STANDARD ARTICLE

Journal of Veterinary Internal Medicine

STANDARD ARTICLE| 1
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2018/10/27 1319
西村

Vet InternIntern Med.
Med. 2018;32:1319–1324.
2018;1–6.
J Vet

Use ofTRH-stimulated
growth hormone
Usebasalof basalandand TRH-stimulated
plasmaplasma
growth hormone
concentrations
todifferentiate
betweenprimary
concentrations to differentiate between primary
hypothyroidism and nonthyroidal illness in dogs
hypothyroidism and nonthyroidal illness in dogs
Tera Pijnacker|Hans S. Kooistra | Cathelijne F. Vermeulen || Jan A. Mol
Merel van der Vinne | Marrit Prins | Sara Galac
背景| Hans S. Kooistra | Cathelijne F. Vermeulen |Tera Pijnacker
・犬の甲状腺機能低下症の診断には総サイロキシン濃度(TT4)、遊離サイロキシン濃度(FT4)、甲状腺刺激
Background:A low plasma
thyroxine(TT ) concentration|in combination
withMola plasma TSH| total
Merel van der Vinne | MarritPrinsSaraGalacJan A.
concentration within reference range does not distinguish between hypothyroidism and nonthyroiホルモン濃度(TSH)の測定が主に使われている。
dal illness (NTI) in dogs. Hypothyroidism is associated with TSH-releasing hormone (TRH)-induced
increased release of growth hormone (GH).
Department of Clinical Sciencesof が基準範囲に入る症例が 30-38%存在する。
・甲状腺機能低下症の犬でTSH
Background:
low plasma
totalGHthyroxine(TTcanin combination with a plasma TSH4) concentration
Hypothesis:
Basal andATRH-inducedplasma
concentrations
be used to distinguishCompanion Animals, Utrecht University,・成長ホルモン(GH)の分泌増加がTSHhypothyroidの増加に関連する。
dogs from NTI
dogs. reference range does not distinguish between hypothyroidism and nonthyroiconcentration
withinUtrecht, The Netherlands
concenAnimals:
Twenty-one
dogs
signsHypothyroidism
consistent with hypothyroidism,
a low plasma
TTdal illness(NTI)
inwithdogs.
is associatedwithTSH-releasinghormone (TRH)-induced
・甲状腺機能低下症の犬ではTSH 放出ホルモン(TRH)刺激試験後にGHが増えるのに対し、tration, and a plasma TSH concentration within reference interval.
Correspondence
increased release of growth hormone (GH).
T.
Pijnacker,
DepartmentofClinical
Methods: Case control study. Thyroid scintigraphy was performed to classify dogs as having hypo甲状腺機能が正常な犬では GH が増えなかった。
Sciences of Companion Animals, Faculty ofthyroidismor NTI. All Basaldogs underwent
a TRH stimulation
test withGH
measurementof plasma can be used to distinguish
Hypothesis:and TRH-induced
plasmaconcentrations
目的
Veterinary Medicine, Utrecht University,
concentrations of GH and TSH before and 30 and 45 minutes after IV administration of TRH.
hypothyroid dogs from NTI dogs.
Yalelaan 108, 3584 CM, Utrecht,
Results: Eleven of the dogs were classified as hypothyroid and 10 as having NTI. Basal plasma GH
TT4 が低値でありTSH が基準範囲である甲状腺機能低下症の犬においてThe Netherlands.
concentration
hypothyroid dogs
(3.2withlg/l; range,
to 12.5 lg/l)withwas significantly
higherAnimals:in theTwenty-one
dogs
signs2.0
consistenthypothyroidism,a low plasma TT4 concenEmail: T.Pijnacker@uu.nl
than that in the NTI dogs (.73 lg/l; range, .45 to 2.3 lg/l), with minimal overlap, and1.GH の基礎値と 2.TRH 刺激後の GH と(p<0.001)
TSHを用いて甲状腺機能低下症と偽甲状腺機能低下症の鑑別がでtration, and a plasma TSH concentration within reference interval.
increased (p5.009) after TRH administration in hypothyroid dogs, whereas it did not change in NTI
dogs. At T545, plasma GH concentrations in hypothyroid dogs and NTI dogs did not overlap. The
Funding information
きるかを評価すること。
Methods: Case control study. Thyroid scintigraphy was performed to classify dogs as having hypoplasma TSH concentration did not change significantly after TRH administration in hypothyroid
American Kennel Club Canine Healththyroidismor NTI.
All indogs
underwenta TRH
test with measurement of plasma
dogs,
whereas it increased(p<.001)
NTI dogs.
At T545, there
was nostimulation
overlap in percentage
動物 n=21 Foundation, Grant/Award Number: CHF
TSHconcentrations
increase from baseline
hypothyroid
dogs. and 30 and 45 minutes after IV administration of TRH.
ofbetween
GH andTSH before
Grant-02138
・甲状腺機能低下症に合致する臨床症状が存在する。
Conclusions and Clinical Importance: Measurement of basal plasma GH concentration andResults: ofElevenof thewere classified
as hypothyroid
and 10andas having NTI. Basal plasma GH
concentrations
GH and TSH
afterdogs
TRH stimulation
can distinguishbetween hypothyroidism
・血漿 TT4 が基準値以下であり血漿 TSH
NTI concentration
inが基準範囲である。
dogs.
in the hypothyroid dogs (3.2 lg/l; range, 2.0 to 12.5 lg/l) was significantly higher
・２ヶ月以内に実験に影響を与える薬剤を与えていない。
(p<0.001) than that in the NTI dogs (.73 lg/l; range, .45 to 2.3 lg/l), with minimal overlap, andcanine,
diagnosis, scintigraphy,
increased(p5.009) thyroid
after TRH administration in hypothyroid dogs, whereas it did not change in NTI
方法
dogs. At T545, plasma GH concentrations in hypothyroid dogs and NTI dogs did not overlap. The
1.放射性過テクネチウム酸（99mTcO–）を用いた甲状腺のシンチグラフィー
plasma TSH concentration did not change significantly after TRH administration in hypothyroid
1 | INTRODUCTION
dogs, whereas it increased (p<.001) in NTI dogs. At T545, there was no overlap in percentage
甲状腺機能低下と偽甲状腺機能低下症に鑑別した。
is one of themost common endocrinopathies
in dogs.
TSH increase fromHypothyroidism
baseline betweenhypothyroid
dogs.
2.TRH 刺激試験
Diagnosing hypothyroidism relies upon measurement of basal plasma.......................................................................................................................................................................................
Conclusions and Clinical Importance: Measurement of basal plasma GH concentration andTRH 薬剤（protirelin）を 10μg/kg、静脈内投与し、投与前15 分(T-15)、0 分(T0)、投与後 30 分(T30)、concentrations of GH and TSH after TRH stimulation can distinguish between hypothyroidism and45 分(T45)の 4 点において GH、TSH の測定を行なった。
NTI in dogs.
|
結果
KEYWORDS
甲状腺シンチグラフィーにより甲状腺機能低下症
11 頭、偽甲状腺機能低下症 10 頭に鑑別した。
canine, diagnosis, scintigraphy, thyroid
GH：基礎値の GH 濃度は甲状腺機能低下症群の方が有意に高かった。カットオフ値は 1.8µg/L であった。
TRH 刺激試験後 GH：甲状腺機能低下症群では T30, T45 ともに基礎値と比べて有意に増加した。
偽甲状腺機能低下症群では有意な変化は認められなかった。
1 | INTRODUCTION
Abbreviations:
TcO , radioactive pertechnetate; GH, growth hormone;
1.95µg/L,
T45 でのカットオフ値は 1.75µg/L であった。
NTI, nonthyroidalT30illness;でのカットオフ値はrhTSH, recombinant human TSH; ROC,receiver
Hypothyroidism is one of the most common endocrinopathies in dogs.1
operating characteristics; TRE, thyroid hormone response element; TRH, TSHTSH：基礎値のTSHについては両群間で違いは認められなかった。
Diagnosing hypothyroidism relies upon measurement of basal plasma
releasing hormone; TSH, thyroid stimulating hormone; TT , total thyroxine.
.......................................................................................................................................................................................
TRH 刺激試験後のTSH：甲状腺機能低下症群では有意な変化が認められなかった。
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction inV 2018T45
any medium, provided theoriginal work is properly cited and is not used for commercial purposes. CopyrightThe Authors.
Journal of VeterinaryInternal
偽甲状腺機能低下症群では基礎値と比較してT30,で有意にTSH が増加した。
Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
TSH の基礎値からの変化率は T45 でのカットオフ値は 57％であった。
| 1
GH/TSH：基礎値のGH/TSH
は両群間で違いは認められなかった。
Vet InternIntern Med.
Med.
2018;1–6.
wileyonlinelibrary.com/journal/jvim 1319
J Vet
2018;32:1319–1324.
wileyonlinelibrary.com/journal/jvim
TRH 刺激試験後の GH/TSH：偽甲状腺機能低下症群では T30, T45 ともに基礎値より有意に低下していた。
甲状腺機能低下症群では T45 に基礎値より有意に増加していた。
T45 の GH/TSH のカットオフ値は 4.6 であった。
ディスカッション・基礎値の GH や TRH 刺激試験後の TSH、GH により甲状腺機能低下症と偽甲状腺疾患を鑑別できる。
・甲状腺シンチグラフィーは甲状腺機能低下症の鑑別で１番優れている。
・甲状腺機能低下症の犬の GH の増加は、成長ホルモン産生細胞が thyrosomatotropes に分化転換したことによる可能性がある。
・甲状腺機能低下症の犬において TRH 刺激で TSH が増加しなかった理由は TSH 産生細胞の消耗か TRH刺激の脱感作が起こった可能性が考えられる。もしくは TSH アッセイで検出できない TSH のアイソフォームが産生されたことによるかもしれない。
・TRH 刺激試験の信頼性と実用性を上げるためにさらに大規模な試験を実施していくことが必要である。
批評
・本研究は甲状腺機能低下症と偽甲状腺機能低下症（fT4↓、TSH→）の鑑別に大いに役立てる。
・現在 GH の測定が商業ベースで行われていないので相関する IGF-1 で代用可能かどうか。
・TRH 刺激試験についての安全性について。
Department of Clinical Sciences ofCompanion Animals, Utrecht University,Utrecht, The Netherlands

4

Correspondence
T. Pijnacker, Department of Clinical
Sciences of Companion Animals, Faculty of
Veterinary Medicine, Utrecht University,
Yalelaan 108, 3584 CM, Utrecht,
The Netherlands.
Email: T.Pijnacker@uu.nl

4Funding information
American Kennel Club Canine HealthFoundation, Grant/Award Number: CHF
Grant-02138

KEYWORDS

Abbreviations: 99mTcO–4 , radioactive pertechnetate; GH, growth hormone;
NTI, nonthyroidal illness; rhTSH, recombinant human TSH; ROC, receiver
operating characteristics; TRE, thyroid hormone response element; TRH, TSHreleasing hormone; TSH, thyroid stimulating hormone; TT4, total thyroxine.

1

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction inC 2018 The Authors. Journal of Veterinary Internal
any medium, provided the original work is properly cited and is not used for commercial purposes. Copyright VMedicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

wileyonlinelibrary.com/journal/jvim 1319
1
wileyonlinelibrary.com/journal/jvim

Vet InternIntern Med.
Med. 2018;32:1319–1324.
2018;1–6.
J Vet

99m–44C

| Journal of Veterinary Internal Medicine

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F I G U R E 2 偽甲状腺機能低下症犬
Boxplot showing the percentage
increase in plasma
10 匹および甲状腺機能低下症
TSH concentrations(%) from baseline,at 30
45 minutes
after
犬 11 匹において、TRH投与後30and分および45 分で、TRH administrationin 10 dogs with TSH
NTI and11 dogs with
ベースラインからの血漿濃度（％）の増加率を示すボックスプロット。点線は、
T =cut-off
45 におけるカ
hypothyroidism.
The dotted line represents thelevel (57%)
T =hypothyroid
45、偽甲状
at T545. Atットオフレベル（57％）を表す。で
T545, there was no overlap between
腺機能低下症と甲状腺機能低下症犬の犬との間に重dogs and dogs
with NTI
複が存在しませんでした。

beca

onal

significant differences in the time intervals T 5 0 to T 5 30 (P 5 .005)

hyparac-and T 5 0 to T 5 45 (P 5 .005), but with some overlap of the absolute

humimalvalues. At T 5 30, the median percentage increase in plasma TSH con-circu

TTSH,

gnifiwas

ypo-tney

centration from baseline in hypothyroid dogs (10%, range, 26%-161%)
was significantly lower (P < .001) than in dogs with NTI (351%, range,96%-1457%). Also at T 5 45 the median percentage increase in plasma
TSH concentration from baseline in hypothyroid dogs (4%, range, 26%-

TRH

ソマトhyr-52%) was significantly lower (P < .001) than in dogs with NTI (311%,gnifi-range, 62%-1167%; Figure 2), and noスタチン
overlap was present between

yroid

hypothyroid dogs and NTI dogs at this time point. Receiver operating

morecharacteristic curve analysis revealed a cut-off level at T 5 45 of 57%.
When the ratio between GH and TSH (the GH/TSH ratio) was cal-yroid

culated (Figure 1C), the median basal GH/TSH ratio in the hypothyroid001)

dogs (12.85; range, 5.38–52.35) did not differ (P 5 .53) from that in theeiver

NTI dogs (11.85; range, 1.37-32.00). The GH/TSH ratio decreased sig-

1.8nificantly (P 5 .001) after TRH administration in the NTI group; post

9 ofhoc analysis revealed significant differences in the time intervals T 5 0to T 5 30 (P 5 .005) and T 5 0 to T 5 45 (P 5 .005). In contrast, then of

GH administraGH/TSH ratio increased significantly (P 5 .038) after TRHTSH009)

tion in the hypothyroid group and post hoc analysis revealed a signifi-postcant difference in the time intervals T 5 0 to T 5 45 (P 5 .008) but not

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Boxplots showing plasma GH concentrations (mg/L;panel A), plasma TSH concentrations (mg/L; panel B) and the ratio
between the plasma concentrations of GH and TSH (GH/TSH;panel C) at baseline, and at 30 and 45 minutes after TRH
administration in 10 dogs with NTI and 11 dogs withhypothyroidism. One outlier is plotted individually. Doubleasterisks (**) indicate significant (P < .01) difference. Triple
asterisks (***) indicate significant (P < .001) difference in baseline
plasma GH concentrations between groups. Dotted lines
in panel A represent cut-off levels (1.95 mg/L for T 5 30 and
1.75 mg/L for T 5 45). At T 5 30 and T 5 45, there was no overlap
between hypothyroid dogs and dogs with NTI. The dotted line inpanel C represents the cut-off level (4.6) at T 5 45. At T 5 45,
there was no overlap between hypothyroid dogs and dogs withNTIFIGURE 1in T 5 0 to T 5 30 (P 5 .091). At T 5 45, no overlap
was present in theTRE が存在しないため
T4に関係なく放出
GH/TSH ratio between the dogs with NTI andthe hypothyroid dogs.

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GHdecrexpl

as s
GHoidisthala

maintorythehypoducttin shypsecr

Receiver operating characteristic curve analysis revealed that at T 5 45

tion

a GH/TSH ratio > 4.60 corresponded with hypothyroidism and a

concvalue < 4.60 with NTI.

roidT4rise

4 | DISCUSSION

marincrDiagnosing primary hypothyroidism can be challenging, as NTI can also

causlead to a decreased plasma TT4 concentration. Our study showsroidthat measurement of basal plasma GH concentration and plasma
concentrations of GH and TSH after TRH stimulation can distinguishindu