Louyse A. Lee

TRANSIENT HYPOGONADOTROPHIC HYPOGONADISM AFTER HEAD TRAUMA: EFFECTS ON STEROID PRECURSORS AND CORRELATION WITH SYMPATHETIC NERVOUS SYSTEM ACTIVITY

Transient hypogonadotrophic hypogonadism commonly occurs after major medical insults. Because data on testosterone precursors are sparse and because little is known about the aetiology of these changes, we studied the interactions of traumatic brain injury with gonadal steroidogenesis and with sympathetic nervous system activation. Patients were divided into two groups based upon the severity of neurological dysfunction using the Glasgow Coma Score (GCS); Group 1 > 8, Group 2 ≥ 8. Group 1 was further divided into those patients treated (Group 1b) and those not treated with dexamethasone (Group 1a). Plasma levels of testosterone, androstenedione, 17‐hydroxyprogesterone, DHEA sulphate, cortisol, LH, FSH, and the catecholamines noradrenaline (NE), adrenaline (EPI) and dopamine were measured in 31 acutely brain injured men, aged 18–95, shortly after their accident and 4 days later. In all patients, NE and EPI were elevated on admission (NE: 841 ± 105 (SEM) pg/ml; EPI: 191 ± 32 pg/ml and there were highly significant inverse correlations between admission NE (r=−0·52, P > 0·003) and EPI (r=0·44, P > 0·02) levels and day 4 testosterone concentrations. Testosterone fell 53% (P>0·001) in 13 Group la men, but only 25% (P=NS) in the less severely injured. Similar reductions occurred in cortisol and the steroid precursors. However, only testosterone, 17‐hydroxyprogesterone, and DHEA sulphate levels were significantly lower than normal on day 4. LH and FSH levels were also significantly reduced from elevated admission levels. In the eight men treated with dexamethasone (8–40 mg/ml) (Group 1b), the decrease in testosterone, LH and FSH concentrations were similar to those present in Group 1a. Thus, severe traumatic brain injury leads to hypogonadotrophic hypogonadism which affects testosterone and its precursors. The magnitude of the hormonal dysfunction is dependent upon the severity of the neurological insult. Finally, the decrease in testosterone is significantly correlated with admission catecholamine levels, which may suggest a role for the sympathetic nervous system (SNS) in mediating this response in men.

Hypoglycemia as a provocative test of prolactin release.

Insulin-induced hypoglycemia has been traditionally used to test growth hormone (GH) and cortisol reserve. In order to determine its usefulness as a provocative test for prolactin (PRL) release, 31 healthy men and women, 38 patients with definite pituitary abnormalities (pituitary tumors, 17; hypopituitarism [other causes]—complete, 4, or partial, 17), and 17 patients with suspected pituitary dysfunction (delayed puberty, 5; short stature, 4; secondary amenorrhea, 6; empty sella, 2, received regular i.v. insulin (0.05–0.15 U/kg), and the plasma was assayed serially for PRL, GH, cortisol, and glucose. In the 31 healthy subjects, PRL increased from 16.3 ± 1.8 ng/ml (mean ± SEM) to 45.5 ± 7.9 (p < 0.001) at 60 min and was still elevated at 120 min (25.8 ± 3.1 ng/ml). The maximal rise to 52.2 ± 8.0 ng/ml occurred between 40 and 90 min. There was no significant sex difference in the maximal PRL increase, maximal increment, or concentration at any time. In 21 of the 31 subjects, PRL increased at least 10 ng/ml with a doubling of baseline levels—criteria for a positive response. In addition, 12 of the healthy subjects received thyrotropin-releasing hormone (TRH) (500 μg i.v.) while 5 received chlorpromazine (50 mg i.m.). There was no significant difference among the maximal prolactin increments following insulin (36.7 ± 7.9 ng/ml), TRH (46.4 ± 6.3 ng/ml), or chlorpromazine (63.4 ± 21.9 ng/ml). In patients with definite pituitary abnormalities, 28 of 38 had diminished PRL release after insulin. Of these 28, 23 also had inadequate GH and 13 impaired cortisol release. In the 10 partially hypopituitary subjects with normal PRL responses, GH increased normally in 7 and cortisol in all. Thirteen of the 17 patients with suspected pituitary dysfunction had adequate PRL increases, while the GH and cortisol responses were intact in 16 and 17 subjects, respectively. Overall, the PRL response was concordant with changes in GH in 44 of 55 patients and in cortisol in 32 of 55 patients. It is concluded that insulin-induced hypoglycemia (1) releases PRL in most normal subjects and (2) is useful in determining the integrity of the hypothalamic pituitary axis for PRL release in patients with suspected abnormalities of pituitary function. Moreover, in combination with TRH, it may aid in localizing the site of abnormality in patients with these disorders.

Dopaminergic modulation of arginine mediated growth hormone and prolactin release in man

Abstract The mechanism of arginine (ARG) induced growth hormone (GH) and prolactin (PRL) release is poorly understood. Though dopamine (DA) is known to inhibit a number of GH and PRL secretagogues, it has been reported not to affect arginine mediated GH release. Our study was undertaken to study the interaction of DA and ARG further. Six healthy male volunteers received DA (4μg/kg/min) or saline from 0–240 min on two separate days. ARG (30 gms) was given 150–180 min on both days (Protocol I). In Protocol II 5 subjects received ARG on different days 30–60 min into a DA or saline infusion. On a third day only DA was given. Arginine alone was given in 2 separate infusions spaced 135 minutes apart to 5 volunteers (Protocol III). In Protocol I when ARG was given at 150 min, the maximal GH peak of 11.1 ± 1.3 ng/ml, which occurred 45 min later, was blunted by DA treatment (5.3 ± 1.1 ng/ml, p