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A 21-Year-Old Woman with Consumptive Hypothyroidism due to a Vascular Tumor Expressing Type 3 Iodothyronine Deiodinase

Division of Endocrinology (S.A.F., S.J.M.), Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104; Thyroid Division and Division of Endocrinology (P.R.L.) and Department of Pathology (D.M.D.), Brigham and Women’s Hospital, Boston, Massachusetts 02115; Department of Pathology (H.P.W.K.) and Division of Endocrinology (S.A.H.), Children’s Hospital Boston, Boston, Massachusetts 02115; and Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica (D.S.), Universita’degli Studi di Napoli "Federico II," 80138 Naples, Italy

Address all correspondence and requests for reprints to: Dr. P. Reed Larsen, Thyroid Division, Harvard Medical School, Room 560, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115. E-mail: rlarsen{at}rics.bwh.harvard.edu.

Abstract

We present a 21-yr-old female with a large hepatic vascular tumor and subclinical hypothyroidism. A high level of the thyroid hormone inactivating enzyme type 3 iodothyronine deiodinase (D3) was detected in her tumor, and the TSH of 26.2 mU/liter returned to normal after surgical resection of the mass. This indicates that the vascular tumor caused this adult’s hypothyroidism as has now been documented in nine infants with this syndrome. This first example of consumptive hypothyroidism in an adult indicates that the inactivation rate of thyroid hormone by D3 in a vascular tumor can stress the secretory capacity even of the TSH-stimulated normal adult thyroid gland.

INFANTILE HEPATIC AND cutaneous hemangiomas often express high levels of type 3 iodothyronine deiodinase (D3; Ref. 1). This selenoenzyme, normally present in human placenta and brain, catalyzes the inner-ring deiodination of T₄ to reverse T₃ (rT₃) and of T₃ to 3,3'-diiodothyronine (T₂), both of which are biologically inactive (2, 3). In infants with large hemangiomas, this tumoral D3 can cause a unique form of hypothyroidism due to the degradation of thyroid hormone at rates that exceed the synthetic capacity of the infant’s thyroid gland. We have termed this condition consumptive hypothyroidism (4). We report here similar pathophysiology in a young woman with subclinical primary hypothyroidism that was relieved by removal of a large D3-expressing tumor by liver transplantation. This confirms the pathophysiology of this syndrome and illustrates that the degradation rate of the thyroid hormones by the D3 expressed in these tumors can approach the synthetic capacity even of the TSH-stimulated normal human adult thyroid.

Subjects and Methods

Case report

A 21-yr-old female presented with abdominal fullness and constipation. Imaging studies confirmed a markedly enlarged liver measuring 27 cm in length. Liver biopsy was performed and revealed a vascular tumor interpreted as a hepatic hemangioendothelioma. Liver function tests at the time of diagnosis were mildly abnormal: total bilirubin, 0.7 mg/dl (normal, 0.0–1.2 mg/dl); alkaline phosphatase, 199 U/liter (normal, 35–125 U/liter); aspartate aminotransferase, 65 U/liter (normal, 14–36 U/liter); and alanine aminotransferase, 51 U/liter (normal, 9–52 U/liter). Because of the possibility of future malignant transformation, liver transplantation was recommended. During evaluation for a living- related liver transplant, the patient’s serum TSH was found to be elevated to 19.6 mU/liter (normal, 0.4–4.0). Only minimal cold intolerance was reported on review of systems, and the patient was otherwise well. Serial photography provided by the patient illustrated the onset of thyromegaly after the age of 17 yr. The past medical history was notable for a hepatic hemangioma in infancy that involuted after a course of oral prednisone. There was no family history of thyroid disease.

Notable on physical examination was a soft, diffusely enlarged, slightly tender thyroid without discrete nodules. There were no physical signs of hypothyroidism. Repeat thyroid function tests confirmed primary hypothyroidism: TSH, 26.2 mU/liter; total T₄, 95 nmol/liter (normal, 58–161 nmol/liter); total T₃, 1.8 nmol/liter (normal, 1.1–2.6 nmol/liter); T₃ resin uptake (RU), 0.89 (normal, 0.77–1.17); estimated free T₄ index, 85 nmol/liter. Antithyroid peroxidase and antithyroglobulin antibody levels were normal. In addition, the serum rT₃ concentration was increased to 2.72 nmol/liter (normal, 0.14–0.54 nmol/liter). A thyroid ultrasound revealed a diffusely enlarged (approximately 2-fold), heterogeneous, and hypervascular gland. The right and left lobes measured 2.5 x 2.3 x 4.3 cm and 2.2 x 1.7 x 4.2 cm, respectively. A tentative diagnosis of consumptive hypothyroidism due to D3 expression by her hepatic vascular tumor was made, and treatment was initiated with oral L-T₄, 88 µg daily.

Eight days later, a living-related donor liver transplant was performed without complication. The resected liver weighed 4.2 kg with diffuse involvement by a neoplastic vascular proliferation that showed an anastomosing network of narrow and ectatic blood-filled channels. The endothelial cells were one or two layers thick and had large nuclei with coarse chromatin, small nucleoli, and sparse clear cytoplasm. The endothelial cells were devoid of cytoplasmic vacuoles. Occasional mitoses were observed. One or two layers of plump pericytes were present. The intervascular stroma was characterized by myofibroblasts and abundant intercellular mucin. The tumoral growth was diffusely infiltrative with entrapment of normal hepatic tissue. Special stains were performed to confirm the cell types of the tumor, illustrating that the endothelial cells stained appropriately for CD31 and that the pericytes stained appropriately for smooth muscle actin. The endothelial cells were negative by immunostaining for glucose transporter-1 protein, unlike many hepatic hemangiomas in infancy that are positive. Although some observers believed the tumor in this patient to be an epithelioid hemangioendothelioma, others felt that it was not fully characteristic and that a diagnosis of hemangioendothelioma (not otherwise specified) seemed most appropriate (5, 6, 7, 8).

L-T₄ therapy was discontinued 6 wk after transplantation, and serum thyroid hormone concentrations obtained 2 wk later were normal: TSH, 2.4 mU/liter; T₄, 91 nmol/liter; T₃RU, 0.91; and rT3, 0.41 nmol/liter (Table 1). The patient was asymptomatic. Physical examination and a repeat ultrasound confirmed that the thyroid was now normal in size with normal vascularity and homogeneous echotexture (right lobe, 1.9 x 1.6 x 4.2 cm; left lobe, 1.8 x 1.6 x 4.1 cm). Endogenous thyroid function remained normal 7 months later.

Studies of human tissue were approved by the Investigative Review Board of the Hospital of the University of Pennsylvania and the Brigham and Women’s Hospital. Term placental tissue from a woman with no known medical problems was used as a control. Portions of the patient’s tumor and control tissue were snap-frozen in liquid nitrogen and homogenized in approximately five volumes of 0.25 M sucrose, 10 mM dithiothreitol in phosphate EDTA buffer (pH 6.9) and assayed for D3 activity as described previously (1). After incubation at 37 C for 60 min, reactions were stopped by the addition of ice-cold methanol and centrifuged. The resultant supernatant was mixed with an equal volume of 0.02 M ammonium acetate (pH 4) and the fraction of ¹²⁵I as [¹²⁵I]T₂ was determined by HPLC as described by Richard et al. (9). The relative radioactivity of each iodothyronine peak was measured using a Radiomatic 500TR Flow Scintillation Analyzer (Packard Instrument Company, Meriden, CT).

Immunohistochemistry

Primary D3 antibodies were prepared in rabbits using two peptides deduced from the hdio3 sequence. Two polyclonal rabbit antibodies, D3–17 and D3–18, were generated against peptide sequences corresponding to amino acids 264 to 278 (ERYDEQLHGARPRRV) and amino acids 53 to 68 (KPEPEVELNSEGEEVP), respectively, of human D3. Both synthetic peptides, commissioned from Neosystem S.A. (Strasbourg, France), were coupled to BSA via m-maleimidobenzoyl-N-hydroxysuccimide ester and injected into New Zealand rabbits. Identical peptides were coupled to ovalbumin via succininidil 4-N-maleimidomethylcyclohexane-1carboxylate and thereafter coupled to an Affi-Gel 10 column (Pierce Chemical Co., Rockford, IL; Ref. 10). The bound antibodies were eluted, dialyzed, and used in the present study. Western blotting of lysates of HEK 293 cells transiently expressing the human D3 coding region revealed a single, appropriately sized band of 32 kDa, corresponding to the D3 protein.

Sections (4 µm) were cut from formalin-fixed, paraffin-embedded tissue blocks and microwaved at 93 C in 10 mM citrate buffer for antigen retrieval. Sections were incubated with primary D3 antibody at 1:100 dilution and then processed with a Vectastain Elite ABC immunoperoxidase kit (Vector Laboratories, Inc., Burlingame, CA). CD31 antibodies (DAKO Corp., Carpinteria, CA) were used at 1:60 dilution after microwave antigen retrieval in citrate buffer. Smooth muscle actin antibodies (Sigma; Immunochemicals, St. Louis, MO) were used at 1:10 dilution. Glucose transporter-1 antibodies (DAKO Corp., Carpinteria, CA) were used at 1:200 dilution. 3,3'-Diaminobenzidine chromagen was used to localize peroxidase activity, and slides were counterstained with 1% Gill’s hematoxylin.

Results

The patient’s tumor expressed D3 activity, confirmed by insensitivity of inner-ring deiodination to inhibition by 6n-propylthiouracil and a characteristic Michaelis constant (K_m) for T₃. The V_max was 3-fold that of term placenta, the normal human tissue with the highest D3 activity (Fig. 1).

View larger version (13K): [in this window] [in a new window]   Figure 1. Lineweaver-Burk analysis of the inner ring deiodination of T3 by the patient’s hepatic tumor tissue. Term placental tissue is included as a positive control.

View larger version (180K): [in this window] [in a new window]   Figure 2. Immunoperoxidase staining of the hepatic tissue. A and C, Low (x100) and high (x200) power hematoxylin and eosin staining of liver and tumor. B and D, Low and high power of D3 antibody staining. E, High power of CD31 antibody staining. F, High power of smooth muscle actin antibody staining. Hematoxylin and eosin staining illustrates the highly vascular nature of the tumor. In A and B, the vascular tumor is present in the top of the panel, and primarily uninvolved hepatic tissue is present on the bottom. In E and F, endothelial cells and perivascular cells (pericytes) are stained by CD31 antibodies and smooth muscle actin antibodies, respectively. D3 immunostaining is specific for the tumor tissue with localization to both endothelial cells and pericytes.

This patient presented with subclinical hypothyroidism manifested by thyroid enlargement, a serum TSH concentration of 26.2 mU/liter, and a normal serum free T₄ index. Despite the normal free T₄ index and total T₃ in the serum, serum rT₃ was 5-fold increased in the absence of significant illness or liver failure. The goiter, thyroid hypervascularity, marked hyperthyrotropinemia, and serum rT₃ elevation all resolved or normalized after removal of the liver (Table 1). Histological examination revealed diffuse involvement with a hemangioendothelioma with D3 activity three times that in term human placenta. Immunoperoxidase staining localized D3 to the endothelial cells and pericytes of the tumor. This clinical course confirms a diagnosis of consumptive hypothyroidism similar to that reported in infants with hepatic hemangiomas.

This is the first adult patient identified with this condition. Since the original report of consumptive hypothyroidism due to high D3 expression in an infant with a large hepatic hemangioma, eight others with acquired hypothyroidism during the proliferative phase of hemangioma growth have been reported to us (personal communication). Three groups have published reports of additional affected children, describing in some patients supernormal requirements for exogenous thyroid hormone and the complete resolution of hypothyroidism after hemangioma involution (1, 11, 12, 13). Using the criteria of hyperthyrotropinemia and hypothyroxinemia during hemangioma growth, a total of nine such patients are identified in the published literature (Table 2; Refs. 1, 11, 12, 13). Other investigators have not tested these tumors for D3 expression, but our prospective analysis of discarded surgical specimens has documented D3 activity in all but one hemangioma sample collected from 11 children under the age of 12 months. The tumoral D3 expression in these vascular lesions together with the disappearance of hypothyroidism after hemangioma involution support the concept that this endocrinopathy is due to an excessive degradation rate of thyroid hormone relative to the functional reserve of the infant thyroid. Two of the eight patients described by Ayling et al. (13) were noted to have hyperthyrotropinemia together with high serum T₄ concentrations. They raised the possibility that some hemangiomas may secrete a TSH-like factor. Although this may be the case, it cannot explain the hypothyroxinemia described in the hypothyroid patients they reported or in the others listed in Table 2.

This is the first adult patient identified with consumptive hypothyroidism, illustrating that this pathophysiology extends beyond infants with hemangiomas. Because the quantity of thyroid hormone degraded by a D3-expressing tumor is a product of the cellular D3 activity and tumor mass, only individuals with large tumor burden are at risk for developing hypothyroidism unless there is also independent pathology of the thyroid. Thyroid function should be monitored in patients with large proliferating vascular lesions, and it has become our practice to obtain monthly TSH measurements in infants with large hepatic hemangiomas through the first year of life. In summary, clinicians should maintain a high index of suspicion for consumptive hypothyroidism in both children and adults with large vascular tumors. If hypothyroidism is identified, higher than normal doses of L-T₄ may be required for normalization of thyroid function until the tumor involutes or is resected.

Acknowledgments

Footnotes

This work was supported by Grants DK07529-16 and DK44128 from the National Institutes of Health; the Lawson Wilkins Abbott Clinical Scholar Award from the Lawson Wilkins Pediatric Endocrine Society; the Charles A. King Trust Postdoctoral Research Fellowship Award from the Medical Foundation (Boston, MA); the Charles A. Janeway Child Health Research Center Award from the Child Health Research Center, Children’s Hospital (Boston, MA); the Doris Duke Clinical Scientist Development Award from Doris Duke Charitable Foundation; and grants from the Chester County Community Foundation: Patricia C. and John Celii Jr. Foundation.

S.A.H. and S.A.F. are sharing first authorship.

Abbreviations: D3, Type 3 iodothyronine deiodinase; rT₃, reverse T₃; RU, resin uptake; T₂, 3,3'-diiodothyronine.

Received April 23, 2002.

Accepted July 10, 2002.

References

1. Huang SA, Tu HM, Harney JW, Venihaki M, Butte AJ, Kozakewich HP, Fishman SJ, Larsen PR 2000 Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med 343:185–189[Free Full Text]
2. Salvatore D, Low SC, Berry M, Maia AL, Harney JW, Croteau W, St Germain DL, Larsen PR 1995 Type 3 iodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme. J Clin Invest 96:2421–2430
3. Koopdonk-Kool JM, de Vijlder JJ, Veenboer GJ, Ris-Stalpers C, Kok JH, Vulsma T, Boer K, Visser TJ 1996 Type II and type III deiodinase activity in human placenta as a function of gestational age. J Clin Endocrinol Metab 81:2154–2158[Abstract]
4. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR 2002 Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 23:38–89[Abstract/Free Full Text]
5. Uchimura K, Nakamuta M, Osoegawa M, Takeaki S, Nishi H, Iwamoto H, Enjoji M, Nawata H 2001 Hepatic epithelioid hemangioendothelioma. J Clin Gastroenterol 32:431–434[CrossRef][Medline]
6. Weiss SW, Enzinger FM 1982 Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma. Cancer 50:970–981[CrossRef][Medline]
7. Makhlouf HR, Ishak KG, Goodman ZD 1999 Epithelioid hemangioendothelioma of the liver: a clinicopathologic study of 137 cases. Cancer 85:562–582[CrossRef][Medline]
8. Lauffer JM, Zimmermann A, Krahenbuhl L, Triller J, Baer HU 1996 Epithelioid hemangioendothelioma of the liver. A rare hepatic tumor. Cancer 78:2318–2327[CrossRef][Medline]
9. Richard K, Hume R, Kaptein E, Sanders JP, van Toor H, De Herder WW, den Hollander JC, Krenning EP, Visser TJ 1998 Ontogeny of iodothyronine deiodinases in human liver. J Clin Endocrinol Metab 83:2868–2874[Abstract/Free Full Text]
10. Bangalore L, Tanner AJ, Laudano AP, Stern DF 1992 Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor. Proc Natl Acad Sci USA 89:11637–11641[Abstract/Free Full Text]
11. Bramswig J, Werner C, von Lengerke HJ, Micke O, Hesselmann S, Successful treatment of severe hypothyroidism in infantile hepatic hemangioma. 6th Joint Meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology in collaboration with the Australasian Paediatric Endocrine Group, Japanese Society for Pediatric Endocrinology, and Latin-American Society of Paediatric Endocrinology, Montreal, Canada, 2001; Abstract PL-927
12. Konrad D, Ellis G, Perlman K Spontaneous regression of severe acquired infantile hypothyroidism associated with multiple liver hemangiomas. 6th Joint Meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology in collaboration with Australasian Paediatric Endocrine Group, Japanese Society for Pediatric Endocrinology, and Latin-American Society of Paediatric Endocrinology, Montreal, Canada, 2001; Abstract PL-928
13. Ayling RM, Davenport M, Hadzic N, Metcalfe R, Buchanan CR, Howard ER, Mieli-Vergani G 2001 Hepatic hemangioendothelioma associated with production of humoral thyrotropin-like factor. J Pediatr 138:932–935[CrossRef][Medline]
14. Thein-Wai W, Larsen PR 1980 Effects of weekly thyroxine administration on serum thyroxine, 3, 5, 3'-triiodothyronine, thyrotropin, and the thyrotropin response to thyrotropin-releasing hormone. J Clin Endocrinol Metab 50:560–564[Abstract/Free Full Text]
15. Wynne AG, Gharib H, Scheithauer BW, Davis DH, Freeman SL, Horvath E 1992 Hyperthyroidism due to inappropriate secretion of thyrotropin in 10 patients. Am J Med 92:15–24[CrossRef][Medline]
16. Losa M, Giovanelli M, Persani L, Mortini P, Faglia G, Beck-Peccoz P 1996 Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 81:3084–3090[Abstract/Free Full Text]

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