Pituitary-dependent Hyperadrenocorticism Dogs Research Articles

Utility of a corticotropin-releasing hormone test to differentiate pituitary-dependent hyperadrenocorticism from cortisol-producing adrenal tumors in dogs.

BackgroundHyperadrenocorticism (HAC) is a common endocrine disorder in dogs; however, there are no reports on the use of the corticotropin‐releasing hormone test (CRHT) to differentiate between pituitary‐dependent hyperadrenocorticism (PDH) and cortisol‐producing adrenal tumors (CPATs), both causative of HAC.ObjectivesTo evaluate the usefulness of CRHT as a tool to differentiate between PDH and CPAT in dogs and to determine the reference intervals for CRHT in healthy, PDH, and CPAT dogs.AnimalsDogs diagnosed with PDH (n = 21), CPAT (n = 6), and healthy beagle dogs (n = 33).MethodsThis prospective study included dogs with a definitive diagnosis of PDH and CPAT and healthy beagle dogs, in which CRHT was performed, were prospectively evaluated. We investigated the correlations of CRHT (endogenous adrenocorticotropic hormone [ACTH] concentration, endogenous ACTH concentration [EAC], and poststimulation ACTH concentration [PAC]) with pituitary‐to‐brain ratio (PBR) (in PDH) and with indices of adrenal ultrasonography (smaller and larger adrenal gland dorsoventral thickness in PDH and CPAT).ResultsFor EAC, the area under the curve (AUC) was 0.95, with a cutoff value of 26.3 pg/mL (sensitivity: 90.62%, specificity: 87.50%). The AUC for PAC was 0.96 with a cutoff value of 54.5 pg/mL (sensitivity: 100.00%, specificity: 66.67%). The 95% reference interval for CRHT in healthy (control) dogs ranged 5.00 to 79.8 pg/mL (1.10‐17.57 pmol/L) for EAC, and 1.92 to 153.42 pg/mL (0.42‐33.78 pmol/L) for PAC. There was no significant correlation between PBR and CRHT, nor adrenal size and CRHT.Conclusions and Clinical ImportanceCRHT appears to be a rapid and reliable test for differentiating PDH from CPAT in dogs.

Metabolic profiling of serum from dogs with pituitary-dependent hyperadrenocorticism

Hyperadrenocorticism (HAC) is one of the most common endocrine diseases in dogs characterized by excessive cortisol production caused by an adrenocorticotropic hormone (ACTH)-secreting tumor, namely pituitary-dependent HAC (PDH) or cortisol-secreting adrenal tumor. Metabolomics presents the ability to identify small molecule metabolites. Thus, the use of metabolomics techniques in canine PDH can provide information about the pathophysiology and metabolic changes in this disease. This study aimed to identify and compare differences in serum metabolites between dogs with PDH and healthy dogs. The metabolomic profile of 20 dogs diagnosed with PDH was compared with 20 healthy dogs using liquid chromatography/mass spectrometry (LC/MS), and metabolite discrimination was performed using partial least squares-discriminant analysis (PLS-DA), the variable important in projection (VIP) and fold changes (FC) group-wise comparisons. The hypergeometric test identified the significantly altered pathways. A total of 21 metabolites were found to be significantly different between the two groups. The major alterations were found in arachidonic and decanoic acid, and phospholipids related to phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI). These metabolites are related to insulin resistance and other complications (i.e. hypertension). Our results indicate that PDH produces changes in serum metabolites of dogs, and the knowledge of these changes can aid to better understanding of pathophysiological processes involved and contribute to potentially detect new biomarkers for this disease.

Laboratory assessment of trilostane treatment in dogs with pituitary-dependent hyperadrenocorticism.

BackgroundResults of ACTH stimulation test (ACTHst), pre‐ and post‐trilostane serum cortisol concentrations (SCCs), urine concentration (urine‐specific gravity [USG]), and urine cortisol : creatinine ratios (UCCRs) are common variables used to monitor trilostane treatment of dogs with pituitary‐dependent hyperadrenocorticism (PDH). However, none has consistently discriminated dogs receiving an adequate dose (A) from those overdosed (O) or underdosed (U).ObjectivesTo assess and compare recommended monitoring variables, including serial SCCs in a cohort of dogs with PDH treated with trilostane.AnimalsPrivately owned dogs with PDH (n = 22) and 3 healthy dogs (controls).MethodsProspective, multicenter, 2‐day study. On day “a” (randomized): ACTHst was completed. Day “b” (>2 to <7 days later): SCCs were assessed −0.5 hours, immediately before, and 1, 2, 2.5, 3, 3.5, 4, 6, 8, and 12 hours after trilostane administration. On the first study day, urine collected at home was assessed for USG, UCCR and owner opinions regarding PDH were categorized as: A (clinical signs resolved), U (remains symptomatic), or ill (possible O).ResultsAt 27 pairs of evaluations, 7 dogs were categorized as A, 19 U, and 1 possible O (excluded from the study). There was overlap in SCC results from the A and U dogs at every time point. Results of USG, UCCR, and ACTHst did not discriminate A from U dogs. Trilostane suppresses SCC within 1 hour of administration and its duration of action in most PDH dogs is <8 hours.Conclusions and Clinical ImportanceNo single variable or group of variables reliably discriminated A dogs from U dogs during trilostane treatment for PDH.

A preliminary evaluation of the circulating leptin/adiponectin ratio in dogs with pituitary-dependent hyperadrenocorticism and concurrent diabetes mellitus

Leptin and adiponectin are thought to modulate insulin sensitivity and pancreatic β-cell function, but there is limited information regarding the adipokine status of hyperglycemic dogs with hyperadrenocorticism. This study aimed to determine whether alterations in the leptin/adiponectin ratio, insulin sensitivity, and/or pancreatic β-cell function are associated with diabetes mellitus (DM) in dogs with pituitary-dependent hyperadrenocorticism (PDH). A total of 48 client-owned dogs were included in this prospective observational study: 20 dogs with PDH (10 normoglycemic and 10 with DM), 15 dogs with DM, and 13 healthy dogs. The serum concentrations of leptin, adiponectin, resistin, interleukin (IL)-1β, IL-6, IL-10, IL-18, and tumor necrosis factor (TNF)-α were measured, and homeostatic model assessment indices (HOMAs) were calculated and compared among the groups. Serum leptin was significantly higher in PDH dogs with and without DM than in healthy and DM dogs, and it was lower in DM dogs than in PDH dogs without DM. Serum adiponectin was significantly lower in PDH dogs with DM than in healthy and PDH dogs, and it was significantly lower in DM dogs than in healthy dogs. Serum IL-10 was significantly higher in PDH dogs with DM than in healthy and PDH dogs without DM. The leptin/adiponectin ratio was significantly higher in PDH dogs with DM than in normoglycemic PDH dogs. Serum IL-6 concentrations were significantly higher in DM dogs than in healthy dogs. Serum IL-1β concentration was significantly higher in DM dogs than in healthy dogs and PDH dogs with DM and without DM. Serum TNF-α and IL-18 concentrations were not different among groups. The HOMAβ-cell function was significantly lower in PDH dogs with DM than in normoglycemic PDH dogs, while HOMAinsulin sensitivity was significantly lower in PDH dogs with DM than in healthy dogs. These results suggest that adipokine dysregulation, a reduction in insulin sensitivity, and a further impairment in pancreatic β-cell function might predispose PDH dogs to DM. Further longitudinal study will be necessary to confirm this result.

The effect of 1 year of trilostane treatment on peripheral lymphocyte subsets in dogs with pituitary-dependent hyperadrenocorticism.

This study investigated the changes in lymphocyte subsets during the trilostane medication of Pituitary-dependent hyperadrenocorticism (PDH) dogs. The cortisol level and lymphocyte subsets of eight dogs with PDH were monitored 0, 1, 3, 6, 9 and 12 months after the initiation of trilostane treatment. White blood cells (WBC), lymphocytes, CD3+ (T lymphocyte), CD4+ (helper T lymphocyte), CD8+ (cytotoxic T lymphocyte) and CD21+ (B lymphocyte) cells were measured. Although the post-ACTH stimulation test cortisol level was significantly lower during trilostane treatment, changes in the CD3+, CD4+, CD8+ and CD21+ counts were not observed. Meanwhile, significant decrease was observed in WBC counts during trilostane treatment. These indicate that long-term trilostane treatment has little effect on the lymphocyte subsets in PDH dogs.

Serum cortisol concentrations in dogs with pituitary-dependent hyperadrenocorticism and atypical hyperadrenocorticism.

BackgroundAtypical hyperadrenocorticism (AHAC) is considered when dogs have clinical signs of hypercortisolemia with normal hyperadrenocorticism screening tests.Hypothesis/ObjectivesTo compare cortisol concentrations and adrenal gland size among dogs with pituitary‐dependent hyperadrenocorticism (PDH), atypical hyperadrenocorticism (AHAC), and healthy controls.AnimalsTen healthy dogs, 7 dogs with PDH, and 8 dogs with AHAC.MethodDogs were prospectively enrolled between November 2011 and January 2013. Dogs were diagnosed with PDH or AHAC based on clinical signs and positive screening test results (PDH) or abnormal extended adrenal hormone panel results (AHAC). Transverse adrenal gland measurements were obtained by abdominal ultrasound. Hourly mean cortisol (9 samplings), sum of hourly cortisol measurements and adrenal gland sizes were compared among the 3 groups.ResultsHourly (control, 1.4 ± 0.6 μg/dL; AHAC, 2.9 ± 1.3; PDH, 4.3 ± 1.5) (mean, SD) and sum (control, 11.3 ± 3.3; AHAC, 23.2 ± 7.7; PDH, 34.7 ± 9.9) cortisol concentrations differed significantly between the controls and AHAC (P < .01) and PDH (P < .01) groups. Hourly (P < .01) but not sum (P = .27) cortisol concentrations differed between AHAC and PDH dogs. Average transverse adrenal gland diameter of control dogs (5.3 ± 1.2 mm) was significantly less than dogs with PDH (6.4 ± 1.4; P = .02) and AHAC (7.2 ± 1.5; P < .01); adrenal gland diameter did not differ (P = .18) between dogs with AHAC and PDH.Conclusions and Clinical ImportanceSerum cortisol concentrations in dogs with AHAC were increased compared to controls but less than dogs with PDH, while adrenal gland diameter was similar between dogs with AHAC and PDH. These findings suggest cortisol excess could contribute to the pathophysiology of AHAC.

Involvement of glucagon-like peptide 1 in the glucose homeostasis regulation in obese and pituitary-dependent hyperadrenocorticism affected dogs

The incretin glucagon-like peptide 1 (GLP-1) enhances insulin secretion. The aim of this study was to assess GLP-1, glucose and insulin concentrations, Homeostatic Model Assessment (HOMAinsulin sensitivity and HOMAβ-cell function) in dogs with pituitary-dependent hyperadrenocorticism (PDH), and compare these values with those in normal and obese dogs. The Oral Glucose Tolerance Test was performed and the glucose, GLP-1 and insulin concentrations were evaluated at baseline, and after 15, 30, 60 and 120 minutes. Both basal concentration and those corresponding to the subsequent times, for glucose, GLP-1 and insulin, were statistically elevated in PDH dogs compared to the other groups. Insulin followed a similar behaviour together with variations of GLP-1. HOMAinsulin sensitivity was statistically decreased and HOMAβ-cell function increased in dogs with PDH. The higher concentrations of GLP-1 in PDH could play an important role in the impairment of pancreatic β-cells thus predisposing to diabetes mellitus.

Low dose of insulin detemir controls glycaemia, insulinemia and prevents diabetes mellitus progression in the dog with pituitary-dependent hyperadrenocorticism

Diabetes is often associated with pituitary-dependent hyperadrenocorticism (PDH). Hypercortisolism causes insulin resistance and affects β-cell function. The purpose of this study was to test if daily administration of a long-acting insulin analogue during the first month of anti-PDH treatment can prevent progress to diabetes in these animals. Twenty-six PDH dogs were divided into three groups: one group with glycaemia <5.83mmol/L and two groups with glycaemia >5.83mmol/L and <9.35mmol/L, one of which received insulin detemir during 4months. Dogs with glycaemia <5.83mmol/L and those with glycaemia >5.83mmol/L which received insulin did not develop diabetes. In the non-insulin group, 6/7 dogs developed diabetes after the third month. There is a 13-fold higher risk of diabetes in dogs with glycaemia >5.83mmol/L and no insulin treatment. Administering insulin detemir to dogs with PDH and glycaemia >5.83mmol/L could prevent progression to diabetes.

Magnetic Resonance Imaging Assessment of Pituitary Posterior Lobe Displacement in Dogs with Pituitary-Dependent Hyperadrenocorticism

The displacement and signal intensity (SI) of the pituitary posterior lobe were evaluated on T1 weighted magnetic resonance (MR) images in 28 dogs with pituitary dependent hyperadrenocorticism (PDH). Compared with normal dogs, the posterior lobe was displaced dorsally in the pituitary of the PDH dogs. Correlation between the pituitary height/brain area (P/B) ratio and the displacement of the posterior lobe in the PDH dogs suggests that dorsal displacement of the posterior lobe increases in accordance with enlargement of the pituitary. As to the SI of the posterior lobe, the PDH dogs showed significantly lower SI in comparison to the normal dogs. Taken together, these results suggest that assessment of the displacement and SI of the posterior lobe of the pituitary on T1-weighted MR images is useful for the diagnosis of pituitary adenoma. In pituitary microadenoma that presents no apparent tumorigenesis on MRI, evaluation of these values may be useful for diagnosis and selection of an appropriate therapy.

Assessing the immune state of dogs suffering from pituitary gland dependent hyperadrenocorticism by determining changes in peripheral lymphocyte subsets

In order to evaluate the immune state of dogs suffering from pituitary-dependent hyperadrenocorticism (PDH), peripheral lymphocyte subsets were examined. Twenty seven PDH dogs and eight healthy control dogs were used in the current study. Eight healthy dogs served as the control group. Twenty seven PDH dogs were categorized into 4 groups based on their post serum cortisol concentrations by ACTH stimulation test: 2-5, excellent control (n = 8); 5-20, fair control (n = 7); >20, poor control (n = 4); and untreated (n = 8). Cell counts were executed with white blood cells (WBC), lymphocytes, CD3(+) (T lymphocytes), CD4(+) (Helper T lymphocytes), CD8(+) (Cytotoxic T lymphocytes), CD21(+) (B lymphocytes) cells in addition to calculating CD4(+)/CD8(+) ratio. Results indicated a significant difference in lymphocyte numbers and lymphocyte subset populations (CD3(+), CD4(+), CD8(+), and CD21(+) cells) between PDH and control dogs. Moreover, comparison of the PDH groups (excellent control; fair control; poor control; untreated) demonstrated that all groups had a significant decrease in lymphocytes numbers (CD3(+), CD4(+) and CD21(+) cell counts) as compared to control group. Meanwhile, no significant differences were observed in WBC counts and CD4(+)/CD8(+) ratio between groups. Furthermore, lymphocyte subset distribution in excellent control PDH dogs without concurrent disease (n = 4) better resembled that of control dogs as compared to PDH dogs with concurrent disease (n = 4). PDH dogs may be suffering from an immuno-depressed state as evidenced by significant differences in lymphocyte subset populations. Furthermore, treatment of both PDH and concurrent disease might improve lymphocyte subset distribution.

Frequency of pulmonary mineralization and hypoxemia in 21 dogs with pituitary-dependent hyperadrenocorticism.

The purpose of this study was to determine the frequency of hypoxemia and pulmonary mineralization using 99mTc-methylene diphosphonate (99mTc-MDP) in dogs with pituitary-dependent hyperadrenocorticism (PDH). Twenty-one dogs with PDH were prospectively evaluated using thoracic radiography, arterial blood gas analysis, and bone phase and pulmonary perfusion scintigraphy (using 99mTc-macro-aggregated albumin [99mTc-MAA]). The radiographs and bone and perfusion studies were evaluated subjectively. An averaged quantitative count density ratio was calculated between the thorax and cranial thoraco-lumbar vertebrae from lateral thoracic 99mTc-MDP images. Thoracic:vertebral ratios were calculated using 99mTc-MDP studies from 21 control dogs. The thoracic:vertebral ratios were compared between the 2 groups (PDH and control). The mean age (+/-SD) of the 21 PDH dogs was 10.2 (+/-3) years, whereas the mean age of the control group was 9.8 (+/-3) years. Seven of the 21 dogs with PDH were hypoxemic (defined as an arterial partial pressure of oxygen [PaO2] < 80 mm Hg) with an average PaO2 (+/-SD) of 62 (+/-15) mm Hg. Of the 7 hypoxemic dogs, 2 were found to have pulmonary mineralization based on bone scintigraphic images. Pulmonary perfusion abnormalities were not identified using 99mTc-MAA in any of the 21 PDH dogs. Six PDH dogs had an abnormal interstitial pulmonary pattern and 5 of these dogs were hypoxemic. The average quantitative thoracic:vertebral ratio was not significantly different between the PDH and control dogs (0.5 +/- 0.4 versus 0.4 +/- 0.1, P = .16). Causes of hypoxemia other than pulmonary thromboembolism should be considered in dogs with PDH. Pulmonary mineralization may contribute to hypoxemia in dogs with PDH.

Expression and mutation analysis of Tpit in the canine pituitary gland and corticotroph adenomas

Pituitary-dependent hyperadrenocorticism (PDH) in dogs is caused by a pituitary corticotroph adenoma. Although PDH is a common disorder in dogs, little is known about the underlying pathogenesis. In the pituitary glands of humans and mice, the pro-opiomelanocortin (POMC)-expressing cell lineages, the corticotrophs and melanotrophs, have a specific marker in common, the T-box transcription factor Tpit (Tbx19), which is obligate for POMC expression. Tpit also regulates the late differentiation of the corticotrophs and melanotrophs, and therefore may contribute to the pathogenesis of the corticotroph adenomas. The aim of this study was to perform an expression and mutation analysis of Tpit in the normal canine pituitary and in corticotroph adenomas. The distribution of the Tpit protein in the pituitary gland was studied with immunohistochemistry and the expression of the gene with RT-PCR. The coding region of Tpit cDNA from 14 dogs with PDH was screened for mutations. Tpit was expressed in corticotroph and melanotroph cells of the normal and adenomatous canine pituitary, and remained present in non-adenomatous corticotrophs of pituitaries from PDH dogs. No tumor-specific mutation in the Tpit cDNA from the corticotroph adenomas was found. However, a missense polymorphism in the highly conserved DNA-binding domain, the T-box, was discovered in one dog. It is concluded that Tpit can be used as a reliable marker for the corticotroph and melanotroph cells in the canine pituitary tissue and that mutations in the Tpit gene are unlikely to play a major role in the pathogenesis of canine corticotroph adenomas.

Secretion of sex hormones in dogs with adrenal dysfunction

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). Prospective study. 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). 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. 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. 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.

Investigation of the role of aldosterone in hypertension associated with spontaneous pituitary-dependent hyperadrenocorticism in dogs.

The aim of this study was to evaluate the role of aldosterone as an initiating and/or perpetuating factor in hypertension associated with pituitary-dependent hyperadrenocorticism (PDH) in dogs. Thirteen dogs with PDH and 11 healthy control dogs were used. In all dogs, arterial blood pressure and plasma sodium, potassium, basal aldosterone, post-ACTH aldosterone, basal cortisol and post-ACTH cortisol concentrations were measured. The tests were repeated 10 days and three months after the beginning of o,p'-DDD treatment in PDH dogs. In untreated PDH dogs, plasma aldosterone was significantly decreased, whereas cortisol, sodium and arterial blood pressure were significantly increased compared to healthy dogs. Hypertension remained in most treated PDH dogs despite normalisation of cortisol and persistently low aldosterone levels. These results did not demonstrate that aldosterone is involved in the development and perpetuation of hypertension in PDH. However, glucocorticoids seemed to play a major role as an initiating and perpetuating factor in PDH in dogs.

Effects of growth hormone-releasing peptides in healthy dogs and in dogs with pituitary-dependent hyperadrenocorticism

The aim of this study is to investigate the effects of ghrelin and GH-releasing peptide-6 (GHRP-6) on the release of growth hormone (GH), adrenocorticotrophic hormone (ACTH), and cortisol in dogs with pituitary-dependent hyperadrenocorticism (PDH) and in healthy dogs of comparable age. In eight healthy dogs, the responses to ghrelin and GHRP-6 were compared to those of GH-releasing hormone (GHRH) and NaCl 0.9% (control). In seven dogs with PDH, the effects of ghrelin and GHRP-6 were compared with their effects in healthy dogs. In the healthy dogs, GHRH, GHRP-6, and ghrelin caused a significant rise in plasma GH concentrations. GHRH administration elicited significantly higher plasma GH concentrations than administration of ghrelin and GHRP-6. In the dogs with PDH, the GHRP-6-induced release of GH was significantly lower than in healthy dogs. Administration of ghrelin elicited a GH release that did not differ significantly between dogs with PDH and healthy dogs. Ghrelin and GHRP-6 did not cause a significant rise in plasma ACTH and cortisol concentrations in either the healthy dogs or the dogs with PDH. It is concluded that in comparison with GHRH, GHRP-6 and ghrelin have a low GH-releasing potency in healthy dogs. In dogs with PDH, the GH release in response to GHRP-6 is impaired. Neither GHRP-6 nor ghrelin activates the pituitary–adrenocortical axis in healthy elderly dogs and dogs with PDH.

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 μg/l) and the control dogs (0.6±0.1 μg/l). The mean area under the curve (AUC) for GH above the zero-level in dogs with PDH (4.6±0.6 μg/l per 6 h) was significantly lower than that in the control dogs (7.3±1.0 μg/l per 6 h). Likewise, the mean AUC for GH above the base-level in dogs with PDH (0.6±0.1 μg/l per 6 h) was significantly lower than that in the control dogs (3.7±1.0 μg/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.

Frequency of Pulmonary Mineralization and Hypoxemia in 21 Dogs with Pituitary‐Dependent Hyperadrenocorticism

The purpose of this study was to determine the frequency of hypoxemia and pulmonary mineralization using99mTc‐methylene diphosphonate (99mTc‐MDP) in dogs with pituitary‐dependent hyperadrenocorticism (PDH). Twenty‐one dogs with PDH were pro‐spectively evaluated using thoracic radiography, arterial blood gas analysis, and bone phase and pulmonary perfusion scintigraphy (using99mTc‐macro‐aggregated albumin [99mTc‐MAA]). The radiographs and bone and perfusion studies were evaluated subjectively. An averaged quantitative count density ratio was calculated between the thorax and cranial thoraco‐lumbar vertebrae from lateral thoracic99mTc‐MDP images. Thoracic: vertebral ratios were calculated using99mTc‐MDP studies from 21 control dogs. The thoracic: vertebral ratios were compared between the 2 groups (PDH and control). The mean age (±SD) of the 21 PDH dogs was 10.2 (±3) years, whereas the mean age of the control group was 9.8 (±3) years. Seven of the 21 dogs with PDH were hypoxemic (denned as an arterial partial pressure of oxygen [PaO2] &lt;80 mm Hg) with an average PaO2(±SD) of 62 (±15) mm Hg. Of the 7 hypoxemic dogs, 2 were found to have pulmonary mineralization based on bone scintigraphic images. Pulmonary perfusion abnormalities were not identified using99mTc‐MAA in any of the 21 PDH dogs. Six PDH dogs had an abnormal interstitial pulmonary pattern and 5 of these dogs were hypoxemic. The average quantitative thoracic: vertebral ratio was not significantly different between the PDH and control dogs (0.5 ± 0.4 versus 0.4 ± 0.1,P= .16). Causes of hypoxemia other than pulmonary thromboembolism should be considered in dogs with PDH. Pulmonary mineralization may contribute to hypoxemia in dogs with PDH.

Corticotropin-releasing hormone and adrenocorticotropic hormone concentrations in cerebrospinal fluid of dogs with pituitary-dependent hyperadrenocorticism.

There is still some controversy concerning the question of whether Cushing's disease in man is caused by a primary dysfunction of the pituitary or a hypothalamic disorder. In the latter option, excessive hypothalamic stimulation of pituitary corticotropes would cause or contribute to the genesis of POMC-secreting adenomas. In the present study cerebrospinal fluid (CSF) CRH levels and levels of ACTH and cortisol in CSF and plasma were measured in clinically healthy dogs, in dogs with pituitary-dependent hyperadrenocorticism (PDH), and in dogs with hyperadrenocorticism due to an adrenocortical tumor (ATH). In CSF from dogs with PDH, CRH concentrations (226.6 +/- 14.4 ng/liter) were significantly (P < 0.05) lower than those in control dogs (309.5 +/- 20.3 ng/liter). In the dogs with ATH, CSF CRH concentrations (211.0 +/- 40.3 ng/liter) were in the range of those in PDH dogs. In dogs with ATH, CSF ACTH levels (13.0 +/- 3.0 ng/liter) were significantly (P < 0.05) lower than those in control dogs (63.4 +/- 3.5 ng/liter), whereas in dogs with PDH, the levels (116.8 +/- 47.5 ng/liter) were not different from those in the control group. In control dogs, the concentrations of CSF CRH and plasma ACTH were significantly correlated (r = 0.635; P < 0.01). This functional dependency appeared to be disturbed in dogs with PDH, as in these dogs CSF CRH concentrations did not correlate with plasma ACTH concentrations. It is concluded that continuous hyperstimulation of pituitary corticotropes with hypothalamic CRH is probably not the cause of excessive ACTH secretion in dogs with pituitary-dependent hyperadrenocorticism.