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Effect of pituitary graft-induced hyperprolactinemia on adrenal circadian rhythmicity.

Prolactin is involved in the regulation of several endocrine functions. In this study, the possible influence of hyperprolactinemia on circadian corticosterone secretion has been investigated. Pituitary grafted male and female rats exhibited increased plasma PRL levels at 1000 when compared to sham-operated controls. This increase was only maintained over the 24 h period in grafted female rats but not in males, thus suggesting a different sex dependent modification of the regulatory mechanisms of prolactin. The corticosterone secretion pattern in sham operated male and female rats was similar to those described earlier but was altered by hyperprolactinemia according to the sex of the animal. There was a significant decrease in the total amount of corticosterone secreted in a 24 h period in grafted males as compared to control animals, whereas no significant differences were observed in grafted female rats as compared to controls. Grafted females showed a 4 h delay in the 24 h secretion rhythm as compared to control animals. These data suggest that pituitary transplant induced hyperprolactinemia, directly or through modifications in catecholamine turnover, is able to modify adrenal rhythmicity.

Adrenal Cortex↗

Treatment versus no treatment of transient hyperprolactinemia in patients undergoing intracytoplasmic sperm injection programs.

The aim of our study was to investigate the effect of increased plasma prolactin levels on oocyte and fertilization rate in patients undergoing in vitro fertilization (IVF) intracytoplasmic sperm injection (ICSI) treatment. We identified 135 patients with transient or borderline hyperprolactinemia, measured in the mid and late follicular phase and in the mid-luteal phase of the cycle before ovarian stimulation. The patients were assigned to either the no treatment group (76 patients) or the treatment group (59 patients). The treated group underwent treatment with cabergoline or bromocriptine before ovarian stimulation, until there was a decrease of plasma prolactin levels, and the therapy was continued also during the ICSI programme. Both groups received a gonadotropin-releasing hormone (GnRH) agonist and were subsequently stimulated with follicle-stimulating hormone (FSH) up to the day of human chorionic gonadotropin (hCG) administration. The untreated group needed a significantly lower number of FSH ampoules than the treated group to reach the day of hCG administration (38.1 +/- 18.2 versus 43.9 +/- 28.5; p < 0.05). No correlation was found between the two groups on the peak estradiol level achieved, the progesterone level at hCG administration and the numbers of oocytes retrieved. The number of oocytes with superior morphology (87.9% versus 80.4%; p < 0.05), the fertilization rate (70.8 +/- 28.0 versus 60.8 +/- 28.5; p < 0.03), and the mean number of embryos transferred (3.6 +/- 1.6 versus 3.2 +/- 1.5; p < 0.05) were significantly higher in the patients whose hyperprolactinemia was left untreated. In conclusion, we found that transient hyperprolactinemia is positively associated with ICSI outcome, in particularly with oocyte quality and fertilization rate.

Adult↗

Oral and injectable long-lasting bromocriptine preparations in hyperprolactinemia: comparison of their prolactin lowering activity, tolerability and safety.

Bromocriptine, a D2 receptor agonist, has been widely used in tumoral and non-tumoral hyperprolactinemia, in reducing both plasma prolactin levels and in restoring fertility and/or menses in most patients. In this study a comparison between the injectable repeatable and the oral slow release formulations of bromocriptine (Parlodel LAR and Parlodel SRO) is reported, with respect to their effectiveness, tolerability and safety. Eleven patients with hyperprolactinemia, submitted to both treatments, were studied for a period of 1-24 months. Among the four patients with macroprolactinoma, three reached normoprolactinemia without complaining of side-effects, with both formulations, while the remaining patient became intolerant of the oral form after 1 year, and is presently being treated with the injectable formulation without presenting any side-effects. Among the five patients with microprolactinoma, two patients had a good response to both drugs; two patients did not reach normoprolactinemia with the injectable formulations, but a progressive decrease of prolactin levels was obtained with Parlodel SRO therapy, and the remaining patient was completely intolerant of the oral form without complaining of side-effects with Parlodel LAR. Two patients had non-tumoral hyperprolactinemia: one was intolerant of both drugs and one tolerated both formulations very well. In conclusion, Parlodel LAR and Parlodel SRO are very effective compounds in the medical treatment of hyperprolactinemic syndromes. The availability of these differing formulations improves the medical therapy, allowing a better choice of therapeutic regimen according to the effectiveness of, and tolerability to, the different drug formulations. In this way also, with poorly tolerant patients, it is possible to choose the better tolerated and more effective formulation of the drug.

Adult↗

Risperidone-induced hyperprolactinemia in adolescents: A case series.

OBJECTIVE: To study the effect of risperidone on prolactin levels in 3 adolescent patients. METHOD: This is a case study of 3 adolescent patients with DSM-IV diagnosis of schizophreni-form disorder, major depressive disorder with psychotic features, or chronic undifferentiated schizophrenia who were treated in inpatient and outpatient psychiatric settings with risperidone. Patients developed hyperprolactinemia with clinical symptoms. Risperidone was discontinued gradually over 2 weeks, and patients were treated with other atypical antipsychotics. RESULTS: Prolactin levels returned to normal, and clinical symptoms of hyperprolactinemia resolved in all 3 patients after 2 weeks of tapering and discontinuation of risperidone. CONCLUSION: Hyperprolactinemia can be a troublesome side effect with potentially serious complications. It is being increasingly reported in younger patients treated with risperidone. Recognition and treatment of this condition including switching to a prolactin-sparing agent are important to prevent this complication.

Adolescent↗

Isolated adrenocorticotropic hormone deficiency, thyroid autoimmunity, and transient hyperprolactinemia.

OBJECTIVE: To describe a case of isolated adrenocorticotropic hormone (ACTH) deficiency associated with thyroid autoimmunity, subclinical hypothyroidism, and transient hyperprolactinemia. METHODS: We present a detailed case report, including results of laboratory studies and magnetic resonance imaging, and discuss potential contributing factors in this setting. RESULTS: In a 23-year-old woman with isolated ACTH deficiency accompanied by thyroid autoimmunity (Hashimoto's thyroiditis), subclinical primary hypothyroidism, and hyperprolactinemia, magnetic resonance imaging of the pituitary showed normal findings but dynamic stimulation testing of the pituitary gland indicated an isolated ACTH deficiency with intact growth hormone and gonadotropin secretory reserves. The cortisol response to the short ACTH stimulation test was subnormal. Therapy with prednisolone (5 mg/day) and levothyroxine (100 microg/day) was initiated. Results of thyroid function tests were normalized after 1 month, the prolactin level decreased to normal after 1 year, and titers of thyroid autoantibodies decreased substantially after 1.5 years of treatment. CONCLUSION: The correction of the related glucocorticoid deficiency resulted in resolution of the hyperprolactinemia and a decrease in titers of thyroid autoantibodies.

Adrenocorticotropic Hormone↗

[Hyperprolactinemia: I. Etiopathogenesis, clinical features].

Hyperprolactinemia is a frequent endocrinological disorder, which can develop in women as well as in men. Constant or periodical increase of prolactin concentrations in serum is an evidence of functional or organic damage of the hypothalamic-pituitary axis. Hyperprolactinemia features are complex, and lead toward hypogonadotropic hypogonadism. A shortened luteal phase, infertility and anovulatory cycles are clinical features in women. In men hyperprolactinemia leads to disorder of spermatogenesis (oligospermia, azoospermia) and infertility, too.

Female↗

The prevalence of hyperprolactinemia in patients with primary Sjögren's syndrome.

OBJECTIVE: To assess the prevalence of hyperprolactinemia in 55 patients with primary Sjögren's syndrome (SS), and its clinical significance. METHODS: Concentrations of serum prolactin (PRL) were determined in 55 consecutive patients with primary SS and 110 controls by a fluoroimmunometric assay in a prospective case-control design. RESULTS: The 55 patients with primary SS had higher serum PRL than 110 matching controls (271.5 vs 205.9 mIU/l; p < 0.02), and this difference was most evident in patients diagnosed before the age of 45 years (374.8 vs 245.5 mIU/l; p < 0.05), a patient population characterized by active immunological disease. Serum PRL did not correlate to disease duration, serum immunoglobulin, autoantibodies, or focus score in biopsies from minor salivary glands, but did correlate to score for internal organ disease (r = 0.33, p < 0.05). Two patients were diagnosed as having primary SS 12 years after hyperprolactinemia was first detected, and both patients had aggressive primary SS as indicated by extraglandular manifestations. One of the patients developed primary SS after being treated with bromocriptine, an inhibitor of PRL synthesis, for 12 years. CONCLUSION: Patients with primary SS have moderately increased levels of serum PRL, especially evident in patients diagnosed at a young age with active immunological disease. Serum PRL is correlated to index for internal organ disease, and primary SS may be preceded by hyperprolactinemia for many years.

Adult↗

Plasma cytokine concentration and the cytokine producing ability of whole blood cell cultures from healthy females with pharmacologically induced hyperprolactinemia.

We investigated the in vitro effect of domperidone-induced hyperprolactinemia on plasma cytokine concentration and blood leukocyte cytokine production in healthy female volunteers. No changes were found in the plasma concentration of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-10, IL-6 and IL-13 during hyperprolactinemia when compared with control values. Using unseparated blood leukocytes, we found that the spontaneous production of IL-6 (4-8 h) and transforming growth factor (TGF)-beta 1 (2-4 h) was significantly decreased and that the in vitro stimulated production of IFN-gamma (2-8 h) and TNF (4 h) was significantly increased compared with control. Our data concerning the increased IFN-gamma and TNF producing capacity of unseparated leukocytes during pharmacologically induced hyperprolactinemia strongly support the possibility that the lymphocyte production of these cytokines can be rapidly amplified by prolactin via a priming mechanism.

Adult↗

Clinical presentation of hyperprolactinemia.

Prolactin is a polypeptide hormone essential for lactation. Its production in the lactotroph cells of the anterior pituitary is regulated primarily by the inhibitory action of hypothalamic dopamine. Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis, occurring mostly in women and presenting most commonly with amenorrhea and galactorrhea. Causes of hyperprolactinemia include physiologic, pharmacologic and pathologic factors; pituitary adenoma is a common pathologic cause. Women may present with decreased libido, infertility, oligomenorrhea/amenorrhea and galactorrhea. Men may present with decreased libido, infertility, gynecomastia or impotence. In the absence of an identifiable and treatable underlying cause, hyperprolactinemia is generally treated with dopamine agonist medications.

Adult↗

Indications for hyperprolactinemia therapy.

Before initiating treatment for hyperprolactinemia, it is necessary to verify the diagnosis. It is also essential to remember that hyperprolactinemia is in itself simply an abnormal "lab value" that reflects the presence of an underlying pathophysiologic cause. All possible causes must be considered and either identified or ruled out before therapy is initiated. The vast majority of people with hyperprolactinemia can be treated medically with dopamine agonist medications. The indications for treatment include: (1) the presence of significant symptoms, such as infertility, ovulatory dysfunction or galactorrhea in women and infertility or gynecomastia in men; (2) the presence of significant signs, such as visual field defects or cranial nerve palsies; and (3) abnormal test results, including visualization of a pituitary mass or lesion or detection of osteopenia.

Adult↗

Implications of not treating hyperprolactinemia.

When a patient with hyperprolactinemia is not treated, a number of ramifications can result, the most significant of which is osteoporosis. Evidence-based analysis shows that bone mineralization also can be affected by such problems as gonadal dysgenesis and possibly adrenal dysfunction. The hypoestrogenism associated with hyperprolactinemia is commonly assumed to be a potential cause of osteopenia in premenopausal women with this disorder, just as decreased estrogen is associated with bone loss following menopause. A number of studies also have shown that hyperprolactinemia decreases bone density independently of the hypoestrogenic state. In most, but not all, such women, bone density may be reestablished if one is successful in restoring normal menstrual function with dopamine agonists. With the availability of safe dopamine agonists like bromocriptine and now cabergoline, it seems prudent to attempt to normalize serum prolactin levels early on, before long-term pathologies set in.

Decision Making↗

[Influence of hyperprolactinemia and tumoral size in the postoperative pituitary function in clinically nonfunctioning pituitary macroadenomas].

OBJECTIVE: To study the influence of hyperprolactinemia and tumoral size in the pituitary function in clinically nonfunctioning pituitary macroadenomas. METHODS: Twenty three patients with clinically nonfunctioning pituitary macroadenomas were evaluated by image studies (computed tomography or magnetic resonance) and basal hormonal level; 16 had preoperative hypothalamus-hypophysial function tests (megatests). All tumors had histological diagnosis and in seventeen immunohistochemical study for adenohypophysial hormones was also performed. Student's t test, chi square test, exact test of Fisher and Mc Neman test were used for the statistics analysis. The level of significance adopted was 5% (p<0.05). RESULTS: Tumoral diameter varied of 1.1 to 4.7 cm (average=2.99 cm +/- 1.04). In the preoperative, 5 (21.7%) patients did not show laboratorial hormonal deficit, 9 (39.1%) developed hyperprolactinemia, 13 (56,5%) normal levels of prolactin (PRL) and 1 (4.3%) subnormal; 18 (78.3%) patients developed hypopituitarism (4 pan-hypopituitarism). Nineteen patients (82.6%) underwent transsfenoidal approach, 3 (13%) craniotomy and 1 (4.4%) combined access. Only 6 patients had total tumoral resection. Of the 17 immunohistochemical studies, 5 tumours were immunonegatives, 1 compound, 1 LH+, 1 FSH +, 1 alpha sub-unit and 8 focal or isolated immunorreactivity for one of the pituitary hormones or sub-units; of the other six tumours, 5 were chromophobe and 1 chromophobe/acidophile. No significant statistic difference was noted between tumoral size and preoperative PRL levels (p=0.82), nor between tumoral size and postoperative hormonal state, except in the GH and gonadal axis. Significant statistic was noted: between tumoral size and preoperative hormonal state (except in the gonadal axis); between normal PRL levels, associated to none or little preoperative hypophysial disfunction, and recovery of postoperative pituitary function. CONCLUSION: Isolated preoperative hyperprolactinemia and tumoral size have not been predictable for the recovery of postoperative pituitary function.

Adenoma↗

[Effect of testosterone on protein synthesis of prostate cells in hypo- and hyperprolactinemia].

The influence of testosterone on the concentration and synthesis of nuclear and cytoplasmic prostate proteins were studied in rats with hypo- and hyperprolactinemia. Hyperprolactinemia was induced by "Lactin", and the hypoprolactinemia was modelled by "Parlodel". The rats were injected with 14C-protein hydrolysate i.p. for the investigation of the proteins biosynthesis and concentration of prostate cells. The androgen inhibited catabolism of nonhistone proteins and the proteins of nuclear juice in intact rats organism. Testosterone increased the synthesis of all proteins in rats with prolactin deficiency, but this enlarge was not connected with an elevation of their concentration. Thus, we suggest that in this case the proteins disintegration may be increased. Under hyperprolactinemia the concentration of all proteins, besides nonhistone proteins, was declined that reflected the enhancement their catabolism.

Animals↗

Diagnosis and management of hyperprolactinemia.

Prolactin is a pituitary hormone that plays a pivotal role in a variety of reproductive functions. Hyperprolactinemia is a common condition that can result from a number of causes, including medication use and hypothyroidism as well as pituitary disorders. Depending on the cause and consequences of the hyperprolactinemia, selected patients require treatment. The underlying cause, sex, age and reproductive status must be considered. We describe the diagnostic approach and management of hyperprolactinemia in various clinical settings, with emphasis on newer diagnostic strategies and the role of various therapeutic options, including treatment with selective dopamine agonists.

Female↗

[Primary dexamethasone-suppressible hyperaldosteronism and hyperprolactinemia].

This report describes a clinical case with rare association: dexamethasone-suppressible hyperaldosteronism (DSH) and hyperprolactinemia. Previous studies reported that endogenous dopaminergic activity would be increased in both primary aldosteronism and in hyperprolactinemic syndromes. By manipulating dopamine tone with metoclopramide, bromocriptine, ACTH and amineptine, the aldosterone and prolactin responsiveness was evaluated. Our results showed a lack of dopamine inhibiting aldosterone secretion, despite dopaminergic tone is known to be increased in hyperprolactinemia. Thus it seems unlikely that dopaminergic control of aldosterone secretion could be account for this type of hyperaldosteronism associated to hyperprolactinemia, where the suggestion is that ACTH represents the principal regulator of aldosterone secretion.

Adrenocorticotropic Hormone↗

Neuroleptic-associated hyperprolactinemia. Can it be treated with bromocriptine?

Six stable psychiatric outpatients with hyperprolactinemia and amenorrhea/oligomenorrhea associated with their neuroleptic medications were treated with bromocriptine. Daily dosages of 5-10 mg corrected the hyperprolactinemia and restored menstruation in four of the six patients. One woman, however, developed worsened psychiatric symptoms while taking bromocriptine, and it was discontinued. Thus, three of six patients had their menstrual irregularity successfully corrected with bromocriptine. This suggests that bromocriptine should be further evaluated as potential therapy for neuroleptic-associated hyperprolactinemia and amenorrhea/galactorrhea.

Adult↗

[Drug-induced hyperprolactinemia and galactorrhea].

A 21 year old female treated for recurring gastric troubles with dopamine-antagonists (domperidone, metoclopramide) developed a clinically manifest hyperprolactinemia (3055 microU/l; normal value < 650 microU/l) with galactorrhea only two days after a new two day course of metoclopramide. The drug was withdrawn and within days mastodynia and galactorrhea subsided. A control of plasmatic prolactin two weeks later yielded a normal value (358 microU/l). After administration of metoclopramide or domperidone hyperprolactinemia is regularly observed and galactorrhea has been described earlier. It is unclear why this patient inspite of repeated administration of one dopamine antagonist remained asymptomatic whereas the other after a short time and only a few doses led to galactorrhea. It is conceivable that differences in passage into the cerebrospinal fluid or the better penetration of the blood-brain barrier favored the development of galactorrhea under metoclopramide. This case served to discuss the pathophysiologic background of drug-induced hyperprolactinemia.

Adult↗

Hyperprolactinemia in children during the peripubertal period--personal observations.

UNLABELLED: There can be many reasons for functional hyperprolactinemia, including polycystic ovary syndrome (PCOS), obesity, insulin resistance and hypoglycemia. Prolactinoma is also a frequent cause. This study included 12 patients (10 girls and 2 boys) aged 14-17 years with hyperprolactinemia. Six patients were treated for PCOS, two for type 1 diabetes mellitus, and one patient suffered from Prader-Willi syndrome. In all patients, TSH, fT3, fT4, FSH, LH, testosterone, and E2 levels were measured. MRI of the pituitary was performed. Prolactin was measured with the metoclopramid dynamic test (MTC). IRI, C-peptide, oral glucose test, and minor pelvis ultrasound examination were performed in patients with PCOS. Pituitary adenoma was diagnosed in four out of 12 patients. In the remaining eight patients, functional hyperprolactinemia was found. All of these patients remain under pharmacological treatment with positive clinical results. CONCLUSIONS: 1. It is necessary to determine prolactin in each girl with unexplained amenorrhea irrespective of galactorrhea. 2. In some patients with prolactinoma the basal prolactin levels may be in the normal range, but they are increased in the MTC test. 3. In girls with various disorders of the menstrual cycle it is necessary to determine the level of prolactin with a provocative test.

Adolescent↗