Successful treatment of a cat with primary hypoadrenocorticism and severe hyponatremia with desoxycorticosterone pivalate (DOCP)

Abstract

A 6-year-old, castrated male Siamese cat was diagnosed with primary hypoadrenocorticism, confirmed by an adrenocorticotopic hormone (ACTH) stimulation test documenting both hypocortisolism and hypoaldosteronism. The cat was successfully treated using a combination of prednisolone and desoxycorticosterone pivalate (DOCP). This case demonstrates that DOCP can be used successfully as mineralocorticoid supplementation in cats with hypoadrenocorticism and may have a longer therapeutic duration than that in dogs.

Hypoadrenocorticism is an endocrinopathy characterized by inadequate production of corticosteroids and mineralocorticoids by the adrenal cortex. Primary hypoadrenocorticism is an uncommon disease in cats, with approximately 40 reported cases (1). This disease is commonly described in humans and dogs, and the etiology is most commonly immune-mediated destruction of the adrenal cortex (2–4). The cause of primary hypoadrenocorticism in cats is unknown, although a previous case series did show lymphocytic inflammation of the adrenal glands, suggesting a similar immune-mediated process (5).

Case description

A 6-year-old castrated male Siamese cat was presented to the University of Georgia Veterinary Teaching Hospital with a 1-month history of decreased appetite that had progressed to anorexia. The cat weighed 4.16 kg, and had a documented weight loss of 2.2 kg over the past 8 mo. The cat had been evaluated by his primary veterinarian 18 d before presentation to the referral institution. Biochemical information obtained at that time revealed a hyponatremia (Table 1), but no other pertinent changes were noted. Subcutaneous isotonic crystalloids were administered, but no other therapies were initiated at that time. Vaccinations were current, and the cat lived exclusively indoors with his littermate.

Table 1.

Initial complete blood cell count and serum chemistry profiles performed on the day of presentation

Complete blood cell count			Serum chemistry profile
Parameter	Result	Reference interval	Parameter	Result	Reference interval
Hct (%)	37.2	30.7 to 46.1	BUN (mmol/L	9.28	6.89 to 11.89
RBC (× 106/μL)	8.35	4.9 to 9.8	Creatinine (μmol/L)	97.2	53.0 to 159.1
Hgb (g/L)	121	103 to 161	Total protein (g/L)	54	55 to 72
MCV (fl)	44.6	41 to 57	Albumin (g/L)	35	27 to 40
MCHC (g/L)	326	306 to 367	ALKP (U/L)	24	1.0 to 48.0
Platelets (× 103/μL)	Clumped		ALT (U/L)	42	27 to 100
WBC (× 103/μL)	3.5	5.8 to 20.5	Glucose (mmol/L)	4.7	3.0 to 6.3
Segmented neutrophils (× 103/μL)	2.485	2.5 to 12.5	Sodium (mmol/L)	127	148 to 155
Band neutrophils (× 103/μL)	0	0 to 0.3	Potassium (mmol/L)	5.4	3.3 to 5.7
Lymphocytes (× 103/μL)	0.665	1.5 to 7	Chloride (mmol/L)	96	114 to 126
Monocytes (× 103/μL)	0.105	0 to 0.9	Calcium (mmol/L)	2.4	2.3 to 2.7
Eosinophils (× 103/μL)	0.245	0 to 0.8	Phosphorus (mmol/L)	1.7	0.9 to 1.9
Basophils (× 103/μL)	0	0 to 0.2	T bili (μmol/L)	1.7	0.0 to 1.9

RBC — red blood cells; Hct — hematocrit; MCV — mean corpuscular volume; MCHC — mean corpuscular hemoglobin concentration; WBC — white blood cells; BUN — blood urea nitrogen; ALKP — alkaline phosphatase; ALT — alanine aminotransferase; T bili — total bilirubin.

Upon physical examination, the cat was lethargic and hypothermic (36.4°C), with a relative bradycardia (150 beats/min), and normal respiratory rate and character. The cat was in poor body condition (BCS 3/9), had weak femoral pulses, and mild to moderate (6% to 8%) dehydration. No abnormalities were found on thoracic auscultation or abdominal palpation.

Hematologic and biochemical testing performed on initial presentation is displayed in Table 1. Pertinent changes included the lack of a leukogram attributable to stress or inflammation, concentrated urine, and a marked hyponatremia [127 mmol/L; reference interval (RI): 148 to 155 mmol/L]. Potassium concentration was normal (5.4 mmol/L; RI: 3.3 to 5.7 mmol/L), but there was a low sodium-to-potassium ratio (26.4; RI: < 27) (6). Urine collected by cystocentesis had a specific gravity of 1.048, pH of 6.5, trace protein, and an inactive sediment. Thoracic radiographs showed evidence of microcardia. Abdominal ultrasonography did not reveal any abnormalities, including adrenal glands that were normal in size and symmetry.

Intravenous fluid therapy was initiated with the purpose of fluid resuscitation and conservative sodium replacement. Following volume repletion, the cat had persistent hyponatremia. A thyroid profile was within normal limits. The cat had a decreased serum osmolality with an increased urine osmolality, but fractional excretion of sodium was calculated to be 0.2% (RI: < 1%); therefore, antidiuretic hormone (ADH) secretion was determined to be appropriate. Baseline serum cortisol and aldosterone concentrations were determined and measured again 1 h after intravenous administration of a synthetic adrenocorticotropic hormone (0.125 μg cosyntropin, Cortrosyn; Amphastar Pharmaceuticals, Rancho Cucamonga, California, USA). The assays for cortisol (Immulite 1000 chemiluminescent enzyme immunoassay; University of Georgia Diagnostic Laboratory, Athens, Georgia, USA), and aldosterone (Radioimmunoassay, coat-a-count; Michigan State University Diagnostic Center for Population and Animal Health, East Lansing, Michigan, USA) have been previously validated in cats (7,8). The results of these assays are displayed in Table 2, and demonstrate a lack of response to adrenocorticotropic hormone (ACTH) stimulation. Based on these results, a diagnosis of hypoadrenocorticism was established.

Table 2.

Serum cortisol and aldosterone concentrations used for the diagnosis of hypoadrenocorticism

	Concentration	Reference interval
Baseline cortisol (nmol/L)	49.7	13.8 to 96.6
1 h post-ACTH cortisol (nmol/L)	44.1	96.6 to 206.9
Baseline aldosterone (pmol/L)	< 14	194 to 388
1 h post-ACTH aldosterone (pmol/L)	< 14	277 to 721

Treatment for hypoadrenocorticism was initiated with injectable dexamethasone sodium phosphate (APP Pharmaceuticals, Schaumburg, Illinois, USA), 0.05 mg/kg body weight (BW), IV, q24h. The cat was also administered desoxycorticosterone pivalate (DOCP, Percorten-V; Novartis Animal Health US, Greenfield, Indiana, USA), 2.2 mg/kg BW, IM. Serum electrolyte concentrations were checked approximately 24 h after initiation of these therapies, and the sodium concentration was noted to be improving. Due to financial concerns the cat was discharged from the hospital 48 h after starting hormone replacement. The cat was started on oral prednisolone (Prednistab; Butler Schein Animal Health, Dublin, Ohio, USA), 0.5 mg/kg BW, q24h.

Six days later, the cat was more active and had regained a normal appetite. A serum biochemical profile showed a mild hypernatremia and normal potassium concentration. Initially, electrolytes were monitored weekly (Table 3) to determine the timing of the next DOCP dose. Mild hyponatremia was noted 44 d after initial diagnosis, and thus a second dose of DOCP was administered. At the time this manuscript was submitted, the cat was clinically normal at day 414 post-diagnosis, managed on a daily oral dose of corticosteroids (Prednisolone 0.2 mg/kg BW per day) and intramuscular administration of DOCP every 35 to 40 d.

Table 3.

Serum electrolyte values prior to and intermittently throughout treatment

Day	Sodium RI: 148 to 155 mmol/L	Potassium 3.3 to 5.7 mmol/L	Na:K ratio > 27
−18	130	4.5	28.8
0	127	4.8	26.4
1	127	5.4	23.5
9	156	4.6	33.9
23	153	3.2	47.8
29	152	4.1	37.1
36	151	4.1	36.8
44	146	4.5	32.4
64	156	4.4	35.4
78	152	4.1	37.0
81	144	3.9	36.9
90	154	4	38.5
112	150	4.6	32.6
177	150	4.2	35.7
264	148	4.4	33.6
378	151	4.3	35.1

Discussion

To our knowledge, this is the first report of the use of DOCP with monitored dosing intervals to treat hypoadrenocorticism in the cat. Most reported feline cases describe the use of fludrocortisone acetate for mineralocorticoid supplementation (5,9–12). In a study of 60 dogs with primary hypoadrenocorticism, DOCP was used to supplement mineralocorticoids in all cases (4). The interval between injections was determined to be between 25 and 28 d in all dogs, but several of those patients did not show alterations in their electrolytes until more than 30 d (13–15). The use of DOCP is not well-described in cats. In a case series of 10 cats with primary hypoadrenocorticism, DOCP was used in 3 of the cats, but time to effect and interval of administration were not reported (5).

The cat herein had a marked hyponatremia that was not responsive to fluid resuscitation. After a dose of DOCP was administered, the sodium trended toward normal within 24 h and had normalized by day 8. Frequent monitoring of the electrolyte concentration was done to identify the ideal dose interval for DOCP in this cat (Table 3). The first biochemical abnormality noted was hyponatremia; therefore, electrolytes were monitored frequently to determine the onset of hyponatremia. The cat did not require another injection of DOCP until 44 d after the initial dose. This may suggest that the dose given initially was too high. A previous study in dogs showed that lower than recommended doses of DOCP may provide adequate mineralocorticoid supplementation (16). Further investigation into the use of DOCP in cats is necessary to characterize its pharmacokinetics. The cat in this report has continued to receive his dose of DOCP approximately every 40 d, but this cannot be extrapolated to all cats with hypoadrenocorticism.

While primary hypoadrenocorticism is an uncommon diagnosis in feline patients, there are similarities among the cats reported in the literature. The cat in this report was presented due to anorexia, weight loss, and lethargy, which is consistent with previous reports (1,5–9,12,17,18). Gastrointestinal signs in cats generally manifest as anorexia, as opposed to the vomiting and diarrhea often noted in dogs (9).

Suspicion of primary hypoadrenocorticism involves identification of compatible clinical signs and suggestive laboratory findings (5,9–12). The cat in this report did not show evidence of hyperkalemia despite significant hyponatremia. The sodium:potassium ratio was only mildly decreased. In the initial case series of cats with primary hypoadrenocorticism, 90% of cats were hyperkalemic at the time of diagnosis (5); however, some had normal serum potassium concentrations. In more recent case reports, hyperkalemia is a common finding but tends to be mild. It is unclear why this cat had a normal serum potassium level, especially with an undetectable serum aldosterone concentration. It is possible that the cat’s normal potassium was a reflection of decreased dietary intake due to prolonged anorexia.

Definitive diagnosis of hypoadrenocorticism is made by demonstrating a lack of cortisol stimulation through the administration of a synthetic adrenocorticotropic hormone (19). Serum cortisol concentrations in the majority of other published cases of feline hypoadrenocorticism were undetectable by the assay (5,9,10). However, in the largest case study of 10 cats the range of serum cortisol reached 30.35 to 35.87 nmol/L (5), which is similar to the serum concentrations found in this cat. In this case, the diagnosis of hypoadrenocorticism was made based on the lack of adrenocortical hormone stimulation and serum cortisol levels < 55.2 nmol/L (19).

There are aspects of this case that do not support the diagnosis of hypoadrenocorticism. These include the lack of hyperkalemia and the finding of concentrated urine and normal adrenal glands on abdominal imaging. The strength of this diagnosis could have been improved by submitting plasma for endogenous ACTH concentration, which should show an increase (1,5). Unfortunately, this test was not performed. The lack of cortisol and aldosterone response to ACTH stimulation, the lack of evidence of a secondary cause, and positive response to therapy supported our diagnosis of primary hypoadrenocorticism (19).

In conclusion, primary hypoadrenocorticism should be considered as a differential for hyponatremia in cats, even without the expected high or high-normal serum potassium. In addition, desoxycorticosterone pivalate (DOCP) can be used as adequate mineralocorticoid supplementation, and can induce dramatic improvement in serum electrolytes within 48 h of administration. Further research into the dosing intervals for DOCP is necessary for cats. CVJ