Hypophysectomy
Surgery is performed for dogs with pituitary and adrenal-dependent disease. In the United States there is limited experience
with hypophysectomy for pituitary tumors but outside the United States this surgery has been performed with good results.
The mortality rate can approach 10% but most dogs obtain a complete remission for several years. In addition to perioperative
mortality, diabetes insipidus may occur but is usually transient. Bilateral adrenalectomy has also been performed in dogs
with PDH. This creates a dog with permanent hypoadrenocorticism and requires life long glucocorticoid and mineralocorticoid
treatment.
Adrenalectomy
Surgery is the treatment of choice for adrenal tumors. An exception might be made for tumors that have metastasized or dogs
with concurrent disease that would make surgery an unnecessary risk. This emphasizes the need for a thorough staging process
prior to surgery. Complete removal of a functional cortisol producing tumor will result in a cure. Benign adenomas would be
more likely to be cured by surgery than adenocarcinomas. Because the contralateral adrenal is often atrophied, glucocorticoids
(dexamethasone, hydrocortisone) are given the day of surgery and continued after surgery. Once dogs have recovered and can
take oral medications, oral glucocorticoids are given. Glucocorticoids are tapered over several weeks. Mineralocorticoids
are no typically required but given as needed. A few dogs develop evidence of a transient, mild mineralocorticoid deficiency
that resolves in 48 to 72 hours and does not necessarily require treatment. For more moderate or prolonged hyponatremia and
hyperkalemia temporary use of mineralocorticoids is recommended. An ACTH stimulation can be performed the day after surgery
to assess for complete removal of the tumor and absence of metastatic disease. ACTH stimulation tests are also performed by
some when on low doses of glucocorticoids to assess return to function of the remaining adrenal gland. It may take several
months for the contralateral adrenal gland to function normally. Another concern in these patients is thromboembolic disease.
Dogs with HAC are hypercoagulable for reasons stated previously. The surgery itself predisposes them to thromboembolism (anesthesia,
hypotension, recumbency, vascular occlusion/stasis). For this reason it is advised to give plasma at a dose of 6 to 10 ml/kg
prior to surgery as a source of antithrombin III. It is also recommended to initiate heparin therapy prior to surgery. The
prognosis is good for dogs that survive the perioperative period. Lysodren
Lysodren continues to be the most commonly used adrenolytic in dogs. It is the first line of therapy recommended for PDH that
is not the result of a pituitary macroadenoma. It is also recommended in dogs with ACH that are not surgical candidates for
whatever reason. Lysodren results in destruction of the cells of the zona fasciculata and zona reticularis. It spares the
zona glomerulosa to some extent so aldosterone synthesis may be spared and electrolyte abnormalities are not typically seen.
Absorption is improved with feeding, particularly of fatty meals. The most common side effects are related to an absolute
or relative cortisol deficiency and include lethargy, anorexia, vomiting and diarrhea. A hepatopathy can occur on rare occasions
with this drug. Dogs are typically induced with 50 mg/kg/day divided into 2 doses. Dogs with diabetes mellitus and cardiac
disease are often induced with a lower dose of 25 mg/kg/day divided. Most dogs are induced in 5 to 9 days. Induction is assumed
complete with any change in water consumption, appetite, onset of lethargy, vomiting or diarrhea. ACTH stimulation tests are
performed weekly and at the completion of induction with a goal of post stimulation values below the reference range. Glucocorticoid
supplementation (0.5 mg/kg/day of prednisone) is recommended if lethargy, vomiting or diarrhea develop. Once signs have resolved
the prednisone is tapered over several days. Mineralocorticoid deficiency is uncommon with treatment but suggests more extensive
destruction of the adrenal gland. In these dogs, permanent glucocorticoid and mineralocorticoid therapy may be necessary.
Once induction is completed dogs are placed on 25 to 50 mg/kg divided into 2 to 3 doses during the week. An ACTH stimulation
test is checked at 1 and 3 months after induction or when signs recur. In a stable dog on lysodren therapy full blood work,
a urinalysis and ACTH stimulation test should be performed every 4 to 6 months. Initial adjustments are typically made by
altering the number of days the lysodren is given, not the dose per day. Occasionally dogs require high daily doses or have
to be induced again. Some dogs fail to respond to lysodren and this may be due to failure to administer the medication, poor
absorption/potency, incorrect diagnosis, medications that interfere with lysodren, presence of an adrenocortical tumor, a
resistant form of the disease or iatrogenic HAC. Lysodren also results in decreased levels of androstenedione, progesterone
and 17-OH progesterone so it may be useful in some cases of atypical hyperadrenocorticism when melatonin and lignins are ineffective.
