Consumptive hypothyroidism in a patient with malignant rhabdoid tumor of the kidney: case report on a newly found association

Abstract

Introduction: Consumptive hypothyroidism is a rare paraneoplastic condition most commonly associated with infantile hemangiomas. It is caused by overexpression of deiodinase type 3 (D3), which leads to preferential conversion of thyroxine to the metabolically inactive reverse triiodothyronine (rT3), paralleled by a decrease of the biologically active T3. Case presentation: A 46-year-old male patient with previously normal thyroid function was diagnosed with a renal carcinoma with rhabdoid differentiation. He was treated with sunitinib, followed by the immune checkpoint inhibitors ipilimumab and nivolumab, and he developed primary hypothyroidism secondary to thyroiditis. Substitution with unusually high doses of levothyroxine as high as 4.3 µg/kg/day did not normalize his thyroid function. Poor compliance was refuted because there was no improvement after observed administration. He had no malabsorption. Although tyrosine kinase inhibitors can increase the expression of D3, this effect tends to be modest. Therefore, the suspicion of tumor-related consumptive hypothyroidism was raised and supported by low free T3 and elevated rT3 levels. The therapy could not be further modified because the patient opted for palliative care and passed twelve days later. Immunohistochemistry of the tumor from a sample obtained prior to systemic therapy documented abundant expression of D3 corroborating the diagnosis of consumptive hypothyroidism. Conclusions: This observation extends the spectrum of malignancies overexpressing D3. Although rare, increased awareness for this paraneoplastic syndrome is key, if persistent hypothyroidism cannot be explained by compliance issues or malabsorption. Substitution with high doses of levothyroxine, and combination therapy with liothyronine, can correct hypothyroidism in these patients.

Unusual causes of hyperthyrotropinemia and differential diagnosis of primary hypothyroidism: a revised diagnostic flowchart

“…In particular, D3 mRNA expression directly correlated with serum TSH levels and the development of hypothyroidism. Although thyroid dysfunction induced by tyrosine kinase inhibitors is multifactorial, consumptive hypothyroidism may contribute to its etiopathogenesis (63,64).…”

“…Large and giant hepatic hemangiomas/endotheliomas are the most common tumors associated with consumptive hypothyroidism in pediatric patients, although cutaneous and parotid hemangiomas and fibrosarcoma have been reported ( 62 ). Less frequently, consumptive hypothyroidism may also affect adult patients with hemangiomas but also non-vascular tumors such as gastrointestinal stromal tumor (GIST) and malignant fibrous tumors ( 63 , 64 ). In GIST, D3 overexpression can be also induced by the administration of tyrosine kinase inhibitor (TKI) such as sunitinib.…”