Karl-Erik Jakobsson

Tumour recurrence and enlargement in patients with craniopharyngioma with and without GH replacement therapy during more than 10 years of follow-up

OBJECTIVE Most patients who have been treated for craniopharyngioma (CP) are GH deficient (GHD). GH replacement therapy (GHRT) may stimulate tumour regrowth; and one of the concerns with long-term GHRT is the risk of tumour progression. Therefore, the objective was to study tumour progression in CP patients on long-term GHRT. DESIGN Case-control study. PATIENTS AND METHODS The criteria for inclusion of cases were: i) GHD caused by CP; ii) GHRT >3 years; and iii) regular imaging. This resulted in 56 patients (mean age at diagnosis 25±16 years) with a mean duration of GHRT of 13.6±5.0 years. As controls, 70 CP patients who had not received GHRT were sampled with regard to follow-up, gender, age at diagnosis and initial radiation therapy (RT). RESULTS The 10-year tumour progression-free survival rate (PFSR) for the entire population was 72%. There was an association (hazard ratio, P value) between PFSR and initial RT (0.13, 0.001) and residual tumour (3.2, 0.001). The 10-year PFSR was 88% for the GHRT group and 57% for the control group. Substitution with GHRT resulted in the following associations to PFSR: GHRT (0.57, 0.17), initial RT (0.16, <0.001), residual tumour (2.6, <0.01) and gender (0.57, 0.10). Adjusted for these factors, the 10-year PFSR was 85% for the GHRT group and 65% for the control group. CONCLUSIONS In patients with CP, the most important prognostic factors for the PFSR were initial RT and residual tumour after initial treatment. Long-term GHRT did not affect the PFSR in patients with CP.

Comparing progression of non-functioning pituitary adenomas in hypopituitarism patients with and without long-term GH replacement therapy

OBJECTIVE An important safety issue with GH replacement therapy (GHRT) in hypopituitary patients with a history of a pituitary adenoma is the risk for tumour recurrence or enlargement. Design Case-control study. SUBJECTS AND METHODS We studied tumour progression rate in 121 patients with hypopituitarism on the basis of non-functioning pituitary adenomas (NFPA) receiving long-term GHRT. A group of 114 NFPA patients not receiving GHRT who were matched in terms of duration of follow-up, gender, age, age at diagnosis and radiotherapy status were used as a control population. The average duration of GHRT was 10+/-4 years (range 2-17). RESULTS In patients with a known residual adenoma, 63% had no detectable enlargement of tumour during the study. In patients who had no visible residual tumour prior to GHRT, 90% did not suffer from recurrence. In total, the 10-year tumour progression-free survival rate in patients with NFPA receiving GHRT was 74%. In the control population not receiving GHRT, the 10-year progression-free survival rate was 70%. Radiotherapy as part of the initial tumour treatment reduced the rate of tumour progression in both GHRT and non-GHRT patients to a similar extent. CONCLUSIONS The rate of tumour progression was similar in this large group of GHRT patients and the control population not receiving GHRT. Our results provide further support that long-term use of GH replacement in hypopituitarism may be considered safe in patients with residual pituitary adenomas.

Transsphenoidal adenomectomy in cushing's disease via a lateral rhinotomy approach

BACKGROUND Cushings disease may be treated by surgical pituitary adenomectomy. We present a surgical approach to the pituitary gland that increases the possibilities of a selective adenomectomy, and compare our results with those of other studies. METHODS A retrospective study of patients with Cushings disease undergoing transsphenoidal selective adenomectomy via a lateral rhinotomy at Sahlgrenska University Hospital from 1984-93 is presented. Thirty-one patients (26 women, five men; mean age: 44 years, range: 13-75 years) with Cushings disease were followed for a median time of 4.5 years after operation (range: 1-10 years). Preoperative and postoperative urinary and serum cortisol, and circadian rhythm of serum cortisol were measured. We also measured serum TSH, T4, PRL, FSH, LH, and testosterone as well as urine and plasma osmolality. RESULTS Our remission rate was 77% and the recurrence rate 3%. Hormonal insufficiency was rare. Hypothyroidism and hypogonadism were present in 3% of the patients, and diabetes insipidus occurred in 6% of the patients. CONCLUSION Selective adenomectomy with its good opportunities for cure and improvement should be regarded as the treatment of choice for Cushings disease. Using the lateral rhinotomy approach to the sphenoidal cavity results in good accessibility to the sella turcica and its pituitary adenomas, a low frequency of postoperative pituitary insufficiency, and a high remission rate.

Ten-year mortality after severe traumatic brain injury in western Sweden: A case control study

Abstract Primary objective: Life expectancy may be substantially reduced for many years after severe traumatic brain injury (TBI). This study investigated the patterns of the short- and long-term all-cause mortality and the rates of primary causes of death in patients with severe TBI. Subjects: This study was of 166 consecutive patients (6–82 years) with severe TBI admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, from 1999–2002. The control group consisted of 809 subjects from the community, matched to the TBI cohort for age, gender and postcode area at the time of the injury. Methods: Survival outcome and cause of death were ascertained 10 years after the injury from the Swedish National Board of Health and Welfare register. The cumulative death rates and causes of death in cases and controls were compared. Results: The risk of death was increased for at least 10 years after severe TBI. The distribution of the causes of deaths differed between cases and controls in the first year of follow-up, but not between 1-year survivors and controls. Conclusion: Further research will be required to determine how to improve treatment so as to lower late mortality among survivors of severe TBI.

Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging

OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p < 0.05 and r = 0.48, p < 0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = -0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial diffusivity differed significantly between controls and patients with VFD, both before and after surgery (p < 0.05); however, no difference was found between patients with and without VFD. Based on the axial diffusivity and fractional anisotropy, a prediction model classified all patients with VFD correctly (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and 17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect pathology and degree of injury in the anterior visual pathways that were compressed by pituitary adenomas. The correlation between radial diffusivity and visual impairment may reflect a gradual demyelination in the visual pathways caused by an increased tumor effect. The low level of axial diffusivity found in the patient group may represent early atrophy in the visual pathways, detectable on DTI but not by conventional methods. DTI may provide objective data, detect early signs of injury, and be an additional diagnostic tool for determining indication for surgery in cases of pituitary adenomas.

OR3,13 Tumor recurrence and enlargement during more than 10 years growth hormone replacement therapy in patients with craniopharyngioma

The GH/IGF-I axis responds to muscular activity by increased hormonal secretion, and plays a role for both metabolic and structural adaptations to exercise. The regulation of GH release depends upon the central motor activity effort in the brain. The importance of GH/IGF-I for muscular growth has been mainly documented in relation to developing muscle, whereas in adult healthy humans muscle hypertrophy with training is not influenced by GH/IGF-I. In contrast, both in vitro and lately also in vivo data document the stimulating role GH/IGF-I has directly upon collagen synthesis in connective tissue of tendon andmuscle. Local IGF-I may be the responsible for the connective tissue protein synthesis. In females, estrogen exerts an inhibitory effect upon collagen synthesis in younger women, a phenomenon that is inversely related to levels of IGF-I. In conclusion, human connective tissue in tendon and skeletal muscle is with regards to collagen regulated largely by GH/IGF-I.