Adrenocortical insufficiency treatment

In the treatment of secondary adrenocortical insufficiency, lower doses of cortisol are generally effective, and fluid and electrolyte disturbances do not have to be considered, since patients with deficient corticotrophin secretion generally do not have abnormal function of the zona glomerulosa. Since cortisol replacement therapy is required for life, adequate assessment of patients is critical to avoid the serious long-term consequences of excessive or insufficient treatment. In many cases, the doses of glucocorticoid used in replacement therapy are probably too high. Patients should ideally be administered three or more doses daily. To limit the risk of osteoporosis, replacement therapy should be carefully assessed on an individual basis and overtreatment avoided. 

Clinically, ACTH stimulation of the adrenals is used diagnostically to detect adrenal insufficiency plasma cortisol levels are measured before and 60 minutes following an intravenous injection of cosyntropin. Adrenocortical insufficiency is known as Addison s disease Addison s classic description, in 1855, namely general debility, remarkable feebleness of the heart, irritability of the stomach, and a peculiar change of the colour of the skin , summarizes the clinical features of this disease, which is uniformly fatal if undetected and untreated. Therapeutically, corticotropin therapy has been essentially abandoned in favor of the direct administration of glucocorticoids. However, ACTH is still rarely used in the treatment of the infantile spasm seizure disorder. 

DIAGNOSIS AND TREATMENT OF DISTURBED ADRENAL FUNCTION Adrenocortical Insufficiency... 

When acute adrenocortical insufficiency is suspected, treatment must be instituted immediately. Therapy consists of large amounts of parenteral hydrocortisone in addition to correction of fluid and electrolyte abnormalities and treatment of precipitating factors. 

This compound, a potent steroid with both glucocorticoid and mineralocorticoid activity, is the most widely used mineralocorticoid. Oral doses of 0.1 mg two to seven times weekly have potent salt-retaining activity and are used in the treatment of adrenocortical insufficiency associated with mineralocorticoid deficiency. These dosages are too small to have important anti-inflammatory or antigrowth effects. 

Treatment of adrenocortical insufficiency. chronic primary and chronic secondary... 

Withdrawal symptoms disappear if the glucocorticoid is resumed, but as a rule they will in any case vanish spontaneously within a few days. More serious consequences can ensue, however, in certain types of cases and if adrenal cortical atrophy is severe. In patients treated with corticoids for the nephrotic syndrome and apparently cured, the syndrome is particularly likely to relapse on withdrawal of therapy if the adrenal cortex is atrophic (SEDA-3,305). In some cases, acute adrenocortical insufficiency after glucocorticoid treatment has actually proved fatal. It is advisable to withdraw long-term glucocorticoid therapy gradually so that the cortex has sufficient opportunity to recover. Table 5 lists methods of... 

Relative adrenocortical insufficiency can follow withdrawal of corticotropin treatment (presumably because the cortex has adapted itself to a constant high level of stimulation) and can persist for some months. Glucocorticoid substitution has to be provided during this period. The risk of this effect can be reduced by keeping the dose of corticotropin as low as possible. 

Fosfestrol is an unusual agent used in Japan for the treatment of prostatic carcinoma but not accepted by experts in Europe. Described as an estrogen, in European studies it had a high incidence of complications, including fluid retention (16%), myocardial infarction (10%), and thromboembolism (6.3%). A case of adrenocortical insufficiency has now been documented in Japan, involving a 59-year-old man who had taken the drug for 10 years (3). 

Diagnosis and Treatment of Disturbed Adrenal Function Adrenocortical Insufficiency Chronic (Addison s Disease)... 

The treatment of adverse effects of corticosteroids includes symptomatic management and dose tapering on slow withdrawal of drug. Sudden withdrawal of corticosteroids may cause adrenocortical insufficiency and may lead to death. Gradual withdrawal of corticosteroids is advisable, and supplementary corticosteroid therapy should be provided for the patient with a history of corticosteroid withdrawal. 

Fludrocortisone is the compound that is most often used at present for long-term mineraiocorticoid treatment. The dose of fludrocortisone needed in chronic adrenocortical insufficiency varies very widely, from 0.05... 

The use of corticosteroids in the treatment of septic shock has been a topic of controversy for many years. A meta-analysis of early studies of steroids in sepsis demonstrated a lack of benefit and potential harm in sepsis and septic shock. There is a renewed interest in corticosteroid use because of the increased awareness of adrenocortical insufficiency in critically ill patients with septic shock. Relative adrenal insufficiency has been defined as a poor adrenal response [<250 nmol/L (9 mcg/dL) irrespective of the initial serum cortisol level] to a dose of synthetic adrenocorticotropic hormone (ACTH), indicating a low fnnctional reserve of the adrenal cortex. Although absolute insufficiency is rare, relative adrenocortical insufficiency in the presence of normal or high cortisol concentrations at baseline is present in 30% to 50% of patients with septic shock and is associated with a poor outcome. ... 

Betamethasone, a glucocorticoid with antiinflammatory properties, is indicated in the treatment of adrenocortical insufficiency, severe inflammation, or immunosuppression (see also Table 11 and Figure 28). 

For the treatment of suspected but unconfirmed acute adrenal insufficiency, 4 mg of dexam-ethasone sodium phosphate can be substituted for hydrocortisone, since dexamethasone does not cross-react in the cortisol assay and will not interfere with the measurement of cortisol (either basaUy or in response to the cosyntropin stimulation test). A failure to respond to cosyntropin in this setting is diagnostic of adrenal insufficiency. Often, plasma ACTH also is measured to provide information about the underlying etiology if the diagnosis of adrenocortical insufficiency is established. 

Pituitary ablation with Y was successful in 2 of 5 patients with diabetic retinopathy but hyporesponsiveness of the hypophysis to stress caused death in 4 patients (Lomsky et al., 1966). However, such implants can control retinopathy and preserve the patient s sight (Jauregui et al., 1968). The procedure was used in 22 patients with 75% showing distinct improvement but 5 others died of complications (Ray et al., 1968). The cotton wool spots of diabetic retinopathy, when treated by Y pituitary implantation, disappear in about 2.3 months but the capillary closure persists (Kohner et al., 1969). New capOlaries arise from the optic disc after Y implantation but results are better in patients below 40 years of age (Panisset et al., 1971). Such treatment is also beneficial in cases of the thyrotoxic malignant exophthalmos but the patients may develop adrenocortical insufficiency and gonadal hypofunction (Molinatti, 1964). 

Definitive diagnosis is achieved by the measurement of VLCFA in plasma. The results of this analysis are abnormal in nearly all males with X-ALD. The specific analyses that are included are the concentration of C26 0, the ratio of C24 0/C22 0, and the ratio of C26 0/C22 0, all of which are elevated in most cases. Increased concentration of VLCFA in plasma and/or cultured skin fibroblasts also is present in approximately 85% of female carriers, although identification of carriers is now available using molecular methods which are more reliable. Testing of at-risk family members is recommended and can identify affected males who may be candidates for therapy (see Therapy). In addition, it facilitates assessment of adrenocortical function in biochemically affected males, permitting treatment of those with adrenal insufficiency. This testing is accomplished byACTH stimulation. 

Mitotane (lysodren) is administered in initial daily oral doses of 2-6 g, usually given in 3 or 4 divided portions, but the maximal tolerated dose may vary from 2 to 16 g/day. Treatment should be continued for at least 3 months if beneficial effects are observed, therapy should be maintained indefinitely. Spironolactone should not be administered concomitantly, since it interferes with the adrenal suppression produced by mitotane. Treatment with mitotane is indicated for the palliation of inoperable adrenocortical carcinoma, producing symptomatic benefit in 30—50% of such patients. Although the administration of mitotane produces anorexia and nausea in 80% of patients, somnolence and lethargy in 34%, and dermatitis in 15—20%, these effects do not contraindicate the use of the drug at lower doses. Since this drug damages the adrenal cortex, administration of corticosteroids is indicated, particularly in patients with evidence of adrenal insufficiency, shock, or severe trauma. 

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