An 8-year-old sexually intact female Dachshund was evaluated because of a 6-week history of bilateral stiffness and muscle hypertrophy of the thoracic and pelvic limbs. The owner reported that the dog had chronic generalized alopecia, cutaneous crusting, skin hyperpigmentation, polydipsia, polyuria, polyphagia, progressive weight loss, and abdominal enlargement and was panting and lethargic. Stiffness became progressively worse until the dog was unable to flex the limb joints. Gait abnormalities were also reported and included difficulty in climbing up stairs and getting up from a recumbent position. Abdominal distention, bilaterally symmetric alopecia, erythema, wet seborrhea, and otitis externa were also observed. On physical examination, bilateral joint stiffness and enlargement of the muscles of the pelvic limbs were observed; limb rigidity was especially noticeable in the stifle and tarsal regions. Gait evaluation revealed that the dog took short-strided steps when walking or running on a flat surface and was unable to climb up a ramp inclined at 20°.

Neurologic examination Observation

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What is the problem? Where is the lesion? What are the most probable causes of this problem? What is your plan to establish a diagnosis? Please turn the page.

Assessment

Anatomic diagnosis

Problem	Rule out location
Bilateral limb stiffness (especially in the pelvic limbs)	Neuromuscular pathwaysmost likely myopathy
Bilateral muscle hypertrophy
Generalized increase in muscle tone
Short-strided gait

Likely location of one lesion

Musculature

Etiologic diagnosis—Disease processes that were considered were various acquired polymyopathies. The diagnostic plan included performing a CBC, serum biochemical analyses, and urinalysis (to evaluate the patient's general condition); electromyography (to evaluate muscle electrical activity); microscopic examination of a muscle biopsy specimen (to rule out inflammatory myopathies); and an ACTH stimulation test (to confirm or rule out hyperadrenocorticism). If results of the ACTH stimulation test confirmed hyperadrenocorticism, ultrasonography of the abdomen or computed tomography or magnetic resonance imaging of the brain would be performed.

Diagnostic test findings—On the basis of the results of a CBC, the neutrophil count was considered high normal (11,508 cells/μL; reference range, 3,000 to 11,500 cells/μL). Lymphopenia (685 cells/L; reference range, 1,000 to 4,800 cells/μL), mild monocytosis (1,370 cells/μL; reference range, 150 to 1,350 cells/μL), thrombo-cytosis (426,725 platelets/μL; reference range, 100,000 to 200,000 platelets/μL), and mild lipemia were also detected. Analysis of a urine sample revealed isosthenuria and the presence of bacteria. Serum biochemical analyses revealed high activities of alanine aminotransferase (340.3 U/L; reference range, 4.8 to 24 U/L), creatine kinase (330.3 U/L; reference range, 1.15 to 28.4 U/L), and alkaline phosphatase (4,486 U/L; reference range, 20 to 156 U/L); mildly high total protein concentration (8.4 g/dL; reference range, 6.0 to 8.0 g/dL); hyperalbuminemia (4.1 g/dL; reference range, 2.60 to 3.30 g/dL); normoglobulinemia (4.3 g/dL; reference range, 2.7 to 4.4 g/dL); hypertriglyceridemia (183 mg/dL; reference range, 20 to 112 mg/dL), and hypercholesterolemia (227.7 mg/dL; reference range, 135 to 207 mg/dL).

Electromyography of the semimembranosus and semitendinosus muscles revealed spontaneous high-frequency discharges, which did not wax and wane in frequency or amplitude; coincident with the high-frequency discharges, the testing unit produced a rapid staccato sound (ie, a machine gun sound), then both abruptly ceased (Figure 1). Histologic examination of a biopsy specimen of the semimembranosus muscle revealed that focal areas of fiber necrosis with and without phagocytosis were common.

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Electromyographic tracing from the semitendinosus muscle of an 8-year-old dog that was evaluated because of a 6-week history of bilateral stiffness and muscle hypertrophy of the thoracic and pelvic limbs. Notice the complex repetitive discharges in the tracing. Results of an ACTH stimulation test subsequently confirmed that the dog had hyperadrenocorticism. Vertical divisions represent 500 μV; horizontal divisions represent 50 milliseconds.

Citation: Journal of the American Veterinary Medical Association 238, 10; 10.2460/javma.238.10.1247

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The results of the ACTH stimulation test were consistent with hyperadrenocorticism; 1 hour following administration of ACTH (0.25 mg of synthetic ACTH, IM), serum cortisol concentration was 500 ng/mL (reference range, 60 to 170 ng/mL). Abdominal ultrasonography revealed that the liver was large and hyperechoic, compared with the appearance of the liver in a healthy dog, but the adrenal glands appeared normal. Dynamic computed tomography (2-mm slice interval) revealed slight contrast enhancement of the neurohypophysis and adenohypophysis, but no abnormality in size or shape of the pituitary gland was detected. A diagnosis of hyperadrenocortical myopathy was made on the basis of the aforementioned test results. The owner refused treatment, and the dog died 11 months later.

Comments

Hyperadrenocorticism (Cushing's syndrome) is a relatively common endocrine disorder of middle-aged and old dogs,^1,2 and female dogs are predisposed to the condition.³ Poodles and some other small breeds are overrepresented among affected dogs.³ Laboratory findings such as neutrophilic leukocytosis, lymphopenia, thrombocytosis, lipemia, high circulating activities of alanine aminotransferase and alkaline phosphatase, hypertriglyceridemia, hypercholesterolemia, isosthenuria, and urinary tract infection are clinicopathologic abnormalities commonly identified in dogs with hyperadrenocorticism.⁴ High alanine aminotransferase activity and cholesterol concentration evident in the dog of this report were the most reliable indicators of hyperadrenocorticism.⁴

The most common musculoskeletal signs in dogs with hyperadrenocorticism are related to muscle weakness.⁵ Affected animals may tire easily, and weakness of the abdominal musculature can contribute to a pot-bellied appearance.⁵ Rarely, dogs with hyperadrenocorticism develop a distinct myopathy,^5,6 which is characterized by persistent, active muscle contraction after cessation of voluntary effort.⁷ The cause for this unusual phenomenon is unknown,^5,7,8 and it has been observed in 8 of > 2,000 dogs with hyperadrenocorticism.⁷ Duncan and Griffiths⁹ and Greene et al¹⁰ reported the relation between naturally occurring or iatrogenic hyperadrenocorticism and myopathy in 5 and 6 dogs, respectively.

The clinical findings of hyperadrenocorticism-related myopathy in the dog of this report, which have been also described for other cases,^8,11 are similar to those of exogenous steroid myopathy (ie, stiff and stilted gait, stiffness of the limbs, enlarged muscles in the proximal regions of the limbs, and weakness).³ Rewerts et al¹² described the clinical abnormalities that usually affect the pelvic limbs during early stages of the disease with progression to generalized muscle weakness. Clinical problems such as bilateral limb rigidity, especially in the stifle and tarsal regions, due to muscular hypertrophy with no signs of pain⁵ were also identified in the dog of this report.

Diagnosis of hyperadrenocortical myopathy is based on laboratory data and clinical and electrodiagnostic findings.^11,13 Results of an electromyographic examination are indispensable to the diagnosis,^14,15 and the myotonic pattern is evident in the graphic and sound alterations detected during testing.¹⁶ In the dog of this report, the electromyographic activity associated with hyperadrenocorticism consisted primarily of complex repetitive discharges (CRDs); typically, the CRDs occasionally wax and wane but generally end abruptly,⁸ and this feature helps in differentiating CRDs from myotonic discharges.¹⁷ Complex repetitive discharges associated with hyperadrenocorticism have been previously described as bizarre high-frequency potentials and pseudomyotonic potentials.^7,9,10,18 It is important to differentiate these findings from those associated with congenital myotonia, which has been previously described in dogs.^19,20 Congenital myotonia is an inherited condition associated with a chloride channel 1 gene mutation and is characterized electromyographically by high-frequency discharges that wax, wane, and fade away over the time,⁸ thereby producing a sound of increasing volume and high, descending pitch (ie, a characteristic so-called dive-bomber sound) via the test equipment's loudspeaker.^5,9–11

Histologic examination of a muscle biopsy specimen obtained from dogs with hyperadrenocorticism may reveal mild degenerative changes, including variation in the size of the muscular fibers, focal necrosis, fiber splitting, and fiber atrophy.¹¹ The muscle biopsy specimen could appear normal histologically, although a type I fiber or fiber hypertrophy and fiber splitting may be found.^5,16 The histologic examination of the muscle biopsy specimen obtained from the dog of this report revealed only focal necrosis (with and without phagocytosis).

In dogs with pituitary or adrenal gland-dependent hyperadrenocorticism, the baseline plasma cortisol concentration may be within the reference range or high and, as evident in the dog of this report, an exaggerated cortisol response to ACTH stimulation may occur.¹³ In animals with iatrogenic hyperadrenocorticism, there is a little or no cortisol response to exogenous ACTH.¹³ Treatment of hyperadrenocorticism improves signs of myopathy, although the improvement is not rapid.⁸ With regard to the dog of this report, the owner refused treatment and the dog's survival time was 11 months.