INTRODUCTION

By definition diabetes insipidus is the tasteless or nonsweet diabetes. This differentiates it, of course, from the sweet diabetes, the better known diabetes mellitus. Diabetes insipidus is caused by a lack of the hormone vasopressin (otherwise known as antidiuretic hormone or ADH), a lack of renal receptors to vasopressin, or an inability of those receptors to respond to vasopressin. The presence of vasopressin and its ability to activate renal receptors are crucial to the kidneys’ urine concentration capabilities. Vasopressin is a nonapeptide (nine amino acids) composed of six amino acids in a disulfide ring and three amino acids in a tail. In small animals the eighth amino acid in vasopressin is arginine, sometimes also called AVP or arginine vasopressin.¹

CENTRAL DIABETES INSIPIDUS

Central diabetes insipidus (CDI) is the most common primary cause of diabetes insipidus. It is caused by a complete or partial lack of secretion of vasopressin from the axon termini in the anterior lobe of the pituitary gland. Documented causes of CDI in small animals include neoplastic, traumatic, inflammatory, congenital, and idiopathic conditions.^4,5 Glucocorticoid administration is thought to decrease vasopressin release in dogs, and therefore can be included in the causes of canine acquired CDI.¹

In humans CDI is associated most commonly with brain surgery, trauma, and immune-mediated disease. Neoplasia, infectious disease, and hereditary disorders are also relatively common in this population.⁶ Following brain trauma, at least 25% of long-term survivors suffer from what is defined in humans as posttraumatic hypopituitarism.⁷ This syndrome most often includes suppression of hormone release from the anterior pituitary gland, but can also include decreased vasopressin secretion from the posterior pituitary gland. Posttraumatic CDI is thought to resolve within a few days in most human cases⁸ but may also be a sign of permanent or late brain damage. Postsurgical CDI may be the most common cause in humans. As intracranial surgery, including hypophysectomies, and better care of head trauma become more and more common in small animal practice, veterinary intensive care units will likely experience more of these cases, as well. In humans pituitary gland radiation therapy can cause long-lasting pituitary gland damage with hormonal deficiencies. Interestingly, these rarely, if ever, include CDI. In dogs, there are no large case series reporting the most common causes of CDI. Documented causes have included traumatic,⁹ neoplastic, and idiopathic conditions⁴ and have occurred secondary to iatrogenic steroid administration or hyperadrenocorticism.¹

NEPHROGENIC DIABETES INSIPIDUS

Nephrogenic diabetes insipidus (NDI) is caused by the failure of the kidney to respond to vasopressin. It is commonly divided into primary and secondary causes. Although primary NDI is uncommon and often congenital, secondary NDI is extremely common and likely the most common cause of diabetes insipidus seen in veterinary practice and intensive care units.

Primary NDI is most often hereditary in humans. Early diagnosis of this condition in humans through genetic screening has allowed for better care and increased survival. Most humans with congenital NDI have the X-linked form, causing the disease to manifest almost exclusively in male children.¹⁰ In small animal patients primary or congenital NDI has been documented in a few rare reports in young dogs, never in cats. The canine reports included a Miniature Poodle, a German Shepherd, and a family of Huskies.¹

By far the more common form of NDI in human¹¹ and veterinary patients is the acquired form. A partial list of causes of acquired NDI is included in Box 70-1. This syndrome is commonly seen in the emergency or critical care setting, caused by conditions such as pyometra or other causes of gram-negative sepsis, hypercalcemia, hypokalemia, liver failure, and hypoadrenocorticism. Each of these conditions causes an inability of the vasopressin to effectively bind and activate its receptor. In gram-negative sepsis bacterial endotoxins, especially from Escherichia coli, are thought to compete with vasopressin for binding sites on the tubular cell membranes, resulting in marked polyuria and polydipsia, and possibly hypernatremia if water intake is insufficient. Similarly, hypercalcemia and severe hypokalemia are thought to interfere with vasopressin binding and subsequent activation of the V₂ receptor.

Another common mechanism of secondary NDI is the abolition of the medullary hypertonicity gradient. As mentioned previously the presence and proper function of vasopressin and its receptors allow water channels to be open in the tubular cells of the collecting duct. The passage of water, then, from the tubular lumen into the interstitium is still passive and based on the hypertonicity of the renal medulla, enabled by the renal counter-current mechanism. If this hypertonicity, a condition referred to as medullary washout, is absent the urine will not become concentrated; it will be isosthenuric or even hyposthenuric. Medullary washout occurs in small animal patients for two common reasons:

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