Exp Clin Endocrinol Diabetes 2002; 110(7): 355-360
DOI: 10.1055/s-2002-34993
Article

© Johann Ambrosius Barth

Surveillance of TSH-Suppressive Levothyroxine Treatment in Thyroid Cancer Patients: TRH Testing Versus Basal TSH Determination by a Third Generation Assay

R. Görges1 , B. Saller2 , E. G. Eising1 , B. Quadbeck2 , K. Mann2 , A. Bockisch1
  • 1 Department of Nuclear Medicine, University Hospital Essen, Germany
  • 2 Department of Endocrinology, University Hospital Essen, Germany
Further Information

Publication History

received 11 February 02 first decision 12 March 02

accepted 6 May 02

Publication Date:
24 October 2002 (online)

Summary

Objective, design and methods: Although TRH testing has been eliminated in the diagnosis of most benign thyroid diseases, it is still controversial whether or not it can be replaced by ultrasensitive determination of basal TSH for monitoring optimal TSH suppression in thyroid cancer patients. We compared basal and TRH-stimulated TSH values measured by a 2nd generation assay (lower detection limit 0.1 mU/l) and by a 3rd generation assay (lower detection limit 0.005 mU/l) in 209 thyroidectomized thyroid cancer patients under suppressive levothyroxine treatment. Results: In the 2nd generation assay all patients had basal TSH values < 0.1 mU/l (criterion of admission in the study), and the TRH-stimulated TSH values were above the lower detection limit in 47% of the patients (range < 0.1-1.0 mU/l). In the 3rd generation assay TSH was above the lower detection limit in 67% under basal conditions (range < 0.005-0.098 mU/l), and in 83% after TRH stimulation (range < 0.005-1.000 mU/l). We observed close correlations (p < 0.001) between basal and TRH-stimulated TSH in the 3rd generation assay (r = 0.86), between TRH-stimulated TSH in the 2nd and 3rd generation assay (r = 0.95), and between TRH-stimulated TSH in the 2nd generation assay and basal TSH in the 3rd generation assay (r = 0.73). The ratio between TRH-stimulated and basal TSH values was in the average range 7-9 : 1. Subdividing the patients in three subgroups based on the TRH-stimulated TSH values from the 2nd generation assay, the corresponding basal TSH values (median and [25.-75. percentile]) from the 3rd generation assay were < 0.005 [< 0.005-0.010] mU/l in subgroup A (2nd generation stim. TSH: < 0.15 mU/l), 0.032 [0.021-0.040] mU/l in subgroup B (2nd generation stim. TSH: 0.15-0.4 mU/l), and 0.066 [0.046-0.085] mU/l in subgroup C (2nd generation stim. TSH: ≥ 0.5 mU/l). Conclusions: Even in those thyroid cancer patients where a high degree of TSH suppression is the therapeutic goal, 3rd generation TSH assays enable a reliable adjustment of the levothyroxine dose by basal TSH determinations. In laboratories still using 2nd generation assays, the monitoring of maximal TSH suppression in patients with high-risk thyroid cancer should be performed by TRH testing.

5. References

  • 1 Biondi B, Fazio S, Carella C, Amato G, Cittadini A, Lupoli G, Sacca L, Bellastella A, Lombardi G. Cardiac effects of long term thyrotropin-suppressive therapy with levothyroxine.  J Clin Endocrinol Metab. 1993;  77 334-338
  • 2 Böhm J, Kosma V M, Eskelinen M, Hollmen S, Niskanen M, Tulla H, Alhava E, Niskanen L. Non-suppressed thyrotropin and elevated thyroglobulin are independent predictors of recurrence in differentiated thyroid carcinoma.  Eur J Endocrinol. 1999;  141 460-467
  • 3 Burmeister L A, Goumaz M O, Mariash C N, Oppenheimer J H. Levothyroxine dose requirements for thyrotropin suppression in the treatment of differentiated thyroid cancer.  J Clin Endocrinol Metab. 1992;  75 344-350
  • 4 Charrie A, Mesnard X, Tourniaire J. Evaluation analytique d'un dosage TSH de troisième generation.  Ann Endocrinol (Paris). 1999;  60 40-44
  • 5 Cooper D S, Specker B, Ho M, Sperling M, Ladenson P W, Ross D S, Ain K B, Bigos S T, Brierley J D, Haugen B R, Klein I, Robbins J, Sherman S I, Taylor T, Maxon H R. Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry.  Thyroid. 1998;  8 737-744
  • 6 Creutzig H, Kallfelz I, Haindl H, Schulle R, Hundeshagen H. Hormone replacement in patients with carcinoma of the thyroid.  Dtsch Med Wochenschr. 1977;  102 1763-1766
  • 7 De Lange W E, Sluiter W J, Doorenbos H. The usefulness of a sensitive thyrotrophin assay in the fine adjustment of thyroxine therapy following ablation for carcinoma.  NJNM. 1989;  35 11-17
  • 8 Derwahl M, Broecker M, Kraiem Z. Clinical review 101: Thyrotropin may not be the dominant growth factor in benign and malignant thyroid tumors.  J Clin Endocrinol Metab. 1999;  84 829-834
  • 9 Dietlein M, Dressler J, Farahati J, Leisner B, Moser E, Reiners C, Schicha H, Schober O. Leitlinie zur Radioiodtherapie (RIT) beim differenzierten Schilddrüsenkarzinom.  Nuklearmedizin. 1999;  38 221-222
  • 10 Erne P, Staub J J, Althaus B, Fleig Y, Girard J. Evaluation of the optimal thyroxine dose with the TRH test for replacement and suppression therapy.  Schweiz Med Wochenschr. 1983;  113 1922-1923
  • 11 Esik O, Tusnady G, Daubner K, Nemeth G, Fuezy M, Szentirmay Z. Survival change in papillary thyroid cancer in Hungary: individual survival probability estimation using the Markov method.  Radiother Oncol. 1997;  44 203-212
  • 12 Exer P, Staub J J, Zulewski H, Müller M, Huber P. Die Beurteilung der TSH-Suppression mit einem TSH-Assay der 3. Generation: diagnostische und therapeutische Konsequenzen.  Schweiz Med Wschr. 1992;  122 1964-1967
  • 13 Francia G, Davi M V, Petroziello A, Sussi P L. Hormonal therapy in differentiated carcinoma of the thyroid gland.  Chir Ital. 1994;  46 56-58
  • 14 Jaffiol C, Daures J P, Nsakala N, Guerenova J, Baldet L, Pujol P, Vannereau D, Bringer J. Contrôle à long terme du traitement médical du cancer thyroïdien différencié.  Ann Endocrinol (Paris). 1995;  56 119-126
  • 15 Kainz H, Weissel M. Can the thyrotropin (TSH) suppressive dose of L-thyroxine (T4) be individually predicted in athyroid patients?.  Acta Med Austriaca. 1990;  17 50-54
  • 16 Kamel N, Gullu S, Dagci Ilgin S, Corapcioglu D, Tonyukuk Cesur V, Uysal A R, Baskal N, Erdogan G. Degree of thyrotropin suppression in differentiated thyroid cancer without recurrence or metastases.  Thyroid. 1999;  9 1245-1248
  • 17 Kosuda S, Arai S, Hohshito Y, Tokumitsu H, Kusano S, Kadota T. Successful TSH suppression therapy with triiodothyronine in a patient with pulmonary metastases from differentiated thyroid carcinoma in the absence of 131I uptake.  Kaku Igaku. 1997;  34 925-931
  • 18 Lamberg B A, Helenius T, Liewendahl K. Assessment of thyroxine suppression in thyroid carcinoma patients with a sensitive immunoradiometric assay.  Clin Endocrinol. 1986;  25 259-263
  • 19 Mann K, Saller B, Mehl U, Hörmann R, Moser E. Highly sensitive determination of TSH in the follow-up of TSH-suppressive therapy in patients with differentiated thyroid cancer.  Nuklearmedizin. 1988;  27 24-28
  • 20 Minebois-Villégas A, Rohmer V, Rachédi F, Berrut G, Boux de Casson-Raimbeau F, Wion-Barbot N, Bigorgne J C, Jallet P. Comparison of the analytical and clinical performances of three thyrotropin immunoassay kits.  Ann Biol Clin. 1995;  83 413-418
  • 21 Nicoloff J T, Spencer C A. Non-thyrotropin-dependent thyroid secretion (Editorial).  J Clin Endocrinol Metab. 1992;  75 343
  • 22 Pujol P, Daures J P, Nsakala N, Baldet L, Bringer J, Jaffiol C. Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer.  J Endocrinol Metab. 1996;  81 4318-4323
  • 23 Saller B, Broda N, Heydarian R, Görges R, Mann K. Utility of third generation thyrotropin assays in thyroid function testing.  Exp Clin Endocrinol Diabetes. 106 ((Suppl 4)) 1998;  S29-S33
  • 24 Salmon D, Rendell M, Williams J, Smith C, Ross D A, Waud J M, Howard J E. ,Chemical hyperthyroidism‘. Serum triiodothyronine levels in clinically euthyroid individuals treated with levothyroxine.  Arch Int Med. 1982;  142 571-573
  • 25 Solomon B L, Wartofsky L, Burman K D. Currents trends in the management of well differentiated papillary carcinoma.  J Clin Endocrinol Metab. 1996;  81 333-339
  • 26 Spencer C A, Lai-Rosenfeld O, Guttler R B, LoPresti J, Marcus A O, Nimalasuriya A, Eigen A, Doss R C, Green B J, Nicoloff J T. Thyrotropin secretion in thyrotoxic and thyroxine-treated patients: assessment by a sensitive immunoenzymometric assay.  J Clin Endocrinol Metab. 1986;  63 349-355
  • 27 Spencer C A, Schwarzbein D, Guttler R B, LoPresti JS, Nicoloff J T. Thyrotropin (TSH)-releasing hormone stimulation test responses employing third and fourth generation TSH assays.  J Clin Endocrinol Metab. 1993;  76 494-498
  • 28 Taimela E, Koskinen P, Nuutila P, Nikkanen V, Saraste M, Taimela S, Irjala K. Free thyroid hormones and a third-generation TSH assay in the detection of hyperthyroidism during long-term thyroxine treatment in thyroid carcinoma patients.  Scand J Clin Lab Invest. 1995;  55 181-186
  • 29 Thomas C G. Role of thyroid stimulating hormone suppression in the management of thyroid cancer.  Sem Surg Oncol. 1991;  7 115-119
  • 30 Thyroid Cancer Task Force .AACE Clinical guidelines for the management of thyroid carcinoma. The American Association of Clinical Endocrinologists and The American College of Endocrinology 1996
  • 31 Vanderpump M P, Neary R H, Manning K, Clayton R N. Does an increase in the sensitivity of serum thyrotropin assays reduce diagnostic costs for thyroid disease in the community?.  J R Soc Med. 1997;  90 547-550
  • 32 Wang P W, Wang S T, Liu R T, Chien W Y, Lung S C, Lu Y C, Chen H Y, Lee C H. Levothyroxine suppression of thyroglobulin in patients with differentiated thyroid carcinoma.  J Clin Endocrinol Metab. 1999;  84 4549-4553
  • 33 Wartofsky L. Use of sensitive TSH assay to determine optimal thyroid hormone therapy and avoid osteoporosis.  Annu Rev Med. 1991;  42 341-345
  • 34 Wemeau J L. Principes et modalites du traîtement hormonal dans la prise en charge therapeutique des cancers thyroidiens differencies.  Ann Endocrinol (Paris). 1997;  58 204-210

M.D. Rainer Görges

Department of Nuclear Medicine

University Hospital Essen

Hufelandstr. 55

45122 Essen

Germany

Phone: ++ 49-201-7232032

Fax: ++ 49-201-7235964

Email: rainer.goerges@uni-essen.de

    >