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Functional defects of platelets are often studied by in-vitro aggregation tests with chemical compounds such as ADP, epinephrine and ristomycin (ristocetin). The aim of the present work was to investigate the effect of some diseases and that of nonsteroidal anti-inflammatory drug treatment on platelet aggregation in dogs. The examination had been carried out on 115 dogs by a Carat TX4 optical aggregometer (Entec GmbH, Ilmenau, Germany) first used in veterinary practice. The dogs were divided in three groups: healthy (control) dogs (n = 43), diseased dogs with normal haemostasis profile (n = 44), and dogs suffering from arthropathies with normal haemostasis profile treated with the nonsteroidal anti-inflammatory drugs ketoprofen or carprofen (n = 21). Following establishment of normal platelet aggregation curves in healthy dogs we found that some diseases such as diabetes mellitus, Cushing's disease, mastocytoma and lymphoma increased or decreased the aggregation maximum of platelets or caused changes in the feature of the aggregation curve. Carprofen treatment had no effect on platelet aggregation while ketoprofen decreased the aggregation maximum. These results showed that Carat TX4 aggregometer proved a useful instrument in studying platelet aggregation in platelet-rich plasma of dogs. For clinical pathologists it is important to know that the effects of some diseases and nonsteroidal anti-inflammatory drug treatments have to be taken into account when in-vitro platelet aggregation is evaluated. Based on our results and on those of other studies, we think standardization in aggregation methodology is highly recommended in veterinary laboratories.
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PMID:Influencing factors of ADP-induced, epinephrine-induced and ristomycin-induced platelet aggregation in dogs. 1818 Jun 10

Systemic cortisol plays an important role in the metabolism of glucose, lipids and proteins, as well as in the regulation of electrolyte balance. It is well known that the development of the microvascular disease of various organs such as the heart and kidney, in patients with diabetes mellitus, hyperlipidemia and hypertension of which disorders are frequently associated with Cushing's syndrome. Thus, we should treat Cushing's syndrome as soon as possible, since many complications, including cardiovascular diseases and infections, will soon occur when the definite diagnosis is delayed. Adrenalectomy is essential for treatment for Cushing's syndrome even in the patients with pituitary or ectopic ACTH-producing tumor. Some case can not be treated with surgical procedures because of worsened conditions with several complications of infection and diabetes. Then we choose medical treatment. Medical adrenalectomy is achieved by using with mitotane which is usually used for adrenocortical cancer. We commonly treat the patients with Cushing's syndrome due to adrenal tumor and pituitary or ectopic ACTH producing tumor by using metyrapone which mainly inhibits 11-hydroxylase. Metyrapone is also recommended to treat the patients who are not well differentiated Cushing's disease from ectopic ACTH syndrome. We rarely use trilostane which is an inhibitor against 3beta-hydroxysteroid dehydrogenase (3beta-HSD). Replacement therapy with hydrocortisone should be considered if adrenal failure will occur during treatment with those drugs.
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PMID:[Medical treatment for Cushing's syndrome]. 1818 63

Measurement of late-night and/or midnight salivary cortisol currently used in US and European countries is a simple and convenient screening test for the initial diagnosis of Cushing's syndrome (CS). Unfortunately, this test has not been widely used in Japan. The purpose of this study was to evaluate the usefulness of the measurement of late-night salivary cortisol as a screening test for the diagnosis of CS in Japan. We studied 27 patients with various causes of CS, consisting of ACTH-dependent Cushing's disease [5] and ectopic ACTH syndrome [4] and ACTH-independent adrenal CS [11] and subclinical CS [7]. Eleven patients with type 2 diabetes and obesity and 16 normal subjects served as control group. Saliva samples were collected at late-night (23:00) in a commercially available device and assayed for cortisol by radioimmunoassay. There were highly significant correlations (P<0.0001) between late-night serum and salivary cortisol levels in normal subjects (r = 0.861) and in patients with CS (r = 0.788). Late-night salivary cortisol levels in CS patients (0.975 +/- 1.56 microg/dl) were significantly higher than those in normal subjects (0.124 +/- 0.031 microg/dl) and in obese diabetic patients (0.146 +/- 0.043 microg/dl), respectively. Twenty-five out of 27 CS patients had late-night salivary cortisol concentrations greater than 0.21 microg/dl, whereas those in control group were less than 0.2 microg/dl. Receiver operating characteristic curve (ROC) analysis showed that the cut-off point of 0.21 microg/dl provides a sensitivity of 93% and a specificity of 100%. Therefore, it is concluded that the measurement of late-night salivary cortisol is an easy and reliable noninvasive screening test for the initial diagnosis of CS, especially useful for large high-risk populations, such as diabetes and obesity.
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PMID:Late-night salivary cortisol as a screening test for the diagnosis of Cushing's syndrome in Japan. 1820 29

We review the clinical and biochemical criteria used for evaluation of the transsphenoidal pituitary surgery results in the treatment of Cushing's disease (CD). Firstly, we discuss the pathophysiology of the hypothalamic-pituitary-adrenal axis in normal subjects and patients with CD. Considering the series published in the last 25 years, we observed a significant variation in the remission or cure criteria, including the choice of biochemical tests, timing, threshold values to define remission, and the interference of glucocorticoid replacement or previous treatment. In this context we emphasize serum cortisol levels obtained early (from hours to 12 days) in the postoperative period without any glucocorticoid replacement or treatment. Our experience demonstrates that: (i) early cortisol < 5 to 7 microg/dl, (ii) a period of glucocorticoid dependence > 6 mo, (iii) absence of response of cortisol/ACTH to CRH or DDAVP, (iv) return of dexamethasone suppression, and circadian rhythm of cortisol are appropriate indices of remission of CD. In patients with undetectable cortisol levels early after surgery, recurrence seems to be low. Finally, although certain biochemical patterns are more suggestive of remission or surgical failure, none has been proven to be completely accurate, with recurrence observed in approximately 10 to 15% of the patients in long-term follow-up. We recommended that patients with CD should have long-term monitoring of the CRH-ACTH-cortisol axis and associated co-morbidities, especially hypopituitarism, diabetes mellitus, hypertension, cardiovascular disturbances, and osteoporosis.
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PMID:Criteria of cure and remission in Cushing's disease: an update. 1820 75

Pre(sub)clinical Cushing's disease is a recently described entity defined by the autonomous secretion of ACTH and the absence of a cushingoid appearance. We screened 77 hospitalized patients with diabetes mellitus for subclinical hypercortisolism and detected pre(sub)clinical Cushing's disease in 2 (2.6%) of them. In both patients, transsphenoidal surgery was performed and a microadenoma was removed. Their metabolic clearance rate of glucose measured by a glucose clamp study, an index of insulin sensitivity, significantly improved after surgery. Our results indicate that screening for subclinical hypercortisolism in diabetic patients might be useful, as surgery improves glucose tolerance and insulin sensitivity.
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PMID:Subclinical hypercortisolism in hospitalized patients with type 2 diabetes mellitus. 1836 53

Herein, we present the case of a 63-year old female patient with initial symptoms of myopathy, hypokaliemia, glucosuria and psychotic symptoms. Laboratory analysis demonstrated elevated plasma levels of ACTH and cortisol. Additionally, urine cortisol excretion was increased approximately 60-fold. MRI imaging revealed a possible pituitary microadenoma. To confirm the diagnosis a bilateral inferior petrosal sinus sampling was performed presenting higher ACTH levels on the right side. However, after surgery cortisol levels did not return to normal range. Histological examination of the tumor revealed a microadenoma. Six days postoperatively, the patient developed several pneumonic infiltrations and fever therefore antibiotic and antifungal therapy was started immediately. In addition aspergillus antigen was elevated. During this septic condition, cortisol levels further increased. The patient died despite optimal intensive care under septical conditions 8 days after surgery. Microbiological analysis identified Aspergillus fumigatus in broncho-alveolar lavage and several organ systems including the heart and brain. Neuropathological autopsy revealed nodular proliferations of corticotropic cells in the pituitary gland that are assumed to be morphological entities between diffuse hyperplasias and adenomas, termed as tumorlets. In single reports, multiple pituitary lesions in patients with Cushing's disease have been demonstrated, but to our knowledge none of these cases presented the combination of an ACTH-producing microadenoma and corticotroph cell hyperplasia in the same patient. Therefore, even after resection of a pituitary microadenoma one should be aware of the possibility of continuously elevated ACTH level being due to multifocal nodular corticotroph hyperplasia which is invisible by neuroradiological examination.
Exp Clin Endocrinol Diabetes 2009 Jun
PMID:Cushing's disease associated with both pituitary microadenoma and corticotroph hyperplasia. 2012 71

Endogenous Cushing's syndrome is a very rare entity, with an incidence of 2-4 cases per million inhabitants per year. Cases caused by ectopic ACTH secretion are under-diagnosed. Cushing's disease is the most frequent cause of endogenous Cushing's syndrome, which is 5 or 6 times more frequent than adrenal Cushing's syndrome, with an incidence of between 1.2 and 2.4 cases per million inhabitants per year. Cushing's disease is 3-8 times higher in women than in men. The frequency of adrenal tumors is 3 times higher in women, while that of Cushing's syndrome due to adrenal tumors is 3-5 times higher. Age at diagnosis of Cushing's syndrome varies according to the etiology. Most cases of Cushing's disease are due to a pituitary adenoma, although the tumor may not be visible on the available imaging techniques. ACTH-independent Cushing's syndrome is found in 20% of cases and is most frequently due to adenomas (10%) or adrenal carcinomas (8). Bilateral micronodular hyperplasia and macronodular hyperplasia are infrequent entities, representing less than 10% of all cases of ACTH-independent Cushing's syndrome. Both familial and sporadic forms exist: the familial form, or Carney complex, and ACTH-independent bilateral macronodular hyperplasia, in which the size of the adrenal glands is considerably enlarged. The signs and symptoms of Cushing's syndrome are a direct result of long-term exposure to excessive glucocorticoids. Most signs and symptoms are highly prevalent in the general population (hypertension, central obesity, diabetes mellitus or carbohydrate intolerance, osteoporosis, and characteristic phenotypical alterations).
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PMID:[Prevalence, etiology and clinical findings of Cushing's syndrome]. 1962 6

Adrenalectomy with adrenal autotransplantation used to be performed frequently for Cushing's disease in the past because of the limitations of conventional radiological techniques and the lack of adequate neurosurgical techniques. Today, however, bilateral adrenalectomy may be still required for selective patients with Cushing's syndrome when partial hypophysectomy has failed to control hypercortisolism or the source for ectopic ACTH syndrome could not be determined. Here, we report a case of recurrent Cushing's syndrome due to a pituitary adenoma, who was treated with bilateral adrenalectomy and autotransplantation for her Cushing's syndrome. Having determined pituitary adenoma as the cause of recurrent Cushing's syndrome after endocrinological investigations and imaging, we were able to treat the patient with transsphenoidal adenomectomy. We suggest that transsphenoidal resection of the adenoma rather than excision of the autotransplants and adrenal remnants should be the preferred treatment method for recurrent Cushing's disease.
Exp Clin Endocrinol Diabetes 2009 Oct
PMID:Recurrent Cushing's syndrome after adrenal autotransplantation. 1988 99

An 11-year-old male mixed breed dog diagnosed with Cushing's disease and diabetes mellitus was treated by hypophysectomy. After surgery, the hypercortisolemia disappeared and the diabetes status improved. The insulin requirement to control hyperglycemia gradually decreased. At 12 weeks after surgery, there was no requirement for insulin and we suspected the diabetes was completely resolved. In the present case, diabetes mellitus seems to be secondary to Cushing's disease. In conclusion, this mixed breed dog with coexisting Cushing's disease and diabetes mellitus is the first case showing the effectiveness of hypophysectomy to treat diabetes mellitus secondary to Cushing's disease in dogs.
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PMID:Hypophysectomy for a dog with coexisting Cushing's disease and diabetes mellitus. 1995 15

Cushing's disease, due to pituitary adrenocorticotropic hormone (ACTH) hypersecretion, is the most common etiology of spontaneous excess cortisol production. The majority of pituitary tumors causing Cushing's disease measure <1 cm and the excess morbidity associated with these tumors is mostly due to the effects of elevated, nonsuppressible, ACTH levels leading to adrenal steroid hypersecretion. Elevated circulating cortisol levels lead to abnormal fat deposition, hypertension, diabetes, coronary artery disease, osteoporosis, muscle weakness and psychological disturbances. At experienced centers, initial surgical remission rate via transnasal, transphenoidal resection approaches 80% for tumors less than 1 cm, but may be as low as 30% for larger lesions and long-term recurrence in all groups approaches 25%. Residual disease may be managed with more radical surgery, pituitary-directed radiation, bilateral adrenalectomy, or medical therapy. This paper addresses current and novel therapies in various stages of development for Cushing's disease.
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PMID:Medical treatment of Cushing's disease: Overview and recent findings. 2036 Sep 6


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