Hypopituitarism following severe traumatic brain injury.

Although hypopituitarism is a known complication of traumatic head injury, it may be under-recognized due to its subtle clinical manifestations. To address this issue, we determine the prevalence of neuroendocrine abnormalities in patients rehabilitating from severe traumatic brain injury (Glasgow Coma Scale < or = 8). 76 patients (mean age 39 +/- 14 yr; range 18-65; 53 males and 23 females; BMI 25.8 +/- 4.2 kg/m2; mean +/- SD) with a severe traumatic brain injury, an average of 22 +/- 10 months before this study (median, 20 months), underwent a series of standard endocrine tests, including TSH, free T4, T4, T3, prolactin, testosterone (males), estradiol (females), cortisol, ACTH, GH, and IGF-I. All subjects also underwent GH response to GHRH + arginine. Growth hormone deficiency (GHD) was defined as a GH response < 9 microg/L to GHRH + arginine and was confirmed by ITT (< 3 microg/L). Pituitary deficiency was shown in 24% of the patients (18/76). 8% (n = 6) had GHD (GH-peak range [GHRH + arginine]: 2.8-6.3 microg/L; GH-peak range [ITT]: 1.5-2.2 microg/L; IGF-I range: 62-174 microg/L). 17% (n = 13) had hypogonadism (total testosterone < 9.5 nmol/L and low gonadotropins in 12 males; low estradiol, and low gonadotropins in 1 female). Total testosterone levels did not correlate with BMI or age. 2 males with hypogonadism also showed a mild hyperprolactinemia (33 and 41 ng/ml). 3% (n = 2) patients had partial ACTH-deficiency (cortisol-peak [ITT] 392 and 417 nmol/L) and 3% (n = 2) had TSH-deficiency. In summary, we have found hypopituitarism in one-fourth of patients with predominantly secondary hypogonadism and GHD. These findings strongly suggest that patients who suffer head trauma must routinely include neuroendocrine evaluations.

Effects of octreotide on sleep apnoea and tongue volume (magnetic resonance imaging) in patients with acromegaly.

OBJECTIVES: Sleep apnoea has been consistently reported to occur in acromegaly. Both obstructive apnoeas, in which apnoeas are due to intermittent obstruction of the upper airways, as well as central apnoeas are known to occur. Because the relationship between disease activity and severity of sleep apnoea is currently unclear, we have performed a prospective study to address this issue. DESIGN AND METHODS: In 14 newly diagnosed patients with active acromegaly (eight females and six males; mean age 57+/-4 years; IGF-I 583+/-48 microg/l; GH 13.5+/-7.0 microg/l (means+/-s.e.m.)), tongue volume and signal intensity of the tongue were examined by magnetic resonance imaging and sleep apnoea was characterised by polysomnography before and after 6 months of treatment with octreotide acetate (Sandostatin LAR 10-30 mg every 4 weeks i.m.). RESULTS: The initial tongue volume was significantly higher in patients with acromegaly (151+/-9 ml; females 133+/-10 ml; males 172+/-10 ml) in comparison with the body mass index (BMI)- and age-matched healthy control group (97+/-5 ml, P<0.001; females 75+/-1 ml, P<0.001; males 120+/-3 ml, P<0.003). After treatment with octreotide, IGF-I was normalised within the age-adjusted normal range in 50% of the patients. In these patients, tongue volume significantly decreased (120+/-14 ml, P<0.05) in comparison with the persistent uncontrolled group of acromegalics (137+/-10 ml, P=not significant). Overall, tongue volume (128+/-8 ml, P<0.05) and the signal intensity ratio of the tongue decreased significantly after treatment with octreotide acetate (120+/-3 vs 105+/-3, P=0.003). The BMI-adjusted tongue volume correlated with IGF-I levels (r=0.60, P<0.002) and the disease duration (r=0.71, P=0.006). At baseline, 50% had obstructive sleep apnoea with a mean respiratory disturbance index (RDI) of >20/h (range 5.1-91.5) and no patient had central sleep apnoea. After 6 months of octreotide treatment, there was a 28+/-10% decrease in RDI. However, RDI did not correlate with IGF-I or GH levels, but correlated positively with BMI (r=0.58, P=0.001) and age (r=0.46, P=0.02). CONCLUSIONS: Obstructive sleep apnoea but not central sleep apnoea frequently occurs in patients with active acromegaly. Successful treatment with octreotide can decrease tongue volume, which may have benefits for coexisting sleep-disordered breathing.