Lack of seasonal variation in abnormal TSH secretion in patients with seasonal affective disorder.

The circadian variations in thyroid-stimulating hormone (TSH) secretion, with particular attention to the nocturnal serum TSH surge and the TSH response to thyrotropin releasing hormone (TRH), were measured in seven patients with seasonal affective disorder (SAD) and in eight normal controls. Both patients with SAD and normal controls were tested in fall/winter, when patients were suffering depressive symptoms, and in spring/summer, when patients were euthymic. The TRH tests were performed in the morning. In all tests, the mean peak TSH response to TRH was significantly lower in the patients with SAD than in the normal controls. No significant differences were observed in either group between spring/summer and fall/winter tests. At both periods, patients with SAD showed normal TSH levels in the morning, but did not experience a nocturnal TSH surge. In this group, morning and night TSH levels were similar. In contrast, normal controls showed significantly higher TSH levels at night than in the morning. Serum-free thyroid hormone levels were in the normal range in all subjects. Morning and night serum cortisol levels and 24-hour urinary cortisol concentrations were similar in all subjects. These data show that the secretion of TSH is impaired in SAD, regardless of the phase of the psychiatric disease. The low TSH response to TRH in the presence of normal serum thyroid hormone levels and the lack of the TSH nocturnal surge suggest that patients with SAD might be affected by mild central hypothyroidism.

Reduction in the arginine vasopressin responses to metoclopramide and insulin-induced hypoglycemia in normal weight bulimic women.

A low plasma arginine vasopressin (AVP) responsiveness to hypertonic saline infusion has been described in bulimic women. At present, it is unknown whether this phenomenon is peculiar for the osmotic regulation of AVP secretion or whether it represents an aspect of a more general disorder of AVP secretion in bulimia nervosa. In order to answer these questions, in the present study the AVP responses to metoclopramide (MCP) (20 mg in an i.v. bolus) and insulin (0.15 IU/kg)-induced hypoglycemia were tested in normal weight bulimic women and in weight- and age-matched normal women. Basal AVP concentrations were similar in normal and bulimic women. In the normal controls, plasma AVP levels rose 2.6 times after MCP and 2.2 times in response to hypoglycemia. Both AVP increments were significantly lower in bulimic patients. In this group, plasma AVP levels rose 2 times after MCP and 1.8 times in response to hypoglycemia. When data of the MCP and insulin tolerance test were combined, regression analyses showed a significant positive correlation between AVP peak responses to MCP and hypoglycemia in the bulimic group. These data show an impaired AVP response to different releasing stimuli in bulimia, suggesting that a more general disorder than a simple change in the sensitivity to osmotic stimulation affects the AVP secretory system in bulimic patients. It is likely that bulimic subjects are affected by a neuroendocrine alteration in the control of AVP secretion, whose mechanisms are still unknown.

Abnormal serotonergic control of prolactin and cortisol secretion in patients with seasonal affective disorder.

The effects of the serotonergic agent d,l-fenfluramine (60 mg PO) or a placebo on serum prolactin (PRL) and cortisol levels were evaluated in seven patients (five men and two women) with seasonal affective disorders (SAD) and in eight normal controls (eight men and two women). Both groups were tested in fall/winter when patients with SAD suffered depressive symptoms and in spring/summer, when patients were euthymic. Spring/summer and fall/winter tests gave similar results. PRL and cortisol patterns were similar in all subjects after placebo, whereas both hormonal responses to d,l-fenfluramine were significantly lower in patients with SAD than in normal controls. Correlation studies between the two hormonal responses revealed that on both periods the amplitudes of PRL and cortisol increments were significantly and positively correlated in patients with SAD. These data show diminished serotonergic responsiveness in SAD regardless of the actual depressive status of the patients. They are consistent with a decrease of central serotonergic activity in SAD.

Abnormal growth hormone and cortisol, but not thyroid-stimulating hormone, responses to an intravenous glucose tolerance test in normal-weight, bulimic women.

Abnormal growth hormone (GH) and adrenocorticotropic hormone (ACTH)/cortisol secretory patterns in response to a glucose load have been observed in underweight anorectic women. The present study was performed in an attempt to establish whether changes in the hypothalamic/pituitary sensitivity to hyperglycemia occur in bulimia in the absence of weight disturbance. Therefore, serum GH, plasma cortisol, and plasma insulin concentrations were measured in eight women with normal weight bulimia and in eight normal women during an intravenous glucose (0.33 g/kg as an IV bolus) tolerance test (IGTT). In addition, since abnormal pituitary hormone responses to a glucose load might reflect alterations in somatostatin (SRIH) release, TSH secretion also was measured, in view of its sensitivity to SRIH inhibition. Both GH and cortisol levels progressively and significantly declined during IGTT in the normal subjects. In the bulimic women, cortisol levels remained unchanged, whereas GH concentrations rose significantly after glucose injection. Plasma cortisol and serum GH levels were significantly higher in the bulimic than in the control subjects. No significant differences between groups were observed in hyperglycemia-induced insulin increments or in TSH decrements. These data indicate that an altered sensitivity to hyperglycemia affects the hypothalamic/pituitary centers controlling the secretion of the counterregulatory hormones GH and ACTH/cortisol in bulimia nervosa. The lack of a simultaneous change in the TSH secretory pattern argues against a possible involvement of SRIH in the pathophysiology of this disorder.

Effect of estrogen or insulin-induced hypoglycemia on plasma oxytocin levels in bulimia and anorexia nervosa.

Plasma oxytocin (OT) levels were measured before and after stimulation with estrogens (1 mg ethynylestradiol orally) or with insulin (0.15 IU/kg)-induced hypoglycemia in seven underweight women with anorexia nervosa, eight normal weight bulimic women, and nine normal controls. Anorectic patients were amenorrhoic; they were tested at their first hospitalization (first tests) and again 8 to 9 weeks later (second tests) when they were eating normally, but were still at a low weight. In addition, anorectic women were tested 16 to 17 weeks after the first test (third tests), when their weight was restored to normal. Normal and bulimic women were tested on the fourth days of normal menstrual cycles. Insulin induced similar hypoglycemic responses in all groups. At each time point of the estrogen tests, plasma estrogen levels were similar in bulimic and normal women, whereas they were significantly lower in anorectic subjects. There were no differences in the basal levels of OT among groups. Both insulin-induced hypoglycemia and estrogen treatment produced striking OT increments in bulimic and control women, without significant differences between groups. During the first tests, no significant increase in plasma OT levels was observed in underweight anorectic women in response to both releasing stimuli. After partial weight recovery, the anorectic women showed a slight, but significant, increase in the OT responses to both insulin-induced hypoglycemia and estrogen administration. Both hypoglycemia- and estrogen-induced OT increases observed during the second tests were significantly lower in underweight anorectic patients than in normal controls. Anorectic subjects regained normal OT responsiveness to both stimuli after complete weight recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of GH response to the GABA-B agonist baclofen in patients with major depression.

In order to establish whether alterations in the GABAergic control of GH secretion occur in male patients with major depression, the GH response to the GABAergic-B agonist baclofen (10 mg PO at 0830h) or to placebo was tested in 9 depressed men and in 10 age- and weight-matched male normal controls. The basal concentrations of GH were significantly lower in the depressed patients (0.87 +/- 0.69 ng/ml) than in the normal controls (1.57 +/- 0.33 ng/ml) (p = 0.011) and were not modified by the administration of placebo. The administration of baclofen induced a striking, significant increase in GH concentrations in the normal controls (mean peak at 90 min = 6.4 +/- 1.5 ng/ml). In contrast, a slight, nonsignificant GH increase occurred in the depressed patients after baclofen (mean peak at 90 min = 1.57 +/- 1.45 ng/ml). The GH response was significantly lower in the depressed than in the control subjects (p less than 0.001). These data indicate the presence of reduced GABAergic control of GH secretion in male depressed patients.

Growth hormone responses to growth hormone-releasing hormone, clonidine and insulin-induced hypoglycemia in normal weight bulimic women.

The growth hormone (GH) responses to GH-releasing hormone (GHRH; 1 microgram/kg BW in an i.v. bolus), clonidine (150 micrograms in a single oral dose) and insulin (0.15 IU/kg BW in an i.v. bolus) induced hypoglycemia were evaluated in 7 normal weight bulimic women with regular menstrual cycles and in 7 age- and weight-matched normal women. In addition, the effect of thyrotropin-releasing hormone (TRH; 200 micrograms in an i.v. bolus) on serum thyroid-stimulating hormone (TSH) and GH levels was measured in the same subjects. Tests were carried out in random order on the 22nd days of the following menstrual cycles. A control test with the i.v. administration of normal saline instead of drugs was carried out 2 days after the TRH test. Basal GH levels were significantly higher in bulimic women than in normal controls; despite higher GH levels, bulimic women showed normal circulating concentrations of somatomedin-C (Sm-C). Serum GH levels remained unmodified during the control test. In contrast, the administration of GHRH, clonidine or insulin induced significant GH responses in all subjects. Bulimic and normal women showed comparable responses after GHRH, clonidine or hypoglycemia. The hypoglycemic response to insulin was similar in bulimic and control subjects. The administration of TRH was unable to increase the circulating levels of GH in the normal controls, whereas it significantly increased GH concentrations in 5 of 7 bulimic women.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of migraine and muscle tension headache in depressive disorders.

This study was undertaken in order to evaluate the prevalence of headache and its subtypes (migraine, muscle tension headache, cluster and psychogenic headache) in a population of 160 depressed patients. Headache was present in 83 subjects (51.9%); 36 (22.5%) were affected by migraine, 39 (24.4%) by muscle tension headache, six (3.7%) by psychogenic headache and two (1.2%) by cluster headache. No significant differences in the prevalence of migraine and muscle tension headache were observed among patients with major depression, bipolar depressive disorder and dysthymic disorder. These data speak against a specific correlation among subtypes of headache and depressive disorders.

Dopaminergic control of TSH secretion in endogenous depression.

To evaluate whether the inhibitory control exerted by endogenous dopamine on thyroid-stimulating hormone (TSH) secretion is altered in patients with major depressive disorder, 11 depressed patients and 9 normal controls were tested with the dopaminergic receptor antagonist domperidone (10 or 20 mg i.v.). The administration of domperidone induced a significant increase in circulating TSH levels in the normal controls, but not in the depressed patients. These data excluded the possibility that the dopaminergic inhibition of TSH secretion is enhanced in depression. To establish whether domperidone failure was due to a reduced dopaminergic tone, domperidone was administered before stimulation of TSH secretion with thyrotropin-releasing hormone (TRH) (200 micrograms i.v.). The TSH response to TRH was significantly lower in the depressed than in the control subjects, regardless of domperidone priming. However, in both groups domperidone enhanced the TRH-induced TSH release by 50%. These data suggest that the dopaminergic control of TSH secretion is not altered in patients with endogenous depression and that a reduced capacity of the pituitary to secrete TSH might be responsible for the reduced TSH responsiveness to TRH and domperidone.

Involvement of a dopaminergic mechanism in the response of growth hormone to thyrotropin releasing hormone in patients with major depression.

In an attempt to establish whether, in patients with major depression, dopaminergic receptors are involved in the release of growth hormone (GH) induced by thyrotropin releasing hormone (TRH), eleven subjects were tested with TRH (200 micrograms in an i.v. bolus) with or without concomitant treatment with domperidone (10 mg in an i.v. bolus 10 min before TRH), an antidopaminergic agent which does not readily cross the blood-brain barrier. In 7 out of the 11 patients, TRH strikingly increased GH levels (responders) (the mean peak level was 9 times higher than basal value), whereas it was without effect in the remaining 4 patients (non-responders). When the responders were treated with domperidone before TRH injection, TRH-induced GH increase was still present, but it was significantly lower (the mean peak level was 5.3 times higher than basal value) than in the TRH test (p less than 0.02). These data suggest that the paradoxical response of GH or TRH in patients with major depression involves a dopaminergic mechanism active at sites situated outside the blood-brain barrier.

Pirenzepine inhibits growth hormone, but not thyrotropin response to thyrotropin-releasing hormone in patients with endogenous depression.

In order to evaluate whether in endogenous depression the anomalous growth hormone (GH) response to thyrotropin-releasing hormone (TRH) is mediated by muscarinic cholinergic receptors, 12 patients were tested with TRH (200 micrograms iv) with and without previous treatment with the muscarinic cholinergic receptor blocker pirenzepine (40 mg iv 10 min before TRH). Control tests with normal saline also were performed. Administration of normal saline did not alter serum GH levels. In contrast, TRH injections significantly increased serum GH concentrations by about three-fold. This response was inhibited by pretreatment with pirenzepine. Another neuroendocrine marker of endogenous depression, the low TSH increase in response to TRH (delta less than or equal to 7 microU/ml), was observed in our patients. Pretreatment with pirenzepine did not modify this response. These data indicate that in patients with endogenous depression a muscarinic cholinergic mechanism is involved in the GH response but not in the TSH response to TRH.