Tuesday, February 15, 2011

Hypothyroid Myopathy: What You Need To Know


One of the most difficult problems my daughter had to deal with early on as a teenager becaming increasingly disabled by a misdiagnosed thyroid condition (which we later learned was a non-functioning thyroid due to Stage II thyroid cancer) was chronic muscles aches and pains. Her complaints of chronic fatigue and muscle cramping and pain were attribute to weight gain and later as fibromyalgia.

After a radical thyroidectomy and over the course of the past 3 years we discovered a pattern of increased muscle pains and aches as her now synthetic hormone levels fluctuated. It has been a nightmare to have a doctor validate how she feels and why. Our own personal research discovered a little known or perhaps a little discussed cause we want to share with you today. 


Hypothyroid Myopathy
Muscle involvement in a variety of forms is a frequent problem in both congenital and adult-onset hypothyroidism. This topic will discuss the clinical manifestations and pathogenesis of hypothyroid myopathy. We will discuss other neurologic manifestations of hypothyroidism separately.

As you may already  know deficiency of thyroid hormone leads to a state called hypothyroidism. Common causes of hypothyroidism include the following:
  • Treatment with radioactive iodine (I131 ) for Graves disease
  • Hashimoto disease - An autoimmune process in which lymphocytic infiltration and fibrous tissue accumulation cause replacement of normal thyroid tissue
  • Drug-induced hypothyroidism - Known to occur with amiodarone and iodine (ie, Wolff-Chaikoff effect)
  • Hereditary disorders of the iodothyronine synthesis pathway (thyroxine [T4] and triiodothyronine [T3])
  • Pituitary tumors and related surgical resections and/or excisions.
  • Thyroid Nodules/tumors and related surgical resections and/or excisions.
Hypothyroidism can cause several symptoms, ranging from mild (eg, fatigue, weight gain, cold intolerance, mental slowing, muscle cramping) to severe (eg, heart enlargement, myxedema coma [rare]).

Without regard to the cause of hypothyroidism, neuromuscular and musculoskeletal manifestations can be observed in many patients with the condition. These manifestations can occur at any time in the hypothyroidism disease process. Usually mild, they include weakness, pain, aching, and stiffness.

Hypothyroid myopathy typically manifests as polymyositis-like myopathy with proximal muscle weakness and an increased creatine kinase level. However, it sometimes manifests as muscle enlargement (pseudohypertrophy); in adults, this condition is called Hoffman syndrome. In children with hypothyroid disease (cretinism), a pattern of proximal weakness and diffuse muscle enlargement is known as Kocher-Debr é -S é m é laigne syndrome.

Several case reports describe rhabdomyolysis associated with hypothyroidism. In these cases, the hypothyroidism is thought to have predisposed individuals to rhabdomyolysis.

Pathophysiology:

Hypothyroidism causes a constellation of changes in the body. The lack of thyroid hormone results in slowed or reduced metabolic function, such as decreased protein turnover and impaired carbohydrate metabolism. These metabolic changes occur in many organ systems, including the muscles. Pain with muscle exertion is characteristic of defective carbohydrate metabolism.

Slowed muscle contraction and relaxation, known as hypothyroid myopathy, may be caused by a shift in the distribution of muscle fiber types from fast-twitch fibers to slow-twitch fibers. A reduction in muscle mitochondrial oxidative capacity and beta-adrenergic receptors, as well as the induction of an insulin-resistant state, may result in these changes.

Evidence from a study by Sinclair and colleagues suggests that a decrease in muscle carnitine in patients with either hypothyroidism or hyperthyroidism may contribute to thyroid myopathy.

The global inhibition of the main oxidative pathways (substrate incorporation, substrate oxidation) and of the respiratory chain within cells also may cause myopathic symptoms. A diminished energetic consumption is related partially to a transition in the myosin isoforms, which express a slower adenosine triphosphatase, and to an impairment of the transsarcolemmal transports. All of these factors may contribute to muscle weakness, fatigue, and exertional pain.

Exercise intolerance could be due to an abnormal recruitment of several metabolic pathways, such as glycolysis, related to the mitochondrial metabolism impairment. An abnormal accumulation of protons and monovalent phosphate ions (which are involved in the actin-myosin interaction), as well as abnormal Ca++ metabolism, also may cause reduced exercise tolerance.

Hyponatremia often is seen in patients with hypothyroidism. The decreased number of Na+/K+ adenosine triphosphatase–dependent pumps could imply an abnormal intracellular Na+ level and explain frequent disorders of membrane excitability.

Myoedema is a phenomenon in which mounding up of muscle tissue occurs after light percussion. Myoedema occurs in approximately one third of patients with hypothyroidism, but it is not entirely specific for hypothyroidism. Myoedema is thought to be caused by delayed Ca++ reuptake by the sarcoplasmic reticulum, which also prolongs muscle contraction. Although not proven, this type of prolongation of muscle contraction is also thought to cause muscle hypertrophy.

Frequency:

United States
  •  In North America, acquired impairment of thyroid function affects about 2% of adult women and about 0.1-0.2% of adult men.
  • Neonatal hypothyroidism occurs with a frequency of 0.02% in the white population. In the black population, the frequency falls to 0.003%. 
  • Of individuals with hypothyroidism, 30-80% manifest neuromuscular symptoms, depending on the severity of hypothyroidism. Weakness is observed in one third of patients with hypothyroidism. Carpal tunnel syndrome, although not part of the myopathy, is a peripheral nerve dysfunction found in 15-30% of patients with hypothyroidism.
International
  • Neonatal screening programs for congenital hypothyroidism in many areas of the world show that hypothyroidism is present in 1 out of every 4000 newborns. In iodine-deficient areas of the world, the incidence of hypothyroidism is 10- to 20-fold higher.
Mortality/Morbidity

Mortality has not been shown to be increased in patients with hypothyroid myopathy. Morbidity is significantly increased, reflected in the performance of activities of daily living (ADL) and in patients' quality of life.

Race

No race predilection has been established.

Sex

The incidence of hypothyroidism is much greater in women than in men. Myxedema coma is extremely rare, but its incidence is higher in elderly women, especially those older than 60 years.

Age

Hypothyroidism is seen more commonly in women aged 40-60 years; however, it can be seen in persons of all ages.

Clinical 

History

Neuromuscular symptoms present in 30-80% of patients with hypothyroidism. These symptoms improve or
disappear with correction of the hypothyroid state.

Patients may complain of muscle cramping, proximal symmetrical muscle weakness, muscle stiffness, and exercise intolerance. These manifestations can occur at any time during the presentation of hypothyroidism. 

Slowness of muscle relaxation and of muscle contraction are noted in hypothyroid myopathy.

Physical

Deep tendon reflexes are delayed in approximately 85% of patients with hypothyroidism.

Mounding of the muscle after light percussion (ie, myoedema) occurs in one third of patients with hypothyroidism, but it is not necessarily specific to hypothyroidism.

Muscle enlargement, stiffness, and cramping are a constellation of findings seen in individuals with hypothyroidism. In adults, these findings are known as Hoffman syndrome. In children, they are called Kocher-Debré-Sémélaigne syndrome.

Myokymia, which may be related to a low sodium level, may be seen.

Causes   (See Pathophysiology.)

Hypothyroidism can impair mitochondrial metabolism, resulting in decreased muscle energy production. A low thyroid hormone level is the main causative factor.

Certain drugs, such as lipid-lowering medications, may exacerbate myopathy in patients with hypothyroidism.

There are reports of an increased risk for statin-induced myopathy in patients with hypothyroidism.

Lipid-lowering drugs include beta-hydroxy-beta-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors; also commonly called statins, they include following:
  • Atorvastatin (Lipitor) 
  • Fluvastatin (Lescol) 
  • Simvastatin (Zocor) 
  • Pravastatin (Pravachol) 
  • Lovastatin (Mevacor)
Interferon-alfa therapy for hepatitis, as well as hepatitis infection itself, has been reported to cause a number of adverse immunologic and/or autoimmune effects.Thyroiditis, seen in 10% of patients, may induce hypothyroidism.

Information Sources and References:

1. Barohn R. Metabolic myopathies. In: Cecil RL, Goldman L, eds. Textbook of Medicine. 21 ed. Orlando, Fla: Harcourt Health Sciences; 2000.

2. Miyake I, Hiromatsu Y. [Hypothyroid myopathy]. Ryoikibetsu Shokogun Shirizu. 2001;(36):294-7.

3. Scott KR, Simmons Z, Boyer PJ. Hypothyroid myopathy with a strikingly elevated serum creatine kinase level. Muscle Nerve. Jul 2002;26(1):141-4.

4. Deepak S, Harikrishnan, Jayakumar B. Hypothyroidism presenting as Hoffman's syndrome. J Indian Med Assoc. Jan 2004;102(1):41-2.

5. Turker H, Bayrak O, Gungor L, et al. Hypothyroid myopathy with manifestations of Hoffman's syndrome and myasthenia gravis. Thyroid. Feb 2008;18(2):259-62.

6. Tuncel D, Cetinkaya A, Kaya B, et al. Hoffmann's syndrome: a case report. Med Princ Pract. 2008;17(4):346-8.

7. Kisakol G, Tunc R, Kaya A. Rhabdomyolysis in a patient with hypothyroidism. Endocr J. Apr 2003;50(2):221-3. 

8. Sinclair C, Gilchrist JM, Hennessey JV, et al. Muscle carnitine in hypo- and hyperthyroidism. Muscle Nerve. Sep 2005;32(3):357-9. [Medline].

9. Lochmuller H, Reimers CD. Exercise induced myalgia in hypothyroidism. In: Year Book of Sports Medicine. St Louis, Mo: Mosby; 1994:999-1001.

10. Casimiro-Lopes G, Alves SB, Salerno VP, et al. Maximum acute exercise tolerance in hyperthyroid and hypothyroid rats subjected to forced swimming. Horm Metab Res. Apr 2008;40(4):276-80.

11. Cakir M, Samanci N, Balci N, et al. Musculoskeletal manifestations in patients with thyroid disease. Clin Endocrinol (Oxf). Aug 2003;59(2):162-7.

12. Horak HA, Pourmand R. Endocrine myopathies. Neurol Clin. Feb 2000;18(1):203-13.

13. Pourmand R. Metabolic myopathies. A diagnostic evaluation. Neurol Clin. Feb 2000;18(1):1-13.

14. Monzani F, Caraccio N, Siciliano G, et al. Clinical and biochemical features of muscle dysfunction in subclinical hypothyroidism. J Clin Endocrinol Metab. Oct 1997;82(10):3315-8.

15. Ghilardi G, Gonvers JJ, So A. Hypothyroid myopathy as a complication of interferon alpha therapy for chronic hepatitis C virus infection. Br J Rheumatol. Dec 1998;37(12):1349-51.

16. Obolonczyk L, Obolonczyk L, Siekierska-Hellmann M, et al. Side effects during interferon-alpha therapy of hepatitis C with special consideration of thyroid dysfunction. Postepy Hig Med Dosw (Online). Jun 26 2007;62:309-21.

17. Takanami I, Imamuma T, Yamamoto Y, et al. The rapid transformation of hyperthyroidism to hypothyroidism complicated by myasthenia gravis. J Thorac Cardiovasc Surg. Sep 1995;110(3):852.

18. Modi G. Cores in hypothyroid myopathy: a clinical, histological and immunofluorescence study. J Neurol Sci. Apr 1 2000;175(1):28-32.



1 comment:

  1. I recently came across your blog and have been reading along. I thought I would leave my first comment. I don't know what to say except that I have enjoyed reading. Nice blog. I will keep visiting this blog very often.


    Susan


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