Serum aldosterone

The major risk related to aldosterone antagonists is hyperkalemia. Therefore, the decision for use of these agents should balance the benefit of decreasing death and hospitalization from HF and the potential risks of life-threatening hyperkalemia. Before and within one week of initiating therapy, two parameters must be assessed serum potassium and creatinine clearance (or serum creatinine). Aldosterone antagonists should not be initiated in patients with potassium concentrations greater than... 

Aldosterone antagonists Hypotension, hyperkalemia, increased serum creatinine BP and HR every shift during oral administration during hospitalization, then once every 6 months baseline SCr and serum potassium concentration SCr and potassium at 48 hours, at 7 days, then monthly for 3 months, then every 3 months thereafter following hospital discharge... 

As nephron mass decreases, both the distal tubular secretion and GI excretion are increased because of aldosterone stimulation. Functioning nephrons increase FEK up to 100% and GI excretion increases as much as 30% to 70% in CKD,30 as a result of aldosterone secretion in response to increased potassium levels.30 This maintains serum potassium concentrations within the normal range through stages 1 to 4 CKD. Hyperkalemia begins to develop when GFR falls below 20% of normal, when nephron mass and renal potassium secretion is so low that the capacity of the GI tract to excrete potassium has been exceeded.30... 

ACE inhibitors decrease aldosterone and can increase serum potassium concentrations. Hyperkalemia occurs primarily in patients with chronic kidney disease or diabetes and in those also taking ARBs, NSAIDs, potassium supplements, or potassium-sparing diuretics. 

Renal function can be grossly assessed by hourly measurements of urine output, but estimation of creatinine clearance based on isolated serum creatinine values in critically ill patients may yield erroneous results. Decreased renal perfusion and aldosterone release result in sodium retention and, thus, low urinary sodium (<30 mEq/L). 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Symptomatic or prior-symptomatic fluid retention responds well to treatment with diuretics and salt restriction if LVEF is reduced. This will usually improve current HF symptoms. Especially, an aldosterone antagonist like spironolactone should be added in selected patients with advanced HF symptoms and reduced LVEF with preserved renal function. Potassium has to be normal and should be carefully monitored. Patients with renal dysfunction and with serum creatinine levels >2.5 mg/dl in men and >2.0 mg/dl in women are contraindicated for aldosterone antagonists. 

The hypotensive response to captopril is accompanied by a fall in plasma aldosterone and angiotensin II levels and an increase in plasma renin activity. Serum potassium levels are not affected unless potassium supplements or potassium-sparing diuretics are used concomitantly this can result in severe hyperkalemia. 

Aldosterone It is a mineralocorticoid. Its actions are retention of sodium and reduction of serum potassium. It acts on distal tubules of kidney to increase sodium reabsorption (details are discussed in chapter Diuretics ... 

Primary aldosteronism usually results from the excessive production of aldosterone by an adrenal adenoma. However, it may also result from abnormal secretion by hyperplastic glands or from a malignant tumor. The clinical findings of hypertension, weakness, and tetany are related to the continued renal loss of potassium, which leads to hypokalemia, alkalosis, and elevation of serum sodium concentrations. This syndrome can also be produced in disorders of adrenal steroid biosynthesis by excessive secretion of deoxycorticosterone, corticosterone, or 18-hydroxycorticosterone—all compounds with inherent mineralocorticoid activity. 

The measurement of these compounds in urine is essential for the study of Cushings disease, glucocorticoid remediable aldosteronism (GRA), apparent mineralocorti-coid excess syndrome (AME), and related conditions. While RIA has been generally satisfactory for serum cortisol assay, urine contains many crossreacting steroids, rendering RIA unreliable. 

Guo and co-workers [24,25] have spearheaded the development of MS/MS serum steroid profiles. Their most recent report describes profiling in 11 min of 12 steroids in 200 pi serum with minimal work-up, comprising acetonitrile protein precipitation. The steroids analyzed were as follows DHEA sulfate, DHEA, aldosterone, cortisol, corticosterone, 11-deoxycortisol, androstenedione, estradiol, testosterone, 17-hy-droxyprogesterone, progesterone, and 25-hydroxyvitamin D3. Stable-isotope-labeled internal standards were incorporated for each steroid. An API-5000 instrument was used with the APPI source in positive-ion mode, with the exception of aldosterone, which had greater sensitivity in negative-ion mode. Separation was carried out on a C8 column, which allowed more rapid separation than the more commonly utilized C18. The MRM transitions utilized are shown in Table 5.3.1. The lower level of sensitivity was between 1.5 and 10 pg/ml, dependent on the steroid. The authors were exhaustive in addressing issues of accuracy, recovery (90-110%) and reproducibility (< 12.2% for same-day and between-day). 

OHF is almost exclusively excreted without undergoing -ring reduction and conjugation and can be measured in urine by HPLC-MS. A useful diagnostic ratio is that of 18-OHF UFF, which is normally about 5 1 and rises to 50 1 in GRA. Serum analysis is used to measure aldosterone (elevated in the disorder) and cortisol, but not typically for 18-OHF. 

In contrast to patients with secondary aldosteronism (see below), these patients have low (suppressed) levels of plasma renin activity and angiotensin II. When treated with deoxycorticosterone acetate (20 mg/d intramuscularly for 3 days—no longer available in the USA) or fludrocortisone (0.2 mg twice daily orally for 3 days), they fail to retain sodium and their secretion of aldosterone is not significantly reduced. When the disorder is mild, it may escape detection when serum potassium levels are used for screening. However, it may be detected by an increased ratio of plasma aldosterone to renin. Patients are generally improved when treated with spironolactone, and the response to this agent is of diagnostic and therapeutic value. 

Aldosterone is secreted at the rate of 100-200 g/d in normal individuals with a moderate dietary salt intake. The plasma level in men (resting supine) is about 0.007 jrg/dL. The half-life of aldosterone injected in tracer quantities is 15-20 minutes, and it does not appear to be firmly bound to serum proteins. 

In general it can be stated that most of the available tests for aldosterone in serum measure more constituents not identical with aldosterone and the question arises whether it is justified to use the name aldosterone for the analyte. 

Fig. 10 YOUDEN diagram of a ring trial for serum aldosterone the virtual dot in the middle represents the IDMS target values for sample A and B and the square demonstrates the limits of acceptance results of test kit 50 emphasised by dark dots... 

Several relatively common disorders result in aldosterone secretion abnormalities and aberrations of electrolyte status. In Addison s disease, the adrenal cortex is often destroyed through autoimmune processes. One of the effects is a lack of aldosterone secretion and decreased Na+ retention by the patient. In a typical Addison s disease patient, serum [Na+] and [CL] are 128 and 96 meq/L, respectively (see Table 16.2 for normal values). Potassium levels are elevated, 6 meq/L or higher, because the Na+ reabsorption system of the kidney, which is under aldosterone control, moves K+ into the urine just as it moves Na+ back into plasma. Thus, if more Na+ is excreted, more K+ is reabsorbed. Bicarbonate remains relatively normal. The opposite situation prevails in Cushing s disease, however, in which an overproduction of adrenocorticosteroids, especially cortisol, is present. Glucocorticoids have mild mineralocorticoid activities, but ACTH also increases aldosterone secretion. This may be caused by an oversecretion of ACTH by a tumor or by adrenal hyperplasia or tumors. Serum sodium in Cushing s disease is slightly elevated, [K+] is below normal (hypokalemia), and metabolic alkalosis is present. The patient is usually hypertensive. A more severe electrolyte abnormality is seen in Conn s syndrome or primary aldosteronism, usually caused by an adrenal tumor. Increased blood aldosterone levels result in the urinary loss of K+ and H+, retention of Na+ (hypernatremia), alkalosis, and profound hypertension. 

Corticotropin-releasing hormone in hypothalamus Pituitary content of adrenocorticotropin and vasopressin Adrenal content of corticosterone and aldosterone Corticosterone and aldosterone blood level, electrolyte (Na+, K+, Ca2+, Cl-) concentrations in serum Urinary excretion of corticosterone and aldosterone... 

Determination of adrenal gland steroid content may be included but is of limited value. Determination of serum concentrations of corticosterone and aldosterone may be included during up week 3 for studies of 4 week-duration, but needs to be performed under well controlled conditions which reduce stress to a minimum. 

Aldosterone retains sodium in exchange for secreting potassium into the renal tubular fluid, serum potassium therefore falls. In liver failure aldosterone is not metabolised so it accumulates. Therefore in liver failure serum sodium will rise and potassium fall. 

In the colon, semifluid material entering from the small bowel is thickened by absorption of water and salts (from about 1000 ml to 150 ml per day). If, owing to the action of an irritant purgative, the colon empties prematurely, an enteral loss of NaCl, KC1 and water will be incurred. In order to forestall depletion of NaCl and water, the body responds with an increased release of aldosterone (p.168), which stimulates their reabsorption in the kidney. However, the action of aldosterone is associated with increased renal excretion of KC1. The enteral and renal K losses add up to K+ depletion of the body, evidenced by a fall in serum K concentration (hypokalemia). This condition is accompanied by a reduction in intestinal peristalsis (bowel atonia). The affected individual infers constipation and again partakes of the purgative, and the vicious circle is closed. 

Metoclopramide, domperidone and prochlorperazine can increase serum prolactin levels, leading to galactorrhoea, irregular periods and gynaecomastia. Raised plasma aldosterone levels have been reported with metoclopramide in both healthy individuals and cirrhotic patients with ascites. 

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