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Recurrent hypokalemic paralysis
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Recurrent hypokalemic paralysis: An atypical presentation of hypothyroidism
Abstract
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INTRODUCTION
Hypokalemic periodic paralysis is the most common periodic paralysis, a rare channelopathy
manifested by episodic flaccid weakness secondary to abnormal sarcolemmal excitability.
Hypokalemic paralysis may be caused by a short-term shift of potassium into cells, seen in
hypokalemic periodic paralysis (caused by familial periodic paralysis or thyrotoxic periodic
paralysis), or a larger deficit of potassium as a result of severe renal or gastrointestinal potassium
loss.
Thyrotoxicosis is the most common cause of secondary hypokalemic periodic paralysis.
Recurrent hypokalemic paralysis is an extremely unusual presentation of hypothyroidism. To the
best of our knowledge, this is the fourth reported case of hypothyroidism associated with
recurrent hypokalemic paralysis.[13]
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CASE REPORT
A 30-year-old female presented with recurrent attacks of acute flaccid paralysis of all four limbs
since last 1 year. Each episode lasted for 2 to 5 days followed by spontaneous complete recovery
without potassium supplement in any form. Frequency of attack gradually increased up to three
episodes per month. It usually started with early morning weakness without any diurnal
variation. There was no history suggestive of altered sensorium, convulsion, visual, respiratory,
or bulbar weakness. She had no symptom suggestive of hypothyroidism.
The patient had quadriparesis with hypotonia, diminished deep tendon reflexes except delayed
relaxation of ankle jerks, flexor plantar response, and prominent neck muscle weakness. She had
normal higher mental function without any cranial nerve, sensory, or sphincter involvement. She
was thin built without pallor or edema. Her thyroid gland was not palpable. Other system
examination including chest and abdomen was within normal limit.
Laboratory investigations showed normal hemoglobin with high ESR, low potassium, and
normal sodium and serum creatine phosphokinase (CPK) level was very high (1067 mg/dl). Her
electromyography and nerve conduction study were normal. Thyroid function test revealed very
low level of thyroxine (both T3 and T4) with very high thyroid-stimulating hormone (TSH >
100). Serum anti-TPO antibody titer was also very high (386.4 IU/ml). Hypokalemia persisted
during attack ranging from 1.6 to 3.2 meq/L. Hypokalemic paralysis was diagnosed based on
clinical and biochemical parameters. No cause of secondary hypokalemia could be detected. Her
24-h urinary potassium excretion was 11.14 meq/L which was much below normal (normal
range 25-120 meq/L). Normal serum magnesium and urinary calcium excretion ruled out the
possibility of Gitelman's syndrome. Urine pH was within normal limit. The computed
tomography (CT) scan of the abdomen demonstrated normal adrenal gland. Her plasma rennin
activity (PRA) was measured normal (2.6 ng/ml/h).
During the acute period in hospital, the patient was treated with intravenous potassium (IV
potassium chloride, 40 meq/L of normal saline through peripheral vein at a rate of 20 meq/h) for
a week that lead to clinical recovery and also biochemical improvement to some extent. After
starting oral levothyroxine replacement, the patient continued with oral potassium replacement
(oral potassium chloride solution 40 meq twice daily) for another 2 weeks after which she could
be safely maintained with levothyroxine only. Hypokalemic state persisted up to 4 weeks of
levothyroxine replacement though the patient was clinically well. Subsequently, serum TSH
became normal with normal serum potassium level. With adequate control of hypothyroidism,
the patient did not have the need to take potassium supplement and no further attack of acute
flaccid weakness has been reported so far (for a period of 1 year during follow up).
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DISCUSSION
Periodic paralysis may be primary or secondary type. The paralytic attack can last from an hour
to several days and the weakness may be generalized or localized.[4] Disturbances of potassium
equilibrium can produce a wide range of disorders including myopathy, marked muscle wasting,
diminution of muscle tone, power, and reflexes.[5] The primary hypokalemic periodic paralysis
is autosomal dominant and is exacerbated by strenuous exercise, high carbohydrate diet, cold and
excitement, which was not found in this case.[4] In the primary type, episodes of weakness recur
frequently.
Many cases of secondary periodic hypokalemic paralysis have been reported in association with
gastroenteritis, diuretic abuse, renal tubular acidosis, Bartter syndrome, villous adenoma of
colon, and hyperthyroidism.[6] There was no history of diarrhea, vomiting, or diuretic abuse in
the present case. The absence of polyuria, polydipsia, nausea, vomiting, constipation,
hypochloremia, and hyponatremia ruled out Bartter syndrome. Normal serum magnesium and
urinary calcium excretion ruled out the possibility of Gitelman's syndrome. Similarly, none of
clinical features of renal tubular acidosis like polyuria, polydipsia, acidotic breathing, rickets,
and pathological fractures were present in this case.[7] Laboratory finding such as normal
urinary pH and lack of hyperchloremia during episode of paralysis also excluded the possibilities
of renal tubular acidosis. Characteristic features of hyperaldosteronism like hypertension and
polyuria were absent with normal adrenal gland in the CT scan of the abdomen.
The levels of thyroid hormones and TSH values in this patient indicate severe deficiency of
thyroxine. The presence of autoimmune thyroiditis is indicated by the high titer positivity of anti-
TPO antibodies in serum. The persistent hypokalemia during early periods of thyroxine
replacement can be due to the fact that thyroxine in pharmacological doses can cause increased
potassium excretion and water diuresis in patients with myxedema during initial part of therapy.
This may result in hypokalemia, especially in a patient with malnutrition and low stores of total
body potassium.
Hypokalemic periodic paralysis though common among Indian population varies greatly in
disease spectrum and magnitude in our country due to the heterogeneous pattern of etiology
behind it. Two case series that studied hypokalemic periodic paralysis in tertiary care centers of
India have observed that around 45% of all those patients had a secondary cause for their
condition and this secondary group had more severe hypokalemia that needed longer time to
recover.[8,9] Thyrotoxicosis, renal tubular acidosis, Gitelman's syndrome, and primary
hyperaldosteronism were among the prime conditions leading to hypokalemic periodic paralysis
but no case of hypothyroidism was found to be the etiology behind it.
The association of periodic hypokalemic paralysis with hypothyroidism has not been established
till now though probably only three similar cases have so far been reported stating the incidence
of recurrent hypokalemic paralysis in the presence of hypothyroidism in different clinical
scenarios.
Thyrotoxic Hypokalemic Periodic Paralysis Last updated Sunday, July 17th, 2011
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Clinical Synopsis
Thyrotoxic periodic paralysis (THKPP) is an uncommon disorder characterized by simultaneous
thyrotoxicosis, hypokalemia, and paralysis that occurs primarily in males of Asian descent,
including patients of Japanese, Chinese, Vietnamese, Korean and Filipino ancestry.
Kilpatrick et al. (1994) found six reports of thyrotoxic hypokalemic periodic paralysis in African-
Americans and described four additional cases, all in males. They concluded that the disorder
may be more frequent in blacks than previously suspected and should be considered when
patients present with unexplained hypokalemia, muscular weakness, and rhabdomyolysis.
Patients with THKPP in the United States reflect the ethnic makeup of the local population: the
predisposition of patients of Asian origin is very evident, but whites are more frequently affected
than most previous reports have recognized. Hispanics and American Indians also appear to be
at increased risk, and blacks have also been affected.
Except for the fact that hyperthyroidism is an absolute requirement for expression of the
disease, THKPP is identical to Hypokalemic periodic paralysis in its clinical presentation but
THKPP is rarely associated with a positive family history. Graves disease is the most common
cause of hyperthyroidism in affected patients, but any cause of thyrotoxicosis (including
administration of excessive amounts of exogenous thyroid hormone) can trigger attacks of
THKPP in susceptible subjects.
Clinical features of thyroid disease may be very subtle or virtually nonexistent; As a result,
thyroid function tests should be routinely monitored in patients with features of HypoKPP. The
thyrotoxicosis may be mild. Attacks can be precipitated by high carbohydrate intake, sleep
(onset of paralysis usually occurs during sleep), unusual exertion, infection, diarrhea, thyroid
hormone or alcohol abuse.
A number of researchers have reported that the serum insulin level is sharply elevated prior to
the attack of paralysis in THKPP. Increased sodium-potassium ATPase pump activity and
enhanced insulin response in patients with THKPP is postulated to contribute to the
hypokalemia. Spontaneous or induced attacks do not occur in persons whose hyperthyroidism
has been corrected.
Patients typically present with an acute episode of paralysis involving the muscles of the
extremities and limb girdles. The lower limbs are more frequently and severely involved than
the upper. Weakness may be asymmetrical. Proximal strength is more severely impaired than
distal strength.
A specific genetic basis is suggested by the fact that although occasional cases occur in
Caucasians the disorder is seen predominantly in Asians. It is primarily found in males,
although the occasional female patient presents. THKPP may be due to a genetic peculiarity of
muscle membranes. Multiple cases in families have been observed but the mode of inheritance
is not clear. (note: one genetic mutation has now been identified. This may not account for all
cases of THKPP, but it does strongly suggest a genetic cause for all cases.)
Genetics and Inheritance
Potassium Channel; In 2010, Ryan et al. identified mutations in KCNJ 18 (Kir 2.6);
Chromosome 17p11.2 as the cause of about 1/3 of cases of susceptibility to Thyrotoxic
HypoKPP. Specific mutations include: Arg399X, Gln407X, T354M; Lys366Arg; Arg205His;
I144fs (c.428 delC)
Laboratory Studies
In one study of 19 men with THKPP initial serum K levels upon admittance to hospital ranged
from 1.1 to 3.4 mmol/L (mean, 1.90.5 mmol/L). Serum Mg level was measured in 18 episodes
during paralysis and in 13 episodes after paralysis. During paralysis episodes, all patients had
low or low-normal Mg levels (0.60-0.80 mmol/L 1.5-1.9 mg/dL). Only two patients received
supplemental magnesium sulphate, but Mg levels increased by 0.1 mmol/L or more (0.24
mg/dL) in all patients who had it checked. Serum creatine phosphokinase levels were obtained
in 18 episodes during paralysis. Twelve patients had elevated creatine phosphokinase values, 5
of which were of 1000 U/L or more. Serum alkaline phosphatase levels were mildly elevated in
12 of 16 patients, ranging from 118 to 268 U/L (normal, 39-117 U/L).
Thyroid Studies
Elevated total thyroxine, triiodothyronine resin uptake, and total triiodothyronine levels.
Radioiodine scan for Graves disease and adenomas
Cardiac Signs
Consistent with Hypokalemia or Thyrotoxicosis; During paralysis, sinus tachycardia, diffuse ST-
T changes, flattening of T waves, prolonged QT intervals, and U waves. Sinus arrest and second-
degree atrioventricular block also have been described in patients with THKPP, ventricular
fibrillation and ventricular tachycardia.
Treatment
The mainstay of emergency treatment has always been potassium replacement, however not all
patients respond to potassium alone and recent evidence suggests that combining potassium
and propranolol is a more effective therapy. It has been recommended that 27 mEq of KCl be
given every 2 hours orally for 6 hours and then every 4 hours with careful monitoring. Because
THKPP patients may develop rebound hyperkalemia, (Manoukian et al 1999) recommends that
K+ replacement therapy should be cautious and should not exceed 90 mEq of KCl per 24 hours
unless there is a reason for K+ loss, such as diarrhea, vomiting or diuretic use.
In the Manoukian study (19 patients) all patients remained attack free as long as they took
methimazole and propranolol hydrochloride or after radioiodine 131 treatment. Eighteen
patients were eventually treated with radioiodine 131 therapy. None of the patients had paralytic
episodes after a euthyroid state was achieved. Nonselective beta-blockers such as propranolol
may be useful to prevent attacks of paralysis once patients begin taking antithyroid medications
but are not yet euthyroid. For information on management of the Hypokalemic aspect of THKPP
see Hypokalemic Periodic Paralysis. http://hkpp.org/physicians/thyrotoxic
Thyrotoxic Hypokalemic Periodic Paralysis FAQ Last updated Saturday, June 25th, 2011
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What is Thyrotoxic Hypokalemic Periodic Paralysis?
Thyrotoxic Hyperkalemic Periodic Paralysis (TPP) is an uncommon disorder with three
characteristics which occur at the same time:
1. too much thyroid hormone
2. low levels of potassium in the blood (hypokalemia)
3. muscle weakness or paralysis
TPP occurs most often in males of Asian descent, including Japanese, Chinese, Vietnamese,
Korean and Filipinos. It also occurs more frequently in those of Native American and Latin
American descent, but only occasionally in those of European descent.
The thyroid gland is part of the endocrine system. It is located in the neck and produces several
hormones that help control growth, digestion, and metabolism. A complex set of mechanisms
control the rate of thyroid gland activity. Too much thyroid hormone (called Hyperthyroidism or
thyrotoxicosis) is due to an overactive thyroid gland. Hyperthyroidism is not a specific disease,
but a symptom of an underlying condition or disease. The causes of hyperthyroidism include
Graves' disease; tumors of the thyroid or other endocrine glands; inflammation or infection of
the thyroid; taking too much thyroid hormone; and taking too much iodine. Graves' disease
accounts for 85% of all cases of hyperthyroidism.
What tests are used to diagnose TPP?
The doctor will do blood tests to check the levels of various thyroid hormones including; TSH
levels, T3, T3 resin uptake and T4. During an attack of weakness the doctor will do a blood test
to check the level of potassium. In TPP, the level of potassium is low during attacks but normal
between attacks.
No one in my family has this disease. How did I get it?
It's been clear for many years that most types of periodic paralysis are inherited, but until
recently the relationship between inheritance and TPP was unclear. It seemed obvious that there
was some genetic factor at work, or TPP wouldn't occur more often in men of Asian ancestry, but
no genetic mutation could be identified. In 2010 a team of researchers discovered a group of
mutations which increase a persons chance of developing TPP. While this does not explain all
cases this is a real breakthrough and helps to establish a genetic basis for the disorder. But even
when a TPP mutation is inherited a person will not develop symptoms unless their thyroid
becomes overactive. This means generations might pass in a family between two affected
individuals.
What triggers attacks of TPP?
The same factors which trigger attacks of Hypokalemic Periodic Paralysis will trigger attacks of
TPP. Meals high in starchy and sweet foods may trigger an attack. Taking thyroid hormones may
trigger an attack. Sleep or resting after exercise may trigger an attack. For a more complete
discussion on triggers see the section on Hypokalemic Periodic Paralysis.
How do I avoid having attacks?
Your physician will treat the underlying thyroid disorder, which will eventually cure your TPP.
In the meantime you should determine what triggers your attacks and avoid those triggers.
Medication is usually necessary until the thyroid problem is brought under control.
What medications are prescribed for TPP?
Beta-blockers like propranolol are used to treat TPP, along with a potassium supplement. But
the overactive thyroid must be treated. Once the underlying thyroid problem is corrected with
medication, radiation or surgery the symptoms of TPP usually disappear.
Low Potassium & Thyroid Relationship
Thyroid hormones help regulate physical development, facilitate energy conversion in cells and affect the
way your organs function. Your body uses potassium to facilitate the proper function of nerve and muscle
cells. Low potassium is associated with high levels of thyroid hormones. Treating low potassium caused
by excess thyroid hormones involves lowering thyroid hormone level.
Hypokalemia Hypokalemia is defined as low levels of potassium in your blood. Normal blood potassium levels should be between
3.6 mEq/L and 4.8 mEq/L, MayoClinic.com says. Hypokalemia means your blood potassium levels have dropped to
less than 2.5 mEq/L. This causes symptoms such as weakness, fatigue, muscle cramps and arrhythmia to occur.
Hypokalemia is fatal if left untreated.
Potassium and Thyroid Gland Thyrotoxic periodic paralysis is a condition that induces moments of muscle weakness and paralysis in people with
elevated levels of thyroid hormones. This form of hyperthyroidism causes your potassium levels to drop. Muscle
weakness or paralysis caused by low potassium commonly occurs in the shoulders and hips and typically lasts
between three hours and a whole day. Hyperthyroidism also causes nervousness, irritability, increased perspiration
and insomnia, KidsHealth notes. Diagnosing potassium and thyroid problems involves testing the blood to
determine blood potassium and thyroid levels. Treating hyperthyroidism sometimes requires surgical intervention to
remove most of the thyroid gland. Thyroid replacement hormones are usually given after surgery to prevent thyroid
hormones from dropping below
Treating Low Potassium and Possible Complications Treating low potassium involves the use of potassium supplements. Eating foods that have potassium
helps prevent hypokalemia. Foods like bananas, bran, kiwi, peaches and tomatoes contain potassium. If
your potassium levels remain low for a prolonged period, complications such as kidney damage are likely
to occur. Consult a doctor before taking potassium supplements in order to determine your treatment
options.
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