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Prolactin secretion in normal adults is characterized by periods of episodic secretion which increase in magnitude during sleep. In this study, we report the 24-h mean prolactin concentrations, prolactin secretory patterns, and associated pituitary hormone function in nine patients (seven women and two men) with hyperprolactinemia of diverse etiologies. Four of the women and one of the men had clinically demonstrable pituitary tumors, one boy had a hypothalamic tumor, and the three other women had “functional” hyperprolactinemia. The 24-h mean prolactin concentrations derived from averaging the 20-min interval samples for 24 h ranged from 28.6 to 1,220 ng/ml. The plasma prolactin patterns in these patients showed persistence of episodic secretion in all and loss of the normal sleep-wake difference in plasma prolactin in seven of nine. Three of the patients with galactorrhea and comparable 24-h mean prolactin concentrations (58.3, 59.7, and 64.3 ng/ml) showed similar prolactin secretory patterns despite different etiologic mechanisms. Evaluation of the secretory patterns of luteinizing hormone (LH) in these patients showed loss of normal pulsatile LH release and a low 24-h mean LH concentration in the patient with the pituitary tumor, while the two patients without clinically demonstrable pituitary tumors (“post-pill” galactorrhea and “idiopathic” galactorrhea) showed normal LH secretory patterns and 24-h mean LH concentrations. The 24-h mean cortisol concentrations and secretory patterns were normal in five of the seven patients who had these parameters measured. The patient with the hypothalamic tumor had a low 24-h mean cortisol concentration and production rate and absent response to metyrapone. The patient with “idiopathic” galactorrhea had an elevated 24-h mean cortisol concentration but normal cortisol production rate and urinary 17-hydroxycorticoid excretion. Growth hormone secretion was abnormal in four of the patients (one with the hypothalamic tumor and three with pituitary tumors). Thyrotropin-releasing hormone (TRH) administration in four patients resulted in normal TSH release in two patients (one of whom developed galactorrhea after the test), an absent response in the patient with the hypothalamic tumor, and a blunted response in one of the women with a pituitary tumor. The two men had low 24-h mean plasma testosterone concentrations (69 and 30 ng/100 ml) and symptoms of impotence and loss of libido. Five of the women (four with pituitary tumors and one with Chiari-Frommel syndrome) had either low 24-h mean LH concentrations, abnormal LH secretory patterns, or both. These data indicate that patients with hyperprolactinemia encompassing a varied etiological range frequently show loss of the normal sleep-associated increase in prolactin secretion as well as abnormalities in the regulation of the other hypothalamic pituitary-regulated hormones. The finding that the abnormalities in LH, growth hormone, thyrotropin, and cortisol (adrenocorticotrophic) secretion were almost uniformly confined to the patients with the clinically demonstrable hypothalamic or pituitary tumors suggests that the size of the lesion is the critical factor.

Equimolar doses ofD-amphetamine and L-amphetamine, and a water placebo were injected intravenously on different days into rhesus monkeys, and their plasma cortisol and GH responses were determined over a 3-hour period. D- and L-amphetaniine (but not the placebo) equally suppressedplasma cortisol concentration and equally increased plasma GH concentration. Pretreatment of the monkeys with large doses of pimozide, a specific dopa- mine receptor blocker, did not appear to block the hormonal responses to either isomer of amphetamine. The results suggest that the hormonal responses to both D- and L-amphetamine were mediated by noradrenergic neurones stimulatory to GH and inhibitory to ACTH, and that D- and L-amphetamine exert equipotent noradrenergic effects in the neuroendocrine system.(Endocrinology 99: 459,1976)

The temporal pattern of growth hormone release at sleep onset was studied in six adult human subjects by frequent blood sampling combined with polygraphic sleep recording. HGH release was associated with sleep onset but not with the transition from waking to sleep. Delta activity consistently preceded the first elevation of plasma HGH.

A prospective study of growth was undertaken in two groups of hyperkinetic children: a d-amphetamine-treated (index) group and a phenothiazine-treated (control) group. This study was coupled with longitudinal overnight sleep-endocrine assessments in the index group. At the end of the first year seven index subjects have been studied for growth and sleep-endocrine measures and eight control subjects have been studied for growth changes only. The significant findings are: (1) growth retardation in the index group; (2) inhibition of mean sleep-related prolactin secretion; (3) a highly significant correlation between loss of expected height percentile during the first year and decrease of mean sleep related prolactin at 6 months, as compared to baseline. These findings suggest that growth inhibition secondary to chronic d-amphetamine administration in hyperkinetic children might be mediated by inhibition of prolactin secretion.

Relaxin was secreted episodically in all 6 human subjects studied. A 24-hr rhythm was detected in the pooled data, with maximum secretion in the early-midmorning hours and a nadir in the early evening.

After 1 week of a normal control (baseline) period, 7 healthy young adult subjects were subjected to a 3-hr sleep-wake schedule, (ultradian) which was adhered to for 10 days. They were allowed eight 1 hr sleep times, equally spaced throughout each 24 hr period. They were then allowed a normal nocturnal 8-hr sleep time for 7 days. During all lights-out sleep periods, poly-graphic definition of sleep stages and waking time was made. On the sixth 24-hr period of the first week (baseline) and on the eighth 24-hr period of the ultradian period, sequential 20-min plasma samples were obtained by means of an indwelling intravenous catheter. Rectal temperature was obtained at regularly spaced frequent intervals. Despite significant sleep deprivation, a circadian pattern of total sleep time persisted throughout the 10-day ultradian condition. The distribution and amount of REM sleep time was most affected with stages 3–4 sleep least affected. The time of maximum sleep was delayed by approximately 6 hr. The...

A group of 7 healthy male subjects was studied in regard to sleep stages and 24 h plasma cortisol and growth hormone patterns during the 4 seasons of the year in an Arctic environment (Tromsø, Norway). No difference in total sleep or sleep stage per cents was found for any of the yearly seasons. A small but statistical significant increase in mean plasma cortisol concentration and amount secreted for 24 h was found for the autumn-winter seasons, as compared with the spring and summer. However, no difference in the circadian curve of cortisol hormonal pattern was found. All subjects secreted growth hormone shortly after sleep onset at night and no difference was found as a function of season of the year.

Human prolactin was measured in plasma by radioimmunoassay at 20 minute intervals for a 24-hour period in each of six normal adults, whose sleep-wake cycles were monitored polygraphically. A marked diurnal variation in plasma concentrations was demonstrated, with highest values during sleep; periods of episodic release occurred throughout the 24 hours.

In response to both insulin-induced hypoglycemia and the ingestion of 500 mg. of L-dopa, unipolar depressed patients (most of whom were postmenopausal women) secreted significantly less growth hormone (GH) than did normal subjects or bipolar depressed patients in the same age range (45 to 70 years). Prolactin responses to L-dopa were normal for nearly all subjects. Since it is believed that prolactin responses to L-dopa are mediated by brain dopamine and GH responses by brain norepinephrine, the data tend to support the hypothesis that there is a disturbance of brain norepinephrine metabolism in unipolar depressive illness. However, further study is needed to determine the effects of the menopause on GH secretion.

Serial plasma growth hormone (GH) concentrations were measured every 20 min for 24 hr before and after the administration of clomiphene citrate (100 mg/day for 7 days) to four healthy young adult male subjects. The number of GH secretory episodes and the magnitude of the peak plasma concentrations during both wakefulness and sleep were decreased after the clomiphene treatment periods.

Further evidence that there is a relationship between prolactin rise and sleep is offered by this study that delayed sleep onset and inverted the normal sleep-waking cycle in 4 normal patients (3 women and 1 man). The inversion schedule lasted 3 weeks, and at its conclusion a final 12-hour laboratory study was carried out measuring the plasma levels of human prolactin and growth hormone by radioimmunoassay. In the first female subject, mean prolactin levels (ng/ml) were, for baseline and after shift, 7 and 8.3; for case 2 (female) the values were 7.3 and 5.9; for case 3 (male) the levels were 6.1 and 6.1; and for the last case, the levels were 4.7 and 4.3, respectively. Values for growth hormone were (ng/ml) 1.5 and 1.5 for Case 1 for baseline and after shift, respectively; 1.1 and 2.5 for Case 2, respectively; 1.8 and 1.1 for Case 3, respectively; and 7.3 and 5.2 for Case 4, respectively. Prolactin release shifted immediately and completely with shifts of sleep onset of 3, 6, and 12 hours. Thus, it is concluded that the nocturnal rise is dependent on the occurrence of sleep, not on the inherent rhythm related to time of day.

Plasma human growth hormone responses to oral administration of 500 milligrams of L-dopa were analyzed in three groups of subjects: normals, age 20 to 32; normals, age 48 to 68; and unipolar depressed patients, age 45 to 68. While only 7 percent of the young normals had deficient human growth hormone responses to this stimulus, 36 percent of the older normals and 77 percent of the depressed patients failed to have adequate responses, suggesting an effect of age and a further effect of depressive illness. Because the release of human growth hormone appears to be closely related to brain catecholamine metabolism, the deficient responses in the depressed patients may provide further support to the concept of a neurochemical defect in depressive illness.

Human growth hormone (HGH) responses to insulin-induced hypoglycemia were measured in ten postmenopausal women suffering from primary unipolar depressive illness, and in ten age-matched normal postmenopausal women. The mean maximal HGH response in the depressed patients was 4.6 plus or minus 4.4 ng/ml, and in the normals 13.3 plus or minus 9.8 ng/ml (P less than .05). All of the normal subjects had clinically adequate HGH responses, in contrast to only four of the depressed patients (P less than .01). The blood glucose responses were virtually the same in the two groups. Since brain catecholamines play a major role in mediating HGH responses to hypoglycemia, the findings are consistent with the hypothesis of diminished functional catecholaminergic activity in the depressed patients.

After ingestion of 500 mg of levodopa, postmenopausal women had significantly diminished human growth hormone (HGH) responses (mean, 4.6 ng/ml), as compared with those of age-matched men (mean, 9.1 ng/ml; P smaller than .05). The differences between the groups were not related to plasma dopa concentrations. The HGH responses to levodopa of age-matched unipolar and bipolar depressed men, and of unipolar depressed postmenopausal women, did not differ significantly from their respective normal control groups. Depressive illness of these types does not appear to affect the HGH response to levodopa, once the effect of the menopause is taken into account.

Under the organizational aegis of Project Sleep and the Association of Sleep Disorders Centers (ASDC), nearly 5,000 patient records from 11 sleep-wake disorders clinics were analyzed in a cooperative study. These cases represented the diagnostic experience of each of these centers over a two-year period. Each patient underwent polysomnographic study, and his or her condition was diagnosed according to the ASDC classification system, a new, standardized nosology of sleep disorders medicine. The most common major diagnostic category was "disorders of excessive sleepiness (hypersomnia)," 42%; this was followed by "disorders of initiating and maintaining sleep (insomnia)," 26%; "penile tumescence evaluations for impotency," 17%; "parasomnias," 3%; and "disorders of the sleep-wake schedule," 2%. If the impotency evaluations performed in the sleep clinics are removed from the total, leaving only the population that was studied because of sleep complaints, the proportions of the diagnostic categories are hypersomnia, 51%; insomnia, 31%; parasomnias, 15%; and sleep-wake schedule disturbances, 3%. The most prevalent diagnoses in the hypersomnia category were sleep apnea (43%) and narcolepsy (25%). Psychiatric disorders (35%) comprised the most frequent group of insomnia diagnoses, though a variety of other disorders were common. The applications of these results for the practicing physician are discussed. ( JAMA 1982;247:997-1003)