The pathogenesis of pituitary-dependent Cushing's syndrome.
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Biomedical subjects
Publications and source records attributed to A Rijnberk.
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In 8 elderly female dogs a syndrome of hypercalcaemia and hypophosphataemia was found in association with a perirectal adenocarcinoma. Following removal of the tumour the hypercalcaemia resolved within two days in four of the five operated animals.
The results of electrocardiogram (ECG) recordings in 19 dogs with primary hypothyroidism are presented. Low voltage and inverted T waves were the most frequently observed abnormalities. In a number of dogs the ECG changes contributed to the diagnosis of hypothyroidism. A few dogs had even been referred to the cardiopulmonary service because of decreased exercise tolerance and the ECG pointed to the need for thyroid function studies.
Hereditary congenital goiter occurring in an inbred breed of goats is reported. The goitrous goats were severely hypothyroid. Thyroglobulin-related antigens could only be detected by radioimmunoassay in amounts of 0.03% of the total protein concentration in the 105,000 x g supernate of the goitrous gland, which corresponded with 8 microgram soluble thyroglobulin-related antigens/g tissue. After treatment with digitonin, 4 microgram thyroglobulin-related antigens/g tissue could be extracted from the sediment. This means that the gland contained about 12 microgram thyroglobulin-related antigens/g tissue (normal about 100 mg/g). However, no thyroglobulin (19S) could be detected by ultracentrifugation experiments, immunodiffusion, or immunoelectrophoresis. Iodinated proteins with sedimentation constants of 3-9S were found. Among these iodinated macromolecular compounds, iodinated "albumin" and some non-hydrolysable iodinated material was found. These last mentioned components were also found in the blood, indicating a leakage from the gland. As described for comparable cases, these results indicate a defect in thyroglobulin synthesis or its regulation.
The biochemical characterization of 22 cases of pituitary-dependent hyperadrenocorticism in the dog, is reported. The principal characteristics of the disease include excessive and non-rhythmic production of cortisol, decreased sensitivity of the hypothalamic-pituitary system to the suppressive effects of dexamethasone, decreased responsiveness of the pituitary-adrenocortical system to the stimulus of insulin-induced hypoglycaemia and increased responsiveness of the system to stimulation with lysine-vasopressin. From these observations it is concluded that pituitary-dependent hyperadrenocorticism in the dog is a valid model for study of the pathogenesis of the disease in man. For the diagnosis of hyperadrenocorticism itself, the measurement of the concentration of corticosteroids in a single sample of plasma obtained 8 h after intravenous injection of 0.01 mg dexamethasone/kg was sufficient. The level of 11-hydroxycorticosteroids was less than 140 nmol/1 plasma in normal dogs, whereas higher values were found in dogs with hyperadrenocorticism. For purposes of differential diagnosis, measurement of the level of corticosteroids in the plasma both before and 4 h after intravenous injection of 0.05 mg dexamethasone/kg is adequage: suppression is obtained only in cases of pituitary-dependent hyperadrenocorticism.
Hypothalamic corticotrophin releasing factor (CRF) activity was determined in five dogs with spontaneous hyperadrenocorticism and in three control animals (one untreated, one treated with high doses of ACTH for 2 months and one treated with high doses of cortisone for 2 months). Hypothalamic CRF activity was low or undetectable in four dogs with Cushing's syndrome due to an adrenocortical tumour. The results are compatible with a pituitary origin for pituitary-dependent hyperadrenocorticism in the dog but are not conclusive; direct information about the rates of hypothalamic CRF secretion is required.
A modified water-deprivation test was performed on 12 polyuric and 4 clinically normal dogs. Immediately after maximal urine osmolality had been achieved with water deprivation, antidiuretic hormone was injected to test further renal concentrating ability. The test provided accurate diagnosis of severe hypothalamic-neurohypophyseal diabetes insipidus in 3 dogs, partial diabetes insipidus in 2 dogs, and primary (psychogenic) polydipsia in 2 dogs. Five polyuric dogs with hyperadreno corticism had a response to the modified water-deprivation test similar to that of dogs with partial diabetes indipidus.
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Gamma camera imaging of the adrenal glands was done in 8 dogs with hyperadrenocorticism and 4 normal dogs given intravenous injections of 131I-19-iodocholesterol. In normal dogs, both adrenal glands could be visualized separately, and there was no difficulty in distinguishing among the images of normal glands, hyperplastic glands, and functional adrenal tumors. In addition, gamma camera imaging enabled the correct surgical site to be selected for removal of adrenal tumors. Hyperadrenocorticism was diagnosed in 8 dogs by evaluation of urinary 17-hydroxycorticosteroid (OHCS) excretion rates, urinary 17-OHCS and plasma 11beta-OHCS RESPONSES TO DEXAMETHASONE SUPPRESSION OF ENDOGENOUS ADRENOCORTICOTROPIN (ACTH) secretion, and plasma 11beta-OHCS response to intravenous administration of ACTH. Base line 17-OHCS excretion increased in 5 of the 8 dogs. Plasma 11beta-OHCS concentrations were not decreased by dexamethasone administration in the 4 dogs subsequently found to have adrenal tumors; however, there was an exaggerated increase in plasma 11beta-OHCS concentration after administration of ACTH in 3 of the 4 dogs which had bilateral adrenocortical hyperplasia.
An introductory part concerned with the distribution of fluid and electrolytes over the various compartments of the body and the acid-base regulation is followed by a discussion of the fluid balance and pathological losses of fluid and electrolytes. An assessment of patients showing dehydration is based on the histories, clinical examination and laboratory studies, in order to gain an impression of the state of hydration, electrolyte deficiencies, acid-base equilibrium, caloric requirements and renal function. The guidelines for fluid therapy include the scheme of this form of treatment, some comments on the available fluids and the techniques in large and small animals.
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