Apr 162014

Cushing's disease is a severe and rather rare endocrine disorder which mainly affects young patients of working age. Development of Cushing's disease is associated with the formation of pituitary adenoma – tumor which releases adrenocorticotropic hormone (ACTH) into the blood in excessive amounts, such tumor is called corticotropinoma.  ACTH normally regulates the adrenal glands which begin to produce cortisol. In case of corticotropinoma ACTH production increases and the adrenal glands respond by increasing cortisol secretion.

Symptoms of cortisol excess are obesity (when fat is on the abdomen and face – “moon” face), high blood pressure, high blood sugar level (up to diabetes), muscle weakness (due to the protein breakdown by cortisol action), skin becomes thinner, in this connection, purple stretch marks also called striae. Immunity in patients weakens, due to this the risk of infectious diseases increases. Patients also face the risk of heart attacks and strokes, and thrombosis. Bones become brittle, spontaneous fractures, mostly the spine, are frequent. Sexual sphere of patient also suffers. In children high cortisol is often manifested by growth retardation. In the absence of diagnosis and treatment, the mortality of patients increases more than twice in comparison with the general population average mortality.

Besides the pituitary adenoma, neuroendocrine tumors can be the source of high ACTH and the cause of ACTH-ectopic syndrome; often they are localized in bronchi and lungs. They may be of very small size. Differential diagnosis of ACTH-dependent Cushing’s syndrome is very important problem. It is necessary to do careful examination of the patient with ACTH-dependent hypercorticism in order to avoid errors and, therefore, improper treatment.
Currently there is no laboratory test that could determine the source of ACTH in 100% cases. Ordinary the high dexamethasone test is used, but often its results are ambiguous. Pituitary MRI can not detect small pituitary adenoma in 100%. On the other hand, various studies show that more than 10% of healthy people have a pituitary adenoma that does not produce any hormones, so called pituitary incidentaloma. Thus, in the case of small size pituitary adenoma and/or questionable data of laboratory tests, one can not exclude that the pituitary adenoma is an accidental finding and has no any relation to ACTH hyper production. In this case, its removal will not lead to a recovery. On the other hand, if laboratory data indicate the presence of a pituitary adenoma, but the MRI can not find it, it does not mean that there is no corticotropinoma indeed.

Now there is only one method that permits to define the localization of the ACTH hyperproduction source with high sensitivity and specificity. It is the blood sampling from the vessels in which blood flows directly from the pituitary gland — so-called catheterization of cavernous and inferior petrosal sinuses with ACTH blood sampling.

This method is minimally invasive and well tolerated by patients. However, it is quite complex in terms of execution, requires appropriate technical equipment and angiosurgeon’s great experience, and therefore can be performed only in large tertiary centers.

Federal North-West Medical Research Centre is one of few centers in Russia where it is possible to perform this test in patients with suspected Cushing's disease, and the only center in Russia where not only inferior petrosal sinuses, but also cavernous sinuses catheterization is performed, the latter improves the method´s accuracy.

Under X-ray control the thin catheter via femoral vein is brought in the brain sinuses, and for monitoring the progress the radiopaque drug is periodically delivered. The patient is conscious and does not feel pain. Blood samples are taken from the both cavernous sinuses, both inferior petrosal sinuses, both internal jugular veins and postcava, and concentration of ACTH is investigated. Thus it is possible to localize if the source of ACTH hyperproduction in the pituitary or outside it. In the cases when corticotropinoma is invisible on MRI, according to the difference of ACTH levels in the right and left sinuses one may assume the localization of micro adenomas in the right or left half of the pituitary gland. Thus the new high-tech method of separate catheterization of the cavernous and inferior petrosal sinuses with blood sampling for ACTH will improve the differential diagnosis of Cushing's disease. Proper diagnosis and prompt treatment of this serious disease will reduce the risk of severe complications and save patients’ lives.