Studies in thyrotoxic periodic paralysis

doi:10.1016/0022-510X(71)90005-0

Journal of the Neurological Sciences

Volume 13, Issue 4, August 1971, Pages 431-442

https://doi.org/10.1016/0022-510X(71)90005-0 Get rights and content

Abstract

A new case of thyrotoxic periodic paralysis (TPP) is described. Prior to treatment by subtotal thyroidectomy, paralysis was induced by a variety of measures which acutely decreased the serum potassium concentration. The magnitude of the potassium ion shifts was not consistent with the degree of clinical paralysis, nor did the serum potassium concentrations rise as the clinical attacks cleared. Hypokalemia was not, therefore, the sole cause of paralysis. Aldosterone excretion seemed to be normal.

EMG studies revealed that the paralytic attacks were caused by an acute myopathy, and the muscle biopsy showed a prominent vacuolar myopathy during paralysis. The vacuoles developed from the sarcoplasmic reticulum (SR) and were absent or much less notable between attacks. Glycogen masses, degenerative changes and other microscopic findings seem to be secondary phenomena; some degree of vacuolization is the only consistent histologic finding in all cases studied thus far. A small but significant increase of the muscle water content in an affected muscle was found in the present case during induced paralysis. Although it is tempting to attribute paralysis to SR distension by fluid, this mechanism of paralysis in TPP is unproven and may also be a secondary phenomenon. The EMG studies indicated a depression of sarcolemmal excitability during paralysis, which should be investigated when possible in the future by means of microelectrode recording of the muscle membrane potential.

A systemic factor appears to trigger paralysis in TPP. The only endocrine abnormality is hyperthyroidism and the attacks recur after thyroid treatment if an excess of hormone is administered. The level of circulating hormone should be studied in future cases in relationship to spontaneous and induced paralytic attacks.

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Cited by (35)

Thyrotoxic Periodic Paralysis: A Review and Suggestions for Treatment
2021, Endocrine Emergencies
Thyrotoxic periodic paralysis (TTP) belongs to the family of diseases called channelopathies, and is manifested by episodes of painless muscle weakness. TPP is an uncommon complication of hyperthyroidism that most often affects young East Asian males, but is increasingly being seen in other ethnic groups. The characteristic presentation is an acute attack, which may present as a spectrum of disease, showing mild weakness to total paralysis. The onset primarily is at night or in the early morning, a few hours either after fasting, a high-carbohydrate meal, a heavy meal, alcohol abuse, or strenuous exercise. It is usually followed by complete recovery within 72 hours. Manifestations of hyperthyroidism may not be obvious. This diagnosis should be contemplated when this demographic of patient presents with marked painless weakness after provocation with exercise or changes in diet. The distinctive indicator is hypokalemia, which develops from increased cellular sodium/potassium-ATPase pump activity with the transport of potassium from the extracellular to the intracellular space in combination with a reduced potassium output. KCNJ18 gene mutations, which alter the function of an inwardly rectifying potassium channel named Kir2.6, have been observed in 0 to 33% of cases. However, two-thirds of TPP patients do not present with mutations in KCNJ18, drawing attention for the need to search other genetic susceptibility mechanisms. Hence, the presentation of TPP includes thyrotoxicosis, a genetic predisposition, along with dietary factors and/or exercise. The relative impact of each of these hereditary and other factors may vary. The initial treatment regimen, which is potassium supplementation, should be given with care, due to a high risk of hyperkalemia. Propranolol is an alternative first-line therapeutic option based on the assumption that hyperadrenergic activity is involved in the pathogenesis. If thyroid function tests are unobtainable in the acute situation, the diagnosis may be supported by the findings of hypokalemia, low spot urine potassium excretion, hypophosphatemia with hypophosphaturia, high spot urine calcium/phosphate ratio, and electrocardiographic abnormalities such as tachycardia, atrial fibrillation, high QRS voltage, and atrioventricular block. The definitive treatment is cure of the hyperthyroidism.
The underlying mechanisms of TPP remain incompletely understood and the true etiology and mechanisms of the disease await further studies
Periodic paralysis
2007, Handbook of Clinical Neurology
Citation Excerpt :
Correcting thyrotoxicosis can sometimes take weeks or months during which time prevention and treatment of acute attacks may be desirable in severely affected patients. In contrast to the familial periodic paralyses no convincing benefit from carbonic anhydrase inhibitors has been described in TPP (Norris, et al., 1971; Yeung and Tse, 1974). Most centers use potassium supplementation, a beta‐blocker, or a combination to treat acute attacks.
This chapter provides a detailed overviewr of current knowledge regarding clinical features, investigations, treatment, genetics, and molecular pathophysiology of the periodic paralyses. Periodic paralysis is a disorder of skeletal muscles in which patients experience attacks of muscle weakness of variable duration and severity. The attacks can last from a few minutes to several days. The weakness in an attack can be generalized or focal. Early in the natural course of the disease muscle strength returns to normal after an attack, but later significant fixed muscle weakness often develops. The variability of the symptoms often leads to delays in the accurate diagnosis and treatment. Although the clinical phenotype of periodic paralysis has been recognized for many years, it is only recently that the underlying pathophysiology has been deduced at a molecular genetic level. In all forms of this disorder, electrophysiological examination during an attack reveals that the skeletal muscle fiber membrane is in a partially depolarized and inexcitable state. Muscle membrane excitability depends on the coordinated interplay of key voltage-gated ion channels. It is now known that in both genetic and acquired forms of periodic paralysis dysfunction of these key membrane-bound ion channels underlies the pathophysiology that explains the altered muscle excitability. Periodic paralysis was one of the first neurological channelopathies to be characterized at a genetic and cellular level.
Thyrotropin-secreting pituitary adenoma presenting as hypokalemic periodic paralysis
2003, American Journal of the Medical Sciences
Citation Excerpt :
In TPP, the most common cause of hyperthyroidism is Graves disease. 2 However, TPP has also been reported in patients who have a toxic nodular goiter, iodine-induced thyrotoxicosis, thyroxine abuse, solitary toxic thyroid adenoma, and lymphocytic thyroiditis. 7–11 TSH-secreting pituitary adenomas are very rare causes of TPP.
Thyrotropin (TSH)-secreting pituitary adenoma presenting with hypokalemic periodic paralysis is extraordinarily rare and may be misdiagnosed. We describe a 44-year-old man who suffered from acute muscle weakness and inability to ambulate upon awakening in the morning. Physical examination showed hypertension, tachycardia, and symmetrical flaccid paralysis of all extremities. The major biochemical abnormality was hypokalemia (K⁺, 2.0 mmol/L) with low urine K⁺ excretion. A thyroid function study revealed elevated thyroid hormone levels and inappropriately high TSH concentrations (2.10 μU/mL). Brain magnetic resonance imaging delineated a pituitary tumor with suprasellar extension. After trans-sphenoidal removal of tumor, he became clinically and biochemically euthyroid without any further attack of paralysis. Pathological findings confirmed a TSH-secreting adenoma with exclusive TSH immunostaining. TSH-secreting pituitary adenoma must be kept in the differential diagnosis in any thyrotoxic periodic paralysis patients with detectable TSH levels to avoid delaying diagnosis and management.
Hypokalaemic thyrotoxic periodic paralysis: Case report and review of an Oriental syndrome
1996, Netherlands Journal of Medicine
Presentations of acute systemic weakness are rare and appear dramatic and frightening to both patients and physicians. Aetiologies are multifactorial and diverse. Morbidity and mortality are associated with the unrecognized disease. One of the underlying disorders is hypokalaemic thyrotoxic periodic paralysis (HTPP), an uncommon disorder. HTPP is characterized by periodic occurrences of muscle weakness during attacks of hyperthyroidism and appears predominantly in Orientals. This article describes a patient of Chinese origin with hyperthyroidism and attacks of paralysis and considers several problems: a lack of familiarity with the syndrome, increasing numbers of patients with this disease in European hospitals as a result of migration of populations, and the importance of patient compliance in therapeutic management. Finally, a review of the literature concerning presentation, differential diagnosis, pathophysiology, and therapeutic management is provided.
Muscle morphology in critical care
1995, Nutrition clinique et metabolisme
Dans les services de soins intensifs, les patients se plaignent souvent de faiblesse et de douleurs musculaires. Les causes sont variées mais la réponse du muscle squelettique à une agression est limitée : atrophie, hypertrophie, dégénérescence vacuolaire, nécrose suivie le plus souvent de régénération.
Ces lésions dépendent du facteur causal mais aussi des propriétés chimiques enzymologiques et physiologiques des fibres musculaires.
Après un rappel de la morphologie du muscle en histoenzymologie et en ultra-structure, les causes des lésions musculaires chez les patients de soins intensifs sont exposées : atrophie de la cachexie, atrophie d'immobilisation, myopathies dues aux injections intramusculaires répétées, myopathies d'origine médicamenteuse, nutritionnelle ou secondaires à des désordres électrolytiques.
Enfin il est rappelé le travail fait par Helliwell [1] portant sur l'étude morphologique et biochimique des muscles des patients en réanimation prolongée.
Pain and muscle weakness are often observed in intensive care patients. Many factors may affect skeletal muscle of critically-ill patients but histopathologic changes are relatively limited : (atrophy, hypertrophy, vacuolar degeneration and necrosis followed by regeneration).
Morphological changes depend on the causal factors but also on the chemical and physiological characteristics of muscle fibers. The histochemical and ultra-structure of normal muscle is reported. The causes of muscle changes in critically-ill patients are described : atrophy due to undernutrition or immobilization ; damage caused by repeated intramuscular injections ; toxic, nutritional and electrolytic disorders.
Helliwell et al's works on muscle pathology and biochemistry in critically-ill patients is also reported.
The periodic paralyses
1988, Neurologic Clinics
Patient history and examination often provide sufficient diagnostic clues to allow appropriate classification of the patient with one of the primary periodic paralyses. This article reviews these disorders, their treatment, and the use of provocative testing in their diagnosis. Dysfunction of the muscle membrane sodium channel may be a “final common pathway” pathogenetic mechanism for many of the periodic paralyses.

View all citing articles on Scopus

^☆: Supported in part by U.S. Public Health Service Research Grant AM-06415 from the National Institute of Arthritis and Metabolic Diseases.

^∗: Aided by the John A. Hartford Foundation, Inc.

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Studies in thyrotoxic periodic paralysis☆

Abstract

Amer. J. Med.

Electroenceph. clin. Neurophysiol.

Amer. J. Med.

Metabolism

Exp. Neurol.

J. biol. Chem.

Interpretation of the rapid intravenous glucose tolerance test in normal individuals and in mild diabetes mellitus

J. clin. Invest.

The effect of epinephrine, insulin and hyperthyroidism on the rapid intravenous glucose tolerance test

J. clin. Invest.

Adynamia episodica hereditaria

Brain

Ultrastructural changes in adynamia episodica hereditaria and normokalemic familial periodic paralysis

Brain

Thyrotoxic hypokalemic periodic paralysis

Arch. Neurol. (Chic.)

Hyperkalemic periodic paralysis

Arch. Neurol. (Chic.)

La paralisi muscolare periodica ipokaliemica

G. Clin. med.

Periodic paralysis associated with hyperthyroidism

Calif. Med.

Electron microscopic observations in thyrotoxic and corticosteroid-induced myopathies

Electron microscopic observations in primary hypokalemic and thyrotoxic periodic paralysis

Acetazolamide treatment of hypokalemic periodic paralysis

Ann. intern. Med.

Severe hypercalcemia from hyperthyroidism with unusual features

Brit. med. J.