An Underdiagnosed Reason for Resistant Hypertension


A 30-year-old lady presents to the emergency division (ED) with headache, nausea, vomiting, diarrhea, and stomach ache that began 1 day in the past. The affected person studies 3 episodes of nonbilious, nonbloody vomiting with concomitant bilateral extremity weak spot lasting about quarter-hour and a pair of episodes of nonbloody diarrhea.

She studies intermittent episodes of generalized physique aches and decrease extremity weak spot over the past 2 months. She denies fevers, chills, weight reduction, neck ache, shortness of breath, palpitations, chest ache, or paresthesias.

The affected person has a medical historical past of hypertension for 3 years and sort 2 diabetes for 4 years. She has been noncompliant with medicines for these circumstances for the final 6 months due to insurance coverage points. It isn’t identified whether or not she was screened for a secondary reason behind hypertension when she initially started remedy.

Her household historical past is noncontributory. She denies smoking in addition to alcohol or drug use. She is a married stay-at-home mother with 2 daughters. She denies a historical past of gestational hypertension or preeclampsia however had a spontaneous abortion at 9 weeks’ gestation inside the final 12 months. The affected person studies potential current influenza publicity and is anxious that one thing is flawed.

Bodily Examination

On arrival, her vitals are as follows: blood strain, 195/126 mm Hg; respiratory fee, 18 breaths per minute unlabored; coronary heart fee, 71 beats per minute; temperature, 98.4 °F; and oxygen saturation, 97% on room air.

On bodily examination, the affected person is somnolent however simply arousable. She is oriented, and her ideas are coherent. She is of common construct with a BMI of 24.8. Her pores and skin is heat and her mucous membranes are moist. She has sweaty palms however no rashes or lesions. Her eyes seem regular with no proptosis. Visible acuity is also regular and extraocular actions are intact.

A small, diffusely enlarged goiter (grade 1 in response to World Well being Group classification) is discovered. A bruit is audible over the goiter however no tenderness or lymphadenopathy is clear. Her lungs are clear to auscultation. Her coronary heart examination reveals clear S1 and S2 with out murmur, rubs, or gallops. Her stomach is flat; no tenderness, lots, or organomegaly are current. Bowel sounds are normoactive. Pelvic and rectal examinations are regular. Peripheral pulses are intact.

No edema is famous within the decrease extremities. The affected person has full vary of movement, each energetic and passive, of the arms, wrists, elbows, shoulders, hips, knees, and ankles. Her power is 5/5 within the higher and decrease extremities bilaterally. Sensations of ache, mild contact, proprioception, and vibration are intact. All reflexes are 2+.

Laboratory Outcomes

Serum laboratory values are outstanding for a low potassium degree, excessive arterial pH, and borderline excessive bicarbonate degree (Desk). Anion hole, blood glucose, hemoglobin A1c, and low-density lipoprotein levels of cholesterol are elevated. Full blood cell depend, troponin degree, and coagulation research are unremarkable. Serum being pregnant take a look at is damaging.

Desk. Irregular Laboratory Outcomes

The affected person’s electrocardiogram reveals regular sinus rhythm at 71 beats per minute with left axis deviation and T-wave inversion within the inferior lateral leads. Lung fields are clear on chest radiograph.

The affected person is admitted to the cardiology service and instantly is began on labetalol 100 mg orally for elevated blood strain. She reveals little enchancment and standing orders for hydralazine and lisinopril are written. Her blood strain stays elevated; the hydralazine dosage is elevated from 50 to 75 mg and, lastly, to 100 mg 3 instances a day with the aim of reducing her blood strain to lower than 130/80 mm Hg.

She additionally receives acetaminophen for ache and ondansetron for nausea and/or vomiting as wanted. The affected person refuses prophylactic remedy for influenza publicity however consents to influenza vaccination.

An echocardiogram analysis reveals a left ventricular ejection fraction of 65% (regular vary, 55%-70%); her valves and anatomy are of regular measurement and performance.

An endocrinologist is consulted for her uncontrolled diabetes and goiter. The affected person is began on insulin lispro and insulin glargine. An ultrasound of the thyroid reveals a 1.7-cm nodule on the left lobe and a 5.2-cm nodule on the correct. Nonetheless, laboratory analysis of thyroid standing is unremarkable. The affected person’s hypokalemia is handled with 3 doses of potassium chloride powder (40 mEq orally each 4 hours). The affected person’s plasma aldosterone degree is 24.7 ng/dL (regular vary, 1-21 ng/dL) and plasma renin focus is undetectable (regular vary with a standard sodium eating regimen, 0.6-4.3 ng/mL/h).

Main aldosteronism (PA) is recognized as a possible reason behind the affected person’s sickness and a contrast-enhanced computed tomography (CT) of the stomach is ordered to judge for adrenal lots. The CT reveals a left-sided adrenal mass measuring 2.5 cm × 1.8 cm.

To substantiate the prognosis of PA, a saline infusion take a look at is ordered. In line with PA, the plasma aldosterone focus will increase to 38.7 ng/dL on the 4-hour mark. The affected person’s signs enhance and she or he is discharged on an angiotensin-converting enzyme (ACE) inhibitor for hypertension and a potassium complement.

She receives diabetes dietary schooling throughout the hospitalization and insulin coaching. She is discharged on insulin injection and instructed to observe up as scheduled with the endocrine clinic. The affected person is contemplating the advice to biopsy the thyroid nodules. A moderate-intensity statin, (atorvastatin 20 mg day by day) is prescribed for hyperlipidemia. She is endorsed to observe a low-fat, heart-healthy eating regimen and keep away from being pregnant whereas taking the statin. The affected person has an intrauterine gadget for contraception.


As soon as thought-about a uncommon situation, PA has emerged as a main reason behind secondary hypertension, accounting for five% to 10% of sufferers with hypertension and 20% of these with resistant hypertension.1-4 The prevalence of PA is estimated to be 5% to 17%, though this situation is underdiagnosed.1,2

Hyperaldosteronism will be labeled as main or secondary. Secondary hyperaldosteronism is attributable to extreme activation of the renin-angiotensin-aldosterone system (RAAS) attributable to extra-adrenal stimuli, equivalent to a renin-producing tumor, renal artery stenosis, or edematous problems (eg, coronary heart failure, being pregnant).2,4

Main aldosteronism is unbiased of the RAAS and is outlined as extreme manufacturing of aldosterone by the adrenal glands.2,4 Extreme manufacturing of aldosterone results in elevated exercise of the sodium-potassium pumps within the cortical amassing ducts of the nephron, which, in flip, causes sodium retention and potassium loss.4 Hyperaldosteronism additionally causes elevated lack of hydrogen ions in medullary amassing ducts, leading to metabolic alkalosis.2

Causes of PA embrace:

  • Aldosterone-producing adrenal adenomas (Conn syndrome): these adenomas sometimes are unilateral however could also be bilateral4
  • Adrenal hyperplasia: this can be unilateral or bilateral; hyperplasia is extra frequent amongst older males2,4
  • Familial PA: this situation is uncommon and infrequently associated to germline mutations of electrolyte channels2,5
  • Ectopic aldosterone-secreting tumors2
  • Aldosterone-producing adrenocortical carcinoma2

The most typical scientific manifestation of PA is hypertension that always is immune to remedy.2,5 Hypertension might result in complaints of complications and, if left untreated, might trigger hypertensive retinal adjustments, stroke, renal insufficiency, hypertensive encephalopathy, and cardiac failure.6 Regardless of having elevated blood strain, sufferers with PA don’t exhibit peripheral edema.4 Sufferers could also be hypokalemic, even within the absence of potassium-depleting diuretics.4 People who’re severely hypokalemic might current with fatigue, muscle weak spot, ileus, and palpitations.2 Extreme lack of potassium might result in hypokalemia-induced nephrogenic diabetes insipidus, which may trigger polydipsia and/or polyuria.2 Different indicators and signs embrace constipation, decreased deep tendon muscle reflexes, and hypomagnesemia.2

Analysis of Main Aldosteronism

The diagnostic method to PA begins with routine laboratory research to evaluate serum ranges of sodium, potassium, magnesium, bicarbonate, glucose, blood urea nitrogen, and creatinine. Plasma aldosterone focus (PAC) and plasma aldosterone to renin ratio (ARR) function screening checks for PA and play an necessary position in distinguishing between main and secondary hyperaldosteronism.5 Regular ranges of PAC are lower than 10 ng/dL2; nonetheless, in PA, elevated ranges of plasma aldosterone with decreased or regular renin exercise improve the ratio. An ARR higher than 30 ng/dL and PAC higher than 20 ng/dL are extremely suspicious for PA, with sensitivity and specificity of higher than 90%.2

Confirmatory diagnostic checks embrace a saline infusion take a look at or oral sodium loading.

  • Saline infusion take a look at: Affected person is both sitting or mendacity down for a minimum of 1 hour earlier than and through a 4-hour infusion of IV regular saline. Plasma ranges for renin, aldosterone, cortisol, and potassium are drawn at hours 0 and 4. Aldosterone ranges of lower than 10 ng/dL after the infusion can rule out the prognosis of PA as a result of ranges don’t lower as they need to in sufferers with PA. Cortisol ranges are taken to exclude adrenocorticotropic hormone shouldn’t be inflicting elevations in aldosterone ranges.2
  • Oral sodium loading take a look at: Sufferers ingest 10 g to 12 g of sodium chloride orally for 3 days earlier than testing. On the finish of three days, serum and 24-hour urine are collected and examined for aldosterone, sodium, and potassium ranges. Urine aldosterone ranges higher than 14 µg/24 hours are confirmatory for PA. Urine sodium ranges are examined to make sure satisfactory salt loading for correct interpretation of the take a look at.2

To tell apart between causes of PA, thin-sliced adrenal CT with distinction is the commonest preliminary diagnostic take a look at to establish aldosteronomas and adrenal cell carcinoma.5 Ranges of aldosterone in adrenal venous blood could also be measured in sufferers in whom there’s excessive suspicion of unilateral PA regardless of regular imaging.5

Therapy of Main Aldosteronism

The general remedy aim in PA is to cut back the morbidity and mortality related to hypertension, hypokalemia, and different related signs.5 The method to remedy is dependent upon the etiology of the PA. For unilateral adrenal adenomas or adrenal hyperplasia, surgical resection usually is healing.5

Sufferers identified with bilateral adrenal hyperplasia and familial PA require a medical method. They need to be began on an aldosterone antagonist equivalent to spironolactone or eplerenone.5 For sufferers with persistent hypertension, clinicians ought to provoke one other antihypertensive agent, equivalent to hydrochlorothiazide or an ACE inhibitor. As well as, they need to advise sufferers to observe a low-salt eating regimen.6

Early prognosis and remedy of PA can enhance a affected person’s general long-term morbidity and mortality. Sufferers with PA have the next threat of growing persistent kidney illness than people with important hypertension. Nonetheless, when surgical adrenalectomy is carried out, there isn’t a distinction in kidney morbidity.7 Sufferers with PA even have an elevated threat for stroke, atrial fibrillation, coronary heart failure, coronary artery illness, diabetes, and metabolic syndrome than sufferers with important hypertension.8


Main aldosteronism ought to be thought-about in any affected person with treatment-resistant hypertension, particularly in a hypokalemic affected person who shouldn’t be taking a diuretic. Hypertension, unexplained hypokalemia, and metabolic alkalosis are the commonest findings. The workup contains serum electrolytes (to judge for hypokalemia, metabolic alkalosis, hypernatremia, and hypomagnesemia), ARR screening, in addition to a saline infusion or oral sodium loading take a look at and adrenal CT with distinction. People with PA have elevated long-term cardiovascular and renal dangers, making early prognosis and remedy important.

Corinne I. Alois, MS, PA-C, is an assistant professor at St. John’s College Doctor Assistant Program in Jamaica, New York; Alyssa C. Quinlan, PA-C, MPAS, is an assistant professor at St. John’s College Doctor Assistant Program.


  1. Monticone S, Burrello J, Tizzani D, et al. Prevalence and scientific manifestations of main aldosteronism encountered in main care observe. J Am Coll Cardiol. 2017;69(14):1811-1820. doi:10.1016/j.jacc.2017.01.052
  2. Dominguez A, Muppidi V, Gupta S. Hyperaldosteronism. In: StatPearls. StatPearls Publishing; 2021. Up to date November 21, 2020. Accessed June 22, 2021.
  3. Brown JM, Siddiqui M, Calhoun DA, et al. The unrecognized prevalence of main aldosteronism: a cross-sectional researchAnn Intern Med. 2020;173(1):10-20. doi:10.7326/M20-0065
  1. Grossman AB. Main aldosteronism (Conn syndrome). In: Merck Handbook Skilled Model. Merck & Co, Inc; 2020. Up to date September 2020. Accessed June 22, 2021.
  2. Funder JW, Carey RM, Mantero F, et al. The administration of main aldosteronism: case detection, prognosis, and remedy: an Endocrine Society scientific observe guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/jc.2015-4061
  3. Iqbal AM, Jamal SF. Important hypertension. In: StatPearls. StatPearls Publishing; 2021. Up to date July 10, 2020. Accessed June 22, 2021.
  1. Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Renal outcomes in medically and surgically handled main aldosteronism. Hypertension. 2018;72(3):658-666. doi:10.1161/HYPERTENSIONAHA.118.11568
  2. Monticone S, D’Ascenzo F, Moretti C, et al. Cardiovascular occasions and goal organ harm in main aldosteronism in contrast with important hypertension: a scientific assessment and meta-analysis. Lancet Diabetes Endocrinol. 2018;6(1):41-50. doi:10.1016/S2213-8587(17)30319-4

This text initially appeared on Medical Advisor


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