Prolactinoma in a Dog.

A 12-year-old male Yorkshire Terrier was presented because of decreased appetite. Physical examination revealed mammary gland swelling and galactorrhea. Contrast-enhanced computed tomographic scanning of the skull indicated an enlarged pituitary gland, compatible with a pituitary tumor. The serum prolactin concentration was markedly elevated. One week after the start of treatment with the dopamine agonist cabergoline, the serum prolactin concentration normalized and the galactorrhea resolved. Cabergoline was administered for approximately 4 months and then discontinued. Subsequently, serum prolactin concentration increased again, and mammary gland swelling and galactorrhea reappeared. The dog was euthanized 10 months after the first detection of the galactorrhea because of problems not directly related to pituitary disease. Postmortem examination revealed an infiltrative adenoma of the pituitary gland with immunolabeling for prolactin. The clinical and histopathologic findings indicated the diagnosis of a functional prolactinoma in a male dog.

Histologic and immunohistochemical characterization of spontaneous pituitary adenomas in fourteen cynomolgus macaques (Macaca fascicularis).

Pituitary adenomas were identified in 14 of 491 (2.9%) cynomolgus macaques evaluated from 1994 to 2004. Cases included male (8) and female (6) cynomolgus macaques ranging from 18 to 32 years of age. Seven of the pituitary adenomas caused gross enlargement of the pituitary gland that was visible on postmortem examination, whereas the remaining 7 were multifocal microadenomas identified on histologic examination. A total of 35 adenomas were identified in the 14 macaques, 6 of which were being treated for diabetes mellitus. Mean (+/- SD) pituitary weight was 0.31 +/- 0.42 g, compared with 0.07 +/- 0.02 g for 430 historical control animals (P < 0.0001). Immunohistochemical staining for follicle-stimulating hormone, luteinizing hormone, prolactin, human growth hormone, thyroid-stimulating hormone, and adrenocorticotropic hormone was applied to pituitary tissue from all cases. Immunostaining revealed 22 of 35 (62.9%) lactotroph adenomas, 5 of 35 (14.3%) plurihormonal cell adenomas, 3 of 35 (8.6%) corticotroph adenomas, 2 of 35 (5.7%) null cell adenomas, 1 of 35 (2.9%) somatotroph adenomas, 1 of 35 (2.9%) mixed corticotroph-somatotroph adenomas, 1 of 35 (2.9%) mixed lactotroph-corticotroph adenomas, 0 of 35 gonadotroph adenomas, and 0 of 35 thyrotroph adenomas. This study represents the first extensive retrospective case series performed to evaluate the histologic and immunohistochemical characteristics of pituitary adenomas in cynomolgus macaques. Our findings indicated that macaque pituitary adenomas frequently had mixed histologic appearance and hormone expression, and that, similar to human pituitary adenomas, prolactin-secreting neoplasms were the most prevalent type.

Resolution of a hyperprolactinemia in a western lowland gorilla (Gorilla gorilla gorilla).

Prolactin-secreting pituitary adenomas are one of the most common causes of infertility in women. Prolactin plays an important role in lactation and is involved in producing some of the normal mammalian breeding and maternal behaviors. Elevated serum prolactin concentrations can adversely affect the reproductive cycle in females by inhibiting the normal lutenizing hormone surge that stimulates ovulation. A 17-year-old western lowland gorilla (Gorilla gorilla gorilla) presented with low fertility and hyperprolactinemia. An MRI confirmed a pituitary mass and treatment was initiated with cabergoline. Following 8 mo of treatment, mass size decreased and serum prolactin was within normal limits. The gorilla began to engage in normal breeding behavior, and within 6 mo of completing treatment, was pregnant. Hyperprolactinemia, secondary to presumed microprolactinoma, may be more common among breeding-age gorillas than is currently diagnosed and in humans is an easily diagnosed and treatable condition.

Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed growth hormone/prolactin cell pituitary adenomas and natural killer cell lymphomas.

Overexpression of HMGA1 proteins is a constant feature of human carcinomas. Moreover, rearrangements of this gene have been detected in several human benign tumors of mesenchymal origin. To define the role of these proteins in cell transformation in vivo, we have generated transgenic mice overexpressing ubiquitously the HMGA1 gene. These mice developed mixed growth hormone/prolactin cell pituitary adenomas and natural killer (NK)-T/NK cell lymphomas. The HMGA1-induced expression of IL-2 and IL-15 proteins and their receptors may account for the onset of these lymphomas. At odds with mice overexpressing a wild-type or a truncated HMGA2 protein, adrenal medullar hyperplasia and pancreatic islet cell hyperplasia frequently occurred and no increase in body size and weight was observed in HMGA1 mice. Taken together, these data indicate an oncogenic role of the HMGA1 gene also in vivo.

Tumour dose response to the antivascular agent ZD6126 assessed by magnetic resonance imaging.

ZD6126 is a vascular targeting agent that disrupts the tubulin cytoskeleton of proliferating neo-endothelial cells. This leads to the selective destruction and congestion of tumour blood vessels in experimental tumours, resulting in extensive haemorrhagic necrosis. In this study, the dose-dependent activity of ZD6126 in rat GH3 prolactinomas and murine RIF-1 fibrosarcomas was assessed using two magnetic resonance imaging (MRI) methods. Dynamic contrast-enhanced (DCE) MRI, quantified by an initial area under the time-concentration product curve (IAUC) method, gives values related to tumour perfusion and vascular permeability. Multigradient recalled echo MRI measures the transverse relaxation rate T(2)*, which is sensitive to tissue (deoxyhaemoglobin). Tumour IAUC and R(2)* (=1/T(2)*) decreased post-treatment with ZD6126 in a dose-dependent manner. In the rat model, lower doses of ZD6126 reduced the IAUC close to zero within restricted areas of the tumour, typically in the centre, while the highest dose reduced the IAUC to zero over the majority of the tumour. A decrease in both MRI end points was associated with the induction of massive central tumour necrosis measured histologically, which increased in a dose-dependent manner. Magnetic resonance imaging may be of value in evaluation of the acute clinical effects of ZD6126 in solid tumours. In particular, measurement of IAUC by DCE MRI should provide an unambiguous measure of biological activity of antivascular therapies for clinical trial.

Prolactinoma in a sheep.

This report describes the incidental finding of an acidophilic adenoma of the pituitary gland in an adult ewe with clinical signs of a nervous disorder. Immunohistochemical examination demonstrated prolactin in the tumour cells, justifying the use of the term "prolactinoma" for the first time in veterinary medicine. This tumour should be considered in the differential diagnosis of nervous diseases of sheep.

Prolactin-secreting pituitary adenomas with mammary dysplasia in New Zealand white rabbits.

Nine aged (mean age = 3.2 years) nulliparous New Zealand white rabbit does were found to have markedly enlarged teats. The teats were frequently engorged with fluid but were not hot and did not cause signs of pain. The number of affected teats per animal ranged from 1 to 8 (mean = 4). The teats and associated glandular tissue were typically discolored grey, blue, or greenish black (n = 6). Prolactin concentrations were evaluated by radioimmunoassay. Serum prolactin concentrations ranged from 22.4 ng/ml to 2.21 micrograms/ml (mean = 397.3 ng/ml), which was 10- to 1000-fold greater than normal values in nonpregnant rabbits. Conventional radiography of the skull of six rabbits did not reveal pituitary enlargement. Necropsy revealed an enlarged pituitary gland and sella turcica in six of nine does. The diaphragma sellae had ruptured in two rabbits. All nine rabbits had pituitary acidophil adenomas. The neoplastic portions of the pituitaries were diffusely immunoreactive when stained immunohistochemically for prolactin. In contrast, only small clusters of five to seven cells stained positively in normal pituitaries selected as controls. Histologic examination of the mammary glands revealed numerous large dilated cystic spaces containing proteinaceous fluid. Many cysts had numerous papillary epithelial infoldings. The cystic dilations extended into and included the teat canal producing the gross appearance. Prolactin-secreting acidophil adenomas have not been previously reported in the rabbit, and the association with mammary dysplasia is unique.