Indian Pediatrics Case Reports

CASE REPORT
Year
: 2022  |  Volume : 2  |  Issue : 1  |  Page : 40--43

Conn's syndrome: A rare cause of acute flaccid paralysis in an adolescent


Suchitra Sivadas1, Nisha Bhavani2, Praveena Bhaskaran1, Jayakumar Chandrasekhara Panicker1, Naveen Viswanath3,  
1 Department of Pediatrics, Amrita Institute of Medical Sciences, Kochi, Kerala, India
2 Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
3 Department of Pediatric Surgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India

Correspondence Address:
Dr. Suchitra Sivadas
Department of Pediatrics, Amrita Institute of Medical Sciences, Ponekkara, Kochi - 682 041, Kerala
India

Abstract

Background: Acute flaccid paralysis is a medical emergency. Hypokalemia secondary to an aldosterone-secreting adrenal adenoma or Conn's syndrome is a rare cause of hypokalemic paralysis. There are very few case reports from the pediatric population of the same. Clinical Description: We report the case of a 17-year-old girl, previously asymptomatic, who presented with sudden-onset, progressive weakness of all four limbs. There was no history of altered sensorium, cranial nerve involvement, or abdominal complaints. On examination, she was found to be hypertensive. Preliminary investigations revealed severe hypokalemia and metabolic alkalosis. There was no history suggestive of gastrointestinal potassium losses. Hence, a possibility of renal losses was considered and she was found to have kaliuresis. Management and Outcome: In view of hypokalemia, with hypertension with increased renal potassium loss, a possibility of hyperaldosteronism was considered. Plasma aldosterone concentration was elevated with levels of 20.3 ng/dl (normal <15 ng/dl). The direct renin concentration was <0.5 μIU/l (normal 5–14 μIU/l). This confirmed a diagnosis of primary hyperaldosteronism. Contrast-enhanced CT of the abdomen showed an adrenal adenoma. She electively underwent a laparoscopic adrenalectomy after her motor power improved with potassium replacement. Currently, she remains normotensive, asymptomatic, and off medications. Conclusion: The case highlights that Conn's syndrome though rare is an important cause that a high index of suspicion is necessary in young hypertensive patients to make an early diagnosis of this potentially treatable condition.



How to cite this article:
Sivadas S, Bhavani N, Bhaskaran P, Panicker JC, Viswanath N. Conn's syndrome: A rare cause of acute flaccid paralysis in an adolescent.Indian Pediatr Case Rep 2022;2:40-43


How to cite this URL:
Sivadas S, Bhavani N, Bhaskaran P, Panicker JC, Viswanath N. Conn's syndrome: A rare cause of acute flaccid paralysis in an adolescent. Indian Pediatr Case Rep [serial online] 2022 [cited 2022 Jul 2 ];2:40-43
Available from: http://www.ipcares.org/text.asp?2022/2/1/40/338481


Full Text

Periodic paralysis due to hypokalemia can be due to a primary genetic disorder resulting from autosomal dominant channelopathy.[1] This condition is characterized by transient attacks of severe flaccid paralysis of varying intensity and duration. However, hypotonia and paresis more commonly occurs due to severe hypokalemia, resulting from a variety of secondary etiologies. These include potassium wasting gastrointestinal disorders, licorice ingestion, barium poisoning, renal tubular acidosis (RTA), thyrotoxicosis, and primary hyperaldosteronism.[2] Conn's syndrome, another name for primary hyperaldosteronism, is characterized by adrenal overproduction and raised serum levels of aldosterone, which leads to arterial hypertension, hypokalemia,[3] and suppressed renin levels.[4] It is very infrequently reported: Kayal et al.[5] found only 1 patient (1.78%) of primary hyperaldosteronism in a study population of 56 adults with hypokalemic paralysis; and there are very few isolated case reports among children.

We report a teenager with primary hyperaldosteronism or Conn's syndrome who presented with hypokalemic paralysis, secondary to an aldosterone-secreting adrenal adenoma. The aim of presenting this case is because of the rarity of the condition in children, and also to highlight the systematic approach that was used to establish the diagnosis.

 Clinical Description



A 17-year-old, previously asymptomatic girl presented to our emergency department with complaints of intermittent fever of 5-day duration, multiple episodes of vomiting for 3 days, and weakness of both upper and lower limbs for 2 days leading to difficulty in walking and performing activities of daily living, independently. There was no history of jaundice, diarrhea, abdominal pain, or abdominal distention. She also had slurring of speech and inability to pass urine on the day of presentation. There was no history of loss of consciousness or seizures. There was no history of difficulty in swallowing or drooling, or any cranial nerve involvement. There was a significant history of easy fatiguability, and weight loss of 2 kg over the past 2 months, despite normal appetite. Her menstrual cycles were normal. There was no family history of similar illness, hypertension, stroke, or renal or adrenal disease. Her immunization had been given as per schedule.

On examination, she appeared drowsy with a Glasgow Coma Scale of 14/15 (E4, V5, and M5). She had bradycardia with a pulse rate of 56 beats/min, shallow respiration respiratory rate of 18 breaths/min, and hypertension with a blood pressure (BP) of 150/100 mm Hg (>95th centile). Her weight was 34 kg (>2 standard deviations [SD] below the median), height 142 cm (>2 SD below the median), suggesting stunting and wasting but corresponding to the acceptable range of mid-parental height centiles (141 ± 8 cm), and a BMI of 17 kg/m2 which was normal for her age and gender.

The patient exhibited signs of some dehydration. The general physical examination was unremarkable with normal spine and no evidence of cushingoid features, hyperpigmentation, edema, or virilization. Sexual maturity rating was Tanner stage IV. Throat examination was normal. The child was conscious with intact higher mental functions. There was no cranial nerve involvement. Fundus examination was normal, with no features of hypertensive retinopathy or papilledema. Severe neck muscle weakness and paresis of bilateral upper and lower limbs (grade 2/5 power in the proximal muscles and grade 3/5 in distal muscles) were present. There was generalized limb and truncal flaccidity with generalized hyporeflexia. Plantar reflexes were equivocal. The sensory system was normal. There were no signs of meningeal involvement or raised intracranial pressure. The abdomen was soft and nondistended. Bowel sounds were sluggish, and the bladder was well palpable. External genitalia were gender appropriate. Cardiovascular and respiratory examination was normal.

In view of the clinical phenotype of acute flaccid paralysis in the presence of vomiting and bradycardia, our first differential diagnoses was hypokalemic weakness (though there was no intestinal hypomotility). Other causes such as acute inflammatory demyelinating polyneuropathy and transverse myelitis were kept lower down. Rarer causes such as botulism and acute intermittent porphyria were not actively considered the other clinical features were not suggestive. The shallow as respiration, bradycardia, severe hypertension, and progressive quadriparesis warranted immediate admission in the pediatric intensive care unit.

Initial investigations confirmed our suspicions of severe hypokalemia (serum potassium 1.5 meq/L), but also identified hypernatremia (serum sodium 150 meq/L), hypophosphatemia (serum phosphorous 0.9 mg/dl), and normal serum calcium and magnesium levels. ECG showed bradycardia with PR prolongation, widened QRS complexes, and J waves. The arterial blood gas analysis showed uncompensated metabolic alkalosis; pH 7.56, pCO2 28.1 mmHg, and bicarbonate 30 mmol/L. Her liver, renal, and thyroid function tests were normal. An echocardiogram was normal.

 Management and Outcome



The child was commenced on intravenous fluids and noninvasive ventilation. Dehydration was corrected, intravenous potassium and phosphorous correction was done; hypertension was controlled with oral nifedipine. She was continued on oral potassium supplements along with oral nifedipine for hypertension. Symptomatic improvement became evident within 48–72 h with normalization of serum potassium, phosphate, and correction of metabolic alkalosis; the weakness and lethargy resolved dramatically.

The severe hypokalemia prompted us to take retrospective history to look for any known attributing cause. There was no history of preceding respiratory illness, polyuria, diarrhea, laxative or diuretic abuse, or intake of nephrotoxic medications. Since history, examination, and initial investigations ruled out the possibility of extrarenal losses, we decided to investigate for renal loss of potassium. Thus, urinary electrolyte estimation was planned. This revealed that her urine spot chloride and urine spot potassium were elevated (104 mmol and 40 mmol, respectively). The biochemical profile of hypokalemia with kaliuresis, metabolic alkalosis, and hypertension raised a strong suspicion of hyperaldosteronism. This warranted investigation to determine the levels of cortisol and renin–angiotensin–aldosterone axis to determine whether it was primary or secondary aldosteronism. Plasma aldosterone concentration (PAC) was elevated with levels of 20.3 ng/dl (normal <15 ng/dl). The direct renin concentration was <0.5 μIU/l (normal 5–14 μIU/l). Thus, the calculated aldosterone/direct renin ratio[6] was elevated at more than 40 (normal <2.4), suggestive of primary hyperaldosteronism. She was hence also started on spironolactone since it is a competitive antagonist of aldosterone and causes loss of sodium and fluid while retaining potassium. An ultrasound abdomen with Doppler was performed to look for an adrenal or extra-adrenal mass or renal artery stenosis that is known to cause secondary hyperaldosteronism and was found to be normal. An abdominal contrast-enhanced computerized tomography (CECT) revealed a normal left adrenal gland, but a hypodense nodule (26 mm × 15 mm in size) with an absolute washout of 65% in the right adrenal gland, suggestive of an adrenal adenoma [Figure 1]. A laparoscopic right adrenalectomy was performed. The histopathological findings were consistent with adrenocortical adenoma [Figure 2]. The postoperative period was uneventful. Three months later, on follow-up, she is asymptomatic, normotensive, normokalemic, and off all medications.{Figure 1}{Figure 2}

 Discussion



We shall be focusing on the step-wise approach to hypokalemic kaliuresis. The common causes of renal potassium losses include RTA, thiazide and loop diuretic use, Bartter and Gitelman syndromes, and mineralocorticoid excess state. In our case, the presence of metabolic alkalosis ruled out RTA. There was no history of any drug consumption, however, in view of the kaliuresis, it was important to see whether there were also accompanying chloride losses. The urinary chloride estimation detected high urinary chloride which ruled out loop or thiazide diuretic use (characterized by low urinary chloride levels). This narrowed down the differentials to Bartter and Gitelman syndromes or mineralocorticoid excess states (that include primary or secondary hyperaldosteronism, 11-beta and 17-alpha-hydroxylase deficiency, and Liddle's syndrome).[7] Both Bartter and Gitelman syndromes are characterized by normal BP, and hence they were excluded. In congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency, there is virilization, hypertension, and hypokalemia with normal aldosterone levels (as mineralocorticoids other than aldosterone are involved). This did not fit our patient's profile. Similarly, despite the presence of hypertension, 17-alpha-hydroxylase deficiency was excluded due to the absence of undervirilization. Liddle's syndrome, an autosomal dominant disorder due to mutations in the distal nephron sodium channel, is characterized by hyperaldosteronism, hypertension, hypokalemia, and alkalosis, but low serum aldosterone levels.[7]

The combination of hypertension, hypokalemia with kaliuresis, metabolic alkalosis, and high urinary chloride, in the presence of an elevated serum aldosterone-to-renin ratio clinched the diagnosis of hyperaldosteronism. Primary hyperaldosteronism is caused by adrenal adenoma, bilateral or unilateral adrenal hyperplasia, ectopic aldosterone-secreting tumors, and familial hyperaldosteronism. Renin producing tumors, renal artery stenosis, left heart failure, and cirrhosis cause secondary hyperaldosteronism due to excess renin production.[8] Both are differentiated by estimation of the renin–angiotensin–aldosterone axis. While elevated aldosterone levels are common to both, low renin with elevated aldosterone-to-renin ratio (as in this case) indicates primary hyperaldosteronism. The European society of Endocrinology recommends screening for primary aldosteronism in all subjects with the following conditions: 1) uncontrolled hypertension; 2) hypertension requiring 4 or more antihypertensives for control; 3) hypertension associated with hypokalemia; 4) hypertension and an incidental adrenal adenoma; 5) hypertension with a positive family history of early onset hypertension or young stroke or; 6) hypertension with a first degree relative with primary hyperaldosteronism.[6]

The morning angiotensin-to-renin ratio is recommended as the standard screening test; >20 suggestive of primary hyperaldosteronism. The next step is to see whether there is aldosterone suppression with any of the four following confirmatory tests: (1) oral sodium loading; (2) saline infusion; (3) fludrocortisone suppression; or (4) captopril challenge. Aldosterone suppression will be absent in PA. However, in the setting of spontaneous hypokalemia, plasma renin below detection levels, plus PAC >20 ng/dL (550 pmol/L), as seen in our patient, these confirmatory tests need not be done. Instead, one can proceed directly with adrenal imaging by CECT.[6]

Genetic testing is recommended for any of the four forms of familial hyperaldosteronism, when PA is identified in patients <20 years of age, there is a family history of PA or history of stroke in an individual <40 years of age.[9] In this case, it should have been done by virtue of the first indication, but we were unable to, because of financial constraints.

Surgery (preferably laparoscopic adrenalectomy) is the modality of choice in primary hyperaldosteronism due to unilateral disease. In contrast, medical management with mineralocorticoid receptor antagonists (spironolactone or eplerenone) is the first line of treatment in bilateral adrenal hyperplasia.[8] Thus, determining etiology is essential, as the management differs. Early diagnosis and treatment is vital, to manage the acute crisis, as well as to prevent the long-term deleterious effects of uncontrolled hypertension on multiple organ systems.

[INLINE:1]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Rajesh R, Bhagat T, Tek CY, et al. Hypokalemic periodic paraysis: A rare presenting manifestation of Conn's syndrome. J Endocrinol Metab 2015;5:196-8.
2Stedwell RE, Allen KM, Binder LS. Hypokalemic paralyses: A review of the etiologies, pathophysiology, presentation, and therapy. Am J Emerg Med 1992;10:143-8.
3Mulatero P, Monticone S, Bertello C, et al. Evaluation of primary aldosteronism. Curr Opin Endocrinol Diabetes Obes 2010;17:188-93.
4Onder A, Kendirci H, Bas V, et al. A pediatric Conn syndrome case. J Pediatr Endocrinol Metab 2012;25:203-6.
5Kayal AK, Goswami M, Das M, et al. Clinical and biochemical spectrum of hypokalemic paralysis in North: East India. Ann Indian Acad Neurol 2013;16:211-7.
6Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: Case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016;101:1889-916.
7Greenbaum Larry A. Potassium. In: Kleigman R, editor. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Elsevier, 2020. p. 2089-91.
8Cobb A, Aeddula NR. Primary hyperaldosteronism. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022. Available form: https://www.ncbi.nlm.nih.gov/books/NBK539779/. [Last updated on 2021 Jul 26].
9Pons Fernández N, Moreno F, Morata J, et al. Familial hyperaldosteronism type III a novel case and review of literature. Rev Endocr Metab Disord 2019;20:27-36.