Category: thyroid drugs

Hashimoto’s thyroiditis versus Hashimoto’s encephalopathy

Is Hashimoto’s encephalopathy related to Hashimoto’s thyroiditis?

• Hashimoto’s thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed, resulting in chronic hypothyroidism.
• Hashimoto’s encephalopathy is a rare neurological condition characterized by encephalopathy and thyroid autoimmunity. It shows a good clinical response to corticosteroids.

Hashimoto’s thyroiditis, so named because it was first described in a medical publication by Hakaru Hashimoto (1881-1934) in 1912, is an autoimmune disease. Typically the autoantibodies include antibodies against thyroid peroxidase (TPO). TPO is an enzyme expressed in the thyroid gland that is essential for the production of thyroid hormones. In Hashimoto’s thyroiditis, the thyroid gland is gradually destroyed, resulting in chronic hypothyroidism unless treated with thyroid hormone replacement. It is the most common form of hypothyroidism, affecting about 5% of people.

Hashimoto’s encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is an extremely rare (2.1 in 100,000) neurological condition characterized by encephalopathy and thyroid autoimmunity, which shows a good clinical response to corticosteroids.  First described by Brain, Jellinek and Ball in 1966, the condition was named for its association with Hashimoto’s thyroiditis, but the pathogenic autoantibodies are thought to be against alpha-enolase, a ubiquitous enzyme invovled in glycolysis. Glycolysis is the metabolic pathway that converts glucose to pyruvic acid releasing energy in the form of adenosine triphosphate (ATP).

Levothyroxine and cancer?

Is there an association between levothryoxine and breast cancer?

The short answer is that there is not sufficient evidence to draw any conclusion at this time. Patients who require levothyroxine should continue to take their medication as prescribed by their doctor. The risk of ultimately fatal myxedema due to severe untreated hypothyroidism is proven and real. The risk of cancer is speculative and not definitively proven.

When this question came up at the end of the lecture, my initial thought was that an association between levothryoxine and cancer is highly improbable. Oral levothyroxine essentially replaces your own endogenous thyroxine (T4). Treatment normalises T4 levels but should not cause supraphysiological levels of T4.  Even the route of absorption is largely physiological as endogenous T4 is recycled through enterohepatic circulation and is absorbed in the small intestine after being excreted in the bile. The only potentially “unnatural” exposure is as the levothryoxine tablet passes from the mouth to the stomach. In theory, there is no reason why taking levothyroxine should expose anyone to greater risk than having physiologically normal thyroid function would.
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Does hyperthyroidism cause constipation or diarrhoea?

Hyperthyroidism causes sympathetic overactivation such that many of the symptoms of thyroid storm can be alleviated by beta-blockers. The sympathetic nervous system “fright, flight or fight” response opposes the parasympathetic nervous system “rest and digest” response and shuts down gastrointestinal function. So hyperthyroidism causes constipation, correct? 

Sorry, not correct. Yes, hyperthyroidism can stimulate overactivation of the sympathetic nervous system. Yes, symptoms of thyroid storm can be treated with sympatholytic beta-blockers. But no, hyperthyroidism does not cause constipation. Hyperthyroidism causes diarrhoea.  Conversely, hypothyroidism causes constipation.

So, next, you will ask “What is the mechanism?”. Unfortunately, the mechanism is not known. Recent reviews have speculated that it might be due to beta-2 adrenoceptor-mediated effects on gastrointestinal motility and secretions (Daher et al., 2015; Kyriacou et al., 2015) but the evidence for this is very limited.  For example, a case report on one patient has suggested that propranolol can control intractable diarrhoea in hyperthyroidism (Bricker et al., 2001) but another study on ten hyperthyroid patients found no effect of propranolol on the gastrointestinal transit time (Bozzani et al., 1985).

For the moment, as we do not know the underlying mechanism, it is just one of those exceptions that you have to remember. In nearly every other respect, hyperthyroidism has a sympathomimetic effect and hypothyroidism has a sympatholytic effect. But for the gastrointestinal system, it is the opposite.

References:

Bozzani A, Camboni MG, Tidone L, Cesari P, Della Mussia F, Quatrini M, Ghilardi G, Ferrar L, Bianchi PA (1985) Gastrointestinal transit in hyperthyroid patients before and after propranolol treatment. Am J Gastroenterol. 1985 Jul;80(7):550-2.

Bricker LA, Such F, Loehrke ME, Kavanaugh K (2001) Intractable diarrhea in hyperthyroidism: management with beta-adrenergic blockade. Endocr Pract. 2001 Jan-Feb;7(1):28-31.

Daher R, Yazbeck T, Jaoude JB, Abboud B (2009) Consequences of dysthyroidism on the digestive tract and viscera. World J Gastroenterol. 15(23):2834-8.

Kyriacou A, McLaughlin J, Syed AA (2015) Thyroid disorders and gastrointestinal and liver dysfunction: A state of the art review. Eur J Intern Med. 26(8):563-71.

Does levothyroxine overdose cause exophthalmos and lid lag?

Graves’ disease, an autoimmune disorder resulting in hyperthyroidism, can be associated with bulging eyes (exophthalmos) and a staring gaze (lid lag). Does overdose of levothyroxine cause the same signs?

Graves’ disease is an autoimmune disease involving production of antibodies against the thyroid-stimulating hormone (TSH) receptor (TSHR), also known as the thyrotropin receptor (Davies, 2017). The autoantibodies to the thyrotropin receptor (TRAb) activate TSHRs. In most patients this results in stimulation of thyroid hormone synthesis and secretion resulting in hyperthyroidism.

Hypothyroidism, for example caused by Hashimoto’s thyroiditis, is often treated with levothryoxine to replace the deficiency in endogenous thyroxine.   Overdose of levothyroxine can cause hyperthyroidism.

But Graves’ disease is not synonymous with hyperthyroidism (Davies, 2017). Some patients produce TRAb but do not have hyperthyroidism and, by mechanisms independent of thyroid hormone secretion, TRAb can cause orbitopathy resulting in exophthalmos, and dermopathy due to pretibial myxoedema.

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