Changes in anterior pituitary hormone secretion and hypothalamic catecholamine metabolism during morphine withdrawal in the female rat

Studies were undertaken to evaluate the acute responses of hypothalamic noradrenergic and dopaminergic neurons and anterior pituitary hormones to naloxone (NAL)-precipitated morphine (MOR) withdrawal in the rat. Ovariectomized female rats were rendered MOR-dependent and injected with NAL (1 mg/kg b.w., s.c.). During precipitated MOR withdrawal, a decline in norepinephrine (NE) concentrations was preceded by an increase in the level of its metabolite normetanephrine (NME) in the medial basal hypothalamus (MBH) as well as the preoptic area-anterior hypothalamus (POA-AH). Both dopamine (DA) and its major acid metabolite, dihydroxyphenylacetic acid (DOPAC), showed increased concentrations in these two hypothalamic regions within 30 min of NAL administration. Elevated luteinizing hormone (LH) and beta-endorphin secretion was evident within 5 min of NAL injection to MOR-dependent rats, while serum prolactin (PRL) increased 15 min into MOR withdrawal. Both growth hormone (GH) and thyroid-stimulating hormone (TSH) were depressed over the course of MOR withdrawal. Although a cause and effect relationship cannot be established, during NAL-precipitated MOR withdrawal, a heightened hypothalamic monoaminergic neuronal activity is accompanied by a differential response of anterior pituitary hormones. The observed responses, which are similar to those seen during acute stress, indicate that MOR withdrawal may activate the same mechanisms which mediate the neuroendocrine response to stress.     

Effects of Morphine and Naloxone on Prolactin and Growth Hormone Gene Expression in the Male Rat Pituitary Gland

It is generally admitted that opioids can stimulate the release of both prolactin (PRL) and growth hormone (GH). In order to investigate the role of opioids in the regulation of PRL and GH gene expression in the rat pituitary, we studied the effects of chronic administration of the opioid drug morphine and an opiate receptor antagonist naloxone on both PRL and GH gene expression as measured by in situ hybridization. Four-day treatment with morphine (40 mg/kg/day) produced a 12% increase in PRL mRNA levels. Conversely, naloxone (4 mg/kg/day) decreased the autoradiographic reaction by 10%. The concomitant administration of morphine and naloxone induced no significant changes in PRL gene expression. On the other hand, treatment with morphine produced a 22% decrease in GH mRNA levels, an effect which was prevented by the concomitant administration of naloxone. When injected alone, naloxone did not modify the hybridization signal. These results clearly indicate that opioids are involved not only in the regulation of GH and PRL release but also in the gene expression of the two hormones. The discordance observed between the acute effects of morphine on GH release and the effect of the opioid drug on mRNA levels remains to be clarified.     

The 24-hour Rhythms in Plasma Growth Hormone, Prolactin and Thyroid Stimulating Hormone: Effect of Sleep Deprivation

Twenty-four hour secretory rhythms of growth hormone (GH), prolactin (PRL) and thyroid stimulating hormone (TSH) were investigated in 9 normal adult men by means of serial blood sampling at 30 min intervals. The profiles of pituitary hormones were compared in 6 subjects between in normal nocturnal sleep condition and in delayed sleep condition. Plasma GH was measured with use of highly sensitive enzyme immunoassay (EIA) recently developed. Plasma TSH was also evaluated by highly sensitive time-resolved fluorometric immunoassay (TR-FIA). Time series analysis of plasma GH and PRL was performed by auto- and cross- correlation and spectral analysis. The detection limit of EIA for GH was 0.3 pg/ml and all plasma GH levels were within the detectable range of this EIA. Cross-correlation and spectral analysis suggested the presence of approximately 2–3 h rhythmicity of plasma GH. Plasma PRL appeared to have some 24-hour rhythmicity besides its sleep-dependent component. Sleep deprivation caused marked elevation of plasma TSH during night time. It is suggested that there appears two mechanisms regulating GH secretion: one has a sleep-independent and ultradian rhythm and another has a sleep-dependent rhythm.     

Cyclosporine Effects on in vitro Responsiveness of Anterior Pituitary Hormone Release to Dopamine and Thyrotropin-Releasing Hormone in Young Female Rats

Endocrine side effects of the immunosuppressive drug cyclosporine (CyA) include changes in anterior pituitary hormone secretion. The aim of the present study was to examine the effects of CyA on the responsiveness of in situ and ectopic anterior pituitary prolactin (PRL), growth hormone (GH) and luteinizing hormone (LH) release response to dopamine (DA) and thyrotropin-releasing hormone (TRH) treatment in young female rats, and to evaluate the possible PRL participation in these effects. Thirty day old rats were rendered hyperprolactinemic by transplanting an anterior pituitary gland of a littermate donor, under the kidney capsule, and were then injected with CyA or vehicle for 2 or 8 days. Sham-operated rats were used as controls and treated in the same way. CyA treatment prevented the increase in plasma PRL levels which occurred in controls after pituitary grafting. In vitro basal PRL release of in situ pituitaries from either sham-operated and/or pituitary-grafted animals was decreased by CyA treatment at any point studied. Basal in vitro secretion of GH was only decreased in the in situ pituitaries from grafted animals after 2 days of CyA therapy. The presence of an ectopic pituitary lead to an increase in the in vitro basal LH secretion from in situ pituitaries as compared to those from sham-operated rats. Basal LH release rates were not changed by CyA treatment, although the LH release in vitro did increase in the in situ pituitaries from sham-operated animals treated with the drug for 2 days. DA addition to the incubation media decreased the in vitro release of PRL, GH and LH from the in situ pituitaries of sham-operated and pituitary-grafted animals treated with vehicle. In CyA treated animals, DA decreased in vitro PRL release from the in situ pituitaries of animals, independently of the presence or absence of an ectopic pituitary. Reductions of the in vitro GH and LH release after DA treatment were higher in the in situ pituitaries from grafted animals on day 8 of CyA or vehicle treatment. TRH increased the in vitro release of the three hormones with differential effects related to the length of the treatment with CyA and/or the presence of an ectopic pituitary. In vitro release of PRL and GH by ectopic pituitaries was inhibited by previous treatment with CyA and this effect was decreased proportional to the duration of the treatment with the drug, while LH secretion was not modified. Addition of DA to the incubation media resulted in a marked reduction of in vitro PRL and GH release, but only at day 8 of vehicle treatment on GH release did DA addition to media further decrease the release of both hormones from ectopic pituitaries from animals treated for 2 or 8 days with the drug, whereas LH secretion was not modified. TRH addition to the incubation media of ectopic pituitaries surprisingly reduced PRL and GH secretion on day 8 of CyA treatment or after surgery. The results of these studies suggest that CyA can act directly at the hypophyseal level modifying pituitary responsiveness to external stimuli. CyA seems to exert its main effects on lactotroph activity while its effects on somatotrophs and gonadotrophs are less.     

Studies of growth hormone (GH), thyrotropin (TSH) and prolactin (PRL) secretion in anorexia nervosa.

(1) Studies of serum thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) responses following TRH administration were performed in 7 subjects with anorexia nervosa (AN). (2) Five patients demonstratod significant increases in circulating GH from a mean of 15.6 ng/ml to a peak of 31.8 ng/ml 30 min after TRH. (3) Basal TSH concentrations were undetectable (< 2μU/ml) in all patients prior to stimulation but following TRH, significant elevations (ΔTSH > 6 μU/ml) in TSH were identified in 3/7 patients. (4) The largest elevations in TSH occurred in the two subjects in whom no GH rises were found, whereas blunted TSH rises were noted in 4/5 subjects who showed substantial GH secretory responses to TRH. (5) Basal PRL concentrations were normal and rose appropriately after TRH in all subjects. (6) These studies demonstrate that GH secretion can be provoked in AN by TRH similar to patterns in other states (acromegaly, uremia, protein-calorie malnutrition), characterized by elevated basal GH concentrations. (7) It is hypothesized that activated GH secretion may favor TRH responsivity of somatotrophs. (8) Obtundation of TSH secretion in AN, moreover, may be related to the augmented secretion of GH, since TSH secretion can be lowered by exogenous GH administration in man.     

Response of anterior pituitary hormones to chronic stress. The specificity of adaptation

The effect of chronic noise stress on the response of anterior pituitary hormones to the same or to another stressor (forced swimming) was studied in adult male Wistar rats. Both acute stressors increased corticosterone, prolactin, LH and TSH secretion and inhibited GH secretion. Previous chronic exposure to noise reduced corticosterone response to the same stimulus without modifying corticosterone response to a novel acute stress. Neither prolactin nor TSH responses to acute noise were reduced by previous chronic exposure to noise. Since chronic noise increased basal levels of LH and decreased those of GH, the response of these hormones to acute stress was expressed as percent changes of their respective basal values. It was found that chronically stressed rats showed diminished LH response to noise but not to forced swimming. GH showed the same pattern without reaching statistical significance. These data indicate that the response of some anterior pituitary hormones can adapt after repeated exposure to the same stressor. When adaptation occurred, this was specific for the stressor which the animals were repeatedly exposed to. The pituitary-adrenal axis appears to be the most reliable index of adaptation to chronic stress among all the anterior pituitary endocrine axes.     

急性颅脑损伤后垂体前叶激素的动态变化及意义

目的探讨急性颅脑损伤患者垂体前叶激素水平的变化与颅脑损伤程度及预后的关系。方法随机抽取90例颅脑损伤患者作为观察组,采用酶联免疫定量分析法动态检测伤后第1、3、5、7、14、30d血清催乳素(PRL)、卵泡刺激素(FSH)、黄体生成激素(LH)和促甲状腺激素(TSH)水平;30例正常人作对照组,损伤程度采用GCS评分评估,预后采用GOS评分评估。结果观察组血清PRL、FSH、LH较对照组显著升高(P<0.05),TSH较对照组略降低(P>0.05);观察组血清PRL、FSH、LH水平伤后升高(72h内尤为明显),后逐渐降低,血清TSH的水平伤后略降低,后逐渐回升;GCS评分较低者垂体前叶激素变化幅度较大;预后恶劣的颅脑损伤患者垂体前叶激素变化幅度较大。结论急性颅脑损伤后血清垂体前叶激素PRL、FSH及LH水平明显升高,变化程度与颅脑损伤严重程度及预后有关。     

Ultradian rhythms in pituitary and adrenal hormones: their relations to sleep

Sleep and circadian rhythmicity both influence the 24-h profiles of the main pituitary and adrenal hormones. From studies using experimental strategies including complete and partial sleep deprivation, acute and chronic shifts in the sleep period, or complete sleep-wake reversal as occurs with transmeridian travel or shift-work, it appears that prolactin (PRL) and growth hormone (GH) profiles are mainly sleep related, while cortisol profile is mainly controlled by the circadian clock with a weak influence of sleep processes. Thyrotropin (TSH) profile is under the dual influence of sleep and circadian rhythmicity. Recent studies, in which we used spectral analysis of sleep electroencephalogram (EEG) rather than visual scoring of sleep stages, have evaluated the temporal associations between pulsatile hormonal release and the variations in sleep EEG activity. Pulses in PRL and in GH are positively linked to increases in delta wave activity, whereas TSH and cortisol pulses are related to decreases in delta wave activity. It is yet not clear whether sleep influences endocrine secretion, or conversely, whether hormone secretion affects sleep structure. These well-defined relationships raise the question of their physiological significance and of their clinical implications.     

Endocrine effects of centrally injected nociceptin in the rat

In the present study we investigated the mechanisms involved in the endocrine effect of nociceptin/orphanin FQ (OFQ) in the rat and the possible interaction between OFQ and morphine in the control of growth hormone (GH) secretion. The intracerebroventricular administration of OFQ (2.3 or 23 microg/rat, i.c.v.) in freely moving male rats caused an increase in the secretion of both GH and prolactin (PRL). The possible involvement of the catecholaminergic (CA) system was studied by administering OFQ to CA-depleted rats (rats given 200 mg/kg of alpha-methyl-p-tyrosine subcutaneously 2 h before the i.c.v. dose of OFQ). In these CA-depleted rats, administration of OFQ (23 microg/rat, i.c.v.) did not stimulate GH secretion, whereas it significantly enhanced PRL secretion. In rats anesthetized with ketamine, which induces a significant increase of GH, PRL and corticosterone secretion by activating the sympathetic tone, OFQ (23 microg/rat, i.c.v.) did not modify GH and corticosterone levels, whereas again it significantly potentiated PRL secretion. Overall these results indicate that CA system is involved in the stimulatory action of OFQ on GH but not on PRL secretion. In fact the stimulation of PRL, but not that of GH, was still evident after impairment of the CA system. Pretreatment with OFQ (23 microg/rat, i.c.v.) attenuated the GH secretion induced by morphine (1 mg/kg, given by intra-arterial injection), thus showing a negative interaction between OFQ and morphine in the control of GH secretion.     

Transgenic studies on the regulation of the anterior pituitary gland function by the hypothalamus

The anterior pituitary gland is composed of five different cell types secreting hormones whose functions include the regulation of post-natal growth (growth hormone, GH), lactation (prolactin, PRL), reproduction (luteinising hormone, LH, and follicle stimulating hormone, FSH), metabolism (thyroid stimulating hormone, TSH), and stress (adrenocorticotrophic hormone, ACTH). The synthesis and secretion of the anterior pituitary hormones is under the control of neuropeptides released from the hypothalamus into a capillary portal plexus which flows through the external zone of the median eminence to the anterior lobe. This review describes the ways that gene transfer technologies have been applied to whole animals in order to study the regulation of anterior pituitary function by the hypothalamus. The extensive studies on these neuronal systems, within the context of the physiological integrity of the intact organism, not only exemplify the successful application of transgenic technologies to neuroendocrine systems, but also illustrate the problems that have been encountered, and the challenges that lie ahead.     

Pyridostigmine, an Acetylcholinesterase Inhibitor, Stimulates Growth Hormone Release, but has no Effect on Basal Thyrotrophin or Adrenocorticotrophin Levels, or the Thyrotrophin Response to Thyrotrophin-Releasing Hormone

Pyridostigmine, an acetylcholinesterase inhibitor, stimulates growth hormone (GH) release and is thought to act by inhibiting hypothalamic somatostatin release. There are few data concerning the effect of pyridostigmine on other pituitary hormones apart from GH. We have studied the effect of pyridostigmine on basal GH, thyrotrophin (TSH), prolactin, adrenocorticotrophin and cortisol release, and thyrotrophin-releasing hormone (TRH)-stimulated TSH and prolactin release, in two studies involving nine healthy male subjects. Pyridostigmine stimulated GH release in all subjects but had no effect on adrenocortocotrophin or cortisol levels, or basal or TRH-stimulated TSH and prolactin levels. There are some data to suggest that somatostatin inhibits TRH-stimulated TSH release. Our findings, however, suggest that either endogenous somatostatin tone has little effect on the TSH response to TRH compared to its effects on GH or pyridostigmine acts through a mechanism other than altering somatostatin tone. Pyridostigmine did not alter adrenocorticotrophin or cortisol levels in the presence of a clear action on GH release, providing further evidence that the previously reported effects of cholinergic drugs on cortisol release are stress-related.     

Effect of dexamethasone implanted in different brain areas on the morphine-induced PRL, GH and ACTH/corticosterone secretion

We studied the effect of dexamethasone (DEX) implantation in male Wistar rats to elucidate the site of action of morphine-induced prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH) and corticosterone (B) secretion. DEX or cholesterol was implanted in the close vicinity of the paraventricular (PVN), or the arcuate nuclei (ARN) of the hypothalamus or into the hippocampus. Five days after implantation blood samples were taken 30 min after i.p. morphine by decapitation or through an indwelling cannula 15, 30, 60 min after i.v. injection. DEX implanted near the PVN resulted in a blockade of morphine-induced ACTH and B secretion. In contrast, GH response to morphine was enhanced, while that of PRL was unchanged. DEX implanted near the ARN significantly inhibited the PRL-releasing effect of morphine, but was without any influence on the PRL secretion induced by haloperidol. There was a partial reduction in the B response to morphine, and GH secretion was unchanged. Dorsal hippocampal implants were without any effect on the morphine-induced GH, PRL or B secretion. We suggest that the site of glucocorticoid inhibitory action in the hypothalamus is the PVN for the opiate-induced ACTH/B secretion, and the ARN for the morphine-induced PRL release. The enhanced GH response to morphine observed in DEX-PVN implanted rats might be due to a decreased somatostatin tone.     

Synchronies between sleep and endocrine rhythms in man and their statistical evaluation.

(1) The transitions between wakefulness and sleep are periodic and quantifiable, and because they represent major changes in the functional activity of the CNS, they have been used as paradigms for the study of CNS influences on endocrine functioning. (2) Sleependocrine studies have shown that hormones are secreted in a pulsatile, episodic fashion, and many have prominent circadian and ultradian rhythms (e.g. adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin (PRL), testosterone). (3) Some of these hormone rhythms are closely linked to the sleep-wake cycle (e.g. PRL) or to the specific stages of sleep (e.g. GH). (4) These findings suggest that ‘open loop’ mechanisms (CNS driving) are important in hormone regulation, in addition to ‘closed loop’ mechanisms (negative and positive feedback between hormones and the CNS). (5) The interaction of hormone rhythms may be important for their final metabolic effects. An example is the possible interrelation of three pituitary hormones, luteinizing hormone (LH), follicle stimulating hormone (FSH), and PRL, in stimulating the secretion of testosterone in adult men: Plasma LH has no circadian rhythm in adult men, whereas plasma PRL and plasma testosterone have similar circadian rhythms, with increasing levels occurring during sleep; plasma testosterone correlates as well with PRL at night as it does with LH. (6) The suggestion from these data that PRL may have a role in testosterone release is being studied by more specific experimental manipulations of the pituitary hormones. (7) The statistical analysis of hormone patterns over time has been inadequate in many studies: because the data comprise repeated measures on the same subjects and therefore are correlated, it is inappropriate to apply statistical tests designed for independent, uncorrelated measures, and some schemes for the analysis of repeated measures data are presented.     

Multiple hormonal responses to morphine: relationship to diagnosis and dexamethasone suppression

Plasma cortisol, prolactin (PRL), growth hormone (GH), and thyroid stimulating hormone (TSH) responses to intravenous morphine (0.1 mg/kg body weight) were investigated in five healthy women and 22 female psychiatric inpatients (eight with major depression, 12 with schizophrenia and two with personality disorders) during a 120 min period. The results were also related to a subsequent dexamethasone suppression test (DST). Morphine caused a strong and progressive decline in plasma cortisol which was uniform in controls, depressed, and nondepressed patients. DST nonsuppressors had significantly higher cortisol levels during the entire period, but the same response to morphine. Morphine strongly stimulated PRL secretion, which was found to be significantly smaller in patients than in controls, but no difference was seen between depressed and nondepressed subjects. GH and TSH showed only minor and variable changes after morphine, with no overall significant differences. The data in this study do not support the assumption of a major alteration in opiate receptor responsivity either in depression or in DST nonsuppressor patients insofar as the regulation of the adrenal, thyroid, GH and PRL hormone secretion is concerned.     

The role of opiates and endogenous opioid peptides in the regulation of rat TSH secretion

The administration of morphine to rats at room temperature is reported to suppress serum thyrotropin (TSH) levels by a hypothalamic mechanism. However, it is unknown whether endogenous opioid peptides (EOP) are involved in the control of TSH secretion. The present studies show that naloxone (10 mg/kg, i.p.), an opiate-receptor antagonist, prevented the decline in rat serum TSH which occurs with heat exposure. Morphine sulfate (20 mg/kg, i.p.) treatment prevented the cold-induced elevation in serum TSH, and pretreatment with haloperidol (0.3 mg/kg, i.p.) eliminated morphine's influence. Medial-basal hypothalamic thyrotropin-releasing hormone (TRH) content, measured by RIA, increased in the morphine-treated rats which were exposed to 4 °C. A submaximal intravenous dose of TRH (300 ng/100 g) was given to determine whether morphine suppresses serum TSH through the release of hypothalamic thyrotropic inhibitors. Morphine pretreatment did not alter TSH stimulation by TRH. Morphine alone or combined with TRH did not alter basal or stimulated TSH secretion in vitro.These studies strongly suggest that, in rats, the EOP modulate TSH secretion under conditions such as acute heat exposure which are associated with a decline in serum TSH. Under specific circumstances, the suppression of serum TSH morphine may be dopamine-dependent.     

Interleukin regulation of prolactin and corticotropin from pituitary adenoma

Recent findings indicate that lymphokines, leukocyte-derived hormones, interact with the hypothalamic-pituitary axis. We examined the role of neurotrophic lymphokines in the neuroendocrine system. Specifically, the action of Interleukin (IL)-1b, IL-2 and IL-6 upon the anterior pituitary hormones, growth hormone (GH), prolactin (PRL) and adrenocoticotropic hormone (ACTH) were studied in rodent pituitary adenoma cell lines. Hormone release by GH and PRL-producing rat adenoma cells (GH3) and ACTH-producing mouse adenoma cells (AtT-20) was analyzed by radioimmunoassay (RIA). Recombinant (r) IL-1beta decreased PRL release from GH3 in a dose-dependent fashion. IL-1 inhibition of PRL production occurred in parallel with IL-1 inhibition of DNA synthesis in GH3 as measured by [(3)H] thymidine incorporation. This result strongly indicates that IL-1 alters PRL production by adenoma cells at the translational level. Low dose IL-2 (10 U/ml) enhanced ACTH production from AtT-20, but higher concentrations of IL-2 failed to affect the release of ACTH. IL-2 did not change the incorporation of [(3)H] thymidine in AtT-20. Previous studies showed that IL-1 and IL-6 induce a significant secretion of ACTH via the hypothalamic-pituitary axis. However, IL-1 and IL-6 failed to affect ACTH secretion by AtT-20. Blood-derived cytokines have direct effects on hormone secretion by pituitary adenoma cells in vitro.     

A case of pituitary adenoma with simultaneous secretion of TSH and GH detected by double immunostaining method

A rare case of simultaneous hypersecretion of thyroid stimulating hormone (TSH) and growth hormone (GH) in a pituitary adenoma is reported. A 59-year-old male complaining of general fatigue, dyspnea on exertion and finger tremor was admitted. Examination on admission, he revealed with hyperthyroidism and hypersecretion of TSH and thyroid hormones. Administration of TRH did not further increase serum TSH level, and administration of T3 also had no effect on TSH secretion. CT scan showed a pituitary macroadenoma 13mm in diameter. MRI demonstrated a homogenously hypointense mass with Gd-DTPA enhancement in the left side of the sella turcica. The entire chromophobic adenoma was removed by trans-sphenoidal surgery. Immunostaining of the specimen showed that the cytoplasm of the adenoma cells was positive for both TSH and GH. Double immunostaining using avidin-biotin-peroxidase complex (ABC) method and immunogold silver staining (IGSS) method, showed that the adenoma cells had been secreting both GH and TSH at the same time. After the adenomectomy, the hyperthyroidism disappeared, and all altered indicators of pituitary function returned to normal.     

Role of the non-canonical notch ligand delta-like protein 1 in hormone-producing cells of the adult male mouse pituitary

To better understand the role of the non-canonical Notch ligand delta-like protein 1 (DLK1), in hormone-producing cells, we studied the cell distribution and subcellular localisation of DLK1 in the pituitary of male adult 129/SvJ mice, and analysed the variations in the hormone-producing cells associated with the lack of this gene in Dlk1 knockout mice. The results obtained showed the presence of DLK1-immunoreactive (ir) cells in all hormone-producing cells of the anterior pituitary. Immunoelectron microscopy showed DLK1-ir in the rough endoplasmic reticulum and inside secretory vesicles, suggesting that DLK1 is released together with pituitary hormones. Moreover, we found that prolactin (PRL)-DLK1-ir cells are in intimate contact with follicle-stimulating hormone (FSH)-ir-DLK1-negative cells. In Dlk1 knockout mice, we detected a significantly lower number of gowth hormone (GH)-ir cells, a reduction in the FSH and PRL immunostaining intensity, and a significant decrease in FSH mRNA expression compared to wild-type mice. An increase in pituitary GH mRNA expression and serum leptin levels was also found. These findings provide evidence supporting several regulatory functions of DLK1 in the pituitary gland.     

Chronic cognitive sequelae after traumatic brain injury are not related to growth hormone deficiency in adults

Objective: The objective of the study was to asses the possible influence of hypothalamo–pituitary deficiencies, and growth hormone (GH) deficiency in particular, on cognition in adult patients with traumatic brain injury (TBI). TBI is a recently identified risk factor for cognitive deficits and hypopituitarism. Even the patients with favorable outcome after TBI may present with persistent bodily, psychosocial, and cognitive impairments, resembling patients with untreated partial or complete pituitary insufficiency. Design: We performed retrospective and cross‐sectional study of endocrine and cognitive function in TBI in 61 patients (aged 37.7 ± 1.7 years) of both sexes (44 m,17 f), at least 1 year after TBI (3.9 ± 0.6 years). Serum insulin‐like growth factor 1 (IGF‐I), thyroxin, thyroid‐stimulating hormone (TSH), follicle‐stimulating hormone (FSH), luteinizing hormone (LH), testosterone (in men), prolactin, and cortisol were measured, and GH secretion was assessed by growth hormone releasing hormone (GHRH) + growth hormone releasing peptide‐6 (GHRP‐6) test. Cognitive function was assessed by using a standard neuropsychological battery. Results: GH deficiency (GHD) and GH insufficiency (GHI) were found in 20 patients (32.8%). After adjustment for confounders [age, body mass index (BMI), education level, time elapsed from TBI], there were no significant differences in results of neuropsychological tests between patients with TBI with GHD, GHI, and normal GH secretion. There were no correlations of neuropsychological variables with stimulated peak GH secretion or IGF‐I level. Conclusions: GHD persists long after the TBI, independently of trauma severity and age at traumatic event. GH secretion is more sensitive to TBI than other pituitary hormones. No evidence is found for an association of cognitive function impairment and somatotropic axis impairment in adult patients tested more than 1 year after the TBI.