Clinical features and their course of pituitary carcinoma with distant metastasis in a dog

An 11-year-old male toy poodle with neurological symptoms was diagnosed with a macroscopic pituitary tumor, which produced adrenocorticotropic hormone. Radiation therapy with a linear accelerator was performed for the pituitary tumor, and resulted in good local tumor control. However, serum endogenous adrenocorticotropic hormone concentrations were uncontrollable even after the tumor disappeared. Abdominal computed tomography revealed splenic masses, and splenectomy was performed. Histopathological examination of the surgical specimen showed tumor cells with eosinophilic and finely granular cytoplasm suggestive of endocrine origin. Since these cells were positive for adrenocorticotropic hormone, the case was diagnosed as a pituitary carcinoma with distant metastasis. Necropsy revealed multiple metastases to the abdominal organs. This is the first case report describing canine pituitary carcinoma with distant metastasis.     

Endocrine disorders and laminitis

Two common endocrine disorders, pituitary pars intermedia dysfunction and equine metabolic syndrome, predispose horses and ponies to laminitis and may even induce the condition. The exact mechanisms involved in endocrinopathic laminitis have not been elucidated but hyperinsulinaemia and insulin resistance are currently being investigated. Obesity and regional adiposity may also contribute to laminitis susceptibility through the release of inflammatory cytokines and adipokines. In the case of pituitary pars intermedia dysfunction, glucocorticoid excess is likely to weaken hoof structures, alter vascular dynamics within the foot and induce or exacerbate insulin resistance. This review will summarise current theories regarding the pathophysiology of endocrinopathic laminitis and provide recommendations for the diagnosis and management of these common equine endocrine disorders.     

Linear-Accelerator-Based Modified Radiosurgical Treatment of Pituitary Tumors in Cats: 11 Cases (1997–2008)

Objective: Determine the efficacy and safety of a linear-accelerator-based single fraction radiosurgical approach to the treatment of pituitary tumors in cats.
Design: Retrospective study.
Animals: Eleven client-owned cats referred for treatment of pituitary tumors causing neurological signs, or poorly controlled diabetes mellitus (DM) secondary either to acromegaly or pituitary-dependent hyperadrenocortism.
Procedures: Cats underwent magnetic resonance imaging (MRI) of the brain to manually plan radiation therapy. After MRI, modified radiosurgery was performed by delivering a single large dose (15 or 20 Gy) of radiation while arcing a linear-accelerator-generated radiation beam around the cat's head with the pituitary mass at the center of the beam. Eight cats were treated once, 2 cats were treated twice, and 1 cat received 3 treatments. Treated cats were evaluated for improvement in endocrine function or resolution of neurological disease by review of medical records or contact with referring veterinarians and owners.
Results: Improvement in clinical signs occurred in 7/11 (63.6%) of treated cats. Five of 9 cats with poorly regulated DM had improved insulin responses, and 2/2 cats with neurological signs had clinical improvement. There were no confirmed acute or late adverse radiation effects. The overall median survival was 25 months (range, 1–60), and 3 cats were still alive.
Conclusions and Clinical Importance: Single fraction modified radiosurgery is a safe and effective approach to the treatment of pituitary tumors in cats.     

Coarse fractionated radiation therapy for pituitary tumours in cats: a retrospective study of 12 cases

This retrospective study describes the clinical progression of 12 cats with pituitary tumours treated with a coarse fractionated radiation protocol delivering a total dose of 37 Gy in five once weekly fractions. A pituitary macrotumour was identified in all 12 cats: 4 with neurological signs only and 8 with insulin‐resistant diabetes mellitus secondary to acromegaly. One of the cats with central neurological signs died before completing the radiotherapy course; the remaining three had partial or complete remissions of their central neurological signs. Of the cats with unstable diabetes mellitus, five no longer required insulin therapy, one required less insulin and two became stable. The overall median survival time was 72.6 weeks; four cats died from related causes, two from unrelated problems and six remain alive. Radiation therapy is confirmed as an effective treatment for feline pituitary tumours, giving prolonged survival and control of both paraneoplastic and mass effect signs.     

Pituitary deficiencies

Diabetes insipidus, arising from damage to or congenital abnormalities of the neurohypophysis, is the most common pituitary deficiency in animals. Hypopituitarism and isolated growth hormone or thyrotropin deficiency may result in growth abnormalities in puppies and kittens. In addition, treatment of associated hormone deficiencies, such as hypothyroidism and hypoadrenocorticism, in patients with panhypopituitarism is vital to restore adequate growth in dwarfed animals. Secondary hypoadrenocorticism is an uncommon clinical entity; however differentiation of primary versus secondary adrenal insufficiency is of utmost importance in determining optimal therapy. This article will focus on the pathogenesis, diagnosis and treatment of hormone deficiencies of the pituitary gland and neurohypophysis.     

Hormonal responses to exercise and training

Current knowledge and understanding of the hormonal response to exercise are limited, whether in relation to horses, humans, or other species. The changes in plasma concentration of some hormones occur early in exercise, apparently owing to a neuronal stimulation, whereas others, being pituitary dependent, require hormonal stimulation. Also, although it is possible to observe changes in plasma concentrations of hormones, the mechanism by which this is achieved is not always understood, and unless the nonprotein-bound, or active, form of the hormone is also determined, changes in plasma concentration are less informative. Both the intensity and duration of exercise may be of importance in initiating or maintaining the hormonal response. Impulses from either the working muscles or motor centers, via the central nervous system, modify the response of the glands of the endocrine system directly via pituitary hormones or indirectly via the sympathoadrenal system. The initial response to the onset of exercise is enhancement of sympathoadrenal activity and secretion of pituitary hormones, which result in a reduction in the plasma concentration of insulin and a rise in that of virtually all other hormones. Because of this shift in hormone balance, a modification of the metabolism of intra- and extra-muscular triglycerides and glycogen as fuels for muscular exercise occurs. The variation in mobilization of one fuel source may well influence its combustion, together with both the mobilization and combustion of the other. When exercise is prolonged, the hormonal response is influenced by additional factors such as temperature, glucose availability, oxygen tension, and changes in plasma volume. The effect of training on hormonal responses is generally an ameliorating one that reflects an increased efficiency of muscular energy metabolism as a result of the training process.     

犬甲状腺机能减退并发糖尿病的中西医结合诊疗

犬甲状腺机能减退是由于甲状腺功能异常而引起甲状腺激素分泌不足或合成减少导致犬的内分泌紊乱的一类综合性疾病。长期的甲状腺激素分泌不足,可能继发糖尿病的发生。通过对1例患犬临床症状表现为全身被毛稀疏,多饮多尿多食,双眼白内障等,结合实验室检查(血常规、生化、甲状腺功能检查),总甲状腺(T4)<6.5,参考范围15 nmol/L^50nmol/L,血糖(GLU)20.7 mmol/L,参考范围3.9 mmol/L^8.0 mmol/L,确诊为甲状腺机能减退并发糖尿病。经补充左甲状腺素片治疗甲状腺机能减退,同时用胰岛素控制血糖,再结合中药和针灸辅助治疗病情得到缓解,为临床诊疗该类病提供了参考。     

The anterior pituitary gland: lessons from livestock

There has been extensive research of the anterior pituitary gland of livestock and poultry due to the economic (agricultural) importance of physiological processes controlled by it including reproduction, growth, lactation and stress. Moreover, farm animals can be biomedical models or useful in evolutionary/ecological research. There are for multiple sites of control of the secretion of anterior pituitary hormones. These include the potential for independent control of proliferation, differentiation, de-differentiation and/or inter-conversion cell death, expression and translation, post-translational modification (potentially generating multiple isoforms with potentially different biological activities), release with or without a specific binding protein and intra-cellular catabolism (proteolysis) of pituitary hormones. Multiple hypothalamic hypophysiotropic peptides (which may also be produced peripherally, e.g. ghrelin) influence the secretion of the anterior pituitary hormones. There is also feedback for hormones from the target endocrine glands. These control mechanisms show broadly a consistency across species and life stages; however, there are some marked differences. Examples from growth hormone, prolactin, follicle stimulating hormone and luteinizing hormone will be considered. In addition, attention will be focused on areas that have been neglected including the role of stellate cells, multiple sub-types of the major adenohypophyseal cells, functional zonation within the anterior pituitary and the role of multiple secretagogues for single hormones.     

Endocrine tumors.

Because of the diverse nature of endocrine organs, and their vast range of physiologic functions, endocrine tumors encompass a wide range of origination sites and disease entities. The clinical picture of affected individuals is highly dependent on the tissue of origin, and the presence or absence of functional hormone secretions. Identification, localization, and therapeutic strategies, as well as prognosis can vary greatly. Many endocrine tumors have been described in human as well as veterinary patients. This article focuses on endocrine tumors of dogs and cats. Various tumors affecting the pancreas, thyroid, parathyroid, adrenal and pituitary glands are described, including insulinoma, gastrinoma, glucagonoma, and thyroid carcinoma, as well as parathyroid hormone- and growth hormone-secreting tumors. The syndrome of multiple endocrine neoplasia is also described.     

Feline acromegaly

Acromegaly, or hypersomatotropism, results from chronic, excessive secretion of growth hormone in the adult animal. The anabolic effects of growth hormone are exerted through the intermediary hormone, insulin-like growth factor 1, which is produced in the liver under the influence of growth hormone. Feline acromegaly is caused by a pituitary adenoma that secretes excessive amounts of growth hormone. Characteristic effects of excessive growth hormone secretion include the development of diabetes mellitus and growth of the acral segments of the body (jaw, extremities, skull, etc.). Acromegaly occurs in older, predominately male cats and is often associated with diabetes mellitus. Other clinical signs include stridor, enlargement of the jaw and extremities, lean weight gain, and organomegaly (heart, liver, kidney, etc.). Diagnosis is made by documentation of increased levels of growth hormone or insulin-like growth factor (or both) and demonstration of a pituitary mass via magnetic resonance imaging or computed tomography. The most effective treatment to date has been radiation therapy. Prognosis is fair to good with proper treatment.     

Depot specific endocrine control of fatty acid synthesis in adipose tissues of foetal lambs

Chronic endocrine control of fatty acid synthesis in perirenal and subcutaneous adipose tissues of foetal lambs has been investigated. Maintenance of explants of subcutaneous adipose tissue in culture for 48 hr with insulin and dexamethasone (a glucocorticoid analogue), either singly or in combination showed that the two acted synergistically to increase the rate of fatty acid synthesis. Growth hormone inhibited the ability of insulin plus dexamethasone to increase the rate of fatty acid synthesis in explants of subcutaneous adipose tissue. In contrast neither insulin nor dexamethasone either singly or together increased the rate of fatty acid synthesis in perirenal adipose tissue; growth hormone also had no effect on the rate of fatty acid synthesis in this depot. These studies show that fatty acid synthesis is under distinct endocrine control in subcutaneous and perirenal adipose tissues in foetal lambs.     

Changes in plasma melanocyte-stimulating hormone,ACTH, prolactin,GH, LH,FSH, and thyroid-stimulating hormone in response to injection of sulpiride,thyrotropin-releasing hormone,or vehicle in insulin-sensitive and -insensitive mares

Six insulin-sensitive and 6 insulin-insensitive mares were used in a replicated 3 by 3 Latin square design to determine the pituitary hormonal responses (compared with vehicle) to sulpiride and thyrotropin-releasing hormone (TRH), 2 compounds commonly used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. Mares were classified as insulin sensitive or insensitive by their previous glucose responses to direct injection of human recombinant insulin. Treatment days were February 25, 2012, and March 10 and 24, 2012. Treatments were sulpiride (racemic mixture, 0.01 mg/kg BW), TRH (0.002 mg/kg BW), and vehicle (saline, 0.01 mL/kg BW) administered intravenously. Blood samples were collected via jugular catheters at −10, 0, 5, 10, 20, 30, 45, 60, 90, and 120 min relative to treatment injection. Plasma ACTH concentrations were variable and were not affected by treatment or insulin sensitivity category. Plasma melanocyte-stimulating hormone (MSH) concentrations responded (P < 0.01) to both sulpiride and TRH injection and were greater (P < 0.05) in insulin-insensitive mares than in sensitive mares. Plasma prolactin concentrations responded (P < 0.01) to both sulpiride and TRH injection, and the response was greater (P < 0.05) for sulpiride; no effect of insulin sensitivity was observed. Plasma thyroid-stimulating hormone (TSH) concentrations responded (P < 0.01) to TRH injection only and were higher (P < 0.05) in insulin-sensitive mares in almost all time periods. Plasma LH and FSH concentrations varied with time (P < 0.05), particularly in the first week of the experiment, but were not affected by treatment or insulin sensitivity category. Plasma GH concentrations were affected (P < 0.05) only by day of treatment. The greater MSH responses to sulpiride and TRH in insulin-insensitive mares were similar to, but not as exaggerated as, those observed by others for PPID horses. In addition, the reduced TSH concentrations in insulin-insensitive mares are consistent with our previous observation of elevated plasma triiodothyronine concentrations in hyperleptinemic horses (later shown to be insulin insensitive as well).     

Coarse Fractionated Radiation Therapy for Pituitary Tumours in Cats: A Retrospective Study of 10 Cases

Introduction:  Pituitary tumours are uncommon in cats. Signs may be due to either an expansile mass or paraneoplastic effects (acromegaly and/or unstable diabetes mellitus). There are a few small case series providing evidence of efficacy for radiotherapy of pituitary tumours in cats. This retrospective study describes the outcome of ten cats with pituitary tumours treated with course‐fractionated radiation.
Methods:  The medical records of cats with MRI‐confirmed pituitary tumours that underwent radiotherapy were reviewed. A standard coarse‐fractioned radiation protocol was used; 37 Gy in 5 once‐weekly fractions using two parallel‐opposed 4MeV X‐ray beams. Survival times were calculated from date of first radiation dose.
Results:  Ten cats with pituitary tumours underwent radiotherapy. 5 cats had CNS signs and 5 had evidence of growth hormone excess (1 cat also showed CNS signs). 2 cats with pre‐existing moderate to severe CNS signs died of unknown causes before completing the radiation course. Of the remaining 4 with CNS signs, 3 had complete resolution of signs and the fourth showed partial improvement. Of the 5 cats with unstable diabetes, 2 no longer required insulin and 3 became stable at a lowered dose. The median survival time was 77.6 weeks. 6 cats died: 2 without completing the radiation course, 2 from unrelated causes (CRF, VAFS) and 2 from relapse and/or progression of CNS signs. 4 cats remain alive (range 34–191 weeks).
Conclusions:  Radiation therapy is confirmed as an effective treatment for pituitary tumours in cats giving extended survival and control of both direct mass effect and paraneoplastic signs.     

Avian reproductive endocrinology.

Hypothalamic-releasing factors regulate the secretion of anterior pituitary hormones. The anterior pituitary gland secretes the same six hormones as found in mammals: FSH, LH, prolactin, GH (somatotropic hormone), ACTH, and TSH, plus the melanotropic hormone. The endocrine hormones of the avian posterior pituitary gland concerned with reproduction are mesotocin and AVT. The pineal gland, through the secretion of the hormone melatonin, modulates the periodic autonomic functions of the central nervous system. The ovary produces estrogens, progestogens, and androgenic compounds. The testes produce testosterones and progesterone. The thyroid glands produce two hormones, T4 and T3. The avian adrenal glands produce corticosterone and aldosterone. The bursa of Fabricius is considered an endocrine organ since it is involved in the production of humoral factors. The male reproductive system undergoes hormonal changes associated with puberty, the breeding season, and molt. Some avian species undergo a type of disintegration and seasonal reconstruction of the testis and epididymis. The relationship of the ovarian follicular hormones and the plasma hormones varies depending on the stage of the reproductive cycle and the seasonal photostimulation. Female birds may conceive in the absence of a mate as a result of the fertile period phenomena. The blood chemistry of laying birds is different from that seen in nonlaying hens. Domestication has had a definite influence on the hormone cycles of some avian species. This may lead to certain reproductive problems.     

脑肠肽激素Ghrelin及其在动物生产中的应用展望

Ghrelin是一种的由28个氨基酸组成的脑肠肽激素,是生长激素促泌素受体的内源性配体,主要由胃的一种内分泌细胞分泌,也分布于其他许多组织中,如下丘脑、垂体和胰腺等。Ghrelin与其特异性受体结合后,会产生一系列生物学效应,如刺激垂体前叶释放生长激素,增加采食,调节能量平衡,促进胃酸分泌和胃肠蠕动等作用。Ghrelin可能是新发现的下丘脑、垂体、胃之间内分泌调节的联系纽带,在动物生产中将起到重要的作用。     

N-甲基-D-天冬氨酸的研究进展

近年来研究表明 ,N 甲基 D 天冬氨酸 (NMDA)对神经和内分泌具有重要的调控作用。适量的NMDA能够显著促进动物腺垂体中生长激素 (GH)、黄体生成素 (LH)、促性腺激素释放激素 (GnRH)以及催乳素 (PRL)的分泌。本文对NMDA的结构、分布、生物合成、检测方法以及生物学功能等作一简要综述 ,并对其在畜牧业上的应用前景作一展望     

Growth hormone excess and the effect of octreotide in cats with diabetes mellitus

In this prospective study 16 cats with diabetes mellitus were examined for concurrent acromegaly by measuring plasma growth hormone (GH) and insulin-like growth factor-I concentrations, and magnetic resonance imaging (MRI) of the pituitary fossa. Additionally, the effects of octreotide administration on the plasma concentrations of glucose, GH, α-melanocyte-stimulating hormone (α-MSH), adrenocorticotrophic hormone (ACTH), and cortisol were measured.Five cats were diagnosed with hypersomatotropism. The pituitary was enlarged in these 5 cats and in 2 other cats. Six cats that required a maximum lente insulin dosage ≥1.5 IU/kg body weight per injection had pituitary enlargement and 5 of these cats had acromegaly. Plasma concentrations of GH, ACTH, and cortisol decreased significantly after single intravenous administration of the somatostatin analogue octreotide in the acromegalic cats. The effect on GH concentrations was more pronounced in some of the acromegalic cats than in others. In the non-acromegalic cats only ACTH concentrations decreased significantly. In both groups plasma glucose concentrations increased slightly but significantly, whereas α-MSH concentrations were not significantly affected.In conclusion, the incidence of hypersomatotropism with concomitant pituitary enlargement appears to be high among diabetic cats with severe insulin resistance. Some of these cats responded to octreotide administration with a pronounced decrease in the plasma GH concentration, which suggests that octreotide administration could be used as a pre-entry test for treatment with somatostatin analogues.     

Alterations in the ability of the bovine pituitary gland to secrete gonadotropins in vitro during the first follicle-stimulating hormone increase of the estrous cycle and in response to exogenous steroids

The objective was to determine if the endocrine status of the animal dictates the responsiveness of gonadotrophs to estradiol, activin, inhibin and follistatin; hormones implicated in the differential release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Bovine pituitaries were obtained at 13 (n=8), 30 (n=24) and 66 (n=8) h after the onset of estrus, corresponding to before, during and the end of the first FSH increase of the estrous cycle which follows the pre-ovulatory gonadotropin surge in heifers. Heifers slaughtered at 30 h received no treatment, or were treated with progesterone with or without estradiol before slaughter to suppress the first transient FSH increase. Secretion of FSH from cultured pituitary cells, reflecting the prior in vivo status, was greater (P<0.01) at 30 h than 13 or 66 h, whereas, LH secretion was less (P<0.01) at 13 h compared with 30 h. Treatment with exogenous steroids decreased (P<0.05) the pituitary gland's ability to subsequently secrete FSH and LH. Inhibin and, to a greater extent, estradiol decreased (P<0.01) mean FSH secretion but increased (P<0.05) mean LH secretion. These findings suggest that estradiol and inhibin both have the ability to differentially modulate basal gonadotropin secretion during the first FSH increase of the bovine estrous cycle. Differential regulation of LH and FSH is mediated via an alteration in gonadotropin biosynthesis and basal secretion. Furthermore, the secretory capability of cultured pituitary cells and basal gonadotropin secretion reflect the prior endocrine status of the animal from which pituitaries were obtained.     

Outcomes of pituitary tumor irradiation in cats

BACKGROUND: Information on tumor control and normal tissue effects of radiotherapy to treat pituitary tumors in cats is limited. HYPOTHESIS: Radiation therapy is effective in controlling the clinical signs associated with pituitary tumors in cats, with a low incidence of adverse effects. ANIMALS: Eight cats were irradiated at Colorado State University between 1991 and 2002 for spontaneous pituitary tumors. METHODS: A retrospective review of records was made to assess tumor control and incidence of radiation-induced adverse effects. RESULTS: Pituitary carcinoma was diagnosed in 2 cats and pituitary adenoma in 6 cats. Total radiation dosage ranged from 4,500 to 5,400 cGy administered Monday through Friday in 270 or 300 cGy fractions. Acute effects were limited to epilation and mild otitis externa. Focal brain necrosis adjacent to regrowth of a pituitary carcinoma and a second tumor in the radiation field were reported as possible late effects. Median survival, regardless of cause of death of the 8 cats, was 17.4 months (range, 8.4 to 63.1 months). Median survival could not be determined if cats were censored for non-tumor-related causes of death. Six cats were alive at 1 year, and 3 cats were alive at 2 years after treatment. Tumor recurrence was seen in 1 cat with a pituitary carcinoma. Neurologic signs improved within 2 months in all 5 cats that presented with abnormal neurologic signs. Clinical signs caused by a concurrent endocrine disorder began to improve within 1-5 months in the 7 cats with hyperadrenocorticism or acromegaly. CONCLUSIONS AND CLINICAL RELEVANCE: Radiation therapy is an effective primary treatment modality for cats presenting with neurologic signs associated with a pituitary mass and can improve clinical signs associated with concurrent hyperadrenocorticism or acromegaly in cats with no neurologic abnormalities.     

Altered “set-point” of the hypothalamus determines effects of cortisol on food intake,adiposity, and metabolic substrates in sheep

Chronic elevation of glucocorticoid concentrations is detrimental to health. We investigated effects of chronic increase in plasma cortisol concentrations on energy balance and endocrine function in sheep. Because food intake and reproduction are regulated by photoperiod, we performed experiments in January (JAN) and August (AUG), when appetite drive is either high or low, respectively. Ovariectomized ewes were treated (intramuscularly) daily with 0.5 mg Synacthen Depot® (synthetic adrenocorticotropin: ACTH) or saline for 4 wk. Blood samples were taken to measure plasma concentrations of cortisol, luteinising hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), leptin, insulin, and glucose. Adrenocorticotropin treatment increased concentrations of cortisol. During JAN, treatment reduced food intake transiently, but increased food intake in AUG. Leptin concentrations were reduced and glucose concentrations were greater in AUG, and insulin concentrations were similar throughout the year. Treatment with ACTH increased leptin concentrations in AUG only, whereas insulin concentrations increased in JAN only. Synacthen treatment increased glucose concentrations, with a greater effect in JAN. Changes in truncal adiposity and ACTH-induced cortisol secretion were positively correlated in JAN and negatively correlated in AUG. Treatment reduced the plasma LH pulse frequency in JAN and AUG, with an effect on pulse amplitude in JAN only. Treatment did not affect plasma GH or FSH concentrations. We conclude that chronically elevated cortisol concentrations can affect food intake, adiposity, and reproductive function. In sheep, effects of chronically elevated cortisol concentrations on energy balance and metabolism depend upon metabolic setpoint, determined by circannual rhythms.