Tiit Rähn

Adrenocorticotropic hormone-producing pituitary tumors: 12- to 22-year follow-up after treatment with stereotactic radiosurgery.

OBJECTIVETo study retrospectively long-term outcomes of patients with adrenocorticotropic hormone-producing pituitary tumors that were treated with stereotactic Leksell gamma knife unit radiosurgery. METHODSEighty-nine patients aged 5 to 67 years were treated between 1976 and 1985. Eighteen patients aged 18 to 68 years (mean age, 41 yr) were followed in detail. Fifteen patients were women. None had previously received conventional radiotherapy, but pituitary microsurgery had been performed in two patients, and one patient had had an adrenalectomy. In the remaining 15 patients, radiosurgery was the primary therapy. RESULTSSixty-four patients had one stereotactic treatment, and 25 patients had two or more treatments. No complications were observed during treatment and the immediate follow-up period. At follow-up, 17 patients had died 1 to 20 years after the first treatment. No deaths were related to the treatment. In our 18 patients, the follow-up time after the first radiosurgical treatment was 12 to 22 years (mean follow-up period, 17 yr). Urinary cortisol levels gradually normalized in 83% of the patients. No recurrences were observed. Pituitary hormone insufficiencies developed in about two of every three patients and occurred even more than 10 years after treatment. Eight patients had transient hyperprolactinemia. The patients’ vision and visual fields were unaffected, and none of them had signs of radiation-induced side effects such as brain tumors or brain necrosis. CONCLUSIONStereotactic radiosurgery is a safe and effective method in the treatment of patients with adrenocorticotropic hormone-producing pituitary tumors, and the effect of treatment is long-lasting. Stereotactic radiosurgery is mainly a complement to microsurgery because of its gradually appearing effect and the occurrence of pituitary insufficiency. New pituitary deficiencies may be found more than 10 years after treatment.

Stereotactic Radiosurgery with the cobalt-60 Gamma Unit in the treatment of growth hormone producing pituitary tumors.

Stereotactic radiosurgery on the pituitary given with the cobalt-60 gamma unit was used in the treatment of 21 patients with growth hormone (GH)-producing pituitary adenomas and acromegaly. All but one patient had locally invasive macroadenomas, and in the majority of cases, there was parasellar growth. Radiosurgery was the initial treatment for seven patients. Fourteen patients were previously treated by pituitary surgery, eight of whom had undergone conventional external pituitary irradiation as well. All patients had clinical signs of active acromegaly before radiosurgery. The radiation doses given to the previously untreated patients or those who only underwent surgery were 40 to 70 Gy in each of one to three irradiations. The patients with previous external irradiation received a lower dose of 30 to 50 Gy in each of one or two irradiations. The patients were observed during a period of 1 to 21 years from the first radiosurgical session. Two young patients had a clinical remission with a substantial decline of GH levels to near normal serum profiles. Another eight patients obtained reduction of GH levels and clinical activity. More than half of the patients (11 of 21) had minor or no effects from the treatment. There were no complications from the radiosurgery except the development of pituitary insufficiency in 2 of 13 patients who did not undergo previous conventional external irradiation. The remission rates were lower than the results previously reported by us for radiosurgery for Cushings disease. This may be a result of the predominance in the present study of invasive macroadenomas and single treatments and to the lower radiation doses used in the patients who underwent conventional irradiation previously.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of gamma knife radiosurgery in the management of pituitary adenomas

No treatment modality has been entirely successful in the management of pituitary adenomas. Although most patients with pituitary microadenomas can be cured by transsphenoidal surgery, the results are less satisfactory in macroadenomas in particular with suprasellar and/or parasellar extension. Additional treatment is then called for. Conventional fractional radiotherapy can often control tumour growth but is limited to 45–50 Gy with a very slow reduction in elevated pituitary hormones and a high incidence of pituitary insufficiency. Stereotactic radiosurgery allows the delivery of radiation with high precision to the target with low doses to the surrounding tissues permitting higher radiation doses. Gamma knife radiosurgery using photon energy with gamma beams from multiple cobalt 60 radiation sources is now used in many centers. It can be carried out in an outpatient setting with one single treatment. A more rapid normalization of pituitary hormone hypersecretion than with conventional radiation can be achieved as well as arrest of tumour growth and reduction of tumour mass. We therefore consider gamma knife radiosurgery as a valuable compliment to pituitary surgery. Long-term prospective studies are needed to evaluate the frequency of pituitary insufficiency in patients where the target area is determined with stereotactic magnetic resonance imaging (MRI).

Demonstration of Insulin-Like Growth Factors I, II and Heterogeneous Insulin-Like Growth Factor Binding Proteins in the Cyst Fluid of Patients with Craniopharyngioma

Insulin-like growth factor (IGF)-II and its binding proteins were demonstrated to be present in human craniopharyngioma cyst fluid using gel filtration and ligand blot analyses. Immunoreactive IGF-II in 3 patients was found to be 274, 232 and 310 ng/ml after gel chromatography whereas IGF-I concentrations were 13, 8 and 15 ng/ml. The IGF-II levels were severalfold higher in cyst fluid than in spinal fluid while the IGF-I levels in both fluids did not differ significantly. The binding proteins showed high affinities for [125I]IGF-II which could be displaced by unlabelled IGF-II. With the ligand blot analysis, [125I]IGF-II shows bands at 300, 175 and 46/43 kilodaltons probably representing IGF-II receptor and IGFBP-3. IGFBP-1 levels 17, 22 and 45 ng/ml, respectively, were undetectable by ligand blot.

Insulin-like growth factor (IGF)-I, -II and IGF-binding proteins in the cyst fluid of a patient with astrocytoma

Insulin-like growth factor (IGF)-I,-II and IGF-binding proteins (IGFBPs) were demonstrated in the cyst fluid of a patient with a hypothalamic astrocytoma. The astrocytoma cyst fluid was subjected to gel chromatography at low pH and the IGF-I and IGF-II levels were measured by specific radioimmunoassays. Immunoreactive IGF-I and IGF-II levels were 19 ng/ml and 78 ng/ml respectively. Several-fold higher IGF-II values were obtained when cyst fluid was not extracted or was extracted with acid ethanol before radioimmunoassay analysis. The immunoreactive IGFBP-1 concentration was 26 ng/ml. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and subsequent Western ligand blotting with [125I]IGF-II revealed bands at ≈200, 34.5, 29.5, 24 and 21 kD as visualized by autoradiography. Binding studies demonstrated that these binding proteins bind specifically [125I]IGF-I and [125I]IGF-II. These observations suggest that IGFs as well as IGF-binding proteins are produced by astrocytoma cells and may act in a paracrine or autocrine fashion capable of modulating the growth of astrocytoma tumours.

Gamma Irradiation Effects on Human ACTH-producing Pituitary Tumors in Organ Culture*

SummaryMorphology (studied by light and electron microscopy) and hormone secretion were followed in organ cultures of adrenocorticotropic hormone (ACTH)-secreting hormones after in vitro irradiation with a single dose of 70 Gy. The increase is ACTH secretion immediately after exposure was interpreted as an irradiation-induced direct effect on cell membrane permeability. The low secretional capacity for 120 h after irradiation is probably caused by an impairment of cell metabolism. Cell morphology slightly deteriorated 24–48 h after exposure. Later, cell morphology was restored and specimens investigated 5 days after irradiation showed normal morphology.It is concluded, that the fluctuations in serum ACTH in patients with Cushings disease treated by stereotactic radiosurgery are caused by changes in the tumor cells proper rather than being due to hypothalamic influence.