Primary hyperaldosteronism associated with vitiligo vulgaris and autoimmune hypothyroidism

Type 3 polyendocrine autoimmune syndrome (PAS) is defined as the association between an autoimmune thyroid disease and 1 or more other autoimmune diseases, except for autoimmune Addison disease or hypoparathyroidism. Here we report an extremely rare case of type 3 PAS in which vitiligo vulgaris and symptomless autoimmune hypothyroidism were observed during the study of primary hyperaldosteronism.     

Primary hyperaldosteronism without suppressed renin due to secondary hypertensive kidney damage

Primary hyperaldosteronism is characterized by high plasma and urinary aldosterone and suppressed PRA. Renin suppression is due to aldosterone-dependent sodium retention and mild extracellular volume expansion. We observed three patients with primary hyperaldosteronism, severe refractory hypertension, and normal to high normal PRA levels whose aldosterone/renin ratios were still elevated because of disproportionately high aldosterone levels. All available medical data on the patients as well as publications on the aldosterone/renin relationship in primary hyperaldosteronism were reviewed to explain the unusual findings. In one patient, histologically proven renal arteriolosclerosis was the probable cause of the escape of PRA from suppression by an aldosterone-producing adenoma. In the other two patients, hypertensive kidney damage due to primary hyperaldosteronism was the most likely explanation for the inappropriately high PRA, as in patient 1. All patients had high normal or slightly elevated serum creatinine levels and responded to 200 mg spironolactone/day with increased serum creatinine and hyperkalemia. Hyperkalemia was probably due to a decreased filtered load of sodium and a spironolactone-induced decrease in mineralocorticoid function. Two patients were cured of hyperaldosteronism by unilateral adrenalectomy but still need some antihypertensive therapy, whereas one patient has probable bilateral adrenal disease, with normal blood pressure on a low dose of spironolactone. In patients with severe hypertension due to primary hyperaldosteronism, PRA can escape suppression if hypertensive kidney damage supervenes. An increased aldosterone/PRA ratio is still useful in screening for primary hyperaldosteronism. These patients may respond to spironolactone therapy with a strong increase in serum creatinine and potassium. Early specific treatment of primary hyperaldosteronism is therefore indicated, and even a patient with advanced hypertension will profit from adrenalectomy or cautious spironolactone treatment.     

Primary hyperaldosteronism.

Primary hyperaldosteronism (PHA) is regarded as a rare disease with prevalence rates of 0.5 to 2% within the hypertensive population. Recent studies using more detailed screening procedures in small hypertensive cohorts have suggested that PHA may be more common than previously thought (3-18%). Since a validated and cost-effective routine screening protocol for this entity is not established, many clinicians are reluctant to consider PHA as an underlying cause for a patient's high blood pressure. The insufficient perception of PHA may have fatal consequences since most patients are curable by an operation and missing the diagnosis often leads to significant and irreversible end-organ damage. This review focuses on the diagnosis of PHA and gives a rational and cost-effective flow chart for routine screening and differential diagnosis of PHA in hypertensive patients.     

Primary hyperaldosteronism is associated with derangement in the regulation of the hypothalamus-pituitary-adrenal axis in humans

Hippocampal mineralocorticoid receptors (MR) play a major role in the control of hypothalamus- pituitary-adrenal (HPA) axis. The functional profile of HPA axis and the impact of MR blockade under chronic exposure to mineralocorticoid excess are unknown. To clarify this issue, ACT H, cortisol, and aldosterone secretions were studied in 6 patients with primary hyperaldosteronism (HA) and 8 controls (NS) during placebo, placebo+human CR H (hCR H) (2 microg/kg iv bolus at 22:00 h), potassium canrenoate (CAN, 200 mg iv bolus at 20:00 h followed by 200 mg infused over 4 h) or CAN+hCR H. During placebo, both aldosterone and ACT H levels were higher (p<0.01) in HA than in NS, while cortisol levels were not significantly different. Both HA and NS showed significant ACT H and cortisol responses to hCR H (p<0.004), although the hormonal responses in HA were higher (p<0.02) than in NS. CAN infusion did not modify aldosterone levels in both HA and NS. Under CAN infusion, ACT H showed progressive rise in NS (p<0.05) but not in HA, while cortisol levels showed a significant (p<0.05) but less marked and delayed increase in HA compared to NS. CAN enhanced hCRH-induced ACTH and cortisol responses in NS (p<0.05), but not in HA. In conclusion, in humans primary hyperaldosteronism is associated with deranged function of the HPA axis. In fact, hyperaldosteronemic patients show basal and hCR H-stimulated HPA hyperactivity that is, at least partially, refractory to further stimulation by mineralocorticoid blockade with canrenoate. Whether this hormonal alteration can influence the clinical feature of hypertensive patients with primary hyperaldosteronism needs to be clarified.     

Treatment of hypertensive urgencies and emergencies with nifedipine

The calcium channel blocker, nifedipine, is an effective antihypertensive agent for the treatment of hypertensive urgencies and emergencies. It produces a prompt, safe, predictable, and consistent reduction in systemic arterial pressure with minimal adverse effects. The reduction in blood pressure is inversely correlated with the pretreatment blood pressure level. Various nonparenteral administration forms (oral, sublingual, buccal, and rectal) permit a versatile, noninvasive, cost-effective alternative to parenteral antihypertensive therapy and continuous hemodynamic monitoring. The overall efficacy in reaching goal blood pressure approaches 98% with a 10 to 20 mg dose of nifedipine. Hemodynamic changes are favorable, and there is rarely any associated morbidity (severe hypotension) or mortality. The role of nifedipine in the treatment of hypertensive emergencies is promising, but further studies are needed to compare it to other approved emergency antihypertensive regimens.     

Therapeutic survey: hypertensive emergencies

The most crucial aspect is to ascertain whether the patient's condition truly warrants emergency management. The choice of oral versus parenteral drug(s) depends on the urgency of the situation as well as the patient's general condition. The level to which the blood pressure should be lowered varies with the type of hypertensive crisis and should be strictly individualized. There is no predestined level for the goal of therapy. Complications of therapy--namely, hypotension and ischemic brain damage, can occur in patients receiving multiple potent antihypertensive drugs in large doses without adequate monitoring. Such complications can be minimized by gentle lowering of blood pressure. An asymptomatic patient who presents with severe hypertension, i.e., a diastolic blood pressure 130-140 mmHg, need not be treated with parenteral drugs. After the resolution of a hypertensive crisis, one should determine the possible factors that might have contributed to the development of the hypertensive crisis such as non-adherence to prescribed therapy or the presence and/or progression of a secondary form of hypertension such as renal artery stenosis.     

The treatment of hypertensive emergencies

Prompt, skillful, parenteral administration of hypotensive agents may be lifesaving when hypertension acutely threatens the integrity of the cardiovascular system. Reserpine given intramuscularly is effective in most hypertensive emergencies. Because of its soporific effect it should be avoided when lesions of the central nervous system make it essential that the patient's level of consciousness be observed closely. Ganglion-blocking agents possess potent antihypertensive properties when given parenterally, but they may cause urinary retention and ileus, and for this reason should not be used in the immediate postoperative state. The intravenous infusion of sodium nitroprusside is the most reliable method of reducing blood pressure promptly, but its administration must be supervised constantly by trained personnel.     

Treatment of hypertensive urgencies and emergencies

Although systemic hypertension is a common clinical condition, hypertensive emergencies are unusual in clinical practice. There are some situations, however, that qualify as hypertensive emergencies or urgencies. It is important, therefore, to diagnose these acute conditions, in which immediate treatment of hypertension is indicated. The diagnosis of hypertensive emergencies depends on consideration of the clinical manifestations as well as the absolute level of blood pressure. Manifestations of hypertensive emergencies can be quite profound, but they vary depending on the target organ that is affected. Thus, an accurate clinical diagnosis is necessary to render appropriate therapy. Fortunately, effective drug therapy is available to lower the blood pressure quickly in hypertensive emergencies. Physicians should be familiar with the pharmacologic and clinical actions of drugs in treating hypertensive emergencies. With proper clinical diagnosis, hypertensive emergencies can be successfully treated, and complications can be largely prevented with timely intervention.     

Treatment of intraoperative hypertensive emergencies in patients with intracranial disease

In patients with neuropathologic processes leading to disturbed cerebrovascular autoregulation, sudden increases in arterial blood pressure may lead to a sudden elevation in cerebral blood flow and intracranial pressure. Therefore, sudden increases in arterial pressure should be assiduously avoided in the perioperative period. Hypertensive episodes may occur at any time during anesthesia, but are more likely to occur (1) during laryngoscopy and intubation, (2) at the time of skin incision, (3) at extubation, and (4) during awakening. In patients with cardiovascular disease, such hypertensive episodes may also cause deterioration of the cardiovascular situation. Catecholamines are the principal mediators of such intraoperative hypertensive reactions. There are 2 options available to the anesthesiologist: (1) attempt to suppress this response after it has occurred, or (2) prevent its occurrence at the outset. Treatment of hypertension often relies on agents that relax vascular smooth muscle. In patients with compromised intracranial compliance, however, cerebral vasodilation must be avoided because it leads to an increase in cerebral blood volume. This, in turn, may raise intracranial pressure and result either in herniation of brain contents or a decrease in cerebral perfusion pressure leading to brain ischemia. Different pharmacologic means of preventing or suppressing such intraoperative hypertensive reactions are reviewed. Many of the drugs reviewed resulted in adverse effects that could preclude their use in patients with reduced intracranial compliance. Alpha- and beta-adrenergic receptor blockers can safely be administered to such patients.     

Converting enzyme inhibition in hypertensive emergencies.

The diagnostic and therapeutic value of the angiotensin converting enzyme inhibitor teprotide (SQ 20881) was assessed in 18 patients with hypertensive emergencies. Mean blood pressure fell 31 +/- 18 mm Hg in the 10 subjects who responded to 1 mg/kg body weight administered intravenously, whereas it fell 5 +/- 3 mm Hg in the eight nonresponders. In patients who had received no previous drug treatment, log baseline plasma renin activity and change in mean blood pressure after SQ 20881 correlated significantly (r = 0.651, P less than 0.05). After acute therapy with SQ 20881, the patients who had a satisfactory response to the drug were treated with propranolol and a relatively normal sodium intake (88 meq/day). Nonresponders were treated with diuretics and sodium restriction (10 meq/day), and intermediate responders were given combination therapy. Mean blood pressure responded favorably within 24 h to the chosen regimen for each group from 152 +/- 47 to 102 +/- 31 mm Hg. SQ 20881 allows prompt evaluation of the role of renin in hypertensive emergencies and permits early choice of appropriate therapy based on the prevailing mechanism.