|Year : 2017 | Volume
| Issue : 1 | Page : 19-24
Radioactive iodine-131 as a definitive treatment in rare association of down syndrome with hyperthyroidism: A case report and review of literature
Shoukat H Khan, Aditya Mahajan, Tanveer A Rather
Department of Nuclear Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
|Date of Web Publication||17-Jan-2017|
Shoukat H Khan
Department of Nuclear Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Down syndrome characterized by trisomy of chromosome 21 is frequently associated with thyroid dysfunctions due to underlying autoimmune disorders. Hypothyroidism is the commonest thyroid dysfunction and hyperthyroidism, usually Graves' disease, is far less common. On literature review, we came across approximately 112 cases reported so far with the first such case report in 1946. The published data from India on hyperthyroidism in Down syndrome is of three case reports. We report one such patient, an adult male of 28 years who was administered Iodine-131 as a definitive treatment after 9-10 years of initial diagnosis.
Keywords: Down syndrome, hyperthyroidism, iodine-131
|How to cite this article:|
Khan SH, Mahajan A, Rather TA. Radioactive iodine-131 as a definitive treatment in rare association of down syndrome with hyperthyroidism: A case report and review of literature. Indian J Nucl Med 2017;32:19-24
|How to cite this URL:|
Khan SH, Mahajan A, Rather TA. Radioactive iodine-131 as a definitive treatment in rare association of down syndrome with hyperthyroidism: A case report and review of literature. Indian J Nucl Med [serial online] 2017 [cited 2019 Dec 7];32:19-24. Available from: http://www.ijnm.in/text.asp?2017/32/1/19/198458
| Introduction|| |
Down syndrome (DS) described by John Langdon Down, a British physician in 1866, is characterized by the common chromosomal disorder of trisomy at chromosome 21 with mental deficiency of varying grades in addition to other ailments and abnormalities. The reported incidence of DS from various countries varies from 1/449 to 2/700 of live births and hypothyroidism in DS due to autoimmune thyroid disease is the commonest thyroid dysfunction having reportedly a high approximate prevalence of 50%., Hyperthyroidism mostly Graves' disease in DS is less common with a prevalence of less than 3%. The first such case was published in 1946 by Gilchrist.
The reported worldwide literature on hyperthyroidism in DS is that of about 112 sporadic cases with only three to four cases from India. We describe one such case in an adult male of DS with hyperthyroidism (Graves' disease) who was administered oral Iodine-131 as a definitive treatment.
| Case Report|| |
A 28-year-old adult male of DS with hyperthyroidism was referred to our department for Iodine-131 treatment. History of the patient revealed that at 19 years of age this patient of DS had complaints of increased frequency of stools, heat intolerance, and increased sweating. On the basis of his clinical profile and laboratory investigations, he was diagnosed with associated hyperthyroidism. He was prescribed antithyroid drug carbimazole and continued to be on endocrinology follow-up for 9 years. The clinical records of the patient confirmed an irregular compliance to antithyroid medication and repeated relapses of hyperthyroidism. At presentation in our department, the patient was conscious, cooperative, and well-oriented in time, space, and person. His height was 157 cm and he weighed 63 kg. He had a chubby appearance with slanted eyes and a short neck. His extremities were short. The nasal bridge was undeveloped. He did not have any tremors and the skin over the palms was dry and warm. He had normal blood pressure with a regular good volume radial pulse of 72 beats/min. On neck examination, there was no visible swelling; however, on palpation the thyroid gland was found to be diffusely enlarged with firm consistence and moving freely on deglutition. There was no bruit over the gland and the margins were well-delineated. There was no lymph node enlargement in the neck. The systemic clinical examination and echocardiography were normal. Prior to scheduling the patient for Iodine-131 treatment a laboratory workup was advised after stopping the antithyroid drug carbimazole for 5 days. During this period he was prescribed oral β-blocker propranolol in divided doses. The thyroid function tests revealed tri-iodothyronine [T3] of 2.7 ng/mL [ref range 0.70-2.50], tetra-iodothyronine [T4] of 14.99 µg/dL [ref range 4.00-13.00] and thyroid stimulating hormone (TSH) of 0.06 µIU/mL [ref range 0.50-6.5]. A Technetium 99m pertechnetate thyroid scan done after 15 minutes of 5 mCi intravenous injection revealed diffusely enlarged thyroid gland with uniformly intense tracer uptake. The 99m Technetium pertechnetate uptake was elevated at 53% [normal range 0.4-6%]. Scan appearance and uptakes were reported as consistent with Graves' disease [Figure 1].
A subsequent 2 and 24 hours Iodine-131 thyroid uptake after oral administration of 25 µCi of Iodine-131 was elevated at 29.3 and 67.4%, respectively. His thyroglobulin and antithyroid peroxidase levels were elevated at 472 ng/mL [ref range 0.00-37] and 702 IU/mL [ref range 0.0-9.0], respectively. Chromosomal karyotyping confirmed 46, XY, der [21; 21] [q10; q10], +21 DS [Figure 2].
The patient was administered a fixed oral dose of 10 mCi [370 MBq] of Iodine-131 on an empty stomach. Two months later his T3 level normalized to 0.86 ng/mL, T4 to 7.61 µg/dL TSH was 0.09 µIU/mL. However, at 4 months after Iodine-131 treatment patient became hypothyroid with a TSH level greater than 100 µIU/mL. He was prescribed a daily substitution dose of 125 μg of oral thyroxine. On his last follow-up at 9 months after Iodine-131 treatment he is relieved of his thyrotoxic symptoms with a weight gain of 8 kg and normalized thyroid hormone levels of T3, T4, and TSH at 1.13 ng/mL, 12.81 µg/dL, 0.50 µIU/mL, respectively.
| Discussion and Review of Literature|| |
Hypothyroidism of autoimmune etiology is the commonest thyroid dysfunction in DS. Prevalence of hyperthyroidism in DS is reportedly far less. The incidence of thyroid dysfunction in DS increases from 0.7% in infants to 12% by adulthood. Neonatal screening program for detecting congenital hypothyroidism has greatly improved the detection of hypothyroidism including the one associated with DS, which otherwise have considerable overlap of signs and symptoms. Association of hyperthyroidism with DS though reportedly under 3% has relatively a higher prevalence among DS than the general population. On bibliographic review approximately 112 patients of DS with hyperthyroidism are documented with the two recently published large series of 28 and 12 patients from Italy and Spain, respectively., In the majority of these patients the diagnosis was made in childhood and the patients appear to have almost equal gender distribution. Autoimmune Graves' disease is the etiology in most of the reported cases. Published literature from India is scanty and documents only four cases including this case report of hyperthyroidism in DS.,, In a published Indian study of 300 children with DS from 2004 to 2014, 82 patients were found to have abnormal thyroid hormone profiles with 76 patients having subclinical hypothyroidism and the rest overt hypothyroidism. No patient in this review study was found to have hyperthyroidism. From the limited data available from India it appears that the patients of DS with hyperthyroidism from India are younger and do not show any gender predilection.,, This observation is consistent with that of the largest published Italian and Spanish series. Considering the 1/449 to 2/700 incidence of DS among the live births the total burden of DS with thyroid dysfunction including hyperthyroidism is likely to be higher in India. Less documentation could be attributed to under diagnosis due to limited access to health care in the remote areas. Overlapping symptoms and social dimensions of DS also complicate the documentation of thyroid dysfunctions in DS. The available literature review of treatment preference in 57 cases of hyperthyroidism associated with DS shows conflicting results. In the largest multi-institutional Italian study based on 28 patients of DS with Graves' disease, no patient required nonpharmacological treatment like Iodine-131 or surgery during the follow-up period of 4.0 ± 2.8 years after the first cycle of methimazole was continued for an average period of 2.8 ± 1.6 years. On the contrary, in the earlier Spanish study based on 12 patients of DS with Graves' disease all the patients' eventually required definitive treatment with Iodine-131 due to shorter remissions on carbimazole. On overall review of 58 cases with available treatment details, Iodine-131 was administered as a definitive treatment in only 16 [27.58%] patients
[Table 1] and [Table 2]. In view of the mental profile of patients with DS, the presumable reluctance in using Iodine-131 as a definitive treatment for reasons of patient cooperation and related issues of radiation safety are understandable. Arguably an upfront (mostly onetime) Iodine-131 therapy seems to be a better option for such patients likely to have issues related to compliance and frequent relapses on long-term medication with conventional antithyroid pharmacological drugs. Iodine-131 treatment doses for hyperthyroidism particularly for patients with special needs like DS is available in capsule packages, which are very convenient to swallow on an outpatient protocol. The patient described in this case report was referred to our department after a long period of noncompliant treatment and repeated relapses on antithyroid drug carbimazole. During the period that he was on antithyroid drug carbimazole, he continued to have toxic symptoms of various grades for reasons of noncompliance and shorter remission periods of 3–4 months after withdrawal. In the reported Spanish series of 12 patients, no patient achieved remission longer than 6 months after carbimazole withdrawal and eventually all such patients who relapsed were given Iodine-131. In the long run, Iodine-131 treatment works out more convenient and economical. Over a period of 6-12 weeks post Iodine-131 oral administration our patient was relieved of all his thyrotoxic symptoms and his thyroid function parameters were within normal limits. Expectedly, he developed a mild form of post Iodine-131 hypothyroidism, which was easily managed with oral thyroxine.
|Table 1: Down syndrome associated with hyperthyroidism (review of literature, 1946–1986)|
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|Table 2: Down syndrome associated with hyperthyroidism (review of literature, 1987 - 2016)|
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Functional disorders of thyroid gland are relatively more common in patients of DS and as such screening of all such neonates with standard thyroid function tests at birth and subsequently till the adulthood must be incorporated in the standard management protocol. Hyperthyroidism associated with DS can be managed conveniently and definitively by an early administration of radioactive Iodine-131. India needs to compile a comprehensive database for DS including the thyroid function among such patients. This would be possible through a well-coordinated multi-institutional effort under the auspices of a national health care program. Based on the observations, a strategy for early diagnosis and treatment of associated thyroid dysfunctions in DS can be formulated to reduce the scale and duration of morbidity in such patients.
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Conflicts of interest
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| References|| |
Prasher VP. Down syndrome and thyroid disorders: A review. Down Syndr Res Pract 1999;6:25-42.
Dias VM, Nunes JC, Araujo SS, Goulart EA. Etiological assessment of hyperthyrotropinemia in children and adults with Down syndrome. J Pediatr (Rio J) 2005;81:79-84.
Zori RT, Schatz DA, Oster H, Williams CA, Spillar R, Riley WJ. Relationship of autoimmunity to thyroid dysfunction in children and adults with Down syndrome. Am J Med Genet 1990;7:238-41.
Fort P, Lifshitz F, Beelisario R, Davis J, Lanes R, Rughese M, et al.
Abnormalities of thyroid function in infants with Down syndrome. J Pediatr 1984;14:545-9.
Gilchrist L. Thyrotoxicosis in a mongol. Br Med J 1946;1:237-8.
Coleman M. Thyroid dysfunction in Down's syndrome: A review. Down Syndr Res Pract 1994;2:112-5.
De Luca F, Corrias A, Salerno M, Wasniewska M, Gastaldi R, Cassio A, et al.
Peculiarities of Graves' disease in children and adolescents with Down syndrome. Eur J Endocrinol 2010;162:591-5.
Ahluwalia AI, Nrayan S. Graves' disease in an eight year old boy of Down syndrome. Indian Pediatr 2005;42:76-7.
Sridhar GR, Nagamani G. Hyperthyroidism in a girl with Down's syndrome. J Pediatr Endocrinol Metab 1997;10:533-4.
Bhat MH, Saba S, Ahmad I, Kamili MMA, Khan SH. Graves' disease in Down's syndrome patient. J Pediatr Endocrinol Metab 2010;23:1181-3.
Dayal D, Jain P, Panigarhi I, Bhattacharya A, Sachdeva N. Thyroid dysfunction in Indian children with Down syndrome. Indian Pediatr 2014;51:751-2.
Goday Arno A, Cerda Esteva M, Flores Le Roux JA, Chillaron Jordan JJ, Corretger JM, Cano Perez JF. Hyperthroidism in a population with Down Syndrome. Clin Endocrinol 2009;71:110-4.
Baxter RG, Larkins RG, Martin FIR, Heyma P, Myles K, Ryan L. Down syndrome and thyroid function in adults. Lancet 1975;2:794-6.
McCuloch AJ, Clark F, Steele NR. Graves' disease and Downs' syndrome. J Med Genet 1983;20:133-4.
Cutler AT, Benezara-Obeiter R, Brink SJ. Thyroid function in young children with Down syndrome. Am J Dis Child 1986;140:479-83.
Bhowmick SK, Grubb PH. Management of multiple antibody mediated hyperthyroidism in children with Down's syndrome. Southern Med J 1997;90:312-5.
Sanj J. Down syndrome and hyperthyroidism. Report of three cases. Rev Med Chile 1999;127:967-9.
Soriano Guillen L, Munoz Calvo MT, Pozo Roman J, Perez JM, Rodrigo AB, Oliver JA. Graves' disease in patients with Down syndrome. Anal Pediatr (Barcelona) 2003;58:63-6.
Mc Girr EM, Murray IPC. Thyrotoxicosis in a Mongol. J Clin Endocrinol 1956;16:160-3.
Sahin M, Tutuncu NB, Kanbay M, Guvener ND. Surgery of hyperthyroidism in Down syndrome: Case report. Mt Sinai J Med 2006;73:791-3.
Esen FM, Mautner H. Hypo and hyperthroidism in mongolism. Arch Pediatr 1957;74:291-302.
Dupuy FI, Madrigal RG. Hipertiroidismo en un mongol. Archivos Del Hospital Universitario 1957;9:389-95.
Diggle JH, Weetch RS. Thyrotoxicosis in a Mongol. Proc R Soc Med 1958;51:293-4.
Nickey LN. Thyrotoxicosis in a Mongol child. Am J Dis Child 1960;99:680-3.
Abrahamsen AM. Thyrotoxicosis in two adult mongols. Acta Endocrinol 1961;37:135-7.
Johnson JE, Cook AR. Hyperthyroidism in patients with mongolism. J Clin Endocrinol 1962;22:665-8.
Timbury GC, McGuire RJ, MacGillivary RC. The effect of antithyroid treatment on the mental functioning of thyrotoxic mongol. Am J Mental Defic 1963;67:822-6.
Kay CJ, Esselborn VM. Hyperthyroidism and mongolism. Am J Dis Child 1963;106:411-4.
Hayles AB, Hinrich WL, Tauxe WN. Thyroid disease among children with Down's syndrome (mongolism). Pediatrics 1965;36:608-14.
Ansari AH, Schneeberg NG. Thyrotoxicosis in a mongol. Can Med Assoc J 1967;96:425-7.
Subrt I, Blehora B, Kucera J. Aberrant chromosome 13-15 in a patient of Down's syndrome, diabetes mellitus and hyperthyroidism and his father. Acta Genet Stat Med 1968;18:38.
Aarskog D. Autoimmune thyroid disease in children with mongolism. Arch Dis Child 1969;44:454-60.
Hollingsworth DR, McKean HE, Rockel I. Goiter, immunological observations, and thyroid function tests in Down syndrome. Am J Dis Child 1974;127:524-7.
Azizi F, Chandler H, Bozorgzadeh H, Baverman LE. The occurrence of hyperthyroidism in patients with Down's syndrome. Hopkins Med J 1974;134:303-6.
Murdoch JC, Ratchiffe WA, Mclarty DG, Rodger JC, Ratchiffe JG. Thyroid functions in adults with Down's syndrome. J Clin Endocrinol 1977;44:452-3.
Morton DA, Jenkins ME. Down's syndrome and thyroid dysfunction. J Natl Med Assoc 1978;70:27-9.
Takahashi H, Bordy MD, Sharma V, Grunt JA. Hyperthyroidism in patients with Down's syndrome. Clin Paediatr 1979;18:273-5.
Loudon MM, Day RE, Duke EM. Thyroid dysfunction in Down's syndrome. Arch Dis Child 1985;60:1149-51.
Nibhanupudhy JR, Streeter OE, King GC, Mahan J, Talley G, Lander C, et al.
Treatment of Down's syndrome patient for hyperthyroidism with radioactive iodine. J Natl Med Assoc 1986;78:139-43.
Blumberg D, Ruskin T. Down's syndrome autoimmune hyperthyroidism, and hypoparathyroidism: A unique triad. Am J Dis Child 1987;141:1149.
Dinani S, Carpenter S. Down's syndrome and thyroid disorder. J Mental Defic Res 1990;34:187-93.
Pozzan GB, Rigon F, Girelli ME, Rubello D, Busnardo B, Baccichetti C. Thyroid dysfunction in patients with Down syndrome. Preliminary results from non-institutionalized patients in the Veneto region. Am J Med Genet (Suppl 1) 1990;7:57-8.
Pueschel SM, Jackson IMD, Giesswan P, Dean MK, Pezzullo JC. Thyroid function in Down syndrome. Res Dev Disabil 1991;12:287-96.
Colombo ML, Bona G, Quaglia P, Zaffroni M, Mania D, Luotti D. La funzionalita tiroidea in bambini affetia da sindromi di Down. Minerva Pediatrica 1992;44:11-6.
Tambyah PA, Cheah JS. Hyperthyroidism in Down syndrome. Ann Acad Med 1993;22:603-5.
Crespo Cuadrado E, Azcona San Julian C, Castro Paz L, Diaz-Tejeiro P, Rodriguez Javier S. Sierrasesumaga Ariznabarreta L, Autiommune hypothyroidism and celiac disease in a girl with Down's syndrome. Rev Esp Pediatr 1996;52:485-8.
Karlsson B, Gustafsson J, Hedov G, Ivarsson SA, Anneren G. Thyroid dysfunction in Down's syndrome;relation to age and thyroid autoimmunity. Arch Dis Child 1998;79:242-5.
Castero Lobera A, Linares Garcia Valdecasas R. Estudio de la function tiroidea on personas con Sindrome de Down. Atencio Primana 1999;23:87-90.
Ali FE, Al-Busairi WA, Al-Mulla FA. Treatment of hyperthyroidism in Down syndrome: Case report and review of literature. Res Dev Disabil 1999;20:297-3.
Gruneiro de Pappendieck L, Chiesa A, Bastida MG, Alonso G, Finkielstain G, Heinrich JJ. Thyroid dysfunction and high thyroid stimulating hormone levels in children with Down's syndrome. J Paediatr Endocrinol Metab 2002;15:1543-8.
Chemli J, Braham N, Boughattas S, Harbi A. Basedow's disease and celiac disease in adolescent with Down syndrome. La Revue de Medecine Interne 2006;27:791-3.
[Figure 1], [Figure 2]
[Table 1], [Table 2]