Plasma pro-opiomelanocortin, pro-adrenocorticotropin hormone, and pituitary adenoma size in dogs with Cushing's disease

It is difficult to predict the size of pituitary corticotroph tumors in dogs with Cushing's disease (pituitary-dependent hyperadrenocorticism [PDH]) without pituitary imaging techniques. The purpose of this study was to examine the relationship between plasma adrenocorticotropin hormone (ACTH) precursor concentration and pituitary size in dogs with Cushing's disease. Plasma concentrations of ACTH precursors (pro-opiomelanocortin [POMC]/pro-ACTH) and pituitary tumor height/brain area were measured in 36 dogs with pituitary corticotroph adenomas of various sizes. There was a correlation between tumor size (measured as the pituitary tumor height/brain area ratio [P/B]) and POMC/pro-ACTH concentration (r = .70; P < .0001). Dogs with P/B > or = 0.40 x 10(-2) mm(-1) had higher concentrations of ACTH precursors than dogs with P/B < 0.40 x 10(-2) mm(-1) (median concentration 85 pmol/L, range 15-1,350 pmol/L, n = 14 versus 15 pmol/L, range 15-108 pmol/L, n = 22; P < .0001). With a threshold of 35 pmol/L of POMC/pro-ACTH concentration, the estimated sensitivity and specificity of the kit were 93% (95% confidence interval [CI], 79-100%) and 86% (95% CI, 73-100%), respectively. We interpret these data as indicating that measurement of POMC and pro-ACTH might be of value in the characterization of tumor size in dogs with Cushing's disease. Low POMC/pro-ACTH concentrations make it unlikely that a large pituitary tumor exists in dogs with PDH.     

Dynamic adrenal function testing in eight dogs with hyperadrenocorticism associated with adrenocortical neoplasia.

The results of adrenocorticotropin (ACTH) stimulation and low-dose dexamethasone suppression tests (LDDST) were evaluated retrospectively in eight dogs with clinical signs of hyperadrenocorticism arising from functional adrenocortical tumours, and compared with the results from 12 dogs with confirmed pituitary-dependent hyperadrenocorticism (PDH). The post-ACTH cortisol concentration in the dogs with adrenocortical tumours ranged from 61 to 345-6 nmol/litre (median 251.5 nmol/litre) and they were within the reference range (150 to 450 nmol/litre) in five and unexpectedly low (< 150 nmol/litre) in three dogs. Both the basal and post-ACTH cortisol concentrations were significantly lower in the dogs with adrenocortical neoplasia than in the dogs with PDH. Eight hours after the LDDST, only two of six dogs with adrenocortical tumours had a cortisol concentration above 30 nmol/litre, and the median resting, three, and eight-hour cortisol concentrations were 31.5, 23.0, and 22.7 nmol/litre respectively. There was no significant cortisol suppression during the LDDST, although interpretation was complicated by the low cortisol concentrations, but two dogs showed a pattern of apparent suppression. Two dogs with adrenal tumours showed a diagnostically significant increase in 17-OH-progesterone concentration in response to ACTH although their cortisol concentrations did not increase greatly. These results differ from previous reports of the response of functional adrenal tumours to dynamic endocrine tests.     

Effect of Desmopresssin in Normal Dogs and Dogs with von Willebrand's Disease

Desmopressin acetate (DDAVP(R)), a synthetic analogue of vasopressin was slowly administered intravenously to 12 healthy dogs of various breeds and 10 Doberman Pinschers with mild-to-moderate type I von Willebrand's disease at a dose of 0.3, 1.0 and 3.0 micro g/kg body weight. Plasma von Willebrand factor:antigen was measured by an electroimmunoassay prior to and 30, 60, 90, 120 and 180 minutes after desmopressin infusion. Desmopressin induced only very modest and statistically insignificant increases in von Willebrand factor in both groups. We conclude that the response to desmopressin as measured by circulating von Willebrand factor is much less pronounced in healthy dogs and in Doberman Pinschers with von Willebrand's disease than in humans.     

Mitotane (o, p''-DDD) Treatment of 200 Dogs with Pituitary-Dependent Hyperadrenocorticism

Two hundred dogs with pituitary dependent hyperadrenocorticism (PDH) were treated with mitotane at an initial daily dosage of 21 to 69 mg/kg (mean = 45.2 mg/kg) for 5 to 14 days. During the induction period, 194 of the dogs also were given daily maintenance dosages of a glucocorticoid. Fifty of the dogs exhibited one or more adverse effects during initial induction, including weakness, vomiting, anorexia, diarrhea, and ataxia. After completion of the induction period, repeat ACTH stimulation testing revealed significant decreases in mean serum cortisol concentrations when compared with initial values. Twenty-five dogs, however, still responded to exogenous ACTH with serum cortisol concentrations above normal resting range, necessitating daily treatment for an additional 5 to 55 days. In contrast, 70 of the 200 dogs had low post-ACTH serum cortisol concentrations after the induction period. These subnormal serum cortisol concentrations generally increased spontaneously to within normal resting range 2 to 6 weeks after cessation of mitotane. In 184 dogs, mitotane was continued at an initial mean maintenance dosage of 49 mg/kg administered weekly in two to three divided doses. Of these dogs, 107 had one or more relapses of hyperadrenocorticism during treatment. In the 75 dogs that had one relapse, the median maintenance dosage was increased by approximately 35%, whereas the median maintenance dosage in the 32 dogs having two or more relapses was eventually increased by 225% over the initial dosage. After a mean maintenance treatment time of 2.0 years, the final maintenance dosage required in the 184 dogs ranged from 26.8 to 330 mg/kg/week.(ABSTRACT TRUNCATED AT 250 WORDS)     

Secretion of sex hormones in dogs with adrenal dysfunction

OBJECTIVE: To evaluate adrenal sex hormone concentrations in response to ACTH stimulation in healthy dogs, dogs with adrenal tumors, and dogs with pituitary-dependent hyperadrenocorticism (PDH). DESIGN: Prospective study. ANIMALS: 11 healthy control dogs, 9 dogs with adrenal-dependent hyperadrenocorticism (adenocarcinoma [ACA] or other tumor); 11 dogs with PDH, and 6 dogs with noncortisol-secreting adrenal tumors (ATs). PROCEDURE: Hyperadrenocorticism was diagnosed on the basis of clinical signs; physical examination findings; and results of ACTH stimulation test, low-dose dexamethasone suppression test, or both. Dogs with noncortisol-secreting ATs did not have hyperadrenocorticism but had ultrasonographic evidence of an AT. Concentrations of cortisol, androstenedione, estradiol, progesterone, testosterone, and 17-hydroxyprogesterone were measured before and 1 hour after i.m. administration of 0.25 mg of synthetic ACTH. RESULTS: All dogs with ACA, 10 dogs with PDH, and 4 dogs with ATs had 1 or more sex hormone concentrations greater than the reference range after ACTH stimulation. The absolute difference for progesterone, 17-hydroxyprogesterone, and testosterone concentrations (value obtained after ACTH administration minus value obtained before ACTH administration) was significantly greater for dogs with ACA, compared with the other 3 groups. The absolute difference for androstenedione was significantly greater for dogs with ACA, compared with dogs with AT and healthy control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with ACA secrete increased concentrations of adrenal sex hormones, compared with dogs with PDH, noncortisol-secreting ATs, and healthy dogs. Dogs with noncortisol-secreting ATs also have increased concentrations of sex hormones. There is great interdog variability in sex hormone concentrations in dogs with ACA after stimulation with ACTH.     

Formal pathogenesis, average age and breed distribution in the comparison of 61 Lysodren-treated and 36 untreated cases of canine hyperadrenocorticism which were dissected in the years 1975 to 1991 at the Institute for Veterinary Pathology of the Free University of Berlin]

61 Lysodren -treated dogs with hyperadrenocorticism are compared with 36 untreated dogs with the same disease. 75.14% of the treated dogs had pituitary-dependent-hyperadrenocorticism (PDH) whereas this diagnosis was found in 63.89% of the untreated dogs. A functioning adrenocortical tumor (FAT) was found in 13.11% of the treated dogs but was evident in 22.22% of the untreated dogs. Simultaneous pituitary and adrenal Cushing's syndrome (PDH/FAT) were found in 11.48% of the treated and 8.33% of the untreated cases. Sex distribution was equal in both groups. Overall slightly more females than males were affected by the disease. Poodles (38.14%) and dachshunds (23.71%) were the mainly affected races. Race-distribution of diseased animals is compared to the overall race-distribution in a ten years statistic (1981-1990) of all necropsied animals (Walter und Schwegler, 1992). The mean age of Lysodren -treated dogs with a PDH diagnosis (10.0 years) is lower as the mean age of untreated dogs with the same diagnosis (10.3 years). Reasons for this unexpected finding are discussed.     

Comparison of mitotane treatment for adrenal tumor versus pituitary-dependent hyperadrenocorticism in dogs.

The purpose of this study was to determine the sensitivity of dogs with hyperadrenocorticism to treatment with the adrenocorticolytic agent mitotane. Specifically, we looked for differences in response to treatment using this drug in dogs with adrenocortical tumors (adrenal tumor hyperadrenocorticism, ATH) vs those with pituitary-dependent hyperadrenocorticism (PDH). For inclusion in this study, each dog must have had clinical signs, data base laboratory abnormalities, and endocrine screening test results consistent with the diagnosis of hyperadrenocorticism. Further, each dog had to have been treated for at least 6 months with mitotane and have histologic evidence for adrenocortical or pituitary neoplasia (all dogs were necropsied). Thirteen dogs with ATH (8 carcinomas, 5 adenomas) were identified. The ages and body weights of these 13 dogs were computer-matched to 13 dogs with PDH. All dogs were initially treated with approximately 50 mg of mitotane/kg/d of body weight. Reexaminations were performed after 7, 30, 90, and 180 days of treatment. Individual dosages varied widely after the initial 5 to 12 days of treatment. The mean (+/- SD) dose of mitotane (mg/kg/d) for the first 7 days of treatment was 47.5 +/- 9.4 for dogs with ATH vs 45.7 +/- 11.9 for dogs with PDH. The mean plasma cortisol concentrations 1 hour after ACTH administration at the 7-day recheck were significantly higher in dogs with ATH (502 +/- 386 nmol/L) than in dogs with PDH (88 +/- 94 nmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum Inhibin Concentration in Dogs with Adrenal Gland Disease and in Healthy Dogs

Background

Studies in humans identified the synthesis and secretion of inhibin from adrenocortical tumors, but not pheochromocytoma (PHEO). Inhibin has not been examined in dogs as a serum biomarker for adrenal gland tumors.

Objective

To determine serum inhibin concentration in dogs with adrenal gland disease and in healthy dogs.

Animals

Forty‐eight neutered dogs with adrenal disease including pituitary‐dependent hyperadrenocorticism (PDH, 17), adrenocortical tumor (18), and PHEO (13), and 41 healthy intact or neutered dogs.

Methods

Prospective observational study. Dogs were diagnosed with PDH, adrenocortical tumor (hyperadrenocorticism or noncortisol secreting), or PHEO based on clinical signs, endocrine function tests, abdominal ultrasound examination, and histopathology. Inhibin concentration was measured by radioimmunoassay in serum before and after ACTH stimulation, and before and after treatment.

Results

In neutered dogs, median inhibin concentration was significantly higher in dogs with adrenocortical tumors (0.82 ng/mL) and PDH (0.16 ng/mL) than in dogs with PHEO and healthy dogs (both undetectable). Median inhibin concentration was significantly higher in dogs with adrenocortical tumors than in those with PDH and decreased after adrenalectomy. Median inhibin concentration was significantly higher in intact than in neutered healthy dogs and was similar in pre‐ and post‐ACTH stimulation. Sensitivity, specificity, and accuracy of serum inhibin concentration for identifying an adrenal tumor as a PHEO were 100, 88.9, and 93.6%, respectively.

Conclusions and Clinical Importance

Adrenocortical tumors and PDH but not PHEOs are associated with increased serum inhibin concentration; undetectable inhibin is highly supportive of PHEO in neutered dogs with adrenal tumors.     

Ultrasonographic adrenal gland measurements in clinically normal small breed dogs and comparison with pituitary-dependent hyperadrenocorticism

Ultrasonography is a sensitive and specific screening method for assessing the adrenal glands. The upper limit of the normal adrenal gland width is used as 7.5 mm. It is not known if adrenal gland width remains consistent with body weight. A reliable criterion of adrenal gland width in small breed dogs should be established. Small breed dogs with body weights of less than 10 kg were divided into two groups: 189 normal dogs and 22 dogs with pituitary-dependent hyperadrenocorticism (PDH). A retrospective study was conducted on dogs seen between January 1, 2006, and February 10, 2008. One hundred eighty-nine dogs of 14 different small breeds were enrolled in the normal adrenal gland group; the median gland width was 4.20 mm. Twenty-two dogs were in the PDH group; the median gland width was 6.30 mm. The cut-off value between normal adrenal glands and PDH was 6.0 mm. This figure gave a sensitivity and specificity of 75 and 94%, respectively, for detecting PDH. The adrenal gland appeared as a peanut shape with homogeneous hypoechoic parenchyma in normal dogs and in most dogs with PDH as well. This study was performed in a large population of small breed dogs and suggests that the normal adrenal gland size in small breed dogs is smaller than previously reported. We believe that a cut-off of 6.0 mm may be used as the criterion for differentiating a normal adrenal gland from adrenal hyperplasia.     

Ultrasonographic Characteristics of the Adrenal Glands in Dogs With Pituitary-Dependent Hyperadrenocorticism: Comparison With Normal Dogs

Ultrasonographic evaluation of the adrenal glands was performed in 10 dogs with pituitary-dependent hyperadrenocorticism (PDH) and in 10 age- and weight-matched healthy control dogs. Thickness, shape, and echogenicity were determined for each adrenal gland. Adrenal thickness in dogs with PDH (median, 10 mm-left; 8.5 mm-right) was significantly greater than thickness in control dogs (median, 6 mm-left; 6 mm-right). Other ultrasonographic characteristics associated with PDH included bilaterally symmetrical adrenomegaly and maintenance of normal adrenal shape. Adrenal echogenicity was homogeneous and less than that of the adjacent renal cortex in 8 of 10 dogs with PDH and in 10 of 10 control dogs. Heterogenous echogenicity was present in 2 of 10 dogs with PDH, and was associated with nodular cortical hyperplasia in one of those dogs. Results of this study confirm the difference in sonographic appearance between PDH-induced bilateral cortical hyperplasia and functional adrenocortical neoplasia, and show a difference in so-nographically determined adrenal size between healthy dogs and dogs with PDH. J Vet Intern Med 1996; 10:110–115. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

Vasopressin secretion in response to osmotic stimulation and effects of desmopressin on urinary concentrating capacity in dogs with pyometra

OBJECTIVE: To determine vasopressin (VP) secretory capacity during osmotic stimulation and the response to desmopressin treatment in dogs with pyometra and control dogs. ANIMALS: 6 dogs with pyometra before and after ovariohysterectomy and 6 control dogs. PROCEDURE: Urine osmolality (Uosm) was measured during 12 hours. Values measured on the first day defined the basal Uosm pattern. On the second day, dogs were given desmopressin to induce a desmopressin-stimulated Uosm pattern. On day 3, the VP response to osmotic stimulation was examined. RESULTS: Median Uosm on day 1 was 340 mOsm/kg (range, 104 to 1,273 mOsm/kg) and 807 mOsm/kg (range, 362 to 1,688 mOsm/kg) in dogs with pyometra before and after surgery, respectively, and 1,511 mOsm/kg (range, 830 to 1,674 mOsm/kg) in control dogs. Median Uosm during desmopressin treatment was 431 mOsm/kg (range, 168 to 1,491 mOsm/kg) and 1,051 mOsm/kg (range, 489 to 1,051 mOsm/kg) in dogs with pyometra before and after surgery, respectively, and 1,563 mOsm/kg (range, 1,390 to 2,351) in control dogs. In dogs with pyometra, threshold for VP secretion was lower before surgery (median, 340 mOsm/kg; range, 331 to 366 mOsm/kg) than after surgery (median, 358 mOsm/kg; range, 343 to 439 mOsm/kg) or in control dogs (median, 347 mOsm/kg; range, 334 to 360 mOsm/kg). Highest maximum plasma VP values were found in dogs with pyometra. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with pyometra had increased urine concentration in response to desmopressin but not to the degree of control dogs, whereas VP secretory ability was not reduced.     

Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism

The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (+/- SD) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 +/- 1.6 micrograms/dl), lowest in 15 control dogs (1.3 +/- 0.5 micrograms/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH; 3.4 +/- 1.2 micrograms/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P less than 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with PDH; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P less than 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 +/- 0.2 microgram/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later. Twenty dogs with hyperadrenocorticism (11 with PDH, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with PDH failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P less than 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (ACTH).(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic imaging findings and endocrine test results in dogs with pituitary-dependent hyperadrenocorticism that did or did not have neurologic abnormalities: 157 cases (1989-2005)

OBJECTIVE: To compare imaging findings in dogs with pituitary-dependent hyperadrenocorticism (PDH) that did or did not have neurologic abnormalities. Design-Retrospective case series. ANIMALS: 157 dogs with PDH that did (n = 73) or did not (84) have neurologic abnormalities. PROCEDURES: Medical records were reviewed for the presence and nature of clinical signs of CNS disease, and computed tomographic and magnetic resonance images were reviewed for evidence of a pituitary tumor. RESULTS: 60 of the 84 (71%) dogs without neurologic abnormalities and 48 of the 73 (66%) dogs with neurologic abnormalities had a detectable pituitary tumor. However, 17 of the 84 (20%) dogs without neurologic abnormalities had a pituitary macrotumor (ie, a tumor > or = 10 mm in height), and 41 of the 73 (56%) dogs with neurologic abnormalities did not have a detectable pituitary tumor or had a pituitary microtumor. Vague signs of CNS dysfunction (ie, lethargy, inappetence, and mental dullness) were more specific for detection of pituitary macrotumors than were CNS-specific signs (ie, seizure or blindness). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that there was no apparent relationship between a pituitary tumor and development of neurologic abnormalities in dogs with PDH. In addition, neurologic abnormalities in dogs with pituitary macrotumors were often vague (ie, lethargy, inappetence, and mental dullness).     

Plasma concentrations of ACTH precursors correlate with pituitary size and resistance to dexamethasone in dogs with pituitary-dependent hyperadrenocorticism

This study was performed to determine whether in dogs with pituitary-dependent hyperadrenocorticism (PDH) excessive release of adrenocorticotrophic hormone (ACTH) is accompanied by secretion of ACTH precursor molecules. In addition, we investigated whether the plasma ACTH precursor concentrations were correlated with the size of the pituitary gland and with the degree of resistance to negative glucocorticoid feedback. In 72 dogs with PDH, the plasma ACTH precursor concentration was determined by calculating the difference between the results of a radioimmunoassay (RIA) in which besides ACTH, ACTH precursors were also measured and a highly specific immunoradiometric assay (IRMA) using a polyclonal antibody against ACTH. The degree of resistance to glucocorticoid feedback was established by determining the effect of dexamethasone administration (0.1 mg/kg) on the urinary corticoid/creatinine ratio. The pituitary height/brain area (P/B) ratio, determined by computed tomography, was used as a measure for the size of the pituitary gland. The plasma ACTH precursors concentration ranged from 18 to 2233 ng/L (median 93 ng/L). In 38 dogs, the pituitary was enlarged and plasma ACTH precursors concentrations in these dogs (median 130 ng/L, range 24–2233 ng/L) were significantly (P<0.05) higher than those in the dogs without pituitary enlargement (median 72 ng/L, range 18–481 ng/L). In concordance, P/B ratios correlated significantly with plasma ACTH precursor concentrations (r=0.35, P<0.01). In addition, the P/B ratios were significantly correlated with the degree of dexamethasone resistance (r=0.42, P<0.001). Plasma ACTH precursor concentrations in the dexamethasone-resistant dogs (median 210 ng/L, range 24–628 ng/L) were significantly higher (P<0.01) than those in the dexamethasone-sensitive dogs (median 72 ng/L, range 18–2233 ng/L). Similarly, the degree of dexamethasone resistance was also significantly correlated with the plasma ACTH precursor concentrations (r=0.33, P<0.01). Dogs with an elevated plasma -MSH concentration (n=14) had significantly (P<0.001) higher plasma ACTH precursor concentrations (median 271 ng/L, range 86–2233 ng/L) than dogs with non-elevated -MSH (median 73 ng/L, range 18–481 ng/L). In addition, the plasma concentrations of -MSH correlated significantly with both plasma ACTH precursor concentrations (r=0.53, P<0.001) and P/B ratios (r=0.26, P<0.05). In conclusion, in all dogs with PDH the ACTH concentrations determined by the RIA were higher than the concentrations measured by IRMA indicating the presence of circulating ACTH precursors. High plasma ACTH precursor concentrations were especially found in dexamethasone-resistant dogs with large corticotroph adenomas, some of them probably of PI origin. In the association of large corticotroph adenoma, dexamethasone resistance and high plasma concentrations of ACTH precursors, the decreased sensitivity of the corticotroph cells to glucocorticoid feedback may play a pivotal role.     

The effects of desmopressin on hemostatic parameters in the normal dog.

Seven normal unanesthetized dogs were infused with desmopressin in saline (doses 0.2, 0.4 and 0.6 micrograms/kg i.v.) or saline alone, on separate occasions in order to determine the effects of desmopressin on circulating factor VIII coagulant and factor VIII-related antigen activities, on partial thromboplastin times and prothrombin times, on blood platelet count and packed cell volume, and on serum osmolarity. Desmopressin caused a rapid dose-dependent elevation in both factor VIII activities peaking at 30-60 minutes postinfusion. At a dosage of 0.6 microgram/kg desmopressin induced rises in factor VIII coagulant activity and factor VIII-related antigen of 150% and 198% of the preinfusion levels respectively, while the half disappearance times were approximately five and six hours respectively. The other parameters were not significantly affected by even the highest dose of desmopressin used. These results indicate that normal dogs respond to desmopressin in a manner similar to man. The major differences are in the dosage required to produce comparable effects (higher in dogs), and in the fact that the factor VIII-related antigen activity consistently responds to a greater degree than the coagulant activity. It is concluded that desmopressin may have particular value in stimulating elevations in plasma factor VIII-related antigen in dogs deficient in this plasma protein. Six dogs were pretreated with the endorphin inhibitor, naloxone, (0.04 mg/kg I.V.) or sterile saline, three minutes prior to infusion with desmopressin at a dose of 0.6 microgram/kg i.v.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diseases of the adrenal cortex of dogs and cats

The most common cause of hypoadrenocorticism in dogs is idiopathic immune-mediated destruction of the adrenal cortex. Other causes include anterior pituitary insufficiency, pituitary or adrenal neoplasia, acute withdrawal of exogenous corticosteroids, and mitotane toxicity. Females are affected more often than males; only 1 feline case has been documented. Animals 2-5 years old are most commonly affected. Clinical signs include lethargy, weakness, weight loss, anorexia, vomiting, diarrhea and bradycardia. Hematologic and biochemical changes can include eosinophilia, lymphocytosis, anemia, hyperkalemia, hyponatremia and hypercalcemia. Diagnosis is by finding negligible resting levels of plasma cortisol and no response to ACTH administration, and a serum Na:K ratio of 20:1 or less. Treatment involves restoring fluid volume, correcting acidosis, and supplementing salt and glucocorticoids. Daily oral use of prednisone at 0.05 mg/kg can safely maintain most affected dogs. Some dogs only require glucocorticoids in stressful situations. Iatrogenic secondary adrenocortical insufficiency (iatrogenic Cushing's disease) may result from a single injection of long-acting glucocorticoids or from long-term use. Clinical signs are the same as for natural hyperadrenocorticism, but endogenous cortisol release is suppressed. Treatment is gradual withdrawal of the offending glucocorticoid and elimination of the cause that initially prompted glucocorticoid therapy.     

Diagnostic efficacy of plasma ACTH-measurement by a chemiluminometric assay in canine hyperadrenocorticism

This retrospective study was performed to investigate the diagnostic efficacy of the chemiluminometric ACTH-measurement to differentiate between pituitary and adrenal dependent hyperadrenocorticism (HAC) in dogs. 49 dogs with pituitary HAC, 10 dogs with adrenal HAC and 1 dog with a combination of both pathologies were included. Dogs with HAC like symptoms, where HAC had been ruled out, served as controls (n = 18). All dogs with adrenal HAC, as well as 9 dogs with pituitary HAC had an ACTH concentration below the detection limit of 2.2 pmol/l (10 pg/dl) plasma. Using 2.2 pmol/l as a cut-off the sensitivity and specificity to diagnose pituitary HAC was 0.82 (95 % CI 0.686 - 0.914) and 1 (95 % CI 0.692 - 1), respectively. With the help of the chemiluminometric assay, a correct classification was possible in 85 % of patients with HAC. As an ACTH-concentration below the detection limit was found in dogs with adrenal as well as pituitary HAC, additional discriminatory tests are necessary in these cases.     

Adrenal response to adrenocorticotropic hormone in dogs before and after surgical attenuation of a single congenital portosystemic shunt

BACKGROUND: Dogs with single congenital portosystemic shunts (CPSS) often develop postoperative hypoglycemia and prolonged anesthetic recovery. These abnormalities could be attributable to inadequate adrenal response. However, adequacy of adrenal response after CPSS surgery is unexplored. HYPOTHESIS: Dogs with CPSS have inadequate postoperative adrenal response. ANIMALS: Eight nonoperated, 8 ovariohysterectomy (OHE), and 16 CPSS dogs. METHODS: Consecutive day ACTH stimulation tests were performed on nonoperated healthy dogs, healthy dogs before and after OHE, and CPSS dogs before and after surgery. Adequate response was defined as >50% or >30 ng/mL increase in cortisol after ACTH administration. Blood glucose (BG) was monitored before and after surgery. Prolonged anesthetic recovery and refractory hypoglycemia episodes were recorded. RESULTS: Results of consecutive day ACTH stimulation tests did not vary in normal dogs. Results of preoperative ACTH stimulation tests of CPSS and OHE dogs were not significantly different. Dogs with CPSS had higher postoperative baseline cortisol concentrations (median, 329 ng/mL) than OHE dogs (median, 153 ng/mL). Postoperative cortisol increase after ACTH in CPSS was < or =50% in 10/16 and < or =30 ng/mL in 6/16. After surgery, BG was < or =60 mg/dL in 7/16 CPSS dogs. Cortisol concentrations were not correlated with BG. Two CPSS dogs had refractory hypoglycemia and 4 had delayed recovery; all improved with dexamethasone administration (0.1-0.2 mg/kg/IV). CONCLUSIONS AND CLINICAL IMPORTANCE: Contrary to previous reports, baseline cortisol concentrations in CPSS and healthy dogs are similar. Many CPSS dogs have postoperative hypercortisolemia. Response to ACTH does not correlate with postoperative hypoglycemia or prolonged anesthetic recovery.     

Pulsatile secretion pattern of growth hormone in dogs with pituitary-dependent hyperadrenocorticism

The amplitude and frequency of growth hormone (GH) secretory pulses are influenced by a variety of hormonal signals, among which glucocorticoids play an important role. The aim of this study was to investigate the pulsatile secretion pattern of GH in dogs in which the endogenous secretion of glucocorticoids is persistently elevated, i.e. in dogs with pituitary-dependent hyperadrenocorticism (PDH). Blood samples for the determination of the pulsatile secretion pattern of GH were collected at 10-min interval between 08:00 and 14:00 h in 16 dogs with PDH and in 6 healthy control dogs of comparable age. The pulsatile secretion patterns of GH were analyzed using the Pulsar program. GH was secreted in a pulsatile fashion in both dogs with PDH and control dogs. There was no statistical difference between the mean (+/-S.E.M.) basal GH level in dogs with PDH (0.7+/-0.1 microg/l) and the control dogs (0.6+/-0.1 microg/l). The mean area under the curve (AUC) for GH above the zero-level in dogs with PDH (4.6+/-0.6 microg/l per 6 h) was significantly lower than that in the control dogs (7.3+/-1.0 microg/l per 6 h). Likewise, the mean AUC for GH above the base-level in dogs with PDH (0.6+/-0.1 microg/l per 6 h) was significantly lower than that in the control dogs (3.7+/-1.0 microg/l per 6 h). The median GH pulse frequency in the dogs with PDH (2 pulses/6 h, range 0-7 pulses/6 h) was significantly lower (P = 0.04) than that (5 pulses/6 h, range 3-9 pulses/6 h) in the control group. The results of this study demonstrate that PDH in dogs is associated with less GH secreted in pulses than in control dogs, whereas the basal plasma GH concentrations were similarly low in both groups. It is discussed that the impaired pulsatile GH secretion in dogs with PDH is the result of alterations in function of pituitary somatotrophs and changes in supra-pituitary regulation.     

Interleukin-6 and insulin incrase and nitric oxide and adiponectin decrease in blind dogs with pituitary-dependent hyperadrenocorticism

In this study, two populations of dogs with pituitary dependent hypercortisolism (PDH) were compared over a 2-year period. One group had normal vision (Group A, n=27) and one group was blind (Group B, n=20). Group B was characterised by the rapid appearance of the clinical signs of PDH that precede blindness. We found increases in pre-adrenocorticotropic hormone cortisol (P=0.002), IL-6 (P=0.0001), insulin, and insulin sensitivity (detected with the Homeostatic Model Assessment, P<0.0001) in Group B but not in Group A. The nitric oxide (NO) and the total adiponectin concentrations decreased (P=0.0001 and P=0.02, respectively) in Group B versus Group A. The IL-6 and insulin concentrations and the HOMA-A index were positively correlated with the cortisol concentration and were negatively correlated with the NO concentration. With the exception of adiponectin, the other variables were associated with blindness. We concluded that blindness in PDH is a haemodynamic event associated with metabolic changes, with the increase in the IL-6 concentration and the decrease in the NO concentration affecting the retinal vasculature and producing a high risk of vision loss.