Thyroid Eyes, a Multidisciplinary Clinic at Gemelli

Palpitations and tachycardia, tremors, insomnia, weight loss, heat intolerance, nervousness, increased appetite. These are all symptoms related to the increase in thyroid hormones in the blood, that is, to a condition of hyperthyroidism, typical for example of Basedow-Graves disease. But one in three patients affected by Basedow may also present extra-thyroid symptoms, associated with phenomena not directly related to the production of thyroid hormones.

"Among the most complex to manage - explains Alfredo Pontecorvi, Professor of Endocrinology at the Università Cattolica del Sacro Cuore and Director of the UOC of Endocrinology and Diabetology of Fondazione Policlinico Gemelli Irccs - is thyroid eye disease (TED), which can manifest itself with nonspecific signs and symptoms, such as red eye, sensation of a foreign body in the eye, increased tearing, up to more critical symptoms such as proptosis, exophthalmos (a protruding eye, which can lead to the serious and dramatic event of dislocation of the eyeball), the appearance of damage to the cornea (due to the fact that the eyelid is no longer able to completely cover the eye), up to much more critical conditions, such as compression of the optic nerve, with the risk of loss of vision".

Ocular involvement may be related to the autoimmune phenomenon, which is the basis of Basedow's disease and therefore to the production of anti-TSH receptor antibodies. "The receptors for TSH - explains Edoardo Vergani, endocrinology specialist at Fondazione Policlinico Gemelli Irccs - are in fact present not only on the thyroid, but also in the adipose tissue of the orbit. However, chronic inflammation can also contribute to the ocular disease, which has as its focal point the fibroblasts that release connective matrix at the orbit level; it is this accumulation of material in the orbit that 'pushes' the eyeball forward and causes exophthalmos. Rarely, Basedow's disease can begin with ocular symptoms, when systemic ones are not yet present".

Among the risk factors for thyroid orbitopathy - a note reports - there is cigarette smoking and inadequately managed thyroid hyperfunction; accidental trauma and stress represent a possible trigger. "In the context of thyroid orbitopathy - continues Vergani - we distinguish between an active phase, which can be managed with pharmacological therapy, and a chronic phase of the disease, where a surgical approach may be indicated. Early diagnosis is therefore very important, which allows for pharmacological intervention and to block the pathology in its infancy, in the 'active' phase of the disease".

At the moment, "the gold standard of treatment - continues Vergani - involves the use of cortisone boluses for 12 weeks, accompanied by oral immunosuppressive therapy (e.g. with mycophenolate mofetil). In the mildest forms, topical therapy is used. New drugs are also being studied on new disease targets that involve fibroblastic activity (e.g. Igf-1 receptor at the endo-orbital level), but also against anti-TSH receptor antibodies (monoclonal antibodies and small molecules that intercept these antibodies either in the blood or at the orbital level) and finally drugs that intercept the cytokine storm, to be used at the onset of inflammation (antibodies against interleukin 6 and anti-interleukin-6 receptor)".

The diagnosis is essentially clinical and can be completed with a series of tests. The fact that there is an underlying thyroid disease and the presence of anti-TSH receptor antibodies (Trab) is very indicative. "The ideal would be to understand, through the dosage of some biomarkers - says Pontecorvi - what the main disease pathway is, to direct oneself towards the most targeted therapy for a given patient. The Policlinico Gemelli is taking part in many of the clinical trials on these new putative therapies".

The ophthalmological evaluation of the patient with thyroid orbitopathy is very important, in order to define the severity of the problem (extent of exophthalmos, intraocular pressure, visual impairment). The heads of the Thyroid Orbitopathy Ophthalmological Clinic are Gustavo Savino, professor of Ophthalmology at the Università Cattolica del Sacro Cuore and director of the Uoc Ocular Oncology of Fondazione Policlinico Gemelli Irccs, and Dr. Giovanni Cuffaro. It may be useful to perform an MRI (to better define the degree of disease activity) or a CT scan (which helps the surgeon, to orient towards a possible orbital decompression intervention, but also for the surgical correction of strabismus or interventions on the eyelid). Once the disease activity and the severity of the clinical picture have been defined, the endocrinologist and the ophthalmologist choose the best therapy for the patient.

"Patients with ocular involvement in Italy - emphasizes Savino, professor - are about 80,000, but the real number is probably much higher considering the mild forms that are often unrecognized. It is certainly the most evident manifestation of Graves' disease and the most complex to treat, with a high impact on social life. It is however likely that, in the near future, thanks to new biological and poly-pharmacological therapies, there will be a significant reduction in the need for surgery".

"The multidisciplinary management of these patients is therefore fundamental," concludes Pontecorvi. "Third-level centers such as the Fondazione Policlinico Gemelli, capable of setting up a complete path for the patient, making use of multiple specialists, represent the gold standard for their management." The clinic is coordinated for the endocrinology part by Professor Alfredo Pontecorvi and Doctor Edoardo Vergani; those responsible for the ophthalmology part are Professor Gustavo Savino and Doctor Giovanni Cuffaro. The specialists who represent the core of this clinic can also, depending on the case, make use of a series of consultants, from the endocrine surgeon, to the nuclear medicine doctor, to the radiotherapist, to the rheumatologist, to the otolaryngologist, to the orthoptist.