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Canine and feline pituitary gland diseases (Proceedings)


Anatomy

The pituitary gland is a small structure that adheres to the base of the diencephalons; just caudal to the optic chiasm. It is comprised of an anterior portion-the adenohypophysis(which is made up of the pars distalis and the pars intermedia) and a posterior portion termed the neurohypophysis (pars nervosa).

The hypophyseal portal system transports regulatory hormones (CRF, TRF, GRF and Growth Hormone Releasing Factor) from the hypothalamus to the anterior pituitary gland.

Physiology

The pars distalis contains cells that produce growth hormone (GH/somatotropin), ACTH, and TSH and ACTH. The pars distalis also manufactures prolactin (PRL), leutinizing hormone (LH) and follicle-stimulating hormone (FSH).

The hypothalamus controls the hormones secreted by the adenohypophysis. Hypothalamic hormones (CRF,GRF, TRF, growth hormone releasing factor and somatostatin) are secreted and carried to the adenopophysis via the hypophyseal portal vesselsand are inhibited their individual negative feedback system as a result of increased concentrations of the anterior pituitary gland.

The anterior pituitary hormones have stimulatory effects upon their target glands (i.e., TSH-T3,T4, ACTH-cortisol, GH-somatomedins, FSH- ovaries/estrogen; testes/testosterone, LH-ovaries/uterus-progesterone-testes-spermatocyte stimulating hormone and PRL-mammary glands in concert with oxytocin for milk production and letdown.

The pars nervosa contains neurons whose cell bodies originate in the hypothalamus and produce vasopressin (ADH) and oxytocin. The above hormones are stored in the pars nervosa and secreted into the circulation. The hypothalamus contains osmoreceptors which detect changes in plasma osmolality; stimulating the release of ADH. ADH increases water permeability in the cells of the renal collecting ducts, resulting in a reabsorption of water back into the circulation, resulting in a decrease in plasma osmolality and a concentrated, reduced volume of urine. Vascular baroreceptors and stretch receptors detect changes in blood pressure and volume, respectively also stimulate the release of ADH in times of need. When the plasma osmolality equililibrates to normal (~295-305 mOsm/L) secretion of ADH is greatly reduced.

Central diabetes insipidus

Central diabetes insipdus (CDI) is an uncommon condition caused by a complete or partial deficiency of ADH and leads to marked polyuria and compensatory polydipsia due to an idiopathic loss of ADH-producing neurons in the hypothalamus. In rare cases CDI can be the result of severe head trauma, CVA or a destructive neoplasm (either primary or metastatic) in the pituitary gland. In those dogs with PDH in which hypophysectomy is chosen as the treatment for the hyperadrenocorticism, CDI can be a severe complication. There is no apparent sex or breed predisposition in dogs or cats. CDI can occur at any age (dogs~2-6 years of age; cats~1.5 years). Without ADH, the cells of distal renal tubules and collecting ducts remain impermeable to water, causing the formation of a hypotonic urine (SG.-1001-1005/295-310mOsm/L); leading to intense compensatory polydipsia.

Clinical signs of affected dogs include intense PU/PD and occasionally weight-loss because the patient's stomach is being continuously filled by water. If the etiology of the CDI is a neoplasm, the clinician should be on the alert for CNS signs (circling, ataxia, stupor, amaurosis and seizures). If the patient is restricted from water, severe dehydration may ensue. PU/PD conditions which are far more common than CDI include: renal failure, hyperadrenocorticism, hypercalcemia, pyometra, hypokalemia (cats), diabetes mellitus and hepatic disease. The above PU/PD conditions can be diagnosed by the utilization of a CBC, urinalysis, biochemical panel, serum bile acids,cortisol testing, radiography, ultrasonogaphy, CT or MRI and renal/liver biopsy. The definitive diagnosis of CDI (The Modified Water Deprivation Test) is based on the failure of the urine to concentrate after the patient has been deprived of water to produce 6% dehydration (the amount of dehydration to cause maximal release of ADH-normal dogs require greater than 24 hours to lose >6% of body weight) The urine usually has a specific gravity of <1.006/<290-310mOsm/L. After the administration of exogenous ADH (vassopressin) patients with CDI will exhibit a 50%-600% increase in urine osmolality. Patients with partial CDI have USPG of 1.008 to 1.020 after water deprivation (>290-310mOsm/L) with an increase of 10-50% in osmolality after the administration of ADH. For clients who are adamant about not leaving their pets for a few days in an animal hospital or have financial concerns, 4 drops of synthetic ADH (DDAVP-Desmopressin) can be instilled into the cunjuctival sac BID with the owner measuring water consumption and urine output for 5 to 7 days. A fresh sample of urine should be submitted to the veterinarian on the 7th day. Patients nephrogenic diabetes insipdus (NDI), obviously do not respond to DDAVP. Patients with Psychogenic Polydipsia may or may not respond to water deprivation depending upon the degree of "medullary washout" in their kidneys.

Treatment of patients with CDI requires the BID administration of DDAVP (1-4 drops;1.5-4.0 micrograms/drop) in the conjunctival sac. It is best to withhold water for a few hours post-administration to prevent overhydration, due to aq lag time between when the urine brgins to concentrate and the thirst subsides. For patients with CDI due to pituitary mass(es) radiation therapy along with CCNU may offer some palliation. Treatment of patients with NDI usually involves the use of thiazide diuretics with some degree of partial success. Obvious the management of the primary, inciting cause of NDI is vital (chronic kidney disease, hyperadrenocorticism, hypercalcemia, hyperthyroidism, pyometra, acromegaly, etc,). Primary polydipsia (Psychogenic Polydipsia) is managed by gradual water restriction (to alleviate renal medullary "washout"), increasing exercise, adding another dog to the house and if necessary the addition of a SSRI, benzodiazepene or other drugs which are anxieolytic.