Reduction of pituitary tumor size with clinical and biochemical improvement with bromocriptine in a normoprolactinemic Cushing's disease

We report a 37-year old Japanese female patient with Cushing's disease who was treated with a large daily dose of bromocriptine, which resulted in the reduction of the pituitary tumor size with clinical and biochemical improvements. On admission, the pituitary tumor size detected by magnetic resonance imaging (MRI) was 12.4 x 11.1 x 6.2 mm. Both the basal plasma prolactin level and its response to TRH test were normal. The patient was treated with bromocriptine at 5 to 35 mg/day. With 35 mg daily, 24-h urinary free cortisol started to decrease and eventually became normal. Four months after initiation of treatment with the drug, there was clinical remission with normalization of suppressibility of plasma cortisol with 1 mg dexamethasone. Repeated examination of the pituitary fossa by MRI showed a marked reduction in the tumor size (6.3 x 6.2 x 2.4 mm). This is a very rare case in which treatment with bromocriptine resulted in a reduction of the pituitary tumor size as well as clinical and biochemical improvements in a patient with normoprolactinemic Cushing's disease.     

Nelson's syndrome: complete remission with cabergoline but not with bromocriptine or cyproheptadine treatment

A woman affected by Cushing's disease underwent bilateral adrenalectomy followed by radiotherapy of the hypothalamic-pituitary area when she was 18 years old. Thereafter, she used hydrocortisone acetate replacement therapy (35.5 mg divided into two daily doses). At the age of 26 years, the patient exhibited the clinical signs of the Nelson's syndrome, i.e. skin and gingival hyperpigmentation accompanied by amenorrhea, and elevated ACTH plasma levels (2,850 pg/ml, normal range 15-80 pg/ml). The magnetic resonance imaging (MRI) analysis of the sellar region evidenced a pituitary macroadenoma, measuring 14 x 13 mm. The patient was initially treated with cyproheptadine hydrochloride (12 mg/day) for 18 months. There was a partial improvement of the symptoms, with a reduction of the ACTH plasma levels to 112 pg/ml, but without any modification of the tumor mass. Due to sleepiness and weight gain, the cyproheptadine treatment was interrupted and substituted by a cabergoline (0.5 mg twice a week) therapy. Soon after cabergoline was applied an improvement of the clinical symptoms and signs was observed such as a regression of the tumor mass and the normalization of the ACTH plasma titers (38 pg/ml). Later, cabergoline was substituted by bromocriptine (7.5 mg/day) and the plasma levels of ACTH increased again (247 pg/ml), and headache and cutaneous hyperpigmentation were recorded. When cabergoline was reintroduced there was a clinical improvement and normalization of ACTH plasma levels (64 pg/ml). The MRI analysis of the sella region demonstrated a complete remission of the pituitary adenoma. The results obtained show for the first time that a long-term treatment with cabergoline also brings about a complete remission of Nelson's syndrome in the presence of a pituitary macroadenoma.     

Positive Prolactin Response to Bromocriptine in 2 Patients with Cabergoline-Resistant Prolactinomas

ObjectiveTo describe a positive prolactin response to bromocriptine treatment in 2 patients with cabergolineresistant prolactinomas.MethodsWe report the patients’ clinical presentations, laboratory test results, imaging findings, and clinical courses.ResultsPatient 1 had a 5-mm pituitary microadenoma that was initially diagnosed at age 30 years. After initial diagnosis, she was treated with transvaginal bromocriptine for 9 years and then subsequently went untreated for 2 years. After developing symptoms of amenorrhea, decreased libido, and hyperprolactinemia, oral cabergoline, 0.5 mg twice weekly, was initiated. Her prolactin concentration remained elevated at 80 ng/mL while taking cabergoline. Her prolactin concentration decreased to 13 ng/mL after her regimen was switched to bromocriptine, 5 mg daily. Patient 2 had a 17-mm pituitary macroadenoma that was initially diagnosed at age 15 years. Oral cabergoline was started at 0.5 mg twice weekly and increased to 1 mg 3 times weekly when prolactin levels continued to rise to 340 ng/mL over 18 months. After visual field defects developed, transsphenoidal surgery was performed. One year after surgery, magnetic resonance imaging showed a 6-to 7-mm pituitary adenoma, and there was a gradual rise in serum prolactin. Her serum prolactin concentration continued to rise to 212 ng/mL with increasing tumor size over 3 years. Cabergoline was discontinued and oral bromocriptine was initiated at a dosage of 10 mg daily. After 4.5 months of bromocriptine therapy, her serum prolactin concentration decreased to 133 ng/mL. However, after 2 months, the macroadenoma continued to increase in size and a visual field defect developed, so another transsphenoidal operation was performed.ConclusionsAlthough cabergoline is generally preferred to bromocriptine for the treatment of patients with prolactinomas because of its better tolerance profile and greater effectiveness, in patients with cabergoline-resistant prolactinomas, a bromocriptine trial should be considered a safe, relatively inexpensive, and well-tolerated alternative. (Endocr Pract. 2011;17:e55-e58)     

Follow-up study on treatment in 27 patients with Cushing's disease: adrenalectomy, transsphenoidal adenomectomy and medical treatment

27 patients with Cushing's disease were treated over a period of 18 years at the Departments of Medicine and Surgery, Nagoya University School of Medicine and the following results were obtained. 1) Adrenalectomy. 21 of 27 patients with Cushing's disease underwent adrenalectomy. 19 patients had total bilateral adrenalectomy and 2 patients unilateral adrenalectomy. 4 patients died, the cause of death not being related directly to adrenalectomy. 9 of 15 bilaterally adrenalectomized patients had hyperpigmentation even though they had been given substitution therapy with cortisol 20-30 mg daily. They had elevated plasma ACTH levels, which were not completely suppressed by 2 mg of dexamethasone or 2.5 mg of bromocriptine per day. 2) Adenomectomy, 5 patients had adenomectomy via the transsphenoidal approach. 3 patients were cured but one of them has required postoperative substitution therapy with cortisol for hypopituitarism for one year until today. 2 of 5 adenomectomized patients had a recurrence of Cushing's syndrome after remission for 6-8 months. One of these recurrent cases has been subsequently treated successfully with bromocriptine, a dopaminergic drug. 3) Medical treatment. 2.5 mg per day of bromocriptine has been effective in 2 patients without a pituitary adenoma and ineffective in the other 4 patients with a pituitary adenoma. 24 mg per day of cyproheptadine, an antiserotoninergic drug was not effective in any of the 4 patients with a pituitary adenoma.     

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.     

Effect of ACE inhibitors on proteinuria and renal functioning in primary glomerulopathies]

Angiotensin converting enzyme inhibitors was given to 16 patients with glomerular nephritis in whom a complete remission of nephrotic syndrome could not be achieved with immunosuppressive-anti-inflammatory therapy. Captopril in the daily dose of 25-75 mg and enalapril in the daily dose of 10 mg were administered for 1-36 months (mean 12.6 months). Daily proteinuria decreased by 40-80% comparing with baseline value in 2/3 of patients. Total protein and albumin serum levels increased simultaneously. No changes in blood creatinine were noted in patients with initially normal renal functioning except one patient. Renal functioning was stable in 50% of patients with increased blood creatinine levels (mean 200 mumol/L). Blood creatinine was increasing in the remaining patients.     

Status of allogeneic bone marrow transplantation in childhood in the GDR

Of 25 HLA-identical, MLC negative transplants 10 patients had acute lymphoblastic leukaemia (ALL), 8 acute nonlymphoblastic leukaemia (ANLL), 3 severe aplastic anaemia, 2 malignant histiocytosis, 1 patients neuroblastoma and 1 Fanconi anaemia. 3 HLA nonidentical, MLC positive transplants were performed, two children had malignant infantile osteopetrosis and 1 child had a severe combined immunodeficiency disease. Patients with ALL and ANLL received cyclophosphamide and single dose total body irradiation. 3 patients received fractionated TBI. The results for the allogeneic group overall indicate that the actuarial disease free survival rate is 0.62. 16 of 25 patients are in continuous complete remission (CCR) periods of 3-78 months posttransplant. All three transplanted children with severe aplastic anaemia alive disease-free for periods of 21-81 months. 10 patients with ALL were transplanted (2 in first remission for high risk ALL, 8 in second remission). 7 of 10 patients are alive and disease-free (CCR rate 0.67). 8 patients underwent BMT for ANNL while in first remission in 7 patients and in third partial remission in 1 patient. 4 of 8 patients are alive and disease-free for periods of 25-56 months (CCR rate 0.50). 1 patient with neuroblastoma stage IV survives 24 months, 1 child with Fanconi anemia died on day +25 of GVHD and septicaemia. 1 of the 2 patients transplanted for malignant histiocytosis relapsed 3 months posttransplant, 1 patient is alive and disease-free 5 months posttransplant. In none of the HLA-nonidentical and MLC positive transplantations T-cell depleted marrow engrafted.     

Single dose cabergoline versus bromocriptine in inhibition of puerperal lactation: randomised,double blind,multicentre study. European Multicentre Study Group for Cabergoline in Lactation Inhibition.

OBJECTIVE--To compare the efficacy and safety of a single dose of 1 mg of cabergoline with that of bromocriptine 2.5 mg twice daily for 14 days in the inhibition of puerperal lactation. DESIGN--Prospective, randomised, double blind, parallel group, multicentre study. SETTING--University of hospital departments of obstetrics and gynaecology in different European countries. SUBJECTS--272 puerperal women not wishing to lactate (136 randomised to each drug). INTERVENTIONS--Women randomised to cabergoline received two 0.5 mg tablets of cabergoline and one placebo tablet within 27 hours after delivery and then placebo twice daily for 14 days. Those randomised to bromocriptine received 2.5 mg of bromocriptine and two placebo tablets within 27 hours and then 2.5 mg of bromocriptine twice daily for 14 days. MAIN OUTCOME MEASURES--Success of treatment (complete or partial) according to milk secretion, breast engorgement, and breast pain; rebound symptomatology; serum prolactin concentrations; and number of adverse events. RESULTS--Complete success was achieved in 106 of 136 women randomised to cabergoline and in 94 of 136 randomised to bromocriptine and partial success in 21 and 33 women respectively. Rebound breast symptomatology occurred respectively in five and 23 women with complete success up to day 15 (p less than 0.0001). Serum prolactin concentrations dropped considerably with both drugs from day 2 to day 15; a prolactin secretion rebound effect was observed in women treated with bromocriptine. cabergoline and 36 receiving bromocriptine (p = 0.054), occurring most during the first treatment day. CONCLUSION--A single 1 mg dose of cabergoline is at least as effective as bromocriptine 2.5 mg twice daily for 14 days in preventing puerperal lactation. Because of the considerably lower rate of rebound breast activity and adverse events and the simpler administration schedule cabergoline should be the drug of choice for lactation inhibition.     

Effect of bromocriptine on lipid plasma levels in rats

Results show that bromocriptine induced marked alterations in plasma levels of cholesterol and lipids in response to acute and chronic administrations in rats. Two hours after an I.P. dose of 10 mg/kg, bromocriptine mesylate caused significant reductions in plasma levels of total high density lipoprotein (HDL) and high density lipoprotein cholesterol (HDL cholesterol). At a dose of 20 mg/kg, bromocriptine mesylate induced significant elevations in plasma levels of total cholesterol, total HDL, HDL cholesterol, total low density lipoproteins (LDL), and low density lipoprotein cholesterol (LDL cholesterol). Injected at a dose of 4 or 10 mg/kg daily for 14 consecutive days, bromocriptine mesylate caused significant increases in plasma levels of total cholesterol, LDL cholesterol and total LDL whereas the levels of HDL cholesterol, total HDL triglycerides (TG) were reduced. At a dose of 20 mg/kg all parameters were significantly increased. Marked hyperglycaemia was noticed in response to doses of 10, 15 and 20 mg/kg injected daily for 14 consecutive days or 2 hrs after a single administration of 15 mg/kg. Plasma insulin activity was reduced 2 hours after injection of bromocriptine at a dose of 15 mg/kg Likewise, a significant reduction in plasma insulin activity was observed in response to daily I.P. injections of bromocriptine at a dose of 15 mg/kg. Hyperglycaemic and hypoinsulinaemic effects of bromocriptine (acute and chronic) were markedly decreased when sulpiride, a dopaminergic D2 antagonist, was injected at an I.P. dose of 10 mg/kg before bromocriptine. Plasma ACTH activity was significantly increased in response to bromocriptine (15 mg/kg I.P.) in acute and chronic experiments. This effect was markedly diminished when sulpiride was injected prior to bromocriptine. In conclusion, bromocriptine induced marked elevations in plasma levels of total cholesterol and lipids which are likely to be related to hyperglycaemic and hypoinsulinaemic effects.     

Mechanisms of precocious puberty induced in male rats by pituitary grafts

Male rats were grafted on Day 21 of age with 'young' (21 days old) or 'adult' (90 days old) pituitary glands and then treated daily with 4 mg bromocriptine/kg or vehicle. Plasma samples were obtained on Days 21, 25 and 35 and when balano-preputial separation occurred. Both types of grafts advanced the age at which balano-preputial separation occurred and increased prolactin concentrations. Bromocriptine treatment reduced the prolactin values in both grafted groups, but did not block the advancement of puberty in rats treated with 'young' pituitary grafts. These results suggest the existence of two possible mechanisms in precocious puberty induced by pituitary grafts: one is prolactin-dependent (when 'adult' pituitary glands were used) and the other not directly related to prolactin (when 'young' pituitary glands were used).     

Long-term bromocriptine treatment and somatostatin in acromegaly

9 active acromegalic patients were treated for 12 months with bromocriptine (Parlodel, Sandoz) in a daily dose of 10 mg, and at the end of this treatment a somatostatin infusion was administered. The glucose tolerance and the serum hGH level were determined, and the changes in the clinical symptoms were evaluated. 7 patients (responder group) reacted favourably to the treatment; the other 2 proved to be non-responders, the hGH increasing as a consequence of bromocriptine treatment. The non-responders were among those patients who reacted to hyperglycaemia with a hGH increase (paradox glucose response). The somatostatin infusion employed in the drug treatment caused a very drastic decrease in the hGH level. The biochemical and clinical changes were not synchronous. The results permit the conclusions that (1) a relatively small dose of bromocriptine has a very good effect in the large majority of acromegalic patients; (2) the behaviour of the glucose response is an important point in the differentiation of the non-responders; (3) with somatostatin infusion during bromocriptine treatment a further considerable hGH decrease may be induced (a role is presumably played in the effect by the substitution of the hypothalamically drug-inhibited somatostatin release by exogenous material); (4) there is not a close parallel between the hGH decrease on bromocriptine treatment and the clinical improvement, which indicates the significance of the peripheral effects of the drug.     

A case of pituitary adenoma producing both growth hormone (GH) and adrenocorticotropic hormone (ACTH).

The authors report a very rare case of pituitary adenoma producing both GH and ACTH. A 29-year-old female was admitted with obesity, amenorrhea, acromegaly, hirsutism, excessive pigmentation, acne, and diabetes mellitus. Computed tomography revealed an intrasellar tumor 16 mm in height, with a destroyed sellar floor. The blood concentrations of GH, ACTH and cortisol were increased (GH: 92 ng/ml, ACTH: 94 pg/ml, cortisol: 18.3 micrograms/dl). No diurnal variation in the amount of cortisol was observed. The urinary 17-OHCS was suppressed by 8 mg but not by 2 mg of dexamethasone. A subtotal adenomectomy was then performed through the transsphenoidal approach, which led to a sufficient reduction of both blood GH and ACTH (cortisol). Histologically the tumor was an acidophilic pituitary adenoma. Immunoperoxidase staining showed diffuse GH and sporadic ACTH producing cells, but failed to show any cells producing both hormones. The electron micrograms of neoplastic cells showed the ultrastructural characteristics of respective GH and ACTH cells. Another increase in both GH and cortisol, which occurred 19 months after the operation, has been controlled by bromocriptine administration. This case may be the first reported case of a pituitary adenoma producing both GH and ACTH, not accompanied by prolactin (PRL) hypersecretion, which has been fully confirmed endocrinologically and histopathologically.     

Atypical Clinical Presentation of Acth-Dependent Cushing's Syndrome in a Patient Treated with Retinoic Acid

ObjectiveThe leading signs and symptoms of Cushing’s syndrome (CS) in adolescents, which depend on the duration and the severity of hypercortisolemia, are: a decrease in growth velocity with an increase in body weight, redistribution of fat tissue (round face), and less commonly, acne due to hyperandrogenization. A widely used antiacne drug, retinoic acid, can change the clinical presentation of CS and delay the diagnosis.MethodsWe report an atypical presentation of adrenocorticotropic hormone (ACTH)-dependent CS in a patient treated with retinoic acid due to severe acne.ResultsThree months after the discontinuation of retinoic acid treatment (at a dose of 40 mg daily for 6 months, with a 4 month break and then for an additional 6 months), a 17.5-year-old male presented with short stature (− 3.0 SD), muscle weakness, difficulty concentrating, insomnia, and depressed mood. Body weight (body mass index, 22 kg/m²), fat tissue distribution, pubertal status (testicular volume equal to 20 mL, pubarche V, axillarche present), and blood pressure were normal, and the patient’s bone age was equal to his chronologic age. His bone mineral density was decreased (Z-score, − 3.5 SD). The morning serum cortisol level was normal (8:00 am, 171.9 ng/mL) and did not decrease in the evening (8:00 pm, 178.9 ng/mL) or after 1 mg of dexamethasone (100.4 ng/mL). The patient’s urinary free cortisol was elevated on 3 occasions (274.5, 217.3, and 253.7 μg/day). Increased ACTH levels in the morning (97.5 to 141.1 pg/mL) and postcorticoliberine (577.6 pg/mL) pointed to ACTH-dependent CS. A magnetic resonance imaging scan of the pituitary gland confirmed the presence of a microadenoma.ConclusionRetinoic acid treatment may alter the clinical presentation of ACTH-dependent CS and consequently delay the diagnosis. (Endocr Pract. 2014;20:e119-e122)     

雷利度胺治疗难治复发急性粒细胞白血病临床观察

目的:观察雷利度胺治疗难治复发急性粒细胞白血病的疗效及不良反应。方法:给予雷利度胺单药治疗,雷利度胺50mg/d,口服给药,连续给药21天,28天为一个疗程。结果:应用雷利度胺4(2～6)个疗程,5例有效,2例获得完全缓解,2例部分缓解,1例因疾病迅速进展死亡退出试验。不良反应主要为疲乏4例,中性粒细胞减少性发热3例,中粒细胞减少4例,血小板减少1例,贫血1例。结论:应用雷利度胺治疗难治复发白血病有效,不良反应轻微且易于耐受。     

Cortisol concentrations in early porcine embryos

A study was conducted to determine the presence of cortisol in body tissue of porcine embryos at days 25 and 35 of gestation. Cortisol concentrations (ng/mg DNA) were low but measurable at day 25 and increased eightfold by day 35 during a time when body weight increased 6.4-fold. At day 35, there was a highly significant positive linear regression of body weight on cortisol concentrations. The source of this embryonic cortisol is not known, but its presence suggests the opportunity for cortisol to influence porcine embryonic development at these early gestational stages.     

High dose busulfan/etoposide as a preparatory regimen for second bone marrow transplants in hematologic malignancies

Five patients with hematologic malignancies who had relapsed between seven months and eight years after their primary bone marrow transplants were prepared with high dose busulfan/etoposide for second marrow transplantations from the same donors who had provided the marrow for the primary transplants. The preparatory regimen was well tolerated. All patients engrafted and entered complete remission. Two patients are alive and in continued remission two and ten months after second transplant. One patient died with acute respiratory failure after two months and two patients relapsed again eight and 17 months after second marrow transplantation. The combination busulfan/etoposide may prove to be a suitable preparatory regimen for second bone marrow transplant attempts in selected patients.     

Effects of bromocriptine on pituitary tumour size.

In a prospective study designed to assess the influence of bromocriptine on pituitary tumour size 12 patients with pituitary tumours, eight of whom had suprasellar extensions, were treated for three months with 20 mg of bromocriptine daily after a gradual increase to this dose. The group comprised eight women and four men, five with prolactin-secreting adenomas, four with acromegaly, two with functionless adenomas, and one with Nelson''s syndrome. All five patients with prolactin-secreting adenomas showed a reduction in pituitary tumour size as assessed by computerised tomography and metrizamide cisternography accompanied by a fall in prolactin concentrations and clinical and biochemical improvement in their hypopituitarism. One patient in this group had a visual-field defect before treatment, and this resolved. There was no radiological evidence of reduction in tumour size in the remaining seven patients, though this might refect the fairly short duration of treatment, particularly in view of the ancillary evidence of clinical, biochemical, and visual-field improvement in some of the patients. These results emphasise the potential value of bromocriptine in treating patients with large prolactinomas or recurrences of such tumours after previous chiasmal decompression and conventional external megavoltage irradiation on the pituitary.     

Mixed pituitary tumours--effects of bromocriptine treatment: Parlodel MR and Parlodel LAR.

Majority of pituitary tumours secrete one of the named hormones: PRL, GH, ACTH, proopiomelanocortine, alpha and beta subunit of TSH, LH, and FSH. Some of those tumours secrete two or more hormones. The aim of this study was to determine the effect of bromocriptine (Parlodel MR and LAR) upon secretion of hormones and tumour size in 10 patients with mixed pituitary tumours. In all patients pituitary and peripheral hormones, CT scan and visual fields were examined before and after treatment with bromocriptine: Parlodel MR and LAR. Bromocriptine treatment decreased PRL secretion in all 10 patients; GH--in all 6 in whom it was increased; TSH--in 2, FSH--in 2 and alpha-subunit in all 6 in whom they were increased. In 5 patients treatment resulted in shrinkage of the tumour mass by 20 to 35%. In all examined subjects clinical improvement was achieved. Our results demonstrate that bromocriptine (Parlodel MR and LAR) is very effective and well tolerated in the treatment of patients with mixed pituitary tumours particularly those with hyperprolactinemia.     

Substitution of inhaled beclomethasone dipropionate for ingested prednisone in steroid-dependent asthmatics

The effect of inhaled beclomethasone dipropionate (dose, 400 μg daily) was investigated in 31 prednisone-dependent asthmatics. In a double-blind noncrossover study of 25 patients dependent on a daily prednisone dose of 17.5 mg or less, the dose of ingested prednisone was significantly diminished through the use of beclomethasone as compared with placebo (P < 0.001). In a subsequent single-blind study of the 12 patients who had received placebo, a similar decrease in prednisone dose was possible when these patients received beclomethasone. In all 25 patients the effect of beclomethasone was maintained for 2 years; 9 came to require less beclomethasone and 1 required more. In an additional single-blind study of six patients with severe asthma, dependent on prednisone in a dose of 20 to 25 mg/d, the response to beclomethasone was more variable and less significant (P < 0.01). However, at 2 years there was no significant benefit (P > 0.05) and there were two treatment failures.In patients in whom reduction of dose or discontinuation of prednisone was possible plasma cortisol values before and after corticotropin administration increased significantly (P < 0.001). Prednisone reduction was associated with the appearance of mild musculoskeletal steroid-withdrawal symptoms of short duration in 15 patients, and recurrence of symptoms of rhinitis in 15 patients. Side effects of beclomethasone included episodes of hoarseness in 6 and easily treated oropharyngeal Candida albicans infection in 14.     

Treatment of Cushing's disease with low dose radiation therapy.

Nineteen patients with Cushing''s disease were treated with low dose external pituitary irradiation (20 Gy (2000 rad) in eight fractions over 10 days). While awaiting the effects of pituitary irradiation all patients were treated with metyrapone. Seven patients had a complete remission of their disease within six to 12 months of irradiation. They did not require any further treatment and were followed up for a mean of three and a half (range one to eight) years. Another patient had a complete remission after a second course of pituitary irradiation. A further two patients showed a significant biochemical improvement after irradiation, although they were not rendered eucorticoid. There were no complications after this dose of irradiation. These results compare favourably with those reported after pituitary irradiation at conventional doses (40-50 Gy (4000-5000 rad) over four or five weeks) but were not associated with any complications. It is therefore recommended that low dose external pituitary irradiation be used as definitive first line treatment for Cushing''s disease.