AEMV-Lafeber Case Report: Pituitary-Dependent Hyperadrenocorticism and Cholangiohepatitis in a Guinea Pig

Key Points

  • This case report earned first place in the 2018 AEMV Lafeber Company Student Case Report Contest.
  • A 3-year old intact male guinea pig (Cavia porcellus) was presented on emergency for suspected bloat and with a history of chronic hair loss.
  • Clinical examination revealed non-pruritic symmetric truncal alopecia, thin skin, severe cachexia, and an abdominal fluid wave.
  • Alkaline phosphatase, alanine transaminase, aspartate aminotransferase, gamma-glutamyl transferase, leukocytes (neutrophils), bilirubin, and serum cortisol were markedly elevated.
  • Abdominal ultrasonography revealed peritoneal effusion, cholestasis, and cholelithiasis.
  • Hyperadrenocorticism was diagnosed based on adrenocorticotropic stimulation testing. The patient’s initial serum cortisol was 6125 nmol/L, which increased to 7063 nmol/L 4 hours post-injection with cosyntropin (20 IU IM).
  • Cholangiohepatitis was treated with enrofloxacin, metronidazole, fluid therapy, metoclopramide, ursodeoxycholic acid, buprenorphine, and nutritional and liver health support; however, the patient further declined over eight days of hospitalization. Surgical correction of cholelithiasis was not elected, as this patient did not appear to be fully obstructed nor stable for general anesthesia. Due to a rapid decline in condition, the patient was humanely euthanized before treatment of hyperadrenocorticism commenced.
  • Post-mortem examination was consistent with pituitary-dependent hyperadrenocorticism of suspected neoplastic origin, necrotizing cholangiohepatitis, and sepsis.
  • Reports of hyperadrenocorticism and cholangiohepatits in guinea pig are rare. A connection between hyperadrenocorticism and cholestatic disease has been proposed in other species but is poorly understood.

History and physical examination

A 3-year old intact male guinea pig (Cavia porcellus) was presented to Louisiana State University Veterinary Teaching Hospital (LSU VTH) on emergency for suspected bloat. The owner reported chronic hair loss and a 5-day history of abdominal distension that appeared to worsen after switching timothy hay sources. The patient was regularly offered free choice timothy hay (Kaytee Products, Inc., WI, USA) and pelleted adult guinea pig food (Oxbow Animal Health, NE, USA). Two months prior to this presentation, the patient was treated for bloat.

Upon physical examination, the patient was found to be underweight at 831 grams and 1/9 body condition, tachypneic (80 breaths/minute), and with moderate abdominal distension. Bilateral truncal alopecia, diffusely thin skin, and lichenification of the footpads were noted during dermatological examination (Fig 1, Fig 2).

A 3-year old intact male guinea pig presented with abdominal distension, non-pruritic, bilateral truncal alopecia, and severe cachexia.

Figure 1. A 3-year old intact male guinea pig (Cavia porcellus) presented with abdominal distension, non-pruritic, bilateral truncal alopecia, and severe cachexia. Click image to enlarge

Diffusely think skin in a 3-year old intact male guinea pig

Figure 2. Diffusely thin skin in a 3-year old intact male guinea pig (Cavia porcellus). Click image to enlarge

Diagnostics

Complete blood count revealed a leukocytosis with neutrophilia (Table 1). Blood chemistry revealed elevated alkaline phosphatase, alanine transaminase, aspartate aminotransferase, gamma-glutamyl transferase, and total bilirubin. Creatine kinase, globulins, and urea nitrogen were also elevated. Bile acids were measured and found to at the upper limit of acceptable values (Table 2).

Table 1. Hematology results detected in the guinea pig one day after presentation with reference values.
ParameterValueReference
Hematocrit0.42 L/L0.39-0.55
Hemoglobin8.84 mmol/L7.26-10.51
Erythrocytes5.57 x 1012/L4.51-6.36
MCV75.1 fL80.3-89.1
MCH1.5887 fmol1.50-1.70
MCHC21.16 mmol/L18.1-19.7
Platelets689 10 9/L273-745
Leukocytes24,300 x 106/L2,910-14,420
Mature neutrophils20,300 x 106/L889-5,097
Lymphocytes3,200 x 106/L1,401-10,665
Monocytes700 x 106/L0-657
Eosinophils100 x 106/L0-1,563
Notes: few platelet clumps, anisocytosis 1+, polychromasia 1+, granular lymphocytes rare
Table 2. Plasma chemistry results detected in the guinea pig one day after presentation with reference values.
ParameterValueReference
Glocose6.60 mmol/L4.95-15.95
AST2,649 U/L0-90
ALT97 U/L0-61
ALP158 U/L0-418
GGT34 U/L0-13
Creatine Kinase2,250 U/L0-2,143
Total Bilirubin20.52 µ mol/L0.0-1.59
Total Protein59 g/L44.4-65.8
Albumin25 g/L25.5-41.1
Globulins34 g/L13.1-33
Cholesterol< 0.65 mmol/L0.31-1.67
Urea Nitrogrn13.57 mmol/L3.34-10.33
Calcium3.1 mmol/L2.4-3.1
Phosporus1.84 mmol/L1.03-6.98
Sodium137 mmol/L130-150
Potassium6.2 mmol/L4.5-8.8
Magnesium1.70 mmol/L0.99-2.56
Bile Acids76µ mol/L0-84.5

Abdominal ultrasound was performed using a Toshiba Apilo 300 (Canon Medical Systems USA, Inc., CA, USA), which showed peritoneal effusion, heterogeneity of the liver, and dilation of the gallbladder and cystic duct (Fig 2). The gallbladder also contained swirling echogenic bile. The right adrenal gland appeared larger than the left. A volume of 110 mL of fluid was removed from the abdomen via abdominocentesis. Cytologic examination confirmed a transudate.

 Ultrasonographic image of the liver, distended gallbladder, and common bile duct in a guinea pigas well as an 8.2 mm cholelith (between “+” symbols) within the common bile duct

Figure 3. Ultrasonographic image of the liver, distended gallbladder, and common bile duct in a guinea pig (Cavia porcellus) as well as an 8.2 mm cholelith (between “+” symbols) within the common bile duct. Click image to enlarge

Based on a suspicion of endocrine disease, total thyroxine (T4) and serum cortisol were measured (Table 3). Total thyroxine was <6.4 nmol/L with reported normal values of 14.2-66.9. The cortisol was too high to be read at >1380 nmol/L with reported normal values of 143-339.13 An adrenocorticotropic releasing hormone (ACTH) stimulation test was performed. A serum sample was drawn, cosyntropin (Cortrosyn, Amphastar Pharmaceuticals, CA, USA) 20 U IM was administered, and another serum sample was taken 4-hours post-stimulation. Samples were evaluated by chemiluminscent immounoassay using a Siemens Immulite 1000 (Siemens Healthcare Diagnostics, Inc., NY, USA). An initial cortisol of 6125 nmol/L that increased to 7063 nmol/L 4-hours post-stimulation confirmed hyperadrenocorticism.

Table 3. Blood cortisol concentrations of current patient in comparison to previous studies in guinea pigs.
Resting2-h post ACTH4-h post ACTHSampleReference
325.4 ± 14.35--plasma7
254 ± 15.26--plasma3
143.451263.452030.34plasma1
6125-7063serumCase report

A repeat abdominal ultrasound was performed 6 days after the initial study. Free abdominal fluid was reduced. The liver remained heterogenous and the gallbladder and cystic duct were still distended. An 8.2 mm cholelith and pinpoint hyperechoic foci were present in the common bile duct, which was previously difficult to appreciate. The adrenal glands were approximated to be 13.7 mm (left) and 17.4 x 9.5 mm (right).

 

Treatment and outcome

The patient was stabilized with lactated Ringer’s solution (Pfizer, Inc., NY, USA) 50 ml/kg SC once, buprenorphine (Par Pharmaceutical, NJ, USA) 0.05 mg/kg IM once, metoclopramide (Pfizer, Inc., NY, USA) 1 mg/kg SC q 12 hours, and thermal support. The patient became hypothermic and hyporexic within 12 hours of hospitalization. Nutritional support was provided with Critical Care formula for herbivores (Oxbow Animal Health, NE, USA) at 80 mL/day over 4 feedings per day. Hydration status was assessed q 12 hours; Vitamins B complex and C (Vet One, ID, USA) were provided in subcutaneous fluids at 27 mg/kg and 30 mg/kg q 24 hours. Enrofloxacin (Baytril: Bayer, PA, USA) 12 mg/kg IM q 12 hours and metronidazole (Unichem Pharmaceuticals, Inc. NJ, USA; compounded at LSU VTH) 20 mg/kg PO q 12 hours were added to treatment plan due to the patient’s leukocytosis with neutrophilia. After ultrasound, ursodeoxycholic acid (Par Pharmaceutical, NJ, USA; compounded at LSU VTH) was started at 20 mg/kg PO q 24 hours. Ultrasound guided abdominocentesis was performed as needed to relieve ascites, which accumulated rapidly over the first three days of hospitalization and stabilized after day four of treatment. A liver protectant supplement (Liver Happy: Jing-Tang Herbal, Inc., FL, USA), was administered daily in the patient’s food. Following the ACTH stimulation test, compounded trilostane (Vetoryl: Dechra Veterinary Products, KS, USA) was ordered to be given at 2 mg/kg PO q 24 hours as was previously successful in a guinea pig.4 This medication was also not able to be administered prior to the patient’s death.

Over the course of hospitalization, the patient exhibited poor thermoregulation, continued muscle wasting, and weight loss. On the eighth day in hospital, the patient was found hypothermic and obtunded. Humane euthanasia was elected.

Post-mortem examination found necrotizing hepatitis, cholelithiasis, sepsis, and suspect pituitary neoplasia. The adrenal glands measured 1.5 x 1 x 0.5 cm (left) and 1.4 x 1 x 0.4 cm (right) (normal: 12.6-17.7 mm in length and 4.3-8.4 mm in width).5 Histopathology showed atrophy of cortical reticularis. The pituitary gland appeared neoplastic; it was subjectively enlarged (0.9 x 0.3 cm) relative to the patient’s size, though reference intervals are not available. Sections examined for histopathology contained of clusters of basophils and/or chromophobes admixed with multifocal acidophils. Sections of the pituitary gland were compared to samples from three endocrinologically normal, adult guinea pigs. Comparison slides were provided by Dr. Drury Reavill of Zoo/Exotic Pathology Service in Carmichael, California.

Histopathology of a suspected neoplastic pituitary gland (top) in a guinea pig

Figure 4. Histopathology of a suspected neoplastic pituitary gland (top) in a guinea pig (Cavia porcellus) and comparison images of endocrinologically normal specimens loaned by Dr. Drury Reavill.Click image to enlarge

Discussion

Hyperadrenocorticism (HAC), or Cushing’s disease, is caused by chronic exposure to excess corticosteroids from pituitary, adrenal, or iatrogenic origin. Cushing’s disease has been studied extensively in dogs and humans but is not well documented in guinea pigs. Five guinea pig cases have been recorded in scientific literature, four which were confirmed by ACTH stimulation testing and one in which HAC was suspected due to ultrasonography.5 Both pituitary- and adrenal-dependent HAC were reported.5 Clinical signs in guinea pigs appear similarly to those seen in dogs,  including non-pruritic bilateral alopecia, inelastic thin skin, polyuria, polydipsia, muscle weakness, bilateral exophthalmos, and weight loss.5

Cholestatic disease has also rarely been reported in guinea pigs. Cholestasis describes the slowing or complete stoppage of bile flow. This condition can result from inflammation, neoplasia, the inappropriate accumulation of mucous within the gallbladder, or the development of gallstones.2,6 There has been one report of a guinea pig that was diagnosed with a cholelith that survived surgical correction via cholecystectomy.2 Studies in dogs have shown a positive correlation between hyperadrenocorticism and cholestasis.6

Information on endocrine diseases in guinea pigs is limited at this time. In females, ovarian cyst formation would be a likely differential for bilateral truncal alopecia and abdominal pain. However, the unusual presentation of these signs in addition to thin skin and cachexia in a male guinea pig prompted endocrinologic testing. Reference ranges for resting cortisol and ACTH stimulation tend to vary greatly due to the variety of methods used for sample collection in the few studies that have been completed in guinea pigs.1,3,7 It appears that increased stress during diagnostic procedures may increase falsely increase cortisol. The previous cases confirmed via ACTH stimulation utilized salivary samples as described by Fenske as a minimally invasive method of sample collection.1 Although salivary testing was not available at LSU VTH, this false elevation is likely not of concern, as the patient’s cortisol was nearly 20 times the upper limit of the reference values also obtained by venipuncture.

Reports in guinea pigs, dogs, and humans have shown a correlation between corticosteroid exposure and cholestatic disease. In a retrospective case-control study of 78 dogs, patients with hyperadrenocorticism were 29 times more likely to develop a gallbladder mucocele.6 A similar relationship may exist in hyperthyroidism.6 Although the presented case had low total T4, this may indicate euthyroid sick syndrome, in which T4 levels are artificially lowered in the face of disease. Despite the recognized correlation between hyperadrenocorticism and cholestatic disease, the exact mechanism remains unknown. One study showed methylprednisolone administration in guinea pigs caused increased bile volume and bile cholesterol levels. These changes predisposed subjects to gallbladder sludge and/or cholelithiasis.8

Vitamin C deficiency may also influence endocrine health. Like humans, guinea pigs are dependent upon dietary sources of this nutrient. It has been long understood that hypovitaminosis C (scurvy) negatively affects collagen production. A study in adult male guinea pigs showed that a marginal deficiency in vitamin C led to a nearly 4-fold increase in cortisol levels.3 These individuals also exhibited signs of hyperadrenocorticism. Prior studies demonstrated adrenal hypertrophy and associated hypercortisolemia due to hypovitaminosis C.3 Though many commercial diets are formulated to supply this nutrient, it can degrade with light exposure, heat exposure, and time. With the slow rate at which a single-pet household may utilize pelleted feed, this loss of nutrients could lead to hypovitaminosis C and increased serum cortisol.

 

Summary

In conclusion, HAC may be underdiagnosed in guinea pigs and testing is warranted in the presence of ample clinical suspicion. Endocrine disease may also predispose patients to cholestatic disease. Blood sampling and imaging to rule in/out cholestasis could be considered in these patients. Appropriate diet selection and storage of feed may affect pets’ endocrine health. More information on endocrine diseases, including diagnostic methods and reference intervals, treatment, and prevention is needed in this species.

 

References