T. H. Schurmeyer

High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas

BACKGROUND Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. METHODS We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. RESULTS Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. CONCLUSION Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.

Effect of fenfluramine on episodic ACTH and cortisol secretion

OBJECTIVE The central serotoninergic system is known to modulate the activity of the hypothalamic‐pituitary‐adrenal axis, but the effect of fenfluramine, a serotonin reuptake inhibitor, on ACTH and cortisol secretion is not well understood. We have therefore evaluated its effects on the hypothalamic‐pituitary‐adrenal axis in healthy controls.

Effect of cyproheptadine on episodic ACTH and cortisol secretion.

To investigate the effect of cyproheptadine on ACTH and cortisol secretion, we obtained blood samples at 10‐min intervals for 24 h in six healthy volunteers under basal conditions and under treatment with 16 mg day−1cyproheptadine. Cyproheptadine caused significant decreases in mean plasma ACTH and cortisol levels in 30% and 19% of samples, respectively, mainly in the afternoon and evening. Analysis of episodic hormone secretion by three different methods demonstrated that the drug did not modulate the frequency but lowered the amplitudes of ACTH and cortisol secretory episodes. ACTH and cortisol responses following ovine CRH injection at 20.00 h were unchanged. We conclude that in the afternoon and evening central serotoninergic mechanisms influence the activity of the hypothalamic–pituitary–adrenal axis at the hypothalamic level by modulating the amplitude of the secretory hormonal bursts, but do not influence the increase in ACTH and cortisol secretion in the morning.

Efficacy and tolerability of a long-acting intramuscularly injectable depot preparation of bromocriptine: the results of a double blind study

The tolerability and efficacy of a long-acting im applicable form of bromocriptine (Parlodel LAR®) was tested in a double-blind approach in 20 patients with hyperprolactinemia or prolactinoma, 17 of them complaining of persistent side effects on oral treatment with dopamine agonists. The study-code revealed similar characteristics for age, sex, weight, clinical symptoms and previous therapy in both groups but prolactin serum levels were higher in the verum group even though the difference was not significant. In all 10 patients receiving Parlodel LAR® prolactin serum concentrations were significantly suppressed and tumor size was reduced in 5 of the 9 patients with visible tumors when controlled after 28 days. In contrast, no significant change in serum prolactin levels was observed in the placebo group and tumor size of all visible tumors was not altered. Side effects typically reported for dopamine agonists started 3 h after application in the verum group and were significantly different to the unspecific side effects reported in the placebo group during the first 72 h. Thereafter systemic tolerability was indistinguishable between both groups. The local tolerability at the injection site was excellent for both, Parlodel LAR® and placebo.

Therapie eines malignen sympathischen Paraganglioms des Zuckerkandl'schen Organs — ein Fallbericht

We present a case report on a 35-year-old patient in whom a malignant sympathetic paraganglioma of the organ of Zuckerkandl was the cause of severe hypertension with excessive perspiration at night. Since curative surgery was not possible medical treatment was initiated. Interferon alfa 2b (Intron A, Essex Pharma) and the somatostatin-analogue SMS 201-995 (Sandostatin, Sandoz) had no effect on catecholamine production and progression of the tumor. Treatment with alpha-methyl-para-tyrosin (MPT, [Metyrosin], Demser, MSD) turned out to be an effective and well tolerable therapy in this patient with peritoneal carcinosis. Clinical and hormonal progression of the paraganglioma resumed only after two years of therapy, which constitutes the longest documented period of time of successful MPT treatment. The superior efficacy of MPT in our patient should encourage postoperative medical treatment with MPT in malignant pheochromocytoma or malignant paraganglioma, particularly when the tumor turns out to be resistent to alpha blocking drugs.SummaryWe present a case report on a 35-year-old patient in whom a malignant sympathetic paraganglioma of the organ of Zuckerkandl was the cause of severe hypertension with excessive perspiration at night. Since curative surgery was not possible medical treatment was initiated. Interferon alfa 2b (Intron A, Essex Pharma) and the somatostatin-analogue SMS 201–995 (Sandostatin, Sandoz) had no effect on catecholamine production and progression of the tumor. Treatment with alpha-methyl-para-tyrosin (MPT, [Metyrosin], Demser, MSD) turned out to be an effective and well tolerable therapy in this patient with peritoneal carcinosis. Clinical and hormonal progression of the paraganglioma resumed only after two years of therapy, which constitutes the longest documented period of time of successful MPT treatment. The superior efficacy of MPT in our patient should encourage postoperative medical treatment with MPT in malignant pheochromocytoma or malignant paraganglioma, particularly when the tumor turns out to be resistent to alpha blocking drugs.