Pituitary pars intermedia dysfunction in horses associated to pituitary adenoma / Disfunção da pars intermedia da hipófise em equinos associado a adenoma pituitário

The clinical syndrome of the pituitary pars intermedia dysfunction (PPID) is the most common endocrinopathy of older horses. This syndrome is characterized by several clinical and pathological changes, which are usually associated with adenomas of the pars intermedia (PI) of the pituitary gland. The aim of this work is to describe five cases of pituitary adenoma of the PI associated with PPID in horses, addressing its clinical and pathological aspects. The horses had a mean of 22 years of age. The main clinical signs were hirsutism and paresis of hind limbs, and at post mortem examination all horses had hirsutism, and a nodule in the pituitary gland, which was histologically characterized as an adenoma of PI (5/5). Furthermore, two horses had gross lesions suggestive of chronic laminitis. Moreover, there was intense parasitism of Sarcocystis neurona (2/5), Strongylus vulgaris (1/5), Parascaris equorum (1/5), Draschia megastoma (1/5), and Klossiella equi (1/5).

A síndrome clínica da disfunção da pars intermedia da hipófise (PPID) é a endocrinopatia mais comum em cavalos idosos. Essa síndrome é caracterizada por várias alterações clínicas e patológicas, geralmente associadas a adenomas da pars intermedia (PI) da hipófise. O objetivo deste trabalho é descrever cinco casos de adenoma hipofisário de PI associado a PPID em equinos, abordando seus aspectos clínicos e patológicos. Os cavalos apresentaram média de 22 anos de idade. Os principais sinais clínicos incluíam hirsutismo e paresia dos membros pélvicos, e no exame post mortem todos os equinos apresentavam hirsutismo e um nódulo na glândula pituitária, que foi histologicamente caracterizada como um adenoma de PI (5/5). Além disso, dois cavalos tinham lesões macroscópicas sugestivas de laminite crônica. Ainda, havia intenso parasitismo de Sarcocystis neurona (2/5), Strongylus vulgaris (1/5), Parascaris equorum (1/5), Draschia megastoma (1/5) e Klossiella equi (1/5).

Juvenile panhypopituitarism in a dog - what are the therapeutic challenges?

Background: Juvenile panhypopituitarism is an endocrinopathy that affects young dogs and must be differentiated from other causes of height disorders, as one could have a deficiency of one or more adenohypophysis hormones, besides growth hormone. Diagnosis consists of excluding endocrine and non-endocrine causes. Treatment requires administration of heterologous porcine growth hormone or progestins, as well as supplementing other hormones that are deficient in the circulation. The prognosis for these patients tends to be unfavorable and they have a shorter life expectancy. The present case aimed to report the therapeutic challenges in a dog diagnosed with juvenile panhypopituitarism. Case: This study presents the case of a 6-month-old crossbred Labrador/Brazilian Fila dog, not neutered, 6.7 kg of body weight (body condition score 5/9), with a growth disorder and persistence of the puppy coat, when compared to other members of the same litter. During inspection, it was possible to observe an undersized dog and soft puppy coat, besides no bone irregularities or joint tenderness was noted. The other physical examination parameters were within the normal range for the species. No changes in complete blood count and only increases in urea, cholesterol and alkaline phosphatase activity were observed. Thyroid and abdominal ultrasound (US) examination did not reveal any remarkable changes. After serum dosage of insulin-like growth factor, thyroxine, thyrostimulating hormone, and cortisol, the patient was diagnosed with juvenile panhypopituitarism and underwent therapy with medroxyprogesterone and thyroid hormone supplementation. Monitoring was instituted at intervals of 3, 6, and 12 weeks, and currently every 3 or 4 months and the IGF-1 values normalized after 6 months with. After 8 months of therapy, the patient had good body growth and bone mineralization compared to the time of diagnosis. However, skeletal development was completed only 12 months after hormone replacement, accompanied by the presence of vertebral osteophytes and coxofemoral osteoarticular alterations. Considering chronic use of progestins, ovariosalpingohysterectomy (OSH) was recommended, but for personal reasons, the owners chose to do not submit her to surgery. After 18 months of treatment, the dog starts to exhibit prostration, selective appetite, and increased abdominal volume. After imaging exam, she was forwarded for OSH, due to consistent findings of pyometra. Subsequently, even the supervision of possible comorbidities involved in the chronic use of progestins was maintained at half-yearly intervals, the bitch returned to the service with skin thickening, increased limb volume, and macroglossia after 60 months of therapy. At this point IGF-1 values were higher when compared to the previous measurements and the application of medroxyprogesterone was suspended. Its supplementation was reintroduced only after 8 months when IGF-1 was significantly reduced. To date, the patient is close to 6 years of age and with a good quality of life. Discussion: The greatest therapeutic challenge for these patients involves dealing with the adverse effects of progestins, mainly related to reproductive disorders and alopecia at the application site, as well as maintaining adequate hormone replacement in order to avoid hypersomatotropism. Although longevity is lower in these individuals, the patient in this report has achieved 6 years of age and has had an excellent quality of life so far.

Central blindness associated with a pituitary adenoma in a mare / Cegueira de origem central associado a adenoma de pars intermedia de hipófise em uma égua

Background: Pituitary pars intermedia (PI) adenoma is a benign adenohypophysis neoplasm, rare in Brazil, which maycompress adjacent structures and lead to dysfunctions of the endocrine organs. The most affected species are equines,particularly aged animals. This neoplastic disease is often associated with Cushing’s syndrome, when the pituitaryadrenocortical axis is affected. However, this neoplasm is seldom associated with clinical blindness. This paper describesa case of pituitary pars intermedia (PI) adenoma which caused blindness in a mare.Case: An emaciated, blind mare that had difficulty finding water and food was referred to “Hospital Veterinário de GrandesAnimais” of “Universidade Federal Rural do Rio de Janeiro”, in Seropédica, state of Rio de Janeiro, Brazil, and later tothe “Setor de Anatomia Patológica” (SAP/UFRRJ) for necropsy. During necropsy it was found that the animal’s pituitarygland consisted of a circumscribed globous mass measuring 3.5x2.5x2.5 cm, symmetrical and well delimited at the sellaturcica. Several organs were collected, fixed in 10% formalin and then processed for histological examination. The brainwas subjected to serial cleavage along the path of the vision organs. All collected tissues were stained with hematoxylinand eosin; the pituitary was stained with Schiff Periodic Acid (PAS) to differentiate neoplastic cells and with Luxol FastBlue to evidence demyelination. Histopathology found that the pars intermedia (PI) was thickened and compressed theneurohypophysis and adenohypophysis. Cells were arranged in a disorganized manner or formed follicles or cysts containing eosinophilic material (colloid), with granules strongly positive after staining with PAS. Proliferated cells werelarge, polyhedral to ovoid, and contained clear basophilic granular material. The nuclei were spherical to ovoid and therewere mild anisocytosis and anisocariasis. Cysts were frequently found in the pars intermedia (PI)...

Central blindness associated with a pituitary adenoma in a mare / Cegueira de origem central associado a adenoma de pars intermedia de hipófise em uma égua

Background: Pituitary pars intermedia (PI) adenoma is a benign adenohypophysis neoplasm, rare in Brazil, which maycompress adjacent structures and lead to dysfunctions of the endocrine organs. The most affected species are equines,particularly aged animals. This neoplastic disease is often associated with Cushings syndrome, when the pituitaryadrenocortical axis is affected. However, this neoplasm is seldom associated with clinical blindness. This paper describesa case of pituitary pars intermedia (PI) adenoma which caused blindness in a mare.Case: An emaciated, blind mare that had difficulty finding water and food was referred to “Hospital Veterinário de GrandesAnimais” of “Universidade Federal Rural do Rio de Janeiro”, in Seropédica, state of Rio de Janeiro, Brazil, and later tothe “Setor de Anatomia Patológica” (SAP/UFRRJ) for necropsy. During necropsy it was found that the animals pituitarygland consisted of a circumscribed globous mass measuring 3.5x2.5x2.5 cm, symmetrical and well delimited at the sellaturcica. Several organs were collected, fixed in 10% formalin and then processed for histological examination. The brainwas subjected to serial cleavage along the path of the vision organs. All collected tissues were stained with hematoxylinand eosin; the pituitary was stained with Schiff Periodic Acid (PAS) to differentiate neoplastic cells and with Luxol FastBlue to evidence demyelination. Histopathology found that the pars intermedia (PI) was thickened and compressed theneurohypophysis and adenohypophysis. Cells were arranged in a disorganized manner or formed follicles or cysts containing eosinophilic material (colloid), with granules strongly positive after staining with PAS. Proliferated cells werelarge, polyhedral to ovoid, and contained clear basophilic granular material. The nuclei were spherical to ovoid and therewere mild anisocytosis and anisocariasis. Cysts were frequently found in the pars intermedia (PI)...(AU)

Morphological and immunohistochemical comparison of the pituitary gland between a tropical Paracheirodon axelrodi and a subtropical Aphyocharax anisitsi characids (Characiformes: Characidae)

Cardinal tetra Paracheirodon axelrodi and bloodfin tetra Aphyocharax anisitsi are two species of characids with high trade value as ornamental fish in South America. Although both species inhabit middle water layers, cardinal neon exhibits a tropical distribution and bloodfin tetra a subtropical one. Generally, these species are difficult to grow, so it becomes essential to know some key components of the neuroendocrine system to achieve their reproduction in captivity. Considering the importance of deepening the knowledge of the reproductive physiology through functional morphology, for the first time in this work we performed an anatomical, morphological and immunohistochemical analysis of the pituitary gland of these two species. In both species, a leptobasic type pituitary is found in the ventral zone of the hypothalamus and it is characterized by a neurohypophysis which has a well-developed pituitary stalk and a globular adenohypophysis. The pituitary components, characterized by histochemistry and immunohistochemistry, shows a distribution pattern of cells types similar to other teleost species, with only slight differences in the distribution of βFSH and βLH for P. axelrodi.(AU)

El cardenal tetra Paracheirodon axelrodi y el tetra Aphyocharax anisitsi son dos especies de carácidos con alto valor comercial como peces ornamentales en América del Sur. Aunque ambas especies habitan en las capas medias de agua, el neón cardenal exhibe una distribución tropical, mientras que el tetra cola roja una distribución subtropical. En general estas especies son difíciles de cultivar, por lo que es esencial conocer algunos componentes clave de los sistemas neuroendocrinos para lograr su reproducción en cautiverio. Considerando la importancia de profundizar en el conocimiento de la fisiología reproductiva a través de la morfología funcional, en este trabajo realizamos, por primera vez, un análisis anatómico, morfológico e inmunohistoquímico de la glándula pituitaria de estas dos especies. En ambas especies, la hipófisis, del tipo leptobásica, se encontró en la zona ventral del hipotálamo y se caracteriza por una neurohipófisis con un tallo hipofisario bien desarrollado y una adenohipófisis globular. Los componentes hipofisarios, caracterizados por la histoquímica y la inmunohistoquímica, mostraron un patrón de distribución de tipos de células similares a otras especies de teleósteos, con solo pequeñas diferencias en la distribución de βFSH y βLH para P. axelrodi.(AU)

Morphological and immunohistochemical comparison of the pituitary gland between a tropical Paracheirodon axelrodi and a subtropical Aphyocharax anisitsi characids (Characiformes: Characidae)

Cardinal tetra Paracheirodon axelrodi and bloodfin tetra Aphyocharax anisitsi are two species of characids with high trade value as ornamental fish in South America. Although both species inhabit middle water layers, cardinal neon exhibits a tropical distribution and bloodfin tetra a subtropical one. Generally, these species are difficult to grow, so it becomes essential to know some key components of the neuroendocrine system to achieve their reproduction in captivity. Considering the importance of deepening the knowledge of the reproductive physiology through functional morphology, for the first time in this work we performed an anatomical, morphological and immunohistochemical analysis of the pituitary gland of these two species. In both species, a leptobasic type pituitary is found in the ventral zone of the hypothalamus and it is characterized by a neurohypophysis which has a well-developed pituitary stalk and a globular adenohypophysis. The pituitary components, characterized by histochemistry and immunohistochemistry, shows a distribution pattern of cells types similar to other teleost species, with only slight differences in the distribution of βFSH and βLH for P. axelrodi.(AU)

El cardenal tetra Paracheirodon axelrodi y el tetra Aphyocharax anisitsi son dos especies de carácidos con alto valor comercial como peces ornamentales en América del Sur. Aunque ambas especies habitan en las capas medias de agua, el neón cardenal exhibe una distribución tropical, mientras que el tetra cola roja una distribución subtropical. En general estas especies son difíciles de cultivar, por lo que es esencial conocer algunos componentes clave de los sistemas neuroendocrinos para lograr su reproducción en cautiverio. Considerando la importancia de profundizar en el conocimiento de la fisiología reproductiva a través de la morfología funcional, en este trabajo realizamos, por primera vez, un análisis anatómico, morfológico e inmunohistoquímico de la glándula pituitaria de estas dos especies. En ambas especies, la hipófisis, del tipo leptobásica, se encontró en la zona ventral del hipotálamo y se caracteriza por una neurohipófisis con un tallo hipofisario bien desarrollado y una adenohipófisis globular. Los componentes hipofisarios, caracterizados por la histoquímica y la inmunohistoquímica, mostraron un patrón de distribución de tipos de células similares a otras especies de teleósteos, con solo pequeñas diferencias en la distribución de βFSH y βLH para P. axelrodi.(AU)

Caracterização estrutural do hormônio folículo estimulante e seu papel na fisiologia de células ovarianas / Structural Characterization of the Follicle Stimulating Hormone and its role in the physiology of ovarian cells

The follicle stimulating hormone (FSH) is a heterodimeric glycoprotein synthesized and secreted in the pituitary anterior portion (adenohypophysis). The FSH performs important actions in the later stages of follicular development and maturation. The FSH exerts multiple functions such as the activation of more than 100 genes encoding different answers. The action of FSH is restricted to the granulosa cells. This gonadotropin acts through the activation of the enzyme adenylate cyclase in the plasma membrane, which forms AMPc from ATP. The AMPc promotes metabolic changes that characterize the gonadotropic action, usually through the phosphorylation of protein kinases. During the physiological process of ovulation, estrogens enhance the stimulatory effect of FSH and cause the release of FSH/LH required for ovulation. The mature follicle itself is responsible for ovulation, as it secrets estradiol, hormone responsible for the pre-ovulatory peak of LH, resulting in ovulation. Thus, the addition of FSH to the culture media characterizes important actions, as the follicular development and the ovulation process. Thus, the revision of the objective was to describe the role of FSH and its mechanism of action and receptor in ovarian follicular development. And as well as the effect of this on survival, activation and follicular growth.

O hormônio folículo estimulante (FSH) é uma glicoproteína heterodímera sintetizada e secretada na porção anterior da hipófise (adenohipófise). O FSH desempenha ações relevantes nos estádios mais avançados do desenvolvimento e maturação folicular. O FSH exerce múltiplas funções como a ativação de mais de 100 genes que codificam diferentes respostas. A ação do FSH está restrita as células da granulosa. Esta gonadotrofina atua por meio da ativação da enzima adenilciclase na membrana plasmática, a qual forma AMPc a partir de ATP. O AMPc promove as mudanças metabólicas que caracterizam a ação gonadotrópica, normalmente por meio da fosforilação de proteínas-quinases. Durante o processo fisiológico da ovulação, os estrógenos melhoram o efeito estimulador do FSH e provocam a liberação de FSH/LH necessária para a ovulação. O próprio folículo maduro é responsável pela ovulação, pois secreta estradiol, hormônio responsável pelo pico pré-ovulatório de LH, resultando na ovulação. Diante disso, a adição de FSH aos meios de cultivo caracteriza ações importantes, como, o desenvolvimento folicular e o processo de ovulação. Desta forma, o objetivo da revisão foi descrever o papel do FSH e seu mecanismo de ação e receptores no desenvolvimento folicular ovariano. E bem como, o efeito deste sobre a sobrevivência, a ativação e o crescimento folicular.

Caracterização estrutural do hormônio folículo estimulante e seu papel na fisiologia de células ovarianas / Structural Characterization of the Follicle Stimulating Hormone and its role in the physiology of ovarian cells

The follicle stimulating hormone (FSH) is a heterodimeric glycoprotein synthesized and secreted in the pituitary anterior portion (adenohypophysis). The FSH performs important actions in the later stages of follicular development and maturation. The FSH exerts multiple functions such as the activation of more than 100 genes encoding different answers. The action of FSH is restricted to the granulosa cells. This gonadotropin acts through the activation of the enzyme adenylate cyclase in the plasma membrane, which forms AMPc from ATP. The AMPc promotes metabolic changes that characterize the gonadotropic action, usually through the phosphorylation of protein kinases. During the physiological process of ovulation, estrogens enhance the stimulatory effect of FSH and cause the release of FSH/LH required for ovulation. The mature follicle itself is responsible for ovulation, as it secrets estradiol, hormone responsible for the pre-ovulatory peak of LH, resulting in ovulation. Thus, the addition of FSH to the culture media characterizes important actions, as the follicular development and the ovulation process. Thus, the revision of the objective was to describe the role of FSH and its mechanism of action and receptor in ovarian follicular development. And as well as the effect of this on survival, activation and follicular growth.(AU)

O hormônio folículo estimulante (FSH) é uma glicoproteína heterodímera sintetizada e secretada na porção anterior da hipófise (adenohipófise). O FSH desempenha ações relevantes nos estádios mais avançados do desenvolvimento e maturação folicular. O FSH exerce múltiplas funções como a ativação de mais de 100 genes que codificam diferentes respostas. A ação do FSH está restrita as células da granulosa. Esta gonadotrofina atua por meio da ativação da enzima adenilciclase na membrana plasmática, a qual forma AMPc a partir de ATP. O AMPc promove as mudanças metabólicas que caracterizam a ação gonadotrópica, normalmente por meio da fosforilação de proteínas-quinases. Durante o processo fisiológico da ovulação, os estrógenos melhoram o efeito estimulador do FSH e provocam a liberação de FSH/LH necessária para a ovulação. O próprio folículo maduro é responsável pela ovulação, pois secreta estradiol, hormônio responsável pelo pico pré-ovulatório de LH, resultando na ovulação. Diante disso, a adição de FSH aos meios de cultivo caracteriza ações importantes, como, o desenvolvimento folicular e o processo de ovulação. Desta forma, o objetivo da revisão foi descrever o papel do FSH e seu mecanismo de ação e receptores no desenvolvimento folicular ovariano. E bem como, o efeito deste sobre a sobrevivência, a ativação e o crescimento folicular.(AU)

Germline mutation analysis of Tpit in Poodle dogs with ACTH-dependent hyperadrenocorticism / Análise de mutação germinativa do Tpit em cães da raça Poodle com hiperadrenocorticismo ACTH-dependente

There is a high incidence of pituitary-dependent hyperadrenocorticism (PDH) in Poodle dogs, with family members being affected by the disease, suggesting a genetic involvement. Tpit is an obligate transcription factor for the expression of pro-opiomelanocortingene and for corticotroph terminal differentiation. The aim of the present study was to screen the Tpit gene for germline mutations in Poodles with PDH. Fifty Poodle dogs (33 female, 8.71±2.8 years) with PDH and 50 healthy Poodle dogs (32 females, 9.4241 2.8 years) were studied. Genomic DNA was isolated from peripheral blood, amplified by PCR and submitted to automatic sequence. No mutation in the coding region of Tpit was found, whereas the new single nucleotide polymorphism p.S343G, in heterozygous state, was found in the same frequency in both PDH and control groups. We concluded that Tpit gain-of-function mutations are not involved in the etiology of PDH in Poodle dogs.(AU)

O hiperadrenocorticismo ACTH-dependente (HACAD) apresenta elevada incidência em cães da raça Poodle, sendo que membros da mesma família têm sido acometidos pela doença, sugerindo envolvimento genético. Tpit é um fator de transcrição obrigatório para a expressão do gene da pro-opiomelanocortina e para a diferenciação terminal dos corticotrofos. O objetivo deste trabalho foi pesquisar mutações germinativas no gene Tpit em Poodles com HACAD. Cinquenta cães da raça Poodle, 33 fêmeas, média de idade de 8,71±2,8 anos, com HACAD, e 50 cães Poodles saudáveis, 32 fêmeas, média de idade de 9,4±2,8 anos, foram estudados. Mutações na região codificadora do gene Tpit não foram identificadas. Foi observado um novo polimorfismo em heterozigose, p.S343G, com a mesma frequência no grupo de cães com HACAD e no grupo-controle. Conclui-se que a mutação ativadora no gene Tpit não está envolvida na patogênese do hiperadrenocorticismo ACTH-dependente em cães da raça Poodle.(AU)