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|LETTERS TO EDITOR
|Year : 2019 | Volume
| Issue : 4 | Page : 1117-1119
A Case Report of Recurrent Hypokalemic Paralysis—missing the “Period”
Siddhesh Rajadhyax1, Bhumir Chauhan1, Vikram Huded1, Siddaramappa J Patil2, Anuradha Kannan3, Venkatraman Bhat4, Subramanian Kannan5
1 Department of Neurosciences, Narayana Health City, Bengaluru, Karnataka, India
2 Department of Medical Genetics, Narayana Health City, Bengaluru, Karnataka, India
3 Department of Reproductive Medicine, Narayana Health City, Bengaluru, Karnataka, India
4 Department of Radiology, Narayana Health City, Bengaluru, Karnataka, India
5 Department of Endocrinology, Diabetology and Bariatric Medicine, Narayana Health City, Bengaluru, Karnataka, India
|Date of Web Publication||10-Sep-2019|
Dr. Subramanian Kannan
258/A, Bommasandra Industrial Area, Hosur Road, Bengaluru - 560 099, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Rajadhyax S, Chauhan B, Huded V, Patil SJ, Kannan A, Bhat V, Kannan S. A Case Report of Recurrent Hypokalemic Paralysis—missing the “Period”. Neurol India 2019;67:1117-9
|How to cite this URL:|
Rajadhyax S, Chauhan B, Huded V, Patil SJ, Kannan A, Bhat V, Kannan S. A Case Report of Recurrent Hypokalemic Paralysis—missing the “Period”. Neurol India [serial online] 2019 [cited 2020 May 30];67:1117-9. Available from: http://www.neurologyindia.com/text.asp?2019/67/4/1117/266245
Periodic paralysis (PP) is a rare neuromuscular disorder, related to a defect in muscle ion channels, characterized by episodes of painless muscle weakness, which may be precipitated by heavy exercise, fasting, or high-carbohydrate meals. PP is classified as hypokalemic or hyperkalemic depending on the serum potassium levels. Most cases of periodic paralysis are hereditary, usually with an autosomal dominant inheritance pattern, whereas acquired cases of hypokalemic PP have been described in association with hyperthyroidism. During the evaluation of hypokalemic PP, in addition to excluding thyrotoxicosis and Andersen syndrome, one should be careful to exclude the secondary causes of hypokalemia related to renal, gastrointestinal, or adrenal causes. One of the rare variants of congenital adrenal hyperplasia namely 17-alpha hydroxylase deficiency (17OHD) can present in young adults in the peripubertal time with severe hypokalemia. The presence of hypertension, poorly developed secondary sexual characteristics, often suggests the diagnosis. We present a case of 17 OHD to highlight the importance of proper clinical evaluation of cases of hypokalemic PP. We also report, for the first time in Indian literature, a novel homozygous intron mutation on chromosome 10 of CYP17A1 gene in our patient with 17OHD.
A 21-year-old female was admitted at our center with 2 days duration of symmetrical flaccid quadriparesis without cranial or respiratory muscle involvement. There was no preceding history of fever, exertion, or high-carbohydrate meal. She had a similar episode 8 months earlier when she was told to have low potassium, and her symptoms recovered in 48 hours with potassium supplementation. She is the eldest of 3 siblings, born to second-degree consanguineous parentage. She is the tallest member in the family and had not yet attained menarche. Family history was negative for similar symptoms in parents or siblings. On general examination, she had a lean body habitus with eunanchoidal proportions (BMI: 15 kg/m 2; height: 154 cm; arm span: 165 cm; upper segment: lower segment ratio: 0.8). Pulse rate was 110 bpm and blood pressure was 150/90 mmHg. There was increased pigmentation, particularly on her skin creases in the palms and buccal mucosa. She had lack of development of secondary sexual characters (Sexual maturity rating: Breast Tanner 2, Axillary and Pubic hair Tanner 1). Her neurological examination revealed symmetrical flaccid quadriparesis with mild axial weakness, intact deep tendon reflexes, and normal cranial nerve examination. She did not have any muscle tenderness or grip/percussion myotonia.
Initial laboratory evaluation revealed severe hypokalemia (1.6 mmol/L) along with metabolic alkalosis (pH 7.49 with bicarbonate of 30 mmol/L) with inappropriate kaliuresis (Urine potassium: 25 mmol/L). Her glucose levels were normal and thyroid functions indicated subclinical hypothyroidism [Table 1]. Her potassium was aggressively corrected with intravenous potassium and her weakness partially improved. Given the combination of hypertension and hypokalemia, serum cortisol, plasma levels of aldosterone, and renin activity were performed. Serum cortisol was undetectable (<1 mcg/dl), plasma renin activity (0.03 ng/ml/h) was suppressed and aldosterone levels were not elevated (11.4 ng/dl). In view of the primary amenorrhea and poorly developed secondary sexual characters, gonadotropins were tested, which indicated primary ovarian failure (Follicle stimulating hormone: 61 mIU/L and luteinizing hormone: 35 mIU/L). Abdominal ultrasound indicated bilateral cystic ovaries and uterus could not be clearly visualized. Karyotyping was 46XX. A combination of adrenal insufficiency along with hypertension, hypokalemia, and primary ovarian failure indicated the possibility of congenital adrenal hyperplasia (CAH) with 17-alpha hydroxylase deficiency (17α-OHD). Magnetic resonance imaging revealed a hyperplastic left adrenal gland and an atrophic uterus with cystic ovaries [Figure 1]. On targeted sequencing of the CYP17A1 gene, a homozygous 3' splice mutation in intron 4 of the CYP17A1 gene (chr10:104592966; C>T) which affects the invariant CT acceptor splice site of intron 4 [c.754-1G>A (ENST00000369887)] was detected.
|Figure 1: Magnetic resonance imaging scan of the abdomen and pelvis showing cystic ovaries (thick arrows), hypoplastic uterus (open arrow head), and hyperplastic left adrenal gland (thin arrow)|
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She was started on dexamethasone 0.125 mg at bedtime. In about 1 week, she was weaned off all potassium supplements and her blood pressure and bicarbonate levels were normal. On follow-up after 6 months, she was normokalemic and normotensive on oral hydrocortisone at 15 mg/day and on conjugated equine estrogen and progesterone. Molecular tests for the parents has not been performed at the time of submission of this report.
The cytochrome P450c17 enzyme (CYP17A1) catalyzes both the 17-hydroxylase reaction, which forms 17-hydroxysteroids, and the 17,20-lyase reaction, which cleaves 21-carbon 17-hydroxysteroids to 19-carbon 17-keto androgen precursors. CYP17A1 metabolizes pregnenolone, progesterone, and their 17-hydroxy derivatives early in the steroidogenic cascades [Figure 2]. Most defects in CYP17A1 impair both enzymatic activities and cause combined 17-hydroxylase/17,20-lyase deficiency (17OHD), which can be complete or partial. Consequently, 17OHD eliminates the synthesis of most steroids and limits steroidogenesis to progesterone, 11-deoxycoricosterone (DOC), corticosterone, and 18-oxygenated derivatives. DOC binds with high affinity to the mineralocorticoid receptor and is not a substrate for 11-beta hydroxysteroid dehydrogenase type 2. DOC excess causes volume expansion, hypertension, and kaluresis despite suppressed renin and aldosterone production. CYP17A1 is expressed both in the human adrenal and gonads, and thus, these deficiencies are forms of CAH that impair both adrenal and gonadal function. The hallmarks of 17OHD, first described in 1966, include hypertension and hypokalemia due to the accumulation of cortisol precursors with mineralocorticoid activity upstream of the block, along with sexual infantilism due to inability to synthesize androgens and estrogens. Unlike most other forms of CAH, mineralocorticoid excess and high corticosterone production mitigate the clinical consequences of cortisol deficiency, and symptomatic adrenal insufficiency is rare., The classic presentation of severe 17OHD in phenotypic females (who can have 46, XX or 46, XY karyotypes) includes hypertension, primary amenorrhea, absence of secondary sexual characteristics, and minimal body hair. Genotypic females have a small uterus and ovaries that may enlarge and become polycystic in adolescence because of high gonadotropins and progesterone. Mild enlargement of breast tissue even in the setting of severe hypogonadism may be seen. The diagnosis of 17OHD is established by demonstrating elevated DOC and corticosterone along with low cortisol (<5 mcg/dL), androgens, and estrogens. Progesterone is also elevated, whereas aldosterone and renin are suppressed. Gonadotropins and adrenocorticotropic hormone (ACTH) are elevated even in children. It should be noted that the presence of high amounts of precursor molecules can interfere with assays of estradiol and aldosterone, and one needs tandem mass spectrometry for accurate estimation of these levels.
|Figure 2: Pathogenesis in 17 alpha-hydroxylase deficiency (17OHD). The blockage at the 17α-OH impairs cortisol and sex steroid synthesis. The low cortisol increases adrenocorticotropic hormone production. Accumulated deoxycorticosterone and corticosterone cause plasma volume expansion, hypertension and hypokalemia, which suppress renin and aldosterone|
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The goals of treatment in classic 17OHD are to mitigate the effects of mineralocorticoid excess, prevent glucocorticoid deficiency, and restore desired secondary sexual characteristics with attendant benefits such as improved bone mineral density. While glucocorticoid administration, to suppress ACTH and stop the accumulation of mineralocorticoids, the effects of axis suppression and the consequences of glucocorticoid excess are unnecessary. Therefore, glucocorticoid therapy should be minimized and remain in physiological replacement doses. Medications are titrated based on monitoring blood pressure and electrolytes. Estrogen and progesterone replacement is started at the time of expected puberty.
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.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]