Adrenal Causes of Hypertension

Hyperaldosteronism Primary hyperaldosteronsim results from the autonomous production of aldosterone from the adrenal gland, independent of renin stimulation. It is a result of a unilateral adrenal adenoma (Conn's syndrome) in 54% of eases and bilateral adrenal hyperplasia in the majority of the rest. Hyperplasia is more common in men, and adenomas are more common in women. The increased aldosterone stimulates excessive renal sodium retention with resultant volume expan-sion and hypertension. The increased intravascular volume alsc augments renal perfusion, and renin secretion is thereby sup-pressed. Associated with the sodium retention is a loss of potassium and hydrogen ions, and, thus, these patients are hypokalemic and alkalotic. Patients are usually asymptomatic unless significant hypokalemia develops, in which ease muscle cramps, palpitations, polyuria, and polydipsia are common.

This diagnosis should be considered in any patient withhypertension and either spontaneous hypokalemia or severe hy-pokalemia after treatment with diuretics. Measurement of plasma renin level is a useful screening test and should be low in patients with the disease. Urine aldosterone levels should be elevated, although a definitive diagnosis can be made by demonstrating an increased serum aldosterone level that does not suppress after saline-induced volume expansion. CT is use-ful in differentiating between adrenal adenomas and hyperplasia. This is an important distinction to make because it has impor-tant implications for therapy: patients with solitary adenomas are treated by resection of the tumor, which results in resolu-tion of the hypertension approximately 50 % of the time. Pa-tients with adrenal hyperplasia are treated with the aldosterone antagonist spironolactone and, if necessary, additional diuretics.

Familial glucocorticoid-suppressible aldosteronism is an uncommon disorder causing hypertension in younger patients. It results from a mutation in the genes encoding for the en-zymes aldosterone synthase and ll-hydroxylase" This muta-tion places aldosterone synthesis under the control of adreno-eorticotropic hormone (ACTH). The administration of dex-amethasone suppresses ACTH and thereby ameliorates this syndrome by suppression of ACTH-induced aldosterone pro- duction. Most patients with Cushing's syndrome have hyper-tension, because of stimulation of mineralocorticoid receptors by the excess glucocorticoids. The diagnosis should be suspect-ed in patients with truncal obesity, muscle weakness, and os-teopomsis. The diagnosis can be confirmed by demonstrating an elevated urine cortisol level or an abnormal dexamethasone suppression test.

Pheochromocytoma A pheochromocytoma is a rare cate-cholamine-producing tumor arising from the chromaffin cells of the neural crest. Approximately 85 % of these tumors are 10-cated in the adrenal medulla, 10% of which are bilateral and 10% of which are malignant. The remaining 15 % are extra-adrenal and may arise anywhere along the sympathetic chain. Multiple tumors are common in familial syndromes, especially the multiple endocrine neoplasia syndrome type 2, in which they occur in association with medullary carcinoma of the thy-roid. Adrenal pheochromocytomas secrete predominantly epinephrine, resulting in mainly systolic hypertension caused by increased cardiac output, as well as tachycardia, hyper. hidrosis, flushing, and apprehension. Extramedullary tumors secrete mainly norepinephrine, which produces systemic vaso. constriction, resulting in systolic and diastolic hypertension, but fewer associated symptoms. The secretion of cate-cholamines by these tumors is often episodic and results in wild fluctuations in blood pressure and sometimes dramatic parox. ysms of adrenergic symptoms. Hypertensive crises and strokes may occur as a result of exceedingly high blood pressure.

The diagnosis is suggested by clinical symptoms. The complex of headaches, sweating episodes, and tachycardia in a hypertensive patient has a 91% sensitivity and 94 % specifici-ty. Laboratory confirmation of the diagnosis can be made by demonstrating elevated levels of serum or urine catecholamines or their metabolites (vanillylmandelic acid or metanephrines) (Table 15). The inability of clonidine to suppress the produc-tion of catecholamines in these patients also has diagnostic im-portance. Once diagnosed, the tumor can usually be localized by CT or MRI, although muclear scanning with specific iso-topes that localize to chromaffin tissue is occasionally needed to identify smaller tumors.

Treatment of these tumors is surgical resection. Patients must receive adequate blockade, a blockade, and volume ex-pansion before surgery to prevent the hemodynamic swings that can occur during manual manipulation of the tumor peri-operatively. For unresectable tumors, chronic therapy with the a-adrenergic blocker phenoxybenzamine is usually effective.

Treatment of Hypertension

The goal of treating hypertension is to prevent the longterm morbidity and mortality associated with prolonged el-evations in blood pressure. To this end, antihypertensive ther-apy should be instituted in patients with blood pressures in ex-cess of 18.6/12.0kPa(140/90 mm Hg). The method and ag-gressiveness of treatment depends on several factors, including the absolute level of blood pressure, the presence of end-organ dam-age, coexisting medical conditions, and overall cardiac risk.

In patients with mild or moderate hypertension without organ damage, it is reasonable to attempt a trial of nonpharma-cologic therapy for 3 to 6 months. This therapy mainly con-sists of lifestyle modifications, including smoking cessation, weight reduction for overweight individuals, regular aerobic exercise, avoidance of alcohol, and restriction of dietary sodi-um intake (less than 6 g of sodium per day). These lifestyle changes may delay progression to sustained hypertension in pa-tients with "high-normal" blood pressure, aid in control of es. tablished hypertension, decrease of eliminate the need for pharmacologic therapy, and reduce other cardiac rish factors. These measures should also be instituted in patients with more severe hypertension [23.9/14.6kPa(£¾180/110 mm Ha)1, with multiple cardiac risk factors, or with evidence of end-or-gan damage; however, in these patients, pharmacologic thera-py should be started concurrently.

Controlling hypertension with medications has clearly been shown to decrease cardiovascular morbidity and mortali-ty, including the rate of stroke, myocardial infarction, heart failure, progressive renal disease, and all cause mortality. Many antihypertensive agents are now available for the treat-ment of high blood pressure. The decision of which agents to use in a particular patient must take into account individual pa-tient characteristics, comorbid conditions that may be affected by particular agents, possible interactions with other medica-tions the patients is taking, as well as convenience of dosing and cost of therapy. Medications should be started at low doses and titrated to higher doses as needed. More than half of pa-tients with mild to moderate hypertension can be controlled with a single antihypertensive medication. If the medication is in-effective at the maximal dose, a second agent should be added. In general, compliance is better with once daily medications.

The latest recommendation from the Joint National Com-mittee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) is that blockers and diuretics should re-main the initial drugs of choice for the treatment of mild to moderate hypertension unless a contraindication to their use exists or there is a clear indication for another 0gent. This rec-ommendation is based on randomized clinical trials that have demonstrated a decrease in morbidity and mortality with these agents. A generalized approach to treatment of the hyperten-sive patient is shown in the following Figure(Figure 3).

The JNC does, however, recognize that contain medica-tions have a real or theoretical advantage over blockers or di-uretics in certain situations or in certain populations. An indi-vidualized approach to drug selection is, therefore, encour-aged. For example, hypertension in African-Americans tends to respond better to treatment with diuretics or calcium chan-nel blockers than with blockers or ACE inhibitors. Patients with CAD should have their hypertension treated with block-ers, given the beneficial effects of these agents in this popula-tion. Similarly, patients with depressed left ventricular systolic function or overt heart failure are best managed with diuretics and ACE inhibitors. ACE inhibitors slow the progression of nephropathy in patients with diabetes and are the first-line agents in this setting. Sex and age do not appear to affect re-sponsiveness to antihypertensives, although the starting dosages of medications should be lower in the elderly popula-tion. Antihypertensive medications may aggravate certain co-existing medical conditions and must be used with caution in specific settings. For instance, blockers may induce bron. chospasm in patients with lung disease, ACE inhibitors and di-uretics may worsen renal insufficiency, and blockers and cal-cium channel blockers may acutely worsen heart failure or con-duction system disease (Table 16).

Severe hypertension requires more aggressive therapy to prevent or limit organ damage. Hypertensive urgencies, with-out evidence of new or progressive end-organ damage, can usu-ally be treated with oral doses of relatively fast-acting medica-tions (e. g. , 1; blockers, calcium channel blockers, or ACE in-hibitors) with the aim of decreasing the blood pressure over the course of several hours to several days. Hypertensive emergen-cies require intravenous medication (e. g. , nitroprusside, la-betalol) to decrease the pressure over several minutes to an hour (Table 17). Such therapy should be given in an intensive care setting with close monitoring of the blood pressure and end-organ function. A precipitous drop in the blood pressure should be avoided because this may precipitate or exacerbate cerebral, renal, or myocardial ischemia. Establishing normal blood pressure is not the initial aim. A reasonable goal is to de-crease the mean arterial pressure by 25 % in the first 6 hours and then to levels less than 21.3/13.3 kPa(160/100 mm Hg) over the next 6 hours. Once the pressure is adequately con-trolled, oral medication should be initiated and intravenous medications weaned. The blood pressure can then be brought to ideal levels with titration of oral therapy.

Diagnosis in Traditional Chinese Medicine

Hypertension may be divided into two kinds--primary hypertension and secondary hypertension. This section only deals with primary hypertension. Its major symptoms are ver-tigo, headache and others, so in traditional Chinese medicine it is included in the categories of "xuan yun" and "to tong".

1. Common symptoms are dizziness, headache, fullness of head, restlessness, temperamental tendency, insomnia, pal-pitation, numbness of extremities.

2. Hypertension is defined as a pressure greater than 18.7/12.0 kPa. The elevation of diastolic pressure is of more significance for clinical diagnosis.

3. In severe cases or cases of long duration, the heart, brain, and kidney may be compromised with the presentation of relevant clinical manifestations.

4. In some patients blood pressure may be markedly ele-vated abruptly under certain precipitating factors accompanied with severe headache, dizziness, nausea and vomiting, which is called hypertensive crisis. If disturbance of consciousness, convulsion, transient hemiplegia or aphasia present, that is called hypertensive encephalopathy.

5. In addition to blood and urine routine examinations and chest roentgenography, fundus examination is very helpful in evaluating the state of disease process.

Differentiation and Treatment of Common Syndromes in

Traditional Chinese Medicine

1. Hyperactivity of Liver-yang:

Clinical manifestations: Dizziness, headache, head disten-sion, vexation, temperamental tendency, flushed eyes, bitter taste, red tongue with thin yellow fur, taut and forceful pulse.

Therapeutic method: Calming the liver and subduing hy-peractivity of liver-yang.

Recipe: Modified Decoction of Gastrodia and Uncaria.

Ingredients:

Rhizoma Gastrodiae 9g

Ramulus Uncariae cure Uncis 15-30g

Flos Chysanthemi 9g

Radix Scutellariae 9g

Concha Haliotidis 30g

Radix Achyranthis Bidentatae 12g

Spica Prunellae 15g

Os Draconis 30g

Concha Ostreae 30g

Cortex Eucommiae 12g

Ramulus Loranthi 15-30g

Administration: Decoct the above drugs in water to get 200-300ml of decoction. Take one half of it in the morning and the other half in the evening.

Modification: In case of constipation, add Radix et Rhi-zoma Rhei 6¡«10g; in case of severe vertigo, add Concha Mar-garitifera Usta 15¡«30g; for those with dry mouth and tongue, add Radix Rehmannia 15g and Radix Scrophulariae 9g; Lumbricus 9¡«15g and Herba Siegesbeckiae 9¡«12g for treating the case with numbness of the limbs.

2. Deficiency of the Liver-yin and Kidney-yin :

Clinical manifestations: Headache, vertigo, tinnitus, dryness of eyes, vexation, palpitation, insomnia, poor memo-ry, feverish sensation in the palms and soles, aching and lassi-tude of the loins and legs, dry mouth, red tongue with a little or no fur, fine and string-like pulse.

Therapeutic method: Nourishing 3dn and suppressing hy-peractive yang.

Recipe : Modified Decoction of Fleece-flower For Longevi-ty.

Ingredients:

Radix Polygoni Multiflori 15g

Radix Rehmanniae 12g

Fructus Lycii 12g

Golla Plastri Testudinis 15g

Cortex Eucommiae 9g

Ramulus Loranthi 15g

Radix Achyranthis Bidentatae 15g

Magnetitum 15-- 30g

Semen Ziziphi Sprinosae 12g

Flos Chrysanthemi 9g

Administration: All the above drugs are to be decocted in water for oral administration.

Modification: In case of oppressive sensation in the chest or precordial pain. add

Radix Salviae Miltiorrihizae 15--30g

Fructus Trichosanthis 15-- 30g

3. Deficiency of Both Yin and Yang:

Clinical manifestations: Dizziness, tinnitus, amnesia, palpitation, lassitude, soreness of the loins and knees. Inclina-tion to yang dificiency gives rise to cold extremities, pale tongue and deep thready pulse, while inclination to yin defi-ciency brings about dysphoria with feverish sensation in the chest, palms and soles, red tongue and fine rapid pulse.

Therapeutic method: Nourishing yin and restoring yang .

Recipe: Modified Decoction of Curculigo and Epimedium.

Ingredients:

Rhizoma Curculiginis 9-15g

Herba Epimedii 9-15g

Radix Morindae Officinalis 9g

Radix Angelicae Sinensis 9g

Cortex PheI|odendri 9g

Rhizoma Anemarrhenae 9g

Cortex Eucommiae 12g

Radix Achyranthis Bidentatae 12g

Administration: The decoction of one dose for a day is 200-300ml. Take one half in the morning and the other half in the evening.

Caution: The recipe is also effective for climacteric hyper-tension in women.