000			05144nam a22007097a 4500
008			200709s20202020 xxu||||| |||| 00| 0 eng d
022			_a2574-3805
024			_a10.1001/jamanetworkopen.2020.1357 [doi]
024			_a2763227 [pii]
024			_aPMC7090965 [pmc]
040			_aOvid MEDLINE(R)
099			_a32202644
245			_aAssessment of Thyroid Function in Patients With Alkaptonuria.
251			_aJAMA Network Open. 3(3):e201357, 2020 03 02.
252			_aJAMA netw. open. 3(3):e201357, 2020 03 02.
252			_zJAMA netw. open. 3(3):e201357, 2020 Mar 02.
253			_aJAMA network open
260			_c2020
260			_fFY2020
265			_sepublish
266			_d2020-07-09
268			_aJAMA Network Open. 3(3):e201357, 2020 Mar 02.
520			_aConclusions and Relevance: The high prevalence of primary hypothyroidism noted in patients with alkaptonuria in this study suggests that serial screening in this population should be considered and prioritized.
520			_aDesign, Setting, and Participants: A single-center cohort study was conducted in a tertiary referral center including patients with alkaptonuria followed up for a median of 93 (interquartile range, 48-150) months between February 1, 2000, and December 31, 2018. The alkaptonuria diagnosis was based on clinical presentation and elevated urine HGA levels. A total of 130 patients were considered for participation.
520			_aImportance: Alkaptonuria is an autosomal recessive disorder caused by pathogenic variants in the HGD gene. Deficiency of the HGD enzyme leads to tissue deposition of homogentisic acid (HGA), causing severe osteoarthropathies and cardiac valve degeneration. Although HGD is vital for the catabolism of tyrosine, which provides the basis for thyroid hormone synthesis, the prevalence of thyroid dysfunction in alkaptonuria is unknown.
520			_aMain Outcomes and Measures: Prevalence of thyroid dysfunction in adults with alkaptonuria compared with the general population. Thyrotropin and free thyroxine levels were measured by immunoassay and repeated in each patient a median of 3 (interquartile range, 2-22) times. Neck ultrasonographic scans were analyzed in a subset of participants. Logistic regression was used to test the association of thyroid dysfunction with age, sex, thyroid peroxidase (TPO) antibodies, serum tyrosine levels, and urine HGA levels.
520			_aObjective: To assess thyroid structure and function in patients with alkaptonuria.
520			_aResults: Of the 130 patients, 5 were excluded owing to thyroidectomy as the cause of hypothyroidism. The study cohort consisted of 125 patients; the median age was 45 (interquartile range, 35-51) years. Most of the patients were men (72 [57.6%]). The prevalence of primary hyperthyroidism was 0.8% (1 of 125 patients), similar to 0.5% observed in the general population (difference, 0.003; 95% CI, -0.001 to 0.04; P = .88). The prevalence of primary hypothyroidism was 16.0% (20 of 125 patients), which is significantly higher than 3.7% reported in the general population (difference, 0.12; 95% CI, 0.10-0.24; P < .001). Women were more likely to have primary hypothyroidism than men (odds ratio, 10.99; 95% CI, 3.13-38.66; P < .001). Patients with TPO antibodies had a higher likelihood of primary hypothyroidism than those without TPO antibodies (odds ratio, 7.36; 95% CI, 1.89-28.62; P = .004). There was no significant difference in the prevalence of thyroid nodules between patients in this study (29 of 49 [59.2%]) vs the general population (68%) (difference, 0.088; 95% CI, -0.44 to 0.73; P = .20) or of cancer (7% vs 5%; difference, 0.01; 95% CI, -0.01 to 0.17; P = .86).
546			_aEnglish
650			_a*Alkaptonuria/me [Metabolism]
650			_a*Hypothyroidism/ep [Epidemiology]
650			_aAdult
650			_aAlkaptonuria/co [Complications]
650			_aAlkaptonuria/ge [Genetics]
650			_aAutoantibodies/bl [Blood]
650			_aAutoantigens/im [Immunology]
650			_aCohort Studies
650			_aFemale
650			_aHomogentisic Acid/ur [Urine]
650			_aHumans
650			_aHyperthyroidism/ep [Epidemiology]
650			_aHyperthyroidism/ge [Genetics]
650			_aHypothyroidism/ge [Genetics]
650			_aIodide Peroxidase/im [Immunology]
650			_aIron-Binding Proteins/im [Immunology]
650			_aLogistic Models
650			_aMale
650			_aMiddle Aged
650			_aPrevalence
650			_aThyroid Function Tests
650			_aThyroid Gland/en [Enzymology]
650			_aThyrotropin/bl [Blood]
650			_aThyroxine/bl [Blood]
650			_aTyrosine/bl [Blood]
651			_aMedStar Washington Hospital Center
656			_aMedicine/Endocrinology
657			_aJournal Article
700			_aBurman, Kenneth D
790			_aAuh S, Avadhanula S, Burman KD, Ciccone C, Filie AC, Hannah-Shmouni F, Introne WJ, Klubo-Gwiezdzinska J, Regier D, Soldin SJ, Stolze B
856			_uhttps://dx.doi.org/10.1001/jamanetworkopen.2020.1357 _zhttps://dx.doi.org/10.1001/jamanetworkopen.2020.1357
942			_cART _dArticle
999			_c5229 _d5229