Electrolyte imbalance always poses challenging situations to the attending intensivists, particularly if it is associated with endocrinopathies and other comorbidities. One such rare clinical scenario is hypokalemic periodic paralysis (HPP) due to hyperthyroidism. The epidemiology of such a condition is slightly higher among males of Asian origin as compared to its universal occurrence. The diagnostic challenges in this clinical situation can lead to higher morbidity if timeliness is compromised from the presentation to active management. Moreover, atypical presentation of this pathologic condition further compounds the problem if it is associated with overt hyperthyroidism. Here, we report a unique case that presented to the emergency medicine department of our institute with weakness of all the four limbs and in which we faced all the diagnostic and management challenges as the clinical condition of hypokalemia was somehow dominated by overt hyperthyroidism.
Keywords: Comorbidities, endocrinopathies, hyperthyroidism, hypokalemic, periodic paralysis
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Garg R, Bajwa SJ, Aseri R, Kajal KS. Clinical and diagnostic challenges in a rare case of motor weakness with endocrinopathy: A case report. Ann Trop Med Public Health 2016;9:67-9
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Garg R, Bajwa SJ, Aseri R, Kajal KS. Clinical and diagnostic challenges in a rare case of motor weakness with endocrinopathy: A case report. Ann Trop Med Public Health [serial online] 2016 [cited 2020 Aug 8];9:67-9. Available from: https://www.atmph.org/text.asp?2016/9/1/67/168699
Endocrinopathies always pose unique challenges to the attending intensivist, particularly if associated comorbidities are also present.  The symptoms of hyperthyroidism can be atypical on presentation if the disease pathology is mild. In such circumstances, it is usually dominated by other comorbidities. Electrolyte disturbances such as hypokalemia can complicate the clinical picture further as these pathologic combinations are very rare in clinical practice. Such situations always pose diagnostic and therapeutic dilemmas to the attending intensivist. We are reporting a rare case of hyperthyroidism presenting as hypokalemic periodic paralysis (HPP), which is an uncommon presentation and difficult to diagnose immediately in any clinical setup.
In the emergency medicine department of our institute, a 38-year-old male reported with chief complaints of repeated attacks of weakness in all four limbs since the past 2 years. Such sudden attacks usually caused weakness to such an extent in all the four limbs that the patient was unable to stand or ambulate. Moreover, the unique feature of such a clinical situation was that it occurred during midnight, particularly if the patient had done some strenuous work through the day. The current management of this clinical condition was carried out by a local practitioner who treated the acute attacks with supplementation of intravenous (IV) fluids that usually provided relief in a very short span of time. The patient was thoroughly examined from all aspects and the only positive finding included active tremors in the fingers of his hand. Even the central nervous system examination did not reveal any abnormality. To accurately diagnose the clinical condition, even the biochemical profile did not help much as all the routine tests were normal including random blood sugar (RBS) 108 mg%, normal serum uric acid 5.2 mg%, serum calcium 5.2 mg%, and normal serum sodium and phosphorus. The only remarkable and eventful finding was that of hypokalemia (2.2 meq/L). Special tests such as that of thyroid function revealed the following values: Total triiodothyronine (T 3 ) 449 ng/dL, total thyroxine (T 4 ) >30.0 μg/dL, and thyroid-stimulating hormone (TSH) <0.01 μIU/mL. The electromyogram and nerve-muscle structure and function analysis also did not reveal any abnormality. Going by the investigation profile, treatment with antithyroid drugs was initiated.
Presentation of HPP in a case of hyperthyroidism is very unusual in clinical sciences. The coexistence of HPP with hyperthyroidism has been described earlier also by Jackman and Jones.  The clinical symptoms of hyperthyroidism are usually hyperactivity, heat intolerance, fatigue, weakness, irritability, dysphoria, sweating, palpitations, weight loss with increased appetite, diarrhea, tachycardia, atrial fibrillation in the elderly, tremor, goiter, warm and moist skin, oligomenorrhea, and loss of libido.  It is a very rare and atypical presentation if hyperthyroid patients present with HPP.  The estimated incidence is approximately 0.1-0.2% among the overall hyperthyroid population in North America and it is 10 times more common in the Oriental population.  The disease is more common in males than females due to the decreased genetic penetrance in females.  Though it is just a single case, it somehow also supports this fact of male preponderance. A genetic mutation in either of the two genes – type 1 and type 2 – is the probable cause of HPP. Type 1, the most common form, is inherited as an autosomal dominant disorder with incomplete penetrance. These patients have mutations in voltage-sensitive, skeletal muscle calcium gene CALCL1A3. The presence of type 2 category mutation is almost a definite finding in 10% of all the cases of HPP that usually arise from mutations in the voltage-sensitive sodium channel gene SCN4A. In either of the instances, the mutations lead to an abnormal gating pore current that predisposes the muscle cell to depolarize when the potassium levels are low. It is also now recognized that some cases of thyrotoxic HPP are caused by a genetic variant in the potassium channel KCNJ18 (Kir 2.6) that is at chromosome 17p11.2 (dominant or sporadic), the expression of which is regulated by the thyroid hormone.  Proximal muscle weakness is the most common clinical manifestation of this pathologic entity. The tendency of involvement of the proximal muscle group and lower limbs more than the upper limbs is a common clinical profile in such patients but may selectively involve recently exercised muscles as well; however, it may be asymmetric. Respiratory and bulbar muscles are also involved in severe attacks. High carbohydrate load and heavy meals, muscle cooling, rest after exercise, and T 4 ingestion are usually the precipitating factors of these randomly occurring attacks. Asian summers exhibit an increased incidence of this rare clinical entity with the lowest incidence in Asian winters. Invariably, the association of this disease with thyrotoxicosis can be traced to positive family history.  The findings of lower serum potassium in our case correlates well with the clinical picture of HPP with hyperthyroidism as serum K + is usually low (<2.5 μmol/L) in such conditions but may be occasionally normal in some cases, especially if the blood sample is drawn after the attack. Hypophosphatemia, lower TSH, and findings of reduced compound muscle action potential (CMAP) during attacks in nerve muscle action studies confirm the diagnosis. Electromyography (EMG) shows myopathic features during the attacks and muscle pathology may reveal vacuolar dilation of the sarcoplasmic reticulum, tubular aggregates, and increased muscle Na + -K + pumps during the attacks.  We had a diagnostic dilemma as EMG and muscle biopsy turned out to be normal that can be explained on the basis of culmination of attack when these clinical investigations were done. Administration of potassium usually improves the acute paralysis state and it should be given orally in a dose of 0.2-0.4 mmol/kg at every 30-min interval. IV therapy is rarely necessary (particularly when upper gastrointestinal tract pathology is present). Counseling of the patient regarding the importance of low carbohydrate and low sodium diet as well as the consequences of intense exercise can help significantly in the control of such attacks. Prophylactic administration of acetazolamide (125-1,000 mg/day in divided doses) can reduce or abolish the attacks. Some patients require triamterene (25-100 mg/day) or spironolactone (25-100 mg/day). However, it is to be remembered that type 2 HPP attacks can get exacerbated with acetazolamide.  The treatment of hyperthyroidism with antithyroid drugs is central to the management of thyrotoxic periodic paralysis (TPP). The administration of antithyroid drugs in the present case led to significant improvement in his clinical condition. The peripheral effects of thyrotoxicosis and improvement in muscle strength can be achieved by addition of propranolol in the initial stages. Control of hyperthyroidism for a long duration of minimum 6 months can ensure a good control of such episodes. However, for refractory episodes, the definite management involves administration of iodine ablation or subtotal thyroidectomy.  However, a thorough preanesthetic evaluation and optimization of clinical comorbidities are essential for achieving a smooth perioperative success. ,
To conclude, this case highlights the importance of anticipating this important possibility of hyperthyroidism in these patients for an early and effective management. Though hyperthyroidism is an uncommon cause of HPP, it can be treated successfully by an early anticipation of their association.
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