Withdrawal of bromocriptine after long-term therapy for macroprolactinomas; effect on plasma prolactin and tumour size

The present study describes the effect on plasma prolactin values and tumour size of bromocriptine withdrawal in 12 patients who had been treated for macroprolactinomas for a period of 3.5-7 (mean 4.9) years. Pretreatment plasma prolactin values ranged from 12,000 to 210,000 (mean: 66,000) mU/l. Immediately before bromocriptine withdrawal plasma prolactin values were in the normal range (less than 350 mU/l for men; less than 450 mU/l for women). Bromocriptine treatment was associated with tumour reduction in all cases. The following observations were made upon withdrawal of bromocriptine: (1) In 11 patients hyperprolactinaemia redeveloped although plasma prolactin levels remained below 600 mU/l in two of these patients during a follow-up period of 1 year. In the other nine patients bromocriptine treatment was reinstituted after 4-12 weeks. (2) Hyperprolactinaemia was associated with tumour reexpansion in one case and increased density of the tumour in two cases. (3) In one patient plasma prolactin remained undetectable during a follow-up period of 1 year and no tumour re-expansion was found. It is concluded that tumour regrowth is uncommon and of small extent after cessation of long-term bromocriptine treatment for macroprolactinomas.     

Sellar granulomatous mass in a pregnant woman with active Crohn's disease.

At the end of her third pregnancy, a woman with a history of chronic active proctocolitis which had been diagnosed as Crohn's disease complained of deterioration of visual acuity. The patient was found to have hypopituitarism and progressive bitemporal hemianopia caused by an intrasellar mass with suprasellar extension. At transsphenoidal surgery an intrasellar granuloma was found without remnants of pituitary tissue. This sellar granuloma could have been an extra-intestinal granuloma of Crohn's disease. However, the possibility that giant cell granulomatous hypophysitis had been present was considered more likely. The occurrence of this disorder in the postpartum period has not been reported before.     

Prolactinoma and body weight: a retrospective study

Body weight and weight history in association with hormone levels were studied retrospectively in 47 patients with prolactinoma; macroprolactinoma was diagnosed in 36, microprolactinoma in 11 patients. At the time of diagnosis a weight history could be traced in 14 patients, 9 patients having gained weight (11.8 +/- 2 kg), 1 with a weight loss of 5 kg, and 4 reporting unaltered body weight. Body weight and Body Mass Index before treatment were 83 +/- 2.4 kg and 27.3 +/- 0.6 kg/m2, respectively. In the male patients the prevalence of BMI greater than or equal to 25 was greater than in the average Dutch male population (p less than 0.001). After 6 months of treatment, mainly with bromocriptine, patients with macroprolactinoma had lost 5.5 +/- 1.6% (p less than 0.002) of initial body weight. No significant weight change occurred in patients with microprolactinoma. Weight loss did not correlate with degree of hyperprolactinemia, nor with decrease of prolactin levels during treatment, in either group of patients. Thyroid or gonadal function were not associated with weight loss either. It appears that prolactinoma is associated with a higher frequency of overweight, as far as patients with macroprolactinoma are concerned.     

Successful treatment with sodium valproate of a patient with Cushing's disease and gross enlargement of the pituitary

Transfrontal hypophysectomy was performed in a patient with Cushing's disease and gross enlargement of the pituitary. Despite some reduction of cortisol production active Cushing's syndrome remained due to the presence of a tumour remnant. Medical treatment with the GABA-transaminase inhibitor sodium valproate induced hypocorticism necessitating corticosteroid substitution therapy. Nine months after sodium valproate withdrawal hypercorticism was documented. Re-institution of sodium valproate treatment induced hypocorticism again. As sodium valproate is known to induce a decrease of plasma ACTH in Nelson's syndrome, it is proposed that large tumours present at the time of diagnosis and those appearing after adrenalectomy may represent the spectrum of a single disorder. A prospective trial to study the effects of sodium valproate and other neurotransmitter modulating agents on the size and endocrine function of ACTH secreting macroadenomas is urgently needed.     

Response of luteinizing hormone secreting pituitary adenoma to a long-acting somatostatin analogue

A large pituitary tumour was discovered in a 20 year old man who came to medical attention because of grand-mal seizures. The tumour produced biologically active LH as demonstrated by supranormal plasma LH and plasma testosterone values. Free alpha-subunit values were also elevated. In contrast, plasma FSH was in the lower normal range. Transsphenoidal operation failed to remove all tumour tissue. Detailed studies were carried out in the postoperative period. TRH and GnRH administration were associated with a rise of plasma LH and alpha-subunit, whereas plasma FSH was low and unresponsive. Bromocriptine treatment was ineffective. In contrast, both during and after treatment with SMS 201-995 for 6 weeks, a decrease of basal plasma LH values was observed. Furthermore, the administration of a single dose of SMS 201-995 reproducibly induced a decrease of plasma LH lasting for a period of about 6 h. The study suggests that SMS 201-995 may be useful in the treatment of patients with gonadotrope cell adenomas.     

Results of primary treatment with bromocriptine of prolactinomas with extrasellar extension

Nineteen patients, seven women and twelve men, with macroprolactinomas characterized by extrasellar extension and basal prolactin levels above 6 U/l were treated with 10-20 mg bromocriptine daily in four divided doses for a mean period of 3.4 years (range 1.5-5.5 years). Plasma prolactin levels fell dramatically in all patients and values in the low normal range were obtained in sixteen patients. Tumor size was reduced by more than 75% in seventeen patients and by 50-75% in two patients. Tumor reduction was associated with the development of a partial empty sella in fourteen cases. In seventeen cases the pituitary became visible. Diminished visual acuity (six patients), bitemporal hemianopia (nine patients), unilateral and bilateral central scotomas (three patients) and oculomotor palsy (two patients) improved or normalized in all cases. Hypogonadism (all patients), hypothyroidism (nine patients) and hypocorticism (four patients) improved or normalized in most cases. It is concluded that in the medical treatment of macroprolactinomas 10-20 mg bromocriptine in four divided doses effectively reduces both plasma prolactin level and tumor size. The good results in this study may be related to the continued use of a fixed dose regimen of bromocriptine regardless of the plasma prolactin lowering effect.     

Work-related critical incidents in hospital-based health care providers and the risk of post-traumatic stress symptoms, anxiety, and depression: a meta-analysis

This meta-analysis reviewed existing data on the impact of work-related critical incidents in hospital-based health care professionals. Work-related critical incidents may induce post-traumatic stress symptoms or even post-traumatic stress disorder (PTSD), anxiety, and depression and may negatively affect health care practitioners' behaviors toward patients. Nurses and doctors often cope by working part time or switching jobs. Hospital administrators and health care practitioners themselves may underestimate the effects of work-related critical incidents. Relevant online databases were searched for original research published from inception to 2009 and manual searches of the Journal of Traumatic Stress, reference lists, and the European Traumatic Stress Research Database were conducted. Two researchers independently decided on inclusion and study quality. Effect sizes were estimated using standardized mean differences with 95% confidence intervals. Consistency was evaluated, using the I(2)-statistic. Meta-analysis was performed using the random effects model. Eleven studies, which included 3866 participants, evaluated the relationship between work-related critical incidents and post-traumatic stress symptoms. Six of these studies, which included 1695 participants, also reported on the relationship between work-related critical incidents and symptoms of anxiety and depression. Heterogeneity among studies was high and could not be accounted for by study quality, character of the incident, or timing of data collection. Pooled effect sizes for the impact of work-related critical incidents on post-traumatic stress symptoms, anxiety, and depression were small to medium. Remarkably, the effect was more pronounced in the longer than in the shorter term. In conclusion, this meta-analysis supports the hypothesis that work-related critical incidents are positively related to post-traumatic stress symptoms, anxiety, and depression in hospital-based health care professionals. Health care workers and their supervisors should be aware of the harmful effects of critical incidents and take preventive measures.