Cushing's disease

Cushing's disease, also called hyperadrenocorticism, is a malfunction of the adrenal gland making it overproduce 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, 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 glucocortoid steroids.

When dealing with concurrent conditions of both Cushing's and diabetes mellitus, the diabetes needs to be under some sort of control and any DKA resolved before testing for Cushing's Disease can be done^[1].

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?[]

The pituitary gland is divided into 2 sections-posterior and anterior^[2]. It's the anterior portion that produces a hormone which controls the amount of cortisol the adrenal gland produces^[3].

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^[4]. 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^[5].

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^[6].

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^[8].

Cushing's/diabetes connection[]

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).

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^[9]. 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.

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^[10].

About 80% of cats^[11] and 10% of dogs with Cushing's are diabetic^[12]. 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^[13].

Cushing's/Cortisone meds connection[]

Like diabetes, Cushing's can be caused by over-use of Cortisone-type medications^[14].

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^[15].

Canine and feline cushing's[]

Cases of Cushing's disease are relatively common in dogs but less so in cats. These are common symptoms in dogs^[16] and these are common symptoms in cats^[17]. Cats with Cushing's often have very fragile skin^[18]; 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^[19], 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^[20].

Another health problem for canine Cushing's patients is high blood pressure (hypertension). 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^[21].

Dogs with Cushing's are, like those with diabetes, prone to Urinary Tract Infections. With both diseases, the infections can be hidden, thus not producing any signs of them. Urine cultures are recommended for both Cushing's and diabetes patients because of lack of symptoms^[22].

Treatment[]

Depending on what's causing the Cushing's, treatment can range from surgery (in some tumor cases)^[23] to courses of treatment with Lysodren^[24](the generic name for Lysodren is mitotane)^[25], Ketaconazole, Anipryl or Trilostane , all of which are described at the link below^[26].

There is sometimes the medical need to either remove or destroy the adrenal glands through medication^[27]. This causes Addison's disease--a lack of enough cortisol, and means replacement cortisone medication must be taken for life.

Trilostane^[28] ^[29]^[30]^[31]^[32], known as Vetoryl when dispensed for veterinary purposes, and Modrenal, Desopan^[33] or Modrastane^[34]^[35]^[36] when prescribed for people, is the only approved treatment for Cushing's in the UK. It has yet to be approved for animals in the US. The drug is approved in the US for use in some human conditions--it is simply not available in the US.

One can now receive it under the Vetoryl brand name minus the FDA red tape from Master's Marketing^[37]^[38] in the UK. A prescription will be needed, even though the ordering process is easier. Masters also has importing and ordering procedure information on its website for residents of Canada, Australia, EU,and the UK. Dechra, also in the UK, is the exclusive distributor of the drug under the veterinary Vetoryl name^[39]. They are also a source of information for how to use the drug for veterinary purposes^[40].

Vetoryl is now approved for use in the US.^[41]^[42]

References[]

[1] Veterinary Partner-The Hard to Regulate Diabetic Pet

[2] School of Veterinary Medicine-Colorado State-Functional Anatomy of Hypothalamus & Pituitary Gland

[3] School of Veterinary Medicine-Colorado State-Adrenocortotropic Hormone

[4] Veterinary Partner-What Exactly is Cushings?

[5] School of Veterinary Medicine-Colorado State-Adrenocorticotropic Hormone

[6] Veterinary Partner-What Exactly is Cushing's Disease

[7] Veterinary Partner-What Exactly is Cushing's Disease?

[8] Veterinary Partner-Classifying Cushing's Syndrome: Pituitary/Adrenal

[9] Exhaustion of Pancreatic Islet Cells With Cushing's Disease Resulting in Diabetes

[10] Successful Treatment of Cushing's May Cure Secondary Diabetes

[11] Cushing's Disease-Hyperadrenocorticism-Drs. Foster & Smith Pet Education Library

[12] Cushing's & Diabetes Concurrently in Pets

[13] Dog Breeds Predisposed to Cushing's Disease

[14] Veterinary Partner-What Exactly is Cushing's Syndrome?

[15] Veterinary Partner-What Exactly is Cushing's Syndrome?

[16] Cushing's Symptoms in Dogs

[17] Cushing's Symptoms in Cats

[18] Fragile Skin in Cats With Cushing's

[19] Cushing's Disease & Neuropathy

[20] Diabetes Mellitus-Petplace.com

[21] Canine Hypertension & Cushing's Disease

[22] Retrospective Evaluation of Urinary Tract Infection in 42 Dogs with Hyperadrenocorticism or Diabetes Mellitus or Both-Journal of Veterinary Internal Medicine-1999

[23] Veterinary Partner-Adrenal Tumor Treatment

[24] Lysodren Treatment Information

[25] Mitotane Drug Information

[26] Drugs Used in Treatment of Cushing's Disease

[27] Removal/Destruction of Adrenal Glands

[28] Trilostane Drug Information

[29] Trilostane Treatment in Dogs With Pituitary-dependent Hyperadrenocorticism-Australian Veterinary Journal-2003

[30] Patient UK-Trilostane Information

[31] Drugs.com-Trilostane Information

[32] British National Formulary (BNF)-Trilostane Drug Interaction Information

[33] Mochida-(Japan)-Desopan

[34] New Drug Information-Modrastane 60mg

[35] New Drug Information-Modrastane 30mg

[36] Other Brand Names-Desopan & Modrastane-for Trilostane

[37] Masters Veterinary Sales-Importing/Purchasing Information for US, Canada, Australia, EU & UK

[38] Masters Marketing--US Phone/Fax Numbers-Now Accepts Visa & Mastercard-May 2006

[39] Dechra Website

[40] NOAH Compendium of Animal Medicine UK--Vetoryl/Trilostane

[41] Dechra-US website

[42] Dechra Press Release-US Approval of Vetoryl

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