Case Report  Rapport de cas

Diagnosis and outcome of a dog with iatrogenic hyperadrenocorticism

and secondary pulmonary mineralization
Shauna L. Blois, Isabelle Caron, Colleen Mitchell

Abstract — A 6-year-old, spayed female dog was evaluated for a history of chronic coughing, excessive panting,
and lethargy. Iatrogenic hyperadrenocorticism was diagnosed, and pulmonary mineralization was documented
with a 99mTechnitium-methylene diphosphonate (99mTc-MDP) scan. Blood gas analysis showed hypoxia. Clinical
signs resolved and blood gas values returned to normal when corticosteroid therapy was discontinued.

Résumé — Diagnostic et devenir d’un chien avec de l’hypercorticisme et une minéralisation pulmonaire
secondaire. Une chienne châtrée âgée de 6 ans est évaluée pour des antécédents de toux chronique, d’halètements
excessifs et de léthargie. L’hypercorticisme iatrogénique est diagnostiqué et une minéralisation pulmonaire est
documentée avec un échogramme au 99m Technétium méthylène disphosphonate (99mTc-MDP). L’analyse des
gaz sanguins a montré de l’hypoxie. Les signes cliniques se sont résorbés et les valeurs de gaz sanguins sont retournées
à la normale lorsque la thérapie aux corticostéroïdes a été discontinuée.
(Traduit par Isabelle Vallières)
Can Vet J 2009;50:397–400

A 6-year-old, spayed female, bichon frisé cross, weighing 8 kg,

was referred to the Ontario Veterinary College (OVC) for
evaluation of excessive panting, intermittent coughing, and
567 3 109/L; reference range: 117 to 418 3 109/L). Results
from a serum biochemical profile and a urinalysis were unre-
markable, but a urine culture from a sample collected via
exercise intolerance. The referring veterinarian had radiographed cystocentesis yielded growth of an Enterococcus sp. Amoxicillin
the thorax and observed a diffuse alveolar pattern throughout (Amoxil; Pfizer), 25 mg/kg BW, PO, q12h for 2 wk, was pre-
the lung fields. Treatment with furosemide did not improve the scribed to treat the urinary tract infection. Iatrogenic hyperad-
radiographic appearance of the lungs. Theophylline (Apotex, renocorticism was suspected because of the dog’s alopecia and
Toronto, Ontario), 6 mg/kg bodyweight (BW), PO, q8h for hepatomegaly, as well as its history of chronic prednisolone
2 mo resulted in minimal improvement of the cough. The dog therapy. An adrenocorticotropic hormone (ACTH) stimulation
had been treated for pruritus with a combination of trimepra- test was performed, 48 h after the dog had received a combina-
zine tartrate and prednisolone (Vanectyl-P; Pfizer, Kirkland, tion dose of trimeprazine tartrate and prednisolone (1.6 mg/kg
Quebec), 1.6 mg/kg BW and 0.25 mg/kg BW, respectively, PO, BW and 0.25 mg/kg BW, respectively, PO), by administering
q12h since she was 4 mo of age. corticotropin (Bexco ACTH; Bexco Pharma, Mississauga,
Ontario), 2.2 U/kg BW, IM, once. Pre and 1-hour post-ACTH
Case description stimulation cortisol levels were , 28 nmol/L (pre-ACTH refer-
Upon examination at the OVC, the dog was moderately over- ence range, 30 to 300; Immulite cortisol assay, Siemens Medical
weight, with a thin hair coat and rat-tailed appearance. The abdo- Solutions Diagnostics, Loa Angeles, California, USA), thus
men was distended, and mild hepatomegaly was palpated. The skin confirming that the dog had iatrogenic hyperadrenocorticism.
over the abdomen appeared thin. Mildly increased bronchovesicu- The endogenous ACTH concentration was low (3.3 pmol/L;
lar sounds were ausculted diffusely throughout the lung fields. The reference range: 7 to 40 pmol/L).
patient became tachypneic and cyanotic when stressed. Results from an arterial blood gas analysis were consistent
A complete blood (cell) count (CBC) revealed a mild leu- with mild to moderate hypoxia. The arterial partial pressure
kocytosis (leukocytes 20.5 3 109/L; reference range: 4.9 to of oxygen (PaO2) was 55.1 mmHg (reference range: 80 to
15.4 3 109/L) characterized by a mild mature neutrophilia 112 mmHg), and the arterial partial pressure of carbon dioxide
(segmented neutrophils 18.45 3 10 9/L; reference range: (PaO2) was 30.2 mmHg (reference range: 23 to 42  mmHg).
2.9  to 10.6 3 109/L), and a mild thrombocytosis (platelets Oxygen saturation in the sample was 86.7% (reference range:
. 95%). An alveolar-arterial oxygen gradient was calculated
Department of Clinical Studies, Ontario Veterinary College, and found to be elevated (56.1 mmHg, reference range:
University of Guelph, Ontario N1G 2W1. , 15 mm Hg).
Address all correspondence to Dr. Shauna Blois; e-mail: Thoracic radiographs revealed a diffuse alveolar pattern
sblois@uoguelph.ca (Figures 1A and 1B). Given the lack of evidence for cardiac

CVJ / VOL 50 / APRIL 2009 397

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R A P P O R T D E CA S

A B
Figure 2.  Left lateral (A) and dorsal (B) images of the 99mTc-
methylene diphosphonate (MDP) scan showing uptake of the
radioisotope by pulmonary parenchyma. Note that the uptake
of the isotope by the lungs (asterix) is similar to the uptake
A B observed in the bones.
Figure 1.  Left lateral (A) and dorsoventral (B) thoracic
radiographs showing diffuse alveolar pulmonary changes,
most prominent in the caudodorsal lung field. body condition with a body weight of 6 kg. Comedones were
noted over the ventral abdominal wall. Mildly increased bron-
disease and the static nature of the radiographic lesions, despite chovesicular sounds were ausculted diffusely throughout the
empirical treatment of the dog with furosemide and predniso- lung fields.
lone, mineralization, fibrosis, and neoplasia were the primary Thoracic radiographs showed changes that were identical to
radiographic differential diagnoses. A thoracic ultrasonograph those observed in the radiographs performed 5 mo previously.
showed mild irregularity of the pleural surface, but it did not Results from an arterial blood gas analysis were normal (PaO 2
demonstrate fluid or cellular infiltration in the pulmonary of 90.1 mmHg; PaCO2 of 38.0 mmHg; oxygen saturation of
parenchyma. Abdominal ultrasonography revealed a diffuse 98.6%). The alveolar-arterial gradient was normal (11.4 mmHg).
hyperechogenic hepatopathy and adrenal glands that were The combined trimeprazine tartrate and prednisolone therapy
considered small bilaterally (0.32 cm at the thickest point for was discontinued. Subsequently, the pruritus and comedones
the right adrenal gland, 0.29 cm for the left), although this were controlled successfully with a hypoallergenic diet.
latter finding was considered subjective, as the lower size limit
for the canine adrenal gland has not been published. The ultra- Discussion
sonographic changes were consistent with those expected with Dystrophic mineralization commonly occurs in association with
chronic administration of exogenous steroid. Bronchoscopy and canine hyperadrenocorticism and can cause calcinosis cutis, as
bronchoalveolar lavage were not performed due to the potential well as mineralization of tracheal rings and bronchial walls, kid-
risk of oxygen desaturation during anesthesia. Transtracheal wash neys, gastric mucosa, liver, skeletal muscle, and branches of the
was declined by the owners due to the cost involved. abdominal aorta (1,2). Thoracic radiographic features of canine
Based on the suspicion that there was pulmonary mineral- hyperadrenocorticism include a moderate to severe generalized
ization, a nuclear scintigraphic examination of the thorax was interstitial lung pattern and ectopic calcification of tracheal
performed. Two hours post IV injection of 141 megabecquerel rings and bronchial walls (3–5). These changes are not specific
(MBq) of 99mTechnitium-methylene diphosphonate (99mTc- for hyperadrenocorticism, as they may be age-related (2,5,6).
MDP), whole body static images were obtained with a gamma Mineralization in dogs with hyperadrenocorticism is likely due
camera (Technicare Omega 500; Technicare, Cleveland, Ohio, to the protein catabolic actions of cortisol. Protein damage can
USA) and a low-energy, all-purpose, collimator. The images then lead to calcium and phosphorus deposition in the organic
were then processed with a dedicated imaging computer and matrix of the abnormal protein, despite normal calcium and
the appropriate software (Mirage-Vets, Link Medical, Bramshill, phosphorus concentrations in serum (1,2).
Hampshire, UK). Uptake of the radiopharmaceutical could be Plain thoracic radiographs are considered to lack sensitivity
seen throughout the pulmonary fields (Figures 2A and 2B), so for the diagnosis of pulmonary mineralization (7). Pulmonary
pulmonary mineralization, suspected to be secondary to iatro- mineralization in this case was diagnosed by using a 99mTc-
genic hyperadrenocorticism, was diagnosed. MDP scan. In human medicine, nuclear scintigraphy or high-
A recheck examination was performed 5 mo after the initial resolution computed tomography are considered the tests of
diagnostic tests. The dose of the combined trimeprazine tartrate choice for establishing a definitive diagnosis of pulmonary
and prednisolone had been gradually tapered to 0.8 mg/kg BW mineralization (7,8). The calcific nature of the pulmonary inter-
and 0.125 mg/kg BW, respectively, PO, q72h by the time of stitial lesions is easily identified with scintigraphy (7). After its
the recheck. According to the client, there had been resolution IV injection, 99mTc-MDP diffuses into the extracellular space
of the cough and the panting when the dose was decreased, but and then rapidly binds to hydroxyapatite crystals in bone or
the exercise intolerance had only partially improved. Upon the soft tissue. Bone uptake of 99mTc-MDP is proportional to its
decreased dose, the client had also observed a recrudescence of osteoblastic activity (9). Pulmonary uptake of 99mTc-MDP in
the pruritus, which was mild and intermittent at the time of canine hyperadrenocorticism has been documented previously
the recheck. The theophylline therapy had been discontinued (3,10): a study of dogs with pituitary-dependent hyperadreno-
5 mo prior to the recheck. On physical examination, the dog corticism revealed that 7 of 21 dogs were hypoxic, but only 2 of
had a normal hair coat, the hepatomegaly and abdominal dis- those dogs showed pulmonary mineralization through uptake of
tention were no longer discernable, and the dog was in good 99mTc-MDP (3). Six other dogs in the study had an abnormal

398 CVJ / VOL 50 / APRIL 2009

 pathologic process affecting the interstitium, and is not consid-
ered an airway disease. No signs of airway disease were observed
on the thoracic radiographs in this case, although the extensive
interstitial lung pattern may have made it difficult to fully
evaluate the patient’s airways and the absence of radiographic
A B
changes do not rule out airway disease. Mineralization of the

CA S E R E P O R T
Figure 3.  Left lateral (A) and dorsal (B) images of a 99mTc- trachea and bronchi was not observed in this case and usually
MDP scan in a dog without pulmonary mineralization. These
images have been provided for reference, and are not directly is not associated with coughing or other clinical signs (2). The
related to the case herein. reported cough in this case was considered chronic but intermit-
tent by the owners, and the risk involved with bronchoscopy
pulmonary interstitial pattern, and 5 of these dogs were hypoxic and airway wash was considered too significant to pursue these
(3). Postmortem studies of dogs with hyperadrenocorticism diagnostic procedures. A transtracheal wash was declined by the
revealed that microscopic pulmonary interstitial mineralization owners, so concurrent airway disease cannot be ruled out as the
was present in over 90% of cases (2). Nonskeletal uptake of cause of the coughing. The source of the coughing is unknown,
99mTc-MDP has also been reported in calcinosis cutis; renal as is why the coughing resolved in conjunction with tapering
infarction with dystrophic mineralization; acute rhabdomy- the dose of the steroid therapy.
olysis; regional lymph nodes, following extravasation of the A poor prognosis has been associated with hyperadrenocorti-
radiopharmaceutical; osteosarcoma metastasis; and dystrophic cism and secondary pulmonary mineralization. In a previous case
mineralization of soft tissues. Normal uptake of 99mTc-MDP report, a dog with iatrogenic hyperadrenocorticism and dyspnea
is evident in lactating mammary tissue, the pregnant uterus, and treated with supportive care died soon after onset of treatment:
the urinary tract (11). examination of postmortem lung biopsy revealed mineralization
Blood gas analysis performed on this patient initially revealed but a complete postmortem examination was not performed, so
hypoxia. An elevated alveolar-arterial oxygen gradient can other underlying diseases related to the patient’s death could not
reflect a ventilation-perfusion inequality, such as pulmonary be ruled out (15). However, Berry et al (10) reported that 2 of
thromboembolism or pulmonary diffusion impairment (12). 4 dogs with pulmonary mineralization and hyperadrenocorti-
Interstitial mineralization may present a diffusion impairment, cism were euthanized due to persistent signs of hypoxia and lack
leading to ineffective gas exchange in the lungs. of response to empirical therapy. The other 2 dogs were treated
Development of pulmonary thromboembolism is a reported, with mitotane and showed persistent pulmonary mineralization
and often fatal, complication of canine hyperadrenocorticism. on radiographs taken 6 mo after the initial diagnosis. One of
Dogs with pulmonary thromboembolism may have acute these 2 dogs remained hypoxic on re-examination but did not
respiratory distress (2). Pulmonary thromboembolism was not show signs of respiratory distress (10).
ruled out in this patient; however, due to the patient’s chronic This case of iatrogenic hyperadrenocorticism and pulmonary
respiratory signs, it was believed to be less likely. In previously mineralization highlights 2 clinically important points. Unlike
reported cases of dogs with pulmonary mineralization, the results previously reported cases, the dog in this report experienced
of perfusion studies were normal (10). Radiographic features of clinical improvement and resolution of clinical signs as the
pulmonary thromboembolism are inconsistent. They may be combined dose of trimeprazine tartrate and prednisolone was
absent or include pulmonary arterial changes, such as blunting first tapered and then discontinued; she continues to be clini-
or truncation; pulmonary parenchymal changes, such as alveolar cally normal 12 mo after her condition was first diagnosed. The
pattern or oligemia; cardiac changes, such as right heart or main improvement observed in clinical signs and blood gas values
pulmonary artery enlargement; or pleural effusion (13,14). occurred despite a lack of radiographic improvement. While
Hyperadrenocorticism can lead to respiratory impairment partial resolution of the pulmonary mineralization upon discon-
in patients without pulmonary mineralization. Mechanical tinuation of the corticosteroid therapy may have been respon-
hypoventilation leading to hypercarbia may be due to a decrease sible for the resolution of the hypoxia, a follow-up scintigraphic
in respiratory excursion effort, secondary to increased fat deposi- pulmonary examination was not performed. Although results
tion in the thoracic wall, muscle wasting and weakness of the of the blood gas analysis were not supportive of hypoventila-
muscles involved in respiration, and increased pressure on the tion, the patient’s weight loss and presumed improvement of
diaphragm from hepatomegaly and abdominal distention (2). respiratory function associated with resolution of the iatrogenic
In the case reported herein, resolution of the iatrogenic hypera- hyperadrenocorticism likely contributed to the resolution of
drenocorticism may have been partly responsible for the normal panting and the improvement in exercise tolerance observed.
blood gas values on follow-up examination, although the normal It is also clinically relevant to note that this case of iatrogenic
PaCO2 was not suggestive of hypoventilation. hyperadrenocorticism and pulmonary mineralization occurred
Coughing is not a typical clinical sign associated with hypera- after chronic use of a low dose (0.5 mg/kg BW/d) of predniso-
drenocorticism, and it has not been reported, in previously doc- lone. Two previously reported cases of iatrogenic hyperadreno-
umented cases of pulmonary mineralization; in the case being corticism and pulmonary mineralization exist (10,15): one dog
reported, it was a historical complaint and its cessation coincided developed respiratory compromise after receiving a high dose
with the tapering of the combined dose of trimeprazine tartrate (2.2 mg/kg BW/d) of prednisone for 4 y (15). The report on
and prednisolone (2,10,15). Pulmonary mineralization is a other case did not include information regarding the dose or the

CVJ / VOL 50 / APRIL 2009 399

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