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Case Study O f TSH-Secreting P ituitary Adenoma

Case Study O f TSH-Secreting P ituitary Adenoma. Dr Hoda . Kadkhodazadeh Endocrinology Fellow Research Institute for Endocrine sciences Shahid Beheshti University of Medical Sciences May 18,2015. يافته‌هاي آزمايشگاهي تاريخ: 90/9/5 (بيمارستان پارس)

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Case Study O f TSH-Secreting P ituitary Adenoma

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  1. Case Study Of TSH-Secreting Pituitary Adenoma Dr Hoda.Kadkhodazadeh Endocrinology Fellow Research Institute for Endocrine sciencesShahidBeheshti University of Medical Sciences May 18,2015

  2. يافته‌هاي آزمايشگاهي تاريخ: 90/9/5 (بيمارستان پارس) LH: 9.3 IU/L (1.7-8.6) FSH: 7.5 IU/L (1.5-12.4) PRL: 7.3 ng/ml (1-18) Testesteron: 5.6 ng/ml (2.5-8.4) Spermogram: Viscosity: normal Total Sperm concentration: 29 M/ml (>20) Sperm with Progressive mot: 33% (>50%) Sperm with normal morphology: 20% (>30%) Function Sperm concentration: 2.9 M/ml (Good: >13 Average: 3-13 poor:0-3)

  3. تاريخ: 90/9/29 (آزمايشگاه دانش) FBS: 95 CBC:NL BUN: 15 U/A: NL Cr: 0.9 تاريخ: 92/5/18 (بيمارستان پارس) T4: 16.3 g/dl (5.1-14.1) T3: 3 ng/ml (0.7-2) TSH:5.7 mIU/ml (0.2-4.2) تاريخ:92/9/12(بيمارستان امام حسين) FBS:115 T4: 13.1 g/dl (4.6-12.5) T3: 1.95 ng/ml (0.8-3.1) TSH:6.61 mIU/ml (0.4-4.5)

  4. تاريخ: 92/10/24 (بيمارستان پارس) TSH:6.3 mIU/ml تاريخ: 93/2/11 (بيمارستان پارس) T4: 17 g/dl (5.1-14.1) T3: 2.5 ng/ml (0.7-2) TSH:5.6 mIU/ml (0.2-4.2) T- uptake: 0.6 (0.8-1.3) FT4I: 28.3 (4.5-12.7) LH:6.3 IU/L (1.7-8.6) FSH: 5.9 IU/L (1.5-12.4) PRL: 10.7 ng/ml (4-13.2) PRL(Diluted, 1/100): 12.3 ng/ml (4-13.2)

  5. Testestron: 7.1 ng/ml (2.5-8) Cortisole Am: 17.6 ng/ml (6.2-20) ACTH Am: 5.7 pg/ml (7.2-61) GH: 1.5 ng/ml (0.1 - 25) IGF1: 184 ng/ml (22-197) تاريخ: 93/6/18 (مركز تصويربرداري بابك) Brain MRI: Enlarged pituitary gland with mild supra sellar extension measuring 11 in AP, 10.4 mm in vertical and 14.2 mm in transverse diameter infavor of macroadenoma and with definite border with optic chiasm

  6. تاريخ: 93/7/22 (مركز تصويربرداري شفا) Brain MRI: T1 Hyposignal intensity lesion is identified in the left paramedian portion of adenohypophysis with 1110mm diameters. That infavor of pituitary macroadenoma with might deviation of pituitary stalk to the right side however optic chiasm appears normal. تاريخ: 93/9/25 پريمتري: در هر دو چشم و در حضور تست هاي قابل اعتماد، نقاط كاهش حساسيت اطراف نقطه كور به نفع بزرگي نقطه كور ديده مي‌شود كه بهتر است با يافته هاي High myopic فاندوس (myopic crescent) مطابقت داده شود.

  7. Assay interference • RTH • TSHoma

  8. Diagnostic Evaluations 1. Ask about other family members regarding abnormal TFT Careful history for other pituitary abnormalities (amenorrhea or visual field defect 2. Repeat a thyroid test in another lab Another strategy is to ask the original lab to assay TSH in serial dilution 3. Measure alpha subunit (50 – 85% high) 4. Measure serum SHBG 5. Measure other pituitary hormones

  9. 6. Analysis of TR-beta gene 7. MRI The presence of a macroadenoma on MRI is strong evidence of a TSH-oma particularly in the presence of an elevated alpha subunit The presence of a microadenoma is not specific for a TSH-oma and can be seen as an incidentaloma in 10% of normal individuals 8. Rarely radiolabeled pentetreotide and inferior petrosal sinus sampling when MRI shows a microadenoma or is normal.

  10. Further Evaluations • T3 suppression test • TRH test • Octerotide suppression test • SHBG • Alpha subunit • Alpha subunit/TSH ratio • TR- beta gene

  11. Acute octerotide suppression test

  12. In favor of TSHoma • TFT • Macroadenoma • Clinical overt thyrotoxicosis after administration of 50 ug/D LT4 for 2 months (weight loss 6 kg , tremor, sweating, heating tolerance) • Fine tremor

  13. Not in favor of TSHoma • No goiter • No clinical thyrotoxicosis symptoms

  14. Other Symptoms • Tachycardia ( PR=100) ( there is in RTH too) • Anxiety & irritability • Decreased libido & impotency

  15. Thyrotropin (TSH)-secreting pituitary adenomas

  16. TSHoma • Overall prevalence: one in one million • Very rare • Account for • 0.5 to 3 percent of all functioning pituitary tumors • Less than 1 percent of all cases of hyperthyroidism

  17. Pathophysiology Thyrotropin (TSH)-secreting pituitary adenomas secrete biologically active TSH in an autonomous fashion. Not increasing by TRH and not decreasing by exogenous thyroid hormone administration.

  18. Most TSHomas secrete only TSH 20 – 25% secrete one or more other pituary hormones mostly GH or prolactin It doesn’t cosecrete with ACTH

  19. Symptoms and Signs • In a review of 225 patients with thyrotropin (TSH)-secreting tumors, Clinical features other than hyperthyroidism included: • A diffuse guiter – 93 percent • Visual field defects – 35 percent • Menstrual disturbances – 33 percent • Galactorrhea (women), with or without consecration of prolactin – 28 percent • Headache – 21 percent • thyrotoxicosis(60-90 percent in other studies) • Time to diagnosis(2mo-20y)

  20. Thyroid Function Tests • Among 255 reviewed patients the ranges of hormone values were; • TSH - < 1.0 to 568 mU/L • total T4 – 11.6 to 53 ug/dL • FT4 – 1.6 to 7.7 ng/dL • total T3 – 195 to 1300 ng/dL • FT3 – 5 to 26 pg/mL

  21. treatment • Initial(medical therapy):LAR SSA & no antithyroid drug therapy • 26 of 43 patients riecievedssA as intial treatment • Reduction more than 50% in TSH in 23 of 26(88%) • Normalization of FT4 in 22 of 26(85%) • Reduce tumor size(tumor shrinkage of more than 20%in 5 of 13 (36%) treated at least for 3months • Dopamin agonists

  22. surgery • TSS is definitive therapy of choice(majority of microadenomas & 50-60% of macroadenoma • Surgury in 36 of 43 • After one year 21 (58.3%) were cured • 15 radiotherapy & 8 LAR ssA • Surgical remission in microadenoma 6 of 7 • Surgical remission in macroadenoma (15 of 29)

  23. LAR ssA • Role for primary treatment requires further investigation • In one report a patient with 1.5 cm complete nl TFT & nl MRI even after withdrawal of LAR in 5y follow up • In another series tumoral shrinkage was not obsereved in 3 of 7 patients treated with octrerotide for 24 months

  24. Why some tumor shrink in response to octreotide & others do not • Expression of SSTRs • Octerotide may inhibit TSH secretion in all tumors that express SSTR2 & type 5 receptor inhance the inhibitory effect of octertide

  25. 43 patients, aged 44+_18y (19–84 y) (23 men, 20women) • followed from 1976 to 20 from six Belgian and French centers. • They represent less than 1% of 4400 pituitary adenoma during that period • macroadenomaswhenthe maximal diameter was more than 10mm • giant adenomas when the diameter exceeded 40mm. • 13 patients presurgically treated with octreotide the percentage change in tumor volume was calculate according to the Di Chiro and Nelson formula: volum= height * length * width *0.5233

  26. latency between onset of hyperthyroidism and diagnosis of 4+_6 years • severe thyrotoxicosis in only 2patients ‘moderate in 20 patients ‘21 patients had only mild hyperthyroidism or no symptoms( 13 patients had had previous treatments targeted to the thyroid) • In one patient hyperthyroidism did not contribute to the diagnosis. • This patient was treated for hypothyroidism and Hashimoto’s thyroiditis. • Although he received substitutive thyroid hormone treatment with L-T4(150 mg) TSH values • were inappropriately elevated with regard to T3 and T4 serum levels. • A T3 test failed to suppress TSH whereas TRH did not stimulate TSH. • There was an associated aSUhypersecretion. • Pituitary MRI identified a 41mm macroadenoma that was successfully operated on and histologically confirmed. • Concomitant hyper- or hyposecretorysyndromes were observed in 18 patients: • eight patients presented with acromegalic features, • six women had amenorrhea–galactorrhea, • four men complained of impotence and reduced libido. • .

  27. Pituitary adenomas and MEN1: • Two women developed a sporadic MEN1 syndrome. • In both patients, hyperthyroidism and pituitary adenoma were diagnosed before the other tumors • one had a mixed TSH/GH/FSH-secreting adenoma • and the other had a pure thyrotropic adenoma. • This last patient also developed Zollinger Ellison syndrome. • Primary hyperparathyroidism occurred later in both patients.

  28. Treatments targeted to the thyroid: • Diagnosis in patients previously treated either with surgery or 131I was significantly delayed compared with patients treated with antithyroid drugs (P < 0:001) • Mean pituitary tumoral diameter at diagnosis was significantly smaller in this last group than in thyroid- operated patients (10.2+_6.1 n= 5 ) vs21.3+_8.5(n=8)mm p= 0:03 • Outcome of pituitary surgery,meantumor volume and TSH levels were not significantly different in patients who had received treatments targeted at the thyroid ( n=13 )and in the thyroid untreated patients( n=30)

  29. Treatment of pituitary adenomas: • Among the 26 patients who received somatostatinanalogs as first-line treatment, 19 underwent surgery while the treatment was pursued chronically in seven. • A reduction of more than 50% in TSH levels was observed • in 23/26 (88%) cases. • Normalization of free thyroid hormones was observed in 22/26 (85%) cases. • Normalization of aSU was recorded in three out of four cases. A tumoralshrinkage of more than 20% was demonstrated in 5/13 (36%) cases

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