Can you rule out a steroid hepatopathy?

Feb 01, 2003

Signalment: Canine, Sheltie, 13 years old, male castrated, 36 lbs.

Clinical history: The dog presents for polydipsia, marked alopecia, hyperpigmentation and skin thickening on ventral cervical, ventral abdomen and dorsal pelvic areas. Right testicle is also enlarged.

Physical examination: The findings include rectal temperature 101.8° F, heart rate 120/min, respiratory rate 20/min, pink mucous membranes, normal capillary refill time, and normal heart and lung sounds. There is marked alopecia, hyperpigmentation and skin thickening on ventral cervical, ventral abdomen and dorsal pelvic areas. Right testicle is enlarged; the left testicle is small.

Laboratory results: A complete blood count, serum chemistry profile and urinalysis were performed and are outlined in Table 1.

Thyroid panel: The serum T4 value (RIA) is 3.55 (normal range 1.0-4.0 µg/dl); the serum free T4 value (RIA) is 1.30 (normal range 0.65-3.00 ng/dl). The dog has been receiving daily thyroid supplementation.

Initial endocrine panel: An ACTH stimulation test was performed, and baseline and two-hour serum samples were submitted to the University of Tennessee Clinical Endocrinology Service for evaluation. The results are listed in Table 2, p. 12S.

Very high hormone levels are noted. The dog should be neutered to start with and see if the dermatological problem will resolve. If signs persist, then an ultrasound study of the adrenal glands would be warranted to pursue the possibility of an adrenal tumor. If not, then melatonin could be tried at 3-6 mg total dose given twice a day.

Immediate follow-up: The dog was castrated and both testicles were submitted for histopathologic examination. The right testicle contained an interstitial cell tumor (Leydig cell tumor). Metastasis of interstitial cell tumor is possible but extremely rare. The left testicle showed diffuse, moderate, testicular atrophy/hypoplasia.

Second endocrine panel: Considerable hair regrowth occurred since neutering was performed. Two months after castration, ACTH stimulation test was performed and baseline and two-hour serum samples were submitted to the University of Tennessee Clinical Endocrinology Service for evaluation (Table 3).

Although the hormone levels are much less than before neutering, the androstenedione and progestins levels are still high for a neutered dog. Steroid levels should be decreased fairly soon after neutering – several days at the most. It still appears that this dog has increased adrenal activity.

Ultrasound examination: Thorough abdominal ultrasonography was performed. The dog was positioned in dorsal recumbency for the ultrasonography.

Comments: The liver is enlarged and shows a uniform increase in echogenicity. No masses noted within the liver parenchyma. The gallbladder is mildly distended, and its walls are not thickened or hyperechoic.

The gallbladder does contain some sludge material. The spleen shows uniform echogenicity - no masses noted. The left and right kidneys are similar in size, shape and echotexture. No masses or calculi were noted in either kidney. The urinary bladder is distended with urine and contains some urine sediment material - no masses or calculi noted. The prostate gland shows a mixed echogenicity. The left and right adrenal glands are similar in size and shape. The stomach is normal. The pancreas shows a uniform echogenicity.

Case management: In this case, most likely idiopathic vacuolar hepatopathy and adrenal gland dysfunction is the clinical diagnosis. I do not see any obvious ultrasonographic evidence of an adrenal tumor in the abdominal images provided for review.

Idiopathic vacuolar hepatopathy Older dogs often are asymptomatic and have increases in serum alkaline phosphatase (ALP). The typical liver histopathologic report usually reads diffuse hepatic vacuolar change suggestive of a steroid hepatopathy - check for hyperadrenocorticism. Evaluating the liver with special stains finds that the hepatocytes contain excess glycogen. Affected dogs look like typical steroid hepatopathies based on histopathology and abnormal serum ALP concentrations.

However, further investigation finds no clinical or laboratory evidence of hyperadrenocorticism. Often, the only laboratory abnormality that initiates the liver investigation is the increase in serum ALP. Most cases have no clinical signs. Conventional adrenal testing (i.e. ACTH stimulation or low-dose dexamethasone suppression test) is normal. If one measures the glucocorticoid isoenzyme of serum alkaline phosphatase (G-ALP) will find that serum ALP is predominately serum G-ALP.

Ultrasound imaging of the liver shows increased echogenicity and frequently, but not always, the adrenal glands appear normal. The clinical course in these dogs is usually unremarkable; however, a small number of dogs may develop typical hyperadrenocorticism at a later date.

Idiopathic vacuolar hepatopathy may be a type of an abnormal steroid hepatopathy. Hepatic glycogen accumulation is generally a steroid-associated event.

Affected dogs given empirical ketoconazole or lysodren therapy may have decrease in serum ALP concentrations and hepatic glycogen accumulation. Because adrenal nodular hyperplasia is a common finding in older dogs, it is possible that some of these dogs may have functional hyperplastic nodules producing some type of adrenal steroid.

It is possible that abnormal concentrations of some of the other adrenal steroids, possibly progesterone, estradiol, androstenedione or 17-OH progesterone, may be responsible for the hepatic changes. The clinical course of idiopathic vacuolar hepatopathy needs further investigation.

It appears most dogs do not progress in their disease state and live a normal life without adverse consequences from their liver changes. At this time, therapy is not indicated for asymptomatic dogs.