Published in IVIS with the permission of the editor
Atypical canine and feline
endocrinopathies
Ghita Benchekroun, DVM
University of Cambridge,
Department of Veterinary
Medicine, Cambridge, UK
Dr. Benchekroun graduated from Alfort
Veterinary School in 2004, where she
then worked in the Internal Medicine
Department with an interest in endocrinology. In 2009
she moved to the University of Cambridge, where she is
currently completing a residency in internal medicine.
Introduction
Certain endocrinopathies in the dog and cat are
seldom diagnosed. This may be because they are
rare, but it may also be due to under-diagnosis;
knowledge regarding a disease clearly has an affect
on its frequency of diagnosis. This article reviews
some of the more unusual hormone disorders. It is
not intended to be an exhaustive assessment,
but rather a synopsis of some of the so-called
“emerging” endocrinopathies, focusing on feline
hyperaldosteronism, feline acromegaly, central
diabetes insipidus, hypophyseal dwarfism, and
primary hypoparathyroidism. The etiology, clinical
presentation, diagnosis, and treatment of each
disease will be discussed.
KEY POINTS
The differential diagnosis of systemic arterial
hypertension in cats should include hyperaldosteronism.
Feline acromegaly is an under-diagnosed cause of
diabetes mellitus in the cat, particularly with insulin-
resistant cases.
Practical problems can arise when performing diagnostic
tests for central diabetes insipidus.
Hypophyseal dwarfism in dogs can be treated by the
administration of progestogens.
The presence of a characteristic cataract is highly
suggestive of hypoparathyroidism in patients with
hypocalcemia.
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Dan Rosenberg, DVM, PhD
National Veterinary School,
Alfort, France
Dr. Rosenberg graduated from Alfort
Veterinary School in 1994 and now
works at the school as a Senior Lecturer
in Internal Medicine. He is particularly
involved in endocrinology and internal medicine
consultations.
Feline primary
hyperaldosteronism
Primary hyperaldosteronism is an emerging feline
endocrinopathy. Initially described in clinical case
reports, it has recently been the subject of retro-
spective case studies (1-2). Most cases are due
to a unilateral adrenal tumor (adenoma/adeno-
carcinoma), but cases of bilateral tumors, mixed
adrenocortical tumors (secreting aldosterone and
progesterone) and bilateral hyperplasia have
also been reported (1). The symptoms in cats
presenting with primary hyperaldosteronism may
be frustrating. The most common presenting signs
are weakness, ventroflexion of the head and
neck (Figure 1), PU/PD and cardiac or ocular
disturbances associated with arterial hypertension
(1-2). Two paraclinical signs that may suggest
hyperaldosteronism are arterial hypertension in
conjunction with hypokalemia associated with
normal or high serum sodium concentration. It is
also common for renal failure to be diagnosed at the
same time (2).
The definitive diagnosis of primary hyper-
aldosteronism is achieved by comparing circulating
aldosterone levels with basal plasma renin activity,
sampled during a hypokalemic episode. The
objective is to demonstrate independent secretion of
aldosterone by the glomerular zone of the adrenal
cortex. Severely reduced plasma renin activity, in
conjunction with normal or high serum aldosterone
levels, confirms the presence of primary hyper-
aldosteronism (1). In secondary hyperaldosteronism
Vol 21 No 1 / 2011 / Veterinary Focus / 35
Published in IVIS with the permission of the editor
© National Veterinary School of Alfort.
Figure 1.
Generalized weakness in a cat with primary hyperaldosteronism.
(e.g. low sodium diet, heart failure, renal failure),
the serum aldosterone increase mirrors that of
renin activity. Unfortunately, measurement of renin
activity is not widely available, thus hindering
diagnosis of the subtle forms of the disease.
The origin of the primary hyperaldosteronism can
be determined by imaging of the adrenal glands. If
a tumor is detected, the search should be widened
to check for metastases. Symmetrical adrenal
glands with a normal shape tend to indicate
bilateral hyperplasia. Adrenalectomy is probably
the treatment of choice in most cases of primary
hyperaldosteronism (assuming no metastasis is
detected). Recorded survival times after surgical
resection are, with the exception of perioperative
complications, usually good (3,4). If the owners
do not consent to surgery, palliative treatment can
be considered, with two main objectives: the
correction of hypokalemia and the control of
arterial hypertension. Correction of hypokalemia
involves potassium supplementation (potassium
gluconate: 2-6 mmoL/cat bid PO), combined with
spironolactone if treatment is prolonged (2.5 to
5 mg/cat sid or bid PO) as it antagonizes
aldosterone. Any anti-hypertensive agents (e.g.
amlodipine 0.125 to 0.250 mg/kg sid PO) can be
considered in cases with marked hypertension.
Feline acromegaly
Feline acromegaly has long been considered to be
extremely rare (5) but recent publications have
challenged this perception, claiming that the
disease incidence is significant amongst diabetic
cats (5,6). It is caused by a (usually large) hypo-
physeal tumor that spontaneously secretes growth
hormone (GH) (5,6). At present there is only one
published example of an analogous case in the
dog. Canine acromegaly is usually of mammary
36 / Veterinary Focus / Vol 21 No 1 / 2011
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origin, under progesterone regulation (8). There is
no apparent breed predisposition but affected
animals are usually older male cats (average age ~
10 years). Typically, acromegaly is associated
with major insulin resistance and morphological
alterations, such as unexplained weight gain,
cardiovascular signs (due to hypertrophic cardio-
myopathy), abdominal organomegaly (hepato-
megaly, nephromegaly, splenomegaly, etc.),
laryngeal stridor secondary to pharyngeal-
laryngeal extension, inferior prognathism or
interdental widening (Figure 2), accelerated
growth of claws, spondylosis, arthropathies (5),
etc. Finally, neurological or behavioral disturbances
may be present due to a hypophyseal macro-
adenoma. However, limiting the suspicion of
acromegaly to these specific clinical contexts
- which are probably late onset - results in under-
diagnosis of the disease. Relatively asymptomatic
forms, where clinical expression is limited to
diabetes mellitus, should also be considered.
The measurement of insulin growth factor-1 (IGF-
1) has a central role in the diagnosis of acromegaly.
More stable than GH and requiring less strict pre-
analytical conditions, this test is offered by many
laboratories and is considered to be a good
reflection of hypophyseal GH secretion over a
period of at least 24h. IGF-1 assay is sensitive and
acromegaly in a diabetic cat can, within reason, be
excluded if the serum IGF-1 is within normal
limits. However, the specificity of this assay
remains debatable (6,7,9) and diagnosis should be
confirmed with other tests, usually brain imaging
(CT or MRI). Two treatment approaches can be
considered: etiological treatment or palliative
control of insulin resistance. The first option
comprises radiotherapy or surgery. To date,
radiotherapy has undoubtedly proven to be the
most effective (10), often enabling a reduction in
insulin requirements and restricting tumor growth.
Hypophysectomy (via conventional or cryo-
surgery) is an alternative to radiotherapy (11). Its
outcome is highly dependent on the surgeon’s
skills. If the owner refuses etiological treatment,
the insulin resistance of acromegalic cats with
diabetes mellitus can be controlled with twice
daily administration of high doses of insulin (6).
Central diabetes insipidus
Central diabetes insipidus (CDI) is caused by a lack
of secretion of anti-diuretic hormone (ADH or
Published in IVIS with the permission of the editor
ATYPICAL CANINE AND FELINE ENDOCRINOPATHIES
vasopressin). CDI is most often diagnosed in dogs
but a few cases have also been recorded in cats
(12). Complete or partial forms are described,
depending on whether ADH secretion is absent or
present but inappropriate (and thus insufficient).
The most common cause of CDI is neoplasia of
the hypothalamo-hypophyseal region (13).
Other causes include inflammatory, infectious,
or traumatic lesions. Iatrogenic cases following
hypophysectomy to treat Cushing’s disease have
been noted and idiopathic cases have also been
described.
The principal sign associated with CDI is the
presence of PD/PU. Neurological signs may also be
present. The PD/PU is associated with hyposthenuric
urine (<1.010) and low urinary osmolality (Uosm
<290 mOsm/kg). Biochemistry may reveal (usually
mild) hypernatremia. However, in the event of
water deprivation – or adipsia due to damage to
the thirst center – major hypernatremia may be
present, resulting in hyperosmolar encephalopathy.
The preferred test for confirming CDI is the water
deprivation test. In preparation for the test,
performed under medical monitoring in a hospital
setting, water intake should be reduced pro-
gressively over a period of several days (3-7 days
for a 50% reduction) to restore the renal cortico-
medullary gradient. After 12h of fasting, access
to water is denied and plasma and urine samples
are collected every hour to measure osmolality,
volume, and urine density. The animal should
also be weighed every hour. The test should be
discontinued if the animal loses more than 3-5% of
its bodyweight, if uremia or natremia increase, if
neurological signs appear, or if urine specific
gravity is >1.030. If urine osmolality (or urine
density) remains low despite appropriate osmotic
stimulation (signs of dehydration or plasma
osmolality >305 mOsm/kg), the result is compatible
with diabetes insipidus and ADH should be
administrated to differentiate between central and
nephrogenic forms. In complete central diabetes
insipidus, urine density or osmolality will double
after the administration of ADH, whilst only a
moderate increase (~ 15%) is seen with the partial
form. In nephrogenic diabetes insipidus, the increase
will be minimal or even absent. There is, however,
one diagnostic pitfall; if the water restriction
imposed in the run-up to the test is insufficient
to restore the cortico-medullary gradient, thus
enabling a response to ADH, the urinary SG may
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© National Veterinary School of Alfort.
Figure 2.
Inferior prognathism with spacing of dental apposition in a cat
with acromegaly.
fail to increase irrespective of the cause of the
PD/PU. Such an absence may lead to the erroneous
diagnosis of nephrogenic diabetes insipidus.
A more direct way of diagnosing CDI is to stimulate
ADH secretion via perfusion of a hypertonic saline
solution. A solution of 20% NaCl is administered at
0.03 mL/kg/min over 2h and ADH and plasma
osmolality are measured every 20 min. This test
may enable a more precise diagnosis of certain
cases of partial CDI but presents more serious risks.
Treatment is based on the administration of a
vasopressin analogue (desmopressin) into the eyes
(1 drop into the conjunctival sac tid) or per os (0.1
to 0.2 mg per animal sid-tid). In the absence of a
hypophyseal lesion, the prognosis is favorable,
with complete clinical remission if the treatment
is correctly administered.
Hypophyseal dwarfism
Any defective organogenesis of the hypophysis
can lead to a defect in the secretion of one or
more hypophyseal hormones. Dwarfism has
been described in the dog, with certain breed
predispositions, and occasionally in the cat.
Autosomal recessive transmission associated
with panhypopituitarism, but sparing corticotropic
function, has been demonstrated in German
shepherd dogs (14).
Affected animals usually present at 2-5 months of
age for proportionate delayed growth (Figure 3),
mental retardation, persistent puppy coat, alopecia
of the trunk, cutaneous hyperpigmentation, flaking,
etc. Disproportionate dwarfism (head and torso
normal but short limbs) is more suggestive of
hypothyroidism. Cryptorchidism is often present
in the male, whilst females present with persistent
anestrus. In general, the animals remain well until
Vol 21 No 1 / 2011 / Veterinary Focus / 37
Published in IVIS with the permission of the editor
2-3 years of age, when systemic signs may start
to appear, sometimes related to renal failure. The
diagnosis can be supported by low IGF-1 or GH
levels, but the definitive diagnosis requires a
stimulation test. GHRH (Growth hormone
releasing hormone 1 μg/kg) or alpha-agonists
(clonidine 10 μg/kg or xylazine 100 μg/kg) can be
used to stimulate GH secretion. Measurements of
GH immediately before, 20, and 30 minutes after
the intravenous injection are required. If GH levels
fail to increase this confirms the diagnosis.
The other hypophyseal functions (thyrotropin,
gonadotropin, corticotropin, and prolactin) may
be assessed using a combined pituitary stimulation
test (15). Medical imaging of the hypophysis often
reveals the presence of cysts in Rathke’s pouch.
Canine GH is not available for the treatment of
dwarfism, but porcine GH has been used (0.1-0.3
IU/kg SC 3 times per week with monitoring of
blood glucose and GH). The use of recombinant
human GH has not yet been reported. The benefits
of the treatment on growth depend on the stage of
the growth cartilages at the start of treatment.
However, cutaneous signs improve after 6-8 weeks.
A therapeutic alternative is the use of progestogens
to stimulate the secretion of growth hormone from
mammary tissue (16,17). Medroxyprogesterone
acetate (2.5-5 mg/kg every 3 weeks, then every 6
weeks SC) as well as proligestone (10 mg/kg
subcutaneously every 3 weeks) have been shown
to induce clinical improvement. In females, ovario-
hysterectomy should be recommended before
starting treatment to limit the risk of pyometra.
Finally, appropriate substitution with levothyroxine
should be prescribed in parallel in cases with
concurrent hypothyroidism. Appropriate treatment
improves the quality of life of affected animals,
provided that treatment is instigated early.
Primary hypoparathyroidism
Primary hypoparathyroidism is caused by the
destruction (or atrophy) of the parathyroid glands.
The spontaneous form is more common in dogs
than in cats; the etiology is probably immune-
mediated in most cases (18). Rarely, it can be
secondary to the destruction of the parathyroid
glands by a tumor of the cervical region. Iatrogenic
hypoparathyroidism can be caused by surgical
damage to the parathyroids (e.g. during thyroid-
ectomy). Deficient parathyroid hormone (PTH)
causes hypocalcemia and moderate hyper-
38 / Veterinary Focus / Vol 21 No 1 / 2011
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phosphatemia. Affected dogs are usually 6
months - 13 years of age; the most commonly
affected breeds are poodles, golden retrievers,
schnauzers, German shepherds, and terriers (18).
Neurological symptoms, including tetany, seizures,
fasciculation, and tremors, are predominant.
Weakness and ataxia have been described
less commonly. Earlier signs of hypocalcemia are
sometimes noted, such as anxiety and occasionally
aggression, probably due to muscle pain. Intense
rubbing of the face against the ground or with the
paws has also been described; this is thought to be
due to contraction of the masseter and temporal
muscles. In a few cases, a cataract typical of chronic
hypocalcemia may be observed: immature, cortical,
diffuse, and punctate, it is characteristic of hypo-
parathyroidism if associated with hypocalcemia
(Figure 4) (18,19).
Concurrent assay of phosphorous levels can
provide additional diagnostic proof. Indeed,
the combination of hypocalcemia and hyper-
phosphatemia, other than in cases of renal failure,
is highly suggestive of hypoparathyroidism. To
confirm the diagnosis, demonstration of a low or
undetectable plasma PTH concentration in an
animal with hypocalcemia is sufficient (18,20). In
all other causes of hypocalcemia, the calcium
regulatory feedback loop is preserved and the
plasma concentration of PTH increases.
Immediate and urgent treatment with intravenous
calcium is required if the patient is presented in
tetany or with seizures (18,20). Once the attack
has been resolved, treatment should be continued
with oral calcium and vitamin D. Initially, both
must be given, as intestinal absorption of calcium
is dependent on vitamin D and is therefore not
very effective at the start of treatment. Calcium
administered in large quantities will enable passive
absorption, and can then be progressively reduced
before being stopped altogether. Long-term
treatment involves the administration of vitamin
D Several different preparations are available; a
hydroxylated 1α form of vitamin D should be used,
since hydroxylation requires PTH. The best forms
are calcitriol and alfacalcidol; both are rapidly
eliminated and their dose rate can therefore be
quickly altered. The objective is not to maintain
normal blood calcium concentration, as this is
more likely to induce erratic calcium precipitates
where there is concurrent hyperphosphatemia;
a mild hypocalcemia is preferable. Regular
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ATYPICAL CANINE AND FELINE ENDOCRINOPATHIES

© National Veterinary School of Alfort.

© National Veterinary School of Alfort.

Figure 3. Figure 4.
2-year-old female German shepherd dog presented for delayed Punctate cataract in a dog with primary hypoparathyroidism.
growth and cutaneous signs due to hypophyseal dwarfism.

monitoring is essential during the course of renal effects of PTH against hypercalciuria or
treatment to guard against hypercalcemia or its effects on bone.
hyperphosphatemia. At the time of writing, there
is no published data concerning the use of human Conclusion
recombinant PTH in the dog. The prognosis is Certain endocrinopathies may be rare, but this
favorable if treatment is well balanced. There is does not mean they do not occur. An awareness of
currently no treatment that enables complete the typical presenting signs and a systematic
compensation of the actions of PTH, so treatment approach will ensure that the veterinarian does not
with vitamin D cannot substitute for the protective miss these interesting and challenging cases.

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