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

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II. Serum Tumor Markers<br />

753<br />

also been identified in dogs with Sertoli cell tumors, making<br />

it a potentially useful marker for identifying testicular<br />

tumors ( Grootenhuis et al. , 1990 ).<br />

2 . Serum Parathyroid Hormone<br />

Increased serum parathyroid hormone (PTH) in the presence<br />

<strong>of</strong> hypercalcemia has been considered sufficient for the<br />

diagnosis <strong>of</strong> primary hyperparathyroidism. However, a retrospective<br />

case-control study suggests that normal PTH concentrations<br />

in the presence <strong>of</strong> hypercalcemia are an inappropriate<br />

physiological response by the parathyroid gland and are also<br />

consistent with primary hyperparathyroidism ( Feldman et al. ,<br />

2005 ). Although primary hyperparathyroidism is an uncommon<br />

disease <strong>of</strong> dogs and cats, both adenomas and carcinomas<br />

<strong>of</strong> the parathyroid glands are reported in the literature and<br />

should be considered among the differential diagnoses.<br />

3 . Parathyroid Hormone-Related Protein<br />

Hypercalcemia <strong>of</strong> malignancy is a well-recognized paraneoplastic<br />

syndrome in animals. Hypercalcemia <strong>of</strong> malignancy<br />

may arise from local bone resorption stimulated by<br />

metastatic bone lesions or through endocrine factors that<br />

disrupt normal calcium homeostasis ( Clines and Guise,<br />

2005 ). Ectopic production <strong>of</strong> PTH by tumors is a rare<br />

phenomenon, and most humoral hypercalcemia <strong>of</strong> malignancy<br />

may be explained by the inappropriate production <strong>of</strong><br />

parathyroid hormone-related protein (PTHrP) by a variety<br />

<strong>of</strong> tumors. Canine PTHrP is similar in structure and function<br />

to PTH ( Rosol et al. , 1995 ). In dogs, PTHrP has been<br />

implicated in hypercalcemia associated with apocrine gland<br />

adenocarcinoma <strong>of</strong> the anal sac and lymphoma ( Rosol<br />

et al. , 1992 ), melanoma ( Pressler et al. , 2002 ), thymoma<br />

( Foley et al. , 2000 ), and poorly differentiated carcinoma.<br />

Increased serum PTHrP concentration has been identified<br />

in a small number <strong>of</strong> cats with humoral hypercalcemia <strong>of</strong><br />

malignancy associated with a variety <strong>of</strong> carcinomas and<br />

lymphoma ( Bolliger et al. , 2002 ). Increased serum PTHrP<br />

has also been described in a horse with hypercalcemia and<br />

multiple myeloma ( Barton et al. , 2004 ).<br />

4 . Thyroxine/Thyroglobulin<br />

Estimates <strong>of</strong> the proportion <strong>of</strong> dogs with thyroid masses<br />

that are revealed to be carcinoma range from 51% to 100%<br />

( Scarlett, 1994 ). It is reported that 70% <strong>of</strong> dogs with thyroid<br />

carcinomas have increased concentrations <strong>of</strong> serum<br />

thyroglobulin, although these findings were not strongly<br />

correlated with serum thyroxine (T 4 ) concentrations<br />

(Verschueren et al. , 1991 ). It is generally accepted that most<br />

dogs with thyroid carcinomas are euthyroid, but the contemporary<br />

peer-reviewed literature is sparse with respect to<br />

the prevalence <strong>of</strong> functional thyroid tumors in dogs.<br />

In cats elevated serum total or free T 4 is generally<br />

diagnostic for hyperthyroidism, although some cats with<br />

nonthyroidal disease may have elevated free T 4 ( Peterson<br />

et al. , 2001 ). Cats with equivocal results may require additional<br />

evaluation with the triiodothyronine (T 3 ) suppression<br />

test to confirm the diagnosis <strong>of</strong> hyperthyroidism ( Graves<br />

and Peterson, 1994 ). Unlike dogs, most cats with hyperthyroidism<br />

have a functional adenoma or adenomatous<br />

hyperplasia rather than an underlying thyroid carcinoma.<br />

Serial T 4 determinations are useful to monitor response to<br />

therapy and detect a relapse following radioiodine treatment<br />

( Peterson and Becker, 1995 ).<br />

5 . Adrenocorticotropin Hormone/Cortisol<br />

Hyperfunctioning adrenocortical tumors can be diagnosed by<br />

measuring basal plasma cortisol concentration or changes in<br />

plasma cortisol concentration from a variety <strong>of</strong> provocative<br />

tests using natural or synthetic adrenocorticotropin hormone<br />

(ACTH) stimulation or dexamethasone suppression. The<br />

measurement <strong>of</strong> endogenous ACTH may help distinguish<br />

primary adrenal disorders from those secondary to pituitary<br />

gland dysfunction. The ratio <strong>of</strong> the precursor hormones<br />

pro-opiomelanocortin and proadrenocorticotropin has been<br />

recently correlated to the size <strong>of</strong> pituitary tumors in dogs with<br />

hyperadrenocorticism ( Granger et al. , 2005 ). Measurement <strong>of</strong><br />

basal ACTH and the use <strong>of</strong> provocative testing with ACTH<br />

have been reported for the diagnosis <strong>of</strong> equine pituitary pars<br />

intermedia adenomas ( van der Kolk et al. , 1995 ).<br />

6 . Sex Steroid Hormones<br />

Measurement <strong>of</strong> plasma sex steroid hormones is useful for<br />

characterization <strong>of</strong> equine GTCT in mares with clinical<br />

signs attributable to high plasma concentrations <strong>of</strong> testosterone<br />

or estrogen ( Meinecke and Gips, 1987 ; Stabenfeldt<br />

et al. , 1979 ). Occasionally plasma progestins are elevated.<br />

Considerable variation in sex steroid hormone pr<strong>of</strong>iles<br />

exists among affected horses and may be due to the presence<br />

<strong>of</strong> abnormal ovarian follicles, defects in aromatase<br />

activity, or possible feedback inhibition affecting gonadotropin<br />

secretion ( Hoque et al. , 2003 ).<br />

Determination <strong>of</strong> plasma concentrations <strong>of</strong> androstenedione,<br />

17-hydroxyprogesterone, and estradiol may be useful<br />

in diagnosing adrenocortical neoplasia in ferrets ( Rosenthal<br />

and Peterson, 1996 ). Likewise, increased plasma concentrations<br />

<strong>of</strong> these adrenal sex hormones have been observed in<br />

dogs with adrenal gland adenocarcinoma with provocative<br />

testing using ACTH ( Hill et al. , 2005 ). Elevated plasma<br />

progesterone has been described in a cat with a welldifferentiated<br />

adrenocortical adenocarcinoma ( Boord and<br />

Griffin, 1999 ).<br />

Much literature exists surrounding the presence <strong>of</strong> estrogen<br />

and progesterone receptors in mammary gland tumors<br />

<strong>of</strong> the dog. Recent findings reveal that dogs with biologically<br />

aggressive inflammatory mammary carcinomas had<br />

increased serum and tissue concentrations <strong>of</strong> androgens

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