Systemic sclerosis (SSc) is a chronic, multi-system disorder of an unknown etiology characterized by abnormalities of the vascular system and complex alterations of the immune system, which eventually end up in fibrosis at variable degrees and specific organ damage. The severity and progression of the disease vary with heterogeneous clinical manifestations involving the main organs and districts such as the skin and the gastrointestinal tract (muscular atrophy and fibrosis) and a progressive and fatal visceral involvement of the kidneys, heart and lungs [pulmonary hypertension (PAH) and fibrosis] (1).

Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disorder associated with lymphocytic infiltration of the thyroid gland, leading to a progressive impairment of the thyroid function, and inducing subclinical and overt hypothyroidism (2). HT is frequently correlated with other organ and non-organ-specific autoimmune disorders (3). Many studies have evaluated the incidence of cases of thyroid autoimmunity and dysfunction in female patients with SSc, showing a high incidence of HT and new cases of hypothyroidism and thyroid dysfunction (4). The autoimmune regulator gene polymorphism has been linked to SSc/HT association (5), and autoimmune hypothyroidism seems to be associated with a higher index level of anti-Scl-70 (6). Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score (7).

Interestingly, asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-T4 malabsorption in patients with SSc/HT.

Thyroid hormone deficiency, when severe and untreated, may be a life-threatening condition especially in patients with comorbidities such as SSc. Although all of the organs and main systems can be interested in this disease, PAH is the major cause of mortality in patients with SSc (8). The onset of autoimmune hypothyroidism can worsen the prognosis of PAH in SSc (9, 10).

The gastrointestinal tract is most frequently involved in SSc. The diagnosis of gastrointestinal sclerosis may be delayed because of the absence of clinical symptoms despite the organ damage. However, the consequences of the drug-impaired absorption and their reduced bioavailability are often dangerous, especially in patients with comorbidities receiving oral drugs (11).

l-Thyroxine, a lifelong treatment in patients with persistent hypothyroidism, is generally orally administered; an empty stomach and a correct storage of l-T4 is necessary (12, 13). A concomitant administration of other medicaments and supplements should be avoided to permit a good absorption of l-T4 (11–14).

In our patient with SSc/HT, we observed the onset of severe and acute hypothyroidism due to l-T4 tablet malabsorption for the esophageal sclerosis. We can hypothesize that the l-T4 tablets were not well absorbed in our patient because: (1) they did not completely reach the stomach and/or had an inadequate dissolution phase (since they did not find the acid pH necessary for their optimal dissolution) or (2) were sequestered by the food abnormally stuck in the esophagus.

More important, our patient reported very mild gastrointestinal symptoms without dysphagia despite the severe alteration of the esophagus motility detected by manometry examination. In fact, SSc determines only an alteration of esophageal motility without the impairment of esophageal mucosa; however, this alteration was able to impair the bolus progression and reduce the l-T4 absorption in our patient. We excluded all of the other causes of l-T4 malabsorption, poor-compliance and incorrect l-T4 administration and concluded that the reduced efficacy of the l-T4 tablets was secondary to SSc esophageal complications.

Current guidelines recommend oral l-T4 in tablets as treatment of choice in patients with hypothyroidism (11). However, liquid formulation of l-T4 is available in Italy (Tirosint drops, distributed by Ibsa Farmaceutici Italia Srl); it is solubilized in ethanol without other excipients, and therefore, better absorbed compared to the tablet form, allowing a quicker absorption of l-T4 without a dissolution phase (15, 16). The literature data have reported positive effects of l-T4 liquid solutions compared to l-T4 tablets in presence of drug interference, food, beverages, gastrointestinal disorders, and/or other factors interfering with l-T4 absorption (11–19). Our patient was unresponsive to oral l-T4 tables despite the increase in the l-T4 dosage. On the contrary, a normalization of thyroid function was achieved when l-T4 formulation was switched to the oral drops in an equivalent dosage.

It is essential to assess thyroid function as part of the clinical screening in the SSc patients due to the high prevalence of HT and antithyroid autoantibodies in presence of systemic autoimmune disease. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because SSc esophageal complications can decrease the efficacy of l-T4 therapy and persistent hypothyroidism can worsen the prognosis of these patients. A periodic follow-up is mandatory to assess the adequacy of l-T4 replacement therapy, considering the possible onset of asymptomatic esophageal complications of SSc.

The patient gave written informed consent for the publication of this case report.

All the authors contributed in writing the manuscript, revised and approved the final version, and agreed to be accountable for the content of the work.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor shares an affiliation with the reviewer, SF.