ABSTRACT
Medical management is currently the most common treatment for pituitary-dependent hyperadrenocorticism and hypersomatotropism/acromegaly in veterinary medicine. Medical management does not provide a cure for either disease process, and rarely is pituitary imaging a part of initial diagnostics. Early pituitary imaging in animals with clinically functional pituitary tumors provides a baseline assessment, allows monitoring of tumor changes, and permits radiation and surgical planning. Surgery is the only treatment for pituitary tumors that has curative intent and allows for a definitive diagnosis. Surgical removal of pituitary tumors via transsphenoidal hypophysectomy is an effective treatment for clinical pituitary tumors in patients exhibiting endocrine abnormalities associated with pituitary-dependent hyperadrenocorticism and hypersomatotropism. Surgery, however, is rarely pursued until patients have failed medical management, and often not until they are showing neurologic signs, making surgical success challenging. It is well documented that dogs surgically treated when the pituitary mass is small have a lower mortality, a lower recurrence rate, and a longer survival than those with larger pituitary masses. Providing owners with the option of early pituitary imaging in addition to medical, surgical, and radiation treatment options should be the standard of care for animals diagnosed with pituitary-dependent hyperadrenocorticism or hypersomatotropism.
Subject(s)
Cat Diseases/surgery , Dog Diseases/surgery , Neoplasm Recurrence, Local/veterinary , Pituitary Neoplasms/veterinary , Adrenocortical Hyperfunction/etiology , Adrenocortical Hyperfunction/veterinary , Animals , Cats , Dogs , Hypophysectomy/veterinary , Neoplasm Recurrence, Local/complications , Neoplasm Recurrence, Local/surgery , Pituitary Neoplasms/complications , Pituitary Neoplasms/surgeryABSTRACT
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.
Subject(s)
Adrenocortical Hyperfunction/veterinary , Dog Diseases/etiology , Ganglioglioma/veterinary , Pituitary Diseases/veterinary , Adrenocortical Hyperfunction/diagnostic imaging , Adrenocortical Hyperfunction/etiology , Adrenocortical Hyperfunction/pathology , Adrenocorticotropic Hormone/blood , Animals , Corticotrophs/pathology , Dog Diseases/diagnostic imaging , Dog Diseases/pathology , Dogs , Ganglioglioma/complications , Ganglioglioma/pathology , Hypophysectomy/veterinary , Magnetic Resonance Imaging/veterinary , Male , Pituitary Diseases/complications , Pituitary Diseases/pathology , Pituitary Gland/diagnostic imaging , Pituitary Gland/pathologyABSTRACT
Cushing's syndrome (CS) is a set of clinical symptoms which occur as a result of hypercortisolemia. Endogenous ACTH-dependent CS related to an ectopic ACTH-secreting tumour constitutes 12%-17% of CS cases and is one of the most common causes of paraneoplastic syndromes. This study presents a case of a 31 year-old man with diabetes, hypertension, rosacea, purple stretch marks and hypokalemia. Findings of diagnostic procedures include high concentrations of cortisol and ACTH, pituitary microadenoma and a tumour in the anterior mediastinum. Dynamic hormone tests determined the source of excess hormone secretion and ectopic ACTH-dependent CS was diagnosed. Due to increasing symptoms of superior vena cava syndrome, an emergency resection of almost the whole tumour was performed, with only a small part of the upper pole left because of the proximity of large vessels and a risk of damaging them. On the basis of histopathological tests, an atypical carcinoid tumour of the thymus was identified. Immediately after the surgical procedure, there was a significant reduction of clinical and laboratory traits of hypercortisolemia, yet, during the 46 weeks of postoperative observation, despite chemotherapy, the progression of residual masses of the tumour occurred with metastases and increased hormone indices. The presented case shows and discusses the differentiation of ACTH-dependent hypercortisolemia and its causes, difficulties in surgical therapy and chemotherapy, as well as prognosis for atypical carcinoid of the thymus, which is a rare disease.
Subject(s)
Adrenocortical Hyperfunction/etiology , Carcinoid Tumor/complications , Cushing Syndrome/etiology , Pituitary Neoplasms/complications , Thymus Neoplasms/complications , Adult , Humans , MaleABSTRACT
ACTH-ectopic syndrome is a severe, multiple-symptom disease characterized by secretion of adrenocorticotropic hormone (ACTH) by ectopic tumor, increased release of adrenal cortical hormones and clinical picture of hypercorticism. Diagnosis and treatment of ACTH-ectopic syndrome is still difficult problem despite the achievements of modern medicine. There are several unresolved issues including optimal diagnostic algorithm, indications for various surgical procedures and their optimal dates. This review is devoted to these questions.
Subject(s)
ACTH Syndrome, Ectopic/surgery , Adrenocortical Hyperfunction/surgery , ACTH Syndrome, Ectopic/diagnosis , ACTH Syndrome, Ectopic/etiology , Adrenocortical Hyperfunction/diagnosis , Adrenocortical Hyperfunction/etiology , Algorithms , HumansABSTRACT
PURPOSE OF REVIEW: Acute drug-induced hypertension, sympathomimetic toxicity, and other hyperadrenergic states can be caused by both xenobiotic toxicity and withdrawal. This manuscript is a selective review of the recent literature regarding pharmacologic causes of hypertensive emergencies and other hyperadrenergic states. RECENT FINDINGS: We will discuss designer stimulants, alpha2 and baclofen agonist withdrawal, and the clinical entity known as posterior reversible encephalopathy syndrome (PRES). Additionally, we examine the controversial "unopposed alpha" phenomenon which may result from use of beta-adrenergic antagonist in the presence of stimulant toxicity. These topics encompass clinical situations and disease entities that are increasingly encountered and are often either unanticipated or under-recognized.
Subject(s)
Adrenocortical Hyperfunction/chemically induced , Hypertension/chemically induced , Substance Withdrawal Syndrome/complications , Sympathomimetics/adverse effects , Adrenocortical Hyperfunction/etiology , Autonomic Nervous System Diseases/chemically induced , Autonomic Nervous System Diseases/etiology , Humans , Hypertension/etiology , Posterior Leukoencephalopathy Syndrome/chemically induced , Posterior Leukoencephalopathy Syndrome/etiologyABSTRACT
BACKGROUND: Traumatic brain injury (TBI) elicits intense sympathetic nervous system (SNS) activation with profuse catecholamine secretion. The resultant hyperadrenergic state is linked to immunomodulation both within the brain and systemically. Dysregulated inflammation post-TBI exacerbates secondary brain injury and contributes to unfavorable patient outcomes including death. The aim of this study was to characterize the early dynamic profile of circulating inflammatory cytokines/chemokines in patients admitted for moderate-to-severe TBI, to examine interrelationships between these mediators and catecholamines, as well as clinical indices of injury severity and neurological outcome. METHODS: Blood was sampled from 166 isolated TBI patients (aged 45 ± 20.3 years; 74.7 % male) on admission, 6-, 12-, and 24-h post-injury and from healthy controls (N = 21). Plasma cytokine [interleukin (IL)-1ß, -2, -4, -5, -10, -12p70, -13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ] and chemokine [IL-8, eotaxin, eotaxin-3, IFN-γ-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, -4, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1ß, thymus activation regulated chemokine (TARC)] concentrations were analyzed using high-sensitivity electrochemiluminescence multiplex immunoassays. Plasma catecholamines [epinephrine (Epi), norepinephrine (NE)] were measured by immunoassay. Neurological outcome at 6 months was assessed using the extended Glasgow outcome scale (GOSE) dichotomized as good (>4) or poor (≤4) outcomes. RESULTS: Patients showed altered levels of IL-10 and all chemokines assayed relative to controls. Significant differences in a number of markers were evident between moderate and severe TBI cohorts. Elevated IL-8, IL-10, and TNF-α, as well as alterations in 8 of 9 chemokines, were associated with poor outcome at 6 months. Notably, a positive association was found between Epi and IL-1ß, IL-10, Eotaxin, IL-8, and MCP-1. NE was positively associated with IL-1ß, IL-10, TNF-α, eotaxin, IL-8, IP-10, and MCP-1. CONCLUSIONS: Our results provide further evidence that exaggerated SNS activation acutely after isolated TBI in humans may contribute to harmful peripheral inflammatory cytokine/chemokine dysregulation. These findings are consistent with a potentially beneficial role for therapies aimed at modulating the inflammatory response and hyperadrenergic state acutely post-injury.
Subject(s)
Adrenocortical Hyperfunction/blood , Adrenocortical Hyperfunction/etiology , Brain Injuries/complications , Cytokines/blood , Adult , Aged , Catecholamines/blood , Female , Glasgow Coma Scale , Humans , Male , Middle Aged , Statistics as Topic , Time Factors , Tomography Scanners, X-Ray ComputedABSTRACT
Cortisol diurnal variation may be abnormal among patients with endogenous Cushing syndrome (CS). The study objective was to compare the plasma cortisol AM/PM ratios between different etiologies of CS. This is a retrospective cohort study, conducted at a clinical research center. Adult patients with CS that underwent adrenalectomy or trans-sphenoidal surgery (n=105) were divided to those with a pathologically confirmed diagnosis of Cushing disease (n=21) and those with primary adrenal CS, including unilateral adrenal adenoma (n=28), adrenocortical hyperplasia (n=45), and primary pigmented nodular adrenocortical disease (PPNAD, n=11). Diurnal plasma cortisol measurements were obtained at 11:30 PM and midnight and at 7:30 and 8:00 AM. The ratios between the mean morning levels and mean late-night levels were calculated. Mean plasma cortisol AM/PM ratio was lower among CD patients compared to those with primary adrenal CS (1.4±0.6 vs. 2.3±1.5, p<0.001, respectively). An AM/PM cortisol ratio≥2.0 among patients with unsuppressed ACTH (>15 pg/ml) excludes CD with a 85.0% specificity and a negative predictive value (NPV) of 90.9%. Among patients with primary adrenal CS, an AM/PM cortisol≥1.2 had specificity and NPV of 100% for ruling out a diagnosis of PPNAD. Plasma cortisol AM/PM ratios are lower among patients with CD compared with primary adrenal CS, and may aid in the differential diagnosis of endogenous hypercortisolemia.
Subject(s)
Adrenal Cortex Diseases/diagnosis , Adrenocortical Adenoma/diagnosis , Adrenocortical Hyperfunction/diagnosis , Circadian Rhythm/physiology , Cushing Syndrome/blood , Hydrocortisone/blood , Adrenal Cortex Diseases/blood , Adrenal Cortex Diseases/etiology , Adrenalectomy , Adrenocortical Adenoma/blood , Adrenocortical Adenoma/etiology , Adrenocortical Hyperfunction/blood , Adrenocortical Hyperfunction/etiology , Adult , Cushing Syndrome/complications , Cushing Syndrome/physiopathology , Cushing Syndrome/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
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.
Subject(s)
Adrenal Hyperplasia, Congenital/complications , Adrenal Rest Tumor/pathology , Adrenocortical Hyperfunction/pathology , Biomarkers/analysis , Cytochromes b5/metabolism , Adrenal Rest Tumor/etiology , Adrenal Rest Tumor/metabolism , Adrenocortical Hyperfunction/etiology , Adrenocortical Hyperfunction/metabolism , Case-Control Studies , Child, Preschool , Cytochromes b5/genetics , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Prognosis , TranscriptomeABSTRACT
Here, we report a case of Steroid cell tumour of ovary--Not otherwise specified variant, who presented with evidences of hyperandrogenism, hypercortisolismn and hyperprolactinemia and hyperestrogenemnia. All hormone abnormalities were resolved after Right Salpingo-Oopherectomy.
Subject(s)
Cushing Syndrome/etiology , Hyperandrogenism/etiology , Hyperprolactinemia/etiology , Ovarian Neoplasms/complications , Ovary/metabolism , Adrenocortical Hyperfunction/etiology , Adrenocortical Hyperfunction/physiopathology , Adult , Biopsy , Diagnosis, Differential , Female , Humans , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Ovariectomy , Ovary/pathology , Treatment OutcomeABSTRACT
Two cases of middle-aged female patients treated by gastric bypass surgery for weight loss presented to our clinic for a follow-up examination 3-6 months after the surgical procedure (a mini gastric bypass and a modified single anastomosis sleeve-ileostomy). In both patients increased ACTH levels and either high serum cortisol or an increased urinary cortisol excretion was apparent and triggered further endocrine testing. Serum cortisol could not be suppressed adequately by 2 and 4 mg dexamethasone in the standardized oral overnight suppression test while midnight salivary cortisol dropped well below the desired cut-off. This led to the hypothesis of an impaired dexamethasone resorption and could be further substantiated by suppression of serum cortisol below the cut-off by an intravenous dexamethasone application. The data presented point to an impairment of enteral synthetic corticosteroid resorption in patients after gastric bypass surgery and could be of importance for individuals in need for immunosuppressive treatment. In view of the growing number of bariatric procedures, pharmacokinetics of corticosteroids and other drugs should be tested in clinical trials.
Subject(s)
Adrenocortical Hyperfunction/metabolism , Dexamethasone/pharmacokinetics , Gastric Bypass/adverse effects , Hydrocortisone/pharmacokinetics , Postoperative Complications/metabolism , Adrenocortical Hyperfunction/etiology , Adult , Female , Humans , Immunosuppression Therapy , Middle Aged , Postoperative Complications/etiologyABSTRACT
Pituitary tumours account for 15% of intracranial neoplasms and are benign monoclonal neoplasms that may be clinically silent or secrete hormones, including prolactin, growth hormone, adrenocorticotrophic hormone or, rarely, thyroid-stimulating hormone or gonadotrophins. These adenomas account for clinical infertility, growth disorders and hypercortisolism or metabolic dysfunctions associated with hypopituitarism. We explored the role of disordered pituitary cell proliferation control in the pathogenesis of these invariably benign adenomas, studying the mechanisms underlying pituitary aneuploidy, premature proliferative arrest (senescence), markers of cell proliferation and tumorigenesis in single, double or triply mutant transgenic mice with mutations of Rb, Pttg and/or p21. Our results provide further insights into the role of cell-cycle control and growth constraints on experimental and human pituitary tumours, which underlie their failure to progress to malignancy. These results improve our understanding of pituitary syndromes associated with infertility, growth disorders, hypercortisolism or adrenal, thyroid and gonadal failure due to abrogated pituitary function.
Subject(s)
Brain Neoplasms/metabolism , Cell Cycle , Cellular Senescence , Mutation , Neoplasm Proteins/metabolism , Pituitary Neoplasms/metabolism , Adrenocortical Hyperfunction/etiology , Adrenocortical Hyperfunction/genetics , Adrenocortical Hyperfunction/metabolism , Adrenocortical Hyperfunction/therapy , Aneuploidy , Animals , Brain Neoplasms/complications , Brain Neoplasms/genetics , Brain Neoplasms/therapy , Growth Disorders/etiology , Growth Disorders/genetics , Growth Disorders/metabolism , Growth Disorders/therapy , Humans , Infertility/etiology , Infertility/genetics , Infertility/metabolism , Infertility/therapy , Mice , Mice, Transgenic , Neoplasm Proteins/genetics , Pituitary Hormones/metabolism , Pituitary Neoplasms/complications , Pituitary Neoplasms/genetics , Pituitary Neoplasms/therapy , Retinoblastoma Protein/genetics , Retinoblastoma Protein/metabolism , SecurinABSTRACT
An 8 year old male castrated Russian Blue cat with polyuria, polydipsia, polyphagia, abdominal enlargement, unkempt and easily epilated hair coat and abdominal alopecia is described. As a first step diabetes mellitus was diagnosed. Further work-up by ultrasonography revealed severe bilateral enlargement of the adrenal glands. Hypercortisolism was suspected and therefore ACTH stimulation test and dexamethasone suppression test were performed. In all samples cortisol concentrations were below the detection limit of the assay used. Various precursor hormones were measured and high progesterone concentrations were found. Histologically, the adrenal masses were characterised as bilateral adrenal carcinomas of the adrenal cortex. The case report demonstrates that adrenal gland tumors are also capable to secrete sex hormones instead of cortisol. Clinical signs of hyperprogesteronism are identical to those of hypercortisolism.
Subject(s)
Adrenal Cortex Neoplasms/veterinary , Adrenocortical Carcinoma/veterinary , Adrenocortical Hyperfunction/veterinary , Cat Diseases/blood , Progesterone/blood , Adrenal Cortex Function Tests/veterinary , Adrenal Cortex Neoplasms/complications , Adrenal Cortex Neoplasms/metabolism , Adrenocortical Carcinoma/complications , Adrenocortical Carcinoma/metabolism , Adrenocortical Hyperfunction/blood , Adrenocortical Hyperfunction/etiology , Animals , Cats , Diabetes Complications/blood , Diabetes Complications/veterinary , MaleABSTRACT
OBJECTIVE: To investigate the feasibility of, and outcome after, laparoscopic adrenalectomy in dogs with unilateral adrenocortical carcinoma. STUDY DESIGN: Case series. ANIMALS: Dogs (n=7) with Cushing's syndrome caused by unilateral adrenocortical carcinoma. METHODS: Laparoscopic adrenalectomy with the dog in lateral recumbency on the unaffected side. Three 5-mm portals (1 laparoscopic portal, 2 instrument portals) were placed in the paralumbar fossa. A fourth instrumental portal (5-12 mm) was placed above the kidney. After dissection and hemostatic control of the phrenicoabdominal vein, the adrenal gland was carefully dissected or when there was capsule fragility, necrotic content was partially aspirated. The remaining glandular tissue was removed through the 12-mm trocar site. RESULTS: Dogs with unilateral adrenocortical carcinoma (3 right-sided, 4 left-sided) without invasion of the caudal vena cava were successfully operated by laparoscopic approach. There were no significant intraoperative complications; 2 dogs died within 48 hours of surgery because of respiratory complications. Five dogs were discharged 72 hours after surgery, and signs of hyperadrenocorticism disappeared thereafter (survival time ranged from 7 to 25 months). CONCLUSIONS: Laparoscopic adrenalectomy is feasible in dogs with either right- or left-sided adrenocortical carcinoma not involving the caudal vena cava. CLINICAL RELEVANCE: When performed by experienced surgeons, laparoscopic adrenalectomy offers a minimally invasive alternative to open laparotomy or retroperitoneal surgery for the treatment of unilateral adrenocortical carcinoma in dogs.
Subject(s)
Adrenal Cortex Neoplasms/veterinary , Adrenalectomy/veterinary , Adrenocortical Carcinoma/veterinary , Adrenocortical Hyperfunction/veterinary , Dog Diseases/surgery , Adrenal Cortex Neoplasms/complications , Adrenal Cortex Neoplasms/surgery , Adrenalectomy/instrumentation , Adrenalectomy/methods , Adrenocortical Carcinoma/complications , Adrenocortical Carcinoma/surgery , Adrenocortical Hyperfunction/etiology , Animals , Dogs , Female , Male , Treatment OutcomeABSTRACT
Adrenal cortex hyperfunction may occasionally be due to stimulation of steroid hormone production by LH/hCG. The recent demonstration of the LH/hCG receptor in a variety of normal and abnormal human adrenal tissues has provided a novel explanation for these clinical observations and offers the possibility of spontaneous remission (as in pregnancy-related hyperfunction) or effective treatment with GnRH-agonists (to down-regulate LH secretion in menopausal patients). Involvement of adrenal LH/hCG receptors should be considered in pregnant or post-menopausal patients with ACTH-independent Cushing's syndrome or androgen excess. Additional investigations are needed to better define the role of the LH/hCG receptor in the normal adult and fetal human adrenal and to understand how this system is excessively activated in rare cases of human disease.
Subject(s)
Adrenocortical Hyperfunction/etiology , Chorionic Gonadotropin/physiology , Luteinizing Hormone/physiology , Adenoma/metabolism , Adrenal Gland Neoplasms/metabolism , Adrenal Glands/metabolism , Aldosterone/metabolism , Androgens/metabolism , Animals , Disease Models, Animal , Estrogens/metabolism , Female , Humans , Menopause/physiology , Pregnancy , Pregnancy Complications/pathology , Receptors, LH/metabolismABSTRACT
The efficacy of low doses of radiotherapy for the treatment of pituitary corticotroph macrotumors in dogs is evaluated retrospectively. Twelve dogs with pituitary-dependent hyperadrenocorticism and a large pituitary tumor treated with 36 Gy of radiation were included. Radiation was delivered in 12 fractions of 3 Gy over a 4- to 6-week period. Effects of radiation therapy on tumor size were assessed by computed tomography scans; a decrease was observed in 11 dogs (decrease > 50% in 6 dogs). Three dogs were reirradiated due to major tumor regrowth or a lack of tumor decrease (mean total dose: 22 Gy given in 3-Gy fractions over 3 or 4 weeks). The mean and median survival times following the initiation of radiotherapy were 22.6 months (688 days) and 17.7 months (539 days), respectively. These data are consistent with previous findings, based on high-dose radiation, showing that radiotherapy is a useful option for treating pituitary corticotroph macrotumors in dogs. Furthermore, computed tomography follow-up of the treated dogs demonstrates objectively the efficacy of radiotherapy against corticotroph tumors in dogs.
Subject(s)
Adrenocortical Hyperfunction/veterinary , Dog Diseases/radiotherapy , Pituitary Neoplasms/veterinary , Adrenocortical Hyperfunction/etiology , Adrenocortical Hyperfunction/radiotherapy , Animals , Dogs , Dose Fractionation, Radiation , Dose-Response Relationship, Radiation , Female , Male , Pituitary Neoplasms/radiotherapy , Retrospective Studies , Survival Analysis , Tomography, X-Ray Computed/veterinary , Treatment OutcomeABSTRACT
Many of the stressor treatments used in animal models of depression have parallels in the normal experiences of domestic pigs. The experiment described here aimed to assess whether a chronic-intermittent stress regime caused behavioural or physiological changes, indicative of depression, in domestic pigs. Ten juvenile male pigs were exposed to a social and environmental stress regime. Over the stressor period, weight gain was significantly lower in test pigs than in control pigs. Stress treatment had a significant effect on salivary cortisol levels, with test pigs having a higher salivary cortisol concentration than control pigs after the stress treatment but not before. Test pigs showed less ventral lying than control pigs in the post-stress observation. A detrended fluctuation analysis (DFA) of postural behavioural organisation showed that test pigs had a more structured pattern of activity than controls in the post-stress observation and a tendency towards a more structured pattern in the pre-stress observation. There were no major behavioural differences between the two groups during three repeated open field tests. The results suggest that the stressor treatment did create a mild chronic stress, as indicated by the hypercortisolaemia and lower weight gain in the test pigs. However, no unambiguous behavioural indicators of depression were seen. The behavioural analysis did show that fractal techniques, such as DFA, could be applied to pig behaviour and that they can reveal extra novel information about the structure of an individual's behavioural organisation and how it changes in response to complex environmental stressors.
Subject(s)
Behavior, Animal/physiology , Stress, Psychological/metabolism , Stress, Psychological/physiopathology , Adrenocortical Hyperfunction/etiology , Analysis of Variance , Animals , Animals, Newborn , Body Weight/physiology , Exploratory Behavior/physiology , Hydrocortisone/metabolism , Male , Saliva/chemistry , Stress, Psychological/complications , Swine , Time FactorsABSTRACT
Several hormones regulate Na(+), K(+)-ATPase content in the muscle cell membrane, which is essential for maintaining muscle cell excitability. Chronic glucocorticoid excess is associated with muscle weakness and reduced endurance. We hypothesized that chronic glucocorticoid excess affects Na(+), K(+)-ATPase content in canine skeletal muscle, and contributes to reduced endurance and muscle weakness associated with pituitary-dependent hyperadrenocorticism (PDH) in dogs. Therefore, Na(+), K(+)-ATPase content in skeletal muscle was evaluated before and after hypophysectomy and hormone replacement (cortisone and l-thyroxin) in dogs with PDH (n=13), and in healthy controls (n=6). In addition, baseline and exercise-induced changes in plasma electrolyte concentrations and acid-base balance were evaluated before and after hypophysectomy in dogs with PDH. Na(+), K(+)-ATPase content of gluteal muscle in dogs with PDH was significantly lower than in control dogs (201+/-13pmol/g versus 260+/-8pmol/g wet weight; P<0.01). Similar differences were found in palatine muscle. After hypophysectomy and on hormone replacement, Na(+), K(+)-ATPase was increased (234+/-7pmol/g wet weight). Both plasma pH and base excess in dogs with PDH (7.44+/-0.01; 1.7+/-0.6mmol/l, respectively) were significantly higher (P<0.05) than after hypophysectomy and hormone replacement (7.41+/-0.01; -0.2+/-0.4mmol/l, respectively). Exercise induced respiratory alkalosis, but did not result in hyperkalemia in dogs with PDH. In conclusion, chronic glucocorticoid excess in dogs with PDH is associated with decreased Na(+), K(+)-ATPase content in skeletal muscle. This may contribute to reduce endurance in canine PDH, although dogs with PDH did not exhibit exercise-induced hyperkalemia. Na(+), K(+)-ATPase content normalized to values statistically not different from healthy controls after hypophysectomy and hormone replacement.
Subject(s)
Adrenocortical Hyperfunction/veterinary , Dog Diseases/enzymology , Muscle, Skeletal/enzymology , Pituitary Neoplasms/veterinary , Sodium-Potassium-Exchanging ATPase/analysis , Adrenocortical Hyperfunction/enzymology , Adrenocortical Hyperfunction/etiology , Adrenocorticotropic Hormone/blood , Animals , Blood , Dogs , Female , Glucocorticoids/blood , Growth Hormone/blood , Hormone Replacement Therapy/veterinary , Hydrocortisone/blood , Hydrogen-Ion Concentration , Hypophysectomy/veterinary , Insulin-Like Growth Factor I/analysis , Male , Ouabain/metabolism , Physical Endurance , Physical Exertion , Pituitary Neoplasms/complications , Pituitary Neoplasms/surgery , Thyrotropin/blood , Thyroxine/blood , TritiumABSTRACT
Cabergoline is a dopaminergic agonist with demonstrated efficiency of for the treatment of prolactin-secreting pituitary tumors. It has also been reported effective for patients with hypercortisolism uncontrolled by conventional therapies. We describe the use of cabergoline in three patients with Cushing's disease, one of them presenting a silent ACTH-secreting pituitary tumor. Those patients underwent surgery and only one has been treated with radiation therapy. However persisting hypercortisolism motivated the use of cabergoline. We describe a decrease or a normalization in hypercortisolism; for one of the subjects, tumor growth seemed to be stopped. While cabergoline can induce a suppression of cortisol secretion or a corticotroph tumor shrinkage, the sites of action remain unclear.
Subject(s)
Adrenocortical Hyperfunction/drug therapy , Ergolines/therapeutic use , Pituitary ACTH Hypersecretion/diagnosis , Adrenocortical Hyperfunction/etiology , Adrenocortical Hyperfunction/surgery , Adult , Cabergoline , Dopamine Agonists/therapeutic use , Female , Humans , Hydrocortisone/urine , Magnetic Resonance Imaging , Middle Aged , Pituitary ACTH Hypersecretion/surgeryABSTRACT
BACKGROUND: The management of subclinical cortisol-secreting adenomas (SCSAs) is controversial, and available evidence to assess the superiority of an operative versus a nonoperative approach is lacking. The aim of this work was to report the postoperative results and the long-term outcomes for patients with incidentally diagnosed SCSAs and to compare the results with those of patients who underwent an operation for cortisol-secreting adenomas (CSAs). METHODS: From 1994-2011, 107 consecutive patients underwent laparoscopic unilateral adrenalectomy for either an SCSA (n = 39) or a CSA (n = 68). Preoperatively, all patients underwent standardized clinical, hormonal, and imaging assessments. Patients were followed up for ≥2 years with serial assessments of body weight, blood pressure, and glycated hemoglobin, HbA1c. RESULTS: Operative resection of SCSAs and CSAs did not significantly differ regarding operative time, conversion rate, overall operative and medical morbidity, and duration of stay. For SCSAs, the comparison between preoperative status and 2-year assessment showed a median weight loss of 6% (P < .001), a decrease in the median HbA1c of 15% (P < .001), and an improvement or normalization of blood pressure in 50% of the patients. The same significant beneficial metabolic effects of the operation with even greater improvement were observed in patients with CSAs. CONCLUSION: Laparoscopic unilateral adrenalectomy for SCSA is associated with low morbidity, no mortality, and significant improvement of various aspects of metabolic syndrome. Until additional evidence from prospective randomized controlled studies is obtained, laparoscopic unilateral adrenalectomy should be considered a valid option in the care of patients with SCSA.
Subject(s)
Adrenal Gland Neoplasms/surgery , Adrenalectomy , Adrenocortical Adenoma/surgery , Adrenocortical Hyperfunction/etiology , Incidental Findings , Laparoscopy , Adrenal Gland Neoplasms/complications , Adrenocortical Hyperfunction/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND AND OBJECTIVE: Our purpose was to assess the utility of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in pre-surgical characterization of adrenal masses. These masses were incidentally discovered in non-oncologic patients or during the study of endocrine hormone overproduction. These nodular lesions showed nonspecific or suspicious radiological features in the imaging tests routinely performed (CT and/or MRI). PATIENTS AND METHODS: This is a cross-sectional and prospective study in 12 patients with adrenal masses which were radiologically non-specific or suspicious for malignancy before adrenalectomy. An 18F-FDG-PET was made and quantitative FDG uptake (SUVmax) in the adrenal region (adrenal SUVmax) and liver (liver SUVmax), and the ratio SUVmax adrenal/liver was calculated. These parameters were related to the pathological findings. We evaluated the accuracy of the test by receive operating curves (ROC). RESULTS: The ROC to discriminate between benign and malignant lesions showed that the SUVmax was a better parameter than size or SUVmax adrenal/liver ratio. Using a SUVmax cutoff value≥3.1, sensitivity, specificity, positive and negative predictive value of the test were 100, 67, 50 and 100%, while a SUVmax adrenal/liver ratio≥1.8 showed a sensitivity, specificity, positive and negative predictive value of 67, 100, 100 and 90%, respectively. The presence of a SUVmax adrenal/liver ratio≥1.8 showed a statistically significant association with carcinoma occurrence. CONCLUSION: 18F-FDG-PET may be useful in the characterization of nonspecific or suspicious adrenal masses discovered in patients without a previous history of cancer. Its use in some cases could avoid unnecessary interventions.