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Case report 

Concurrent Adrenal and Pituitary Adenomas in a Dog: A Case 
Report of Cushing's Disease 
Ecaterina Semzenisi1, Romelia Pop1, Dragoș Hodor1, Alexandra Morar1, Ibrahima Mamadou Sall1, Alexandru-Fla-
viu Tăbăran1.  

1. Department of Anatomic Pathology, Faculty of Veterinary Medicine, 
University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania 
* Correspondence: e-mail romelia.pop@usamvcluj.ro 

Abstract:  Neoplasms of endocrine organs occur in all animal species and are more commonly observed in dogs, cats, and horses. 
The simultaneous occurrence of pituitary and adrenal gland neoplasia can appear isolated or as a part of multiple endocrine neo-
plasias-like syndromes. This report describes a case of isolated simultaneous neoplasia of the pituitary and adrenal glands in a dog, 
leading to the development of Cushing's disease. The necropsy revealed a large adenoma 2.5 cm of the pituitary gland and medullary 
neoplasia of the left adrenal gland. This case, due to its rarity and complexity, presents a significant interest for the veterinary com-
munity. 
 
Keywords: endocrine neoplasm; pituitary neoplasia; adrenal gland neoplasia; pituitary adenoma. 

 

1. Introduction 
 Pituitary tumors are relatively common in dogs and have been increasingly recog-

nized in cats in recent decades [1,2]. Pituitary abnormalities occur in a 2:1 dog-to-cat ratio. 
Sporadically, we can also find pituitary neoplasms in horses [3] and lama Alpaca [4]. In  
 dogs, the most common pituitary tumor is corticotroph adenoma, characterized by a 
large number of chromophobe cells and often associated with the clinical syndrome of 
cortisol excess (Cushing's syndrome). However, invasive adenomas and adenocarcino-
mas have also been reported [5,6]. In contrast, in cats, the most common pituitary tumor 
is the somatotroph adenoma but hormonally silent adenomas are underdiagnosed due to 
the lack of a hormonal syndrome [7]. Adrenal gland neoplasia is the most commonly af-
fected endocrine disorder in domestic ferrets and older dogs (aged 7 years and above). 
Numerous cases of adrenocortical adenoma and carcinoma have also been reported in 
cattle [8,9].  In contrast, such neoplasms are rare in cats [10], horses [11], and small rumi-
nants. 

Whether occurring simultaneously or separately, neoplasia of the pituitary and ad-
renal glands accounts for approximately 90% of Cushing's disease cases in dogs. Also 
known as hyperadrenocorticism, Cushing's disease has several underlying causes, all 
leading to excessive cortisol production. In cases involving just pituitary adenoma, the 
condition is classified as Pituitary-Dependent Hyperadrenocorticism (PDH). In contrast, 
neoplasia (benign or malign) of one or both adrenal glands results in Adrenal-Dependent 
Hyperadrenocorticism (ADH). Regarding prevalence, studies indicate a rate of 0.20%, 
suggesting that around 2 out of every 1,000 dogs in general veterinary practice may pre-
sent with Cushing's syndrome [12].  Notably, there is a marked sex prevalence; among 
107 dogs diagnosed with PDH, 74.8% were females, while 25.2% were males [13]. 

This study describes the macroscopic and histological features observed in simulta-
neous neoplasia of the adrenal and pituitary glands. 

 

Received: 12.12.2024 

Accepted: 09.01.2025 

Published: 19.03.2025 

DOI: 10.52331/cvj.v30i1.73 

 

 

Copyright: © 2025 by the authors. Sub-

mitted for possible open access publica-

tion under the terms and conditions of 

the Creative Commons Attribution (CC 

BY) license (http://creativecom-

mons.org/licenses/by/4.0/). 



Cluj Vet J 2025, vol 30, issue 1 51 of 68 
 

2. Casse description 
A 12-year-old mixed-breed female dog was submitted for necropsy following a history of cachexia, 

enophthalmos, lethargy, polyuria, and polydipsia, along with significant abdominal distention and bilateral 
alopecia. While the biochemical blood parameters were within normal ranges, alkaline phosphatase (ALP) 
and alanine aminotransferase (ALT) levels were elevated. These clinical signs suggest a potential endocrine 
disorder. 

 

Figure 1. Brain and pituitary gland. Dog. A well-demarcated mass measuring approximately 2.5 cm was ob-
served within the pituitary gland (indicated by the white circle), compressing the surrounding tissue (Image A). 

The cross-section of the pituitary gland revealed a heterogeneous mass displaying a white-to-red appearance (Im-
age B). (Scale bar 2 cm). 

During the necropsy, several findings were noted. The pituitary gland was enlarged due to a mass meas-
uring approximately 2,5 cm, which exhibited significant expansive growth and compression of adjacent tis-
sues. Although the mass was not encapsulated, it was well vascularized and showed no visible infiltration 
into the surrounding tissue (Figure 1). The left adrenal gland is enlarged, measuring approximately 3x1.5 cm, 
with a smooth, well-defined surface. On the cross-section, a soft and yellow mass, exhibiting homogeneous 
features was observed partially replacing the adrenal medulla. The mass is well-circumscribed, with no infil-
tration into surrounding tissues. Adjacent adrenal tissue appears compressed but intact, with no signs of ma-
lignant transformation. The right adrenal gland showed medular  hiperplasia with nodular aspect (Figure 2), 
while normal  ratio of cortex and medulla in dogs is 1:2 [14].  



Cluj Vet J 2025, vol 30, issue 1 52 of 68 
 

 

 

Figure 2. Left adrenal gland (Image A). Replacing the adrenal medulla, a well-demarcated, yellow mass was observed 
(arrow) within the left adrenal gland. The right adrenal gland showed hiperplasia of cortex with nodular aspect 

showed with doted line. (Image B) (Scale bar 1 cm). 

 
For histological evaluation, pituitary and adrenal masses were fixed in 10% neutral buffered formalin 

(NBF) and subsequently embedded in paraffin following standard protocols. According to the manufacturer's 
protocols, two-micrometer-thick sections were prepared and stained with hematoxylin and eosin (H&E). The 
histological slides were examined under an Olympus BX51 microscope, and bright field images were captured 
using an Olympus SP350 digital camera and processed with Olympus cellSens software for further analysis. 

Replacing the pituitary gland, a well-demarcated, unencapsulated mass was observed. The mass is sup-
ported by a discrete fibrovascular stroma and consists of packets of hypertrophied polygonal to round cells 
with distinct cell borders arranged in nests with trabecular patterns. The cytoplasm is basophilic and lightly 
granulated with one central nucleus. Minimal nuclear and cellular pleomorphisms with rare mitotic figures 
are observed (Figure 3 images A and B).  

Within the adrenal medulla, a well-demarcated and encapsulated mass composed of sheets and cords, of 
polygonal cells was observed. The cells resemble normal adrenocortical cells. The tumoral cells have abundant 
clear and occasionally vacuolated cytoplasm. The cytoplasm is slightly eosinophilic, resembling zona reticu-
laris cells. The nuclei are round to oval with dispersed chromatin and discrete nucleoli. Mitotic figures are 
rare. The tumor is surrounded by a thin fibrous capsule, separating it from the adjacent normal adrenal tissue. 
The capsular invasion was not observed (Figure 3 images C and D). 



Cluj Vet J 2025, vol 30, issue 1 53 of 68 
 

 

Figure 3. Histological features of pituitary adenoma (Image A and B).  The tumor consists of packets of hypertro-
phied polygonal to round cells with a trabecular pattern. The cytoplasm is basophilic and lightly granulated with 
minimal polymorphism. No infiltration in adjacent tissue was noted. Histological features of adrenal gland ade-

noma. (Image C and D). Within the adrenal medulla, a well-demarcated, encapsulated mass composed of sheets of 
polygonal cells is observed. The tumor cells have abundant clear and occasionally vacuolated cytoplasm, with a 

slight eosinophilic feature. The nuclei are round to oval with dispersed chromatin and small nucleoli. Mitotic fig-
ures are rare. Hematoxylin and eosin stain. Ob. x20 (Image A and C), Ob. x40 (Image B and D). Scale bar 100 µm 

(Image A and C) and 50 µm  (Image B and D). 

3. Discussion 
Neoplasia of the pituitary and adrenal cortex both contribute to hyperadrenocorticism. However, there 

are several mechanisms of cause-effect in Cushing disease. In most cases, pituitary-dependent and adrenal-
dependent hyperadrenocorticism occur independently of each other. In cases when they appear simultane-
ously they can have an adrenal or pituitary-driven mechanism [14,15]. The majority of Cushing’s cases in dogs 
are pituitary-dependent, where a pituitary adenoma overproduces ACTH [16]. Adrenal hyperplasia is com-
monly seen as a secondary effect of pituitary tumors in pituitary-dependent adrenocorticism (PDH) but it 
does not typically progress to malignancy. This transformation is rare because most hyperplastic adrenal cells 
do not undergo malignant changes [17]. 

Cushing's disease constitutes about 2% of total clinical practice and has a diverse range of underlying 
causes, including incidentalomas (incidental findings of adrenal tumors) and large pituitary adenomas. In the 
majority of cases, the adenohypophyseal neoplasms associated with Cushing's disease are solitary and are 
predominantly classified as adenomas rather than carcinomas [13]. According to veterinary literature, the ma-
jority of pituitary tumors arise from adenohypophysis [1,18]. 



Cluj Vet J 2025, vol 30, issue 1 54 of 68 
 

Adrenal neoplasia in dogs, particularly with adrenocorticism, is assessed using protocols like those of 
the ACVIM [19]. Besides hematological testing, the ACTH stimulation test is another diagnostic tool, espe-
cially helpful in differentiating iatrogenic from spontaneous cases [20]. Further differentiation between pitui-
tary-dependent hyperadrenocorticism (PDH) and adrenal-dependent hyperadrenocorticism (ADH) can be 
achieved with the high-dose dexamethasone suppression test (HDDST) or endogenous ACTH levels. Imaging, 
such as abdominal ultrasound or MRI, is essential for visualizing adrenal or pituitary abnormalities. The in-
tegration of clinical signs, hormonal test results, and imaging findings ensures an accurate diagnosis. Misdi-
agnosis can occur if concurrent conditions mimic Cushing's disease, highlighting the need for careful evalua-
tion. Most adrenal incidentalomas are benign, but excluding ACC or metastases remains critical. Challenges 
arise from breed differences, variable tumor presentations, and limited diagnostic tools, often necessitating 
reliance on statistical data, which may not be universally applicable [20]. Species-specific variability further 
complicates standardization, emphasizing the need for a tailored, multidisciplinary approach [21]. 

Adrenalectomy is usually the primary treatment for adrenal tumors that cause clinical signs or manifest 
malignant characteristics, such as local invasion or thrombus formation. Although, the risk or perioperative 
mortality rate for adrenalectomy in dogs ranges from 20% to 24% [22].Previously there existed hypotheses 
that dogs could be a suitable model for comparative analysis of Cushing disease. However, recently it was 
proved that several main differences can not make it possible. Firstly, incidence and susceptibility make it 
tricky. Cushing's disease is significantly more common in dogs, with an incidence of 1–2 cases per 1,000 dogs 
annually, compared to 1.2–2.4 cases per million humans annually [23]. Initially, the differences in hormonal 
receptor expression and absence of human ACTH-producing cell lines complicate efforts to draw parallels 
between dog and human Cushing’s. As well as differences in tumor behavior [17]. 

4. Conclusions 
This report highlights a relatively rare case of simultaneous adrenal and pituitary tumors in a dog. Both 

tumors were benign but contributed to Cushing’s syndrome. Despite the large size of the pituitary tumor, 
neither neoplasm caused notable clinical symptoms during the dog’s life, with tumors only identified during 
necropsy. Concurrent adrenal and pituitary neoplasia is uncommon and usually occurs separately. 

Cushing’s disease remains a challenging disorder to diagnose in animals due to the unclear onset of pa-
thology and limited access to diagnostic technology. As a result, it is often diagnosed too late for effective 
classical treatment. This case also reinforces the importance of the hypothalamic-pituitary axis as a critical 
area for further study, offering valuable insight into the complex nature of endocrine disorders in veterinary 
medicine. 

 
Author Contributions: Conceptualization, methodology, formal analysis,writing—original draft preparation, E.S. and 
R.P. D.H.; validation, data curation, resources, writing—review and editing, A.M. I.M.S.  visualization, supervision,  
project administration, A.F.T.  

Funding: Please add:  This study was suported by the University of Agricultural Scinces and Veterinary Medicine Cluj-
Napoca.  

Institutional Review Board Statement: Not aplicable. 

Data Availability Statement: In this section, please provide details regarding where data supporting reported results 
can be found, including links to publicly archived datasets analyzed or generated during the study. You might choose 
to exclude this statement if the study did not report any data. 

Acknowledgments: In this section, you can acknowledge any support given which is not covered by the author contri-
bution or funding sections. This may include administrative and technical support, or donations in kind (e.g., materials 
used for experiments). 

Conflicts of Interest: The authors declare no conflict of interest. 

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500859/
https://pubmed.ncbi.nlm.nih.gov/19153526/

