Adrenocortical hormones disease

In patients with longstanding hypothyroidism and those with ischemic heart disease, rapid correction of hypothyroidism may precipitate angina, cardiac arrhythmias, or other adverse effects. For these patients, replacement therapy should be started at low initial doses, followed by slow titration to full replacement as tolerated over several months. If hypothyroidism and some degree of adrenal insufficiency coexist, an appropriate adjustment of the corticosteroid replacement must be initiated prior to thyroid hormone replacement therapy. This prevents acute adrenocortical insufficiency that could otherwise arise from a thyroid hormone-induced increase in the metabolic clearance rate of adrenocortical hormones. 

In studies on the rate of intestinal absorption of various sugars, Verzar164 found that L-sorbose is absorbed much more slowly than D-glu-cose and that adrenalectomy165 does not affect the intestinal absorption of L-sorbose, while Thaddea and Sarkady166 found that the rate of absorption of L-sorbose from the blood stream was reduced in patients with Addison s disease when adrenocortical hormone was administered to them. 

Some of the most important physiological steroids are the adrenocortical hormones, synthesized by the adrenal cortex. Most of these hormones have either a carbonyl group or a hydroxyl group at Cl 1 of the steroid skeleton. The principal adrenocortical hormone is cortisol, used for the treatment of inflammatory diseases of the skin (psoriasis), the joints (rheumatoid arthritis), and the lungs (asthma). Figure 25-10 compares the structure of natural cortisol with two synthetic corticoids fluocinolone acetonide, a fluori-nated synthetic hormone that is more potent than cortisol for treating skin inflammation and beclomethasone, a chlorinated synthetic hormone that is more potent than cortisol for treating asthma. 

Metabolic changes over a long period may induce disease, e.g. thiazide diuretics (diabetes meUitus), adrenocortical hormones (osteoporosis), phenytoin (osteomalacia). Drugs may also enhance their own metabolism, and that of other drugs (enz5mie induction). 

The evidence in favour of a relationship between non-steroidal antirheumatic activity and the pituitary-adrenal system is based mainly on experiments involving salicylates and phenylbutazone. No attempt will be made to discuss these problems in detail since they have been adequately reviewed by Smith and Done for salicylates, and by Rechenburg for phenylbutazone. Smith argued persuasively that the available experimental evidence on salicylates does not support the view that they either mimic or reinforce the actions of the natural adrenocortical hormones, and that the similar clinical effects of salicylates and these steroids in rheumatic diseases must therefore be produced by different mechanisms. Done, on the other hand, suggests that the concept cannot be prematurely dismissed and believes that the possibility that salicylate simultaneously affects the production and disposition of adrenocortical hormones deserves further consideration. He emphasizes that the antirheumatic effects of salicylates are not dependent on the maintenance of elevated circulating levels of corticoids. 

Steroid hormones (Section 21.8) are produced by the adrenal cortex and the gonads (testes in males, ovaries in females). The adrenocortical hormones include glucocorticoids, which affect carbohydrate metabolism, modulate inflammatory reactions, and are involved in reactions to stress. The mineralocorticoids control the level of excretion of water and salt by the kidneys. If the adrenal cortex does not function adequately, one result is Addison s disease, characterized by hypoglycemia, weakness, and increased susceptibility to stress. This disease is eventually fatal unless it is treated by administration of mineralocorticoids and glucocorticoids to make up for what is missing. The opposite condition, hyperfunction of the adrenal cortex, is frequently caused by a tumor of the adrenal cortex or of the... 

If a patient suspected of developing clinical hypothyroidism is investigated only with routine tests, namely total T4, FTI, and the ETR or a similar estimation, there is no way of determining whether the patient has idiopathic myxedema or hypothyroidism secondary to hypothalamic or anterior pituitary disease. The distinction should be made, however, because it is dangerous to treat pituitary hypothyroidism with thyroid hormone without simultaneously treating with adrenocortical hormones. 

Adrenocortical hormones are employed by nature to treat the effects of inflammatory diseases. 

The adrenocortical hormones have been highly effective drugs in many diseases (arthritis, skin disorders, inflammations). Modification of the chemical structure, particularly by introduction of fluoro or methyl groups, has provided substances with different action spectra and with much greater effectiveness than the natural hormones. From the multitude of such compounds we present the following two formulas. Both substances have strong anti-inflammatory properties, but relatively low mineral-corticoid effects. 

The ghicocorticoids are used as replacement therapy for adrenocortical insufficiency, to treat allergic reactions, collagen diseases (eg, systemic lupus erythematosus), dermatologic conditions, rheumatic disorders, shock, and other conditions (see Display 50-1). The anti-inflammatory activity of these hormones make them valuable as anti-inflammatories and as immunosuppressants to suppress inflammation and modify the immune response... 

Types of Hormones Adrenocorticosteroids Prednisone Prednisolone Others Primary Antineoplastic Indications(s) Acute lymphoblastic leukemia chronic lymphocytic leukemia Hodgkin disease Common Adverse Effects Adrenocortical suppression general catabolic effect on supporting tissues [see Chapter 29]... 

In addition to the attempts described below to interfere with the onset or progression of neurological disease, it is also important to carry out endocrine testing on all biochemically identified males to assess their adrenocortical axis. In particular, all patients who have adrenal insufficiency require adrenal hormone replacement to prevent life-threatening complications of insufficiency. 

The adrenal cortex (AC) produces the glucocorticoid cortisol (hydrocortisone) in the zona fasciculata and the mineralocorticoid aldosterone in the zona glomerulosa. Both steroid hormones are vitally important in adaptation responses to stress situations, such as disease, trauma, or surgery. Cortisol secretion is stimulated by hypophyseal ACTH aldosterone secretion by angiotensin II in particular (p. 128). In AC failure (primary adrenocortical insuf ciency, Addison disease), both cortisol and aldosterone must be replaced when ACTH production is deficient (secondary adrenocortical insuf ciency), cortisol alone needs to be replaced. Cortisol is effective when given orally (30 mg/day, 2/3 a.m 1 /3 p.m.). In stress situations, the dose is raised 5- to 10-fold. Aldosterone is poorly effective via the oral route instead, the mineralocorticoid fludrocortisone (0.1 mg/day) is given. 

Hench P S et al 1949 The effect of a hormone of the adrenal cortex (17-hydroxy-ll-dehydrocorticosterone Compound E) and of pituitary adrenocorticotrophic hormone on rheumatoid arthritis. Proceedings of the Staff Meetings of the Mayo Clinic 24 181,277 (acute rheumatism). The classic studies of the first clinical use of an adrenocortical steroid in inflammatory disease. See also page 298 for an account by E C Kendall of the biochemical and pharmaceutical background to the clinical studies. Kendall writes of his collaboration with Hench, he can now say "17-hydroxy-ll-dehydrocorticosterone" and in turn I can say "the arthritis of lupus erythematosus". In sophisticated circles, however, I prefer to say, "the arthritis of L.E. ". 

A deficiency of adrenocortical secretion of aldosterone is usually accompanied by a reduction in the secretion of other adrenal steroid hormones as well. The loss of adrenocortical steroids is known as Addison s disease. 

Cortisol. Cortisol, secreted by the adrenal cortex in response to adrenocorticotropic hormone (ACTH), stimulates gluconeogenesis and increases the breakdown of protein and fat. Patients with Cushing s syndrome have increased cortisol owing to a tumor or hyperplasia of the adrenal cortex and may become hyperglycemic. In contrast, people with Addisons disease have adrenocortical insufficiency because of destruction or atrophy of the adrenal cortex and may exhibit hypoglycemia. ... 

The oversecretion of hormone molecules is most often caused by a tumor. Several types of pituitary tumor cause endocrine diseases. For example, one of the most common causes of Cushing s disease is an abnormal proliferation of ACTH-producing cells. Cushing s disease is characterized by obesity, hypertension, and elevated blood glucose levels. Patients with Cushing s disease develop a characteristic appearance a puffy moon face and a buffalo hump caused by fat deposits between the shoulders. Occasionally, Cushing s disease is caused by adrenocortical tumors. 

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