.2
Potassium (ref. range: 3.4-5.6 mEq/L)
3.8
3.5
2.7
Magnesium (ref. range: 1.5-2.5 mEq/L)
1.5
1.4
1.0
CPK (ref. range: 56-529 IU/L)
342
269
663
T4 (ref. range: 0.8-4 ug/dL)
1.7
2.6
2.4
1.040
1.037
1.023
1+
1+/5.5 mg/dL
1+
Urine specific gravity
Proteinuria/Microalbuminuria
Blood pressure
Systolic 91-130
Systolic 120-263
Diastolic 40-79
Diastolic 75-196
Mean 48-119
Mean 92-217
Oscillometric device Oscillometric device
“Autumn” was started on oral potassium
supplementation (Tumil-K® tablets, 2 mEq PO
BID) to address her severe hypokalemia. Her
potassium was rechecked one week later and
it had increased to 3.3 mEq/L so she was
maintained on this dosage of Tumil-K®.
Amlodipine was recommended as an antihypertensive; however, the owner desired a
more natural initial approach. A Feliway®
pheromone diffuser was instituted and the
owner agreed to start amlodipine the following
week if “Autumn” remained hypertensive.
CURRENT HISTORY
“Autumn” was lost to follow up after the May
Systolic 218-220
Doppler
regular veterinarian referred her immediately to
VCA Veterinary Specialty Center of Seattle for
further evaluation.
“Autumn” was seen through the Neurology
Service due to her initial presenting clinical
signs and her neuro-anatomic localization was
central vestibular. There are many differentials
for feline central vestibular disease (see Table
3). After the neurologist reviewed “Autumn’s”
medical record with her history of chronic renal
failure, untreated hypertension, hypokalemia
and hypomagnesemia, a metabolic
derangement was suspected to be the most
likely etiology of her neurologic signs.
“Autumn” was admitted to the hospital and
transferred to the Critical Care Service for
further evaluation and treatment.
DIAGNOSTICS AND ASSESSMENT
Upon admission, “Autumn’s” systolic blood
pressure was 250-260 mmHg. Bloodwork
(see Table 4) was compared to her May 2014
values and revealed progression of her
azotemia and further decrease of urine specific
gravity. She was markedly hypokalemic,
hypomagnesemic, and her CPK was markedly
elevated. Together with her clinical signs of
cervical ventroflexion, these values were
consistent with hypokalemic polymyopathy.
Although “Autumn’s” marked hypertension
and metabolic derangements could have
explained her neurologic signs, a thorough
evaluation was warranted due to the severity of
her neurologic presentation. Appropriate
infectious disease testing was performed.
FeLV, FIV and FCV antibody titers were
negative. A toxoplasma IgM antibody titer was
negative but an IgG antibody titer was positive
at 1:128. The elevated IgG titer was suspected
to reflect chronic exposure and since the IgM
titer—which tends to be positive in cases of
active clinical infection—was negative,
“Autumn” was not treated for active
toxoplasmosis. Clinical Note: Cats presenting
with neurologic abnormalities should ideally
have a cryptococcus latex antigen sample
submitted.
Due to “Autumn’s” long-standing heart
murmur and hypertension, THREE-VIEW
THORACIC RADIOGRAPHS were obtained as
an initial evaluation for cardiac disease and to
serve as an evaluation for metastasis. The
films revealed moderate to marked
cardiomegaly (see Figure 1). The cardiac
silhouette had a valentine-like appearance with
biatrial enlargement on the ventrodorsal view.
The cardiac silhouette was tilted cranially on
the lateral views and the aortic arch was
prominent. No cranial mediastinal masses,
FIGURE 1.
pulmonary infiltrates or pleural effusion were noted. Mild multifocal spondylosis deformans was noted and there was a mild amount of air and fluid
in the esophagus.
A follows-up ECHOCARDIOGRAM revealed marked enlargement of the left atrium with no spontaneous echo-contrast noted. There was concentric
thickening of the ventricle that was felt to be consistent with hypertension or primary hypertrophic cardiomyopathy. Clopidogrel (Plavix® 18.75 mg
PO q day) for clot prevention was the only recommended therapy. The cardiologist recommended extreme caution in regards to fluid administration.
TABLE 2.
BLOOD PRESSURE MEASUREMENT
Systemic hypertension is defined as sustained, high arterial blood pressure
• Normal systolic arterial blood pressure (SAP) ranges from 110-160 mmHg
• Normal diastolic arterial blood pressure (DAP) ranges from 60-90 mmHg
• Normal mean arterial pressure (MAP) ranges from 85-120 mmHg
Hypertension is classified based on the risk of target organ (e.g., brain, kidney, eye, heart) damage. The four risk categories developed and set forth in
the 2007 ACVIM guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats are as follows:
• Risk Category I (minimal): systolic BP <150 mmHg, diastolic BP <95 mm Hg
• Risk Category II (mild): systolic BP 150-159 mmHg, diastolic BP 95-99 mmHg
• Risk Category III (moderate): systolic BP 160-179 mmHg, diastolic BP 100-119 mmHg
• Risk Category IV (severe): systolic BP >180 mmHg, diastolic BP >120 mmHg
Diagnosis of systemic hypertension requires measurement of either DIRECT or INDIRECT blood pressure
• The gold standard measurement is a DIRECT blood pressure measurement
• Made by inserting a needle or catheter into an artery
• This provides a highly accurate reading but requires specialized equipment, experience and is not practical for the repetitive measurements
necessary for monitoring
• Used more in the surgical setting
• Due to these limitations, the INDIRECT method of blood pressure measurement is used more commonly
• The equipment is readily available and affordable
• Experience is necessary to make this technique accurate and repeatable
• The DOPPLER and OSCILLOMETRIC methods are most commonly used to measure indirect blood pressure
• Regardless of method used, the following criteria must be met for an accurate blood pressure measurement:
• Pressure cuff should have a width of 40% of the circumference of the limb or tail
• Position the animal so the artery is at the same height as the heart
• Patient acclimation for 5-10 minutes in order to reduce anxiety
• Discard the first measurement and average 3-7 subsequent readings
Doppler Method
• Uses ultrasound to detect blood flow through an artery. As the
moving blood passes the piezoelectric crystal of the unit a sound is
generated
• Technique: A piezoelectric crystal transducer is placed over a
peripheral artery (e.g., dorsal pedal, palmar, plantar, coccygeal)
and ultrasound gel is used to achieve close contact with the skin.
A pressure cuff is wrapped around the limb/tail proximal to the
transducer and inflated until the audible signal of blood flow is
lost. The cuff is slowly deflated until the first sound of blood flood
is heard which is recorded as the systolic blood pressure
• Diastolic measurements are inaccurate using this method
• This technique works very well and many feel is superior to other
techniques for blood pressure measurement in cats
Oscillometric Method
• Measures oscillations in the arterial wall caused by the flow of
blood through the artery as a pressure cuff is deflated
• Technique: Cuffs have an arrow indicator that should be placed
over the artery to be used (e.g., brachial, dorsal pedal, palmar,
plantar, coccygeal). The machine is automated and the cuff will
be inflated and provide a systolic blood pressure measurement
• Diastolic and mean pressure are calculated values. The machine
also records pulse rate
• Oscillometric readings do not correlate as well as Doppler readings
with direct measurements of blood pressure in cats
DISCUSSION
TABLE 3.
COMMON DIFFERENTIALS FOR FELINE CENTRAL VESTIBULAR DISEASE
Vascular
Ischemic injury—caused by hypertension or thromboembolic disease
Non-ischemic or hemorrhagic injury
Neoplasia
Lymphoma, meningioma, etc.
Infectious disease
Toxoplasmosis, cryptococcosis, feline infectious peritonitis, bacterial otitis
interna to brain stem, etc.
Inflammatory disease
Granulomatous meningoencephalitis, etc.
Metabolic disease
Uremia
Hypertension
Thiamine deficiency
Hypokalemia and other electrolyte derangements
Primary Hyperaldosteronism
Etiology
An ABDOMINAL ULTRASOUND was also
performed to more fully evaluate “Autumn’s”
renal disease and as a metastasis check. Both
kidneys were markedly hyperechoic with
decreased cortico-medullary distinction and
the left kidney was mildly decreased in size.
The urinary bladder appeared normal. The
gastrointestinal tract, liver, gallbladder, spleen
and pancreas were all considered normal. A
multi-lobulated hypoechoic mass measuring
2 cm in length x 1.5 cm thick x 2 cm in width
was identified in the right cranial abdomen
adjacent to the vena cava and encircling the
portal vein (see Figure 2). Margins of this
mass could not be clearly differentiated from
the liver or the right adrenal gland. The right
adrenal could not be conclusively identified.
The left adrenal was found and felt to be
normal in size and shape.
This was felt to be consistent with an
aldosterone-secreting adrenal mass; with
adenoma or carcinoma both being
considerations.
ADDITIONAL DIAGNOSTICS
Hypokalemic polymyopathy
Given “Autumn’s” history of hypertension,
marked hypokalemia and the abdominal mass
found in the area of the right adrenal gland, an
aldosterone-secreting mass was suspected.
An aldosterone level was submitted for
evaluation. The aldosterone level returned one
week later and was markedly elevated at
>4,572 pmol/L (ref. range 194-388 pmol/L).
FIGURE 2.
DIAGNOSIS
Chronic renal failure
Hypertension—with end-organ
damage present in eyes, CNS
and heart
Cardiomegaly—suspect
secondary to hypertension or
hypertrophic cardiomyopathy
Primary Hyperaldosteronism—
presumptive aldosteronesecreting adrenal mass
TABLE 4.
“AUTUMN’S” LABORATORY
ABNORMALITIES ON EMERGENCY
PRESENTATION
1/2015
BUN (ref. range: 14-36 mg/dL)
55
Creatinine (ref. range: 0.6-2.4 mg/dL)
3.1
Potassium (ref. range: 3.4-5.6 mEq/L)
2.4
Magnesium (ref. range: 1.5-2.5 mEq/L)
1.1
CPK (ref. range: 56-529 IU/L)
Urine specific gravity
Proteinuria/Microalbuminuria
Detailed discussions of chronic renal failure
and hypertension are beyond the scope of
this article and the reader is referred to the
listed references. This report will focus on
primary hyperaldosteronism as an
increasingly common diagnosis in
hypertensive cats.
4,091
1.013
1+/14.3
mg/dL
Primary hyperaldosteronism (PHA) has
previously been considered a rare endocrine
disorder in cats, however, it has likely gone
under-recognized in veterinary patients
because routine measurement of blood
pressure is not performed. Additionally,
chronic renal disease is presumed to be the
underlying etiology for most cats diagnosed
with hypertension and hypokalemia and further
diagnostic testing is not pursued. In fact, PHA
is the most common adrenocortical disorder
in cats and is likely to be an important cause
of arterial hypertension in cats just like it is
in humans. With improved screening for
hypertension and more thorough evaluations,
PHA is being diagnosed more commonly in
cats.
PHA is characterized by excess autonomous
secretion of aldosterone from one or both
adrenal glands. Aldosterone secretion is
normally regulated by changes in extracellular
fluid volume and/or pressure (via the reninangiotensin-aldosterone system), as well as
potassium concentrations in blood. When
physiologically required—such as in response
to decreased renal blood flow—aldosterone is
secreted from the adrenal gland. Through its
actions in the kidney, aldosterone acts to retain
sodium and water resulting in volume
expansion and increased blood pressure.
Aldosterone also enhances excretion of
potassium and hydrogen when necessary.
Autonomous aldosterone secretion—when
there is not a physiologic demand—results in
clinical signs referable to systemic hypertension
and hypokalemia and is called primary
hyperaldosteronism or Conn’s syndrome.
PHA may be caused by either adrenal
hyperplasia (usually bilateral disease) or benign
or malignant adrenal neoplasia (usually
unilateral disease). In humans, the most
common cause of PHA is bilateral adrenal
hyperplasia and it is rare for humans to
develop adrenal carcinomas as a cause of
PHA. In cats, the most common cause of PHA
is an approximately equal incidence of
unilateral adrenal adenomas or carcinomas.
TABLE 5
DIAGNOSTIC TESTING FOR PHA
A diagnosis of PHA is ideally made based on the following criteria:
• Hypertension
• +/- Hypokalemia (may be a late stage finding)
• Elevated plasma aldosterone levels (6x higher than normal)
• Increased urinary potassium excretion (6x higher than normal)
• Elevated aldosterone:renin ratio. The gold standard finding in PHA is an elevated aldosterone with
very low renin activity which indicates persistent aldosterone synthesis in the absence of normal
stimulation from the renin-angiotensin-aldosterone system. Clinical Note: Plasma renin
measurement is technically difficult and not widely available as a commercial assay therefore
the diagnosis of PHA often hinges on the other criteria together with advanced diagnostic
imaging.
• Adrenal mass or bilaterally enlarged adrenal glands identified on abdominal ultrasound.
Clinical Note: The absence of adrenal changes does NOT rule out PHA as some masses are too
small to be detected by ultrasound.
A fludrocortisone suppression test has recently been evaluated (2013) and appears to be a practical
method of confirming most cases of PHA in cats and of substantiating the absence of PHA with
otherwise questionable diagnostic results.
• The urinary aldosterone-to-creatinine ratio (UACR) was determined before, during and after 4 days
of fludrocortisone (0.05 mg/kg PO BID) administration
• Findings:
• All cats with PHA had UACR >7.5 x 10-9
• Fludrocortisone failed to suppress or resulted in <50% suppression in 6/9 PHA cats
• In non-PHA cats with UACR >7.5 x 10-9 fludrocortisone resulted in >50% suppression
Clinical Signs and Physical Examination
Findings
PHA most commonly affects older cats with a
median age of 13 years. Common presenting
clinical signs include weakness, neck
ventroflexion, stiffness, collapse, plantigrade
stance or other signs related to hypokalemic
polymyopathy. Ocular abnormalities are a
common owner complaint and physical exam
findings of anisocoria, anterior/posterior
chamber hemorrhage, retinal hemorrhage,
retinal detachment, and blindness are regularly
identified as a result of systemic hypertension.
Affected cats will often present with varying
degrees of polyuria, polydipsia, and abdominal
distention and heart murmurs are commonly
detected.
Diagnosis
There are no specific CBC findings associated
with PHA in cats. The chemistry panel will
frequently reveal hypokalemia and
hypomagnesemia (often severe),
hypophosphatemia, elevated CPK, and varying
degrees of azotemia. If blood gas analysis is
performed, affected cats may have metabolic
alkalosis due to the excess excretion of
hydrogen ions in PHA. Clinical Note: Any cat
presenting with hypertension and/or
hypokalemia should be screened for the
presence of PHA. Keep in mind,
hypokalemia may represent a much later
development in the natural course of PHA.
Failure to suspect PHA because of normal
potassium levels may result in underdiagnosis of PHA in the hypertensive feline
population and delay identification and
management of this treatable disease.
Plasma aldosterone levels are readily available
(and not prohibitively expensive!) and are
required to establish the diagnosis of PHA.
The presence of marked hyperaldosteronism—
typically 6 times higher than normal—is
supportive of a diagnosis of PHA. Clinical
Note: Cats with chronic renal failure present
a diagnostic dilemma as they may be
hypertensive, hypokalemic and if measured,
their aldosterone levels may be elevated.
Generally aldosterone will only be elevated 2
to 3 times normal in cats affected by chronic
renal failure as opposed to at least 6 times
normal in cats affected by PHA. See Table 5
for available diagnostic testing for PHA.
Abdominal ultrasound imaging remains part of
the gold standard for diagnosis of PHA.
Ultrasound commonly confirms the presence
of a unilateral adrenal mass in affected cats,
however, failure to find a mass DOES NOT
exclude neoplasia as a differential as some
lesions are very small and may not be
visualized for months after the diagnosis.
CT can be performed and may be particularly
helpful for identifying small lesions and
vascular invasion. The ability to use contrast
enhancement is also potentially advantageous
for challenging cases.
Treatment and Prognosis
As most cats with PHA are affected by
unilateral adrenal neoplasia, adrenalectomy is
the treatment of choice. Adrenalectomy offers
a chance of a complete cure—resolution of
hypertension and hypokalemia should be
expected if resection is complete and no
metastatic disease is present. In one recent
(2014) study, none of the surviving cats
required continued medical management after
surgery. In other studies, over 80% of cats do
not require additional therapy for hypertension.
While adrenalectomy may be a technically
challenging surgery and peri-operative
complications such as hemorrhage,
hypotension and cardiac arrhythmias have
been reported, it can be a very successful
surgery. Additionally, laparoscopy provides a
minimally invasive means of performing an
adrenalectomy with a shortened procedure
time and post-procedural morbidity.
Laparoscopy is a viable option for the treatment
of affected cats if diagnostic imaging has ruled
out intravascular invasion of the adrenal tumor
or overt metastatic disease. Laparoscopy is a
very good option to consider for the right
patient and in a location where an experienced
surgeon is available. The overall median
survival time for cats undergoing unilateral
adrenalectomy was reported to be 1,297 days
(2-1,582 days). The 2014 study found
anesthesia time to be strongly correlated with
prognosis; cats with <4 hours of anesthesia
time had a MST of 1,329 days and cats with
>4 hours of anesthesia time had a MST of 10
days. Survival did not depend on the presence
of an adenoma versus carcinoma or sidedness
of the tumor.
Medical management is a viable option for cats
whose owners will not consider surgery, who
have advanced or metastatic disease, bilateral
adrenal hyperplasia, or who are poor anesthetic
or surgical candidates. Clinical Note:
Medical management can also be instituted
in order to metabolically stabilize a patient
prior to surgery.
The cornerstones of medical management
include control of systemic hypertension and
weakness associated with hypokalemia by the
use of the following therapies:
• Amlodipine 0.625-1.25 mg/cat q day up to BID
• Spironolactone 2-4 mg/kg/day
• Potassium gluconate 2-6 mEq/day
The MST of cats with PHA treated solely with
medical management has been reported to be
50-984 days. Many cats treated with medical
management will have marked clinical
improvement—like “Autumn”—but are
unlikely to have full resolution of hypokalemia
and hypertension. The underlying mass and
associated complications such as tumor
hemorrhage or distant metastasis are obviously
also not addressed with this approach.
“AUTUMN’S” TREATMENT AND
OUTCOME
Upon admission, immediate control of
“Autumn’s” blood pressure and marked
hypokalemia were pursued. She received
amlodipine (1.25 mg PO) and her blood
pressure improved within 4 hours to 140
mmHg. Due to the severity of her cardiac
chamber enlargement, “Autumn” was unable
to tolerate maintenance intravenous fluids so
her potassium and magnesium
supplementation was administered as ultra-low
volume continuous rate infusions. Potassium
was given at 1.35 mEq/hr (0.5 mEq/kg/hr) and
magnesium sulfate at 0.25 mEq/hr (0.1 mEq/
kg/hr) to address her severe electrolyte
deficiencies. Clinical Note: When potassium
chloride is given intravenously, the infusion
rate is more critical than the total amount
administered. The rate should generally not
exceed 0.5 mg/kg/hr. Slow increases in her
serum potassium were noted but exceedingly
high dosages (up to 0.8 mEq/kg/hr) were
required to increase her potassium to 2.9
mEq/L over the first 24 hours. Spironolactone
was started at 6.25 mg PO BID (approximately
2.5 mg/kg PO BID) as another means to
increase her serum potassium levels. Clinical
Note: Spironolactone works by antagonizing
aldosterone receptors in the distal renal
tubules and as such will increase serum
potassium concentrations. It is commonly
used in cats with primary hyperaldosteronism.
Within 24 hours “Autumn’s” neurologic status
had improved dramatically. She began eating
on her own and Tumil-K® (2 mEq PO BID)
was added as an oral potassium supplement.
By 48 hours after presentation, “Autumn” had
a normal serum potassium concentration of
4.39 mEq/L. Her continuous IV potassium
infusion was gradually decreased to
0.7 mEq/kg/hr and then to 0.3 mEq/kg/hr. Oral
Tumil-K® was increased to 3 mEq PO BID to
maintain her serum potassium concentration.
Magnesium sulfate was gradually decreased
(0.2 mEq/hr to 0.1 mEq/hr) as her serum
magnesium concentrations became normal.
“Autumn” required a decrease of her
amlodipine to 0.625 mg PO q day to best
address her blood pressure.
By the third day of hospitalization, “Autumn’s”
intravenous potassium and magnesium were
discontinued and her potassium remained
stable at 4.18 mEq/L. Unfortunately her
magnesium decreased when off intravenous
supplementation to 1.27 mEq/L and she
required oral supplementation with Milk of
Magnesia®. “Autumn” was monitored for an
additional 24 hours and serum potassium and
magnesium concentrations remained stable on
oral supplementation. Her renal parameters
were stable (BUN 37, creatinine 3.1) and
blood pressure was well controlled.
“Autumn” was discharged to her owner with
instructions to give the following at home:
spironolactone (6.25 mg PO BID), amlodipine
(0.625 mg PO q day), Tumil-K® (3 mEq PO
BID), Milk of Magnesia® (1ml PO BID) and
prednisolone acetate eye drops (1 drop OS x 7
days) to address her anterior chamber
hemorrhage. The plan was to institute
clopidogrel therapy once “Autumn’s” anterior
chamber hemorrhage resolved and her
hypertension remained well controlled.
“Autumn” continued to improve clinically at
home and her neurologic signs resolved. At
her first recheck one week after release from
the hospital, her blood pressure was stable
between 130 and 160 mmHg on the lower
dosage of amlodipine but her potassium had
declined to 2.8 mEq/L. Her magnesium was
not rechecked. Unfortunately, the owner had
been relying on “Autumn’s” appetite for
administration of her medication. Clinical
Note: Cats commonly develop food aversions
when owners attempt to hide medication
within their food. In a patient like “Autumn”
who requires multiple life-saving
medications, it is imperative to teach owners
how to directly pill their cat.
The aldosterone level was reported at the time
of “Autumn’s” first recheck and confirmed the
presumptive diagnosis of PHA. Additional
therapeutic options for PHA were discussed
with the owner, including abdominal
exploratory for adrenalectomy/mass resection
in order to best control “Autumn’s” electrolyte
abnormalities and hypertension. However,
given the appearance of the mass on
ultrasound, surgery was considered potentially
high risk and a CT scan was advised to
determine the relationship of the mass to the
vena cava and portal vein for surgical planning
purposes.
“Autumn’s” owner declined surgery and has
continued to see her RDVM. Her owner has
more consistently been able to administer the
spironolactone and amlodipine although the
potassium supplement is a bit more sporadic.
The Milk of Magnesia® has not been required
to maintain her magnesium levels. The owner
reports “Autumn” is doing very well at home
with great energy and is even able to jump onto
the furniture at home.
Although a definitive histopathologic diagnosis
of “Autumn’s” adrenal lesion was not obtained,
her case highlights many important points
about feline hypertension and the medical
management of cats with primary
hyperaldosteronism.
COMMENTS
The most important take-home message is that
we should be screening older cats for the
presence of hypertension in order to diagnose
systemic hypertension earlier—before target
organ damage occurs. If a cat is
hypertensive—especially if it is refractory—
keep primary hyperaldosteronism on your list
of differentials as it is more common than once
thought. While PHA should certainly be
considered a differential in cats presenting with
systemic hypertension and hypokalemia, using
hypokalemia as a definitive criterion for
screening is likely to result in under-diagnosis
of PHA in the hypertensive feline population.
Clinical Note: Idiopathic hypertension is
RARE in the cat. While many of these cats
have CKD, some of these hypertensive cats
may actually have PHA. Aldosterone levels
should be measured and the adrenal glands
imaged in all cases of apparently “idiopathic”
feline hypertension.
REFERENCES
Polzin, David J. Chronic Kidney Disease, Chapter 311. The Textbook of Veterinary Internal Medicine, Ettinger and Feldman editors, 7th edition, Elsevier,
St. Louis, 2014.
Stepien, Rebecca L. Pathophysiology of Systemic Hypertension and Blood Pressure Assessment, Chapter 151. The Textbook of Veterinary Internal
Medicine, Ettinger and Feldman editors, 7th edition, Elsevier, St. Louis, 2014.
Lo, AJ, DE Holt, DC Brown, et al. Treatment of Aldosterone-Secreting Adrenocortical Tumors in Cats by Unilateral Adrenalectomy: 10 cases (2002-2012). J
Vet Intern Med 2014, 28: 137-143.
Djajadiningrat-Laanen SC, Galac, MH Boeve, etc. al. Evaluation of the oral fludrocortisone suppression test for diagnosing primary hyperaldosteronism in
cats. J Vet Intern Med 2013 Nov-Dec 27(6): 1493-9.
Djajadiningrat-Laanen S, S Galac, H Kooistra. Primary hyperaldosteronism: expanding the diagnostic net. J Feline Med Surg Sept 2011; 13(9): 641-50.
Schulman, Rhonda L. Feline primary hyperaldosteronism. Vet Clin North Am Small Anim Pract. March 2010; 40(2): 353-9.
Brown, S., C. Atkins, R. Bagley, et al. Guidelines for the Identification, Evaluation, and Management of Systemic Hypertension in Dogs and Cats. J Vet Intern
Med 2007; 21: 542-558.
Roderick, Andrew Ash, AM Harvey, S Tasker. Primary hyperaldosteronism in the cat: a series of 13 cases. J Feline Med Surg June 2005; 7(3): 173-82
CLINICAL ASSESSMENT
1
2
Idiopathic hypertension is common in
cats. True or False?
An appropriate initial workup for any cat
presenting with hypertension includes all EXCEPT the following:
a.Minimum database (CBC, Chemistry
panel, T4, Urinalysis)
b.Chest radiographs
c.Abdominal ultrasound
d.Aldosterone levels
3
Aldosterone levels 2 times above normal
are consistent with primary hyperaldosteronism. True or False?
4
5
6
Adrenal hyperplasia is the most common
cause of PHA in cats and medical management is the treatment of choice.
True or False?
What is the general guideline for maximum
intravenous rate of potassium infusion?
Proper indirect blood pressure technique
includes all EXCEPT the following:
a.Patient acclimation for 5-10 minutes
prior to blood pressure measurement
b.Pressure cuff 60% of the circumference
of the limb or tail
c.Artery positioned at the same level as
the heart
d.Discard first value and average 5-7
subsequent readings
7
Complete resolution of clinical signs can be
expected with medical management for PHA in affected cats. True or False?
8
What is the mechanism of action of
spironolactone and why is it used in the
management of PHA?
9
Medical management of PHA includes all
EXCEPT the following:
a.Spironolactone
b.Furosemide
c.Amlodipine
d.Potassium gluconate
e. Magnesium
10
Hypomagnesemia may cause refractory
hypokalemia. True or False?
CLINICAL ASSESSMENT ANSWERS:
1.
False. Idiopathic hypertension is rare in cats. Secondary hypertension is the most common cause of systemic hypertension and accounts for at least
80% of cases in both dogs and cats.
2.
d) Aldosterone levels. Aldosterone levels should not necessarily be performed during the INITIAL screening workup of systemic hypertension. They are
indicated if there is no apparent underlying disease, if the chemistry panel reveals hypokalemia or a cat is exhibiting signs of hypokalemic polymyopathy,
if the abdominal ultrasound reveals adrenal abnormalities or if hypertension becomes refractory to treatment.
3.
False. Aldosterone levels are expected to be 6 times (or more) above normal in cats affected by PHA. In addition, most affected cats will have systemic
hypertension, hypokalemia, increased urinary excretion of potassium and an adrenal mass apparent on imaging. The diagnosis is sometimes imperfect
and if aldosterone levels are not as dramatically elevated, a fludrocortisone suppression test could be considered as cats affected by PHA will fail to
suppress or have <50% suppression of their UACR (urinary aldosterone: creatinine ratio).
4.
False. Unilateral neoplasia (either adenoma or carcinoma) is the most common cause of PHA in cats and adrenalectomy is the treatment of choice.
Resolution of hypertension and hypokalemia should be expected post-operatively with full resection.
5.
When potassium chloride is given intravenously, the rate is more critical than the total amount administered. The rate should generally not exceed 0.5
mEq/kg/hr. If the infusion rate needs to be higher than this, a sampling line for aggressive serum potassium monitoring and close monitoring of
cardiovascular status are required.
6.
b) The pressure cuff should measure 40% of the circumference of the limb or tail to prevent erroneous blood pressure readings.
7.
False. Most cats treated with medical management will have marked clinical improvement but they are unlikely to experience full resolution of
hypokalemia and hypertension. The underlying mass and associated complications such as tumor hemorrhage or distant metastasis are obviously also
not addressed with medical management. While surgery is the treatment of choice, medical management is a viable option for cats whose owners will
not consider surgery, who have advanced or metastatic disease, bilateral adrenal hyperplasia, or who are poor anesthetic or surgical candidates.
8.
Spironolactone is an aldosterone-antagonist which makes it useful for the management of PHA in cats. Aldosterone is competitively inhibited by
spironolactone in the distal renal tubules with resultant increased excretion of sodium, chloride and water and decreased excretion of potassium,
ammonium and phosphate.
9.
b) Furosemide. Furosemide may induce fluid and electrolyte (particularly potassium) imbalances. Spironolactone is used in PHA primarily as an
aldosterone antagonist and not specifically as a diuretic.
10. True. If you are unsuccessful at correcting hypokalemia with oral or intravenous potassium supplementation, measure serum magnesium as
hypomagnesemia may be responsible. Milk of Magnesia® is a readily available source for oral magnesium supplementation.