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1 Med J Chin PLA, Vol. 42, No. 7, July 1, [ ] (TSH) TSH [57.7%(15/26) vs. 45.0% (9/20)] [ (18~67) vs (17~74) ] [73.1%(19/26) vs. 55.0%(11/20)] TSH 5.06(2.97~6.27)mU/L 6.16( )mU/L TSH [57.7%(15/26) vs 40.0%(8/20)] TSH [34.6%(9/26) vs. 20.0%(4/20)] [20.0%(4/20) vs. 7.7%(2/26)] 66.7%(6/9) 75.0%(3/4) 24h TSH 37.4%~91.8% 46.5%~94.1% 8 3 TSH 12 2 TSH TSH TSH TSH [ ] [ ] R736.4 [ ] A [ ] (2017) [DOI] /j.issn A comparative study of the clinical features of thyrotropin-secreting pituitary adenomas FAN Xiao-jing, ZANG Li, JIN Nan, DU Jin, WANG Lin, GU Wei-jun, CHEN Kang, YANG Guo-qing, GUO Qing-hua, WANG Xian-ling, LV Zhao-hui *, BA Jian-ming, DOU Jing-tao, MU Yi-ming Department of Endocrinology, Chinese PLA General Hospital, Beijing , China * Corresponding author, metabolism301@126.com [Abstract] Objective To comparatively analyze the clinical characteristics of thyrotropin-secreting pituitary adenomas (TSH-omas). Methods The clinical features, laboratory variables, imaging and pathological results were retrospectively compared and analyzed of 26 cases with TSH-omas admitted in Chinese PLA General Hospital from Feb to Oct and 20 cases with TSH-omas admitted in Shanghai Huashan Hospital from Apr to Apr Results The female ratio was slightly higher in patients of Chinese PLA General Hospital than in Huashan Hospital [(57.7%(15/26) vs. 45.0%(9/20)], while the mean age was similar [ (18-67 years) vs (17-74 years)]. The most common chief complaint was thyrotoxicosis [73.1%(19/26) vs. 55.0%(11/20)], and mild-to-moderate goiter was the most common symptom. The mean serum TSH levels in Chinese PLA General Hospital and in Huashan Hospital were 5.06( )mU/L and 6.16( )mU/L respectively, and patients with normal serum TSH levels were more common in Chinese PLA General Hospital than in Huashan Hospital [57.7%(15/26) vs. 40.0%(8/20)]. Microadenoma was more common in Chinese PLA General Hospital than in Huashan Hospital [34.62%(9/26) vs. 20.0%(4/20)], while macroadenoma was more common in Huashan Hospital than in Chinese PLA General Hospital [20.0%(4/20) vs. 7.7%(2/26)]. Microadenoma was more common in female patients of the both groups [66.7%(6/9) vs. 75.0%(3/4)], while macroadenoma was all found in male patients. Tumor invasion of surrounding tissue and structure was often found in macroadenoma. In terms of octreotide inhibition test, the range of 24h TSH inhibition rate was roughly the same in the two groups (37.4%-91.8% and 46.5%-94.1%, respectively). Mixed adenoma was rare among all the pathologically confirmed cases. In [ ] [ ] ( ) [ ] metabolism301@126.com

2 Chinese PLA General Hospitals, TSH immunoreactive negative neoplastic cells were found in 3 of 8 cases, and octreotide scanning showed negative in 2 of 12 cases. Conclusions Patients with TSH-omas in the two hospitals show similarities but also some significant differences in the clinical features. Overall, the domestic patients with TSH-omas are diagnosed without gender difference according to the reports in China. The mean age at diagnosis is significantly younger than that in foreign data. Microadenoma is more common in females, while macroadenoma is more common in males. Serum TSH levels can be normal in patients with TSHomas. Immunostaining and/or octreotide scanning for TSH can be negative. [Key words] thyrotropin-secreting pituitary adenoma; hyperthyroidism; pituitary neoplasma; clinical characteristics (TSH) 0.5%~2.8% [1] 1960 Jailer 450 [2] 1981 [3] 1 TSH [4] TSH 10 TSH 20 [4-6] TSH TSH [5] TSH TSH ( ) TSH ~ [1-2] ( ) FT 3 FT 4 TSH ( ) (TRH) T 3 TSH [5] [TSH (GH) (LH) (FSH) (PRL) (ACTH)] PRL FSH LH GH ACTH mg h TSH MRI ( )CT 1.3 SPSS 16.0 x±s M(Q) Student-t (%) χ 2 Fisher's P< TSH ( ) 20 ( 11 9 ) [ (18~67) (17~74) P>0.05] ( 1) TSH 73.1%(19/26) 55.0%(11/20) ( 1)

3 Med J Chin PLA, Vol. 42, No. 7, July 1, Tab.1 Comparison of clinical data, chief complaint and goiter between subjects in Chinese PLA General Hospital and Shanghai Huashan Hospital Item Chinese PLA General Hospital (n=26) Shanghai Huashan Hospital (n=20) t/χ 2 P value Age (year) (18-67) (17-74) Male/Female 11/15 11/ Disease course [n(%)] a <1 year 12(46.2) 7(35.0) 1-5 year 10(38.5) 6(30.0) 6-10 year 3(11.5) 3(15.0) >10 year 1(3.8) 4(20.0) Chief complaint [n(%)] Thyrotoxicosis 8(30.8) 9(45.0) SEM 4(15.4) 4(20.0) Thyrotoxicosis and SEM 7(26.9) 2(10.0) Goiter 1(3.9) 1(5.0) Goiter and SEM 3(11.5) 1(5.0) Pituitary incidentaloma 3(11.5) 3(15.0) Goiter Grading [n(%)] b N 18(69.2) 8(40.0) 4(15.4) 2(10.0) 4(15.4) 7(35.0) 0(0) 3(15.0) SEM. Symptoms of expanding mass; N. No goiter. a. Disease course was divided into 5 years and >5 years when performed by continuity correction formula; b. Goiter grading was divided into grade and > grade when performed by Pearson Chi-square test TSH 5.06(2.97~6.27)mU/L TSH [6.12(4.52~8.81)mU/L 3.14(2.55~5.84)mU/L P =0.040] TSH 6.16(3.76~10.91)mU/L TSH [6.04(3.74~10.41)mU/L vs. 6.27(3.30~12.36)mU/L P>0.05] TSH 15 8 TSH TSH [57.7%(15/26) vs. 40.0%(8/20)] TSH TSH (P>0.05) 2 TSH 30%(6/20)TPOAb 10%(2/20)TgAb 14 TRAb 15 2 TPOAb Tg Ab 1 TRAb PRL 3 PRL g/l g/l g/l( 2.8~29.2 g/l) 2 1 TSH/ PRL PRL g/l ( 2.10~17.70 g/l) TSH 1 PRL g/l( 3.86~22.80 g/l) 1 FSH 15.60U/L( 1.50~12.40U/L) ACTH GH LH h TSH 37.4%~91.8% 46.5%~94.1% CT MRI [34.6%(9/26) vs. 20.0%(4/20)] [20.0%(4/20) vs. 7.7%(2/26)] 46mm 54mm( 2) 17 10mm 82.4% (14/17) ( 1)

4 Tab.2 Comparison of laboratory data and imaging features between subjects in PLA General Hospital and Shanghai Huashan Hospital Item Chinese PLA General Hospital (n=26) Shanghai Huashan Hospital (n=20) Z/χ 2 P value TSH level (mu/l) 5.06( ) 6.16( ) TSH group Normal TSH level 3.10( ) 3.32( ) Elevated TSH level 6.71( ) 10.02( ) Thyroid hormones (pmol/l) FT ( ) 9.22( ) FT ( ) 30.05( ) Octreotide suppression test (%) Inhibition rate of TSH Inhibition rate of FT Inhibition rate of FT Imaging feature (mm) Tumor size 14.00( ) 19.50( ) Microadenoma (<10) 9(34.6) 4(20.0) Macroadenoma (10 39) 15(57.7) 12(60.0) Giant adenoma ( 40) 2(7.7) 4(20.0) Normal reference range in Chinese PLA General Hospital: FT 3 : pmol/L; FT 4 : pmol/L; TSH: mU/L. Normal reference range in Shanghai Huashan Hospital: FT 3 : pmol/L; FT 4 : pmol/L; TSH: mU/L Sagittal plane Coronal plane 1 MRI Fig.1 MRI image of pituitary macroadenoma ( 3) TSH(+) 3 (TSH+PRL TSH+GH+LH TSH+FSH 1 ) 3 TSH ( 1 ACTH GH PRL FSH ) 15 TSH 13 TSH+FSH 1 TSH+PRL l 3 Tab.3 Results of octreotide scanning and octreotide suppression test in patients of PLA General Hospital Case Gender Age (year) Octreoscan TM Imaging Tumor size (mm) TSH inhibition rate (%) TSH baseline (mu/l) 1 Female 54 ( ) Micro Female 52 ( ) Macro Male 43 (+) Macro Male 47 (+) Giant Male 29 (+) Macro Female 59 (+) Micro Female 45 (+) Micro Male 54 (+) Micro 5 None Female 66 (+) Micro 6 None Female 48 (+) Macro 21 None Female 28 (+) Macro 10 None Male 39 (+) Macro 13 None Male 50 None Macro Female 38 None Micro

5 Med J Chin PLA, Vol. 42, No. 7, July 1, %~45% TSH TSH 0.5%~2.8% [1] TSH 0.6%(26/4162) %(12/1000) [7] % (19/1849) [8] TSH 50~60 [1,9] ( ) [7-8] TSH [10] TSH TSH [9] [11-13] [14-15] (57.7%) (55.0%) [7] [8] [10] ( : =49:44) TSH TSH TSH 3.14(2.55~5.84)mU/L 6.12(4.52~8.81)mU/L (P=0.040) TSH 6.27(3.30~12.36)mU/L 6.04(3.74~10.41)mU/L(P>0.05) 34.6%(9/26) 66.7%(6/9) 20.0%(4/20) 75.0%(3/4) 2 4 TSH ( ) TSH TSH TSH 90% [15] TSH TSH [10] TSH PRL 5%~10% [16] TSH PRL (Pit-1) TSH PRL (TRH) PRL TSH TSH TSH Beck- Peccoz [1] Socin [14] 30% 58% TSH TSH [ 40.0%(8/20) 57.7%(15/26)] 75.0%(12/16) [10] 15.8%(3/19) [8] TSH TSH TSH TSH TSH [2] TSH [ 2.97(2.44~6.22)mU/L vs. 5.57(4.53~6.42)mU/L 6.94(3.20~12.13)mU/L vs. 5.99(3.76~10.91)mU/L P>0.05] TSH 75%~80% 20%~25% ( GH/TSH PRL/TSH ) [9] (TSH+PRL TSH+GH+LH TSH+FSH 1 ) 15 2 (TSH+FSH TSH+PRL l ) 21.7%(5/23)

6 TSH 11 [10] 19 [8] 2 TSH TSH TSH GH/TSH [14] TSH 2013 TSH [9] [10] 9 24h TSH ( 37.39%~91.80% 46.5%~94.1%) 5.19%~99.15% TSH 24h TSH 77.02% 13.43% 52.33% 15.02% TSH TSH ( ) TSH [1] Beck-Peccoz P, Persani L, Lania A. Thyrotropin-secreting pituitary adenomas[ J/OL]. Endotext [Internet]. ncbi.nlm.nih.gov/books/nbk278978/. [2] Amlashi FG, Tritos NA. Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management[ J]. Endocrine, 2016, 52(3): [3] Shi FX. Secreting pituitary tumor secreting thyrotropin: 1 case report[ J]. New Chin Med, 1981, 12(1): [. 1 [ J]., 1981, 12(1): ] [4] Bian LG, Sun QF, Jiang XH, et al. Diagnosis and treatment of thyrotropin-secreting pituitary adenomas[ J]. Chin J Neurooncol, 2013, 11(4): [,,,. [ J]., 2013, 11(4): ] [5] Zhao W W, Yang YH, Ye HY, et al. A clinical analysis of thyrotropin-secreting pituitary adenomas in 20 patients[ J]. Chin J Intern Med, 2014, 53(1): [,,,. 20 [ J]., 2014, 53(1): ] [6] Ye L, Han RL, Jiang XH, et al. Syndrome of inappropriate secretion of TSH: Differential diagnosis in 61 patients[ J]. Chin J Endocrinol Metab, 2015, 31(11): [,,,. 61 [J]., 2015, 31(11): ] [7] Wang GJ, Bi ZY, Qian K, et al. Diagnostic and therapeutic considerations of thyrotropin-secreting pituitary adenomas (Report of 12 cases)[ J]. Chin J Neurosurg, 2008, 24(8): [,,,. ( 12 )[ J]., 2008, 24(8): ] [8] Xing B, Ren ZY, Su CB, et al. Thyroid-stimulating hormone pituitary adenomas: clinical characteristics, diagnosis and treatment[ J]. Chin J Surg, 2011, 49(6): [,,,. [ J]., 2011, 49(6): ] [9] Beck-Peccoz P, Lania A, Beckers A, et al European thyroid association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors[ J]. Eur Thyroid J, 2013, 2(2): [10] Jiang XH, Cai J, Wang WQ, et al. Clinical characteristics and diagnostic analysis of thyrotropinoma[ J]. Chin J Endocrinol Metab, 2012, 28(9): [,,,. [J]., 2012, 28(9): ] [11] Yamada S, Fukuhara N, Horiguchi K, et al. Clinicopathological characteristics and therapeutic outcomes in thyrotropinsecreting pituitary adenomas: a single-center study of 90 cases[ J]. J Neurosurg, 2014, 121(6): [12] Ónnestam L, Berinder K, Burman P, et al. National incidence and prevalence of TSH-secreting pituitary adenomas in Sweden[ J]. J Clin Endocrinol Metab, 2013, 98(2): [13] Malchiodi E, Profka E, Ferrante E, et al. Thyrotropin-secreting pituitary adenomas: outcome of pituitary surgery and irradiation[ J]. J Clin Endocrinol Metab, 2014, 99(6): [14] Socin HV, Chanson P, Delemer B, et al. The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients[ J]. Eur J Endocrinol, 2003, 148(4): [15] van Varsseveld NC, Bisschop PH, Biermasz NR, et al. A long-term follow-up study of eighteen patients with thyrotrophin-secreting pituitary adenomas[ J]. Clin Endocrinol, 2014, 80(3): [16] Chinese Pituitary Adenoma Cooperation Group. Consensus in diagnosis and treatment for pituitary prolactin adenoma (2014 ed.)[ J]. Natl Med J Chin, 2014, 94(31): [. (2014 )[ J]., 2014, 94(31): ] ( ) ( )

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