De-masking oxytocin-deficiency in craniopharyngioma and assessing its link with affective function.

Despite the high prevalence of panhypopituitarism and diabetes insipidus in patients with craniopharyngioma (CP), little is known about the functioning of the neuropeptide oxytocin in these patients. This is of special interest as tumor-associated lesions often impair sites critical for oxytocin production and release, and affective dysfunction in CP links with elsewhere reported prosocial, antidepressant and anxiolytic oxytocin effects. Using a prospective study-design, we tested whether oxytocin is reduced in CP-patients, and whether altered oxytocin levels account for affective and emotional dysfunction. 26 adult CP-patients and 26 healthy controls matched in sex and age underwent physical exercise, a stimulus previously shown to induce oxytocin release. Baseline and stimulated salivary oxytocin levels, as well as empathy, depression and anxiety scores were measured. Results showed that patients overall did not present with lower baseline oxytocin levels than controls (F[1,30]=0.21, p=0.649), but baseline oxytocin levels were indeed reduced in patients with hypothalamic damage, as assessed by MRI-based grading (F[2,9.79]=4.54, p=0.040). In response to exercise-induced stimulation, all CP-patients showed a blunted oxytocin-release compared to controls (F[1,30]=9.36, p=0.005). DI was not associated with oxytocin levels. Regarding affective function, unexpectedly, higher baseline oxytocin was related to higher trait anxiety (b=2.885, t(43)=2.421, p=0.020, CI[.478; 5.292]); the positive link with higher depression failed to reach statistical significance (b=1.928, t(43)=1.949, p=0.058, CI[-0.070; 3.927]). A blunted oxytocin-release was linked with higher state anxiety (b=-0.133, t(43)=-2.797, p=0.008, CI[-0.230; -0.037]). Empathy was not associated with oxytocin measures. In conclusion, we observed reduced baseline oxytocin levels only in CP-patients with hypothalamic damage. Exercise-induced stimulation de-masked an oxytocin-deficiency in all CP-patients. Baseline oxytocin levels and stimulated OT-responses might have different effects on affective function, which should be considered in future substitution paradigms.

Selenium substitution has no direct effect on thyroid hormone metabolism in critically ill patients.

BACKGROUND: In severe illness, plasma selenium levels are decreased; a decreased activity of the selenoenzyme 5'-deiodinase has been hypothesized to contribute to low tri-iodothyronine (T3) levels in non-thyroidal illness (NTI) syndrome in these patients. OBJECTIVE: To analyse the influence of selenium substitution on thyroid hormone metabolism in patients with severe sepsis. DESIGN: A prospective, randomized, controlled study at the medical internal intensive care unit of the University of Munich. Results are for 41 consecutive patients with severe sepsis with an APACHE II score >15. Patients received either sodium selenite (500 microg/day for the first 3 days, reducing to 250 and then 125 microg/day every 3 days) or a placebo. RESULTS: At study entry, APACHE II score and demographics were identical in both groups. The mean levels of TSH, free tri-iodithyronine and total T3, as well as plasma selenium and selenium-dependent peroxidase (GSH-Px) activity, were decreased. Plasma selenium and GSH-Px activity were normalized on days 3, 7 and 14 in patients receiving selenium (n=21), but remained below normal in the control patients. Patients receiving selenium had a better clinical outcome and thyroid hormone levels normalized earlier. Thyroid hormone levels increased in patients who showed clinical improvement, independent of selenium levels or selenium substitution. CONCLUSIONS: Selenium substitution in patients with NTI improves morbidity, but has no direct effect on the free and total thyroid hormones. In severely ill patients, decreased deiodinase activity due to low plasma selenium levels seems unlikely. After clinical revival, TSH and then the thyroidal hormones normalize independently of selenium substitution.