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Endocrine Manifestations of Cancer

Ectopic Hormone Production
Cory Brown, DVM, DACVIM (SAIM)

VetScan Mobile Diagnostics, Powell, OH, USA

Ectopic hormone production of endocrine origin from The diagnosis of ectopic ACTH production is based on
nonendocrine tumors is a particular type of paraneo- hormonal evidence of pituitary‐dependent hyperadren-
plastic syndrome. Some of the more common manifesta- ocorticism (PDH), normal to high endogenous ACTH
tions, such as hypoglycemia and hypercalcemia, are levels, and normal pituitary imaging. Therapy for ectopic
covered in Chapter 132. Those more particular to the corticotropin production has not been well defined in
endocrine system are covered in this chapter. animals, although treatment of the primary tumor
should be attempted. Treatment with trilostane, an adre-
nal enzyme blocker, resulted in adequate resolution of
Cushing Syndrome symptoms in one dog.

Recently, production of sex hormone steroid precursors
Etiology/Pathophysiology from adrenal cortical tumors has been identified as a
Corticotropin (also known as adrenocorticotropic hor- source of Cushing symptoms. These animals may demon-
mone – ACTH) is produced by the anterior pituitary and strate typical signs of Cushing disease, including polyuria/
stimulates cortisol production by the adrenal cortex. polydipsia, polyphagia, weight gain, potbellied appear-
Corticotropin has been demonstrated to be produced by ance, thin skin, and alopecia. Despite the clinical findings
a variety of tumors in human medicine, resulting in a consistent with hyperadrenocorticism, these animals
Cushing‐like syndrome. Although primarily reported test negative for hyperadrenocorticism by conventional
with small cell lung carcinoma, other tumor types screening methods (ACTH stimulation, low‐dose dexa-
include carcinoid tumors of the thymus, gastrointestinal methasone suppression test). However, an assay for par-
tract, thyroid, pancreas, and adrenal medulla. Ectopic ticular cortisol precursors (such as progesterone and
production of corticotropin is not well described in vet- 17‐OH‐progesterone) may reveal elevated concentrations.
erinary medicine, although sporadic case reports exist. It Although this condition is classically related to the pres-
is theorized by some that ectopic corticotropin produc- ence of an adrenal cortical tumor, cortisol precursors may
tion is underestimated in animals due to diagnostic be noted with pituitary‐dependent disease as well. This is
limitations. Routine pituitary imaging is not typically considered eutopic hormone production as opposed to
pursued in dogs diagnosed with Cushing disease. ectopic, as the hormone produced by the tumor is a prod-
Therefore, dogs with ectopic production of the hormone uct of the tumor itself. However, as the particular hor-
may be assumed to be pituitary dependent and treated mone being produced is atypical for expected forms of
accordingly. Based on this assumption, ectopic cortico- hyperadrenocorticism, it is worthy of mention.
tropin production may be more prevalent than is In the presence of a cortical tumor, surgical excision is
currently reported in the veterinary literature. generally recommended if presurgical staging allows.
Abdominal ultrasonography is particularly useful to
identify a tumor, local vascular invasion, and metastases.
Diagnosis and Treatment
Approximately 50% of adrenal cortical tumors are malig-
At a minimum, ectopic corticotropin production should nant, and presurgical screening may identify local
be considered in dogs with neoplastic disorders that vascular invasion, metastatic disease to distant organs
show concurrent symptoms of hyperadrenocorticism. (particularly the liver), and irregularity of the affected

Clinical Small Animal Internal Medicine Volume II, First Edition. Edited by David S. Bruyette.
© 2020 John Wiley & Sons, Inc. Published 2020 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/bruyette/clinical