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Year : 2021  |  Volume : 1  |  Issue : 1  |  Page : 70-72

The case of the paradoxical elixir

Department of Pediatrics, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India

Date of Submission04-Oct-2020
Date of Decision16-Oct-2020
Date of Acceptance27-Oct-2020
Date of Web Publication27-Feb-2021

Correspondence Address:
Dr. Girish Chandra Bhatt
Room No 1023, 1st Floor Academic Block, All India Institute of Medical Sciences, Saket Nagar, Bhopal - 462 020, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_19_21

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How to cite this article:
Shinde M, Bhatt GC, Dhingra B, Malik S. The case of the paradoxical elixir. Indian Pediatr Case Rep 2021;1:70-2

How to cite this URL:
Shinde M, Bhatt GC, Dhingra B, Malik S. The case of the paradoxical elixir. Indian Pediatr Case Rep [serial online] 2021 [cited 2021 Nov 29];1:70-2. Available from: http://www.ipcares.org/text.asp?2021/1/1/70/310217

  Recreation of the Scene of the Crime… Top

An 11-year-old boy presented to the hospital emergency with acute onset, recurrent episodes of nonbilious, nonprojectile vomiting. This was associated with a severe, throbbing headache localized to the back of his head. The mother gave a history that the child had been diagnosed with hypertension (HT) 3 months earlier and was on multiple hypertensives. Even though drug compliance was good, his high blood pressure (BP) was poorly controlled.

Dr Watson: Could this be a hypertensive emergency? Find out how and when it started.

The boy had been admitted 3 months earlier with persistent headache, vomiting, and seizures. He had been managed in the emergency with antihypertensives and antiepileptics. He was currently on a beta blocker (metoprolol), a calcium channel blocker (nifedipine), a diuretic (aldactone), and a central alpha agonist (clonidine).

Dr Watson: Does he have any history suggestive of end-organ damage or family history of HT?

There was no history of confusion, lethargy, altered sensorium, breathing difficulties, chest pain, palpitations, disturbances in vision, early morning peri-orbital puffiness, or decreased frequency or amount of urination. The mother had HT that had been detected when she was 20 years old.

Dr Watson: Let me assess Airway (A), Breathing (B), Circulation (C), Disability (D), and BP.

A, B, C, and D are normal. All pulses are well palpable. The BP is 160/100 mm Hg (right upper limb), 162/104 mm Hg (left upper limb), 174/124 mm Hg (right lower limb), and 168/118 mm Hg (left lower limb).

Dr Watson: Hmm, Headache, vomiting with age and sex stratified systolic and diastolic BP >95th +12 centile confirms HT emergency. I've ruled out coarctation of aorta. After starting the hospital protocol for a hypertensive emergency, I will need to do a focused evaluation to look for end-organ damage and probable cause.

There is no history of intake of any other medication, recreational drug abuse or allergies (drugs causing HT), fever with dysuria (urinary tract infection), no preceding skin lesions or sore throat (poststreptococcal glomerulonephritis), and no tachycardia. Flushing, excessive sweating (phaeochromocytoma); normal thyroid with the absence of excessive weight loss, heat intolerance or anxiety (hyperthyroidism); normal sensorium, absence of Cushing's triad, and papilledema (increased intracranial tension); focal neurological deficits (intracranial space-occupying lesion); no pedal edema and normal cardiovascular and respiratory systems (heart failure); no periorbital edema, abdominal bruit (renovascular disease); no abdominal mass (Wilm's tumor, neuroblastoma, and renal anomalies); normal looking genitalia (congenital adrenal hyperplasia); there was no history of umbilical catheterization after birth. The child's body mass index is 15.2 kg/m2.

Dr Watson: Given that the clinical phenotype is childhood onset sustained HT with hypertensive emergency, which common differentials need to be excluded first?

Glomerulonephritis, renovascular causes, and endocrinal causes, since they are common in this age group.

Dr. Watson: Let me plan preliminary investigations rationally, so that I can narrow down my differentials.

Since HT encephalopathy is a diagnosis of exclusion, magnetic resonance imaging of the brain was done which revealed posterior reversible encephalopathy syndrome. The kidney function test and urine analysis were normal; creatinine 1.11 mg/dl, urea 26.6 mg/dl, no proteinuria or hematuria. The serum electrolytes were as follows: Na + 136 mmol/l, K + 3.11 mmol/l, Cl - 103 mmol/l, Ca2 + 9.02 mg/dl, and PO43 - 3.76 mg/dl. Arterial blood gas analysis revealed metabolic alkalosis (pH-7.49, Bicarb-31 mmol/L, and pCo2-42 mmHg). Abdominal ultrasonogram and renal Doppler were normal.

Dr. Watson: Hmm. I think I will defer the thyroid function test. Childhood onset of HT with metabolic alkalosis and hypokalaemia warrants a different investigative approach. Could be due to chronic diuretic use? But the pattern is also suggestive of monogenic causes of HT. What are the points in favor of this?

Childhood onset of HT is present in both the index case, while onset in young adulthood is noted in the mother. The patient's renovascular status is normal. His HT has not responded to multiple drugs, despite good drug compliance, in the past. Even now, his response to the emergency management of HT is not as well controlled as I would have expected.

Dr. Watson: Let me check the algorithm [Figure 1]. Yes, I think getting renin and aldosterone levels are worth consideration.
Figure 1: Approach to low renin hypertension

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Renin levels are low (0.95 ng/dl/h [normal 7–30 ng/dl/h]) and aldosterone levels are high (24.7 ng/dL [normal 3–16 ng/dL]). The aldosterone/renin ratio is 26 (normal <20).

Dr Watson: Hmm. So that means it may be Familial hyperaldosteronism (FHA)-I or FHA II (FHA-II). Let me review the pertinent history and examination in both, and see what applies to my patient.

Dr Watson diligently reviews the clinical features of both and also decides to review the clinical knowledge of other subtypes of monogenic HT with metabolic alkalosis while he is at it [Table 1].
Table 1: Differentiating features of subtypes of monogenic causes of hypertension Figure 1

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Dr. Watson: Now as per protocol, let me get a baseline cortisol level followed by a High Dose Dexamethasone Suppression Test (DST).

The baseline early morning serum cortisol level was 11.6 ug/dL (normal 10–20 ug/dL). Oral dexamethasone (8 mg) was administered at 11 p.m. The aldosterone and cortisol levels sampled at 8 a.m. the next morning were found to be decreased; 5.2 ng/dL and 0.68 ug/dL, respectively. Subsequently, during the course of the day, a few BP recordings with lower values are observed. The diagnosis of FHA I is clinched and the boy is started on oral prednisolone (1 mg/kg/day). The BP normalizes further is maintained between the 50th and 90th centile for age and gender.

Dr. Watson: Is there anything else that I need to do further?

Yes, specific genetic testing. Dr Watson decides to wait for the report of child before recommending parental screening and telling them that he will need to be monitored for cerebrovascular accidents throughout life.

Dr Watson: I must add the follow up details to my diary. The BP monitoring over the last month remains fine. The boy's headache has abated. I have advised them to monitor BP regularly. Once I get the results of the genetic test, I will proceed further. This case was a paradox, because his HT responded to steroids. If Holmes was here, I would have been the one saying “Elementary my dear Sherlock!”

  Discussion Top

Monogenic or Mendelian forms of HT refer to dysregulation of BP resulting from single genetic mutations that cause either gain or loss of function within the mineralocorticoid, glucocorticoid, or sympathetic pathways.[1] FHA I, also known as Glucocorticoid remedial hyperaldosteronism (GRA) is a rare form of monogenic HT with an autosomal dominant inheritance.[2] The CYP11B1 and CYP11B2 genes lie adjacent to each other on chromosome 8q24.3. Unequal crossover between these genes results in the formation of a chimeric variant. The adrenocorticotropic hormone (ACTH) responsive 5'promoter region of CYP11B1 (11 beta hydroxylase gene) fuses with the coding sequence of CYP11B2 (aldosterone synthase gene).[3] Normally, aldosterone is secreted by the zona glomerulosa of the adrenal gland under the regulation of the renin-angiotensin system. However, the chimeric gene results in aldosterone being ectopically secreted from the adrenal zona fasciculata and under ACTH regulation. This hyperaldosteronism causes retention of water and salt by the distal tubules leading to the key clinical features of HT and hypokalemia in the setting of suppressed renin levels.[1],[4],[5]

A high index of suspicion of monogenic HT should be kept in pediatric or young adult onset HT (once common causes of childhood and adolescence are ruled out), since the modality of management is quite different and chronic sequelae of HT can be prevented by regular follow-up. The diagnosis of GRA is supported by the DST. Most patients show a significant improvement in BP following DST. Confirmation is by genetic testing for the chimeric gene. Treatment is by the administration of the smallest effective dose of short-acting agents like prednisone or hydrocortisone at night to suppress the early morning ACTH peak.[4] The target BP should be guided by age-specific percentiles.[4] Spironolactone and Triamterene are alternative options for treatment.[4],[5] These patients also suffer from a high incidence of intracerebral hemorrhage (11%–18%) with a high associated mortality rate (61%) at an early age (31.7 ± 11.3 years). The high risk of cerebrovascular accidents warrant screening of affected individuals every 5 years after puberty.[1]

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Conflicts of interest

There are no conflicts of interest.

  References Top

Raina R, Krishnappa V, Das A, et al. Overview of monogenic or mendelian forms of hypertension. Front Pediatr 2019;7:263.  Back to cited text no. 1
Rich GM, Ulick S, Cook S, et al. Glucocorticoid-remediable aldosteronism in a large kindred: Clinical spectrum and diagnosis using a characteristic biochemical phenotype. Ann Intern Med 1992;116:813-20.  Back to cited text no. 2
Vehaskari VM. Heritable forms of hypertension. Pediatr Nephrol 2009;24:1929-37.  Back to cited text no. 3
Halperin F, Dluhy RG. Glucocorticoid-remediable aldosteronism. Endocrinol Metab Clin North Am 2011;40:333-41, viii.  Back to cited text no. 4
McMahon GT, Dluhy RG. Glucocorticoid-remediable aldosteronism. Cardiol Rev 2004;12:44-8.  Back to cited text no. 5


  [Figure 1]

  [Table 1]


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