The correct answer is A

Comment: This patient has classic features of aortic coarctation. He has a pulse delay between the upper and lower extremities (radial artery to femoral artery delay). The BP in the lower extremities, when measured, will be lower than the BP noted in the upper extremities. The patient also has an ejection click and an early systolic murmur consistent with a bicuspid aortic valve, which is present in more than 50% of patients with aortic coarctation. The systolic and diastolic murmurs noted over the back are related to collateral vessels, which also cause the sign of rib notching, seen on this patient’s chest radiograph on the inferior surface of the posterior upper thoracic ribs bilaterally.

Essential HTN is a common cause of systemic HTN, but the physical examination features of this patient are not explained by this diagnosis. In addition, a family history of HTN is common in patients with essential HTN.

Pheochromocytoma causes paroxysmal HTN in about half of affected patients; other pheochromocytomas present similar to patients with essential HTN. The signs and symptoms of pheochromocytoma are variable. The classic triad of sudden severe headaches, diaphoresis, and palpitations carries a high degree of specificity (94%) and sensitivity (91%) for pheochromocytoma in hypertensive patients. The absence of all three symptoms reliably excludes the condition. Finally, the physical examination features in this patient do not reflect this diagnosis.

Renovascular HTN resulting from fibromuscular disease of the renal arteries usually presents in patients younger than 35 years of age. Atherosclerotic renovascular disease is more common in older patients and is frequently associated with vascular disease in other vessels (carotid or coronary arteries and peripheral vessels). Azotemia is often observed in patients with atherosclerotic renovascular HTN. Renal artery stenosis cannot explain this patient’s cardiac and peripheral vascular examination findings.

The correct answer is A

Comment: Nonpharmacological interventions are effective in lowering BP and may aid patients with HTN in achieving their target BP. The 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease Studies suggests that the DASH diet had the greatest impact on lowering systolic BP compared with physical activity, salt restriction, and weight loss. The DASH diet reduced systolic BP levels within 2 weeks of starting the plan. Not only was BP reduced, but total cholesterol and low-density lipoprotein were lower, too.

The correct answer is D

Comment: VHL disease is an autosomal dominant disorder with variable penetrance. The VHL protein gene is on chromosome 3p25 and functions normally as a tumor suppressor by inhibiting transcription elongation. Missense mutations outside the elongation binding domain can cause the VHL disease. Affected persons can develop cerebellar and retinal hemangiomas, pheochromocytoma, renal cell carcinoma, pancreatic cysts, and endolymphatic inner ear tumors. Although some VHL families present with MEN-2, others may present only with pheochromocytoma. Thus, patients presenting with apparently isolated pheochromocytoma should be evaluated for VHL disease and MEN-2.

Correct answer is A

Comment: Spironolactone is the most effective fourth medication for treating HTN in patients already on treatment with triple regimens that include an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), amlodipine, and a thiazide-like diuretic.

The correct answer is C

Comment: Dry cough, which is the most common side effect reported with ACE inhibitors, would be intolerable to a singer, and develops in approximately 10% of patients treated with ACE inhibitors. In half of these patients, the ACE inhibitor has to be discontinued.

Correct answer is C

Comment: This patient has medically complicated obesity, as evidenced by his body weight and multiple weight-related comorbid conditions (HTN, hyperlipidemia, impaired fasting glucose level, and obstructive sleep apnea). Additional weight loss, including consideration of bariatric surgery, will be paramount to improving BP control and lowering his overall cardiovascular risk. However, in the meantime, maintaining his current drug regimen is not appropriate. Further titration of his beta-blocker dose is unlikely to provide additional BP lowering and would likely induce symptomatic bradycardia given his current resting heart rate. His HTN was considered to be resistant because he had been unable to reach his BP goal despite taking three appropriate medications.

After completing a thorough review of adherence to lifestyle decisions and medications, the most appropriate next step in management would be to evaluate for identifiable secondary causes of HTN such as sleep apnea, renovascular disease, primary aldosteronism, Cushing syndrome, pheochromocytoma, and thyroid disease. This patient’s history of developing HTN at a young age (<10 years) and hypokalemia with diuretic use are additional factors that suggest the need to evaluate for other contributors to his HTN.

Clonidine can be used as therapy for essential HTN and would be a reasonable agent to add; however, at this point, it is important to pursue other etiologies.

Further laboratory tests revealed: a thyroid-stimulating hormone level of 3.14 mIU/mL (0.30–5.0 mIU/mL); 24-hour urinary free cortisol level, 17 µg (3.5–45 µg/24 h); plasma free metanephrine level, <0.20 nmol/L (<0.50 nmol/L); plasma free normetanephrine level, 0.24 nmol/L (<0.90 nmol/L); plasma aldosterone concentration (PAC), 16 ng/dL (1–21 ng/dL); plasma renin activity (PRA) level, <0.6 ng/mL/h (0.6–3.0 ng/mL/h); and PAC:PRA ratio, 27 (<20). ^–

The correct answer is B

Comment: In the setting of a normally responsive renin-angiotensin-aldosterone (RAA) axis, hypoaldosteronism (e.g., primary adrenal insufficiency) would cause an elevated PRA, not a suppressed one as in this patient. In contrast, primary aldosteronism promotes negative feedback on the RAA axis, resulting in a low PRA level, making this the correct answer. Concomitant antihypertensive drug therapy is important to consider when interpreting the results of renin and aldosterone levels. ACE inhibitors (ACEIs) block conversion of angiotensin I to angiotensin II, which in turn decreases aldosterone levels. This inhibition actually causes elevated renin secretion through the RAA axis feedback. As a result, a low PRA level in a patient taking an ACEI or ARB should increase clinical suspicion for primary aldosteronism, as in this case. Restriction of dietary sodium results in increased aldosterone production via increased renin secretion. In pheochromocytoma, catecholamines are released that increase sympathetic neural tone and increase renin levels.

The correct answer is A

Comment: An increased PAC/PRA ratio alone is not diagnostic for primary aldosteronism. Primary aldosteronism must be confirmed by demonstrating inappropriate aldosterone secretion. Confirmatory testing can be done by evaluating 24-hour urine aldosterone levels after a sodium load, making this the correct answer. This functions to maximally suppress intrinsic aldosterone secretion. CT of the adrenal glands is not a good confirmatory study because it does not provide information regarding the functional status of any potentially visualized abnormalities. Surgical removal of an adenoma, which has not been proven to be functional, would be premature, so this would not contribute to the patient’s current management. Adrenal venous sampling is useful to distinguish between subtypes of primary aldosteronism but is only indicated after confirmatory blood testing is complete. Empirical treatment with a mineralocorticoid antagonist would be premature because some patients may benefit from surgical intervention. Fine-needle aspiration biopsy of the adrenal glands has no role in the workup of primary aldosteronism. Occasionally, fine-needle aspiration biopsy is useful in the investigation of an adrenal mass suspected to be metastatic disease in the setting of a known malignancy.

However, it has no role in an isolated adrenal mass workup because cytology cannot distinguish a benign adrenal mass from adrenal carcinoma.

The patient was referred for a sodium-loading test with measurement of 24-hour urine aldosterone excretion. The patient consumed a 6000-mg sodium diet for 3 days. His 24-hour urine collection revealed the following results: urine volume, 3008 mL; creatinine concentration, 0.8 mg/dL (0.8–1.3 mg/dL); 24-hour urine sodium level, 343 mmol/24 h (40–217 mmol/24 h); sodium concentration, 114 mmol/L (135–145 mmol/L); and aldosterone, 17 µg/24 h (<12 µg/24 h if 24-hour urine sodium level is >200 mmol).

Because the urine aldosterone level was well above the 12 µg/24 h cutoff, the diagnosis of primary aldosteronism, resulting from either adrenal adenoma or idiopathic adrenal hyperplasia, was entertained. CT of the abdomen with 3-mm cuts through the adrenal glands did not demonstrate adrenal masses.

The correct answer is E

Comment: Radionuclide scintigraphy with iodocholesterol was formerly used to correlate adrenal function with visualized anatomic lesions to help clarify a target for possible surgical resection. However, this patient has no clear radiographic evidence of an adrenal adenoma. An MRI of the adrenal glands cannot rule out unilateral aldosterone-producing disease and would not contribute any additional information for this patient. Although serial CT imaging, like MRI, may reveal a new adrenal lesion, nonfunctioning adrenal incidentalomas are relatively common in patients older than age 40 years, and this would not provide any information regarding whether the lesion was hormonally functional. Moreover, aldosterone-producing adenomas can be very small, so CT imaging may not universally exclude this disorder. Adrenal venous sampling performed by an experienced interventional radiologist is the only means of detecting laterality of disease. Even though AVS is not available at all medical centers, it should be considered in all patients willing to pursue surgical management. If not initially pursued, it should be reconsidered in patients who either do not tolerate or do not benefit from medical management. Proceeding directly to adrenalectomy without prior AVS in this case would not be indicated because the disease could be bilateral. AVS was offered, but the patient did not wish to pursue surgical treatment. In the absence of an obvious adrenal carcinoma or adrenal adenoma, he was thought most likely to have the idiopathic bilateral hyperplasia subtype of primary aldosteronism.

The correct answer is B

Comment: Low-dose glucocorticoid is only used as first-line therapy in the subtype of primary aldosteronism known as glucocorticoid-remediable aldosteronism, which is a very rare genetic condition that needs to be confirmed with specific genetic testing before initiating treatment. The best treatment option for this patient with bilateral disease is medical treatment with a mineralocorticoid receptor antagonist such as spironolactone or eplerenone. Triamterene is a potassium-sparing diuretic agent that also targets the distal renal tubule; however, unlike spironolactone and eplerenone, it is not an aldosterone antagonist and is therefore not the preferred agent. A low-salt diet is a reasonable recommendation for all patients with HTN but would not be sufficient for this patient. Percutaneous radiofrequency ablation is occasionally used to treat unilateral adrenal lesions but would clearly not be useful in this scenario.

The patient began a therapeutic trial of an aldosterone antagonist, eplerenone, at a dose of 50 mg by mouth twice daily. After 2 months of therapy, his valsartan and metoprolol doses were decreased by 50%, with systolic BP maintained in the range of 135 to 145 mm Hg.

The correct answer is C

Comment: Resistant HTN is defined as HTN that is poorly responsive to treatment and requires the use of multiple medications to achieve acceptable BP ranges.

The correct answer is E

Comment: The following can all contribute to the development of both hypertension and resistant hypertension: obesity, physical inactivity, a diet high in salt, heavy alcohol drinking, and poor adherence to medication.

The correct answer is D

Comment: The most likely of these to need immediate treatment is the child with bronchiolitis who has a hypertensive emergency; the elevation of the BP combined with the end-organ symptom of lethargy is highly concerning, especially in a setting of few other causes. Though option B could be considered hypertensive urgency, the BP is likely increased by the pain associated with the abscess, and therefore pain medications could be tried first. The asthmatic only has stage I HTN, which is most likely influenced by the steroid treatment of asthma, and his tachypnea is likely from the asthma. Finally, the patient with a history of HTN and renal failure would be considered a chronic patient, and though oral medications could be used, a conversation with the nephrologist should occur.

The correct answer is B

Comment: In chronic kidney disease (CKD) with proteinuria, either ACEIs or ARBs reduce urinary protein and slow the progression of renal failure.

Hypertension is present in approximately 80% to 85% of patients with CKD and is thought to be multifactorial (sodium retention, increased activity of the renin-angiotensin system, and enhanced activity of the sympathetic nervous system).

In patients with proteinuria (defined as protein excretion above 500–1000 mg/day) CKD, first-line therapy consists of an ACEI or ARB as first-line therapy for the treatment of HTN. ^, ACEIs, in addition to reducing intraglomerular pressure, reduce the excretion of urinary protein (both of which delay the progression of renal failure). ARBs have a similar effect. ^, Aside from BP control, the aim is to reach less than 1000 mg/day of protein spilling into the urine.

In patients with edema, a thiazide diuretic can be added as a second-line drug; chlorthalidone is preferred over hydrochlorothiazide because of its longer duration of action. A dihydropyridine calcium channel blocker (CCB) is appropriate as a second-line drug for patients without fluid retention. Neither a beta-blocker nor a sympathetic, such as Aldactone, demonstrate the protective effect of ACEIs or ARBs.

The correct answers are A and B

Comment: Evidence suggests greater cardiovascular protection with other classes of antihypertensive agents (ACEIs/CCBs) versus beta-blockers (atenolol). Hydrochlorothiazide is not as effective a diuretic agent as chlorthalidone.

To initiate therapy to lower this patient’s BP, hydrochlorothiazide should be changed to chlorthalidone, and next, a substitute should be found for hydralazine (either amlodipine or combination ACEI/ARB, preferably in a combination tablet).

Three maneuvers can lead to better BP control over shorter periods. First, use combination antihypertensive agents earlier and more often, especially in HTN stage II or higher; second, identify resistant HTN earlier and use spironolactone when possible. Third, avoid less efficacious medications (hydralazine and clonidine) from days gone by.

Correct answer is B

Comment: Resistant HTN is defined as BP not controlled on a complementary three-drug regimen with a diuretic as one of the agents. Spironolactone has become a “go-to” agent for treating resistant HTN. ^, If it works, it may allow the patient to discontinue other antihypertensive agents. It is a pharmaceutical backbone for resistant HTN treatment.

The correct answer is B

Comment: The patient qualifies for a diagnosis of stage II HTN (BP >160/>100 mm Hg). A single agent will not suffice to lower the patient’s BP to target level. Many studies have also demonstrated that combination therapy reduces the risk of cardiac events, is more efficacious, and improves adherence, BP control, and time-to-target BP. Combination therapy with appropriately chosen agents (such as amlodipine and an ARB) augments effects of either agent taken alone. The days of “maxing out” monotherapy before initiating combinations are over.

The correct answer is A

Comment: When two or more drugs are used, they should be from different antihypertensive drug classes. In most patients, the drugs should be selected from among the three preferred classes (i.e., ACEIs [or ARBs], CCBs, and thiazide diuretics).

Evidence suggests treating with the combination of an ACEI (or ARB) and a CCB, preferably a dihydropyridine calcium blocker. In addition, it is also recommended to prescribe these two agents as a single-pill combination, if feasible. Single-pill combinations lead to greater BP reduction, increased attainment of BP goals, and better medication adherence as compared with free equivalents, in which the two drugs are prescribed separately.

The combination of an ACEI (or ARB), a CCB with a thiazide diuretic is a reasonable alternative, particularly in patients who have conditions that can benefit from a thiazide diuretic (e.g., edema, osteoporosis, calcium nephrolithiasis with hypercalciuria).

Initially, serum electrolytes and serum creatinine should be monitored 1 to 3 weeks after initiation or titration of ACEIs, ARBs, mineralocorticoid receptor antagonists, and diuretics. In patients on stable doses of medications, electrolytes and creatinine are typically monitored annually.

If BP is uncontrolled, it is typically recommended to escalate doses of individual antihypertensive drugs to at least half the maximum recommended dose (i.e., to a moderate or high dose) before adding additional therapy. After goal BP is attained, patients should be followed every 3 to 6 months.

The correct answer is D

Comment: Thiazides are known to produce mild hyperglycemia. It is typically not of clinical consequence in nondiabetics and can be minimized by correcting any associated hypokalemia (the two side effects appear to be linked). The effect on plasma glucose is typically very small, with the low doses of thiazides typically prescribed for treating hypertension because low doses have minimal natriuretic effects.

The correct answer is B

Comment: Angiotensin II (Ang II) is necessary for maintaining efferent arteriole resistance in this setting. Reducing Ang II levels, or Ang II effects, can reduce GFR and cause kidney failure in this setting. In general, contraindications to ACEI use include hyperkalemia (>5.5 mmol/L), renal artery stenosis, pregnancy, or prior adverse reaction to ACEIs including angioedema.

The correct answer is B

Comment: HTN is a frequent finding in patients with NF1 and may develop during childhood. If the vascular stenosis resulting from loss of neurofibromin expression occurs in the renal arteries, the patient develops renovascular HTN. The RAS plays an important role in the development of HTN. In unilateral RAS, decreased kidney blood flow stimulates the production of renin, angiotensin II, and aldosterone. Aldosterone production causes sodium and water retention, but these excesses of sodium and water are rapidly excreted by the contralateral kidney by pressure natriuresis. But in bilateral RAS, as in our patient, although there is water and salt retention with a similar mechanism, natriuresis cannot be achieved because of decreased blood flow in both kidneys. The increased plasma volume suppresses plasma renin activity, and it causes volume-mediated HTN not renin-mediated. HTN in NF1 is a complicated problem. Approximately 15% of NF1 patients have HTN, either primary HTN or secondary HTN because of RAS. Because of stenosis, kidney blood flow decreases and plasma renin level is measured as high. ^,

In our patient, because the plasma renin level was high and bilateral RAS was detected, treatment was started with antihypertensive medications, then PTRA was performed and a stent was placed in a renal artery. The patient was normotensive in the follow-up period, and antihypertensive drugs were discontinued. However, over the years, our patient developed mild HTN, and RAS overactivity developed again in follow-up. In our patient, the renin level was normal, and it was seen that renal artery blood flow was patent after PTRA. HTN was seen to regress.

The correct answer is E

Comment: Patients with stage I hypotension (BP 130–139/80–89 mm Hg) who are at low risk for cardiovascular (CV) disease should be initially treated with nonpharmacologic, lifestyle improvements, with reassessment after 3 to 6 months to determine if they have met their BP goal of <130/<80 mm Hg.

The correct answer is E

Comment: The correct answer is a thiazide diuretic. Studies have shown that alpha-blockers actually double the risk of heart failure compared with a diuretic, and both CCBs and ACEIs are also inferior to a diuretic for preventing congestive heart failure (CHF).

Among patients selected for antihypertensive drug treatment, therapy should be initiated with either one drug (i.e., monotherapy) or two drugs (i.e., combination therapy, preferably in a single pill to improve adherence). ^,

In general, patients with a SBP 10 to 20 mm Hg above goal and/or a diastolic BP 10 mm Hg above goal should have antihypertensive drug therapy initiated with low to moderate doses of two agents with complementary mechanisms of action. Some experts begin with two agents in patients with stage II hypertension (i.e., SBP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg), whereas other experts would initiate therapy with two drugs in patients whose SBP is ≥150 mm Hg and/or diastolic BP is ≥90 mm Hg.

The correct answer is C

Comment: This patient will need at least two drugs to reduce her SBP from 145 to <130 mm Hg. If she is successful in losing weight, with concomitant reduction of BP, one of the two drugs can be reduced in dosage or discontinued. The 2017 American College of Cardiology/American Heart Association recommends therapy with two drugs consisting of either a thiazide, an ACEI (or ARB), and a CCB. Note that the side effects of the thiazide (mild hypokalemia) can be countered by either an ACEI or an ARB (which can produce mild hyperkalemia).

Combination therapy lowers BP more than monotherapy and increases the likelihood that target BP will be achieved in a reasonable time. In addition, using two drugs may lead to attainment of goal BP with lower doses of each medication, and this reduces the risk of dose-related side effects.

Regardless of whether treatment is begun with one or two drugs, the initial drug dose should generally be low. However, by far the most important strategy for ultimately achieving BP control is to avoid therapeutic inertia. Therapeutic inertia is defined as failing to initiate or adjust/intensify prescribed drug therapy despite the recognition of uncontrolled HTN.

When two drugs are used, they should be from different antihypertensive drug classes. In most patients, the drugs should be selected from among the three preferred classes (i.e., ACEIs [or ARBs], CCBs, and thiazide diuretics).

The correct answer is C

Comment: Patients with a history of either diabetes or kidney disease should be given an ACEI or an ARB to prevent the development, or further progression, of kidney disease.

Patients treated with antihypertensive drug therapy should be evaluated (either in person or by telehealth) every 2 to 4 weeks until their BP is at goal. Waiting 4 weeks to reevaluate after starting or intensifying therapy is typically appropriate to permit long-acting antihypertensive drugs enough time to manifest their full BP-lowering effect. If BP is uncontrolled, we typically escalate doses of individual antihypertensive drugs to at least half the maximum recommended dose (i.e., to a moderate or high dose) before adding additional therapy. After goal BP is attained, we usually follow patients every 3 to 6 months.

The correct answer is E

Comment: This is the best choice. It would increase the atrioventricular node’s effective refractory period and slow his ventricular rate, while also reducing arterial BP. This is an example of treating a patient with a comorbid condition atrial fibrillation (AF).

AF is an increasingly prevalent condition and the most common sustained arrhythmia encountered in ambulatory and hospital practice. Several clinical risk factors for AF include age, sex, valvular heart disease, obesity, sleep apnea, heart failure, and HTN.

Of all the risk factors, hypotension is the most commonly encountered condition in patients with incident AF.

The RAA system has been demonstrated to be a common mechanistic link in the pathogenesis of hypertension and AF.

The correct answer is D

Comment: Methyldopa has the best, most well-established track record for safety as an antihypertensive drug in pregnancy.

ARBs are contraindicated in pregnancy. Women contemplating pregnancy should be counseled to discontinue these medications before conception. Exposure to such drugs may result in a decrease in placental blood flow, which can result in oligohydramnios, renal failure, low birth weight, cardiovascular anomalies, spontaneous abortions, and other abnormalities.

The correct answer is D

Comment: Intravenous sodium nitroprusside is one of the drugs of choice for rapid lowering of SBP to <120 mm Hg (within 20 minutes) in the setting of a dissecting aorta. Most other hypertensive emergencies do not call for such rapid changes in BP because of the overriding concern about reductions in cerebral blood flow associated with rapid drops in BP.

The traditional drug of choice for therapy of hypertensive emergencies is sodium nitroprusside.

Intravenous labetalol produces a prompt, controlled reduction in BP and is a promising alternative.

Other agents used are diazoxide, trimethaphan camsylate, hydralazine, nitroglycerin, and phentolamine. However, all these agents have disadvantages, including unpredictable antihypertensive effects, difficult BP titration, and serious potential adverse effects such as profound hypotension, reduced renal blood flow, and increased myocardial workload. Most patients with hypertensive urgencies can be effectively treated with orally or sublingually administered agents. Older regimens of reserpine, methyldopa, or guanethidine, with their slow onsets and long durations of action, have been largely replaced by clonidine and nifedipine. Captopril and minoxidil have also been used with some success. Despite the lack of comparative trials with traditional agents, demonstrated efficacy and desirable pharmacologic characteristics have made several new agents acceptable for therapy of hypertensive crises.

The correct answer is A

Comment: Tobacco smoking is a potent promoter of endothelial dysfunction and activates vasoconstriction by inhibition of endothelium-dependent vasodilatation.

The correct answer is B

Comment: The elevated serum sodium, high serum bicarbonate, and low serum potassium levels reflect a high probability of mineralocorticoid effect, which would explain the recent development of resistant hypertension. Therefore, measurements of aldosterone and renin are most likely to reveal this disturbance. Measurement of GFR, catecholamines, and microalbuminuria would not explain the electrolyte changes and are far less likely to add useful information regarding identifying the cause of treatment resistance, making options A, C, and D incorrect.

The correct answer is B

Comment: A review of the DASH diet studies indicates that the greatest benefit was seen among African-American women who were hypertensive, and the least significant effect on BP reduction in normotensive women. The DASH diet lowers BP but not weight or glucose control.

The correct answer is B

Comment: Clearly, this patient is obese and has impaired glucose tolerance. Moreover, she has HTN and is being treated with a drug at a very low dose, given her body size, that worsens glucose tolerance. Getting her to lose weight will take a long time, and even if successful, it will increase her total BP load over time. Increasing the dose of metoprolol will increase the likelihood of diabetes and worsen her morbidity. Adding an ACEI to an underdosed beta-blocker such as metoprolol does not alleviate the risk for diabetes development and, although it may improve HTN, will not have the same effect as a drug combination that is well documented in having additional BP-lowering effects in such patients.

The correct answer is A

Comment: Stenting of the left renal artery reflects the benefit of renal revascularization when renal stenosis affects the entire functioning mass for patients with recurrent CHF. ACEIs have established survival benefits and should be continued, not stopped. Unilateral nephrectomy of the occluded kidney might lower BP levels, but low BPs are counterproductive and may worsen fluid retention when the remaining kidney has high-grade vascular disease.

The correct answers are B and E

Comment: Sleep apnea interferes with the nocturnal fall in BP. Lack of nocturnal fall in BP predicts risk of left ventricular hypertrophy. ABPM BP readings are lower than those obtained under office conditions, and normal levels are below 135/85 mm Hg, not 140/90 mm Hg. The use of ABPM defines white coat HTN rather than home BPs, and the specific range of day-night variability does not guide specific drug therapy. ^,

The correct answer is D

Comment: This patient has systolic HTN associated with hypokalemic metabolic alkalosis with normal renal function. Given the patient’s history and existing laboratory studies, the most likely diagnosis is either primary hyperaldosteronism or pseudo-hyperaldosteronism (Liddel syndrome). The most sensitive and specific test to rule out primary aldosteronism is a 24-hour urinary aldosterone level. Other tests, such as plasma renin or aldosterone, have many problems, and their value in this setting has not been validated.

The correct answer is E

Comment: This patient has severe hypertension. The clinical and laboratory findings suggest renal vascular hypertension. The best choice for a study would be a magnetic resonance angiography.

The correct answer is C

Comment: In this patient, low potassium is a clear contributor to persistent HTN. Potassium channels tend to close when hypokalemia is present, causing vasoconstriction that leads to a sustained elevation in BP. This patient needs potassium supplementation along with a potassium-sparing diuretic such as spironolactone.

The correct answer is C

Comment: It is clear from the physical examination that the patient has an abdominal aneurysm and renal insufficiency. Attempting to lower this patient’s pressure with vasodilators that will cause reflex tachycardia could result in further stress to the aortic wall and rupture the aneurysm, which is exactly what happened to this patient. The use of intravenous beta-blockers is ideal therapy in patients with a selective dopamine-1 receptor agonist to vasodilate without increasing heart rate.

The correct answer is B

Comment: Studies have shown that dialysis patients, like those non-dippers with normal renal function (i.e., those failing to decrease their normal SBP by at least 20 mm Hg), have a higher risk of CV events and death than do dippers.

The correct answers are A and D

Comment: In addition to losing weight and modifications in lifestyle, based on her cardiovascular risk factor profile, the elevated BP, the ideal therapy for her would be an ACEI with a diuretic.

The correct answer is D

Comment: Adducin 1 ( ADD1 ) is a protein coding gene. Diseases associated with ADD1 include HTN and essential and esophageal atresia. Among its related pathways are activation of cAMP-dependent protein kinase A (PKA) and unfolded protein response. Gene ontology annotations related to this gene include RNA binding and protein heterodimerization activity. An important paralog of this gene is ADD3.

In an analysis of almost 1000 patients, it was noted that carriers of the adducin variant had a lower risk for CV events or stroke when they received diuretic therapy compared with other antihypertensive drugs. It was also noted that those with the adducin variant had greater reductions in BP in response to a diuretic compared with other therapies. ^, None of the other genotypes listed has been associated with this type of relationship to BP response and outcomes with a particular class of agents.

The correct answer is E

Comment: Constellation of hypertension and hypokalemic metabolic alkalosis associated with decreased serum aldosterone and plasma renin activity, unresponsive to spironolactone, is strongly suggestive of Liddle syndrome.

An improvement in HTN and correction of hypokalemia and metabolic alkalosis is expected following amiloride administration (option E), ^, although genetic testing is the gold standard and can identify congenital defects.

The correct answer is C

Comment: Treatment of HTN in children with heart failure must be tailored, depending on the pathophysiology mechanism, status of systolic or diastolic function of the heart, severity of HTN, presence of end‐organ damage, and coexisting renal abnormalities.

Our patient presents with congestive heart failure associated with low cardiac output or reduced systolic ejection fraction. About half of the patients with CHF have systolic dysfunction and develop the classical symptoms of CHF, including edema. Systolic dysfunction is best treated with beta-blockers, ACEIs, ARB, and spironolactone plus a low-sodium diet (option C). A loop diuretic is recommended in the presence of edema.

For patients who have normal systolic fraction ejection with left ventricular hypertrophy or diastolic dysfunction, ACE or ARB and CCB tend to induce significantly more regression than beta-blockers.

The correct answer is D

Comment: The patient presented with polydipsia, polyuria, weight loss, and HTN. HTN was sufficiently severe in both cases to develop hypertensive cardiomyopathy and/or hypertensive retinopathy. Serum and urine laboratory tests revealed hyponatremia, hypokalemia with a high TTKG, hypochloremia, metabolic alkalosis, and proteinuria. Unilateral renal artery stenosis was found in imaging studies. Wilms tumor was the culprit of this case. This condition is known as hyponatremic-hypertensive syndrome.

Hyperactivation of the RAA axis is regarded to be the key pathophysiologic mechanism behind specific symptoms and electrolyte imbalances in hyponatremic-hypertensive syndrome. If unilateral RAS is severe enough to induce renal ischemia in the affected kidney, the ischemic kidney secretes a large amount of renin, which leads to increased levels of Ang II, a potent vasoconstrictor. Arterial pressure rises, and hyperfiltration in the contralateral kidney results in hyponatremia and volume depletion, known as pressure natriuresis. Increased aldosterone levels, another effect of Ang II, lead to hypokalemia. Both Ang II and volume depletion stimulate antidiuretic hormone secretion, which is responsible for thirst and polydipsia, further worsening hyponatremia. Proteinuria is a result of glomerular hyperfiltration and the proteinuric effect of Ang II.

The correct answer is D

Comment: In this patient with a parotid mass, headaches, and episodic hypertension, considerations include catecholamine-secreting tumors as well as a mass effect on the sympathetic ganglion or vascular supply resulting in compensatory hypertension to maintain cerebral perfusion. Plasma metanephrines were sent and a 24-hour urine collection for catecholamines was started. The results of her plasma and urinary metanephrines confirmed a catecholamine-secreting tumor. She underwent a subsequent positron emission tomography Ga68-DOTATE scan, which showed that her neck mass, along with multiple lesions in the chest and abdomen, were all somatostatin-receptor-rich, consistent with a metastatic catecholamine-secreting paraganglioma.

Pheochromocytomas and paragangliomas are rare tumors that are seen in approximately 2% of children who present with hypertension. A patient with a pheochromocytoma and paraganglioma typically presents with intermittent, recurrent symptoms of catecholamine excess, such as hypertension, headaches, or diaphoresis. Other, less specific symptoms include anxiety and panic attacks, as well as nausea, vomiting, and tremors. Although most patients will present with hypertension and headaches, up to 25% of cases will be entirely asymptomatic. ^,

Pheochromocytomas and paragangliomas can be diagnosed with blood tests and imaging. The most sensitive biochemical tests are plasma-free metanephrines and normetanephrine, the breakdown products of catecholamines, which have a sensitivity of up to 100% in children. Urinary metanephrines can be used in equivocal cases, with sensitivities that are similarly high in many studies. If biochemical testing shows elevated levels of catecholamines, contrast-enhanced CT of the abdomen, specifically protocolized to the adrenal gland, is a reasonable first imaging study. This can be followed by MRI, which is more sensitive for the detection of extraadrenal masses. If neither of these studies visualizes any masses despite biochemical evidence of disease, functional iodine-123 metaiodobenzylguanidine scintigraphy can be considered. Alternatively, positron emission tomography with fluorine-18-labeled dihydroxyphenylalanine may offer better sensitivity than metaiodobenzylguanidine because of better visualization of anatomy and less radiographic artifact and is preferred in patients with metastatic disease.

The correct answer is D

Comment: Hypokalemia is generally due to either urinary or gastrointestinal tract losses, a shift from the extracellular to intracellular fluid compartment, or in rare cases, decreased oral intake. In our patient, renal losses were thought to be most likely given the elevated urinary potassium concentration.

Metabolic alkalosis is often classified as chloride responsive (urine chloride <20 mEq/L) or chloride resistant (urine chloride >20 mEq/L). When urine chloride excretion is <20 mEq/L, the metabolic alkalosis is usually saline responsive. In metabolic alkalosis, urine chloride concentration may be a more accurate indicator of intravascular volume depletion than urine sodium concentration because bicarbonaturia in early stages of development of a chloride-depletion metabolic alkalosis results in sodium and potassium excretion in urine (as accompanying cations with bicarbonate). Thus, urine sodium and potassium concentrations may be elevated in the first 24 to 72 hours of volume depletion, then decline subsequently. Urine chloride concentration will remain low because of ongoing sodium and chloride reabsorption in the proximal tubule from activation of the RAA axis and other factors in response to volume depletion.

Our patient developed chloride-resistant metabolic alkalosis (urine chloride >20 mEq/L). Given the presence of hypertension along with urine potassium excretion >20 mEq/L and low levels of both serum renin and aldosterone, the differential diagnosis includes Liddle syndrome, syndrome of apparent mineralocorticoid excess, Cushing syndrome, congenital adrenal hyperplasia, and excessive licorice use.

Given the patient’s elevated morning cortisol level, markedly increased 24-hour urine cortisol excretion, and high serum corticotropin (ACTH) level, ACTH-dependent Cushing syndrome was diagnosed. ^,

ACTH-dependent Cushing syndrome could result from either an ACTH-secreting pituitary tumor or an ectopic ACTH-secreting tumor. Findings from MRI of the pituitary gland and CT of the chest were unremarkable. CT of the abdomen revealed peritoneal nodules consistent with his history of recurrent carcinoid tumor. Ectopic ACTH-dependent Cushing syndrome, most likely from the active carcinoid tumor, was diagnosed. There are few case reports that describe Cushing syndrome attributed to the presence of carcinoid tumor. ³ What are treatment options for this patient? Cortisol has the capacity to bind mineralocorticoid receptors in principal cells of the cortical collecting duct. Normally, this is limited by conversion of cortisol to cortisone, which is unable to bind to the mineralocorticoid receptor, by the enzyme 11 hydroxysteroid dehydrogenase type 2. Excess production of cortisol, as in our patient, saturates the enzyme, allowing cortisol to persist and activate mineralocorticoid receptors. This causes translocation of epithelial sodium channel proteins into the luminal membrane, increasing basolateral adenosine triphosphatase sodium/potassium pump activity and increasing renal outer medullary potassium channel activity, leading to sodium reabsorption and hypertension, hypokalemia, and metabolic alkalosis.

The correct answer is A

Comment: Based on clinical features and imaging findings, a diagnosis of renal lymphangiectasia was made. Needle aspiration of the perinephric fluid was performed, with laboratory analysis showing a predominance of lymphocytes. The differential diagnosis must include polycystic kidney disease as well as cystic renal tumors (especially multilocular cystic renal tumors). Polycystic kidney disease commonly has a familial history, with multiple cysts arising from the renal parenchyma and often within the liver. Most cystic kidney tumor lesions are solitary and arise from renal parenchyma with solid content in contrast CT. In uncertain cases, fine-needle biopsy is useful to establish the diagnosis.

Renal lymphangiectasia is a rare benign disorder of lymphatic malformation characterized by disruption of the perirenal lymphatic system. The renal capsule lymphatics and perinephric tissue empty into the renal sinus lymphatics, which drain into the para-aortic, paracaval, and interaortic nodes. The lymph then flows through the lumbar trunk and thoracic duct before emptying into the left brachiocephalic vein, superior vena cava, and right heart. Renal sinus drainage disturbances lead to an ectatic perirenal, peripelvic, and intrarenal lymphatic system, which explains the classic imaging findings. Clinically, renal lymphangiectasia can be detected incidentally by ultrasonography or CT in patients who undergo abdominal imaging procedures. The most common concerns are flank pain and abdominal distension, but hematuria, proteinuria, cyst hemorrhage, hypertension, fever, and, rarely, decreased kidney function can develop. On occasion, renal lymphangiectasia can present with infection and bleeding that result in acute pain. The clinical evolution and prognosis of renal lymphangiectasia are unclear. Owing to the rarity of the condition, no standard treatment is established. Asymptomatic and localized cases can be managed conservatively because the condition does not affect kidney function. If kidney function decreases or collections become symptomatic, percutaneous drainage can relieve compression. Recurrent collections may require marsupialization into the peritoneum. In severe uncontrollable cases, nephrectomy may be performed. Our patient’s perinephric collections were large and resulted in discomfort, so percutaneous drainage was performed to relieve compression and protect kidney function. After 1 month, drainage decreased to 5 mL per day and the tubes were removed. No fluid reaccumulation appeared during 6 months of follow-up.

The correct answer A

Comment: The most common causes of hypertension in young women are essential hypertension or hypertension as part of metabolic syndrome. Secondary causes include fibromuscular dysplasia, overproduction of aldosterone, and hormonal causes such as those related to oral contraceptive use or pregnancy-induced hypertension. In this age group, additional endocrine explanations for secondary hypertension include thyroid or parathyroid disorders and low vitamin D levels. A rare but important cause is coarctation of the aorta. Finally, exogenous factors such as licorice consumption, substantial alcohol intake, and use of nonsteroidal antiinflammatory drugs should be investigated and/or ruled out.

In the present case, the patient was pregnant, but hypertension in gestational week 7 should not be regarded as gestational hypertension or preeclampsia.

Renin is produced by juxtaglomerular cells in the kidney and plays a major role in BP regulation by inducing the RAA system. Hypertensive high renin states can be secondary or primary. Secondary causes of a high renin state include renovascular disease, most commonly fibromuscular dysplasia of the renal artery in young women. Additionally, hypertensive states per se are associated with a slight increase in renin levels, but this is much more pronounced in the malignant hypertensive condition. This might be explained by renovascular ischemia resulting from intimal hyperplasia. As for primary causes of hypertensive high renin states, renin-producing renal tumors can be seen with simultaneous high aldosterone levels. Duplex ultrasound examination of the kidneys and echocardiography were performed to exclude renal artery stenosis and coarctation of the aorta. Magnetic resonance tomography of the upper abdomen identified a mass in the caudal area of the left kidney. Plasma renin and aldosterone concentrations in the left renal vein were 1230 mIU/L and 3900 pmol/L, respectively. In a peripheral vein, values were 726 mIU/L and 1330 pmol/L, respectively.

This high secretion of renin from the left tumor-containing kidney supports the diagnosis of reninoma.

¹¹¹ In-octreotide scintigraphy was performed, showing high uptake of the radionuclide in the left renal mass. This uptake is due to the high expression of somatostatin receptor type 2 (SSTR2) by tumor cell. This was further supported by immunohistochemical analysis of the surgical specimen, which demonstrated strong membranous staining of tumor cells by a monoclonal anti-SSTR2 antibody. Most reninomas are benign, but metastatic cases have been reported. The patient underwent surgical resection of the tumor with normalization of BP (110/70 mm Hg without medication) and renin and aldosterone levels (18.0 mU/L and 232 pmol/L, respectively). Because the tumor was clearly visible on ¹¹¹ In-octreotide scintigraphy and expressed SSTR on immunohistochemical staining, a neuroendocrine phenotype for the tumor was identified. This suggests the opportunity to control hormone secretion and tumor cell proliferation in these tumors by long-acting somatostatin analogues or targeted radiotherapy in the case of unresectable masses. ^, The final diagnosis was hypertension from a juxtaglomerular cell tumor (reninoma) secreting large amounts of renin.