Megavoltage pituitary irradiation in the management of prolactinomas: long-term follow-up

OBJECTIVE To determine the long-term effects of external beam megavoltage radiotherapy (RT: 4500 cGy via three portals at 180 cGy or less total daily dose) on endocrine function in prolactinomas. DESIGN Longitudinal study following radiotherapy with periodic re-assessment at regular intervals, at least 2 months off dopamine agonist therapy. PATIENTS Thirty-six female patients, age range 19-50 years, with either macroprolactinomas (12 patients) or microprolactinomas (24 patients), but without significant suprasellar extensions. MEASUREMENTS Clinical appraisal, and anterior and posterior pituitary assessment: basal levels at yearly intervals or less, with dynamic screening with TRH, LHRH and hypoglycaemic stimulation every 2-3 years. RESULTS Before RT, serum prolactin (PRL) levels ranged from 1150 to 34,000 mU/l; after RT (mean 8.5 years, range 3-14), serum PRL fell to normal (i.e. less than 360 mU/l) in 18 of the 36 patients (50%), and to just above the normal range (378-780 mU/l) in a further 10 (28%). Two patients had PRL levels at their last follow-up higher than those at presentation, with one patient showing evidence of tumour recurrence on CT scan. A total of eight of the 36 patients (23%) developed post-RT gonadal deficiency by the end of follow-up at 8 +/- 3.1 years (+/- SD, range 3-11), but six were aged over 40 years at that time. GH deficiency was frequent, occurring in 94% of patients, usually from 2 to 3 years post-RT, while TSH deficiency and reduced ACTH reserve was uncommon (each 14%), and occurred later. In the subgroup of 12 patients with macroprolactinomas, results were broadly comparable. CONCLUSIONS Megavoltage RT produces a progressive fall in serum prolactin in the great majority of patients with prolactinomas, with a relatively low incidence of TSH or ACTH deficiency. As it is now clear that dopamine agonist therapy alone provides sufficient management for microprolactinomas, RT may be used for the long-term control of macroprolactinomas, together with interim dopamine agonist therapy. It allows pregnancy to be safely undertaken but, in view of the delayed onset of gonadal deficiency, its administration should be timed with respect to the desired onset of conception in women.     

Isolated ACTH deficiency with absent response to corticotrophin-releasing factor--41. Evidence for a primary pituitary defect.

An 8-year-old girl presenting in hypoglycaemic coma was shown to have isolated deficiency of adrenocorticotrophic hormone (ACTH) secretion. Failure to secrete ACTH in response to intravenous administration of synthetic ovine corticotrophin-releasing factor (CRF-41) suggests that this disorder was due to a primary pituitary defect, rather than of hypothalamic origin.     

MR of sarcoidosis in the head and spine: spectrum of manifestations and radiographic response to steroid therapy.

PURPOSETo evaluate the role of MR in the diagnosis and treatment of patients with neurosarcoidosis.METHODSThe MR studies of 24 patients who satisfied stringent criteria for the diagnosis of sarcoid were retrospectively reviewed. All patients had signs and symptoms referable to the head and/or spine. The majority, 17 patients (71% of the total), were examined at least once with gadolinium enhancement. Fifteen of 24 patients (63%) underwent serial examinations during steroid therapy.RESULTSA wide spectrum of findings was noted: white matter and periventricular high signal intensity on long-repetition-time/long-echo-time sequences, mimicking multiple sclerosis (11 patients); leptomeningeal enhancement (11 patients); brain parenchymal mass (seven patients)--six demonstrated enhancement, one did not receive contrast; lacrimal gland mass (three patients); hydrocephalus (three patients); enlarged ventricles, apparently atrophic (one patient); periventricular enhancement (three patients); extraaxial mass, mimicking meningioma (two patients); chiasmal enhancement or swelling (one patient); enhancing nerve roots (two patients); enlarged pituitary stalk (two patients); pontine infarct (one patient); and enhancing parenchymal spinal cord mass (three patients). Partial or complete resolution of the radiographic abnormality occurred in 13 of 15 cases (87%), which paralleled clinical improvement. No response was detected in the remaining two. Abnormal enhancement was the finding that was most responsive to steroid therapy, with response seen in nine of 10 patients with leptomeningeal enhancement, in six of six patients with enhancing brain parenchymal masses, in three of three patients with enhancing cord masses, and in all three patients with periventricular enhancement.CONCLUSIONS1) MR shows a spectrum of protean central nervous system abnormalities associated with neurosarcoidosis. 2) This high sensitivity for associated abnormalities aids in differentiating central nervous system sarcoid from the many diseases that it can mimic. In particular, enhancement was a useful clue to the diagnosis in 15 of 17 cases in which it was used (88%). 3) MR demonstrates regression of central nervous system abnormalities during steroid therapy, in particular abnormal meningeal, periventricular, and parenchymal enhancement.     

Dapsone-induced hemolytic anemia: effect of N-hydroxy dapsone on the sulfhydryl status and membrane proteins of rat erythrocytes.

Dapsone hydroxylamine (DDS-NOH), a known metabolite of dapsone, has recently been shown to be a direct-acting hemotoxin responsible in part for dapsone-induced hemolytic anemia in the rat. The effect of DDS-NOH on the morphology, sulfhydryl status, and membrane skeletal proteins of the rat red cell has been investigated. Exposure of rat red cells to a TC50 of DDS-NOH induced transformation of about 50% of the cells to an extreme echinocyte morphology. Reduced glutathione content of the cells was rapidly lost with concomitant increase in the formation of mixed disulfide between glutathione and the soluble protein of the cell. Oxidized glutathione content of the cells did not increase at any time during exposure to DDS-NOH. Examination of the skeletal membrane proteins by SDS-PAGE indicated that DDS-NOH caused the apparent loss of band 4.2, decrease in peaks 1, 2.1, and 3, and the appearance of new bands at about 16, 27, 40, and 54 kDa. Bands 4.1 and 7 appeared unchanged. Treatment of DDS-NOH altered proteins with dithiothreitol, reversed the protein changes, and indicated that the observed alterations were due to the formation of disulfide-linked adducts between hemoglobin and the various skeletal proteins as well as between hemoglobin monomers. The possible significance of the parallel changes in cell morphology and in membrane skeletal proteins for the premature splenic sequestration of the injured rat red cells is discussed.