The adreno-genital syndrome.
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Naturally occurring hyperadrenocorticism (Cushing's syndrome) is extremely common in dogs, with an incidence far greater than that in humans. The incidence of the syndrome in cats, much less frequently diagnosed than in dogs, probably is similar to that in humans. Many features of canine hyperadrenocorticism are strikingly similar to those in humans; however, several alterations in dogs are unique and not observed in other species. Clinical features and hospital testing abnormalities are reviewed in this article.
The corticosteroid therapy of multiple sclerosis was modified in relation to the biorhythms of the hypothalamic-pituitary-adrenal axis (HPAA). Prednisolone was prescribed per os in a dose of 1.5 mg/kg bw daily to be taken only in the morning once every three days for 30-45 days. In the control group, prednisolone was administered daily in a dose of 30-60 mg. In the test group, remissions were attained even in hormone-resistant forms of the disease and HPAA function was not seriously affected. Unlike control patients, no severe and persistent complications were observed in that group. The authors believe that the emergence of such complications following the corticosteroid treatment is partially related to the iatrogenic desynchronism of the regulatory biorhythmical processes in the HPAA with the suppression and perversion of adrenal function of steroidogenesis.
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Clinico-roentgenological study of the gastrointestinal tract was carried out in 86 patients with diseases of the adrenal cortex. A hyperplastic relief of the gastric mucosa was revealed in the adreno-genital syndrome, Itsenko-Cushing's disease, androsteroma and glucosteroma; the relief was hypoplastic in Addison's disease. Ulcerative lesions found in Addison's disease were erosive and associated with the corticosteroid therapy instituted. Functional changes in small intestine in Itsenko--Cushing's disease, glucosteroma and Addison's disease were chiefly hypomotor-hypotonic in character, and in the adreno-genital syndrome and androsteromas--hypermotor-normotonic. Electrogastrography revealed different disturbances in the rhythm and amplitude of oscillations in the gastric biopotentials pointing to the changes in the vegetative innervation.
OBJECTIVE: To evaluate the effect of oral administration of melatonin on clinical signs, tumor size, and serum steroid hormone concentrations in ferrets with adrenocortical disease. DESIGN: Noncontrolled clinical trial. ANIMALS: 10 adult ferrets with clinical signs of adrenocortical disease (confirmed via serum steroid hormone concentration assessments). PROCEDURES: Melatonin (0.5 mg) was administered orally to ferrets once daily for 1 year. At 4-month intervals, a complete physical examination; abdominal ultrasonographic examination (including adrenal gland measurement); CBC; serum biochemical analyses; and assessment of serum estradiol, androstenedione, and 17alpha-hydroxyprogesterone concentrations were performed. Serum prolactin and dehydroepiandrosterone sulfate concentrations were evaluated at the first, second, and last examinations, and serum cortisol concentration was evaluated at the first and last examinations. RESULTS: Daily oral administration of melatonin greatly affected clinical signs of adrenocortical disease in ferrets; changes included hair regrowth, decreased pruritus, increased activity level and appetite, and decreased vulva or prostate size. Mean width of the abnormally large adrenal glands was significantly increased after the 12-month treatment period. Recurrence of clinical signs was detected in 6 ferrets at the 8-month evaluation. Compared with pretreatment values, serum 17alpha-hydroxyprogesterone and prolactin concentrations were significantly increased and decreased after 12 months, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that melatonin is a useful, easily administered, palliative treatment to decrease clinical signs associated with adrenocortical disease in ferrets, and positive effects of daily treatment were evident for at least an 8-month period. Oral administration of melatonin did not decrease adrenal gland tumor growth in treated ferrets.
Large posterior abdominal masses, particularly those in the right upper abdomen, may be difficult to localize correctly into the peritoneal or retroperitoneal compartments. The following signs were found to be reliable CT indicators of retroperitoneal location: obliteration of the perinephric fat outlining the psoas muscle; lateral displacement of the fat outlining the posterior right lobe of the liver; rotation of the intrahepatic portal veins to the left; anterior displacement of the inferior vena cava and renal veins; and anterior displacement of the ascending colon, descending duodenum, or pancreatic head.
Canine hyperadrenocorticism is one of the most common endocrinopathies in dogs. Diagnosis remains difficult in some cases due to factors such as the presence of non-adrenal illness and limitations in the tests. Differentiation between the pituitary and adrenal forms is important for providing accurate prognostic information and delineating treatment options and protocols. This article reviews the tests available for diagnosis (screening) and differentiation and evaluates their advantages and disadvantages. Recommendations for testing are made.
The literature on corticosteroid binding globulin (transcortin) in the human is reviewed under the following headings: physicochemical properties, biosynthesis, measurement, and physiological, pharmacological and pathological variations with particular emphasis of the effects of pregnancy and oral contraceptives. Finally, the physiological implications of corticosteroid binding globulin are discussed.
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Adrenarche refers to the onset of dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) production from the adrenal zona reticularis that can be detected at around 6 years of age. The phenotypic result of adrenarche is pubarche or the development of axillary and pubic hair that occurs in both girls and boys at about age 8. The phenomenon of adrenarche is unique to human beings and to some Old World primates, and a reversal of adrenarche appears to occur in the ageing process. Premature and exaggerated adrenarche can be indicative of future onset of adult diseases, thus increasing the clinical relevance of adrenarche. The physiological triggers of adrenarche and the role(s) of DHEA-S remain speculative. However, the biochemical pathways that define adrenarche have been characterized in detail, and the appearance of key enzymes and cofactors in the adrenal zona reticularis track with the progression of adrenarche. This article reviews the clinical manifestations of adrenarche, the biochemistry of the enzymes involved in DHEA-S production, and the cell biology of the adrenal zona reticularis.
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Patients suffering from AIDS tend to have symptoms that resemble those encountered in adrenocortical insufficiency. Serum sodium concentrations and blood pressure values were monitored and found to be subnormal, despite the fact that renin activity and aldosterone levels were either normal or elevated. We report the presence of autoantibodies directed against hydrocortisone among such AIDS patients. Indirect immunofluorescence technique using patients' sera and adrenal glands from AIDS patients as antigen showed antibodies to adrenocortical cells in sera from 9 of the 12 AIDS patients and in none from patients with autoimmune diseases and viral diseases or healthy blood donors. No similar reaction was seen in normal human or monkey adrenal glands. An ELISA technique was developed using hydrocortisone as antigen and using this technique 45% of the AIDS patients were found to have antibodies to hydrocortisone. It is possible that anti-corticosteroid antibodies (ACSA) may play a role in the pathophysiology of the Addison's like syndrome seen in terminal phases of AIDS.
Referral patterns from internists to departments of nuclear medicine or radiology are important determinants of whether adrenal glands are imaged by computed tomography (CT) or by radioisotope scintigraphy. To assist clinicians in making an informed choice, computed tomographic scans were compared with isotope scintigrams using 131I-19-iodocholesterol (19-IC) and 131I-6 beta-iodomethyl-19-norcholesterol (NP-59). In general, imaging techniques serve to localize diseases that are diagnosed on the basis of biochemical tests of adrenal function. Computed tomographic scanning and NP-59 scanning are of comparable diagnostic accuracy. Both are superior to 19-IC scanning in the diagnosis of Cushing's syndrome and primary aldosteronism. Computed tomographic scanning is faster and less expensive, and involves lower radiation doses to the patient than scintigraphy. Adrenocortical isotope scanning as a routine procedure has been superseded by computed tomographic scanning at the Mayo Clinic.
Monoclonal adrenocortical lesions have been characterized by an inverse correlation between proliferation and apoptosis, and polyclonal lesions show a direct correlation. Their relationship with the vascular pattern remains unknown in adrenocortical nodular hyperplasias (ACNHs), adenomas (ACAs), and carcinomas (ACCs). We studied 20 ACNHs, 25 ACAs, and 10 ACCs (World Health Organization classification criteria) from 55 women. The analysis included X-chromosome inactivation assay (on microdissected samples), slide and flow cytometry, and in situ end labeling. Endothelial cells were stained with anti-CD31, and the blood vessel area and density were quantified by image analysis in the same areas. Appropriate tissue controls were run in every case. Regression analyses between kinetic and vascular features were performed in both polyclonal and monoclonal lesions. Polyclonal patterns were observed in 14 of 18 informative ACNHs and 3 of 22 informative ACAs, and monoclonal patterns were seen in 4 of 18 ACNHs, 19 of 22 ACAs, and 9 of 9 ACCs. A progressive increase in microvessel area was observed in the ACNH-ACA-ACC transition but was statistically significant between benign and malignant lesions only (191.36 +/- 168.32 v 958.07 +/- 1279.86 microm(2); P < .0001). In addition, case stratification by clonal pattern showed significant differences between polyclonal and monoclonal benign lesions; 6% of polyclonal and 57% of monoclonal lesions had microvessel area >186 microm(2) (P = .0000008). Monoclonal lesions showed parallel trends (but with opposite signs) for microvessel area and density in comparison with proliferation and apoptosis, whereas polyclonal lesions showed inverse trends. In conclusion, the kinetic advantage of monoclonal adrenal cortical lesions (increased proliferation, decreased apoptosis) is maintained by parallel increases in microvessel area and density.
Six pathologists from Japan and the United Kingdom evaluated four different cases of adrenocortical disorders independently. These adrenocortical disorders included an adrenal tumor in a 45-yr-old female without any endocrine abnormalities, bilateral adrenocortical lesions in a 55-yr-old female with Cushing syndrome, an adrenocortical mass in a 44-yr-old man with hypertension, and an adrenocortical lesion in a 62-yr-old female with chronic hypertension for 30 yr. In this article, we provide a clinical summary, macroscopic and histologic findings, and histologic diagnosis of these four adrenocortical cases.