Balbino Barceló

The Long-Term Outcome of Pituitary Irradiation after Unsuccessful Transsphenoidal Surgery in Cushing's Disease

BACKGROUND Irradiation of the pituitary is widely considered the most appropriate treatment for patients with Cushings disease in whom transsphenoidal microsurgery has been unsuccessful. However, there is little information about the long-term efficacy of this treatment. METHODS We used external pituitary radiation to treat 30 adult patients with persistent or recurrent Cushings disease after unsuccessful transsphenoidal surgery. The mean (+/-SD) dose of radiation was 50+/-1 Gy. Pituitary and adrenal function was assessed every six months after radiation therapy. Remission was defined as the regression of symptoms and signs of Cushings syndrome, normal urinary cortisol excretion, and a low plasma cortisol concentration in the morning after the administration of 1 mg of dexamethasone at midnight. RESULTS Twenty-five patients (83 percent) had remissions during a median follow-up of 42 months (range, 18 to 114). The remissions began 6 to 60 months after radiation therapy, but in most cases (22 patients) remission occurred during the first 2 years. None of the 25 patients had a relapse of Cushings disease after remission was achieved. There was no relation between the response to radiotherapy and sex, age, urinary cortisol excretion before radiotherapy, the interval between surgery and radiotherapy, whether a pituitary adenoma was found by pathological examination, or tumor size. Seventeen patients had a deficiency of growth hormone after radiation therapy, 10 had a deficiency of gonadotropins, 4 had a deficiency of thyrotropin, and 1 had a deficiency of corticotropin. CONCLUSIONS Pituitary irradiation is an effective and well-tolerated treatment for patients with Cushings disease in whom transsphenoidal surgery is unsuccessful.

PETROSAL SINUS SAMPLING FOR DIAGNOSIS OF CUSHING'S DISEASE: EVIDENCE OF FALSE NEGATIVE RESULTS

OBJECTIVE While inferior petrosal sinus (IPS) sampling correctly diagnoses pituitary‐dependent Cushings syndrome if a significant ratio of plasma ACTH between the IPS and the peripheral blood is demonstrated, little has been said about the significance of a negative ratio in Cushings disease (e.g. a false‐negative result). This study evaluates the results of IPS sampling in patients with Cushings disease, and compares them with both imaging findings and transsphenoidal examination.

Experience in management of 51 non-functioning pituitary adenomas: Indications for post-operative radiotherapy

Object: The indications for additional radiotherapy (RT) after surgery for non-functioning pituitary adenoma are controversial. The goal of this retrospective study was to evaluate the outcome of surgically treated patients, with or without post-operative irradiation. Methods: Review of cases treated for non-functioning pituitary adenoma. Fifty-one patients were identified, with a mean post-operative follow-up of 6.4±3.5 yr. Twenty-nine patients showed residual tumor after surgery and 22 did not. Serial endocrine, visual and radiological evaluations were made after treatment to assess the efficacy and toxicity of surgery and RT. Twenty-seven patients with residual tumor after surgery received RT (22 of them during the post-operative period and 5 after an interval of several yr: 3 because of increased tumor size and 2 with stable residual lesion); tumors in 14 of these patients decreased in size, 11 appeared to be stable on imaging and one patient showed some increase in tumor size (one patient was not followed-up). The residual tumors of the 2 non-irradiated patients remained stable after 5 and 7 yr, respectively. Twenty-two patients without residual disease after surgery (11 with post-operative irradiation, 1 with RT 5 yr after transsphenoidal surgery because of tumor recurrence, and 10 without RT) have shown no evidence of tumor regrowth on serial images. Conclusions: Radiotherapy can be avoided in patients with complete macroscopic resection and absence of residual tumor in post-operative images; they must be carefully followed using imaging techniques and, in the case of recurrence, they should be re-operated and/or irradiated.

Apparent cure of Graves-Basedow disease after sibling allogeneic bone marrow transplantation.

Evidence that allogeneic bone marrow transplantation (BMT) can cure or alter the course of intractable autoimmune diseases comes from both extensive experimental work in animal models and anecdotal case reports in humans.

Cushing's syndrome due to autonomous macronodular adrenal hyperplasia: long-term follow-up after unilateral adrenalectomy

This report describes a case of Cushings syndrome due to autonomous macronodular adrenocortical hyperplasia in which unilateral resection of the right adrenal resolved the Cushings syndrome.

LEYDIG CELL TUMOUR OF THE TESTIS WITH GYNAECOMASTIA AND ELEVATED OESTROGEN, PROGESTERONE AND PROLACTIN LEVELS: CASE REPORT

The successful surgical removal of a feminizing interstitial cell tumour of the testis is described. The high oestradiol, progesterone and prolactin levels fell after surgery and the suppressed testosterone, FSH and LH recovered. Oestrogen secretion by the tumour could explain most of the observed hormonal changes.

Serum growth hormone-binding protein is decreased in prepubertal children with idiopathic short stature.

The causes for growth failure in children with idiopathic short stature (ISS) are not definitely established. Peripheral GH resistance due to changes at the level of the GH receptor has been suggested as one of the most probable explanation. In this study, we have selected a group of prepubertal children with ISS to evaluate the GHBP/receptor status by measuring the GH binding protein (GHBP) activity in plasma. Thirty prepubertal children with ISS (18 boys and 12 girls; age range: 4.79 to 11.33 yr) and twenty age-matched children with normal growth (11 boys and 9 girls) were studied. The ISS group presented growth retardation of −2.3±0.43 SD score (mean±SD) and normal GH secretion. Plasma IGF-I levels were below or in the low normal range (mean±SD: 136.3±62.3 μg/l, a concentration that was significantly different from IGF-I levels in the normal group (mean±SD: 187±57.5 μg/l p<0.005). Plasma GHBP activity using a GH-binding/gel chromatography assay showed significantly lower values in ISS group (mean±SD: 7.17±1.5%) as compared with those of the control group (mean±SD: 12.02±2.04%; p<0.001). There were no significant age-or sex-related differences in GHBP values in either group. The decreased GHBP levels observed in this group of children with ISS suggest that they may present a certain degree of GH insensitivity, probably due to a defect at the GH-receptor level.

Usefulness of thyrotropin-releasing hormone test, SMS 201–995, and bromocriptine in the diagnosis and treatment of gonadotropin-secreting pituitary adenomas

Five patients with gonadotropin-secreting pituitary adenomas were studied. The utility of gonadotropin response to TRH stimulation in the diagnosis and follow-up of these tumors was evaluated, as well as the effects of somatostatin analogue SMS 201–995 and bromocriptine on gonadotropin release. Three patients had FSH and LH secreting adenomas while the other two tumors secreted FSH and a-subunit. Transsphenoidal resection of the pituitary adenomas were performed in all patients. Following preoperative TRH administration (400 μg iv), marked increases were observed in FSH levels in two cases, in LH levels in three and in α-subunit in one. The FSH and LH responses to this stimulus persisted in the same patients after surgery. Following acute bromocriptine administration (5 mg orally), FSH was reduced in all cases by 19% to 46%; LH in three cases by 50–67% and α-subunit in one by 33%. In patient no. 5, with persistent high FSH levels in the immedi.ate postoperative period, long-term bromocriptine treatment was administered (15 mg/d orally), resulting in normalization of FSH levels 6 months later, although the size of the tumor was not reduced. After acute SMS 201–995 administration (100 μg sc) FSH decreased in two cases by 38% and 76%, LH in three by 30–56% and a-subunit in one by 20%. We conclude that gonadotropin response to TRH stimulation is useful in the diagnosis and follow-up of patients with gonadotroph adenoma. Bromocriptine and SMS 201–995 may be effective as coadjuvant treatment following surgery and radiotherapy in these patients, although long-term studies will be necessary to confirm these proposals.