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.

Graves’ disease orbitopathy can result in a gritty or foreign object sensation in the eyes, excessive tearing, periorbital oedema (swelling around the eyes), and proptosis or exophthalmos (abnormal protrusion of the eyes) (Davies & Burch, 2018). In severe cases, there can be diplopia (double vision), colour vision desaturation, and even loss of vision. Graves’ disease orbitopathy is an autoimmune disease of the retroocular tissues. The orbital fibroblasts and pre-adipocytes/adipocytes express TSHR and respond to TRAb resulting in retroocular adipogenesis (growth of fatty tissue), inflammatory infiltrates, and accumulation of glycosaminoglycans (GAGs). This causes swelling of the orbit and displacement of the eye. This mechanisms is due to direct actions of TRAb in the orbital tissues independent of thyroid hormone synthesis and secretion. Thus overdose of levothyroxine does not cause exophthalmos.

Patients with hyperthyroidism due to Graves’ disease also often exhibit a staring gaze and lid lag (a delay in movement of the upper eyelid on looking down). These signs are thought to be due to the sympathetic overactivity, perhaps mediated by increased alpha-adrenoceptor expression in some tissues, resulting from hyperthyroidism. Hyperthroidism due to levothyroxine overdose can likewise overactivate the sympathetic nervous system and cause staring gaze and lid lag.

References:

Davies TF (2017) Pathognesis of Graves’ disease. Ross DS, Mulder JE ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on March 14, 2018).

Davies TF, Burch HB (2018) Clinical features and diagnosis of Graves’ orbitopathy (ophthalmopathy). Ross DS, Mulder JE ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on March 14, 2018).