Case Report - (2023) Volume 13, Issue 1
Primary Hyperaldosteronism is an underdiagnosed cause of hypertension. The classic presentation of PA includes hypertension and hypokalemia. However, in reality, most patients will present without hypokalemia. The two primary causes are aldosterone-producing adenomas (33%) and bilateral adrenal hyperplasia of the zona glomerulosa (66%). Familial cases have been found and are classified into Type I, Type II, and Type III familial hyperaldosteronism. Diagnosis can initially be confirmed with the elevated morning aldosterone to plasma renin activity ratio. If the ratio is higher than 20 to 1; then the excess aldosterone points to the adrenal gland as the primary source. The preferred treatment is adrenalectomy in those with unilateral disease. Those who are poor surgical candidates or have bilateral adrenal hyperplasia can be treated medically with mineralocorticoid antagonists as well as antihypertensive agents for further blood pressure control. We have a patient who presented in the emergency with uncontrolled hypertension (on 3 antihypertensive drugs) and unexplained hypokalemia. On further evaluation, she was detected to have metabolic alkalosis. On the above findings, she was suspected to have Primary hyperaldosteronism and was evaluated accordingly
Primary Aldosteronism . Hypertension.Hypokalemia, Metabolic alkalosis.Secondary HT. Nephrology. Endocrinology. Cardiology
Primary Aldosteronism (PA), also known as primary hyperaldosteronism or Conn's syndrome, refers to the excess production of the hormone aldosterone from the adrenal glands, resulting in low renin levels and high blood pressure. This abnormality is caused by hyperplasia or tumors. Many experience fatigue, potassium deficiency and high blood pressure which may cause poor vision, confusion or headaches.
Symptoms may also include muscular aches and weakness, muscle spasms, low back and flank pain from the kidneys, trembling, tingling sensations, dizziness/vertigo, nutria and excessive urination. Complications include cardiovascular diseases such as stroke, myocardial infarction, kidney failure and abnormal heart rhythms.
Some recommend screening people with high blood pressure who are at increased risk, while others recommend screening all people with high blood pressure for the disease. Primary aldosteronism is present in about 10% of people with high blood pressure [1]. It occurs more often in women than men. [2] Often, it begins in those between 30 years to 50 years of age.
People often have few or no symptoms [1]. They may get occasional muscular weakness, muscle spasms, tingling sensations, or excessive urination [3]. High blood pressure, manifestations of muscle cramps (due to hyper excitability of neurons secondary to low blood calcium), muscle weakness (due to hypo excitability of skeletal muscles secondary to hypokalemia), and headaches (due to low blood potassium or high blood pressure) may be seen.
Causes
1.Bilateral idiopathic (micro nodular) adrenal hyperplasia: 66%of cases [1].
2. Adrenal adenoma (Conn's disease): 33% of cases [4].
3.Primary (unilateral) adrenal hyperplasia: 2% of cases.
4.Aldosterone-producing adrenocortical carcinoma: <1% of cases.
5.Familial Hyperaldosteronism (FH):
a) Glucocorticoid-remediable aldosteronism (FH type I): <1% of cases.
b) FH type II (APA or IHA): <2% of cases.
6.Ectopic aldosterone-producing adenoma or carcinoma: < 0.1%of cases.
Epidemiology
In the past, the prevalence of primary aldosteronism was considered to be less than 1% of patients with hypertension. More recent studies have reported much higher prevalence of primary aldosteronism, upto 12.7% in primary care and to 29.8% in referral centers [5]. Very low rates of compliance with screening guidelines lead to the underdiagnoses of primary aldosteronism.
Pathophysiology
Aldosterone has effects on most or all cells of the body but, clinically, the most important actions are in the kidney, on cells of the late distal convoluted tubule and medullary collecting duct. In the principal cells, aldosterone increases the activity of basolateral membrane sodium-potassium ATPase and apical epithelial sodium channels, ENAC, as well as potassium channels, ROMK. These actions increase sodium reabsorption and potassium secretion. Since more sodium is reabsorbed than potassium secreted, it also makes the lumen more electrically negative, causing chloride to follow sodium. Water then follows sodium and chloride by osmosis. In Conn syndrome, these actions cause increased extracellular sodium and fluid volume and reduced extracellular potassium. Aldosterone also acts on intercalated cells to stimulate an apical proton ATPase, causing proton secretion that acidifies urine and alkalizes extracellular fluid [6].
In summary, hyperaldosteronism causes hypernatremia, hypokalemia, and metabolic alkalosis [7].
The sodium retention leads to plasma volume expansion and elevated blood pressure. The increased blood pressure will lead to an increased glomerular filtration rate and cause a decrease in renin released from the granular cells of the juxtaglomerular apparatus in the kidney decreasing sodium reabsorption and returning sodium renal excretion to near normal levels allowing sodium to 'escape' the effect of mineralocorticoids. If there is primary hyperaldosteronism, the decreased renin (and subsequent decreased angiotensin II) will not lead to a decrease in aldosterone levels (a very helpful clinical tool in the diagnosis of primary hyperaldosteronism) [8].
Diagnosis
creening may be considered in people with high blood pressure presenting with low blood potassium, high blood pressure that is difficult to treat, other family members with the same condition, or a mass on the adrenal gland [9].
Measuring aldosterone alone is not considered adequate to diagnose primary hyperaldosteronism. Rather, both renin and aldosterone are measured, and a resultant Aldosterone-to-Renin Ratio (ARR) is used for case detection [10, 11]. A high aldosterone-to-renin ratio suggests the presence of primary hyperaldosteronism. The diagnosis is made by performing a saline suppression test, ambulatory salt loading test, or fludrocortisone suppression test [12].
Measuring sodium and potassium concentrations simultaneously in serum and urine specimens has been suggested for screening purposes.
If primary hyperaldosteronism is confirmed biochemically, CT scanning or other cross-sectional imaging can confirm the presence of an adrenal abnormality, possibly an adrenal cortical adenoma, adrenal carcinoma, bilateral adrenal hyperplasia, or other less common changes. Imaging findings may ultimately lead to other necessary diagnostic studies, such as adrenal venous sampling, to clarify the cause.
Differential Diagnosis
Primary hyperaldosteronism can be mimicked by Liddle syndrome, and by ingestion of licorice and other foods containing glycyrrhizin.
Treatment
The treatment for hyperaldosteronism depends on the underlying cause. In people with a single benign tumor (adenoma), surgical removal (adrenalectomy) may be curative. This is usually performed laparoscopically, through several very small incisions. For people with hyperplasia of both glands, successful treatment is often achieved with spironolactone or eplerenone. With its antiandrogen effect, spironolactone drug therapy may have a range of side effects in males and females, including gynecomastia and irregular menses. These symptoms occur less frequently with eplerenone drug therapy [13].
In the absence of treatment, individuals with hyperaldosteronism often have poorly controlled high blood pressure, which may be associated with increased rates of stroke, heart disease, and kidney failure. With appropriate treatment, the prognosis is considered good [14].
In this case report, there is a female patient who presented with uncontrolled hypertension and hypokalemia. She was on 3 antihypertensive medications but still, her blood pressure was not controlled. In view of the above findings, she was suspected to have secondary hypertension of adrenal cause and was evaluated accordingly [15]. She was worked up for Primary Aldosteronism as a cause for her hypertension. On evaluation, with PRA ratio and CT scan imaging of the Adrenals, her diagnosis was confirmed. She was offered surgery for a cure for her disease but she opted for medical management. She was started on Spironolactone with a good effect on the control of hypertension and hypokalemia [16, 17].
A 53-year-old Filipino female, Miss PA, presented to Emergency Department with complaints of abdominal pain, low back pain, and muscle cramp. She had a history of being diagnosed with hypertension 4 months back when she was evaluated at a private clinic with the same complaints. She was investigated and her blood investigations were suggestive of mild renal dysfunction (sr. creat-1.5mg/dl) and low potassium levels (sr. K- 2.7). She was started on telmisartan and oral potassium supplements for correction of unexplained hypokalemia [18-21].
Later, after 3 months she presented with the same complaints at another health facility. Here, in view of her back pain, the USG abdomen was done, which revealed bilateral cortical renal cysts, with no other abnormality. Her BP was still not controlled on the previous medication and there was no compliance issue. In view of the above findings, her anti-hypertensive was changed to an amlodipine valsartan and hydrochlorothiazide combination. She started her new medications but both hypertension and low back pain are still not relieved.
She came to our Emergency Department with the above complaints and uncontrolled hypertension. She was admitted for a workup for uncontrolled hypertension. Her previous reports and medications were evaluated. Her results showed alarmingly low potassium levels of 1.8 with normal renal functions. In view of low potassium levels and unresponsive hypertension, she was suspected to have Endocrinal causes of HT [22, 23]. Her Blood Gas analysis was done in view of the above and it showed metabolic alkalosis, consistent with the above finding. In view of the above findings, she was suspected to have Primary aldosteronism as a cause of her hypertension, for which her Sr. Aldosterone and Sr. Renin levels were sent after her potassium corrections were done using oral and intia viens potassium supplements. She also underwent a CT abdomen with contrast, to look for bilateral adrenal glands for any abnormality. She was started on Tab Aldactone after her blood investigations were sent. During her hospital stay, complained of back pain and muscular cramps. In view of her chronic low potassium levels, she was suspected to have hypokalemia-induced myositis as the cause of the muscular pain. In view of this, her Sr CPK was also sent which was elevated. After doing potassium correction, her body pain reduced, and repeat CPK levels were also low. Her BP was controlled on Aldactone after its dose modification and K levels also normalized.
Her CT abdomen was reported as having a small hypo-dense lesion in Right adrenal gland suspected to be adrenal adenoma, whereas the left adrenal gland was reported as normal. Her Sr aldosterone level was high and sr. rennin level was low and the ratio of Sr. aldosterone to rennin was increased. In view of these findings, diagnosed as having she was Primary aldosteronism secondary to right adrenal tumor which was the reason for her high unresponsive hypertension to previous routine also known antihypertensive and low Sr. K levels.
Her Aldactone dose levels were adjusted for control of Blood pressure and potassium levels. She was also started on Potassium citrate tablets in view of CT finding of medullar calculi. Surgery reference was taken for right adrenalectomy, as the definitive cure for her hypertension and chronic hypokalemia. She was reviewed by the surgeons and planned for laparoscopic Rt adrenalectomy.
The patient deferred the surgery and wanted to get it done at home country. She discharged on Aldactone and Potassium citrate tablets with controlled BP and stable normalized K levels. She was advised to follow up under Nephrology OPD for review
Although initially considered a rarity, primary aldosteronism now is considered one of the more common causes of secondary Hypertension (HTN). Litynski reported the first cases, but Conn was the first to well characterize the disorder, in 1956. Conn syndrome, as originally described, refers specifically to primary aldosteronism due to the presence of an adrenal aldosteronoma (aldosterone-secreting benign adrenal neoplasm).
Based on older data, it was originally estimated that primary aldosteronism accounted for less than 1% of all patients with HTN. Subsequent data, however, indicated that it may actually occur in as many as 5%-15% of patients with HTN. Primary aldosteronism may occur in an even greater percentage of patients with treatment-resistant HTN and may be considerably underdiagnosed; this is especially true if patients with treatment-refractory HTN are not specifically referred for evaluation to an endocrinologist.
Although prior studies suggested that aldosteronomas were the most common cause of primary aldosteronism (70%-80% of cases), later epidemiologic work indicated that the prevalence of aldosteronism due to bilateral idiopathic adrenal hyperplasia (IAH) is higher than had previously been believed. These reports suggested that IAH may be responsible for as many as 75% of primary aldosteronism cases. Moreover, reports have described a rare syndrome of primary aldosteronism characterized by histologic features intermediate between adrenal adenoma and adrenal hyperplasia, which often is unilaterally localized (also referred to in earlier literature as “intermediate aldosteronism”) (Figure 1 and 2).
Figure 1: Magnetic resonance imaging (MRI) scan in a patient with Conn syndrome showing a left adrenal adenoma. Scintigram obtained by using iodine-131-beta-iodomethyl-norcholesterol (NP-59) in a 59-yearold man with hypertension shows fairly intense radionuclide uptake in the right adrenal tumor. At surgery, a Conn tumor was confirmed.
Figure 2: Scintigram obtained by using iodine-131-beta-iodomethylnorcholesterol (NP-59) in a 59-year-old man with hypertension shows fairly intense radionuclide uptake in the right adrenal tumor. At surgery, a Conn tumor was confirmed.
Entities known to cause aldosteronism include the following (see the image below):
1.Aldosterone-producing adenomas (APAs)
2.Aldosterone-producing renin-responsive adenomas (AP-RAs; also abbreviated as RRAs)
3.Bilateral idiopathic adrenal (glomerulosa) hyperplasia or IAH (also known as primary adrenal hyperplasia or PAH)
4.Familial forms of primary aldosteronism
5. Ectopic secretion of aldosterone (The ovaries and kidneys are the 2 organs described in the literature that, in the setting of neoplastic disease, can be ectopic sources of aldosterone, but this is a rare occurrence.)
6. Pure aldosterone-producing adrenocortical carcinomas (very rare; physiologically behave as APAs)
Although primary aldosteronism is still a considerable diagnostic challenge, recognizing the condition is critical because primary aldosteronism–associated HTN can often be cured (or at least optimally controlled) with the proper surgical or medical intervention. The diagnosis is generally 3-tiered, involving an initial screening, a confirmation of the diagnosis, and a determination of the specific subtype of primary aldosteronism.
Among the major goals of therapy for primary aldosteronism are:
1. Normalization of blood pressure.
2. Normalization of levels of serum potassium and other electrolytes.
3. Normalization of serum aldosterone levels.
The appropriate treatment for primary aldosteronism depends on its cause. Although hypertension is frequently cured after unilateral adrenalectomy in patients with primary aldosteronism secondary to an adrenal aldosteronoma, the mean HTN cure rate is only 19% after unilateral or even bilateral adrenalectomy in patients with Idiopathic Adrenal Hyperplasia (IAH). Therefore, medical management is the treatment of choice for the IAH variant of primary aldosteronism.
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Citation: Tripathi. M. Case of Hidden Hypertension. Prim Health Care. 2023, 13(01), 481
Received: 07-Jan-2023, Manuscript No. JPHC-22-85464; Editor assigned: 10-Jan-2023, Pre QC No. JPHC-22-85464 (PQ); Reviewed: 24-Jan-2023, QC No. JPHC-22-85464 (Q); Revised: 26-Jan-2023, Manuscript No. JPHC-22-85464 (R); Published: 29-Jan-2023, DOI: 10.35248/2376-0389.23.13.1.481
Copyright: ©2023 Tripathi, M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
