Serum Prolactin and Macroprolactin Levels among Outpatients with Major Depressive Disorder Following the Administration of Selective Serotonin-Reuptake Inhibitors: A Cross-Sectional Pilot Study

Clinical trials evaluating the rate of short-term selective serotonin-reuptake inhibitor (SSRI)-induced hyperprolactinemia have produced conflicting results. Thus, the aim of this study was to clarify whether SSRI therapy can induce hyperprolactinemia and macroprolactinemia. Fifty-five patients with major depressive disorder (MDD) were enrolled in this study. Serum prolactin and macroprolactin levels were measured at a single time point (i.e., in a cross-sectional design). All patients had received SSRI monotherapy (escitalopram, paroxetine, or sertraline) for a mean of 14.75 months. Their mean prolactin level was 15.26 ng/ml. The prevalence of patients with hyperprolactinemia was 10.9% for 6/55, while that of patients with macroprolactinemia was 3.6% for 2/55. The mean prolactin levels were 51.36 and 10.84 ng/ml among those with hyperprolactinemia and a normal prolactin level, respectively. The prolactin level and prevalence of hyperprolactinemia did not differ significantly within each SSRI group. Correlation analysis revealed that there was no correlation between the dosage of each SSRI and prolactin level. These findings suggest that SSRI therapy can induce hyperprolactinemia in patients with MDD. Clinicians should measure and monitor serum prolactin levels, even when both SSRIs and antipsychotics are administered.     

Surgical treatment of prolactinomas. Short- and long-term results, prognostic factors

All 347 patients surgically treated for a prolactinoma from January 1, 1976 to December 31, 1982, in the neurosurgical ward of Foch Hospital, were retrospectively studied. The frequency of postoperative normalisation of plasma prolactin (PRL) depends on prolactinoma size, preoperative PRL level, duration of first clinical symptom, previous oestroprogestative contraception, and adenoma necrosis. Postoperative PRL values were normalized in 75% of small prolactinomas (grade 0, 1 or 2) with preoperative PRL values less than 200 ng/ml, and clinical duration less than 5 years (n = 102). There was no operative death and minor morbidity (2.7%). Among the 96 patients with postoperative PRL normalisation, operated between 1976 and 1979, 70 were followed up for an average time of 4.4 +/- 0.2 years. 17% of patients had hyperprolactinemia recurrence with a delay of 1.5 +/- 0.4 years. Postoperative PRL levels near the upper normal limit, and weak PRL response to TRH tests were found to be unfavourable prognostic factors for hyperprolactinemia recurrence. Pregnancy did not increase the risk of recurrence, but could reflect genuine long-lasting remission. Selective adenomectomy remains an interesting treatment for prolactinoma, particularly if the adenoma is small, recent and with PRL moderately increased. The frequency of postoperative PRL normalisation after surgery is less than with bromocriptine, but surgery is the only treatment able to achieve a definitive cure with a low iatrogenic risk.     

Role of vasoactive intestinal polypeptide (VIP) in regulating the pituitary function in man

Intramuscular injection of synthetic VIP (200 micrograms) resulted in a rapid increase in plasma prolactin (PRL) concentrations in normal women, which was accompanied by the 4- to 7-fold increase in plasma VIP levels. Mean (+/- SE) peak values of plasma PRL obtained 15 min after the injection of VIP were higher than those of saline control (28.1 +/- 6.7 ng/ml vs. 11.4 +/- 1.6 ng/ml, p less than 0.05). Plasma growth hormone (GH) and cortisol levels were not affected by VIP in normal subjects. VIP injection raised plasma PRL levels (greater than 120% of the basal value) in all of 5 patients with prolactinoma. In 3 of 8 acromegalic patients, plasma GH was increased (greater than 150% of the basal value) by VIP injection. In the in vitro experiments, VIP (10(-8), 10(-7) and 10(-6) M) stimulated PRL release in a dose-related manner from the superfused pituitary adenoma cells obtained from two patients with prolactinoma. VIP-induced GH release from the superfused pituitary adenoma cells was also shown in 5 out of 6 acromegalic patients. VIP concentrations in the CSF were increased in most patients with hyperprolactinemia and a few cases with acromegaly. These findings indicate that VIP may play a role in regulating PRL secretion in man and may affect GH secretion from pituitary adenoma in acromegaly.     

Absence of suppressive effect of somatostatin on prolactin levels in patients with hyperprolactinemia

The effect of somatostatin (SRIF: 10 micrograms/min during 120 min) on serum prolactin (PRL) levels was studied in eleven patients with hyperprolactinemia of varying causes: 2 patients with acromegaly; 2 with primary hypothyroidism; 4 with prolactinoma and 3 with drug (sulpiride) induced hyperprolactinemia. During SRIF infusion, no significant change in PRL levels was observed in any of the 4 groups studied except in one female patient with a prolactinoma. The biological activity of SRIF was demonstrated by the significant inhibition (P less than 0.05) of insulin levels seen in all 11 patients (52% fall in relation to basal) without simultaneous modification of glycemia. These data suggest that SRIF does not decrease PRL secretion in most patients with hyperprolactinemia.     

A retrospective hormonal and immunohistochemical evaluation of 47 acromegalic patients: prognostic value of preoperative plasma prolactin.

This study was performed to investigate the correlations between preoperative prolactin (PRL) plasma values, immunohistochemical picture and the clinical course in growth hormone (GH) secreting pituitary adenomas. In 47 patients (19 males and 28 females; mean age 40 years; range 13 - 70 years), we measured GH, IGF-1 and prolactin plasma values both before and after transsphenoidal surgery, and basal IGF-1 and GH after an oral glucose tolerance test (OGTT) during four years of follow-up. We considered those patients as "controlled" who presented an undetectable growth hormone after OGTT (GH < 1 microg/l), IGF-I plasma values in the normal range, matched for age and sex, and no clinical activity or neuroradiological recurrence after a four-year follow-up. We considered patients as "poorly controlled" who still showed elevated GH and IGF-I plasma levels, uninhibited GH after OGTT (GH > 1 microg/l), presence of clinical activity and/or radiological signs of adenoma recurrence, even if a reduction of tumor size had been demonstrated. RESULTS: Controlled patients (n = 22) exhibited mean preoperative PRL levels (+/- SEM) lower than the group of poorly controlled (n = 25) ones (21.40 +/- 5.51 vs. 38.44 +/- 5.16 microg/l; p < 0.03). From 3 to 12 months after surgery, postoperative PRL levels were also lower in the controlled patients compared to the poorly controlled ones (8.31 +/- 1.20 vs. 25.32 +/- 3.20 microg/l; p < 0.0001). Eighty percent (20/25) of poorly controlled patients showed both PRL and GH positivity after immunostaining. Only 3/22 (13.6 %) of controlled patients showed the same double positivity. In conclusion, preoperative hyperprolactinemia identifies a group of acromegalic patients at elevated risk of disease persistence after surgery. We hypothesize that most of these high-risk patients may have more aggressive mixed GH-PRL secreting adenomas.     

Paradoxical prolactin response to growth hormone-releasing hormone in a patient with hyperprolactinemia and empty sella.

In a 30-year-old woman with amenorrhea due to hyperprolactinemia, serum PRL increased to twice the basal amount in response to growth hormone-releasing hormone (GHRH). Roentgenological studies revealed no pituitary adenoma but empty sella. Bromocriptine therapy normalized serum PRL and made the paradoxical response to GHRH disappear. The paradoxical response did not occur in any of eight other patients with hyperprolactinemia due to prolactinoma. Although this case is rare, GHRH stimulates PRL as well as GH release remarkably in some cases with hyperprolactinemia without a GH-producing tumor.     

Hyperprolactinemia and sexual function in men

Male hyperprolactinemia (HPRL) is known to induce different types of sexual dysfunctions. In order to determine the incidence of HPRL among patients referred for sexual dysfunction, serum prolactin (PRL) was assayed in 1053 clinically idiopathic cases. Among 850 cases complaining of erectile impotence, 10 with marked HPRL (1.1%, PRL above 35 ng/ml) were found, of whom 6 cases were associated with a pituitary adenoma. 17 mild HPRL (2%, PRL 20-35 ng/ml) were also found. Among 124 cases with premature ejaculation, 13 (10%) mild HPRL were found. Serum PRL was normal in 51 cases complaining of an ejaculation without orgasm, and 27 patients exclusively complaining of reduced sexual desire. Our results lay stress on the fact that serum PRL must be assayed in every case of clinically idiopathic erectile impotence. Indeed, 5 of the 10 marked HPRL patients would have been misdiagnosed if we had only assayed this hormone when plasma testosterone was below the normal range. Moreover, in order to shed some light on the mechanisms by which HPRL disturbs male sexual function, the sexual behaviour of 17 markedly HPRL males was compared to their serum levels of PRL and testosterone, first before treatment, then at regular intervals during treatment. Our main conclusion is that impotence cannot be totally explained by a decrease in plasma testosterone, because this steroid hormone was within the normal range 7 of the 16 impotent patients. Moreover, when serum PRL was lowered by bromocriptine, 6 patients recovered their potency before plasma testosterone clearly increased, and in 3 of those patients before it reached the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prolactin secretion in patients with idiopathic diabetes insipidus.

It has been demonstrated that hyperprolactinemia is sometimes present even in patients with idiopathic diabetes insipidus (DI). In this study, we examined the responses of serum prolactin (PRL) to hypertonic saline infusion and TRH injection in 11 patients with idiopathic DI diagnosed by clinical examinations. Serum sodium in these patients (147.5 +/- 3.2 mEq/L) was significantly higher at baseline than in normal subjects (139.7 +/- 2.4 mEq/L). The plasma arginine vasopressin (AVP) level was significantly lower in DI (0.42 +/- 0.24 pg/ml) at baseline than in normal subjects (2.53 +/- 1.03 pg/ml). However, the serum PRL level in both groups did not differ significantly except in one patient with idiopathic DI (35.6 ng/ml). There was no significant correlation between the basal serum sodium and basal serum PRL in either group. After an infusion of hypertonic saline, the serum sodium level gradually increased to 155.6 +/- 3.4 mEq/L in DI and to 146.5 +/- 4.3 mEq/L in the normal subjects. However, this increase did not affect PRL secretion in either group. PRL response to TRH was essentially normal in all patients with idiopathic DI. These results indicate that the secretion of PRL is not generally affected by chronic mild hypernatremic hypovolemia in the patients with idiopathic DI.     

Prolactin release in polycystic ovarian syndrome

To evaluate the prevalence of hyperprolactinemia in patients with polycystic ovarian syndrome (PCO), 72 patients with oligo- or anovulation were studied. All of the patients had persisting elevated LH (greater than 25 mIU/ml), normal FSH, high LH/FSH ratio (greater than 2.5), and exaggerated LH responses to LHRH. Mean testosterone and androstenedione concentrations were appreciably increased in these patients. Out of 171 samples for prolactin (PRL) determination from these 72 patients, only 5 patients had a PRL value above 30 ng/ml during the first sampling. The next sampling from these same 5 women disclosed that they were transiently hyperprolactinemic because the next samples showed a normal PRL value. To further investigate the PRL secretory capacity 500 micrograms of TRH and 10 mg of metoclopramide (MCP) were administered to these 72 and 44 patients, respectively. The PRL response to MCP was significantly blunted in these patients compared to normal women while the PRL response to TRH in these patients was not indistinguishable from that in normal women. These results indicate that the true prevalence rate of hyperprolactinemia in PCO may be low rather than high and the association of hyperprolactinemia with PCO may be coincidental rather than a pathogenically related phenomenon.     

Disturbed prolactin responses to dopamine-related substances in patients with acromegaly and hyperprolactinemia

We undertook this study, because conflicting data were reported about the dopaminergic regulation of prolactin (PRL) secretion in patients with acromegaly and hyperprolactinemia. In order to clarify the dopaminergic regulation of PRL secretion in patients with acromegaly and hyperprolactinemia, the effects of nomifensine, a central dopamine agonist, FK 33-824, a centrally antidopaminergically acting agent, and domperidone, a peripheral dopamine antagonist, on plasma PRL in these patients were studied. The results were compared with those observed in normal subjects and hyperprolactinemic patients, with or without a pituitary tumor. Nomifensine did not lower the PRL levels and FK 33-824 did not raise the PRL levels in acromegalic patients. In hyperprolactinemic patients, nomifensine did not lower the PRL levels and FK 33-824 failed to raise the PRL levels. Domperidone did not increase PRL in about a third of acromegalic patients, while TRH increased PRL in the all normoprolactinemic acromegalic patients. These results suggest that in acromegalic patients there may be a disturbance in dopamine related neurotransmission and that such disorders also seem to be present in patients with hyperprolactinemia, with or without a pituitary tumor.     

Relation between surgery-induced prolactin increase and the menstrual cycle phase at time of surgery in premenopausal breast cancer

It has been suggested that both the menstrual cycle phase and postoperative changes in prolactin (PRL) secretion at the time of surgery may influence the prognosis of breast cancer. The present study was carried out to evaluate the relation between menstrual cycle period and surgery-induced PRL variations. We evaluated 32 premenopausal women with operable breast carcinoma; 17 were in perimenstrual phase (days 1-6 and 21-28) and 15 were in the mid-cycle (days 7-20) period at the time of surgery. To investigate serum levels of PRL, venous blood samples were collected before and 7 days after surgery. Postoperative hyperprolactinemia occurred in 17/32 patients and it was statistically more frequent in patients surgically treated during the perimenstrual phase than in the mid-cycle phase (12/17 vs 5/15; p less than 0.05), while no other parameter (including axillary node and estrogen receptor status) showed a significant influence on hyperprolactinemia rate. The results suggest that in premenopausal breast cancer patients surgery-induced hyperprolactinemia may be influenced by the menstrual cycle phase at the time of surgery.     

Catecholamines and pituitary function. VI. Effect of different dopamine doses on TRH-induced prolactin release in women with pathological hyperprolactinemia

The present study was designed to examine the effect of low-dose dopamine (DA) infusion rates (0.02 and 0.1 microgram/kg X min) on both basal and TRH-stimulated prolactin release in normal and hyperprolactinemic individuals. Sixteen normally menstruating women in the early follicular phase of a cycle and 23 hyperprolactinemic patients were studied. 0.1 microgram/kg X min DA was infused in 8 normal women and 15 patients with pathological hyperprolactinemia, while 8 normal controls and 8 patients received 0.02 microgram/kg X min DA TRH (200 micrograms, i.v.) was administered alone and at the 180th min of the 5-hour DA infusion in all controls and patients. A significant reduction in serum PRL levels, which was similar in normal women (-59.5 +/- 4.0%, mean +/- SE) and hyperprolactinemic patients (-48.2 +/- 5.5) was observed in response to 0.1 microgram/kg X min DA. In normal cycling women DA infusion significantly (P less than 0.02) reduced the PRL response to TRH with respect to the basal TRH test (delta PRL 45.0 +/- 7.0 vs. 77.9 +/- 15.4 ng/ml). On the contrary, the PRL response to TRH was significantly higher during 0.1 microgram/kg X min DA than in basal conditions in hyperprolactinemic patients, both in absolute (delta PRL 91.8 +/- 17.6 vs. 38.4 +/- 6.8, P less than 0.03) and per cent (198.5 +/- 67.6 vs. 32.1 +/- 7.5, P less than 0.02) values. A normal PRL response to TRH, arbitrarily defined as an increase greater than 100% of baseline, was restored in 11 out of 15 previously unresponsive hyperprolactinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Catecholamines and pituitary function. III. Restoration of the prolactin response to thyrotropin-releasing hormone by low-dose dopamine infusion in women with pathological hyperprolactinemia

Previous studies in Rhesus monkeys have demonstrated that a dopamine (DA) infusion rate of 0.1 microgram/kg X min induces peripheral DA levels similar to those measured in hypophysial stalk blood and normalizes serum prolactin (PRL) levels in stalk-transected animals. We therefore examined the effect of such DA infusion rate on basal and thyrotropin-releasing hormone (TRH)-stimulated PRL secretion in both normal cycling women and women with pathological hyperprolactinemia. 0.1 microgram/kg X min DA infusion fully normalized PRL serum levels in 8 normal cycling women whose endogenous catecholamine synthesis had been inhibited by alpha-methyl-p-tyrosine (AMPT) pretreatment. Furthermore, DA significantly reduced, but did not abolish, the rise in serum PRL concentrations induced by both acute 500 mg AMPT administration and 200 micrograms intravenous TRH injection in normal women. A significant reduction in serum PRL levels in response to 0.1 microgram/kg X min DA, similar to that observed in normal cycling women when expressed as a percentage of baseline PRL, was documented in 13 amenorrheic patients with TRH-unresponsive pathological hyperprolactinemia. However, a marked rise was observed in the serum PRL of the same patients when TRH was administered during the course of a 0.1-microgram/kg X min DA infusion. The PRL response to TRH was significantly higher during DA than in basal conditions in hyperprolactinemic patients, irrespective of whether this was expressed as an absolute increase (delta PRL 94.4 +/- 14.2 vs. 17.8 +/- 14.1 ng/ml, p less than 0.002) or a percent increase (delta% PRL 155.4 +/- 18.9 vs. 17.9 +/- 7.1, p less than 0.0005), and there was a significant linear correlation between the PRL decrements induced by DA and the subsequent PRL responses to TRH. These data would seem to show that the 0.1-microgram/kg X min DA infusion rate reduces basal PRL secretion and blunts, but does not abolish, the PRL response to both TRH and acute AMPT administration. The strong reduction in PRL secretion and the restoration of the PRL response to TRH by 0.1 microgram/kg X min DA infusion in high majority of hyperprolactinemic patients, seem to indicate that both PRL hypersecretion and abnormal PRL response to TRH in women with pathological hyperprolactinemia are due to a relative DA deficiency at the DA receptor site of the pituitary lactotrophs.     

Effect of growth hormone-releasing factor on plasma growth hormone, prolactin and somatomedin C in hypopituitary and short normal children

We studied the effect of a single intravenous bolus of 0.5 microgram/kg of growth hormone-releasing factor (GRF) on plasma GH, prolactin (PRL) and somatomedin C (SMC) in 12 short normal children and 24 patients with severe GH deficiency (GHD), i.e. GH less than 5 ng/ml after insulin and glucagon tolerance tests. GRF elicited an increase in plasma GH in both short normal and GHD children. The mean GH peak was lower in the GHD than in the short normal children (8.2 +/- 2.5 vs. 39.2 +/- 5.1 ng/ml, p less than 0.001). In the GHD patients (but not in the short normals) there was a negative correlation between bone age and peak GH after GRF (r = -0.58, p less than 0.005); GH peaks within the normal range were seen in 5 out of 8 GHD children with a bone age less than 5 years. In the short normal children, GRF had no effect on plasma PRL, which decreased continuously between 8.30 and 11 a.m. (from 206 +/- 22 to 86 +/- 10 microU/ml, p less than 0.005), a reflection of its circadian rhythm. In the majority of the GHD patients, PRL levels were higher than in the short normal children but had the same circadian rhythm, except that a slight increase in PRL was observed 15 min after GRF; this increase in PRL was seen both in children with isolated GHD and in those with multiple hormone deficiencies; it did occur in some GHD patients who had no GH response to GRF. Serum SMC did not change 24 h after GRF in the short normal children. We conclude that: (1) in short normal children: (a) the mean GH response to a single intravenous bolus of 0.5 microgram/kg of GRF is similar to that reported in young adults and (b) GRF has no effect on PRL secretion; (2) in GHD patients: (a) normal GH responses to GRF are seen in patients with a bone age less than 5 years and establish the integrity of the somatotrophs in those cases; (b) the GH responsiveness to GRF decreases with age, which probably reflects the duration of endogenous GRF deficiency, and (c) although the PRL response to GRF is heterogeneous, it does in some patients provide additional evidence of responsive pituitary tissue.     

Delayed puberty and hypoplastic uterus associated with hyperprolactinemia: successful treatment with bromocriptine

A 15-year-old girl referred because of primary amenorrhea was found to have a hypoplastic uterus and persistent hyperprolactinemia (72-110 ng/ml). The gonadotrophin-dependent pubertal signs, i.e. breast and vulvar development, were significantly retarded (Tanner stage 2-3) while sexual hair was well developed; bone age was 13 years. The endocrinological evaluation revealed gonadotrophin secretion (LH-basal: 0.85-1.25; peak after LH-RH: 10.4 mIU/ml; FSH-basal: 1.63-2.5; peak: 8.2 mIU/ml) and E2 levels (26-68 pg/ml) which were appropriate for Tanner stage 3. The high basal levels of PRL were nonresponsive to either stimulatory (TRH) or inhibitory (nomifensine) agents. CT scan of the brain suggested the presence of a pituitary microadenoma. Following therapy with bromocriptine (2.5 mg/day) plasma PRL levels dropped to normal (5-6.8 ng/ml) with an accompanying catch-up of pubertal development and linear growth and a marked increase in size of the uterus as documented by repeated ultrasonographic examinations. Menarche occurred 5 months after initiation of therapy, followed by regular menses thereafter. Repeated CT scan of the brain showed a decrease in the density and size of the still persisting lesion. This patient demonstrates that hyperprolactinemia can cause delayed puberty with a particular inhibitory effect on uterine growth and development.     

Catecholamines and pituitary function. VII: Effects of acute and chronic dopamine-receptor blockade on pituitary response to TRH-GNRH in normal women and in patients with hyperprolactinemic amenorrhea

To investigate whether an enhanced dopamine (DA) inhibition on pituitary thyrotrophs and gonadotrophs may account for the abnormal TSH and LH dynamics in pathological hyperprolactinemia, we examined the effect of an acute lysis of the putative DA overinhibition, as obtained with continuous domperidone (DOM) infusion, on both basal and TRH-GnRH stimulated PRL, TSH and LH release in both normal cycling women and patients with pathological hyperprolactinemia. The effect of TRH-GnRH administration was also examined in women with DA-antagonist induced hyperprolactinemia, in order to evaluate the effect of a chronic lack of the physiological DA inhibition on pituitary hormone dynamics. Patients with both pathological and DA-antagonist induced hyperprolactinemia displayed an evident TSH and LH hyper-responsiveness to TRH-GnRH. The PRL response was reduced in the former but enhanced in the latter group. Domperidone infusion resulted in a marked increase in serum PRL levels in normal cycling women, but not in patients with pathological hyperprolactinemia. The abolition of the putative DA-overinhibition at the pituitary level with DOM infusion in patients with pathological hyperprolactinemia was followed by a slight increase in basal TSH output but did not modify the TSH and LH hyperresponsiveness to TRH-GnRH. The similarities in TSH and LH dynamics between patients with pathological and DA-antagonist induced hyperprolactinemia and the ineffectiveness of DOM infusion in modifying the TSH and LH hyper-responses to TRH-GnRH in the former group, seem to exclude the widely accepted idea that endogenous DA overactivity is responsible for the abnormal thyrotroph and lactotroph dynamics in women with hyperprolactinemic amenorrhea.     

Galactorrhea in subclinical hypothyroidism

Galactorrhea was found in 5 patients with subclinical hypothyroidism. The galactorrhea consisted of the discharge of a few drops of milk only under pressure. Serum T4 was in the lower level of the normal range, but serum T3 was normal (T4: 6.3 +/- 1.2 micrograms/dl, T3: 113 +/- 7 ng/dl). Basal serum TSH and PRL were slightly increased only in 2 and 1 cases, respectively. The PRL responses to TRH stimulation were exaggerated in all cases, although the basal levels were normal. An enlarged pituitary gland was observed in 1 patient by means of CT scanning. All patients were treated by T4 replacement. In serial TRH tests during the T4 replacement therapy, the PRL response was still increased even when the TSH response was normalized. Galactorrhea disappeared when the patients were treated with an increased dose of T4 (150-200 micrograms/day). Recurrence of galactorrhea was not observed even though replacement dose of T4 was later decreased to 100 micrograms/day in 4 cases. In patients with galactorrhea of unknown origin, subclinical hypothyroidism should not be ruled out even when their serum T4, T3, TSH and PRL are in the normal range. The TRH stimulation test is necessary to detect an exaggerated PRL response, as the cause of the galactorrhea. To differentiate this from pituitary microadenoma, observation of the effects of T4 replacement therapy on galactorrhea is essential.     

Increase of circulating levels of thymulin in hyperprolactinemia and acromegaly

The production of thymulin by the thymic epithelium is under complex control involving the endocrine system. Experimental models have suggested that prolactin (PRL) and growth hormone (GH) participate in this regulation but this has not been documented in humans. Using a bioassay we measured circulating thymulin levels in patients with hyperprolactinemia (n = 21), acromegaly (n = 15), or both (n = 6). Thymulin was elevated in these three groups of patients compared with normal subjects or with patients with pituitary disease but no excess in PRL or GH. Contrasting with observations in control groups, thymulin did not decrease as a function of age in patients. No correlation between thymulin and PRL or GH levels was observed while thymulin and insulin-like growth factor 1 levels were correlated. A new radioimmunoassay used in some patients for thymulin determination yielded similar results. Overall these data demonstrate that PRL and GH are involved in the hormonal control of thymulin production by the thymic epithelium in the human.     

Short-Term Decline in Prolactin Concentrations Can Predict Future Prolactin Normalization,Tumor Shrinkage,and Time to Remission in Men with Macroprolactinomas

Objective: To identify early follow-up measures that will predict the dynamics of prolactin (PRL) decrease and adenoma shrinkage in men harboring macroprolactinomas.Methods: A single-center historical prospective study including a consecutive group of 71 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (PRL >7 times the upper limit of normal &lsqb;ULN]) treated medically with cabergoline. Comparisons of PRL normalization rates were performed according to PRL levels achieved at 6 months, maximal adenoma shrinkage during follow-up, and other patient characteristics. Correlations were analyzed to identify characteristics of PRL suppression dynamics.Results: PRL levels after 6 months of treatment correlated positively with current PRL levels (r = 0.74; P<.001), with time to PRL normalization (r = 0.75; P<.001), and with adenoma diameter following treatment (r = 0.38; P = .01). Adenoma shrinkage depicted by first magnetic resonance imaging on treatment correlated with maximal adenoma shrinkage during follow-up (r = 0.56; P = .006). Five patients had nadir PRL levels ≥3 times the ULN (51 ng/mL) and showed slower response to cabergoline treatment, with consistently higher PRL levels compared with responding patients throughout follow-up (mean 6-month PRL levels, 519 ± 403 ng/mL versus 59 ± 118 ng/mL; P<.001).Conclusion: Six-month PRL level might serve as a surrogate marker for PRL normalization and adenoma shrinkage dynamics among men harboring macroprolactinomas.Abbreviations: CAB = cabergoline MRI = magnetic resonance imaging PRL = prolactin RMC = Rabin Medical Centre ULN = upper limit of normal     

Hormonal regulation of prolactin release by human prolactinoma cells cultured in serum-free conditions

Thyrotropin-releasing hormone (TRH) stimulates the prolactin (PRL) release from normal lactotrophs or tumoral cell line GH3. This effect is not observed in many patients with PRL-secreting tumors. We examined in vitro the PRL response to TRH on cultured human PRL-secreting tumor cells (n = 10) maintained on an extracellular matrix in a minimum medium (DME + insulin, transferrin, selenium). Addition of 10(-8) M TRH to 4 X 10(4) cells produced either no stimulation of PRL release (n = 6) or a mild PRL rise of 32 +/- (SE) 11% (n = 4) when measured 1, 2 and 24 h after TRH addition. When tumor cells were preincubated for 24 h with 5 X 10(-11) M bromocriptine, a 47 +/- 4% inhibition of PRL release was obtained. When TRH (10(-8) M) was added, 24 h after bromocriptine, it produced a 85 +/- 25% increase of PRL release (n = 8). This stimulation of PRL release was evident when measured 1 h after TRH addition and persisted for 48 h. The half maximal stimulatory effect of TRH was 2 X 10(-10) M and the maximal effect was achieved at 10(-9) M TRH. When tumor cells were pretreated with various concentrations of triiodothyronine (T3), the PRL release was inhibited by 50% with 5 X 10(-11) M T3 and by 80% with 10(-9) M T3. Successive addition of TRH (10(-8) M) was unable to stimulate PRL release at any concentration of T3. The addition of 10(-8) M estradiol for up to 16 days either stimulated or had no effect upon the PRL basal release according to the cases. In all cases tested (n = 4), preincubation of the tumor cells with estradiol (10(-8) M) modified the inhibition of PRL release induced by bromocriptine with a half-inhibitory concentration displaced from 3 X 10(-11) M (control) to 3 X 10(-10) M (estradiol). These data demonstrate that the absence of TRH effect observed in some human prolactinomas is not linked to the absence of TRH receptor in such tumor cells. TRH responsiveness is always restored in the presence of dopamine (DA) at appropriate concentration. This TRH/DA interaction seems specific while not observed under T3 inhibition of PRL. Furthermore, estrogens, while presenting a variable stimulatory effect upon basal PRL, antagonize the dopaminergic inhibition of PRL release.