Etiology.
Cushing’s disease accounts for 70% of the etiology of Cushing’s syndrome, adrenal tumors account for 10-15%, and ectopic ACTH-secreting tumors account for 10-15%. Among the 519 cases of Cushing’s disease in our hospital, the proportions of pituitary ACTH adenoma, ACTH-secreting cell hyperplasia and pathologically negative were 74.4%, 8.7% and 16.9%, respectively. Hematoxylin-eosin staining and immunohistochemical staining for all anterior pituitary hormones were routinely performed on surgical specimens at our institution. If there was a definite adenoma with ACTH staining (+), the diagnosis of pituitary ACTH adenoma was clear. Pituitary ACTH secretory cell hyperplasia was classified as diffuse hyperplasia, nodular hyperplasia and Crooke cell hyperplasia, and the percentage of patients with pathology of hyperplasia in which Crooke cells showed nodular hyperplasia was 54.2%. In addition to adenomas and hyperplasia, 11.8% of our patients with Cushing’s disease had pathology of anterior or posterior pituitary lobes with no tumor seen, and some patients were cured or in remission after butterfly exploration surgery. Reasons for pathology failure to detect tumor include.
1, tumor is too small or tumor is too dilute and soft; aspiration away by suction during surgery; postoperative formalin-fixed specimen, paraffin-fixed specimen or failure to cut to the level where the tumor is located during paraffin sectioning or failure to cut to the level where the tumor is located; surgical failure to explore the tiny adenoma and the tumor is still located in the pituitary gland and no specimen is taken.
2. the posterior pituitary lobe is easily confused with adenoma tissue under the surgical microscope, and the posterior pituitary lobe is mistakenly recognized as tumor tissue.
3, the tumor is located in the pterygoid sinus, suprasellar diaphragm, pituitary stalk or cavernous sinus and other rare sites, and the specimen taken intraoperatively is normal pituitary tissue, which is rare, but has been reported in the literature.
Diagnosis.
The diagnosis of Cushing’s disease consists of three aspects.
(1) typical signs and symptoms, including full moon face, buffalo back, polycythemia, purple striae, hypertension, hyperglycemia, hydroelectrolyte disturbances, osteoporosis, fractures, and psychiatric symptoms, although not all patients have all of these changes, and some patients have atypical symptoms or present with periodic changes.
(2) Endocrine examination: In typical patients with Cushing’s disease, their blood cortisol (F) or 24-hour urinary free cortisol (UFC/24hr) is higher than normal, blood ACTH level is elevated, blood F rhythm disappears, which cannot be suppressed by small-dose dexamethasone suppression test (dexamethasone 0.5mg,q6hr x2 days, check UFC/24hr), and high-dose dexamethasone suppression test (dexamethasone 2mg, q6hr x 2 days, UFC/24hr); in addition, thyroid hormone, gonadotropin, prolactin and growth hormone were checked before and after surgery. Not all endocrine tests in patients with pathologically confirmed pituitary adenoma in Cushing’s disease are consistent with the above; atypical cases may show F or UFC/24hr in the normal range, with normal ACTH or not suppressed by high-dose dexamethasone suppression tests.
Surgical technique.
Cushing’s disease is predominantly characterized by microadenomas, and the butterfly saddle is mostly of normal size, with some of them being pre-saddle and nail mediated. For saddle bases that are difficult to determine intraoperatively, intraoperative C-arm fluoroscopic monitoring or nerve navigation localization is routinely performed. The following steps are listed after exposing the saddle base with micro adenoma as an example.
1, saddle base opening, you can use the narrowest bone chisel or high-speed grinding drill and the narrowest, thinnest kaired pine bite clamp, butterfly saddle if it is pre-saddle type or A mesial type, after chiseling or grinding open the bone cancellous, bone bleeding should be fully hemostatic with bone wax, to ensure that there is no bleeding in the operative field before cutting the dura; when grinding or biting off the saddle base bone, pay attention not to bite open or abrade the dura of the saddle base.
The main purpose is to avoid the possible intercavernous sinus in the saddle base and further clarify the nature of the lesion in the saddle when cutting the dura. If there is more venous blood gushing out from the puncture point, consider the intercavernous sinus, change the puncture point and puncture again. For the puncture point which is difficult to stop bleeding, use small cotton gauze of suitable size to stop bleeding by local compression, not by bipolar electrocoagulation cautery, the latter may enlarge the bleeding area.
3, radially incise the dura along the puncture point, paying attention to the fact that there are two layers of dura in the saddle base, try to incise only the dura without first incising the pituitary.
4.Firstly, use the smallest scraper to probe the pituitary surface under the dura to see if there is tumor tissue, if no tumor is found, then radially incise the anterior pituitary lobe and then perform a whole pituitary exploration.
5.If micro adenoma is found, the tumor specimen should be retained first, and the tumor and peritumoral pituitary tissue should be sent to pathology separately.
6. To ensure postoperative efficacy, we recommend that a large portion of the peritumoral pituitary gland be removed along with the adenoma. The peritumoral pituitary can be removed with tissue taking forceps and microscissors, while the posterior lobe should be explored and a part of the posterior lobe should be removed. In our experience, there may be scattered aggressive growth of tumor cells in the anterior lobe of the peritumoral pituitary. Intraoperatively, it is sometimes not easy to determine whether the posterior lobe of the pituitary or the tumor, both of which may be soft grayish-white tumor-like tissue.
7. For scar tissue in the anterior lobe of peritumoral pituitary or recurrent Cushing’s disease, low-power bipolar electrocoagulation or laser knife electrocautery can be used. The laser knife is more advantageous in the case of a smaller operative field, with a smaller cautery point, less thermal damage, and easy to operate. Overall the peritumoral pituitary gland is removed about 3/4, and the residual anterior pituitary function is sufficient to maintain the hormonal regulation of the pituitary-target gland axis.
8.For the cerebrospinal fluid leak that occurs intraoperatively, autologous fat can be taken to fill the leak in the saddle, and the saddle base can be reconstructed with artificial dura and biologic glue, and it can be cured by itself without placing lumbar subarachnoid drainage in most cases after 5-7 days of postoperative lying down. Using the above methods, there have been no cases of releakage or combined meningitis after intraoperative cerebrospinal fluid leak repair in our department so far.
Perioperative management.
As hypertension, hyperlipidemia, hyperglycemia, electrolyte disorders, osteoporosis and fracture appear in Cushing’s disease before surgery, the relevant indexes should be closely monitored and treated symptomatically. For those who have mental disorders before surgery, under active symptomatic treatment, the preoperative preparation time should be grasped and operated as soon as possible. Pay close attention to changes in blood F, electrolytes, blood pressure and urine volume after surgery, and measures include.
1.Electrolytes and blood glucose should be checked urgently every morning after surgery and treated symptomatically. If electrolyte disturbance occurs, the ion concentration in the infusion should be adjusted promptly.
2. Since the posterior pituitary gland is routinely explored during surgery for Cushing’s disease, the possibility of postoperative urinary collapse is higher than that of other hormone-secreting pituitary adenomas, so the patient should be closely observed for hourly and 24-hourly urine output after surgery, and the treatment measures for definite urinary collapse include: oral dihydroclonidine (50mg tid) and painkillers (400mg tid) or mydriasis (recommended dose is 0.05mg- 0.1mg q8h-q6h, tapered to stop depending on urine output) and appropriate active water restriction. In most cases, it is a transient urinary collapse, but sometimes there is a delayed urinary collapse, which appears around one week postoperative discharge, and can be cured after the above treatment.
3. Closely observe the patient’s symptoms and signs, mainly including obvious weakness, poor appetite, palpitations, shortness of breath, etc. After excluding or correcting blood volume deficiency and water-electrolyte disorders, it is likely to be a symptom when the state of high cortisol is quickly reduced to normal or low cortisol. Pre-operative education is very important, informing patients of the above possible post-operative changes during their pre-operative conversation, and informing them that the occurrence of the above conditions is a reflection of tumor removal and successful surgery. Under the condition that patients have psychological expectation, once the above discomfort reactions occur, patients will easily cooperate with the treatment of medical and nursing staff.
4. Postoperative hormone determination: Routinely check blood F and ACTH in the morning of the second day after surgery, and start to keep urine for 24 hours to check UFC. In the case of hypocortisolism symptoms that appear soon after surgery, make sure to check blood F after keeping blood specimens, and then supplement glucocorticoids, and after supplementing hormones, check blood F again and indicate the amount of hormones used on the lab application form. Anterior pituitary hormones are routinely checked before discharge and the decision to give hormone replacement therapy is made in conjunction with the hormone values and the patient’s symptoms and signs. Our experience is that if the postoperative manifestation of hypocortisolism is not serious and can be relieved by symptomatic treatment, even if the cortisol level is low, hormone supplementation can be temporarily withheld; if the postoperative manifestation of severe palpitations and electrolyte disturbance cannot be relieved by symptomatic treatment alone, hydrocortisone 50-100mg q12hr can be administered intravenously into 500ml of fluid and then changed to prednisone 5mg tid after 3-5 days. 5mg tid, and then gradually reduce the dosage according to the situation. If preoperative or postoperative hypothyroidism occurs, give Eugenol symptomatic treatment.