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Results of external pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease.

Fourteen adult patients (10 females and 4 males; age range 20-60 years) with persistent Cushing's disease after transsphenoidal microsurgery were treated with pituitary irradiation. Supervoltage multiportal administration was employed at a total dose of 50 Gy (+/- 0.65 SD). The interval between microsurgery and pituitary irradiation was less than 6 months in 6 patients and more than 6 months in 8. The pituitary-adrenal axis was evaluated postsurgically, before irradiation and every 6 months thereafter. The remaining anterior pituitary function was simultaneously tested. Remission rates at 12 months and 24 months after radiotherapy were 61 and 70%, respectively. Two patients developed TSH deficiency and another gonadotropin deficiency during the follow-up after radiation. We conclude that pituitary irradiation is the treatment of choice for persistent Cushing's disease after unsuccessful surgery because of its high efficiency and low incidence of adverse reactions when compared with other forms of treatment.

Adrenocorticotropic Hormone↗

Conventional pituitary irradiation is effective in normalising plasma IGF-I in patients with acromegaly.

OBJECTIVE: For patients in whom acromegaly persists despite pituitary surgery, conventional pituitary irradiation represents an additional treatment option. A 30-60% cure rate is described in the literature, but these studies did not utilise strict rules of remission, such as "safe" GH levels <2.5 microg/l, and age-adjusted normal IGF-I levels. DESIGN AND METHODS: We report the outcome of 41 patients with acromegaly who received pituitary conventional external irradiation. The median follow-up time was 12.8 years (3.7-43.4 years) post-radiotherapy. RESULTS: The median pre-irradiation GH level was 31.0 microg/l (7.0-210 microg/l). Information on IGF-I levels was only available for 6 patients prior to therapy. Utilising strict rules of remission, one-third (14/41) of our patients had normal biochemical parameters, i.e. "safe" GH (0.5 microg/l (range 0.2-1.6 microg/l)) and normal age-adjusted IGF-I levels (multiple of upper limit of normal range (xULN); 0.45 (0.2-1.0)) at the end of the follow-up period. An additional 9 patients achieved normal levels with adjunctive drug therapy. Furthermore, disease activity was reduced in a considerable proportion of the 18 patients who did not achieve normal biochemical levels (GH: 3.6 microg/l (1.9-15.7 microg/l); xULN of IGF-I: 1.6 (0.9-2.6)). In retrospect, remission is unlikely in patients who had a GH level greater than 52 microg/l (mean+2 s.d. of cured patients) prior to radiotherapy. In addition to the 12 patients with pre-irradiation pituitary functional deficiency, another 11 patients developed symptoms of panhypopituitarism during the 3-year period following irradiation. Within a 6-year period, partial pituitary insufficiency was observed in a further 7 patients, thus necessitating hormone substitution treatment. CONCLUSION: Using strict rules of remission, in our cohort we found both a normalisation of IGF-I and safe GH levels in 34% of patients treated for acromegaly with conventional irradiation therapy.

Acromegaly↗

Progression of cardiovascular disease in acromegalic patients treated by external pituitary irradiation.

Cardiovascular complications are a major cause of morbidity and mortality in acromegaly and seem to be related to the long duration of the disorder. Conventional external pituitary irradiation for acromegaly produces a consistent, but slow, fall in elevated serum growth hormone (GH) levels. It has not been established whether such treatment is effective in preventing the development of cardiovascular complications. The evolution of cardiovascular disease has therefore been studied in 11 acromegalic patients followed up for a mean 10 years (range 3-17) after external pituitary irradiation. At the final follow-up fasting serum GH were significantly (P less than 0.01) lower than pre-irradiation levels, but cardiovascular events (myocardial infarction, dysrhythmias, hypertension, major arterial disease, heart failure) increased significantly in prevalence (P less than 0.01) during this period. Electrocardiographic abnormalities also increased in prevalence. At the final follow-up 6 patients had cardiomegaly on chest X-ray and echocardiographs (10 patients) were abnormal in every case. All 11 patients had evidence of complete or partial anterior hypopituitarism. We confirm that external pituitary irradiation is effective in reducing elevated serum GH levels in acromegaly, but suggest that such a slow reduction in serum GH levels does not retard the development of cardiovascular complications.

Acromegaly↗

Cell proliferation and death in the irradiated pituitary gland and its modification by growth stimulants.

PURPOSE: This study was undertaken to show whether the rate of expression of radiation injury in the rat pituitary gland could be accelerated by the use of growth stimulants. METHODS AND MATERIALS: Rat pituitary glands were irradiated in situ with a range of single doses up to 20 Gy. The rats were then given subcutaneous slow-release implants containing 17beta-estradiol (E2) and sulpiride (S) to stimulate lactotroph proliferation. Two sequential cycles were used, each consisting of stimulation (3 weeks) and withdrawal (2 weeks). Measurements were made of gland weight; BrdU-labeled, giant, and apoptotic cells; lactotrophs; as well as pituitary prolactin content, in response to exogenous thyroid-releasing hormone (TRH). RESULTS: The two cycles of stimulation/withdrawal resulted in marked changes in gland weight, BrdU-labeling index, and serum prolactin (PRL) levels in unirradiated rats. The proportion of immunopositive growth-hormone-producing (GH) cells increased after irradiation. Radiation inhibited the hypertrophic response to E2 + S and also inhibited increases in BrdU-labeling index and serum PRL levels. Also, giant lactotrophs were observed in the irradiated pituitaries. However, they were not seen in the unirradiated rats or in the irradiated rats treated with E2 + S. TRH promoted PRL secretion in the unirradiated rat. In contrast, TRH inhibited PRL secretion in the irradiated rat and in all treatment groups receiving E2 + S. Apoptosis was induced by irradiation and was substantially increased in lactotrophs and in other cell types by withdrawal of the E2 and S stimulus, although the highest observed incidence was only 7 per 10,000 cells. CONCLUSION: Both irradiation and E2 + S treatment removed the hypothalamic control of PRL secretion, which reveals this important inhibitory action of TRH upon PRL secretion. This suggests that it is not suitable as a dynamic test of pituitary PRL reserves in such abnormal situations, where there may also be damage to the hypothalamic-pituitary vasculature. The increasing proportion of GH cells after irradiation indicates that lactotrophs respond more rapidly to irradiation. The stimulation by E2 + S somehow prevented the radiation-damaged lactotrophs from becoming giant cells. Also, the ratio of apoptotic cells to BrdU-labeled cells was increased by the E2 + S treatment, indicating that the E2 + S did enhance radiation-induced cell death relative to cell renewal. However, overall, the E2 + S stimulus protocol did not promote a dramatic increase in cell death (apoptosis) nor a marked decrease in residual gland weight after irradiation. Hence, its use would probably not be beneficial in the treatment of slow-responding prolactinomas, if malignant lactotrophs respond similarly to the normal pituitary lactotrophs. However, the observation of induced apoptosis after hormone and drug withdrawal suggests that agents which promote tumor shrinkage may be effective by causing rapid apoptosis of tumor cells in vivo.

Animals↗

Successful treatment of Cushing's disease with o,p'-DDD followed by pituitary irradiation in a 19-year-old male patient.

A 19-year-old male patient with Cushing's disease was treated for 15 months with a gastric-insoluble preparation of o,p'-DDD. The daily o,p'-DDD dose (range, 2 to 12 g) was adjusted periodically according to the urinary excretion of 11-hydroxycorticosteroids. Because of a rise in the plasma ACTH level from 135 to 300 pg/ml 12 months after the start of the o,p'-DDD therapy, the dose was reduced from 6 to 2 g/day and external pituitary irradiation (4,480 rads) was initiated. Insulin-induced hypoglycemia and stimulation tests with luteinizing-hormone-releasing factor and thyrotropin-releasing hormone, performed before initiation of o,p'-DDD and six months after pituitary irradiation, did not reveal any disturbance in the secretion of human growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone or prolactin. The clinical and laboratory signs of Cushing's disease disappeared gradually, and the patient tolerated the drug well, even at a dose of 12 g/day. The only abnormalities found during o,p'-DDD treatment were low serum thyroxine levels, which returned to normal after discontinuation of the drug, and a transient drop in thrombocyte count. At present, two years after the discontinuation of o,p'-DDD therapy and pituitary irradiation, the patient is symptom free and receives no medication.

Adult↗

Long term follow-up of Cushing's disease treated with reserpine and pituitary irradiation.

Twenty adult patients with Cushing's disease treated with long term reserpine administration in combination with a single course of external pituitary irradiation were followed. Eleven patients experienced long term remissions of 15.5 +/- 8.9 (mean +/- SD) yr (55%) after a mean irradiation dose of 53.9 +/- 11.4 Gy and a mean duration of reserpine administration of 24.3 +/- 9.3 months. The long term remission rates of the patients irradiated with 50 Gy or less (n = 9; 45.0 +/- 7.1 Gy) and those with more than 50 Gy (n = 10; 61.3 +/- 3.3 Gy; excluding 1 irradiated with 66 Gy who developed brain necrosis) were 56% (5 of 9) and 60% (6 of 10), respectively, and did not differ significantly. There were no significant differences between the 2 groups with regard to the duration of reserpine administration or pretreatment clinical features. At the latest examination, regardless of the irradiation dose, all 9 patients with long term remission showed a higher level of plasma cortisol or 11-hydroxycorticosteroids in the morning than in the evening, normal suppressibility of plasma cortisol with overnight 1 mg dexamethasone (9 of 10), and well preserved responses of other pituitary hormones to various loading tests: normal responses of plasma ACTH to CRH (6 of 9), TSH (7 of 8), and PRL (5 of 8) to TRH and age-related normal responses of GH to GRH (4 of 8), LH (6 of 8), and FSH (6 of 8) to GnRH. These findings suggest that long term reserpine administration in combination with a conventional dose of pituitary irradiation is useful in the treatment of Cushing's disease.

Adolescent↗

Conventional pituitary irradiation in acromegaly. Effect on growth hormone and TSH secretion.

Thirty-one patients who had been treated for acromegaly for 1-21 years with conventional pituitary irradiation were re-examined. Immunoreactive growth hormone (GH) was measured in connection with an oral glucose load. Adrenal and gonadal functions were assessed on the basis of plasma cortisol and the urinary excretion of 17-ketogenic steroids, 17-ketosteroids and gonadotrophins. In evaluating the thyroid-pituitary axis the thyrotrophin-releasing hormone stimulation test (TRH) was used. Initially 30 patients had experienced definite benefit from the treatment but at the time of re-examination 10 still had clinically active disease and required another type of treatment. Normal GH levels (less than 5 ng/ml/1) were seen in only 12 patients. Skin thickness was normal in 15 out of 30. Thus the remission rate can be evaluated as being 67% as regards clinical activity, 50% with regard to skin thickness and 39% in terms of GH levels. Hypogonadism occurred in 12 patients (39%) and adrenal and thyroid failure in 5 patients each (16%). The response to TRH was within the normal range in 2 of the hypothyroid patients. In 22 euthyroid patients the mean increment in serum TSH in response to 200 mug of synthetic TRH was only 5.8 mU/1 which was significantly below the normal mean 12.5 mU/1. Furthermore, in 7 of these patients (32%) the response was absent or subnormal (less than 3.0 mU/1). This indicated that the pituitary is capable of secreting enough TSH for maintenance of an euthyroid state but that its capacity is limited. Conventional pituitary irradiation is not a very effective treatment in acromegaly but may still be recommended in selected cases.

Acromegaly↗

Combined reserpine and pituitary irradiation therapy for Cushing's disease patients following unsuccessful transsphenoidal microsurgery.

The effectiveness of treatment with reserpine and pituitary irradiation, and with reserpine alone was evaluated in three female patients with Cushing's disease whose transsphenoidal pituitary microsurgery (TPM) had been unsuccessful. In these patients, endocrinological examination after the surgery demonstrated a recurrence of the disease although the microadenomas had apparently been curetted out from the pituitary in all patients. The first patient therefore received 1.0-2.0 mg/day of reserpine with 60 Gy x-ray irradiation, and there was complete remission within 3 months and the patient remained asymptomatic even when reserpine was reduced to 0.1 mg/day 10 years later. The second case was treated with low dose x-ray (20 Gy) and reserpine (0.5-2.0 mg/day), which were also effective. However, 2 weeks discontinuation of the drug caused urinary 17-hydroxycorticosteroids (17-OHCS) and serum cortisol to increase abnormally again, but these were finally re-normalized by an additional administration of reserpine. The third case was given reserpine alone (1.0-2.0 mg/day). She also had a remission in 3 months and the treatment was continued for one year, requiring no further treatment. These results suggest that additional treatment with reserpine and pituitary irradiation or with reserpine alone after unsuccessful TPM may be an effective alternative for patients with Cushing's disease.

17-Hydroxycorticosteroids↗

Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease.

Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. Two of these received no further active treatment, one underwent successful pituitary surgery, one underwent a second course of low-dose external irradiation (as yet unsuccessful) and one has been treated with metyrapone for a total of 75 months. One of the 13 patients who did not respond received a further course of low-dose pituitary irradiation with prompt remission and two have received metyrapone for 41 months and 15 years without ill effect. One patient died from cerebrovascular disease. The remaining nine patients underwent bilateral adrenalectomy (one after unsuccessful pituitary surgery) with rapid resolution of hypercortisolism. Five of these patients have developed hyperpigmentation and elevated ACTH levels (range 505-1150 ng/l). A pituitary microadenoma has been demonstrated on CT scan in three and successfully removed by microadenomectomy. In the present series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy.

Adolescent↗

The effect of external pituitary irradiation on elevated serum prolactin levels in patients with pituitary macroadenomas.

The response of serum prolactin to external radiotherapy was studied in 58 patients (32 women) with pituitary tumours, aged between 16 and 75 years. Forty-four patients underwent pituitary surgery before radiotherapy. Six patients were irradiated with a regimen of 20 Gy in eight fractions over 10-11 days and the remainder received 35-42.5 Gy in 15 fractions over 20-22 days. Following radiotherapy, 44 patients received additional treatment with dopaminergic agonists. Prolactin levels ranged from 1078 to 491,000 mU/l (median 11,750 mU/l) before radiotherapy and all but three patients showed a fall in serum prolactin (measured 4 weeks after stopping bromocriptine in those on dopamine agonist therapy) during observation over periods of up to 154 months. All patients had evidence of pituitary fossa erosion or expansion at presentation and large tumours (Hardy-Vezina Grade 3-4) were more common in male patients (chi 2 = 10.08, p less than 0.01). The rate of fall of serum prolactin levels was greater in patients with true prolactin-secreting tumours when compared with those who had stalk or hypothalamic damage (p less than 0.005). The rate of decline of serum prolactin was also significantly related to the pre-radiotherapy value (rho = 0.519, p less than 0.01). A serum prolactin level less than 500 mU/l was achieved in 31 out of 44 patients treated with radiotherapy and dopaminergic agonist but only nine remained normoprolactinaemic when medication was discontinued for 4 weeks or more. The serum prolactin level fell permanently to less than 500 mU/l in two of 14 patients treated with radiotherapy only. Actuarial analysis of data from all patients indicated a 50 per cent probability that prolactin would be reduced to less than 500 mU/l by 10 years; this increased to 58 per cent for patients with smaller tumours (Hardy-Vezina grade 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Long-term visual changes following pituitary irradiation.

PURPOSE: To analyze possible long-term effects of pituitary irradiation on visual fields and acuity. METHODS AND MATERIALS: Eighty-six patients were treated with radiotherapy for pituitary tumors at the National Cancer Institute between 1980 and 1991. Twenty-one patients had baseline preradiation and long-term follow-up visual fields. Eyes were followed with serial Goldmann or Humphrey visual field testing. Neuroradiologic correlation was made with the available brain scans. There were 12 females and 9 males with an median age of 44. Eighteen patients had hormone-secreting tumors and three had chromophobe adenomas. All but one patient with an inoperable invasive macroadenoma were irradiated after one or more transphenoidal resections or a craniotomy. The indications for radiation in the operable patients were: nine patients, partial tumor resection; nine patients, tumor recurrence; and two patients, persistent hormonal elevation after surgery. The median dose delivered was 50 Gy (45-59.4 Gy). The average field size was 6 x 6 cm (5 x 5 cm to 10 x 12.5 cm). RESULTS: With a median follow-up of 48 months (14-128) after radiotherapy, 1 out of 21 patients has recurred (at 8 months) and all patients are alive. Of the 38 sighted eyes, 27 had normal visual fields before and after radiation, 7 eyes showed improvement, and 4 eyes had a stable defect, mostly in the superior temporal region. There were no cases of radiation-induced visual field or acuity deterioration. Six out of 21 patients (29%) had neurologic symptoms in follow-up, most of which appeared vascular in nature. Four patients complained of atypical migranous-like headaches that first began 1.5-3 years following treatment. One patient complained of recurrent vertical diplopia and one patient had a cerebral vascular accident 7 years following therapy. A dose-related association with these neurovascular symptoms approached statistical significance. Only 1 out of 11 (9%) patients who received doses less than or equal to 50 Gy developed these symptoms, whereas 5 out of 10 (50%) patients who received doses greater than 50 Gy developed symptoms (p2 = 0.064). CONCLUSION: Postoperative radiation for partially resected or recurrent pituitary adenomas using megavoltage radiation, as well as modern field arrangements and fractionation, is extremely effective and safe. Ninety-five percent of patients are free of recurrence with not deterioration in the visual fields or acuities. Some patients experienced neurovascular symptoms (mostly vascular headaches) following surgery and radiation. There is a trend (p2 = 0.064) toward increased symptoms following higher radiation doses.

Adenoma↗

Treatment of Cushing's disease by interstitial pituitary irradiation: short- and long-term follow-up.

Trans-sphenoidal intrasellar implantation of radioactive rods was employed to treat Cushing's disease in our Institution between 1958 and 1981. The patients were followed at regular intervals after the procedure. The aim of this work is to assess retrospectively the results, comparing the short- (1 year) and long-term (average 21.8 years) effects of this treatment. Seventy-six patients received pituitary implantation of 90Y- and one of 198Au-labelled rods, delivering a dose of 100-150,000 rad. Complete remission was obtained in a few weeks to months in 57/76 patients (5 of whom required a second implantation); 2 patients died of meningoencephalitis and 3 of cardiovascular complications associated with hypercortisolism 1 to 2 months after surgery. In 12 patients bilateral adrenalectomy or external pituitary irradiation were required to achieve remission; one of them developed Nelson's syndrome 15 years after implantation. Two were lost at follow-up. Long-term follow-up was possible in 41 patients of the initial series. Of these, 40 were cured of the disease, with hypoadrenalism developing in 25, while recurrence was observed only in the patient treated with 198Au. The incidence of hypothyroidism was 50%, and that of hypogonadism 54%. Permanent diabetes insipidus developed in 1 subject. GH deficiency resulting in retarded growth was found in the youngest patient, who had been operated at the age of 14. In conclusion, interstitial irradiation of pituitary adenomas was a safe and effective procedure for the treatment of Cushing's disease.

Adolescent↗

Recurrent Cushing's disease: successful treatment by pituitary irradiation or trans-sphenoidal hypophysectomy in two cases.

Two patients developed recurrent Cushing's disease 3 and 7 years after total bilateral adrenalectomy. In the first patient, a 65-year-old man, the adrenal tissue was not localized by radioactive cholesterol scintigraphy. Plain x-ray films of the skull revealed a normal sella turcica. Although clinical improvement resulted from the discontinuation of cortisone replacement therapy, urinary free cortisol levels remained elevated and the patient was treated with pituitary irradiation. Serum and urine cortisol levels gradually returned to normal. Four years after irradiation, the plasma adrenocorticotropic hormone (ACTH) concentration was elevated, but tomography of the sella turcica and urinary cortisol excretion remained normal. The second patient, a 41-year-old man, displayed elevated ACTH levels and x-ray evidence of a pituitary tumor at the time of recurrent Cushing's disease. After trans-sphenoidal hypophysectomy, the hypercortisolism abated and the ACTH concentration returned to normal. Adrenal scintigraphy frequently locates cortisol-secreting tissue in patients with recurrent Cushing's disease, and some investigators suggest treatment by the surgical removal of the adrenal remnant. Although the etiology of Cushing's disease is controversial, current evidence suggests that most cases result from ACTH-producing pituitary tumors. We suggest, therefore, that the anterior pituitary gland may be a more suitable target than the adrenal remnant for the treatment of recurrent Cushing's disease.

Adenoma↗

Damage to the anterior visual pathway and brain parenchyma following external pituitary irradiation.

Three cases of damage to the optic nerves and chiasma following pituitary irradiation with Co60 teletherapy are described. All of them presented with progressive visual impairment months following irradiation and simulated recurrence of the tumour. CT scan was also not helpful in differentiating radionecrosis from tumour recurrence. On exploration the optic nerves and chiasma appeared discoloured and scarred. One case, who also had diffuse radionecrosis of brain parenchyma, died. No satisfactory therapy is currently available for this grave complication but proper safeguards can prevent it.

Adult↗

Survival following alpha particle pituitary irradiation for diabetic retinopathy.

The purpose of this study was to evaluate the mortality experience of persons with longstanding diabetes who had received pituitary irradiation for diabetic retinopathy compared to a matched group of persons with diabetes who had not had pituitary ablation. The irradiated cohort consisted of 167 patients treated at the Donner Pavilion (Lawrence Berkeley Laboratory, University of California, Berkeley), and the comparison cohort was the population evaluated in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Survival analyses were performed comparing the two cohorts using three different sets of matching criteria, each more restrictive than the previous analyses. The three different strategies were (1) matched only on severity of diabetic retinopathy; (2) matched on severity of retinopathy and age; and (3) matched on severity of retinopathy, age, gender, and hypertension status. Tests of comparison were the log-rank test, the Wilcoxon test, and the likelihood ratio test. For the model matching only on severity of retinopathy, mean survival was 8.3 years for the WESDR group and 9.4 years for the ablated group (p > 0.05 for all three statistical tests). For the model matched on retinopathy and age, mean survival was 8.9 years for the WESDR group and 9.2 years for the ablated group (p=0.05 log-rank test, 0.32 Wilcoxon test, and 0.06 likelihood ratio test). For the model matching on retinopathy, age, gender, and hypertension status, mean survival was 8.9 years for the WESDR group and 11.6 years for the ablated group (p=0.72 log-rank test, 0.08 Wilcoxon test, and 0.82 likelihood ratio test). These data are compatible with the notion that pituitary ablation, and therefore induced pituitary growth hormone deficiency, may not decrease survival in those with severe diabetic retinopathy.

Adult↗

Progressive visual failure in acromegaly following external pituitary irradiation.

Four out of twenty-three acromegalic patients selected for treatment with external megavoltage pituitary irradiation between 1961 and 1975 developed progressive visual failure. They had received megavoltage external irradiation through multiple portals from a cobalt-60 unit over a period of 3 weeks. Visual deterioration began 2 months to 6 years after irradiation. In two patients the optic nerves were explored. In both, post-mortem later confirmed radiation damage to the optic nerves and hypothalamus. In one case there was also necrosis of the right frontal lobe with necrosis and inflammation of the bone surrounding the pituitary fossa. In the two other patients, extensive clinical and neuroradiological investigation excluded the presence of a suprasellar mass as a cause for this visual failure and a clinical diagnosis of radiation necrosis was made.

Acromegaly↗

Sustained remission of Cushing's disease with mitotane and pituitary irradiation.

Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly to the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest.

Adrenal Glands↗