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Adrenal

Adrenal gland. Cortisol or cortisone is produced by the outer, or cortex (shown at right) area.

PDH Dog Sono

Sonographic view of an enlarged left adrenal gland in a Dachshund affected by pituitary-dependent hyperadrenocorticism. In this case, the "root" of the Cushing's is a problem with the pituitary gland.


Cushing's disease, also called hyperadrenocorticism, is a malfunction of the adrenal glands or the anterior portion of the pituitary gland causing overproduction of the hormone cortisol. One of the normal functions of cortisol is to raise blood sugar, and so the high cortisol levels keep blood glucose levels at continual high levels, causing a form of secondary diabetes.

Like anything that causes prolonged hyperglycemia, [1] one of the side effects over time can be permanent diabetes. Some causes of Cushing's are pituitary or adrenal gland tumors and overuse of glucocortcoid steroids. Because of the hyperglycemia Cushing's creates, it's possible (but not frequent) to find ketones in the urine. [2]

When dealing with concurrent conditions of both Cushing's and diabetes mellitus, the diabetes needs to be under some sort of control and any ketone problems resolved before testing for Cushing's Disease can be done. [3] Testing done for the disease until a ketoacidosis episode has passed will result in false positive reports. These tests can't be run until a minimum of 2 weeks after a ketoacidosis episode to receive valid results.[4]

Another disorder of the adrenal gland causes it to produce less than normal cortisol. It is known as Addison's disease and is the direct opposite of Cushing's disease.

Pituitary or Adrenal Cause?Edit

Cushing's Disease in Dogs.
Pituitary gland representation

The pituitary gland--anterior and posterior sections.


The pituitary gland is divided into 2 sections-posterior and anterior. [5] It's the anterior portion that produces adrenocorticotropic hormone, also known as ACTH, which controls the amount of cortisol the adrenal gland produces. [6]

Tumors of the pituitary gland upset the natural balance of its ability to sense when there's enough cortisol in the body so it keeps producing the hormone which tells the adrenal gland that more cortisol is needed. [7]. Because the pituitary gland erroneously continues to produce adrenal-stimulating hormone, the adrenal gland continues to respond to it and produces more cortisol than is necessary to the system [8]

The "root" cause of this type of Cushing's Disease is actually the malfunction of the anterior pituitary. It is known as pituitary-dependent Cushing's because the Cushing's exists due to the pituitary's overproduction of the adrenal-stimulating hormone. This is the most common (85%) cause of Cushing's Disease. [7]

In adrenal-dependent Cushing's, a tumor in the adrenal gland is responsible for the cortisol over-production. Adrenal-dependent Cushing's accounts for 15% of diagnosed cases. [7]

The distinction between them is important because the manner of treatment protocol can vary substantially. [9]

Cushing's/diabetes connectionEdit

Cushing's Disease-Pet Doctors of America.

The basic connection between Cushing's and diabetes is this: the excess cortisol produced by the faulty adrenal gland is a signal for the body to produce new, non-sugar sourced glucose (Gluconeogenesis).[10]

When this additional glucose reaches the bloodstream, another signal goes off; this one to the endocrine pancreas to produce more insulin to handle the glucose present in the blood.

When the insulin production ability of the pancreas can no longer keep up with the additional blood glucose which the excess cortisol from the malfunctioning adrenal gland keeps emitting, the islet cells of the endocrine pancreas are exhausted, and diabetes results. [11] In effect, the overproductive adrenal gland has the capability to "burn out" the insulin producing capability of the pancreas.

If the islet cells of the pancreas are still able to produce sufficient endogenous insulin for the body's needs, controlling the Cushing's will also control the blood glucose, meaning there would be no need for insulin injections. If the pancreas' islet cells have sustained such damage as to be unable to produce enough insulin for the body, insulin shots are necessary. Most cases of diabetes and Cushing's begin as Cushing's disease alone. [12]

For dogs with both Cushing's and diabetes, the key to starting or maintaining regulation is effective control of the Cushing's. Ending the excess of cortisol production allows the diabetes to be managed. In cases where Cushing's is the primary condition, causing transient, or secondary diabetes, it may be possible to return to non-diabetic status with successful management of Cushing's. [13]

About 80% of cats [14] and 10% of dogs with Cushing's are diabetic. [15] In dogs, breeds such as Boston Terriers, German Shepherds, Poodles, Boxers, Dachshunds and Scotties, seem to be genetically predisposed to Cushing's Disease. This is to say that it is most commonly diagnosed in dogs of the breeds above; any dog can be diagnosed with Cushing's regardless of his/her breed. [16]

Cushing's/Cortisone meds connectionEdit

Like diabetes, Cushing's can be caused by over-use of Cortisone-type medications. [7]

Because the pituitary gland also acts as a sensor, it detects the high levels of cortisol in the body and does not signal the adrenal gland to produce more. The adrenal gland becomes inactive and can atrophy from disuse, much in the way non-used muscles do, losing the ability to function normally.

Exogenous cortisone puts the adrenal gland into a sort-of hibernation. While they are being administered, they furnish the body's cortisol needs in addition to treating the condition they were prescribed for. The adrenal gland needs to be "awakened" from its rest gradually so it can begin full function once again. This is why cortisone and similar drug treatment is slowly and carefully withdrawn. Simply stopping the medication means leaving the body without sufficient cortisone--exogenous or endogenous. [7]

Canine cushing'sEdit

Cases of Cushing's disease are relatively common in dogs but less so in cats. These are common symptoms in dogs: [17] Pets with Cushing's often do not heal as quickly regarding surgeries or injuries.

It is also possible for pets to develop forms of neuropathy from Cushing's, [18] since it is considered an endocrine disease.

And, as with diabetes mellitus, Cushing's can cause polydipsia and polyuria, making it sometimes difficult to determine what the real problem is. [19][20]

Another health problem for canine Cushing's patients is high blood pressure (hypertension). [21] A 1996 JAVMA study found 86% of study dogs with Cushing's to be suffering from hypertension. It also found that 40% of them continued having high blood pressure after effective management of the Cushing's. [22]

Dogs with Cushing's are, like those with diabetes, prone to Urinary tract infections.[23] With both diseases, the infections can be hidden, thus not producing any signs of them.[24] Urine cultures are recommended for both Cushing's and diabetes patients because of lack of symptoms. [25]. Like dogs with diabetes mellitus and hypothyroidism, dogs with Cushing's are at an increased risk of acute pancreatitis [26]

The over-production of cortisol in Cushing's disease increases calcium excretion in the urine. This in turn can form into calcium oxalate bladder stones. [27]

Dogs with Cushing's, diabetes, or hypothyroidism have a tendency to have less than normal tear production. [28]. The permanent lack of enough lubrication can lead to dry eye. [29][30] They are also at risk for other eye-related disorders as a result of the Cushing's.[31]

TreatmentEdit

Depending on what's causing the Cushing's, treatment can range from surgery (in some tumor cases) [32][33] to courses of treatment with Lysodren [34] (the generic name for Lysodren is mitotane), [35] Ketaconazole, Anipryl [36] or Trilostane, all of which are described at the link below. [37]

There is sometimes the medical need to either remove or destroy the adrenal glands through medication. [38] This causes Addison's disease--a lack of enough cortisol, and means replacement cortisone medication must be taken for life.

Trilostane, [39] [40][41][39] known as Vetoryl when dispensed for veterinary purposes, and Modrenal, Desopan [42] or Modrastane [43][44][45] when prescribed for people, is the only approved treatment for Cushing's in the UK.

Vetoryl is now approved for use in the US. [46][47] These FDA letters, dated September 11, 2009, indicate that the only approved US source of trilostane is the Dechra product and further state that should compounding to obtain the proper strength for the patient be necessary, only the Dechra Vetoryl may be used for that purpose. [48][49] I16

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ReferencesEdit

  1. Urine Glucose. Cornell University.
  2. Schermerhorn, Thomas (2001). Persistent Hyperglycemia in Dogs and Cats-page 11. Standards of Care-Compendium.
  3. Brooks, Wendy C.. The Hard to Regulate Diabetic Dog. Veterinary Partner.
  4. Huang, Alice, Scott-Moncrieff, J. Catherine (April 2011). Canine Ketoacidosis. Clinician's Brief.page 3
  5. Functional Anatomy of Hypothalamus & Pituitary Gland. School of Veterinary Medicine-Colorado State.
  6. Adrenocortotropic Hormone. School of Veterinary Medicine-Colorado State.
  7. 7.0 7.1 7.2 7.3 7.4 Brooks, Wendy C.. What Exactly is Cushings?. Veterinary Partner.
  8. Adrenocorticotropic Hormone. School of Veterinary Medicine-Colorado State.
  9. Brooks, Wendy C.. Classifying Cushing's Syndrome: Pituitary/Adrenal. Veterinary Partner.
  10. Hormones Which Raise or Lower Blood Glucose. Chronolab.
  11. Exhaustion of Pancreatic Islet Cells With Cushing's Disease Resulting in Diabetes-Vetsulin. Intervet.
  12. Greco, Deborah (2009). Dietary Treatment of Diabetes Mellitus in Cats and Dogs-Concurrent Endocrinopathies. DVM 360.
  13. Davidson, Gigi (2000). Providing Care for Veterinary Diabetic Patients-page 1. International Journal of Pharmaceutical Compounding.
  14. Cushing's Disease-Hyperadrenocorticism. Drs. Foster & Smith Pet Education Library.
  15. Cushing's & Diabetes Concurrently in Pets. MarVista Vet.
  16. Dog Breeds Predisposed to Cushing's Disease. PetsHealth.
  17. Cushing's Symptoms in Dogs. MarVista Vet.
  18. Peripheral Neuropathy. Southpaws (1999).
  19. Diabetes Mellitus. Petplace.com.
  20. Lunn, Katharine F., James Katherine M. (2007). Normal and Abnormal Water Balance: Polyuria and Polydipsia. Compendium.
  21. Novellas R, de Gopegui RR, Espada Y. (2008). Determination of renal vascular resistance in dogs with diabetes mellitus and hyperadrenocorticism. Veterinary Record.
  22. Martinez, Nivia I. (2003). Hypertension in canine hyperadrenocorticism more common than previously thought. DVM Newsmagazine.
  23. Daniels, Joshua B., Chew, Dennis J. (2011). Diagnosis and Treatment of Routine and Difficult Urinary Infections in Dogs. Western Veterinary Conference.
  24. Bartges, Joe (2011). Urine Heaven: Of Bugs and Drugs-Urinary Tract Infections. Western Veterinary Conference.
  25. Forrester SD, Troy GC, Dalton MN, Huffman JW, Holtzman G. (1999). Retrospective Evaluation of Urinary Tract Infection in 42 Dogs with Hyperadrenocorticism or Diabetes Mellitus or Both. Journal of Veterinary Internal Medicine.
  26. Washabau, Robert J. (2009). Canine Pancreatic Disease: What's New in Diagnosis and Therapy?. WSAVA.
  27. Brooks, Wendy C.. Calcium Oxalate Bladder Stones. Veterinary Partner.
  28. Williams DL, Pierce V, Mellor P, Heath MF. (2007). Reduced tear production in three canine endocrinopathies. Journal of Small Animal Practice.
  29. Dry Eye. ProVet UK.
  30. Dry Eye and Endocrine Diseases. NAVC (November 2007).
  31. Plummer, Caryn E., Specht, Andrew, Gelatt, Kirk N. (December 2007). Ocular Manifestations of Endocrine Disease. Compendium.
  32. Brooks, Wendy C.. Adrenal Tumor Treatment. Veterinary Partner.
  33. Axlund, Todd W., Behrend, Ellen N., Winkler, James T. (2003). Surgical Treatment of Canine Hyperadrenocorticism. Compendium.
  34. Lysodren Treatment Information. PetsHealth.
  35. Mitotane Drug Information. Rxlist.com.
  36. Braddock JA, Church DB, Robertson ID, (2004). Selegiline Treatment of Canine Pituitary-Dependent Hyperadrenocorticism. Australian Veterinary Journal.
  37. Drugs Used in Treatment of Cushing's Disease. MarVista Vet.
  38. Removal/Destruction of Adrenal Glands. Gulf Coast Veterinary Specialists.
  39. 39.0 39.1 Trilostane Drug Information. Drugs.com.
  40. Braddock JA, Church DB, Robertson ID, Watson AD. (2003). Trilostane Treatment in Dogs With Pituitary-dependent Hyperadrenocorticism. Australian Veterinary Journal.
  41. Trilostane Information. Patient UK.
  42. Desopan. Mochida-(Japan).
  43. Modrastane 60mg. New Drug Information.
  44. Modrastane 30mg. New Drug Information.
  45. Modrenal and Other Brand Names-Desopan & Modrastane-for Trilostane. Drug Bank-University of Alberta.
  46. Dechra-US website. Dechra US.
  47. Vetoryl Approval. US Food and Drug Administration (5 December 2008). Dechra Press Release-US Approval of Vetoryl
  48. Vetoryl-trilostane letter to veterinarians. US Food and Drug Administration.
  49. Vetoryl-trilostane letter to pharmacists. US Food and Drug Administraion.

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