Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

II. Anterior Lobe and Intermediate Lobe
575
Pig FCIPTEYMMHVERKECAYCLTINTTICAGYCMTRDFNGKLFLPKYALSQDVCTYRDFMYK 60
Horse -----------------------------------I------------------------
Cattle -------------------------V---------V------------------------
Dog --F----T---------------------------I------------------------
Cat --F--------------------------------I---------------------L--
Human -------T--I--R---------------------I---------------------I-R
Rat ---------Y-D-R---------------------I---------------------T-R
Mouse -------T-Y-D-R---------------------I---------------------I-R
** **** * * *********** ********* ********************* *
Pig TVEIPGCPHHVTPYFSYPVAISCKCGKCNTDYSDCIHEAIKTNYCTKPQKSYVLEFSI 118
Horse --------D-----------V--------------------A-----------V----
Cattle -A------R-------------------------------------------MVG---
Dog --------R-----------V--------------------------------VG---
Cat --------------------V------C---------------D-------D-VGV--
Human --------L--A--------L------C------------------------LVG--V
Rat -----------A--------L------C-------T---V---------TF-LGG--G
Mouse ----------------F---V------C---N-------VR--------SF-LGG--V
* ****** ** **** *** ****** *** *** *** * ***** *
FIGURE 18-8 Sequence comparison of the β -subunit of TSH. See the legend for Figure 18-6 .
Horse
Pig
Cattle
Cat
Dog
Human
Rat
Mouse
et al. , 2003 ) at the pituitary and hypothalamic level. The
prohormone thyroxine (T 4 ) must therefore be converted
locally to the active 3,3 ,5-triiodothyronine (T 3 ) by type 2
iodothyronine deiodinase (D2) before binding to the nuclear
thyroid hormone receptor of the thyrotrope ( Christoffolete
et al. , 2006 ). Superimposed on this regulatory system, hypothalamic
factors (somatostatin, dopamine) may inhibit TSH
synthesis and release. Intrapituitary growth factors can also
stimulate (EGF) or inhibit (Neuromedin B) TSH release
(Pazos-Moura et al. , 2003 ). Evidence has been presented on
an ultra-short-loop feedback control by TSH through pituitary
folliculostellate cells ( Prummel et al. , 2004 ).
In the dog, TRH stimulates plasma TSH concentrations.
Single administration of TRH results in slightly
higher plasma TSH concentrations than measured after
combined stimulation with four releasing hormones ( Meij
et al. , 1996b ). In euthyroid dogs, cTSH release is relatively
stable with hardly any pulses as measured during a
6-h pulse study, whereas in hypothyroid dogs, an increased
basal concentration coincides with higher pulse frequencies
( Kooistra et al. , 2000b ).
d . Action
TSH stimulates both synthesis and secretion of thyroid
hormones from the thyroid gland. After receptor binding,
TSH stimulates via the Gs alpha protein the production of
cAMP, which acts as an intracellular second messenger. In
addition, intracellular Ca 2 may modulate the biological
effect of TSH via the phosphoinositol pathway. As a result
of receptor activation T 4 , and to a much lesser extent T 3 , is
secreted into the blood. Prolonged stimulation of the thyroid
with TSH results not only in hypersecretion of thyroid hormone
but also in enlargement of the thyroid gland. Genetic
analysis of DNA from hyperplastic or adenomatous thyroid
nodules in cats has revealed that somatic mutations in
the TSH-receptor or in the Gs alpha protein are the cause
of feline thyroid hyperplasia ( Peeters et al. , 2002 ; Watson
et al. , 2005 ). Apart from the thyroid, TSH receptors have been
found in brain and pituitary where they may have a function
in feedback mechanisms, and in lymphocytes, thymus, testis,
kidney, adipose tissue, and bone ( Davies et al. , 2005 ).
e . Disease/Tests
Since 1995, sensitive TSH assays have become available
for the dog ( Williams et al. , 1996 ). Since then numerous
reports have been published on the usefulness of cTSH measurements
in the diagnosis of canine hypothyroidism. Low
total plasma T 4 concentrations may be caused by decreased
binding to plasma TBG—such as seen after long-term glucocorticoid
excess in Cushing’s syndrome or interference of
T 4 binding to TBG by, for instance, NSAIDs or antiepileptic
drugs—and they are therefore not conclusive for the diagnosis
of hypothyroidism. Unfortunately some 25% to 40%
of dogs with proven hypothyroidism will have plasma cTSH
concentrations within the reference range for healthy dogs
( Boretti and Reusch, 2004 ; Peterson et al. , 1997 ). In dogs
with nonthyroidal disease also low serum concentrations
of total T 4 are seen with serum TSH concentrations that
remain within the reference range ( Kantrowitz et al. , 2001 ).
In a recent study, quantitative measurement of thyroidal
99 mTcO 4 showed no overlap between dogs with primary
hypothyroidism and nonthyroidal illness ( Diaz Espineira
et al. , 2007 ) and may together with a thyroid biopsy be the
ultimate proof of primary hypothyroidism.
Secondary hypothyroidism caused by a pituitary tumor
( Rijnberk, 1971 ) or panhypopituitarism caused by a suprasellar
tumor ( Eigenmann et al. , 1983b ) is rare . German shepherd
dogs with dwarfism have a secondary hypothyroidism,
which can be demonstrated by a blunted TSH response on
TRH in a combined pituitary function test ( Kooistra et al. ,
2000c ). For further details, refer to Chapter 20 on thyroid
function .
Chemical induction of hypothyroidism in horses using
the antithyroid drug PTU results in a steady increase of
plasma TSH concentration and an exaggerated response to
TRH administration ( Breuhaus, 2002 ).