Syndrome Treatment of Cushing's
Endocrinology / / May 18, 2016
Cushing's syndrome - Cushing, caused by adrenal hyperplasia, the main methods of treatment are radiotherapy (irradiation of the hypothalamic-pituitary region), followed by removal of the adrenal gland, as well as total or subtotal removal of both adrenal glands.If you have a tumor of the adrenal cortex of the adrenal gland is produced corresponding removal.
Radiotherapy followed by removal of the adrenal gland
basis for the X-ray irradiation of the hypothalamic-pituitary region is the presence of the majority of patients with hyperplasia and hyperfunction of basophil cells of the adenohypophysis, producing ACTH.Usually the course is assigned to p 5000- 6000, 100 p daily from three fields (two temporal and parietal).
Apply one or more courses in the 4000-4500 district on the region of the pituitary with an interval of 4-5 weeks.It often takes six months to produce remission.
Radiotherapy has no damaging effect on the pituitary gland and the central nervous system and causes the part of
Radiotherapy as an independent method gives a pronounced effect lasting only a small proportion of patients in the initial stages of the disease.The majority of the patients undergoing radiotherapy, by up to 6 months after radiation therapy should be made of the removal of the adrenal gland.
In 15 of the 23 patients had marked with remission.If no sufficient effect is produced subsequently removing the second adrenal.
patients with the presence of hypertension, not controlled by reserpine, with severe osteoporosis and the presence of other severe complications produced dvuhmomentnaya total or subtotal adrenalectomy without prior radiotherapy.When subtotal adrenalectomy is stored no more than 10% of the second tissue of the adrenal gland.
Many surgeons prefer total subtotal adrenalectomy because the adrenal hyperplasia remaining part can negate the effect of the initial operation.
total and subtotal adrenalectomy performed dvuhmomentno.The time interval between the removal of one of the second and adrenal usually at least three weeks.
After these interventions require replacement therapy with cortisone or hydrocortisone or their analogues - prednisone, prednisolone, etc. When any
adrenalectomy is necessary to conduct an audit of both the adrenal glands and in the case of one of them is limited to the respective tumor surgery unilateral adrenalectomy..If the removal process adrenal tumor manifestations with Cushing syndrome - Cushing stored, further clears the second adrenal.
Preparation for surgery
In step removal of the adrenal gland, even in the absence of clinically detectable tumors can be no assurance in the presence of hormonally active, clinically detectable tumor.Hormonally active adrenal gland tumor with Cushing's syndrome - Cushing leads to atrophic processes of the second with a sharp adrenal suppression products they hydrocortisone.Consequently, removal of the adrenal gland, comprising a tumor may lead to surgery during the postoperative period and in severe acute adrenal insufficiency second.Severe adrenal insufficiency inevitably develops after total and usually after subtotal adrenalectomy.
To prevent the development of postoperative adrenal insufficiency are used in the pre- and postoperative massive doses of cortisone or hydrocortisone parenterally.Recommend the day before surgery intramuscular cortisone appoint 100 mg 2 times a day, and immediately before surgery to introduce an additional 100 mg of cortisone.
After operation for several days cortisone injected intramuscularly with 50 mg every 4-6 hours followed by a gradual decrease in doses up to 50 mg per day.Dates are determined by reducing the dose of the patient condition.Recommend
as cortisone administered at 150 mg per day for two days prior to surgery.On the day of surgery and one - two days after the cortisone is administered in a daily dose of approximately 300 mg followed by a gradual reduction in the dose to 50-25 mg per day and with the transition to receiving cortisone tablets.
Hartenbach applied within 3-4 days before surgery potassium chloride preparations with anabolic protein effect (durabolin), plasma transfusions and antibiotics.Furthermore, it is immediately before the operation proceeds to intravenous administration of 100 mg of hydrocortisone which takes 4 hours. During the first postoperative day total number of hydrocortisone administered is 400 mg.At the time of removal of the adrenal gland it introduces additional 10 mg of deoxycorticosterone acetate.However plasma transfusion manufacture and application of antibiotics to operational days was unnecessary.
In case of occurrence in the postoperative period, acute adrenal insufficiency must enter intravenous hydrocortisone hemisuccinate, 100 mg or prednisolone drug for intravenous administration of 20 mg.In the absence of drugs hydrocortisone or its analogs need for intravenous administration of 150 mg intramuscularly cortisone or hydrocortisone with its subsequent administration of 50 mg every 4-6 hours. Therapy is otherwise the same as in acute adrenal insufficiency of any origin.
acute adrenal insufficiency and mortality of patients with adrenal tumor removal or resection of their common in cases of the correct application in the pre and postoperative period of cortisone or hydrocortisone are rare.In the absence of irreversible complications and malignant tumors of the adrenal cortex recover over 90% of the operated patients, the rest comes a significant improvement.
When choosing a method of surgery, some surgeons are abdominal, lumbar other way.Abdominal route has advantages in view of the fact that it makes it possible to simultaneously perform an audit of both adrenal glands.However, in patients with sharp fatty deposits in the subcutaneous tissue of the abdomen lumbar path may be advantages.
In the subsequent management of patients when the dose of hydrocortisone or cortisone is reduced to maintenance doses, it is necessary in patients with total and the majority of patients with subtotal removal of the adrenal constant application maintenance doses of hydrocortisone, cortisone or their analogues, varying doses depending on the patient and oftenchanging needs in these preparations.Maintenance doses of cortisone: from 12.5 to 50 mg of prednisone for 5-10 mg per day.All these drugs are prescribed to the patient during treatment inside a tablet.
In the case of surgery, childbirth, various injuries, acute infections and other types of stress you must immediately move to the use of high doses of these drugs, adhering schemes recommended by the removal of the adrenal glands.However, the dose should be modified depending on the nature and force of the stress factor and the condition of the patient.
after total or subtotal removal of the adrenal glands in some patients developing pituitary tumor, chromophobe in structure, but is produced in large amounts of ACTH.
Nelson et al. Describe the development of such tumors in 8 patients, and they are having from 1 to 8 years after adrenalectomy.These tumors have been described by other authors.The absence of occurrence of pituitary tumor removal by bilateral adrenal produced about hypertension or adrenal cancer, indicating at Jailer believe that adrenalectomy alone can not be the cause of the pituitary tumor.The cause of the tumor in the pituitary gland in Cushing syndrome - Cushing undoubtedly lies in a particular disease state or pituitary may thalamo hypo-pituitary system.
There are observations about the successful use of the syndrome of Cushing - Cushing, caused by adrenal hyperplasia, implantation of radioactive gold region of adenohypophysis, radon, yttrium-90, produced under the control steriotakticheskogo device.Total activity of yttrium-90 and 3.4 ms;they formed? -rays extend a short distance from the site of implantation.Treatment is based on the suppression of increased incretion adenogipofizmom ACTH.Treatment results come after 4-5 months after implantation and are very encouraging.Implantation is sometimes accompanied by mild secondary adrenal insufficiency.
With the same purpose, the electrocoagulation pituitary also gives favorable results.Electrocoagulation destroys, apparently throughout pituitary tissue, and after the gonads, thyroid and adrenal glands continue to function.
There is a tendency to treat Cushing's syndrome - Cushing, caused by adrenal hyperplasia, drugs that suppress the synthesis of hydrocortisone.
Nelson et al. Have shown that the compound 2,2-bis (p-chlorophenyl) -1,1-dichloroethane (DDD) makes dogs adrenocortical atrophy.Clinical application of the first to obtain an isomer ortho-para-prime DDD (o, p 'DDD).
According Southren et al. (1961), if it is applied quickly suppressed the function of the adrenal cortex, and there comes a marked clinical improvement with small side effects.Initial dose - 4 g per day, followed by its reduction;maintenance dose - 1-2 grams per day.However, the observation period is still small, to speak of a persistent beneficial effect.The drug can be recommended for inoperable adrenal cancer forms in the presence of its metastases.Hertz observed in its application a significant reduction in the size of metastases and a decrease in allocation of corticosteroids.But, according to Hertz, in the treatment of o, p 'DDD often observed toxic effects - anorexia, skin rash, vomiting, diarrhea, drowsiness, lethargy, and depression.Changes in the central nervous system often forced the author to abandon the treatment with this drug.In humans, long treated o, p 'DDD, autopsy detected adrenal atrophy.
In 1950, was synthesized amfenon (3,3-di (p- aminophenyl) -butanone-2), which blocks the biosynthesis of corticosteroids in the adrenal healthy and in tumor tissues by inhibiting the enzyme activity.In addition to blocking the synthesis of corticosteroids, amfenon also blocks the synthesis of thyroid hormones.Amfenon eventually causes adrenal hyperplasia and there is also their toxic degradation.Patients with Cushing syndrome - Cushing caused both hyperplasia and cancer, it reduces the release of urine 17-hydroxycorticosteroids.Prolonged use amfenona can have toxic effects on the liver, kidneys, nervous system, and in patients with liver disease - even induce hepatic coma.
In 1958, was synthesized SU-4885 (2-methyl-1,2-bis- (3-pyridyl) -1-propanone), also called metopironom or metopiranonom.SU-4885 has a specific effect by inhibiting 11-hydroxylation, through the blocking of the respective enzyme system.This leads to disruption of the synthesis of hydrocortisone and corticosterone, which stop at phase 11 dezoksigidrokortizona and 11-deoxycorticosterone.
Application SU-4885 also has a therapeutic effect in cancer of the adrenal cortex, reducing tumor hydrocortisone products, but, however, does not cure the disease.SU-4885 is usually given at a dose of 1-2 grams per day, 250-500 mg every 6 hours. Toxicity even with prolonged use of high doses of a small, much less than amfenona.
described preparations SU-8000, SU-8874, SU-9055, SU-10603, etc., Which suppress the function of the adrenal cortex, but unlike the SU-4885 they block 17 a-hydroxylation, reduce the release of hydrocortisone and increase the release of adrenal corticosteroneand deoxycorticosterone.
to suppress increased action of aldosterone, which sometimes occurs in the syndrome pituitary - Cushing may be applied spironolactone - SC-5233, SC-8109, SC-9420, known as aldactone, SC-9456, etc. The antagonistic effect of drugs against.aldosterone is shown in the distal convoluted tubules of the kidneys, where they block the increased reabsorption of sodium, chloride and potassium excretion caused by aldosterone, and normalized so the exchange of electrolytes.However, the mechanism of action of spironolactone on the kidney is still poorly understood.In the presence of edema in patients with Cushing syndrome - Cushing caused increased production of aldosterone recommended combination therapy with diuretics - hydrochlorothiazide and spironolactone (400 mg daily) with supplementation of potassium chloride, as these long-term use of diuretics cause hypokalemia.
- Cushing syndrome - Cushing
- diagnosis and for Cushing's syndrome
- Physiology of the adrenal cortex
- Chronic adrenal insufficiency.Addison's disease
- androgen-producing tumors of the adrenal cortex
- Primary aldosteronism (Conn's syndrome)
- Clinical evaluation of laboratory studies of the functional state of the adrenal cortex
- feminizing tumor of the adrenal cortex
- Diagnosis and differential diagnosis of congenital adrenal hyperplasia
- Treatment of chronic diseaseadrenal
- congenital (inborn) hyperaldosteronism
- congenital virilizing adrenal hyperplasia
- Treatment of congenital adrenal hyperplasia
- Acute failure of the adrenal cortex
If you have osteoporosis, anabolic steroids are used- methandrostenolone 5-10 mg per day, metilandrostendiol 25-50 mg per day sublingually, durabolin 25 mg intramuscularly 1 time per week.
Children with incomplete growth of methandrostenolone and metilandrostendiol should be applied in the form of courses 1,5-2 months with the inclusion of the same duration interruptions.
case of violation of the menstrual cycle in women and hypoplasia of the testicles in men need to treat the underlying disease.
Summing up the issues of treatment of Cushing's syndrome - Cushing, it must be emphasized once again that the main method of treatment is total or subtotal removal of the adrenal cortex hyperplasia.In mild cases of the disease can be tried out the removal of the adrenal gland after radiotherapy previously held (hypothalamic-pituitary region) and in the absence of a sufficient effect is also necessary total or subtotal removal of the second adrenal gland.When a tumor of the adrenal cortex is removed the affected adrenal gland.Only in the lungs, the primary forms of the disease can be used as an independent method of treatment of radiotherapy.
In severe, inoperable forms of Cushing's syndrome - Cushing, including cancer of the adrenal cortex and its metastases, can be applied drugs (SU-4885-metopiron), blocking the synthesis of hydrocortisone.