Age-dependent effects of Armc5 haploinsufficiency on adrenocortical function.

Inactivating mutations in the Armadillo repeat-containing 5 (ARMC5) gene have recently been discovered in primary macronodular adrenal hyperplasia (PMAH), a cause of Cushing syndrome. Biallelic ARMC5 inactivation in PMAH suggested that ARMC5 may have tumor suppressor functions in the adrenal cortex. We generated and characterized a new mouse model of Armc5 deficiency. Almost all Armc5 knockout mice died during early embryonic development, around 6.5 and 8.5 days. Knockout embryos did not undergo gastrulation, as demonstrated by the absence of mesoderm development at E7.5. Armc5 heterozygote mice (Armc5+/-) developed normally but at the age of 1 year, their corticosterone levels decreased; this was associated with a decrease of protein kinase A (PKA) catalytic subunit α (Cα) expression both at the RNA and protein levels that were also seen in human patients with PMAH and ARMC5 defects. However, this was transient, as corticosterone levels normalized later, followed by the development of hypercorticosteronemia in one-third of the mice at 18 months of age, which was associated with increases in PKA and Cα expression. Adrenocortical tissue analysis from Armc5+/- mice at 18 months showed an abnormal activation of the Wnt/ß-catenin signaling pathway in a subset of zona fasciculata cells. These data confirm that Armc5 plays an important role in early mouse embryonic development. Our new mouse line can be used to study tissue-specific effects of Armc5. Finally, Armc5 haploinsufficiency leads to Cushing syndrome in mice, but only later in life, and this involves PKA, its catalytic subunit Cα, and the Wnt/ß-catenin pathway.

Hyperadrenocorticism Caused by a Pituitary Ganglioglioma in a Dog.

An 11-year-old castrated male Chihuahua dog was presented with complaints of polyuria, polydipsia, abdominal enlargement, and alopecia. Hyperadrenocorticism was diagnosed on the basis of clinical signs, blood tests, adrenocorticotropin-stimulation test results, and an elevated serum adrenocorticotropin concentration. Contrast-enhanced magnetic resonance imaging showed that the pituitary gland was enlarged, compatible with a pituitary macroadenoma. Pituitary-dependent hyperadrenocorticism was suspected, and transsphenoidal hypophysectomy was thus performed for complete resection of the tumor. After surgery, the serum adrenocorticotropin concentration normalized and the hyperadrenocorticism resolved. Histological and immunocytochemical analyses revealed a benign tumor composed of mature neuronal cells and glial cells, suggestive of a ganglioglioma with immunolabeling for adrenocorticotropin. Careful analysis of the resected tumor revealed no pituitary adenoma tissue. The clinical and histopathologic findings indicated that the ganglioglioma was directly responsible for the hyperadrenocorticism. This is the first case of hyperadrenocorticism caused by a ganglioglioma in a dog.

Lack of association between clinical signs and laboratory parameters in dogs with hyperadrenocorticism before and during trilostane treatment.

INTRODUCTION: Trilostane therapy, the treatment of choice for pituitary- dependent hyperadrenocorticism (HAC) in dogs, is monitored by assessing resolution of clinical signs and measuring adrenocortical reserve capacity with an ACTH-stimulation test. The aim of this prospective study was to evaluate agreement between clinical signs reported by owners and cortisol or ACTH concentrations before and during trilostane therapy (starting dose 1-2 mg/kg once daily). A questionnaire on signs of HAC was used and a clinical score calculated as the sum of the 9 questions. Eighteen questionnaires at diagnosis and 97 during therapy were filled out by owners of 32 dogs. An ACTH-stimulation test was performed at each reevaluation. There were weak correlations between abdominal girth, appetite or weight gain and cortisol concentrations during therapy. However, the clinical score did not correlate with cortisol or cACTH values. In 50% of dogs, trilostane application had to be changed from once daily to twice daily during the study. Clinical signs reported by owners matched poorly with cortisol or cACTH concentrations at any time point. If low-dose trilostane is used, treatment frequency often has to be increased.

INTRODUCTION: Le traitement au trilostane, médicament de choix dans les cas d'hyperadrénocorticisme hypophyso-dépendant chez le chien, est évalué sur la base de la disparition des symptômes cliniques et des résultats des tests de stimulation à l'ACTH. Le but de la présente étude prospective était de comparer les symptômes cliniques (évalués par les propriétaires) avec les concentrations de cortisol et d'ACTH endogène avant et durant un traitement au trilostane (dose initiale 1­2 mg/kg, 1× par jour). On a utilisé un questionnaire composé de 9 questions relatives aux symptômes cliniques sur la base desquels on a calculé un score clinique total. Dix-huit questionnaires ont été remplis au moment du diagnostic et 97 durant le traitement par les propriétaires de 32 chiens. Un test de stimulation à l'ACTH a été réalisé lors de chaque contrôle. Il existait de faibles corrélations entre le périmètre abdominal, l'appétit et la prise de poids et les taux de cortisol durant le traitement. Le score clinique total n'était toutefois pas corrélé avec les concentrations de cortisol ou d'ACTH. Chez la moitié des chiens, la dose de trilostane a du être répartie en deux prises journalières. Les symptômes cliniques jugés par les propriétaires montraient une mauvaise corrélation avec les taux de cortisol et d'ACTH durant le traitement au trilostane. Si on dose ce médicament de façon faible, il y a souvent lieu d'augmenter la fréquence des prises.

Risk of concomitant malignancy in hyperfunctioning adrenal incidentalomas.

BACKGROUND: Adrenal masses are common incidental findings on radiologic imaging. The association between malignancy and hormonal hyperactivity found in incidentally discovered adrenal tumors, however, remains unclear. METHODS: A retrospective analysis of prospectively collected data from patients who underwent adrenalectomy for incidentally discovered adrenal tumors at a single institution. Outcomes and operative data were compared by univariate analysis. Area under the curve was used to analyze the effect of tumor size in predicting malignancy. RESULTS: There were 49 patients who initially presented with adrenal incidentalomas that underwent adrenalectomy. Most patients were Caucasian women with an average age of 51 ± 14 years. Of this group, 24 patients underwent resection for hyperfunctioning adrenal glands. There were no significant differences in malignancy rates between hyperfunctional and nonfunctional tumors (4.1% vs. 12.0%, P = 0.32). On final histopathology, there were four patients with adrenal malignancies: two adrenocortical carcinomas and two metastatic from renal carcinoma. Only one patient with a hyperfunctioning adrenal tumor had underlying malignancy. Overall, invasion of adjacent structures (P < 0.001), presence of lymphadenopathy (P = 0.02), metastasis (P = 0.03), irregular tumor margins (P = 0.01), heterogeneity (P = 0.05), and tumor size >6 cm (P = 0.04) on radiologic imaging were strongly associated with malignancy in adrenal incidentalomas. CONCLUSIONS: The risk of concomitant malignancy and hormonal hyperactivity in adrenal incidentalomas is very low. Tumor size (>6 cm) and radiographic features remain the most important predictors of adrenal malignancy, regardless of tumor function.

Contrast-enhanced ultrasonographic characteristics of adrenal glands in dogs with pituitary-dependent hyperadrenocorticism.

A noninvasive method for quantifying adrenal gland vascular patterns could be helpful for improving detection of adrenal gland disease in dogs. The purpose of this retrospective study was to compare the contrast-enhanced ultrasound (CEUS) characteristics of adrenal glands in 18 dogs with pituitary-dependent hyperadrenocorticism (PDH) vs. four clinically healthy dogs. Each dog received a bolus of the contrast agent (SonoVue®, 0.03 ml/kg of body weight) into the cephalic vein, immediately followed by a 5 ml saline flush. Dynamic contrast enhancement was analyzed using time-intensity curves in two regions of interest drawn manually in the caudal part of the adrenal cortex and medulla, respectively. In healthy dogs, contrast enhancement distribution was homogeneous and exhibited increased intensity from the medulla to the cortex. In the washout phase, there was a gradual and homogeneous decrease of enhancement of the adrenal gland. For all dogs with PDH, there was rapid, chaotic, and simultaneous contrast enhancement in both the medulla and cortex. Three distinct perfusion patterns were observed. Peak perfusion intensity was approximately twice as high (P < 0.05) in dogs with PDH compared with that of healthy dogs (28.90 ± 10.36 vs. 48.47 ± 15.28, respectively). In dogs with PDH, adrenal blood flow and blood volume values were approximately two- to fourfold (P < 0.05) greater than those of controls. Findings from the present study support the use of CEUS as a clinical tool for characterizing canine adrenal gland disease based on changes in vascular patterns.

Potential variant of multiple endocrine neoplasia in a dog.

This report describes multiple endocrine neoplasia in a dog, which is a rare hereditary disorder characterized by the presence of two or more neoplasms of different endocrine tissues within a patient. A 14 yr old dog was evaluated for polyuria/polydipsia, polyphagia, and abdominal enlargement. Adrenal-dependent hyperadrenocorticism with concomitant left thyroid enlargement and a presumed abdominal metastatic lesion were diagnosed by an adrenocorticotropic hormone stimulation test, ultrasonography, and computed tomography. Trilostane therapy was initiated and resolved the clinical signs for 2 yr at which time the dog presented with left testicular enlargement. The dog was euthanized and was diagnosed with adrenocortical carcinoma, thyroid carcinoma, an abdominal mass compatible with a metastatic lymph node, and bilateral interstitial cell testicular adenomas. To the authors' knowledge, this is the first report to describe the concomitant association of these types of endocrine neoplasms in a dog. The concomitant presence of these neoplasms could represent a potential variant of multiple endocrine neoplasia; however, the presence of the interstitial cell testicular adenomas may have only been an incidental finding. If any of these tumors are diagnosed, veterinarians should perform a thorough clinical assessment to evaluate for the presence of additional endocrine neoplasms or hyperplasia.

Morphologic and Molecular Characterization of Adrenals and Adrenal Rest Affected by Congenital Adrenal Hyperplasia.

Introduction: Adrenocortical hyperplasia and adrenal rest tumor (ART) formation are common in congenital adrenal hyperplasia (CAH). Although driven by excessive corticotropin, much is unknown regarding the morphology and transformation of these tissues. Our study objective was to characterize CAH-affected adrenals and ART and compare with control adrenal and gonadal tissues. Patients/Methods: CAH adrenals, ART and control tissues were analyzed by histology, immunohistochemistry, and transcriptome sequencing. We investigated protein expression of the ACTH receptor (MC2R), steroidogenic (CYP11B2, CYP11B1, CYB5A) and immune (CD20, CD3, CD68) biomarkers, and delta-like 1 homolog (DLK1), a membrane bound protein broadly expressed in fetal and many endocrine cells. RNA was isolated and gene expression was analyzed by RNA sequencing (RNA-seq) followed by principle component, and unsupervised clustering analyses. Results: Based on immunohistochemistry, CAH adrenals and ART demonstrated increased zona reticularis (ZR)-like CYB5A expression, compared to CYP11B1, and CYP11B2, markers of zona fasciculata and zona glomerulosa respectively. CYP11B2 was mostly absent in CAH adrenals and absent in ART. DLK1 was present in CAH adrenal, ART, and also control adrenal and testis, but was absent in control ovary. Increased expression of adrenocortical marker MC2R, was observed in CAH adrenals compared to control adrenal. Unlike control tissues, significant nodular lymphocytic infiltration was observed in CAH adrenals and ART, with CD20 (B-cell), CD3 (T-cell) and CD68 (macrophage/monocyte) markers of inflammation. RNA-seq data revealed co-expression of adrenal MC2R, and testis-specific INSL3, HSD17B3 in testicular ART indicating the presence of both gonadal and adrenal features, and high expression of DLK1 in ART, CAH adrenals and control adrenal. Principal component analysis indicated that the ART transcriptome was more similar to CAH adrenals and least similar to control testis tissue. Conclusions: CAH-affected adrenal glands and ART have similar expression profiles and morphology, demonstrating increased CYB5A with ZR characteristics and lymphocytic infiltration, suggesting a common origin that is similarly affected by the abnormal hormonal milieu. Immune system modulators may play a role in tumor formation of CAH.

Computed tomography and low-field magnetic resonance imaging of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism: 11 cases (2001-2003).

OBJECTIVE: To compare the results of computed tomography (CT) and magnetic resonance imaging (MRI) of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism (PDH) caused by histologically confirmed pituitary adenoma. DESIGN: Retrospective case series. ANIMALS: 11 dogs with PDH that underwent transsphenoidal hypophysectomy. PROCEDURES: Medical records of dogs examined between January 2001 and March 2003 were reviewed. Dogs were included in this study if they had clinical signs of hypercortisolism at the time of admission (for which PDH was diagnosed) and underwent transsphenoidal hypophysectomy. Pre- and postcontrast CT and low-field MRI (0.2-Tesla magnet) were performed on the same day as surgery for each dog. RESULTS: An abnormal pituitary gland was found in 7 dogs by use of MRI and in the same 7 dogs by use of CT. Significant differences were found between postcontrast CT and MR images for height, width, and length of the pituitary gland; brain area; and thickness of the sphenoid bone. However, the pituitary gland height-to-brain area ratio determined from postcontrast CT and MR images was not significantly different. The signal-to-noise ratio and contrast-to-noise ratio of pre- and postcontrast MR images were significantly higher than those of the CT images. CONCLUSIONS AND CLINICAL RELEVANCE: Low-field MRI and dynamic CT imaging of the pituitary gland provided comparable information on the presence of pituitary adenomas in dogs with PDH.

Adrenal hypersensitivity precedes chronic hypercorticism in streptozotocin-induced diabetes mice.

Previous studies have demonstrated that type 1 diabetes is characterized by hypercorticism and lack of periodicity in adrenal hormone secretion. In the present study, we tested the hypothesis that hypercorticism is initiated by an enhanced release of ACTH leading subsequently to adrenocortical growth and increased output of adrenocortical hormones. To test this hypothesis, we used the streptozotocin (STZ)-induced diabetes mouse model and measured hypothalamic-pituitary-adrenal axis activity at different time points. The results showed that the expected rise in blood glucose levels induced by STZ treatment preceded the surge in corticosterone secretion, which took place 1 d after diabetes onset. Surprisingly, circulating ACTH levels were not increased and even below control levels until 1 d after diabetes onset and remained low until d 11 during hypercorticism. In response to ACTH (but not vasopressin), cultures of adrenal gland cells from 11-d diabetic mice secreted higher amounts of corticosterone than control cells. Real-time quantitative PCR revealed increased expression of melanocortin 2 and melanocortin 5 receptors in the adrenal glands at 2 and 11 d of STZ-induced diabetes. AVP mRNA expression in the paraventricular nucleus of the hypothalamus was increased, whereas hippocampal MR mRNA was decreased in 11-d diabetic animals. GR and CRH mRNAs remained unchanged in hippocampus and paraventricular nucleus of diabetic mice at all time points studied. These results suggest that sensitization of the adrenal glands to ACTH rather than an increase in circulating ACTH level is the primary event leading to hypercorticism in the STZ-induced diabetes mouse model.

Ultrasonographic evaluation of skin thickness in small breed dogs with hyperadrenocorticism.

The purpose of this study was to propose a standard for differentiation between normal dogs and patients with hyperadrenocorticism (HAC) by measuring skin thickness via ultrasonography in small breed dogs. Significant changes in skin thickness of patients treated with prednisolone (PDS) or patients with HAC treated with trilostane were evaluated. Skin thickness was retrospectively measured on three abdominal digital images obtained from small breed dogs weighing ＜ 15 kg that underwent abdominal ultrasonography. Mean skin thickness of normal dogs was 1.03 ± 0.25 mm (mean ± SD). Both the HAC and PDS groups showed significantly thinner skin than that in the normal group. Seven of the 10 HAC patients treated with trilostane had increased skin thickness. The area under the curve value of 0.807 was based on the receiver operating characteristics (ROC) curve for differentiating normal dogs from HAC patients. Sensitivity was 76% and specificity was 73% when skin thickness was less than the 0.83 mm cutoff value. In conclusion, measurement of skin thickness in small breed dogs by using ultrasonography is likely to provide clinical information useful in differentiating HAC patients from normal dogs. However, exposure to PDS, trilostane, and other conditions may have a significant effect on skin thickness.

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).

Histological evaluation of the adrenal glands of seven dogs with hyperadrenocorticism treated with trilostane.

The lesions in the adrenal glands of seven dogs with hyperadrenocorticism that had been treated with trilostane were studied histologically. The glands of the six dogs with pituitary-dependent hyperadrenocorticism had moderate to severe cortical hyperplasia that was either diffuse or nodular. The lesions were more pronounced in the zona fasciculata than in the zona reticularis, and the zona glomerulosa was normal. In the dog with a functional adrenal tumour the non-tumour bearing adrenal gland showed mild nodular hyperplasia. Five of the seven dogs had variable degrees of adrenal necrosis, which was severe in two of them. The terminal deoxynucleotidyl transferase-mediated DUTP nick-end labelling (TUNEL) reaction specified areas of cell death as apoptosis in three of the dogs, and was positive in one of the dogs without visible areas of cell death. There were variable degrees of cortical haemorrhage in three of the dogs. In some of the dogs the lesions were severe enough to lead to hypoadrenocorticism.

Hyperadrenocorticism associated with sex steroid excess.

Diagnosis of sex steroid excess or hyperadrenocorticism in dogs may be challenging. Unlike Cushing's disease, sex steroid excess may have a multitude of manifestations that differ from standard hyperadrenocorticism. In particular, the clinical scenario of a dog with sex steroid imbalance involves one of three systems: dermatologic, reproductive, or hepatic. The history of a dog with hyperadrenocorticism manifesting as sex steroid imbalance often lacks the classical clinical signs of polydipsia and polyuria. Dogs with sex steroid imbalance will often be of specific breeds such as miniature poodles and exhibit trunkal hair loss as the only sign. There is often involvement of the reproductive system, manifested as the growth of perianal adenomas in neutered male or female dogs. The most common laboratory findings consist of elevations in serum alkaline phosphatase and serum alanine transferase. The following article reviews the etiology, common signalment, clinical signs, and laboratory findings associated with atypical hyperadrenocorticism caused by sex steroid imbalance and then explores the medical, surgical, and radiation treatment options.

Concurrent hyperadrenocorticism and diabetes mellitus in dogs.

Hyperadrenocorticism (HAC) and diabetes mellitus (DM) are two diseases that can occur concurrently in dogs. The objective of this study was to evaluate the coexistence of HAC and DM, and the risk factors involved that could contribute to the development of DM in dogs with HAC. A total of 235 dogs with HAC were studied and, according to their fasting glycemia, they were divided into three groups: <5.6mmol/L, between 5.6 and 10.08mmol/L and >10.08mmol/L. The following parameters were evaluated: age, gender, cause of HAC, body condition, glycemia, total cholesterol, triglycerides, urinary cortisol:creatinin ratio (UCCR) and survival time. A 13.61% concurrence of HAC and DM was observed. Dogs with a fasting glycemia >5.6mmol/L, with dislipemia, with Pituitary-Dependent Hyperadrenocorticism, UCCR >100×10-6 and non-castrated females showed a higher risk of developing DM. The development of DM in dogs with HAC reduces the survival time.

Polycystic ovary syndrome and its differential diagnosis.

UNLABELLED: Polycystic ovary syndrome (PCOS) is a common disorder of reproductive-aged women. It affects between 3.4-6.8% of this population. Common clinical symptoms of PCOS include menstrual irregularities, hirsutism, and often obesity. Long-term sequelae include anovulatory infertility, endometrial carcinoma, and an increased risk for cardiovascular disease due to type II diabetes mellitus, dyslipidemia, and systolic hypertension. The diagnosis of PCOS is one of exclusion and is defined by the Rotterdam criteria which were established in 2004. However, several other endocrine disorders can closely resemble PCOS. It is important for practitioners to recognize and distinguish PCOS from other disorders in its differential. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to summarize the short-term reproductive and long-term metabolic consequences of polycystic ovary syndrome (PCOS), point out the importance of meeting the current criteria for diagnosis, and recall the recommended treatment related to the clinical presentation of the patient.

Suspected case of hyperadrenocorticism in a golden hamster (Mesocricetus auratus).

Dermatologic disease is a common problem in pet rodents. This article describes the case of a pet golden hamster (Mesocricetus auratus) with dermatologic and other clinical signs (polyuria, polydypsia) similar to those found in other mammalian species with hyperadrenocorticism. Among other diagnostic tests, the urine cortisol/creatinine ratio was measured and was found to be increased, which appeared to support the diagnosis. Treatment with ketoconazole was initiated, without apparent success.

Myocardial disarray: an architectural disorganization linked with adrenergic stress?

BACKGROUND: Myocardial disarray is a structural abnormality found in specific zones of the normal heart. In some conditions, such as hypertrophic cardiomyopathy (HCM), its occurrence represents a pathological process leading to myocardial asynergy. The incidence of "pathological" myocardial disarray in humans is still not known. It has been suggested that a link exists between adrenergic overactivity and myocardial disarray. The aim of the present study is to compare heart findings in conditions with and without chronic sympathetic overtone for evidence of possible linkage in humans. MATERIALS AND METHODS: A total of 340 hearts were studied. They were divided into seven groups: sudden/unexpected coronary death; sudden/unexpected death in silent Chagas' disease; brain haemorrhage following berry aneurysm rupture; transplanted hearts; congestive heart failure, AIDS and cocaine abuse. Findings in these hearts were compared with anatomic changes in 92 control hearts, where the decedent had died from head trauma, electrocution, or carbon monoxide intoxication. The frequency and presence of myocardial disarray were recorded and correlated to heart weight, extent of myocardial fibrosis, and contraction band necrosis (CBN). RESULTS: Hearts from patients with conditions that increased sympathetic tone showed an association of myocardial disarray and contraction band necrosis without any relationship to heart weight. CONCLUSIONS: Myocardial disarray was observed in cardiac areas where it is not found normally. It was associated with adrenergic myocardial stress morphologically expressed by a higher number of foci (p<0.01) and myocells (p<0.001) with CBN versus findings in normal subjects. The condition deserves further study as a possible myocardial asynergic and arrhythmogenic factor especially in sudden/unexpected death.

[Asymptomatic tumors of the adrenals (incidentalomas): criteria for the endoscopic removal].

An algorithm of using modern methods of the laboratory and X-ray examination and of operative treatment of patients by laparoscopic techniques was developed on the basis of an analysis of the results of diagnosis, endovideosurgical treatment of 132 patients with adrenal tumors without clear clinical signs, hypercortisolism and hyperadrenalinectomy (incidentalomas). Laparoscopic techniques were shown to be less traumatic and dangerous under conditions of regular using them in specialized clinics.

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

BACKGROUND: Atypical hyperadrenocorticism (AHAC) is considered when dogs have clinical signs of hypercortisolemia with normal hyperadrenocorticism screening tests. HYPOTHESIS/OBJECTIVES: To compare cortisol concentrations and adrenal gland size among dogs with pituitary-dependent hyperadrenocorticism (PDH), atypical hyperadrenocorticism (AHAC), and healthy controls. ANIMALS: Ten healthy dogs, 7 dogs with PDH, and 8 dogs with AHAC. METHOD: Dogs 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. RESULTS: Hourly (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 IMPORTANCE: Serum 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.

Development of pituitary-adrenal endocrine function in the marmoset monkey: infant hypercortisolism is the norm.

Early life stress, involving activation of the hypothalamic-pituitary-adrenal (HPA) system, is associated with altered functioning of stress-related systems in adulthood. In the rat, postnatal development is characterized by low basal HPA activity and stress hyporesponsiveness, and infant exposure to atypical glucocorticoid levels leads to chronic alteration of HPA function and HPA-dependent peripheral and central processes. There have been few studies of primate HPA ontogeny, and here we report a study of changes in pituitary-adrenal function between birth and adulthood in the common marmoset monkey. In this simian primate, basal plasma ACTH and cortisol levels were actually elevated in neonates (ACTH, 141 +/- 28 pg/ml; cortisol, 1903 +/- 326 microg/dl) and wk 4 infants (ACTH, 114 +/- 9 pg/ml; cortisol, 290 +/- 8 microg/dl) relative to month 2 infants, juveniles (month 6), subadults (month 12), and adults (>2 yr; ACTH, 37 +/- 4 to 61 +/- 8 pg/ml; cortisol, 101 +/- 2 to 195 +/- 4 microg/dl). In contrast to older life stages, neonates lacked circadian change in their plasma cortisol levels, and this state of consistently high cortisol was associated with large adrenal glands in addition to high ACTH levels. Cerebrospinal fluid cortisol levels were, in accord with plasma levels, higher in wk 4 infants than in juveniles and subadults. In terms of stress response, month 2 infants demonstrated ACTH and cortisol peak stress responses similar to those at older life stages (infant stress cortisol, 185 +/- 36% of basal; subadult stress cortisol, 174 +/- 6% of basal); whereas infant ACTH recovery was also similar to that in older subjects, their cortisol poststress recovery was retarded. This primate, it is proposed, provides an excellent complementary model in which to test hypotheses derived from the rat model relating to HPA system ontogeny and the chronic effects and biomedical implications of hypercorticoidism during early life.