Consumptive Hypothyroidism Research Articles

Pediatric Angiosarcoma with Novel Phenotypic and Genotypic Profile in Chinese Children

Introduction: Angiosarcoma is an exceedingly rare entity in pediatric population. Herein, we report two pediatric angiosarcoma with novel phenotypic and genotypic profile. Methods: The two patients’ information was summarized by clinical data, histopathology, immunohistochemistry, genetic, treatment, and prognosis. Results: Two Chinese children presented with abdominal mass or consumptive hypothyroidism at 2 and 6 years. A patient presented with a unique histopathology of epithelioid AS with smooth muscle hyperplasia, and carried a novel somatic mutation in FAT1 (c.3929C > T/p. Ser1310Leu) along with germ-line variants in CDK8 (c.895A > C/p. Lys299Gln), FANCI (c.3906-07inv/p. Glu1303Lys), and MST1R (c.3581-83delinsACG/p. Arg1194-Ser1195delinsHisGly). The other patient presented with a novel ­clinical phenotype of consumptive hypothyroidism. They received postoperative treatment and were monitored for 20 and 26 months, showing good recovery. Conclusion: The phenotypic and genotypic spectrum of AS in pediatric population was expanded by these two patients, which requires the accumulating more cases to gain a deeper understanding.

THU230 Consumptive Hypothyroidism Secondary To Hemangioma

Abstract Disclosure: R. Thirunagari: None. D. Taha: None. Background: Peripheral Hypothyroidism also known as consumptive hypothyroidism has been rarely described in association with vascular tumors such as hemangiomas. It is due to excessive production of type 3 iodothyronine deiodinase (D3) enzyme by the hemangioma leading to increased rate of deiodination of T4 and T3 to inactive forms. Clinical case: We report a 4-year-old girl who was diagnosed with consumptive hypothyroidism at the age of 2 months. She was born at full term via scheduled C-section. Mother has hypothyroidism. She was admitted to NICU for respiratory distress and needed oxygen supplementation. She had a large hemangioma covering most of her back on exam. An ultrasound of the head/neck soft tissue showed an ill-defined lobular heterogeneous mass measuring 3.4 x 1.2 x 4.5 cm, markedly hypervascular with both arterial and venous flow likely consistent with hemangioma. At follow up plastic surgery clinic she had respiratory distress which necessitated readmission to the NICU for further workup and possible initiation of Propranolol. An abdominal ultrasound showed enlargement of the right adrenal and on further dedicated ultrasound a right suprarenal lobulated mass as well as intrathoracic soft tissue mass were found. MRI of the abdomen and thorax, revealed multiple large bilateral paraspinal masses throughout the thoracic and lower cervical spine(largest measuring 3.3 x 7 x 15 cm AP) invading the neural foramen at multiple levels, and causing mass effect on the spinal cord which is displaced to the left. There was mass effect on adjacent vascular structures without significant vascular compromise. Biopsy was consistent with hemangioma. Thyroid Newborn screening result was normal. Thyroid evaluation done at 3 months age revealed, free T4 level of 1.04 ng/dL and TSH level of 11.3 µIU/mL. She was started on Levothyroxine 50 mcg daily. Reverse T3 was elevated at 139.2 ng/dl (reference range 13-107 ng/dl) 2 weeks after treatment initiation. She was initiated on propranolol and was followed up by plastic surgery and oncology. She had a very good response to Propranolol. Follow up MRI at 4 years shows almost complete resolution of the mass. She continues to be on Levothyroxine but is requiring smaller dose. Conclusion: Infantile hemangiomas can express high levels of type 3 iodothyronine deiodinase (D3), an enzyme that catalyzes the inner-ring deiodination of T4 to reverse T3 (rT3) and of T3 to 3,3'-diiiodothyronine (T2), both of which are biologically inactive. The hypothyroidism is a result of degeneration of thyroid hormones at rates that exceed the synthetic capacity of the infant's thyroid gland. Our case illustrates the importance of closely monitoring thyroid function tests in infants with large hemangiomas even if newborn thyroid screening result is normal. Some infants may require higher Levothyroxine doses than usual. Hypothyroidism usually resolves after resolution of the mass. Presentation: Thursday, June 15, 2023

SAT477 Consumptive Hypothyroidism In A Patient With Plasma Cell Neoplasm

Abstract Disclosure: G. Sidhu: None. I. Madahar: None. A. Haider: None. J. Giordano: None. Introduction: Thyroxine (T4) is converted into metabolically active form triiodothyronine (T3) by deiodinase enzyme 1 & 2 (D1 & D2). Deiodinase 3 converts T4 and T3 into metabolically inactive form reverse T3 (rT3)& di-iodothyronine (T2) . Consumptive hypothyroidism syndrome (CHS) is a very rare form of hypothyroidism seen in patients with neoplasms, which express high levels of D3 enzyme. Case: 68-year-old female withhistory of Multiple Myeloma (MM), POEMS, hyperlipidemia and hypothyroidism was admitted with acute kidney injury, cirrhosis of unclear etiology, large volume ascites and anasarca. She weighed 92 kg on admission. She was complaint with her 50 mcg of levothyroxine and on admission her TSH was 7.14 (N: 0.43-3.55 uIU/ml), Free T4 (FT4): <0.42 (N: 0.7-1.25 ng/dl), total T4 (TT4): 2.6 (N: 4.8-11.7 ug/dl), total T3 (TT3): <20 (N: 80-200 ng/dl). Oral LT4 was switched to IV form due to underlying concerns of malabsorption from anasarca. rT3 was noted to be 40 (N: 8-25 ng/dl). Despite escalated intravenous levothyroxine doses for seven days her FT4, FT3 continued to remain undetectable So her LT4 dose was increased to 75 mcg IV daily initially and eventually to 100 mcg IV daily and 125 mcg daily. On 10th day of hospitalization, after her IV LT4 dose was increased to 200 mcg daily, (almost 2.5 mcg/kg/day) her FT4 levels became detectable, 0.50, rT3: 68 and TT3: <20 and TT4: 3.1. Since her rT3 levels were noted to rise after increasing the dose of LT4, liothyronine (LT3) 5 mcg BID was added to her regimen. PET scan showed small sclerotic bone lesions suspicious for active malignancy. Chromogranin A was elevated 313 (N: <311 ng/ml). IR guided biopsy of scapular sclerotic lesion was done and specimen was sent University of Chicago to measure DI-3 activity in the specimen Pathology results were suggestive of plasma cell neoplasm but unfortunately deiodinase activity could not be quantified. Patient developed hepato-renal syndrome during hospitalization and her family decided to pursue hospice care. Discussion: Critical care illness thyroid disease is also associated with increased DI-3 activity and increases rT3, however T4 and TSH are also low in the setting of critical care illness, and most patient do not require supraphysiologic T4 replacements. The presence of D3 in normal tissues such as the brain & placenta has been hypothesized to protect tissues from the effects of excessive thyroid hormone. However, aberrant expression of the enzyme can lead to severe hypothyroidism from inactivation of both endogenously produced and exogenously administered thyroid hormone. Previously this rare syndrome was described in association with massive hemangiomas in children and in a single case of a hemangioendothelioma in an adult. However case reports in adults have been described in nonvascular tumors who required supraphysiologic doses of levothyroxine prior to the resection of a large malignant solitary fibrous tumor. Presentation Date: Saturday, June 17, 2023

Consumptive hypothyroidism in a patient with metastatic melanoma: A case report on a new association

Consumptive hypothyroidism in a patient with metastatic melanoma: A case report on a new association

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

The clinical consequences of primary hypothyroidism include cardiovascular morbidity, increased mortality, and poor quality of life; therefore guidelines endorsed by several Scientific Societies recommend measuring circulating thyroid-stimulating hormone (TSH) in patients at risk. The assessment of serum TSH levels is also deemed to be the most robust and accurate biomarker during the management of replacement therapy in patients with a previous diagnosis of primary hypothyroidism. In line with a reflex TSH laboratory strategy, free thyroxine is measured only if the TSH falls outside specific cutoffs, in order to streamline investigations and save unjustified costs. This serum TSH-based approach to both diagnosis and monitoring has been widely accepted by several national and local health services; nevertheless, false-negative or -positive testing may occur, leading to inappropriate management or treatment. This review aims to describe several infrequent causes of increased circulating TSH, including analytical interferences, resistance to TSH, consumptive hypothyroidism, and refractoriness to levothyroxine replacement treatment. We propose a clinical flowchart to aid correct recognition of these various conditions, which represent important potential pitfalls in the diagnosis and treatment of primary hypothyroidism.

Infantile hepatic hemangioendothelioma associated with pulmonary arterial hypertension and cardiac insufficiency successfully treated with oral propranolol—a rare case report

BackgroundInfantile hepatic hemangioendothelioma (IHHE) is a benign liver tumor associated with a varied spectrum of presentations ranging from asymptomatic hepatomegaly and cutaneous hemangiomas to some life-threatening complications like cardiac failure, consumptive hypothyroidism, pulmonary arterial hypertension, gastrointestinal bleeding, and coagulopathy. Hypothyroidism results from increased activity of type 3 iodothyronine deiodinase in the liver. Clinico-radiological correlation is essential for a definite diagnosis. Although children with asymptomatic lesions may experience spontaneous regression within a year, those with symptomatic lesions require aggressive management due to the risk of mortality once the symptoms commence. Treatment modalities can be either pharmacologic or interventional depending on the clinical presentation, with propranolol being considered the first-line agent.Case presentationHere, we describe a 2-month-old female infant with progressive abdominal distension, signs of congestive cardiac failure, and pulmonary arterial hypertension, confirmed as IHHE by abdominal ultrasonography and contrast-enhanced MRI. It was complicated by consumptive hypothyroidism and coagulopathy. The child was successfully treated with oral propranolol, levothyroxine, and supportive measures.ConclusionEarly aggressive treatment in a symptomatic patient is linked to successful outcomes. Hypothyroidism should be focused on and managed earlier to prevent intellectual and growth retardation.

Consumptive Hypothyroidism due to Hepatic Hemangiomas: A Case Series and Review of the Literature.

Here, we report a case series of 3 patients and a systematic review of the literature. Hypothyroidism (mean serum TSH 52.03 mIU/L) was detected at a mean age of 4.6 months (range 3-6) in 3 infants with infantile hepatic hemangiomas, treated with thyroxine (mean dose 12 µg/kg/day). All received treatment with propranolol (1-3 mg/kg/day) from the mean age of 4 months. Hormonal treatment was stopped at a mean age of 20 months (range 12-30). Hypothyroidism reoccurred in a patient concurrently with the increase of liver lesions, requiring liver transplantation (LT) at age 39 months.Literature review retrieved 42 studies (48 patients): HH (n = 43) were isolated in 24 infants and associated with cutaneous hemangiomas in 19. Hemangiomas were only cutaneous in 5.In the first 43 patients, hypothyroidism was detected at a mean age of 1 month; 21 of 43 patients were prescribed propranolol alone (n = 8) or associated with other medicaments (n = 13); 2 of 43 patients underwent LT. Hormonal treatment consisted of T4 in 35 of 43 patients and T3 in 10.CH associated with only cutaneous and extrahepatic visceral hemangiomas (n = 5), detected at a mean age of 7 months (TSH mean levels at diagnosis of 150.3 mIU/L). Three of 5 patients received treatment with propranolol ± other medicaments. All 5 patients were treated with T4. Periodical thyroid function assessment is necessary in patients with hepatic hemangiomas, particularly when lesions' size and number increase rapidly.

ODP478 Effects of peripheral iodothyronine deiodinases on thyroid hormone economy: Insights from the overexpressing mice

Abstract Background In peripheral tissues, triiodothyronine (T3) production and consequent thyroid hormone actions are mainly regulated by iodothyronine deiodinases (DIOs) classified into 3 types: D1, D2, and D3. Although thyroid hormone economy in the DIO-deficient mice and patients carrying genetic variants of DIOs was well clarified, a condition of DIOs upregulation was not enough elucidated. We aimed to investigate effects of peripheral DIOs on thyroid hormone economy and consequent thyroid hormone action using novel DIO-overexpressing mice that were not yet generated. Methods We cloned coding sequences of human DIOs with FLAG-tag and HiBiT-tag sequences into a pcDNA3.1 vector. To obtain full-length proteins, we modified these vectors by cloning selenocysteine insertion sequence of each DIO (SECIS vectors). Western blot analyses and HiBiT lytic assay using HEK293T cells revealed that SECIS vectors expressed full-length proteins with substantial activity. Subsequently, in vivo transfections of pLIVE-based SECIS vectors into male C57BL/6J mice were performed by hydrodynamic gene delivery to generate mice overexpressing DIOs (D1, D2, and D3 mice). Results First, we verified that DIOs were successfully overexpressed in the livers using HiBiT lytic assay as well as RT-PCR. Analyses of multiple organs of D3 mice assured that full-length protein was not significantly expressed in the heart, the kidney, and the skeletal muscle. RT-PCR analyses also suggested that the pituitary glands and the thyroid glands were not transfected. We evaluated thyroid hormone economy of DIO-overexpressing mice compared to Empty mice transfected with pLIVE-Empty vector. D1 mice did not have changes in serum thyroid hormone levels, whereas D2 mice had higher serum fT3 levels. Clearer changes were found in D3 mice. They had hypothyroidism with higher serum rT3 levels. Correspondingly, in their livers, rT3 concentration was higher and T3-responsive genes were downregulated. We elucidated by adding the cohort with levothyroxine (LT4) administration because DIO-overexpressing mice had liver T4 insufficiency probably due to consumption by DIOs. Comparisons between the DIO-overexpressing mice with and without LT4 administration revealed that D2 mice presented upregulation of T3-responsive genes by LT4 administration distinct from Empty mice. Conclusions We generated DIO-overexpressing mice that expressed human DIOs predominantly in the liver. They provided physiological evidence to integrate the phenotypes of the knockout mice and specific clinical situations. D2 mice seemed to recruit T3 into the circulation as well as in the liver. D3 mice had an overt phenotype characterized by consumptive hypothyroidism. In addition, D3 mice are expected to be a novel hypothyroidism model that does not involve disruption of thyroidal hormone secretion. DIO-overexpressing mice can be generated by single injections of plasmid vectors of interest and can contribute to progress in the field of thyroid hormone economy and action. Presentation: No date and time listed

Thyroid hormone economy in mice overexpressing iodothyronine deiodinases.

In peripheral tissues, triiodothyronine (T3) production and consequent thyroid hormone actions are mainly regulated by iodothyronine deiodinases (DIOs) classified into 3 types: D1, D2, and D3. We aimed to investigate the effects of peripheral DIOs on thyroid hormone economy independent of the hypothalamus-pituitary-thyroid axis. We cloned coding sequences of human DIOs with FLAG-tag and HiBiT-tag sequences into a pcDNA3.1 vector. To obtain full-length proteins, we modified these vectors by cloning the selenocysteine insertion sequence of each DIO (SECIS vectors). Western blot analyses and HiBiT lytic assay using HEK293T cells revealed that SECIS vectors expressed full-length proteins with substantial activity. Subsequently, in vivo transfections of pLIVE-based SECIS vectors into male C57BL/6J mice were performed by hydrodynamic gene delivery to generate mice overexpressing DIOs predominantly in the liver (D1, D2, and D3mice). After 7days from transfections, mice were analyzed to clarify phenotypes. To summarize, serum thyroid hormone levels did not change in D1mice but D2mice had higher serum free T3levels. D3mice developed hypothyroidism with higher serum reverse T3 (rT3) levels. Transfections with levothyroxine administration suggested that thyroid hormone action was upregulated in D2mice. Our DIO-overexpressing mice provided insights on the physiological properties of upregulated DIOs: D2 augments local thyroid hormone action and recruits T3 into the circulation: D3 decreases circulating T3 and T4levels with elevated rT3, leading to consumptive hypothyroidism. As D3mice are expected to be a novel hypothyroidism model, they can contribute to progress in the field of thyroid hormone economy and action.

Infantile hepatic hemangioma complicated consumptive hypothyroidism

Infantile hepatic hemangioma (IHH) is the most common benign liver tumor in infancy, some life-threatening complications like abdominal compartment syndrome, consumptive hypothyroidism and cardiac failure may occur in these patients. Hypothyroidism should be focused on and managed earlier to prevent intellectual and growth retardation. We described a 4 months old infant complaint of progressive abdominal distention, who was diagnosed with diffuse hepatic hemangiomas by ultrasonography and MRI, treated successfully with propranolol and levothyroxine for consumptive hypothyroidism. At 8 months old levothyroxine was stopped, she grew up with a normal growth trajectory and neurodevelopment at her last follow-up at the age of 13 months. Our study suggests that thyroid function should be evaluated even though negative neonatal screen and propranolol should be first-line agent for diffuse IHH. It is instrumental that simultaneous anti-tumor and thyroid replacement make diffuse IHH patients with consumptive hypothyroidism recovery better.

Consumptive Hypothyroidism: T3 or Not T3, That Is the Question

Consumptive hypothyroidism is often the clinical condition that results from neoplasms producing their own selenodionases that convert T4 needed to be converted to active T3 into an active form of thyroid hormone, rT3. This often requires treatment with high doses of IV T4, with or without doses of T3 as well, until the neoplasm is treated. This principle is demonstrated in the below case of a 65 y/o female with medical history significant for Ia Kappa multiple myeloma, complete heart block s/p AICD placement, and papillary thyroid cancer status post thyroidectomy in 2020, who had initially presented with persistent bone pain, progressive encephalopathy and failure to thrive with more than a 50 lb weight loss over a few months. Labs on presentation were not remarkable for progression of her underlying multiple myeloma, however, she was found to have a new significantly elevated TSH. She underwent imaging with a CT chest, abdomen, and pelvis, which showed new hepatic lesions, subcutaneous nodules, and new pulmonary nodules with associated lymphadenopathy and a left-sided pleural effusion. CT-guided liver biopsy evinced a metastatic neuroendocrine carcinoma, further supported by an elevated calcitonin and chromogranin. She was treated with high dose IV T4 at 1.38 mcg/kg however continued to worsening thyroid function labs. She was then started on Liothyronine at 20 mcg and subsequently improved. This patient’s case illustrates the importance of considering consumptive hypothyroidism when thyroid profile abnormalities and symptoms of severe hypothyroidism are seen in the context of malignant neoplasms, and further illustrates the important of considering T3 as part of the treatment regimen when IV T4 is not resulting in improvement.

Hemangioma-related syndromes.

There is a growing understanding of complications and anomalies associated with infantile hemangiomas. The current review will discuss recent clinical advances in syndromes associated with segmental hemangiomas, including PHACE and LUMBAR syndrome. In addition, the importance of recognizing visceral hemangiomatosis is highlighted. Ongoing longitudinal studies of PHACE and LUMBAR syndromes associated with segmental infantile hemangiomas have led to improved diagnosis and recommendations for screening for associated anomalies. Characterization of a growing spectrum of associated anomalies as well as better classification of at-risk patients will improve diagnosis and outcomes. In addition, visceral hemangiomatosis recognition and understanding of the potential association with consumptive hypothyroidism will improve initiation of appropriate screening. Clinicians should be aware of infantile hemangiomas associated with potential syndromic complications and recognize the need to initiate appropriate work-up. Segmental hemangiomas of the head and neck region may indicate a risk of PHACE syndrome and associated developmental anomalies. Although LUMBAR syndrome is the association of lower body segmental hemangioma with developmental anomalies. Visceral hemangiomas most commonly affect the liver and may be associated with complications such as consumptive hypothyroidism and heart failure.

Consumptive Hypothyroidism Due to Diffuse Hepatic Hemangiomas Treated With Propranolol Therapy

Infantile hepatic hemangioma (IHH)-related consumptive hypothyroidism is rare and occurs as a result of excess thyroid hormone inactivating enzyme, type-3 iodothyronine deiodinase. We present an infant with IHH-related hypothyroidism, in whom treatment with propranolol led to regression of tumor and subsequent euthyroid status.

Combination therapy of propranolol, levothyroxine, and liothyronine was effective in a case of severe consumptive hypothyroidism associated with infantile hepatic hemangioma.

.Infantile hepatic hemangioma (IHH) can be accompanied by consumptive hypothyroidism. We report the case of a 4-mo-old boy who showed massive hepatomegaly, peripheral coldness, lethargy, and failure to thrive. An enhanced computed tomography scans demonstrated multiple hemangiomas in both lobes of the liver, and a thyroid function tests showed severe hypothyroidism: TSH 561.5 µIU/mL, free triiodothyronine (fT3) 1.0 pg/mL, and free thyroxine (fT4) < 0.7 ng/dL. IHH gradually regressed following propranolol treatment and fT4 increased to a low normal level (1.0 ng/dL) by high dose replacement of levothyroxine, while fT3 remained very low (< 1.0 pg/mL), even following high doses of levothyroxine; fT3 eventually normalized following the administration of liothyronine. We suggest that treatment strategies should be individualized based on thyroid function, and that the combination therapy of propranolol for anti-tumor treatment and levothyroxine and liothyronine for respective thyroid hormone replacement is effective, particularly in cases of severe consumptive hypothyroidism due to multiple IHHs.

CONSUMPTIVE HYPOTHYROIDISM: AN UNUSUAL PARANEOPLASTIC MANIFESTATION OF A GASTRIC GASTROINTESTINAL STROMAL TUMOR

A 42-year-old hypothyroid shepherd presented with a progressive abdominal lump accompanied by nausea and abdominal fullness. In addition, he had worsening hypothyroidism, despite supranormal doses of thyroxine. Computed tomography of the abdomen was suggestive of a mass lesion in relation to the stomach. A resection of the mass was done and the histopathology was suggestive of gastrointestinal stromal tumor. After surgery, the patient became euthyroid. We believe the patient had consumptive hypothyroidism due to the tumor.

Liver haemangiomas and consumptive hypothyroidism in association with three cutaneous haemangiomas

Liver haemangiomas and consumptive hypothyroidism in association with three cutaneous haemangiomas

Consumptive hypothyroidism associated with hepatic hemangiomas

Consumptive hypothyroidism associated with hepatic hemangiomas

Hemangiomas and β-Blockers: On the Rebound.

* Abbreviations: IH — : infantile hemangioma OP — : oral propranolol Infantile hemangioma (IH) is the most common tumor of childhood, and although most lesions eventually involute, the proliferative phase may be associated with complications, such as ulceration, bleeding, functional compromise, and anatomic disfigurement. Rarely, IH can have major or life-threatening consequences, such as airway obstruction, high-output congestive heart failure, and consumptive hypothyroidism. It is for reasons such as these that therapy may be indicated. Propranolol, a nonselective β-adrenergic receptor antagonist, has been used off-label in children for years in the treatment of cardiac dysrhythmias, congestive heart failure, and hypertension. In 2008, Leaute-Labreze et al1 reported their discovery of its benefits against IH, an observation confirmed in their follow-up report of 32 infants 1 year later.2 Oral propranolol (OP) has evolved to become the standard of care for IH therapy. In 2014, a pediatric formulation was approved by the US Food and Drug Administration (March) and the European Medicines Agency (April).3,4 The results of the multicenter, randomized, double-blind, adaptive phase 2-3 trial assessing its efficacy and safety in treating IH were published in 2015.5 Although the precise mechanisms of … Address correspondence to Anthony J. Mancini, MD, Ann and Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Ave, Mailbox 107, Chicago, IL 60611. E-mail: amancini{at}northwestern.edu

Difuse Infantile Hemangiomatosis with Consumptive Hypothyroidism in an Infant: A Case Report

We report a case of a male newborn who was evaluated due to persistent jaundice. Evaluation showed hypothyroidism associated with infantile hemangioma of the liver. Euthyroidism and regression of the hepatic hemangiomas were obtained with L-thyroxin and Propranolol treatment. This case emphasizes the importance of screening for hypothyroidism in patients with neonatal hemangiomatosis.

Decade in review-thyroid disease: The endocrinology of thyroid disease from 2005 to 2015.

The past decade has seen exciting progress in the field of thyroid disease, especially in the evaluation of thyroid nodules, the genomic characterization of carcinomas and the treatment of carcinomas after surgery. An improved understanding of hyperthyroidism during pregnancy, as well as the causes of 'low T3 syndrome' and consumptive hypothyroidism have also been achieved.