Prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism.

OBJECT: The aim of this study was to determine prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism (PDH). METHODS: One veterinary neurosurgeon performed transsphenoidal hypophysectomies in 181 dogs with PDH over a 12-year period. Survival analysis was performed with the Kaplan-Meier method. Prognostic factors were analyzed with the univariate Cox proportional hazard analysis followed by stepwise multivariate analysis. The log-rank test was used to assess disease-free fractions in three groups categorized according to early postoperative urinary corticoid/creatinine (C/C) ratios. RESULTS: Multivariate analysis revealed that old age, large pituitary size, and high preoperative concentrations of plasma adrenocorticotropic hormone were associated with an increased risk of PDH-related death. In addition, large pituitary size, thick sphenoid bone, high C/C ratio, and high concentration of plasma alpha-melanocyte-stimulating hormone (alpha-MSH) before surgery were associated with an increased risk of disease recurrence in the dogs that went into remission after hypophysectomy. Disease-free fractions were significantly higher in dogs with postoperative urinary C/C ratios in the lower normal range (< 5 x 10(-6)) than in dogs with postoperative C/C ratios in the upper normal range (5-10 x 10(-6)). CONCLUSIONS: The results of this study indicate that pituitary size, sphenoid bone thickness, plasma alpha-MSH concentration, and preoperative level of urinary cortisol excretion are predictors of long-term remission after transsphenoidal hypophysectomy for PDH in dogs. Urinary C/C ratios measured 6 to 10 weeks after surgery can be used as a guide for predicting the risk of tumor recurrence.

A prospective analysis of 151 cases of patients with acromegaly operated by one neurosurgeon: a follow-up of more than 23 years.

BACKGROUND: Transsphenoidal adenomectomy has been the accepted surgical management for treatment of growth hormone (GH)-secreting pituitary adenomas. Although the goal of treatment might be to keep the GH level in the reference range, the actual definition of success in control of acromegaly is not yet clear. METHODS: The aim of this study was to analyze prospectively the result of transsphenoidal adenoctomy performed over 23-year period by a single neurosurgeon in one center. The analysis has been performed to determine which preoperative factor could significantly influence the long term outcome. This series consisted of 151 patients. The preoperative hormonal studies documenting the high GH and/or insulin-like growth factor were available in all the cases. At least 1 laboratory report documenting the postoperative level of hormones was also available for all of them. Transsphenoidal microsurgical adenomectomy was performed in all the cases. RESULTS: There were 90 patients with pure GH-secreting adenoma (59.6%) with the highest GH level of 235 mU/L. A second group of 12 patients had normal GH level but elevated serum level of insulin-like growth factor 1 (8%). The group with mixed secretion of GH and prolactin included 49 cases (32.4%). There was no postoperative mortality. Cerebrospinal fluid leakage occurred in 12 patients. Transient diabetes insipidus was encountered in 19 cases (12.6%) and long lasting diabetes insipidus in 2 patients (1.3%). Early and minor hypopituitarism was encountered in 14 patients, whereas a persistent condition occurred mainly after irradiation in 14 other cases. Normal postoperative serum GH level could be achieved in 98 patients (94.2%) of 104 cases with full follow-up. CONCLUSION: In the developing countries, early diagnosis and proper surgical extirpation of the GH-secreting adenoma by an experienced and dedicated pituitary surgeon is mandatory to reduce the mortality and increase the chance of cure of this rather mortal endocrionopathy.

Tumores de hipófisis: presentación clínica y evaluación del tratamiento por cirugía transfenoidal / Pituitary tumors: clinical presentation and assesment of transphenoidal surgical treatment

The clinical manifestations and the surgical treatment results of 280 patients (179 female), undergoing a total of 319 operations at the Asenjo Institute of Neurosurgery were retrospectively analyzed. The surgical approach for the first operation was transphenoidal in 89.3 per cent of patients and transcraneal in the rest. Tumors were non secretory in 169 (60.4 per cent)patients, prolactinomas in 75 (27.8 per cent) and produced acromegalia in 29 (10.4 per cent) and Cushing syndrome in 7 (2.5 per cent) patients. There was extraselar extension in 42 per cent of women and 71 per cent of men. The surgical treatment of prolactinomas corrected endocrine alterations in 25 of 29 and visual alterations in 18 of 27 patients assessed. Surgical treatment of acromegalia improved endocrine alterations in 11 of 13 and visual alterations in 4 of 10 patients assessed. Treatment of non secretory tumors corrected visual alterations in 38 of 64 patients assessed. The principal complication of transphenoidal surgery was transient diabetes insipidus in 6.8 per cent of patients. Overall mortality was 2.3 per cent for transphenoidal surgery and 5.6 per cent for transcraneal surgery. It is concluded that transphenoidal surgery is effective for the management extraselar complications of pituitary tumors and endocrine management of selected cases

Hydroxyurea: relationship between toxicity and centrally-induced adrenal activation.

The anticancer drug hydroxyurea (HU) at doses of 300-800 mg/kg/day causes a dramatic lethality (up to 100% after a 5-day treatment) in hypophysectomized as well as in adrenalectomized rats drinking physiological saline + 5% glucose. Mortality in controls was less than 10% over a 5-day period. Adrenal stimulatory or replacement therapies protect pituitary- or adrenal-ablated rats against HU toxicity. They also counteract white blood cell changes induced by the drug. HU (30-800 mg/kg) induces a dose-dependent increase of plasma corticosterone in normal rats after single or repeated treatments that is not observed in hypophysectomized animals. HU also increases plasma levels of epinephrine, although this finding cannot account for the rise in plasma corticosterone; indeed, it is secondary to a strong rise in plasma corticosterone. The stimulation of the hypothalamic-hypophyseal-adrenal axis induced by HU is responsible for the drug-induced adrenocortical activation. This activation appears to be a valuable defence mechanism protecting intact rats against HU lethality, and its failure causes the dramatic HU lethality in pituitary- or adrenal-ablated animals.

Study of long-term survival after transsphenoidal hypophysectomy in clinically normal dogs.

Experimental hypophysectomies were performed in 7 clinically normal dogs, using a new modification of the transsphenoidal approach. This approach facilitated centering of the sphenoid bone trephination and allowed safe exposure of the hypophysis regardless of the size or shape of a dog's skull. Complications did not occur during surgery and all dogs recovered well from surgery. Growth hormone secretory capacity was measured over a 3-month period to assess completeness of hypophysectomies. One dog was euthanatized 2 months after surgery, 4 dogs were euthanatized at 3 months after surgery, and 2 dogs were allowed to survive and their progress was followed for 2.5 years. Soft palate dehiscence and keratoconjunctivitis sicca developed in 2 of the dogs. The technical deficiencies responsible for these complications were corrected shortly after the beginning of the study. In 4 of the 5 necropsied dogs, minute remnants of adenohypophyseal tissue were found in the sellae turcica. Measurement of in vivo growth hormone secretory capacity revealed that these remnants had an altered stage of functional activity. Although complete hypophysectomy was not achieved consistently, the main technical obstacle of hypophysectomy, the reliable identification and the avoidance of the vascular structures surrounding the hypophysis, has seemingly been overcome. The surgical technique proved to enhance the safety of hypophysectomy, and the procedure can be recommended to treat clinical cases of canine pituitary-dependent hyperadrenocorticism. The clinical significance of potential subtotal hypophysectomy remains yet to be evaluated.

Survival and weight increase in the fetal rat after selective hypophysectomy in utero.

Rat fetuses were subjected to selective hypophysectomy in utero on day 16, 17 or 18 of gestation and inspected on day 22 (the day before birth). The survival rate of fetuses operated on day 17 and 18 was about 20 and 50%, respectively. Losses were mostly caused by the surgery preceding the removal of the pituitary, and no significant survival-promoting activity of the gland could be demonstrated. The surgical injuries, as such, also reduced the weight increase substantially. Still, the loss of the pituitary was followed by a further reduction in weight gain, which on day 22 was about 10% lower than that of the sham-operated fetuses.

Incidence and management of complications of transsphenoidal operation for pituitary adenomas.

Two hundred fifty-five consecutive transsphenoidal procedures for pituitary adenomas were reviewed to evaluate complications and their management. There were no operative deaths. Cerebrospinal fluid (CSF) rhinorrhea was the most common complication, occurring in 2.7% of cases; diabetes insipidus was next, lasting less than 1 year in 1.6% of patients and over a year in 0.4%. Sinusitis occurred in 1.2% of patients, and delayed epistaxis occurred in 0.8%. Postoperative hematomas, meningitis, hydrocephalus, and deep venous thrombosis each occurred in 0.4% of cases. These results are discussed in the context of previous reports, including an international survey of pituitary surgeons. Although transsphenoidal surgery has a low morbidity and mortality, it is nevertheless associated with potentially serious difficulties that should be expeditiously recognized and managed.

[Effect of hypophysectomy on survival, weight gain and food intake in chickens]. / Effet de l'hypophysectomie sur la survie, la croissance pondérale et la consommation alimentaire du poulet.

Hypophysectomy has been performed in 1, 20, 50, 90 and 110-day-old chickens. The effect of the pituitary ablation depended on both the age and the sex of the birds. Chicks hypophysectomized on the day of birth survived no more than 5 days. In the other experimental groups, the later the operation was done, the longer the chicks survived, with some rare exceptions. Survival was generally better in females. The weight gain was significantly slower in 50-day-old hypophysectomized chicks than in the controls. In the 90-day-old operated animals, slackening of weight gain was less pronounced; a catch-up weight gain began at 24 weeks and reached the control levels at about 45 weeks. These differences were still less marked in 110-day-old hypophysectomized chickens in which the catch-up weight gain was faster. In all the hypophysectomized chicks, food intake was less than in the controls, but its utilization was better than in the controls, especially the pair-fed controls.

Hypophysectomy in the treatment of disseminated carcinoma of the breast and prostate gland.

Transsphenoidal hypophysectomy offers gratifying palliative relief of pain to patients with metastatic cancer of the breast and prostate. This report represents the results of two years' experience with this procedure at Emory University School of Medicine. The physiologic rationale and clinical indications for hypophysectomy are described, as is the operative technic using the open transsphenoidal microsurgical approach. The series of cases reported here includes 20 men with disseminated prostatic carcinoma and 23 women and one man with metastatic carcinoma of the breast. All 44 procedures were done by the transsphenoidal microsurgical approach. Pain was the preoperative indication for surgery in 41, while three patients were operated on for extensive disease without pain. Satisfactory relief of pain was obtained in 76% of the patients with prostatic cancer and in 83% of the breast cancer patients. While the results are gratifying with regard to relief of pain, the duration of follow-up is not sufficient to comment on the value of the procedure in significantly prolonging life.

PIP: The indications for and the results of hypophysectomy for advanced cancer of the breast or prostate gland are reviewed. The technic of open microsurgical transsphenoidal hypophysectomy is described. Since the metabolism of some breast cancers is influenced by estrogenic hormones, the major effect of hypophysectomy seems to be the complete suppression of estrogen production by the gonads and adrenal glands by removal of gonadotropin and ACTH, respectively. Other specific substances, such as growth hormone or prolactin, may also be factors. In cases of prostate cancer which relapse after castration, the adrenals seem to elaborate a significant amount of extradgonadal androgen. Hypophysectomy removes the source of ATCH and thus stops androgen production by the adrenal glands. Other hormones may also be important. In premenopausal patients with advancing cancer of the breast, oophorectomy should be the initial procedure. Most patients after a previous favorable response to oophorectomy get a subsequent objective improvement from hypophysectomy. In postmenopausal patients the effects of hormone therapy should 1st be tried. Many patients responding favorably to hormone therapy will also be benefited later by hypophysectomy. Remission rates are higher in older women. However, hypophysectomy should be carried out relatively early to obtain a useful remission. About 25% of those not responding to other methods will obtain a remission following hypophysectomy. Along interval after the mastectomy before metastases occurs is a favorable prognostic sign. While bony metastases respond best, other sites of metastases do not contraindicate the operation. Most patients with prostatic metastases obtain relief after hypophysectomy, even some of those who have not been benefited by other methods. Advanced age alone is not a contraindication. A preoperative evaluation should be done including a series of endocrine studies. Open microsurgical transsphenoidal hypophysectomy is considered the operation of choice. Complete removal of the gland is accomplished with less disturbance to the patient than an intracranial operation. General anesthesia is used. After the operation tests for pituitary reserve are repeated and a maintenance regimen of hydrocortisone prescribed. Thyroid replacement therapy is often needed. Subjective remissions are more common than objective ones, particularly relief of pain. This operation was done on 20 men with metastatic cancer of the prostate and 23 women and 1 man with metastatic cancer of the breast. Of the prostate cases, 3 patients died during the early postoperative period. Of the other 17, there have been 7 deaths from the cancers after 1-7 months. Of the 23 breast cases, severe body pain was the indication for the operation. Relief occurred in 19 (83%). There have been 7 deaths from the cancers. Hypophysectomy does not predispose to or lead to alterations in emotional state or mental function. Others with larger series of cases have reported that those responding favorably have lived an average of 25.8 months while average survival of those not so responding has been only 5.6 months.

[Transsphenoidal hypophysectomy in metastasizing breast cancers. Experience from 160 cases]. / Hypophysectomie transsphénoïdale dans les cancers du sein métastatiques. Expérience de 160 cas

160 patients suffering from advanced metastatic cancer of the breast had transsphenoidal open surgical hypophysectomy. Mortality (1,8 p.cent) and morbidity were extremely low in view of the general conditions of the patients. Immediate relief of pain due to bone metastasis was obtained in 92 p.cent of cases. Such results emphasized the important point of achieving total hypophysectomy.

Trans-sphenoidal hypophysectomy in disseminated carcinoma of the breast.

One hundred and eight patients with advanced carcinoma of the breast were treated by trans-sphenoidal hypophysectomy and followed up for at least 1 year. The results were assessed both by clinical response and objectively by survival following hypophysectomy, as expressed by the survival ratio. The two methods showed close correlation. The results show that there is a variation in response relating to menopausal status and age at diagnosis, subsequent hormonal manipulaton and physical condition at hypophysectomy. Younger patients whose carcinoma is diagnosed after menopause carry a good prognosis, yet the older premenopausal patients, especially if their clinical condition is poor, do not benefit. Easily available clinical information can be a guide to prognosis.