naloxone and Adenoma

We report a patient with acromegaly who had severe, intractable headache unrelated to tumor size which dramatically resolved with the somatostatin analog octreotide. The analgesic effects of octreotide were neither related to significant inhibition of growth hormone nor influenced by naloxone. Our data suggest that octreotide should be considered in patients with intractable headache associated with pituitary adenomas. Mechanisms other than tumor size or interaction with the opioid system, such as non-opioid algesic peptide secretion, may be the explanation for severe head pain in some pituitary adenomas.

Topics: Acromegaly; Adenoma; Adult; Growth Hormone; Headache; Humans; Male; Naloxone; Octreotide; Pain, Intractable; Pituitary Neoplasms; Receptors, Opioid

The investigators assessed the effects of the opioid antagonist naloxone on anterior pituitary hormone release in hyperprolactinemic females with pituitary microadenoma (n = 6) and macroadenoma (n = 7). In those with microadenoma, intravenous bolus injection of naloxone significantly increased serum luteinizing hormone (LH) concentrations but had no significant effect on serum prolactin (PRL), follicle-stimulating hormone, and thyroid-stimulating hormone concentrations. In patients with macroadenoma, naloxone significantly decreased serum LH and serum PRL concentrations. The response of LH to naloxone differed considerably between the two groups of patients. The results suggest that LH and PRL secretion is influenced by changes in endogenous opiates and in gonadotropin-releasing hormone and PRL inhibitory factor due to hypothalamic dysfunction.

Topics: Adenoma; Adolescent; Adult; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Naloxone; Pituitary Neoplasms; Prolactin; Thyrotropin

In order to elucidate whether pituitary peptides other than ACTH which are derived from the proopiomelanocortin (POMC) are involved for aldosterone secretion in primary aldosteronism, we administered ovine corticotropin releasing factor (CRF), beta-endorphin and naloxone to seven patients with aldosterone producing adenoma. One hundred micrograms of CRF produced an augmented aldosterone response in patients with aldosteronism, while 500 micrograms of beta-endorphin infusion failed to cause any significant changes in neither normal subjects nor patients. An opioid antagonist, naloxone (10 mg, iv) produced no noticeable change in plasma aldosterone in normal subjects, while it caused a slight increase in patients with primary aldosteronism. Plasma cortisol increased to a similar degree in response to CRF and naloxone in normal subjects and patients. In three patients with isolated ACTH deficiency, neither aldosterone nor cortisol responded to these stimuli. The present results indicate that POMC-derived pituitary peptides other than ACTH are unlikely to participate in the aldosterone secretion in normal subjects or in patients with primary aldosteronism.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Adult; Aldosterone; beta-Endorphin; Corticotropin-Releasing Hormone; Female; Humans; Hydrocortisone; Hyperaldosteronism; Injections, Intravenous; Male; Middle Aged; Naloxone; Pituitary Hormones; Pro-Opiomelanocortin

Endogenous opioids have been suggested to play a pathogenetic role in idiopathic hyperaldosteronism (IHA). To investigate this issue, the opiate antagonist naloxone was administered to 8 normals and 14 patients with primary aldosteronism, 6 with an aldosterone-producing adenoma (APA) and 8 with IHA. In normals, APA, and IHA, naloxone caused a significant increase in plasma cortisol and no change in ACTH, renin activity (PRA), and aldosterone levels. All subjects were retested after dexamethasone 2 mg. ACTH and cortisol were reduced and PRA was unchanged without modifications after naloxone. Baseline aldosterone was unaltered in all. While normals and APA failed to show any aldosterone response to naloxone under dexamethasone, IHA patients demonstrated a significant decrease. beta-Endorphin concentrations were in the normal range before and after dexamethasone. In normals as well as in APA and IHA, naloxone may act directly on the adrenal cortex increasing zona fasciculata responsiveness to physiological levels of ACTH. The decrease of aldosterone induced by naloxone in IHA under dexamethasone may be due to an intra-adrenal opioid control of zona glomerulosa in this disorder.

Topics: Adenoma; Adrenal Cortex; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Aldosterone; Dexamethasone; Humans; Hydrocortisone; Hyperaldosteronism; Naloxone; Renin

Excess production of proopiomelanocortin (POMC)-derived peptides with aldosterone-stimulating activity has been suggested to play a pathogenetic role in idiopathic hyperaldosteronism (IHA). To further investigate this issue, the opiate receptor antagonist naloxone was administered to 14 patients with primary aldosteronism, 6 with an aldosterone-producing adenoma (APA) and 8 with IHA. Clinical and hormonal effects of iv administration of naloxone (10 mg as a bolus) were compared with those obtained in 8 normal subjects. In normals as well as in APA and IHA patients, naloxone caused a significant increase in plasma cortisol, and no change in ACTH, plasma renin activity (PRA) and aldosterone levels. All subjects were retested after 2 mg dexamethasone. ACTH and cortisol were reduced and PRA was unchanged in all groups, without modifications after naloxone. Baseline aldosterone showed no significant changes in all groups. While normal subjects and APA failed to show any aldosterone response to naloxone after dexamethasone, IHA patients demonstrated a significant decrease. beta-endorphin concentrations were in the normal range before and after dexamethasone. In conclusion, naloxone may have a direct action upon adrenal zona fasciculata increasing the cortisol responsiveness to physiological levels of ACTH in either normals or APA and IHA patients. The decrease of aldosterone induced by naloxone in IHA may be due to an intraadrenal opioid control of zona glomerulosa in this disorder.

Topics: Adenoma; Adrenal Cortex; Adrenal Gland Neoplasms; Adult; beta-Endorphin; Dexamethasone; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Naloxone

The cause of the amenorrhea that occurs in patients with hyperprolactinemia is unknown. The involvement of endogenous opioid peptides in the inhibition of GnRH release as a central factor leading to the hypogonadotropic state has been recently described. This study analyzed the LH response to opiate receptor blockade by naloxone (4 mg, iv) in groups of subjects with amenorrhea due to hyperprolactinemia of different etiologies. Patients presenting with a PRL-secreting pituitary adenoma (n = 7), idiopathic hyperprolactinemia (n = 9), or hyperprolactinemia during pharmacological treatment for schizophrenia (n = 5) were studied. Furthermore, to evaluate whether high circulating PRL levels influence the activity of the opioid system after the menopause, a group of seven postmenopausal subjects was tested before and 1 week after the administration of metoclopramide (10 mg, three times a day), a dopamine receptor antagonist. Normal premenopausal women (n = 6) served as controls. Naloxone significantly increased plasma LH levels in both prolactinoma and idiopathic hyperprolactinemic patients (P less than 0.01 vs. basal and placebo). In neither of those groups was a significant correlation found between the plasma LH response to naloxone and basal plasma PRL levels. In contrast to pathological hyperprolactinemia, blockade of opiate receptors did not significantly change LH secretion in either amenorrheic women with pharmacologically induced hyperprolactinemia or postmenopausal women. These results suggest that the effect of hyperprolactinemia on opioid modulation of LH secretion is related to the nature of the hyperprolactinemic state, supporting the existence of increased opioid inhibition of LH levels in pathological hyperprolactinemia.

Topics: Adenoma; Adult; Amenorrhea; Antipsychotic Agents; Dopamine Antagonists; Endorphins; Female; Humans; Hyperprolactinemia; Iatrogenic Disease; Luteinizing Hormone; Menopause; Metoclopramide; Naloxone; Pituitary Neoplasms; Schizophrenia

Endogenous opiate peptides are considered to inhibit LH secretion via a dopaminergic mechanism, and increased opioid inhibition of LH secretion has been found in some hyperprolactinemic women with a pituitary microadenoma. To assess the role of endogenous dopaminergic tone in the opioid regulation of LH secretion in such patients, LH responses to an opioid antagonist (naloxone) and a dopamine antagonist (metoclopramide) were determined in 11 women with a prolactinoma. Neither naloxone nor metoclopramide administration induced any change in serum LH levels in normal women during the early follicular phase. In contrast, 7 of the 11 hyperprolactinemic women responded to both antagonists with a significant increase in LH levels. The parallelism in the LH responses to both antagonists in these hyperprolactinemic patients lends further support to a functional link between opioid and dopamine regulation of LH secretion.

Topics: Adenoma; Adult; Dopamine Antagonists; Female; Humans; Hyperprolactinemia; Luteinizing Hormone; Metoclopramide; Naloxone; Pituitary Neoplasms; Prolactin

With the aim of examining central opioid influences on the control of luteinizing hormone (LH) secretion, we evaluated the LH response to naloxone, an opioid receptor antagonist, in patients affected by normo-, hyper-, and hypogonadotropic amenorrhea, polycystic ovarian disease and hyperprolactinemia. The results indicate that opioid influences are altered in well-defined pathologic conditions (hyperprolactinemia, obesity), in addition to being modified by gonadal steroids.

Topics: Adenoma; Adolescent; Adult; Amenorrhea; Body Weight; Female; Gonadotropin-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Menstruation Disturbances; Naloxone; Oligomenorrhea; Ovary; Pituitary Neoplasms; Prolactin

Systemic administration of the enkephalin analog FK 33.824 was previously shown to inhibit ACTH secretion in man. In this study, the direct action of this analog on cortisol release was studied. The enkephalin analog (1 microM and 10 microM) did not influence basal or ACTH-stimulated cortisol production by cultured isolated adrenocortical cells prepared from the hyperplastic adrenal glands from three patients with Cushing's disease. Naloxone (10 microM) had also no direct effect on cortisol release. It is concluded that the met-enkephalin analog used in this study and naloxone do affect the hypothalamo-pituitary-adrenal axis via a central effect.

Topics: Adenoma; Adrenal Cortex; Adrenal Gland Neoplasms; Cells, Cultured; Cosyntropin; Cushing Syndrome; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Enkephalin, Methionine; Growth Hormone-Releasing Hormone; Hormones; Humans; Hydrocortisone; Naloxone

ACTH excretion by cultured nonenzymatically dispersed pituitary tumor cells from a patient with Nelson's syndrome was studied. Hormone release was suppressed by 74 +/- 6% by the addition of 1 microM of the met-enkephalin analog FK 33824, while naloxone (1 microM) stimulated ACTH release by 70 +/- 5%. Somatostatin, dexamethasone, bromocriptine, and cyproheptadine in a concentration of 1 microM each inhibited ACTH release by 25 +/- 2%, 35 +/- 2%, 52 +/- 2%, and 61 +/- 4%, respectively, while lysine vasopressin (0.1 microM) and dibutyryl cAMP (5 mM) stimulated ACTH release by 112 +/- 8% and 220 +/- 4%, respectively. In conclusion, it was shown that the stimuli mentioned above directly affect ACTH secretion by the pituitary tumor cells. The inhibitory action of the met-enkephalin analog and the stimulatory action of naloxone on ACTH secretion make the presence of opiate receptors on this type of tumor likely.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Cells, Cultured; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Enkephalins; Female; Hormones; Humans; Naloxone; Nelson Syndrome; Pituitary Neoplasms

This study assessed the effect of the opiate antagonist naloxone on anterior pituitary hormone release in normal subjects and patients with disturbances of the gonadotropic axis. Intravenous bolus injections of naloxone resulted in a rise of plasma LH, but had no significant effect on plasma levels of FSH or PRL. It also failed to alter the LH, FSH, or TSH response to LRF and TRH, although it did augment the PRL response to TRH. Slow iv infusion of naloxone resulted in increased plasma LH and FSH concentrations in both normal subjects and patients with hyperprolactinemia. The rise of LH correlated with the mean basal LH concentrations; a low basal level only responded to naloxone with a small increase in circulating LH concentration and vice versa. This relationship of the response of LH to the resting levels also held in several other pathological states in which there were marked differences of androgen and estrogen status as well as up to a 100-fold variation in basal LH concentrations. It is concluded that LH is under inhibitory opioid control both in normal subjects and in widely differing pathological states of the gonadotropic axis.

Topics: Adenoma; Adult; Craniopharyngioma; Female; Follicle Stimulating Hormone; Humans; Hypothyroidism; Luteinizing Hormone; Male; Naloxone; Pituitary Neoplasms; Polycystic Ovary Syndrome; Prolactin

Topics: Adenoma; Adult; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Kinetics; Luteinizing Hormone; Naloxone; Pituitary Neoplasms; Prolactin

The inhibiting role of endogenous opioid peptides on gonadotropin secretion was evaluated by the infusion of an opioid receptor antagonist, naloxone (1.6 mg/h for 4 h), in 10 hyperprolactinemic patients with pituitary microadenoma (prolactinoma) and 5 normal women during the early follicular phase of the cycle. In normal women, naloxone infusion induced no significant changes in any of the three pituitary hormones measured. Six prolactinoma patients with low normal levels of basal LH [10.0 +/- 1.0 mIU/ml +/- SE)] responded to naloxone infusion with an increment of circulating LH in the form of an amplified pulsatile pattern of release, which lasted for at least 2 h after the infusion. The other 4 patients with prepubertal levels of LH (4.9 +/- 0.8 mIU/ml) exhibited no LH response to naloxone. There were no significant changes in FSH or PRL levels in either group of patients. These findings suggest that an increased endogenous opioid inhibition of LH release occurs in patients with PRL-producing microadenoma.

Topics: Adenoma; Adult; Endorphins; Female; Follicle Stimulating Hormone; Follicular Phase; Humans; Luteinizing Hormone; Naloxone; Pituitary Neoplasms; Prolactin