Prevention of congenital adrenal hyperplasia.
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The concentration of 17-OH-progesterone (17-OHP) was measured retrospectively in a second-trimester amniotic-fluid sample obtained from a mother who had an infant with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The concentration was more than three times the mean amniotic-fluid-17OHP concentration determined in pregnancies of comparable gestational age with normal outcome. In four further pregnancies tested, where the parents were heterozygous for CAH, amniotic-fluid concentrations of 17-OHP were normal. To date, three of the mothers have delivered normal infants. CAH can be detected in early pregnancy by specific radioimmunoassay techniques for steroid-hormone analysis in amniotic fluid. This antenatal test could be useful in those cases in which parents do not wish to risk having affected offspring.
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Congenital adrenal hyperplasia (C.A.H.) due to 21-hydroxylase deficiency is an HLA-linked recessive disorder. HLA-A and B antigens are expressed on amniotic cells. Prenatal diagnosis of C.A.H. by HLA typing of families and amniotic cells was attempted in two at-risk families. In one family HLA typing indicated that the fetus would have C.A.H., and this prediction was confirmed after birth. In the second family, HLA typing indicated that the fetus would be an unaffected, phenotypically normal carrier of the disease gene, and this prediction was also confirmed after birth.
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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.
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There are a multitude of possible side effects when using high levels of or chronic administration of glucocorticoid treatment. Several of the studies referred to in this discussion used large amounts of glucocorticoids for rather lengthy periods. The endocrine, as well as nonendocrine, effects of glucocorticoids are minimized when the lowest effective doses are used, when treatment is terminated as soon as reasonably possible, and when an alternate-day therapy schedule is followed. However, an occasional individual may appear with a particular susceptibility to one or more of the side effects of glucocorticoid treatment even when these measures are followed.
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In conclusion, interaction between the immune and endocrine systems is highly complex. Generally, abnormalities of T suppressor cells, a result of HLA antigen genetic abnormalities, result in autoimmunity that causes endocrine gland destruction and hormone deficiency, as seen in lymphocytic thyroiditis of dogs, type I DM, hypoparathyroidism, hypoadrenocorticism, and APS. On the other hand, endocrine deficiency (hypothyroidism, DM) or excess (hyperadrenocorticism) states may cause abnormalities of cell-mediated and antibody-associated immunity, leading to susceptibility to a variety of viral, bacterial, and fungal infections. It is hoped that this article sheds some light on the complex and highly integrated endocrine-immune interactions.
Diagnosis of canine hyperadrenocorticism can only be made when a suspicion of the disorder persists after completion of a thorough history and physical examination. The first diagnostic testing steps include a complete blood count, serum biochemical tests, and urinalysis with urine culture. Radiography or ultrasonography may also be necessary, depending on physical findings. Screening tests are next applied to support or exclude the clinical diagnosis of hyperadrenocorticism. After the diagnosis has been made, discrimination tests are applied to determine whether the cause is pituitary or adrenal. The limitations of screening tests, particularly in the presence of nonadrenal diseases, cannot be overemphasized. We recommend that neither screening tests nor discrimination tests for hyperadrenocorticism be used in dogs with concurrent nonadrenal disease.
Mitotane (o,p'-DDD; Lysodren) is the drug most commonly used to treat dogs with pituitary-dependent hyperadrenocorticism. Although variations of the original protocol, suggested more than 20 years ago, have been reported, most clinicians still use an initial loading dose of mitotane followed by a weekly maintenance dose. Although a gratifying response to treatment is seen in most dogs, some dogs are neither easy nor straightforward to treat and present the practitioner with one or more therapeutic challenges, including failure to respond adequately, development of adverse effects, or development of relapse during treatment. Nevertheless, with careful management and follow-up, such problems can be overcome and a successful outcome achieved in most cases.
In this chapter we have discussed the pathogenesis of canine PDH focusing on its relationship to aging, dopamine deficiency, and neurodegenerative disease. We have outlined the successful management of canine PDH patients with l-deprenyl, a selective MAO-B inhibitor. Treatment with l-deprenyl results in clinical and endocrinologic improvement (partial to complete) in approximately 83% of dogs, with improvement noted within the first 1 to 2 months of therapy. The safety profile of l-deprenyl is excellent, especially in light of the fact that the majority of patients are elderly. l-Deprenyl is a safe and effective first-line therapy for the medical management of uncomplicated cases of canine PDH.