Although hemangiomas are the most common vascular tumors of the liver in infancy, data regarding hypothyroidism and heart failure related to hepatic hemangiomas are limited. Here, we present a 15- day -old girl who presented with prolonged jaundice at the age of 15 days. Because her TSH level was found to be 74 μIU/mL, she was initially diagnosed with congenital hypothyroidism and L-Thyroxine replacement therapy was initiated. On follow-up examination performed two months later, it was observed that her TSH level was not suppressed and a mass was noticed in the right upper abdomen on physical examination. Abdominal ultrasonography revealed multiple masses with sizes of about 3-3,5 cm covering the whole liver. When evaluated with clinical and radiological appearance, oral methylprednisolone at a dose of 5 mg/kg/day and propranolol at a dose of 2 mg/kg were initiated with a diagnosis of hepatic hemagioma/hemangioendothelioma. Consumptive hypothyroidism due to hepatic hemangioma and congestive heart failure were considered in the patient who had findings of heart failure. The dose of L-Thyroxine was increased 2-fold. The patient received intensive care treatment for severe heart failure. Because his findings resolved, he was started to be followed up with propranolol, steroid and L-Thyroxine treatment.
Consumptive hypothyroidism is a rare condition usually described in association with diffuse infantile hemangioma of the liver, over-expressing type 3 iodothyronine-deiodinase. We report a case of acquired hypothyroidism associated with a parotid hemangioma in a male child, who was initially evaluated at 48 days of age due to persistent jaundice. Replacement hormonal therapy was promptly started, but resolution of the clinical and laboratory findings of hypothyroidism was only achieved at 3 months of age, when propranolol treatment was added to the therapeutic regimen. Our review of the literature retrieved only one case of proven consumptive hypothyroidism associated with a parotid infantile hemangioma, making a real incidence an underestimate: we believe one should consider this association a real possibility.
Infantile hemangiomas (IHs) are common, although systemic therapy has been generally limited to circumstances of potential compromise of vital functions (airway, vision, feeding, or cardiac), risk of disfigurement, or bleeding. IHs have previously been shown to express high levels of type III deiodinase, which catabolizes active thyroid hormone, resulting in a state of severe hypothyroidism, termed "consumptive hypothyroidism." We describe an infant with diffuse hepatic hemangiomas who developed consumptive hypothyroidism who was initially treated successfully with systemic glucocorticoids and β-blockers. Several efforts to wean her medications were unsuccessful. She subsequently developed severe growth restriction and treatment alternatives were sought. Although previously limited to treatment of life-threatening hemangiomas, a trial of vincristine was initiated. She was ultimately weaned from all systemic therapies, with recovery of a normal growth trajectory. This case highlights broader indications for vincristine as a safe and effective systemic therapy for treatment of IHs. It also stresses the importance of close anthropometric monitoring of infants and toddlers receiving glucocorticoid therapy and intervention when growth compromise becomes evident.
CONTEXT: Consumptive hypothyroidism (CH) is a rare form of hypothyroidism due to increased catabolic activity of type 3 iodothyronine deiodinase (DIO3) that can occur in large tumors. PATIENTs with CH typically present with markedly increased requirements for exogenous thyroid hormone and resolution after removal of the source of ectopic DIO3. DIO3 is encoded by DIO3, an imprinted gene expressed on the paternal allele that is located in a DIO3/delta-like 1 homolog (DLK1) gene locus regulated by a common control region, intergenic differentially methylated region (IGDMR). Because DIO3 is an imprinted gene, loss of imprinting at the IGDMR is thought to play a role in its increased expression; however, the molecular mechanism for DIO3 in CH currently is not known.
OBJECTIVE: The aim of the study was to determine the molecular mechanism for CH in an adult patient.
SETTING: The study was conducted in the Department of Endocrinology of a tertiary care center in Singapore.
PATIENT: We report the case of an adult Asian female patient with a large intrathoracic fibrous tumor and severe hypothyroidism that resolved after tumor resection.
RESULTS: The patient's tumor expressed increased levels of DIO3 and DLK1 mRNA and protein levels. Methylation-specific PCR of the IGDMR showed similar hypomethylation in placenta, thyroid, leukocytes, and tumor. Western blotting showed activation of sonic hedgehog (SHH) and MAPK signaling pathways that can increase DIO3 and DLK1 expression.
CONCLUSIONS: Loss of imprinting did not account for overexpression of DIO3 in the patient's tumor. Instead SHH and MAPK/ERK pathway activation was associated with systemic thyroid hormone catabolism and growth of the tumor. These findings raise the possibility that other tumors that have increased SHH and MAPK/ERK signaling also may have intratumor or systemic effects on thyroid hormone function.
INTRODUCTION: Benign neonatal hemangiomatosis is a condition in which multiple cutaneous hemangiomas appear at birth or shortly thereafter; visceral complications are absent. Here, we report a case of a consumption hypothyroidism in an Egyptian baby with benign neonatal hemangiomatosis.
CASE PRESENTATION: An 8-month-old Egyptian boy with benign neonatal hemangiomatosis was referred to our institution for evaluation of developmental delay. Initial examination revealed a quiet baby who was able to sit only with support. He had hypotonia, a large anterior fontanelle, puffy eyes, cold extremities, hypothermia, bradycardia, and abdominal distension. An examination of his skin revealed more than 100 dome-shaped red-purple cutaneous hemangiomas that varied in size from 5 to 10mm on the back, the abdomen and the extremities without mucus membrane involvement. He had low serum free thyroxine concentration and triiodothyronine levels and high thyroid-stimulating hormone and reverse-triiodothyronine levels. A work-up that involved appropriate imaging ruled out visceral involvement. Based on the above mentioned data, a diagnosis of consumptive hypothyroidism due to benign neonatal hemangiomatosis was made. He was started on oral thyroid medication which was gradually increased to 90μg L-thyroxine daily (15μg/kg/day). After three months of treatment, he was able to sit alone without support and he had normal levels of thyroid-stimulating hormone and serum free thyroxine.
CONCLUSION: Thyroid function should be assessed periodically in babies with benign neonatal hemangiomatosis, especially if symptoms of hypothyroidism appear or the size and number of hemangiomatosis increase rapidly. Moreover, high doses of L-thyroxine may be needed to achieve euthyroidism during the infancy.
Infantile hepatic hemangioma can be associated to consumptive hypothyroidism due to overexpression of type 3 deiodinase in the endothelium of vascular tumor, which catalyzes the conversion of T4 to reverse T3 (rT3) and of T3 to T2, both of which are biologically inactive. Here, we report an infant with a massive biopsy-proven infantile hepatic hemangioma who developed thyroid dysfunction without a typical biochemical profile consistent with severe consumptive hypothyroidism, despite the large tumor burden. Our patient was treated with propranolol that rapidly resolved both hepatic hemangioma and thyroid dysfunction. We propose propranolol as a first-line therapy of thyroid dysfunction associated with infantile hepatic hemangioma, in order to avoid interference with neurological development caused by hypothyroidism in the first months of life.
