A Ribka

D Jüngst

D. Jüngst

EC Ridgway

H. J. Karl

JJ Staub

P Vogt

U. Büll

English

Jüngst, Dieter

Büll, U.

Karl, Hans Josef

Open Access LMU ( Ludwig-Maximilians-Univ. München)

Klin Wochenschr (1982) 60:477°478 Kiinische Wochen- schrift (~ Springer-Verlag 1982 Kurze wissenschaftliche Mitteilungen Results of Oral TRH Test in the Differentiation of Compensated and Decompensated Autonomous Thyroid Nodules D. J f ingst 1, U. B/ill 2, and  H. J .  Kar l  1 Departments of Medicine 2 ~ (Director Prof. Dr. G. Paumgartner) and Radiology g(Director Prof. Dr. J. Lissner), Klinikum Grosshadern, University of Munich Summary. In 17 patients with compensated autonomous adenomas of the thyroid, iv thyrotropin releasing hormone (TRH) tests (200 pg) and oral TRH tests (40 rag) were performed. In nine of these patients, thyroid-stimulating hormone (TSH) 30 min after iv TRH showed a normal (>2.7 ~U/ml) and in eight patients a subnormal (<2.7 gU/ml) or negative response. However, after prolonged oral stimulation with 40 mg TRH, after 120-180 rain TSH was normal (>2.7 laU/ml) in 15 and subnormal ( <2.7 pU/ml) in two patients. In 20 patients with decompensated autonomous thyroid nod- ules, TSH was not detectable ( <0.8 gU/ml) after iv or oral TRH stimulation. Therefore, theoral TRH stimulation test seemed to be superior to the iv TRH test in the discrimination ofcompensated and decompensated autonomous adenomas of the thyroid. Key words: Autonomous thyroid nodules- Oral TRH test- Results Ergebnisse des oralen TRH-Tests zur Unterscheidung yon kompensierten and dekompensierten autonomen Adenomen der Schilddriise Zusammenfassung. Bei 17 Patienten mit kompensierten autonomen Adenomen der Schilddr%e wurden TRH-Teste mit 200 gg i.v. und 40 mg oral durchgeffihrt. Bei 9 Patienten war TSH 30 min nach TRH i.v. normal (> 2.7 ltU/ml), dagegen zeigten 8 Patienten einen subnormalen (<2.7 laU/ml) oder fehlenden TSH-Anstieg. Nach verlfingerter Stimulation mit 40 mg TRH oral war TSH 120-180 min bei 15 Patienten im Normbereich (>2.7 pU/ml) und nur bei 2 Patienten subnormal (< 2.7 gU/ml). Bei 20 Patienten mit dekompensierten autonomen Adenomen der Schilddrtise lag TSH sowohl nach i.v. als auch nach oraler TRH-Stimuladon in allen F/illen unter der Nachweisgrenze ( < 0.8 laU/ml). Die Befunde sprechen daf/ir, dab der orate TRH-Test geeig- neter ist als der i.v. TRH-Test, um zwischen kompensierten u d dekompensierten autonomen Adenomen der Schilddrfise zu unter- scheiden. Sehliissetw6rter: Autonomes Adenom - Oraler TRH-Test - Er- gebnisse Introduction Patients with scintigraphically decompensated autonomous thyroid nodules usually reveal negative intravenous 200 gg TRH tests [3]. Offprint requests to : Dr. D. Jfingst (address ee page 478) However. surprisingly comparable t st results have been obtained in about 30% of patients with scintigraphically compensated auton- omous adenomas [2]. Therefore, diagnosis of compensated and decompensated autonomous thyroid nodules is based primarily on scintigraphic findings and only to a small extent on the results of in vitro parameters of thyroid function. However, the oral TRH stimulation test was introduced recently and has been believed to be useful in the evaluation of patients with impaired TSH reserve but euthyroid function [I. 4, 5]. In these studies, about 10%-12% of apparently euthyroid patients revealed negative ntravenous 200 lag TRH tests. In 50%-60% of these patients, autonomous production of thyroid hormones could be excluded by the 40-rag oral TRH test. It was the aim of this study to evaluate whether the oral TRH test is superior to the iv TRH test in the discrimina- tion of compensated and decompensated autonomous adenomas classified by nuclear imaging. Materials and Methods The study included a total of 37 outpatients (12 males and 25 females) with an age ranging from 30 to 82 years. Diagnosis of autonomous thyroid nodules was based on the results of nuclear imaging with 99~Tc-pertechnate (employing a 20% uptake of the paranodular tissue as the discriminating value), including scintigra- phy, after suppression with 60 gg T3 tbr 10 days in cases uspected to have compensated autonomous adenomas. In all patients, intra- venous TRH tests were performed after an overnight fasting period with a boluslike injection f 200 gg TRH and TSH-RIA (Henning, Berlin), 30 rain aRer TRH application. For oral TRH tests, a 40 mg tablet of TRH (Thyroliberin, Merck, FRG) was used and single TSH determinations were done after 120-180 min. There was an interval of 2-6 weeks between the iv and oral TRH tests. T4 was measured by enzyme immunoassay (Syva Company, Palo Alto, USA) and T 3 by radio immunoassay (Amersham-Buchler, Braunschweig, FRG). Results In 17 patients (5 males and 12 females), scintigraphy after suppres- sion revealed a formerly compensated autonomous adenoma. Con- centrations of thyroid hormones were measured prior to appIica- tion ofT~. T 4 (5.4-10.8 ~tg/dl, 2=7.4 pg/dl) and T3 (1.0-2.9 ng/ml, 2,:: 1.9 ng/ml) concentrations i  plasma were mainly in the normal range. Thyroid-stimulating hormone, 30 min after 200 gg iv TRH (0.8-14.6 gU/ml, 2=2.7 laU/ml), showed in nine patients a normal 478 Kurze wissenschaftliche Mitteilungen (>2.7 btU/ml) and in eight patients a subnormal (<2.7 laU/ml) or negative response. However, TSH 120-180 min after 40 mg orat TRH was normal (>2.7 laU/ml) in 15 patients and subnormal (<2.7 gU/mt) in only two patients. In 20 patients (7 males and 13 females) scintigraphy demon- strated a primarily decompensated autonomous adenoma. In such cases, 30%-40% of T, (4.0-14.6gg/dl, 2=7.8~tg/dl) and T a (1,6 4.3 ng/ml, ~7=2.3 ng/ml) values were elevated. Thirty minutes after 200 gg iv TRH and 120-180 rain after 40 mg oral TRH, TSH was not detectable (<0.8 laU/ml) in all cases in accordance with the scintigraphic findings of decompensated autonomous thyroid nodules. Discussion Patients with scintigraphically decompensated autonomous thyroid nodules usually reveal negative iv 200 lag TRH tests. These data could be confirmed in the present study. Nearly 50% of the 17 patients with scintigraphically compen- sated autonomous thyroid nodules revealed a subnormal or nega- tive response to iv TRH in accordance with prior studies [2]. How- ever, prolonged stimulation with 40 mg oral TRH in these patients was associated with normal TSH response in 15 (88%) and subnor- mal in two (12%). All patients with decompensated autonomous thyroid nodules howed a failing TSH response to iv TRH and even to prolonged oral TRH stimulation. These findings point to a possible clinical validity of the oral TRH test as a help in the differentiation of compensated and decompensated autonomous adenomas, especially in borderline cases. In addition, in patients cintigraphically suspected to have compensated thyroid no ules, a negative result of an oral TRH test may help to exclude this diagnosis and prevent further diagnos- tic procedures, e.g., the T3-suppression-test. Acknowledgements. T4, T3 and TSH determinations were provided by Prof. Dr. W. Vogt, Bereich Endokrinologie und Stoffwechsel- chemie, Institute of Clinical Chemistry (Direktor Prof. Dr. M. Knedel), Klinikum Grosshadern University of Munich. References 1. J/ingst D, Schineis E, Vogt W, Mann K, Karl HJ (1980) Parame- ters of thyroid function in thyroid autonomy. J Mol Med 4:103-109 2. Ribka A, Mayr B, Bfill U, Leisner B, Scriba PC (1979) Wertigkeit nuklearmedizinischer und endokrinologischer Methoden zur Klassifizierung autonomer Schilddriisenadenome. Med Klin 74:511-.515 3. Ridgway EC, Weintranb BD, Cellalos JL, Rack MC, Maloof F (1973) Suppression of pituitary TSH secretion in tile patient with a hyperfunctioning thyroid nodule. J Clin Invest 52: 2783-2790 4. Staub JJ, Girard J, Gemsenjfiger E (1976) Entwicklung eines einfachen oralen Kurztestes mit dem TSH-Releasing-Hormon (TRH) und dessen Anwendung in der Schilddrtisendiagnostik. Schweiz Med Wochenschr 106 : 1839 1842 5. Vogt P, Girard J, Staub JJ (1978) Thyroid-Stimulating Hormone (TSH), Triiodothyronine (T3) and Thyroxine (T~) response to intravenous and oral stimulation with synthetic Thyrotropin- Releasing-Hormone (TRH) in young healthy adults. Klin Wo- chenschr 56: 31-35 Received October 23, 1981 Accepted November 8, 1981 Dr. D. Jfingst Med. Klinik 2 Klinikum Groi3hadern Marchioninistr. 15 D-8000 Mfinchen 70 Federal Republic of Germany Verantwortlich ffirden Texneil: Prof. Dr. Herbert Schwiegk und Prot: Dr. Hans JahrmS.rker. Medizinische K linik (Innenstadt) er Universitb.t, Ziemssenstrage 1. D-8000 Mfinchen 2; fiir den Anzeigenteih E. Lfickermanm R. Eicke, Springer-Verlag. Kuff~rstendamm 237. D-1000 Berlin 15. Springel~Verlag. Berlin Heidelberg New York und J.F. Bergm~nn Verlag, Miinchen. - Druck der Universitgtsdruckerei H. Sttirtz AG. Wiirzburg. Printed in Germany.- @~ Springer-Verlag GmbH & Co KG, Berlin Heldelberg 1982 

2; fiir den Anzeigenteih

Parameters of thyroid function in thyroid autonomy. J Mol Med 4:103-109 2. Ribka

Thyroid-Stimulating Hormone (TSH), Triiodothyronine (T3) and Thyroxine (T~) response to intravenous and oral stimulation with synthetic ThyrotropinReleasing-Hormone (TRH) in young healthy adults.

Results of oral TRH test in the differentiation of compensated and decompensated autonomous thyroid nodules

Universität München: Elektronischen Publikationen

Klin Wochenschr (1982) 60:477°478 Kiinische 
Wochen- 
schrift 
(~ Springer-Verlag 1982 
Kurze wissenschaftliche Mitteilungen 
Results of Oral TRH Test in the Differentiation 
of Compensated and Decompensated Autonomous Thyroid Nodules 
D.  J f ings t  1, U.  B/ill 2, a n d  H.J .  K a r l  1 
Departments of Medicine 2 ~ (Director Prof. Dr. G. Paumgartner) and Radiology g (Director Prof. Dr. J. Lissner), 
Klinikum Grosshadern, University of Munich 
Summary. In 17 patients with compensated autonomous adenomas 
of the thyroid, iv thyrotropin releasing hormone (TRH) tests 
(200 pg) and oral TRH tests (40 rag) were performed. In nine of 
these patients, thyroid-stimulating hormone (TSH) 30 min after 
iv TRH showed a normal (>2.7 ~U/ml) and in eight patients 
a subnormal (<2.7 gU/ml) or negative response. However, after 
prolonged oral stimulation with 40 mg TRH, after 120-180 rain 
TSH was normal (>2.7 laU/ml) in 15 and subnormal ( <2.7 pU/ml) 
in two patients. 
In 20 patients with decompensated autonomous thyroid nod- 
ules, TSH was not detectable ( <0.8 gU/ml) after iv or oral TRH 
stimulation. Therefore, the oral TRH stimulation test seemed to 
be superior to the iv TRH test in the discrimination of compensated 
and decompensated autonomous adenomas of the thyroid. 
Key words: Autonomous thyroid nodules- Oral TRH tes t -  Results 
Ergebnisse des oralen TRH-Tests zur Unterscheidung 
yon kompensierten and dekompensierten autonomen Adenomen 
der Schilddriise 
Zusammenfassung. Bei 17 Patienten mit kompensierten autonomen 
Adenomen der Schilddr%e wurden TRH-Teste mit 200 gg i.v. und 
40 mg oral durchgeffihrt. Bei 9 Patienten war TSH 30 min nach 
TRH i.v. normal (> 2.7 ltU/ml), dagegen zeigten 8 Patienten einen 
subnormalen (<2.7 laU/ml) oder fehlenden TSH-Anstieg. Nach 
verlfingerter Stimulation mit 40 mg TRH oral war TSH 
120-180 min bei 15 Patienten im Normbereich (>2.7 pU/ml) und 
nur bei 2 Patienten subnormal (< 2.7 gU/ml). 
Bei 20 Patienten mit dekompensierten autonomen Adenomen 
der Schilddrtise lag TSH sowohl nach i.v. als auch nach oraler 
TRH-Stimuladon in allen F/illen unter der Nachweisgrenze 
( < 0.8 laU/ml). 
Die Befunde sprechen daf/ir, dab der orate TRH-Test geeig- 
neter ist als der i.v. TRH-Test, um zwischen kompensierten und 
dekompensierten autonomen Adenomen der Schilddrfise zu unter- 
scheiden. 
Sehliissetw6rter: Autonomes Adenom - Oraler TRH-Test - Er- 
gebnisse 
Introduction 
Patients with scintigraphically decompensated autonomous thyroid 
nodules usually reveal negative intravenous 200 gg TRH tests [3]. 
Offprint  requests to : Dr. D. Jfingst (address see page 478) 
However. surprisingly comparable test results have been obtained 
in about 30% of patients with scintigraphically compensated auton- 
omous adenomas [2]. Therefore, diagnosis of compensated and 
decompensated autonomous thyroid nodules is based primarily 
on scintigraphic findings and only to a small extent on the results 
of in vitro parameters of thyroid function. However, the oral TRH 
stimulation test was introduced recently and has been believed 
to be useful in the evaluation of patients with impaired TSH reserve 
but euthyroid function [I. 4, 5]. In these studies, about 10%-12% 
of apparently euthyroid patients revealed negative intravenous 
200 lag TRH tests. In 50%-60% of these patients, autonomous 
production of thyroid hormones could be excluded by the 40-rag 
oral TRH test. It was the aim of this study to evaluate whether 
the oral TRH test is superior to the iv TRH test in the discrimina- 
tion of compensated and decompensated autonomous adenomas 
classified by nuclear imaging. 
Materials and Methods 
The study included a total of 37 outpatients (12 males and 25 
females) with an age ranging from 30 to 82 years. Diagnosis of 
autonomous thyroid nodules was based on the results of nuclear 
imaging with 99~Tc-pertechnate (employing a 20% uptake of the 
paranodular tissue as the discriminating value), including scintigra- 
phy, after suppression with 60 gg T3 tbr 10 days in cases suspected 
to have compensated autonomous adenomas. In all patients, intra- 
venous TRH tests were performed after an overnight fasting period 
with a boluslike injection of 200 gg TRH and TSH-RIA (Henning, 
Berlin), 30 rain aRer TRH application. For oral TRH tests, a 40 mg 
tablet of TRH (Thyroliberin, Merck, FRG) was used and single 
TSH determinations were done after 120-180 min. There was an 
interval of 2-6 weeks between the iv and oral TRH tests. T4 was 
measured by enzyme immunoassay (Syva Company, Palo Alto, 
USA) and T 3 by radio immunoassay (Amersham-Buchler, 
Braunschweig, FRG). 
Results 
In 17 patients (5 males and 12 females), scintigraphy after suppres- 
sion revealed a formerly compensated autonomous adenoma. Con- 
centrations of thyroid hormones were measured prior to appIica- 
tion ofT~. T 4 (5.4-10.8 ~tg/dl, 2=7.4 pg/dl) and T3 (1.0-2.9 ng/ml, 
2,:: 1.9 ng/ml) concentrations in plasma were mainly in the normal 
range. 
Thyroid-stimulating hormone, 30 min after 200 gg iv TRH 
(0.8-14.6 gU/ml, 2=2.7 laU/ml), showed in nine patients a normal 
478 Kurze wissenschaftliche Mitteilungen 
(>2.7 btU/ml) and in eight patients a subnormal (<2.7 laU/ml) 
or negative response. However, TSH 120-180 min after 40 mg orat 
TRH was normal (>2.7 laU/ml) in 15 patients and subnormal 
(<2.7 gU/mt) in only two patients. 
In 20 patients (7 males and 13 females) scintigraphy demon- 
strated a primarily decompensated autonomous adenoma. In such 
cases, 30%-40% of T, (4.0-14.6gg/dl, 2=7.8~tg/dl) and T a 
(1,6 4.3 ng/ml, ~7=2.3 ng/ml) values were elevated. Thirty minutes 
after 200 gg iv TRH and 120-180 rain after 40 mg oral TRH, TSH 
was not detectable (<0.8 laU/ml) in all cases in accordance with 
the scintigraphic findings of decompensated autonomous thyroid 
nodules. 
Discussion 
Patients with scintigraphically decompensated autonomous thyroid 
nodules usually reveal negative iv 200 lag TRH tests. These data 
could be confirmed in the present study. 
Nearly 50% of the 17 patients with scintigraphically compen- 
sated autonomous thyroid nodules revealed a subnormal or nega- 
tive response to iv TRH in accordance with prior studies [2]. How- 
ever, prolonged stimulation with 40 mg oral TRH in these patients 
was associated with normal TSH response in 15 (88%) and subnor- 
mal in two (12%). All patients with decompensated autonomous 
thyroid nodules showed a failing TSH response to iv TRH and 
even to prolonged oral TRH stimulation. 
These findings point to a possible clinical validity of the oral 
TRH test as a help in the differentiation of compensated and 
decompensated autonomous adenomas, especially in borderline 
cases. In addition, in patients scintigraphically suspected to have 
compensated thyroid nodules, a negative result of an oral TRH 
test may help to exclude this diagnosis and prevent further diagnos- 
tic procedures, e.g., the T3-suppression-test. 
Acknowledgements. T4, T3 and TSH determinations were provided 
by Prof. Dr. W. Vogt, Bereich Endokrinologie und Stoffwechsel- 
chemie, Institute of Clinical Chemistry (Direktor Prof. Dr. M. 
Knedel), Klinikum Grosshadern University of Munich. 
References 
1. J/ingst D, Schineis E, Vogt W, Mann K, Karl HJ (1980) Parame- 
ters of thyroid function in thyroid autonomy. J Mol Med 
4:103-109 
2. Ribka A, Mayr B, Bfill U, Leisner B, Scriba PC (1979) Wertigkeit 
nuklearmedizinischer und endokrinologischer Methoden zur 
Klassifizierung autonomer Schilddriisenadenome. Med Klin 
74:511-.515 
3. Ridgway EC, Weintranb BD, Cellalos JL, Rack MC, Maloof 
F (1973) Suppression of pituitary TSH secretion in tile patient 
with a hyperfunctioning thyroid nodule. J Clin Invest 
52: 2783-2790 
4. Staub JJ, Girard J, Gemsenjfiger E (1976) Entwicklung eines 
einfachen oralen Kurztestes mit dem TSH-Releasing-Hormon 
(TRH) und dessen Anwendung in der Schilddrtisendiagnostik. 
Schweiz Med Wochenschr 106 : 1839 1842 
5. Vogt P, Girard J, Staub JJ (1978) Thyroid-Stimulating Hormone 
(TSH), Triiodothyronine (T3) and Thyroxine (T~) response to 
intravenous and oral stimulation with synthetic Thyrotropin- 
Releasing-Hormone (TRH) in young healthy adults. Klin Wo- 
chenschr 56: 31-35 
Received October 23, 1981 
Accepted November 8, 1981 
Dr. D. Jfingst 
Med. Klinik 2 
Klinikum Groi3hadern 
Marchioninistr. 15 
D-8000 Mfinchen 70 
Federal Republic of Germany 
Verantwortlich ffir den Texneil: Prof. Dr. Herbert Schwiegk und Prot: Dr. Hans JahrmS.rker. Medizinische K linik (Innenstadt) der Universitb.t, Ziemssenstrage 1. 
D-8000 Mfinchen 2; fiir den Anzeigenteih E. Lfickermanm R. Eicke, Springer-Verlag. Kuff~rstendamm 237. D-1000 Berlin 15. Springel~Verlag. 
Berlin Heidelberg New York und J.F. Bergm~nn Verlag, Miinchen. - Druck der Universitgtsdruckerei H. Sttirtz AG. Wiirzburg. 
Printed in Germany.- @~ Springer-Verlag GmbH & Co KG, Berlin Heldelberg 1982 


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Ergebnisse des oralen TRH-Tests zur Unterscheidung von kompensierten und dekompensierten autonomen Adenomen der Schilddrüse

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Results of oral TRH test in the differentiation of compensated and decompensated autonomous thyroid nodules

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