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Despite strong evidence of a physiologic relationship between cholecystokinin (CCK) and corticotropin-releasing hormone (CRH) in the rat central nervous system (CNS), evidence of such a relationship between the two hormones in the human CNS is lacking. A post hoc analysis of serial concentrations of immunoreactive CCK and CRH, obtained every ten minutes from CSF continuously collected over six hours, was performed. A total of 30 subjects were studied: 15 normal volunteers, 10 patients with major depression, and 5 recently-abstinent, alcohol-dependent patients. Overall, we observed an average intra-subject correlation of +.273 (P

We used the technique of continuous cerebrospinal fluid (CSF) sampling to test the following hypotheses regarding CNS monoaminergic systems in depression:(1) absolute concentrations of the informational substances tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) are altered in the CNS of depressed patients (2) abnormal rhythms of tryptophan and/or 5-HIAA, or defective conversion of tryptophan to serotonin (5HT), exist in the CNS of depressed patients, and (3) the relationship between the CNS 5HT and norepinephrine (NE) systems is disrupted in depressed patients. We obtained 6-h concentration time series of tryptophan, 5-HIAA, NE, and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF of 10 patients with major depression and in 10 normal volunteers. No significant differences in CSF tryptophan, 5-HIAA, NE, or MHPG concentrations or rhythms were observed between normal volunteers and depressed patients. Neither were there differences in the mean tryptophan-to-serotonin ratio. However, a negative linear relationship was observed between mean concentrations of 5-HIAA and NE in the CSF of the normal volunteers (r = 0.916 [r2 = 0.839], df = 9, P < 0.001) while, in contrast, depressed patients showed no such relationship (r = +0.094 [r2 = 0.00877], df = 9, n.s.). Furthermore, the correlation coefficients expressing the relationship between CSF MHPG and CSF 5-HIAA within the normal and depressed groups were significantly different. These data support the hypothesis that a disturbance in the interaction between the serotonergic and noradrenergic systems can exist in depressive illness in the absence of any simple 5HT or NE deficit or surplus. Depression and Anxiety 6:89–94, 1997.© 1997 Wiley-Liss, Inc.

Objective: We hypothesized that abnormal entry of glucose into the central nervous system (CNS) might exist in some chronic binge eaters of carbohydrates, as either a cause or consequence of binge eating. The purpose of this study was thus to determine fasting and postprandial glucose concentrations in the cerebrospinal fluid (CSF) of healthy women, and to obtain similar data in an obese, irritable woman with chronic binge eating of postpartum onset. Method: CSF was sampled continuously at 0.1 ml/min from 1100 hr to 1700 hr from the binge eating patient, who consumed 5,000 to 10,000 calories per day (preferentially binging on refined carbohydrates), and 4 healthy women via an indwelling, flexible spinal canal catheter. CSF aliquots were obtained at 10-min intervals for measurement of glucose concentrations. Simultaneously, blood was withdrawn at 30-min intervals to obtain serum for glucose assay. A glucose-rich mixed liquid meal was consumed by participants at 1300 hr. Results: In striking contrast to the normal women, our bulimic patient showed no postprandial rise whatever in CSF glucose concentrations. Fasting CSF glucose concentrations were slightly lower whereas fasting serum glucose levels were normal in the bulimic patient, compared with the normal women. After eating, serum glucose levels increased in all participants, but less so in our patient. Discussion: This is the first description of a lack of postprandial elevation in CSF glucose concentration in a patient with a binge eating disorder. Defective transport of glucose across the blood-brain barrier might account for the observed abnormality. While considering other possiblities, we conjecture that our patient's binge eating was an attempt to compensate for impaired postprandial entry of glucose into her CNS. © 1995 by John Wiley & Sons, Inc.

Abnormalities in central nervous system (CNS) noradrenergic concentrations or dynamics have been postulated to occur in major depression, although direct measurements of norepinephrine concentrations in single samples of lumbar cerebrospinal fluid (CSF) have failed to find significant differences between depressed patients and normal or neurological controls. However, the study of CNS noradrenergic dynamics under physiologic conditions has not been achieved because of the technical limitations of lumbar puncture. In the present study, we used a serial sampling technique in order to longitudinally assess CSF norepinephrine concentrations in ten healthy volunteers and ten depressed patients, smokers as well as non-smokers, while fasting and after the physiologic perturbation of eating. We continuously sampled CSF via indwelling subarachnoid catheters from 1100 to 1700 h and measured norepinephrine at 10 min intervals. A standardized mixed liquid meal was administered at 1300 h, breaking a 17 h fast. We found wide inter-individual variability in CSF norepinephrine concentrations in both groups, but no difference in CSF norepinephrine concentration between depressed patients (1.20 ± 0.85 pmol/ml, mean ± SD) and normal subjects (1.07 ± 0.15 pmol/ml). Significant intra-individual concentration variability over time was observed, which did not differ between healthy subjects and depressed patients. Hourly plasma norepinephrine concentrations were similar in normal volunteers and depressed patients. Mean plasma norepinephrine levels tended to correlate modestly with mean CSF norepinephrine concentrations. Body mass index was inversely correlated with CSF norepinephrine concentration but showed no significant relationship to plasma norepinephrine. Elevated CSF and plasma norepinephrine concentrations were, however, seen in depressed cigarette smokers compared to non-smokers. A rise in CSF norepinephrine was observed during the experiment in all subjects combined, suggesting either a response to a meal or a normal circadian rhythm. These data indicate that CSF norepinephrine concentrations do not distinguish between depressed patients and normal volunteers. Depression 1:149–155 (1993). © 1993 Wiley-Liss, Inc.

The authors present a case of Munchausen syndrome notable for an extended premorbid length and lack of early identifiable antisocial behavior. The patient's life history has been reconstructed, and an integrated psychobiological evaluation of the patient is given including neuroanatomical, neurohormonal, and neuropsychological assessments. Frontotemporal cerebral atrophy and lack of thyroid-stimulating hormone response to thyroid-releasing hormone infusion were found. Although self-object losses did appear to precipitate the Munchausen syndrome in a step-wise fashion, it appears that central nervous system deterioration might have been related to the development of the disorder.

The effects ofacute gonadal suppression on sexual function and behavior were studied in eight normal men. Administration ofa newly developed, potent gonadotropin-releasing hormone antagonist induced azoospermia and reduced levels of serum testosterone, luteinizing hormone, and follicle-stimulating hormone. These effects coincided with a reduction in outward-directed aggression in all men. Self-reported measures ofanxiety and sexual desire revealed less consistent change over time. Measures ofanger control, inward-directed anger, and affective state were unaffected. (Am J Psychiatry 1994; 15 1:271-273)

Background One night of sleep deprivation induces a brief remission in about half of depressed patients. Subclinical hypothyroidism may be associated with depression, and changes in hypothalamic-pituitary-thyroid function may affect the mood response to sleep deprivation. We wished to define precisely the status of the hypothalamic-pituitary-thyroid axis of depressed patients during sleep deprivation and the possible relationship of hypothalamic-pituitary-thyroid function to the mood response. Methods We studied 18 patients with major depressive disorder and 10 normal volunteers. We assessed mood before and after sleep. We measured serum thyrotropin every 15 minutes during the night of sleep deprivation, thyrotropin bioactivity, the thyrotropin response to protirelin the next afternoon, and other indexes of hypothalamic-pituitary-thyroid function. To determine if the changes were limited to the hypothalamic-pituitary-thyroid axis, we measured serum cortisol, which also has a circadian secretory pattern. Results Nocturnal serum thyrotropin concentrations were consistently higher in responders, entirely because of elevated levels in the women reponders. Responders had exaggerated responses to protirelin the next afternoon. The bioactivity of thyrotropin in nonresponders was significantly greater than in responders (F 1,8.99 = 7.52; P = .02). Other thyroid indexes and serum cortisol concentrations were similar among groups. Conclusions Depressed patients have mild compensated thyroid resistance to thyrotropin action, not subclinical autoimmune primary hypothyroidism. Sleep deprivation responders compensate by secreting more thyrotropin with normal bioactivity; nonresponders compensate by secreting thyrotropin with increased bioactivity.

This study sought to examine the feasibility of prolonged assessment of acetylcholinesterase (AChE) activity in the cerebrospinal fluid (CSF) of volunteers and to test the hypothesis that rivastigmine (ENA-713; Exelon, Novartis Pharma AG, Basel, Switzerland) selectively inhibits AChE in CSF in humans at a dose producing minimal inhibition of the peripheral enzyme. Lumbar CSF samples were collected continuously (0.1 mL x min(-1)) for 49 hours from eight healthy volunteers who took either placebo or a single oral dose of rivastigmine (3 mg). CSF specimens and samples of blood cells and blood plasma were analyzed at intervals for rivastigmine and its metabolite NAP 226-90 ([-] [3-([1-dimethylaminolethyl)-phenol]), erythrocyte AChE activity, CSF AChE activity, and plasma and CSF butyrylcholinesterase (BuChE) activity. Safety evaluations were performed 23 hours after drug dosing and at the end of the study. Evaluable data were obtained from six subjects. The mean time to maximal rivastigmine plasma concentration (tmax) was 0.83 +/- 0.26 hours, the mean maximal plasma concentration (Cmax) was 4.88 +/- 3.82 ng x mL(-1), the mean plasma area under the concentration versus time curve (AUC0-infinity) was 7.43 +/- 4.74 ng x hr x mL(-1), and the mean plasma t1/2 was 0.85 +/- 0.115 hours. The concentration of rivastigmine in CSF was lower than the quantification limit for assay (0.65 ng x mL(-1)), but NAP 226-90 reached a mean Cmax of 3.14 +/- 0.57 ng x mL(-1). Only minimal inhibition of erythrocyte AChE activity (approximately 3%) was observed. Inhibition of AChE in the CSF after rivastigmine administration was significantly greater than after placebo for up to 8.4 hours after the dose and was maximal (40%) at 2.4 hours. Plasma BuChE activity was significantly lower after rivastigmine than after placebo, but this was not clinically relevant. BuChE activity in CSF was significantly lower after rivastigmine than after placebo for up to 3.6 hours after dosing, but this difference was not sustained. This study confirms the feasibility of using continuous measurement of AChE activity in CSF over prolonged periods, that rivastigmine markedly inhibits CSF AChE after a single oral dose of 3 mg, and that the inhibition of central AChE is substantially greater than that of peripheral AChE or BuChE.

Certain neuroendocrine abnormalities (e.g., blunted plasma adrenocorticotropic hormone [ACTH] response to corticotropin-releasing hormone [CRH] administration and blunted serum TSH response to thyrotropin-releasing hormone [TRH] administration) are common in alcoholic patients. It was the objective of this study to evaluate whether they are centrally mediated: that is, whether they are secondary to increased activity of CRH and/or TRH neurons. We evaluated the nocturnal secretion (2200 hours to 1000 hours, q 15 min) of plasma ACTH, serum Cortisol, and serum TSH, and their responses to the combined administration of CRH and TRH, in 28 acutely abstinent alcoholic (age range: 32 to 57 years; mean: 42.4 years) and 19 normal men (age range: 21 to 52 years; mean: 32.1 years). To assess the validity of administering CRH and TRH simultaneously, we gave 10 additional abstinent alcoholic men (age range: 36 to 53 years; mean: 45.8 years), in random order and at least 4 days apart, either CRH, TRH, placebo, or CRH plus TRH. Nocturnal ACTH, Cortisol, and TSH secretion, as well as Cortisol and TSH responses after CRH plus TRH administration, were similar in alcoholic and normal men. However, ACTH peak responses to CRH plus TRH were reduced in the alcoholic men (p < 0.05). The ACTH, but not Cortisol, response was greater after combined CRH plus TRH administration than after CRH alone (p < .002). The blunted ACTH response does not appear to be the result of increased endogenous CRH activity, because all parameters of nocturnal ACTH pulsatility were normal in the alcoholics. It rather appears to be secondary to an intrinsic defect in the CRH responsiveness of the pituitary corticotroph, possibly due to genetic vulnerability or to the toxic effects of prolonged alcohol abuse.

Support for the many relationships between thyroid hormones and brain function comes from both laboratory and clinical studies. Studies in laboratory animals provide convincing evidence for a neuroregulatory role of thyroid hormones in the brain, suggesting that they may affect behavior. This notion is supported by human studies which have revealed that the effects of thyroid hormones on brain function are most important during the development and maturation of the brain; thereafter, age does not seem to critically affect brain-thyroid hormone relationships.

We evaluated 20 patients with Cushing's disease (i.e., Cushing's syndrome due to ACTH-secreting pituitary microadenoma) and 20 patients with Major Depressive Disorder (MDD) using the Structured Clinical Interview for DSM-III-R (SCID) and Research Diagnostic Criteria. The diagnosis of Generalized Anxiety Disorder (GAD) was most common in Cushing's disease (79%), followed by MDD (68%), and Panic Disorder (PD) including subthreshold PD (53%). The combination of MDD and GAD and/or PD was also common in Cushing's disease (63%). Behavioral symptoms, if present, usually first occurred at or after the onset of the first physical symptoms. However, the onset of PD was associated with more chronic stages of Cushing's disease. In both Cushing's disease and MDD, more female than male relatives suffered from MDD, whereas more male than female relatives suffered from substance abuse. The data demonstrate a syndrome of anxious depression in patients with active Cushing's disease; such comorbidility has not been previously noted. The data also point to intriguing epidemiological, clinical, and biological associations between Cushing's disease, MDD and substance abuse.

Twenty-nine alcoholic men who had been abstinent for more than 2 years were evaluated behaviorally and neuroendocrinologically and then followed for 2 years. Mean length of abstinence at intake was shorter in the eight patients with histories of depression (3.3 years) than in the patients without such histories (6.8 years). Six patients relapsed during follow-up, all of whom had been sober less than 5 years. None of the neuroendocrine variables studied was predictive of outcome. In summary, abstinence of less than 5 years and comorbidity with depression were most predictive of poor outcome.

1. 1. The relationship between serum cortisol and thyrotropin (TSH) was studied in 15 normal subjects and in 7 depressed, 15 alcoholic and 13 schizophrenic patients. Serum TSH was measured in the basal state and in response to the intravenous administration of 0.5 mg thyrotropin-releasing hormone (TRH). Cortisol was measured in the basal state immediately before TRH injection. 2. 2. Basal cortisol and TSH peak response (max. TSH concentration observed after TRH injection) showed a significant inverse relationship in normal controls (p < 0.005) and in depressed patients (p < 0.04). Schizophrenic patients, however, tended to show a positive correlation between these two parameters (p < 0.09). 3. 3. Basal cortisol and basal TSH were inversely related in normal subjects (p < 0.05, but in none of the three patient groups. 4. 4. Blunted TSH responses after TRH were found in three depressed and five alcoholic patients but not in schizophrenic patients or normal controls. 5. 5. The present data suggest that physiologic cortisol serum concentrations may suppress TRH-induced TSH response in normal subjects and depressed patients. This seems not to be true for schizophrenic patients in whom cortisol tends to enhance TRH-induced TSH release, suggesting an endocrine dissociation in these patients.

Fifteen patients with a primary diagnosis of borderline personality disorder were studied with the thyrotropin-releasing hormone (TRH) test. Twelve carried the additional diagnosis of depression, substance abuse, or both. A blunted thyroid-stimulating hormone (TSH) response to TRH was found in seven patients, two of whom were neither depressed nor had the additional diagnosis of depression and/or substance abuse. TSH blunting was unrelated to such factors as thyroid status, serum cortisol, weight, height, or body surface. Since TSH blunting occurs in about 25% of patients with major depression but not in schizophrenia, the findings suggest that some patients with borderline personality disorder share a neuroendocrine abnormality with some affective disorder patients.

To evaluate the feedback control of thyroid hormones on TSH release, 18 normal subjects and 16 depressed patients received two TRH injections: on days one and nine. Forty eight hours before the second TRH injection subjects and patients received either T3, 100 micrograms orally, or matched placebo. T3 administration resulted in a highly significant and similar reduction of delta max TSH and FT4-index levels in both subjects and patients whereas serum T3 levels were unchanged. These data suggest that the pituitary response to the negative feedback signal of T3 is intact in depressed patients.

In an evaluation of the possible role of dopamine on TRH test results, 21 depressed patients were given TRH before and after one week of treatment with a low dose of haloperidol. Haloperidol significantly increased serum prolactin (both basal and after TRH) and cortisol levels, decreased body temperature, and had no effect on serum TSH, growth hormone, or thyroid hormone levels. Five of six patients with initial TSH blunting were retested with TRH; in four patients the TSH response remained blunted. These data render it unlikely that dopamine exerts a major inhibitory input on TSH secretion in depression.

The effects of pretreatment with a single dose of thyroid hormones (TH) on the subsequent endocrine and behavioral response to TRH was evaluated in unipolar depressed women. TH pretreatment altered neither serum levels of thyroid hormones nor the TRH-induced TSH response. It antagonized, however, the behavioral response to TRH. This was apparent in 2 self-assessment scales but not in an objective rating scale. Taken together the data suggest that (a) there is an impaired pituitary response to TH feedback in depressed patients; (b) TH pretreatment may affect self-assessment of behavioral effects of TRH in depression.

In a double-blind crossover design we treated 20 normal women with thyrotropin-releasing hormone (TRH), 0.5 mg i.v., abd saline in random sequence. Both injections were preceded, 48 hours before, by a single dose of oral thyroid hormones (TH). TRH caused a shift toward mild euphoria, both on objective and subjective ratings. Although statistically significant, the effect was less than that observed in a previous study of normal women in which TH pretreatment was not used. Thus, TH pretreatment appeared partly to block psychological response to TRH. As expected, TH pretreatment also partly blocked thyroid-stimulating hormone (TSH) responses to TRH. Nevertheless, just as in our previous study, psychological responses were significantly negatively correlated with TSH responses. TH appears to exert two independent negative feedback effects: one on the brain (diminished psychological response); and one on the anterior pituitary (diminished TSH response).

• Chronic alcoholics with secondary depression were treated with protirelin in a double-blind, placebo-controlled study. Behavioral data, collected only during the acute alcohol withdrawal state, indicated a beneficial effect of protirelin three hours after injection, but not during subsequent days. Injections caused only mild and infrequent subjective side effects and no cardiovascular effects. Endocrine data were recorded in the acute withdrawal state and after clinical remission. Findings in the acute state suggested thyroid activation and increased central dopaminergic activity, as evidenced by elevated baseline levels of growth hormone, low baseline levels of prolactin, and blunted thyroid-stimulating hormone (TSH) response to protirelin. The first two abnormalities returned to normal levels in the remission state. A blunted TSH response was observed in both the acute and the remission states. Partial persistence of this finding suggests that TSH blunting may not be solely statedependent. In the acute withdrawal state, TSH blunting was associated with favorable behavioral responses to protirelin.

The finding of a diminished TSH response to exogenously administered TRH in a significant proportion of depressed patients has now been established as one of the most reproducible findings in biological psychiatry. More than 50 reports, in which more than 1000 patients have been studied, reveal that the TSH response is blunted in approximately 25% of patients with major depression. TSH blunting is clearly not specific for depression, because it also has been observed in mania, alcoholism, and borderline personality disorder. It is doubtful that TSH blunting represents a non-specific response to mental stress: it was found only rarely in schizophrenic patients, and the TSH response to in vivo flooding therapy in phobic patients was normal. In both depression and alcoholism, TSH blunting has been reported to be sometimes a state marker and sometimes a trait marker, i.e. the fault was found to persist into remission in more than half the patients. In both conditions, TSH blunting was unrelated to the patients' age, body weight, height, body surface, thyroid status, and serum cortisol concentrations. It also is unlikely that TSH blunting was due to increased dopaminergic inhibition of thyrotroph cells: serum prolactin concentrations in TSH blunters were found to be normal, and pretreatment with haloperidol had no effect on either basal TSH levels or TSH blunting. In depression, TSH blunting was not associated with previous drug intake, dexamethasone suppression test abnormalities, or variables of biogenic amine metabolism, nor did it usefully segregate between primary and secondary depression or between unipolar and bipolar subgroups. Preliminary evidence suggests that TSH blunting in depression may be related to duration of illness, history of violent suicide attempts, and a reduced 24 h TSH secretion. In alcoholism, TSH blunting was unrelated to family or personal history of depression and duration of abstinence. With reference to clinical utility, TSH blunting may aid in assessing the response to antidepressant treatment, predicting outcome to such treatment, assessing the risk for violent suicide attempts, and describing relationships between different psychiatric populations (e.g. depression and alcoholism).

The prolactin (PRL) response to thyrotropin-releasing hormone (TRH) was studied in depressed patients (while ill or during remission) and in normal volunteers. Depressed women were shown to have lower basal PRL and lower PRL after TRH, but similar proportional PRL responses, compared to normal women. Depressed women also had basal thyroxine levels that were higher than those of the control women. No significant changes in PRL were noted in depressed men; in fact, there was almost complete overlap of all PRL variables between depressed and normal male subjects. Examination of the responses of PRL and of thyrotropin (TSH) to TRH revealed a significant positive relationship between the two in depressed women, but no association in men.

We recently reported that some patients with borderline personality disorder (BPD) exhibit a blunted thyrotropin (thyroid-stimulating hormone; TSH) response to thyrotropin-releasing hormone (TRH). Because it is known that dopamine can inhibit the TSH response to TRH and that some patients with BPD show improvement with antipsychotic (dopamine-blocking) medication, we investigated whether haloperidol could reverse the blunted TSH response in BPD. Of 12 patients with BPD, three showed a blunted TSH response that did not normalize with haloperidol. Furthermore, there were no overall group changes in TSH response with haloperidol. The present study suggests that reductions in TSH response in BPD are not secondary to dopamine.

Chronic alcoholics who had been abstinent from alcohol for more than 2 years were evaluated with the thyrotropin-releasing hormone (TRH) test. The findings suggest the following profound disturbances in the hypothalamic-pituitary-thyroid axis: 1) a "euthyroid sick syndrome," evidenced by low levels of triiodothyronine (T3), high levels of reverse T3, and normal levels of thyroxine (T4) (this syndrome implies a decreased 5'-deiodination of T4 to T3 and of reverse T3 to its lesser iodinated metabolites), 2) an increased binding capacity for thyroid hormones, evidenced by a decreased T3-uptake value and an increased level of T4-binding globulin, and 3) thyroid-stimulating hormone (TSH) blunting in 31% of patients. Paradoxically, there was a positive correlation between basal T4 and delta max TSH in subjects with blunted TSH, but baseline TSH levels were reduced in subjects with and without blunted TSH.

(1) The hypothalamic tripeptide TRH was injected in normal controls and in schizophrenic, alcoholic and depressed patients. Behavioral and endocrine data were assessed and relationships between the two evaluated. (2) After TRH there was a brief and partial salutary behavioral change in all groups studied, suggesting that the behavioral effects of TRH are not disease specific. (3) A blunted TSH response after TRH was seen in some depressed and some alcoholic patients but not in schizophrenics, indicating that this fault is not simply a nonspecific attribute of mental illness. (4) In depression, but not in alcoholism, the blunting was accounted for by increased levels of serum cortisol. (5) In alcoholic patients, the TSH blunting was related to a favorable behavioral response to TRH. (6) While the relationship between ambient levels of serum cortisol and the TSH response was negative in normal subjects and depressed patients, it was positive in schizophrenic patients. The relative frequency of this finding in the various subtypes of schizophrenia is unknown. (7) The above data, taken together, suggest that both the behavioral and the endocrine effects of TRH render the tripeptide useful for psychoneuroendocrine investigation.

To evaluate the diagnostic utility of TSH blunting, the TRH-induced TSH response was measured in 168 normal subjects and 176 psychiatric patients. It was blunted in some acutely depressed, alcoholic, and borderline patients, but not in schizophrenic patients. In both depression and alcoholism the fault also occurred during symptomatic recovery, though with reduced frequency. Although TSH blunting was useful in distinguishing between borderline and schizophrenic patients, its diagnostic utility in identifying or confirming an existing psychiatric disorder appears to be limited. TSH blunting is not specific for any particular psychiatric diagnosis, and its sensitivity generally is low. However, the fault has promising research utility, particularly for study of the biologic interface between depression, alcoholism and borderline personality disorder. Beyond this, further study of the possible trait nature of TSH blunting in both depression and alcoholism appears warranted.

We studied the effects of intravenous protirelin (thyrotropin-releasing hormone) in 17 schizophrenic patients and 17 normal subjects. A total of 12 patients received protirelin, 0.5 mg, and, on another occasion, niacin, 2 mg, in a double-blind, crossover design. Both behavioral and endocrine data were collected. Five patients received protirelin in an open trial; only endocrine data were collected. Protirelin caused about a 50% prompt decrease in psychotic symptoms. Patients then tended slowly to experience a relapse. Side effects were about as infrequent after protirelin as after niacin. We assayed serum prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), L-triiodothyronine (T3) and thyroxine (T4). Free T4 (FT4) index was calculated. The values for PRL, GH, and TSH at baseline and after protirelin stimulation were normal. Patients showed lower T3 values at baseline, but a brisker T3 response to protirelin, than controls. Their FT4 indices were higher at baseline. Patients showed diminished T4 binding sites rather than increased total T4. The causes of these alterations in thyroid dynamics are unidentified.