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Department of Medical Sciences University of Milan, Italy Endocrinology and Diabetology Unit Fondazione Policlinico IRCCS Milan, Italy Paolo Beck-Peccoz.

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Presentation on theme: "Department of Medical Sciences University of Milan, Italy Endocrinology and Diabetology Unit Fondazione Policlinico IRCCS Milan, Italy Paolo Beck-Peccoz."— Presentation transcript:

1 Department of Medical Sciences University of Milan, Italy Endocrinology and Diabetology Unit Fondazione Policlinico IRCCS Milan, Italy Paolo Beck-Peccoz TSH-secreting pituitary adenomas

2 Pure TSH-omas GH PRLFSH/LH 72.2% 16.0% 10.4% 1.4% Number of cases TSH-omas mixed tumor Beck-Peccoz et al., Endocrine Reviews 1996;17:610–638. Classification of TSH-secreting pituitary tumors

3 Euthyroid Thyroid Peripheral tissue Pituitary TSH T3 T4 Hypothalamus TRH RTH Peripheral tissue Pituitary TSH T3 T4 TRH Hypothalamus Thyroid Hyperthyroid Peripheral tissue Pituitary TSH T3 T4 TRH Hypothalamus Thyroid & TSH-oma

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5 Positive MRI in RTH patients 9 out of 22 (40%) patients with RTH showed the presence of a pituitary lesion at MRI/CT scan Pituitary incidentaloma diagnosed in 8 cases Possible association between RTH and TSH-oma was suspected, but not yet proved, in only one 62-yr-old woman Nevertheless, the prevalence of pituitary incidentaloma appears higher in RTH patients (40%) than in the general population (20-30%)

6 Central Hyperthyroidism: serum levels of TSH and FT4 TSH mU/L Serum FT4 pmol/L RTH (n=59) TSH-omas (n=13)

7 CIRCULATING FACTORS MAY INTERFERE WITH MEASUREMENT OF TSH OR TOTAL AND FREE THYROID HORMONES OVERESTIMATION OF SERUM LEVELS CENTRAL HYPERTHYROIDISM? Heterophylic Ab directed against mouse  -globulins: interference with monoclonal Ab used in the IRMA Anti-TSH Ab or Ab cross-reacting with TSH Anti-T4 and/or anti-T3 Ab Abnormal forms of albumin or transthyretin (FDH)

8 DIFFERENTIAL DIAGNOSIS BETWEEN TSH-OMAS AND RTH Age (years) NS Sex (F/M ratio) NS TSH mU/L2.7± ±0.3 NS FT4 pmol/L 40.0± ±2.5 NS FT3 pmol/L14.5± ±1.0 NS SHBG nmol/L 113.0± ±4.0 < Familial cases 0% 81% < Lesions at CT scan or MRI 98% 10% < High  -subunit levels 65% 2% < High  -subunit/TSH m.r. 81% 2%< Abnormal TSH response to TRH test 83% 4% < Abnormal TSH response to T3 suppression test 100% 100% NS PARAMETER TSH-omas RTH P

9 TSH biological activity in various thyroid disorders RTH TSHomas Circulating TSH B/I Persani et al., J Clin Endocrinol Metab. 1994; 78:1034–1039.

10 Net increments after TRH injection in RTH FT pmol/L * FT pmol/L * TSH mU/L Controls RTH * P<0.01 vs controls controls Beck-Peccoz&Persani, Eur J Endocrinol, 1994; 131:

11 DIFFERENTIAL DIAGNOSIS BETWEEN TSH-OMAS AND RTH Age (years) NS Sex (F/M ratio) NS TSH mU/L2.7± ±0.3 NS FT4 pmol/L 40.0± ±2.5 NS FT3 pmol/L14.5± ±1.0 NS SHBG nmol/L 113.0± ±4.0 < Familial cases 0% 81% < Lesions at CT scan or MRI 98% 10% < High  -subunit levels 65% 2% < High  -subunit/TSH m.r. 81% 2%< Abnormal TSH response to TRH test 83% 4% < Abnormal TSH response to T3 suppression test 100% 100% NS PARAMETER TSH-omas RTH P

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13 DIFFERENTIAL DIAGNOSIS BETWEEN TSH-OMAS AND RTH Age (years) NS Sex (F/M ratio) NS TSH mU/L2.7± ±0.3 NS FT4 pmol/L 40.0± ±2.5 NS FT3 pmol/L14.5± ±1.0 NS SHBG nmol/L 113.0± ±4.0 < Familial cases 0% 81% < Lesions at CT scan or MRI 98% 10% < High  -subunit levels 65% 2% < High  -subunit/TSH m.r. 81% 2%< Abnormal TSH response to TRH test 83% 4% < Abnormal TSH response to T3 suppression test 100% 100% NS PARAMETER TSH-omas RTH P

14 DIFFERENTIAL DIAGNOSIS BETWEEN TSH-OMAS AND RTH Age (years) NS Sex (F/M ratio) NS TSH mU/L2.7± ±0.3 NS FT4 pmol/L 40.0± ±2.5 NS FT3 pmol/L14.5± ±1.0 NS SHBG nmol/L 113.0± ±4.0 < Familial cases 0% 81% < Lesions at CT scan or MRI 98% 10% < High  -subunit levels 65% 2% < High  -subunit/TSH m.r. 81% 2%< Abnormal TSH response to TRH test 83% 4% < Abnormal TSH response to T3 suppression test 100% 100% NS PARAMETER TSH-omas RTH P

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17 Acute somatostatin analog injection Variations (% of basal values) TSHFT4FT3 RTH TSH-omas Mannavola et al., Clin Endocrinol 2005; 62:

18 2-3 months somatostatin analog administration Variations (% of basal values) TSHFT4FT3RTHTSH-omas Mannavola et al., Clin Endocrinol 2005; 62:

19 In summary: normal elevated SHBG and  -sub negativepositive Imaging NOYES Family members YESNO YESNO YESNO TRH test T3-suppression test TRH test post T3 TR  NO Molecular study FT3 & FT4 two step or TSH Ultrasensitive methods TSH- oma RTH

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21 All patientsPrevious thyroid ablation No thyroid ablation Percent of cases Intrasellar Extrasellar Invasive

22 Different therapeutical approaches None TH analogs TRIAC, DT4, GC1 (binds wtTR  >TR  ), HY1 (acts on TR  mut R320C) Cardiac selective blockers Inhibition of mutant gene expression Neurosurgery Radiotherapy SRIH analogs Octreotide Lanreotide SOM 230 RTH TSH-oma

23 Reduction of tumor mass complete 34% 29% 0% partial 34% 40% 51% absent 32% 31% 49% Resolution of clinical symptoms yes 57% 62% 95% no 43% 38% 5% Surgery Surgery +Rx SMS analogs (n=125) (n=57) (n=84) TSH producing adenomas: results of different therapeutic approaches

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25 Results of chronic somatostatin analog treatment of TSH-secreting pituitary adenomas  TSH/  -GSU reduction92%  Thyroid hormone normalization95%  Vision improvement75%  Tumor mass shrinkage52%  True resistance4%  Discontinuation due to side effects 10%

26 TSH a-GSU FT4 FT3 GH Months Hormone levels Hormone levels after somatostatin analog in one patient with mixed GH/TSH adenoma IGF-I normalized after 2 months

27 ACKNOWLEDGEMENTS Luca Persani Deborah Mannavola Irene Campi Laura Fugazzola Guia Vannucchi Marco Bonomi Andrea Lania Sabrina Corbetta Giovanna Mantovani Carmela Asteria Krishna Chatterjee Samuel Refetoff Anna Spada


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