Adrenal deficiency

The goals of treatment for Cushing s syndrome are to limit morbidity and mortality and return the patient to a normal functional state by removing the source of hypercortisolism without causing any pituitary or adrenal deficiencies. 

Other, more rare, forms of congenital adrenal hyperplasia are the result of deficiencies of other steroidogenic enzymes, particularlyl7-hydroxylase (P450cl7) and 11 (3-hydroxylase (Bondy, 1985 White and Speiser, 2000). As with P450c21 deficiency, impaired activity of either of these other enzymes also results in decreased cortisol production, enhanced ACTH secretion, and thus increased tropic drive to the adrenal. Deficiency of ll 3-hydroxylase is characterized by increased production of adrenal mineralocorticoids (e.g., corticosterone, aldosterone), resulting in sodium retention, potassium excretion, and increased blood pressure. In addition, adrenal androgens are produced in... 

Hypercalcemia is occasionally seen in hyperthyroidism (K2) and in adrenal deficiency (L3). These conditions should present no diagnostic problem. 

Pantothenic acid deficiency induced either by a deficient diet or by the administration of pantothenic acid antimetabolites causes adrenal deficiency in rats. The ACTH content of the adrenal venous blood is reduced, and the concentration of coenzyme A is decreased in the gland. Pantothenic acid administration normalizes the coenzyme A concentration. The administration of growth hormone to pantothenic acid-deficient rats that have also been hypophysecto-mized increases the death rate and the incidence of adrenal necrosis. How the vitamin deficiency affects the humoral interrelationship remains to be investi-... 

Proopiomelanocortin (POMC) is the precursor peptide of hormones and neuropeptides expressed in the pituitary and the hypothalamus (adrenocorticotropic hormone (ACTH), lipotropin, a-melanocyte-stimulating hormone (aMSH), yMSH, 3-endorphin, and others). The main clinical consequences of POMC deficiency are adrenal insufficiency (due to absence of ACTH), red hair pigmentation (due to absence of MSH) and severe early-onset obesity (due to the lack of aMSH). 

Congenital adrenal hyperplasia ° Familial glucocorticoid deficiency and hypoplasia... 

Damage and destruction of the pituitary gland may result in secondary hypothyroidism, hypogonadism, adrenal insufficiency, growth hormone deficiency, hypoprolactinemia, or... 

Congenital adrenal hyperplasia A rare inherited condition resulting from a deficiency in cortisol and aldosterone synthesis with resulting excess androgen production. The clinical presentation depends on the variant of the condition, but it typically manifests as abnormalities in sexual development and/or adrenal insufficiency. 

Cavalli, A., Lattion, A. L., Hummler, E. etal. Decreased blood pressure response in mice deficient of the alphalb-adrener-gic receptor. Proc. Natl Acad. Sci. U.S.A. 94 11589-11594, 1997. 

Primary adrenal insufficiency (Addison s disease) most often involves the destruction of all regions of the adrenal cortex. There are deficiencies of cortisol, aldosterone, and the various androgens. Medications that inhibit cortisol synthesis (e.g., ketoconazole) or accelerate cortisol metabolism (e.g., phenytoin, rifampin, phenobarbital) can also cause primary adrenal insufficiency. 

Numerous physiological and environmental factors such as age, stress, nutritional deficiency, and infections may affect the immune system (Sullivan, 1989). Thus, adverse findings in animal studies may reflect these indirect immunotoxic effects rather than the direct immunotoxic potential of a chemical or drug. Indirect immunotoxic effects may be assessed through histopathologic evaluations of endocrine organs such as the adrenals and pituitary. 

Many different types of lesions have been observed (very often at autopsy) in animals suffering from severe pantothenic acid deficiency. These may involve the skin, the adrenals, the entire gastrointestinal tract, nerves, and spinal cord. Functionally, in chickens fertility may be reduced by pantothenic acid deficiency to practically zero64 without any outward signs being shown by the fowls. Recently, pantothenic acid deficiency has been found to produce duodenal ulcers in about 60 per cent of the rats tested.65 It is required for bone development66 and is implicated in antibody responses.67... 

In relatively recent years, it has become clear that under-nntrition of mother leads to low birth weight of the baby and this can increase the risk of development of degenerative disease in later life, e.g. hypertension, obesity, type 2 diabetes. One hypothesis is that the foetus adapts meta-bolically to deficiencies by increasing the number of cells in organs that perform specific functions that can overcome the deficiency, e.g. an increase in the number of liver cells that carry out gluconeogenesis, an increase in cells in the adrenal cortex to produce more of the chronic stress hormone, cortisol. These changes are carried over into adnlthood which can lead to an inadequate response of the liver to insulin so that insulin resistance develops. So far, however, it is unclear whether deficiencies in specific nntrients or undemutrition per se are responsible for snch changes (Chapter 15). 

Biflavanoids in vegetables and fruits play a vital role in the storage of ascorbic acid in leukocytes, in the core of adrenal glands and in other organs. It also causes more effective expenses under ascorbic acid s deficiency in the organism. Phenolic compounds present in the organism, activate detoxication processes in the liver. The flavanoids exceed the tocopherols and carotenoids in terms of antioxidant effect. 

Replacement therapy - Replacement therapy in hypogonadism associated with a deficiency or absence of endogenous testosterone. Prior to puberty, androgen replacement therapy is needed for development of secondary sexual characteristics. Prolonged treatment is required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty. Appropriate adrenal cortical and thyroid hormone replacement therapy are still necessary, however, and are of primary importance. 

Pharmacology The naturally occurring adrenal cortical steroids have both anti-inflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties. These compounds are used as replacement therapy in adrenocortical deficiency states and may be used for their anti-inflammatory effects. 

Deficiency of adrenal medullary catecholamines appears to give no ill effects, and replacement therapy is therefore not used, but adrenal medullary tumours, phaeochromocytomas, secrete excess catecholamines often causing hypertension with dramatic episodes of headache, palpitations, pallor, sweating and anxiety. This condition is normally treated surgically, but preoperative preparation is mandatory to avoid catastrophic effects of surges of catecholamine release. A combination of alpha- and beta-adrenergic receptor blockade is normally used, with drugs such as phenoxybenzamine or doxazosin as alpha-blockers, and propranolol as a non-selective beta-blocker. 

Jacobson L, Muglia LJ, Weninger SC, Pacak K, Majzoub JA (2000) CRH deficiency impairs but does not block pituitary-adrenal responses to diverse stressors. Neuroendocrinology 71 79-87... 

Turnbull AV, Smith GW, Lee S, Vale WW, Lee KF, Rivier C (1999) CRF type 1 receptor deficient mice exhibit a pronoimced pituitary-adrenal response to local inflammation. Endocrinology 140 1013-1017... 

Congenital enzymatic defects in the adrenal biosynthetic pathways lead to diminished cortisol and aldosterone production and release. In these conditions, corticotrophin secretion is increased, and adrenal hyperplasia occurs, accompanied by enhanced secretion of steroid intermediates, especially adrenal androgens. More than 90% of cases of congenital adrenal hyperplasia are due to 21-hydroxylase deficiency, which is cre-afed by mufafions in fhe CYP21 gene encoding fhe en-... 

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