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Adrenocortical function tests in dogs with hyperfunctioning adrenocortical tumours.

The response has been studied in nine dogs with hyperadrenocorticism due to adrenocortical tumours to the administration of dexamethasone, insulin, lysine-vasopressin and tetracosactide by measuring the changes in plasma cortisol concentration. Administration of dexamethasone did not produce a decrease in the plasma concentration of cortisol in any of these dogs. Administration of insulin caused slight increases in the plasma concentration of cortisol in four out of eight dogs. Lysine-vasopressin increased the plasma concentration of cortisol in eight out of nine dogs, three responded supranomally. Eight out of the nine dogs responded to tetracosactide administration, three responded supranormally, It is concluded that in the dog, in contrast to man, the lysine-vasopressin test cannot be used to differentiate between pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to an adenocortical tumour. Apparently pituitary ACTH is not completely depleted in dogs with hyperfunctioning adrenocortical tumours.

Adrenal Cortex Function Tests

HLA antigens in patients with adrenocortical hyperfunction.

The HLA antigen frequencies in 100 Caucasian patients with adrenocortical hyperfunction were compared with those found in 352 healthy unrelated subjects. Fourteen antigens on the HLA--A locus, seventeen antigens on the HLA--B locus and three antigens on the HLA--C locus were determined using the standard NIH microlymphocytotoxicity test. The frequency of HLA--A1 antigen in the patient group was 49% as compared with 28% in the controls (pcorr less than 0.01). An increased frequency of HLA--B8 and HLA-BW35 antigens was also found, but the difference was not significant. Increased A1--B8 and A1--BW35 haplotype frequencies were observed. The relationship between the HLA system and various endogenous and exogenous factors eliciting hypercorticism, together with complementary family studies indicate that the HLA system may be a useful genetic marker of the disease susceptibility gene.

Adrenocortical Hyperfunction

The prevalence of antibodies against Toxoplasma gondii among hospitalized animals and stray dogs.

Hospitalized animals and stray dogs were serologically tested for antibodies against Toxoplasma gondii. In addition, the data were examined for the possibility of toxoplasmosis infection being associated with the clinical diagnosis and with the discharge status (alive vs. dead). Among 1056 hospitalized animals, 17 (20%) of 86 cats, 112 (14%) of 804 dogs, 34 (26%) of 133 horses and 6 (18%) of 33 cattle had serological evidence of infection with T. gondii. Only 22 (6%) of 342 young (median age = one year) stray dogs were seropositive. The difference in antibody prevalence between hospitalized and stray dogs was thought to be due to age and dietary factors. Of 249 dogs grouped by clinical diagnosis, there was significantly (p less than 0.01) higher prevalence of seropositives among dogs with diseases of the kidney or with adrenocortical hyperfunction than among dogs hospitalized for other diseases. Of 19 dogs with diseases of the kidney and 12 with adrenocortical hyperfunction 37% and 42%, respectively, were seropositive.. There was higher risk of being discharged from the hospital dead among seropositive dogs, cattle and horses than among seronegative animals of the same species. The exception was cats, where of 69 seronegative cats 29% were dead at discharge and where of 17 seropositive cats 18% were dead at discharge. The possible effects of stress due to hospitalization need further research.

Animals

Evaluation of steroid laboratory tests and adrenal gland imaging with radiocholesterol in the aetiological diagnosis of Cushing's syndrome.

Basal values of the urinary excretion of 17-oxogenic steroids and serum levels of cortisol were not satisfactory in the differentiation of 'suspected' subjects from patients with true Cushing's syndrome. With an RIA method for serum cortisol determination, the overnight dexamethasone suppression test provided the most reliable single test in establishing adrenocortical hyperfunction. Thirty-five normal subjects, fifty-nine obese patients, thirteen 'suspected' patients, and thirteen patients with disease states other than Cushing's syndrome had suppressed values below 4.0 microgram/100 ml. None of the ten patients with Cushing's syndrome had a cortisol concentration less than 16.3 microgram/100 ml. Adrenal gland scintigraphy after radiocholesterol injection is a more valuable tool than the metyrapone test and the high-dose dexamethasone suppression test in the localization and differential diagnosis of adrenocortical lesions causing Cushing's syndrome. It obviates the need for angiographic procedure in the localization of adenomas. It is a reliable technique for identifying functioning adrenal remnants. We therefore propose a schedule for studying patients with suspected adrenocortical hyperfunction.

17-Ketosteroids

Studies on ectopic ACTH-producing tumors. II. Clinical and biochemical features of 30 cases.

This report describes the clinical and biochemical features of 30 cases of ectopic ACTH-producing tumors diagnosed by the detection of ACTH in the tumor tissues. Several uncommon tumors, such as tumors of the esophagus, stomach, and larynx, were included in this series. None of the patients with bronchogenic carcinoma showed signs of classical Cushing's syndrome, whereas 7 of the remaining 13 patients with other tumors were Cushingoid in appearance. Adrenocortical hyperfunction was present in 61 percent at the first examination and developed during the course of the disease in 18 percent more. In the remaining patients (21 percent), adrenocortical function remained within normal limits. These results indicate that there exist ectopic ACTH-producing tumors without clinical and biochemical sequelae of excess hormone. In some of the tumor extracts studied, MSH and CRF-like activities and serotonin were detected. This suggests that multiple hormone production is not uncommon in ectopic ACTH-producing tumors.

Adrenocortical Hyperfunction

Gastrinoma associated with common bile duct obstruction and the ectopic production of ACTH.

A case of adrenocortical hyperfunction due to ectopic production of ACTH by a gastrin-producing tumor of the pancreas is described. Cushing's syndrome preceded the appearance of the overt Zollinger-Ellison syndrome by 2 years and was treated by bilateral adrenalectomy. The Zollinger-Ellison syndrome was initially treated with cimetidine, which successfully reduced the secretion of gastric acid. Because the pancreatic gastrinoma continued to grow, causing obstruction of the common bile duct, biliary diversion and total gastrectomy were performed. There is evidence that the pancreatic gastrinoma was the source of the ectopic production of ACTH and possibly secretion. The role of Histamine-2 blocking agents as therapy in the Zollinger-Ellison syndrome is discussed.

Adrenocorticotropic Hormone

The effect of carbenoxolone sodium on the plasma 11 hydroxycorticoid levels in chronic gastric ulceration.

The mineralcorticoid effects of carbenoxolone sodium are well established and seem related to the ulcer healing of the drug. In the present study the plasma 11 hydroxycorticoid responses were assessed in 12 patients undergoing treatment with carbenoxolone for chronic gastric ulceration. After treatment with carbenoxolone for one month the plasma 11 hydroxycoticoid levels rose significantly, suppression by dexamethosone was less marked and the normal diurnal periodicity was abolished. Carbenoxolone therapy influences the results of tests designed to assess the function of the pituitaryadrenal axis and may lead to sub-clinical adrenocortical hyperfunction.

Adult

Effects of the obese (ob/ob) genotype on spleen cell immune function.

Spleen cells from mice homozygous for the obese (ob) mutation killed DBA/2 mastocytoma target cells less well than spleen cells from lean littermates or unrelated age-and sex-matched controls of the same strain. Killing was impaired only when the attacker cells were primed in vivo, not following in vitro priming. Hence the effect of the ob/ob genotype is not to produce an irreversible functional change in the lymphocyte, but rather to produce an environment in which lymphocytes are less able to react to priming antigen. Not only were the spleen cells of in vivo primed obese mice less active than those of lean controls, but also their number per spleen was significantly decreased. Such a quantitive difference was no longer found in adrenalectomised animals, but the qualitative difference in spleen cell cytotoxic activity still occurred. This suggests that adrenocortical hyperfunction may affect immune function in obese mice, without necessarily being the only factor in the in vivo environment of obese mouse spleen cells capable of depressing cellular immune reactivity.

Adrenalectomy

Adrenal function testing.

Glucocorticoid stimulation and suppression tests are essential to the definitive diagnosis of diseases of the hypothalamic-pituitary-adrenal axis, because they document abnormal physiologic control of hormonal secretion. Similarly, diseases of the renin-angiotensin-aldosterone axis are diagnosed by mineralocorticoid stimulation and suppression testing. [Ed. Note: See Moore TJ, Williams GH: Adrenal causes of hypertension, in this issue.] Unlike tests of glucocorticoid function, testing of the renin-angiotension-aldosterone system is more complicated, because knowledge of posture and dietary sodium are necessary to interpret the results. However, measurement of the tropic hormone renin and plasma levels of aldosterone can be accurately made, allowing precise definition of this system. Errors are most commonly encountered when dynamic tests of cortisol output are performed in patients taking medications that may interfere with the assays or with the metabolism of the administered compounds, such as dexamethasone or metyrapone. Abnormal, spurious values may also be obtained in some individuals who do not have adrenocortical hyperfunction if they are very obese or if testing is performed in a setting of clinical stress. Careful attention to these pitfalls will avoid errors and allow the clinician to arrive at the correct diagnosis.

17-Hydroxycorticosteroids