Adrenal Failure

Note In addition to the conditions listed, all other agents that cause septic shock can also cause secondary acute adrenal failure by direct tissue damage to the adrenal or pituitary gland. 

Consciousness - loss, prolonged (coma) Consciousness - loss, sudden (syncope) Dizziness (lightheaded) 

Heart rate - rapid (tachycardia) Mentation - confused Muscles - movement, slow/sluggish Muscles - weak [ 1 ] 

434 SECTION THREE CLINICAL GUIDE—ACUTE COMPLICATIONS 

Sweating - increased (hyperhydrosis) [3] Temperature, body - elevated (fever) [2] Weight - loss Vomiting 

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If it is necessary to use systemic corticosteroids for long-term control therapy, once-daily or every-other-day therapy should be used and repeated attempts should be made to decrease the dose or discontinue the drug. Withdrawal of chronic therapy may precipitate adrenal failure or unmask underlying inflammatory disorders such as Churg-Strauss syndrome. 

Samaras K, Pett S, Gowers A, McMurchie M, Cooper DA. Iatrogenic Cushing s syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors six cases. J Clin Endocrinol Metab 2005 90(7) 4394-8. 

Shibata S, Kami M, Kanda Y, Machida U, Iwata H, Kishi Y, Takeshita A, Miyakoshi S, Ueyama J, Morinaga S, Mutou Y. Acute adrenal failure associated with fluconazole after administration of high-dose cyclophosphamide. Am J Hematol 2001 66(4) 303-5. 

Both forms of PEM are associated with hy-percortisolemia.The level of cortisol in kwashiorkor is lower, however, than in marasmus, likely due to decreased adrenocortical function caused by low protein intake (and not adrenal failure). If a sufficiently high level of cortisol is not maintained, then adequate muscle protein is not mobilized to sustain hepatic protein synthesis. Indeed, hypoproteinemia, evident by the decreased serum albumin and transferrin levels, is more acute in kwashiorkor than marasmus. 

See also Withdrawal of corticosteroid pharmacotherapy, below) This occurs in patients who have recently received prolonged pharmacotherapy with a corticosteroid which inhibits h)rpothalamic production of the corticotropin releasing hormone and so results in secondary adrenal failure. It is treated by reinstituting therapy or as for acute insufficiency, as appropriate. To avoid an acute crisis on stopping, steroid therapy must be withdrawn gradually to allow the hypothalamus. 

Apart from unrecognized Addison s disease, previous ablative adrenal surgery and virilizing hyperplasia are causes of primary adrenal failure. Hypopituitarism and previous hypophysectomy are examples of secondary adrenal failure, but secondary adrenal unresponsiveness due to prior treatment with corticosteroids is much more common and is liable to prevent patients from responding normally to even minor degrees of stress (J5). 

Adrenal failure has been reported more than one year after withdrawal of steroid treatment. A preoperative test to detect patients who will fail to respond to surgery is important. The adrenal may be stimulated by injections of ACTH or synthetic analogs with measurement of changes in plasma cortisol levels (M4). This test, however, only gives information about the adrenal capacity to secrete and tells nothing of the ability of the pituitary adrenal axis to respond to stress. 

Interpretation Serum cortisol values more than 20ixg/dL exclude primary adrenal insufficiency. Glucocorticoid withdrawal would be required before assessing secondary or tertiary adrenal insufficiency in such cases. Little or no increase in cortisol secretion is seen in primary adrenal failure even over-successive days. A progressive staircase rise is seen over 2 to 3 days in adrenal insufficiency caused by pituitary or hypothalamic disease or steroid concentration suppression. Little or no response is also seen in congenital adrenal hyperplasia (CAH) caused by 21- and 17-hydroxylase deficiencies. 

In practice the measurement of serum or plasma 11-deoxycortisol (compound S) is used to document an Up-hydroxylase deficiency or as part of the metyrapone stimulation test. Because metyrapone inhibits the lip-hydroxylase enzyme, a fortyfold to eightyfold increase in plasma 11-deoxycortisol is observed in patients with normal pituitary-adrenal reserve. Consequently, immunoassay methods for 11-deoxycortisol in metyrapone test specimens need not be higlily sensitive. In these patients, a corresponding drop in serum cortisol is observed. A failure to demonstrate an increase in 11-deoxycortisol to at least 4 U,g/dL suggests either an inadequate pituitary ACTH reserve or primary adrenal failure. 

Hermus AR, Pieters GF, Pesman GJ, Smals AG, Benraad TJ, Kloppenborg PW. ACTH and cortisol responses to ovine corticotrophin-releasing factor in patients with primary and secondary adrenal failure. CUn Endocrinol (Oxf) 1985 22 761-9. 

Whenever one encounters the combination of hyponatraemia with hyperkalaemia, adrenocortical failure must be suspected. There is a modest increase in the serum creatinine with a normal serum urea which is not typical of Addison s disease. In adrenal failure the patient usually has pre-renal ureamia which causes the serum urea to rise more than the creatinine. The low serum bicarbonate is a feature of adrenal failure. 

It is essential that a Synacthen test is performed in this patient to exclude or confirm the diagnosis of adrenal failure. As the patient has severe skeletal muscle pain the creatine kinase should be measured as the hyperkalaemia may be due to potassium released from damaged muscle. If rhabdomyolysis were detected, it would be important to monitor renal function and calcium status carefully. 

This presentation is classical of acute adrenal failure with characteristic symptoms, physical findings and electrolyte pattern. 

Administration of a synthetic ACTH preparation (Synacthen) stimulates the adrenal cortex. An impaired cortisol responscloSynaclhen is seen in Addison s disease (primary adrenal failure). 

Fomierly, adrenal gland destruction was often due to tuberculosis autoimmune disease is now the main cause of primary adrenal failure. Both cortisol and itldosterone production may be affected. Secondary failure to produce cortisol is more common. Frequently, this is due to long-standing suppression and subsequent impairment of the hypothalamic-pituitary-adrenocortical axis from therapeutic administration of corticosteroids. The causes of adrenal insufficiency are summarized in Figure 2. 

Disraption of the P450 llAl gene has been associated with premature birth, sex reversal, and adrenal failure [1929]. Genetic variations have also been linked to adrenal and gonadal deficiency [1930, 1931]. 

The relationship of P450 llAl genetic variation and PCOS has already been mentioned in Sect. 7.41.3 vide supra), including premature birth, sex reversal, and severe adrenal failure [1926, 1929, 1972]. 

Hiort O, Holterhus PM, Werner R, Marschke C, Hoppe U, Partsch CJ, Riepe FG, Achermann JC, Struve D (2005) Homozygous disruption of P450 side-chain cleavage (CYPl 1A1) is associated with prematurity, complete 46,XY sex reversal, and severe adrenal failure. J Clin Endocrinol Metab 90 538-541... 

The risk of iatrogenic Cushing s syndrome followed by secondary adrenal failure, which is unusual after only a single-dose of a synthetic glucocorticoid, may... 

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