Surgery versus conservative care for Rathke's cleft cyst.

BACKGROUND: Rathke's cleft cysts are benign cystic lesions of the sellar region, which may cause headache, pituitary deficiencies and visual disturbances from mass effect. Their management is not standardized yet. This study is about establishing a consensus for medical care of RCC. MATERIAL AND METHODS: We performed a retrospective observational study of all patients that were diagnosed or followed for RCC between 2008 and 2018 (11 years), in the neurosurgical and the adult endocrine departments of our institution. The study's average time length of follow-up is 72.9 months (from 2 to 385 months). RESULTS: The 57 included patients were divided into 2 groups: group A, which included 39 patients that were conservatively managed and group B, which included 18 surgically treated patients. Group A showed either an improvement or a spontaneous resolution of headaches in 56.1% of the cases (P<0.01); a resolution of hyperprolactinemia in 70% of the cases (P=0.21); and of hypogonadism, ACTH deficiency, growth hormone deficiency in 100% of the cases. There was no spontaneous improvement of visual disturbances (P<0.01) or diabetes insipidus (P=0.29) during follow-up. Regarding group B, surgery allowed improvement or complete resolution of headaches in 60% of the cases; visual troubles in 100% of the cases (P<0.01); and hyperprolactinemia in 100% of the cases. Pituitary deficiencies were not improved by surgery. CONCLUSIONS: This study offers guidance in decision-making regarding the management of RCC patients. Surgery is particularly suitable for treating visual disturbances caused by RCC. Regular follow-up is more appropriate than surgery concerning headaches, hyperprolactinemia, endocrine disruptions and diabetes insipidus.

Löfgren Syndrome with Hypercalcemia and Neuroendocrinological Involvement: A Case Report.

BACKGROUND: Sarcoidosis is a systemic inflammatory disease of unknown etiology that can affect virtually any organ. Löfgren syndrome, characterized by erythema nodosum, hilar lymphadenopathy, fever and polyarthritis, represents only 20-30% of the cases of sarcoidosis. Only 2- 10% of the cases feature hypercalcemia. CASE: The case of a 42-year-old Hispanic woman with a history of erythema nodosum and three weeks of nausea, emesis, constipation, asthenia, adynamia, polydipsia, and somnolence, concomitant with hypercalcemia, but normal parathyroid hormone (PTH) and 25-hydroxyvitamin D has been presented. The initial diagnostic approach was based upon the suspicion of multiple myeloma or bone metastases; however, further findings of bilateral hilar lymphadenopathy, elevated serum angiotensin-converting enzyme (ACE) and a right inguinal lymphadenomegaly suggested an alternate diagnosis. Biopsy of the latter supported sarcoidosis as the diagnosis. She was successfully treated in the hospital with zoledronic acid and as an outpatient with immunosuppressive therapy. Persistence of a previously undisclosed symptom of oligomenorrhea led to the detection of hyperprolactinemia secondary to hypophyseal infiltration, refractory to immunosuppressive therapy but with an adequate response to cabergoline. CONCLUSION: This case strays from Löfgren Syndrome's expected behavior, presenting a more progressive, multisystemic disease. This case report was written in adherence to the CARE guidelines of 2013 to include information in it.

Clinical Consultation Guide on Imaging in Male Infertility and Sexual dysfunction.

Imaging can benefit clinicians in evaluating men with infertility or sexual dysfunction by giving an overview of a patient's overall clinical condition before undertaking an invasive procedure. An understanding of the limitations and advantages of image modalities used in clinical practice will ensure that clinicians can optimize patient care with imaging when necessary. PATIENT SUMMARY: The objective of this article was to review the current literature on imaging modalities used for the diagnosis and management of male infertility and sexual dysfunction. An understanding of the advantages and limitations of these imaging modalities will ensure that clinicians can optimize patient care with imaging when necessary.

Clinical and Radiographic Characteristics Related to Hyperprolactinemia in Nonfunctioning Pituitary Adenomas.

OBJECTIVE: Hyperprolactinemia in patients with nonfunctioning pituitary adenomas (NFPAs) has been explained by the stalk compression of large pituitary adenomas. However, not all large NFPAs are associated with high serum prolactin levels. We aimed to elucidate and compare clinical, hormonal, and radiographic characteristics of NFPAs with and without hyperprolactinemia. METHODS: We included 201 patients with clinically NFPAs who underwent transsphenoidal surgery performed by a single surgeon during 2010-2017 at a single center in Korea. We measured the three-dimensional diameters (anteroposterior [AP], width, height) and volumes of NFPA on magnetic resonance imaging. We conducted morning basal hormone measurements and dynamic tests preoperatively and 3 months postoperatively. RESULTS: All NFPAs were macroadenomas, and mean tumor volume was 10.4 ± 7.7 cm3. Of 201 patients, 59 (29.4%) had preoperative hyperprolactinemia. Hormone recovery rate was higher in patients with hyperprolactinemia compared with patients without hyperprolactinemia after age, sex, body mass index, tumor volume, and gross total resection adjustments (odds ratio [95% confidence interval]: 2.55 [1.10-5.92]). Tumor width/AP diameter ratio positively correlated with serum prolactin levels (r = 0.186, P = 0.008). Tumor volume was not significantly different between the 2 groups. CONCLUSIONS: Preoperative prolactin level is a useful marker to predict hormone recovery after surgery. Patients with NFPA and hyperprolactinemia tended to have a higher width/AP diameter ratio. Hyperprolactinemia of NFPA is more likely affected by tumor growth pattern, such as width/AP diameter ratio, than tumor volume.

Hyperprolactinemia Secondary to Pituitary Microadenoma Versus Haloperidol- A Diagnostic Enigma. A Case Report and Brief Review.

BACKGROUND: Hyperprolactinemia can be caused by medications, primarily antipsychotics, or by anterior pituitary tumors. The consequences of hyperprolactinemia including gynecomastia, galactorrhea, and sexual dysfunction are very disturbing for males and females. It is sometimes difficult to differentiate the etiology of hyperprolactinemia from a clinical perspective. OBJECTIVE: Identification of the etiology of hyperprolactinemia requires a careful review of the causes and appropriate work-up. METHODS: A 55-year-old African American male with extensive psychiatric history and non-adherence to treatment was admitted from nursing home for aggression and psychotic symptoms. The patient was noted to have mild bilateral breast enlargement about ten days after hospitalization. Prolactin level done on August 26, 2014 was 93.8 ng/mL, and on September 5, 2014 was 112 ng/mL. The patient's medications included haloperidol decanoate 150 mg q28d, haloperidol 10 mg po bid and benztropine 0.5 mg po bid. He did not have any other clinical signs or symptoms of hyperprolactinemia. He was also seen by an endocrinologist. MRI of the pituitary gland done on September 3, 2014, showed a 2.4 mm pituitary microadenoma. Bromocriptine was started at 1.25 mg qhs and titrated to 2.5 mg bid. RESULTS: Prolactin level dropped from 112 ng/mL on September 5, 2014 to 99 ng/mL on September 9, 2014, 61.2 ng/mLon September 23, 2014 and 3.0 ng/mL on February 9, 2015. CONCLUSION: Diagnosis and etiology of hyperprolactinemia were complicated by the minimal nature of clinical symptoms, the type of antipsychotic agent and the prolactin level. The MRI facilitated the diagnosis of pituitary microadenoma and further treatment option with bromocriptine. MRI of the pituitary is indicated for patients with hyperprolactinemia where the etiology is not clearly due to medication.

Primary Hypothyroidism with Exceptionally High Prolactin-A Really Big Deal.

BACKGROUND: Primary hypothyroidism can cause both hyperprolactinemia and pituitary hyperplasia. The degree of hyperprolactinemia is generally modest, and rarely do prolactin concentrations exceed 100 ng/mL (4.34 nmol/L). This combination of hyperprolactinemia and pituitary gland enlargement might raise suspicion for a prolactinoma or a nonfunctioning adenoma limiting the ability of hypothalamic dopamine to inhibit prolactin production, the so-called "stalk effect." CASE DESCRIPTION: We describe a 30-year-old female with headaches, galactorrhea, and hyperprolactinemia with a presumptive diagnosis of a prolactinoma. She had hypothyroidism after treatment of Graves disease at age 17 years but was noncompliant with levothyroxine replacement. Thyroid-stimulating hormone (TSH) was 263 mIU/L, FT4 was 3.01 pmol/L, and prolactin was 323 ng/mL (14.06 nmol/L). Magnetic resonance imaging (MRI) demonstrated increased volume of the pituitary gland with homogeneous enhancement with gadolinium. Levothyroxine treatment for 2 weeks decreased her TSH to130 mIU/L, but her total prolactin remained elevated at 386 ng/mL (16.78 nmol/L). Further testing identified that 76% of the total prolactin was macroprolactin. CONCLUSIONS: Primary hypothyroidism can cause hyperprolactinemia, and prolonged disease may lead to pituitary hyperplasia. However, a marked elevation of prolactin should raise suspicion to investigate additional etiologies for hyperprolactinemia. Our case exemplifies a dual etiology for hyperprolactinemia and pituitary hyperplasia caused by both hypothyroidism and macroprolactin. This knowledge is invaluable for clinicians to avoid unnecessary management with dopamine agonists and/or surgery. This patient's prolactin was 323 ng/mL (14.06 nmol/L). Before our case, the highest prolactin in a hypothyroid patient reported in the literature was 253 ng/mL (11.0 nmol/L).

Association between Hyperprolactinemia and Granulomatous Mastitis.

Granulomatous mastitis (GM) is a relatively uncommon inflammatory breast lesion with multiple suggested etiologies. Although most GM cases show association with lactation and pregnancy, a minority of cases have been linked to hyperprolactinemia caused by either dopamine antagonist medications or with intracranial lesions, such as pituitary adenoma. The goal of this study is to review the GM cases reported in the literature with a specific emphasis on those cases associated with hyperprolactinemia and prolactinomas and to identify cases of GM seen at the Cleveland Clinic Florida which demonstrate co-occurrences of GM and intracranial lesions. CoPath and Epic data bases at Cleveland Clinic Florida were searched for cases describing inflammatory breast lesions in patients with pituitary pathology. Chart reviews were conducted and pertinent medical history was extracted for case reports. H&E-stained paraffin-embedded sections retrieved from Cleveland Clinic Florida pathology storage were evaluated by light microscopy. Four cases showing a co-occurrence of GM and hyperprolactinemia were consequently identified. A prolactin-secreting pituitary adenoma was present in two of the three GM cases. The third case demonstrated a concomitant craniopharyngioma, which was also associated with a rise in serum prolactin. This phenomenon was presumably attributable to compression, resulting in compromised transport of dopamine to the adenohypophysis and subsequent disinhibition of prolactin secretion by lactotrophs. The fourth patient with GM had a similar history of elevated prolactin. Classical histopathological features of GM were found in all four cases, including noncaseating granulomas, multinucleated giant cells, epithelioid histiocytes, and chronic inflammation. Intriguingly, complete resolution of inflammatory breast lesions along with normalization of prolactin levels occurred following the surgical excision of the craniopharyngioma, suggesting that intracranial lesion-induced hyperprolactinemia might be directly causal in GM. Therefore, the authors would suggest screening for pituitary tumors and evaluate prolactin levels in the workup of GM patients without a recent history of lactation and pregnancy and no other identified etiology.

Color Doppler analysis of uterine, spiral, and intraovarian artery blood flow before and after treatment with cabergoline in hyperprolactinemic patients.

Prolactin (PRL) may have stimulatory effects on vascular resistance. We aimed to analyze uterine, spiral, and intraovarian artery blood flow by Doppler ultrasonography in hyperprolactinemic patients prior to and after treatment with cabergoline. The study was conducted in Sisli Etfal Training and Research Hospital gynecology outpatient clinic between 1 March 2010 and 30 September 2011. Twenty-four women with symptomatic hyperprolactinemia in reproduction age were included in the study. All hyperprolactinemic patients were studied prior to and following the suppression of circulating PRL levels by cabergoline. Patients were examined by standard B-mod and color transvaginal ultrasonography. Pulsality index (PI), resistance index (RI), and systolic/diastolic ratio (S/D) were recorded. The median PRL value was 86 (62-120) ng/ml before treatment and 4.0 (2.5-6.4) ng/ml after the treatment (p < 0.001). We found a significant association among PRL, uterine, spiral, and intraovarian artery RI with linear regression analysis (p < 0.001 for all three arteries). Uterine, spiral, and intraovarian artery PI (p = 0.021, p < 0.001, and p < 0.001, respectively) and RI (p = 0.001, p < 0.001, and p < 0.001, respectively) significantly decreased after cabergoline treatment. In conclusion, this is a pilot study which shows for the first time that PRL increases the uterine, endometrial, and intraovarian vascular resistance and cabergoline reverses this effect.

[Dopamin agonist treatment and fibrotic heart valve disease in hyperprolactinaemia patients]. / Behandling med dopaminagonister og udvikling af hjerteklapsygdom hos patienter med hyperprolaktinæmi.

Treatment with dopamin agonists, particularly cabergoline, is the primary and preferred therapy for prolactinomas and symptomatic hyperprolactinaemia due to its effectiveness and tolerability. However, an association has been demonstrated between fibrotic heart valve disease and high-dose dopamin agonist use in patients with Parkinson's disease in several echocardiographic studies. Such observations have prompted a number of studies of valvular function in cabergoline-treated hyperprolactinaemia patients. These studies have failed to show an increased prevalence of clinically significant valvular regurgitation.

A cross-sectional study of the prevalence of cardiac valvular abnormalities in hyperprolactinemic patients treated with ergot-derived dopamine agonists.

CONTEXT: Concern exists in the literature that the long-term use of ergot-derived dopamine agonist drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease. OBJECTIVE: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking dopamine agonists as treatment for lactotrope pituitary tumors and to explore any associations with the cumulative dose of drug used. DESIGN: A cross-sectional echocardiographic study was performed in a large group of patients who were receiving dopamine agonist therapy for hyperprolactinemia. Studies were performed in accordance with the British Society of Echocardiography minimum dataset for a standard adult transthoracic echocardiogram. Poisson regression was used to calculate relative risks according to quartiles of dopamine agonist cumulative dose using the lowest cumulative dose quartile as the reference group. SETTING: Twenty-eight centers of secondary/tertiary endocrine care across the United Kingdom participated in the study. RESULTS: Data from 747 patients (251 males; median age, 42 y; interquartile range [IQR], 34-52 y) were collected. A total of 601 patients had taken cabergoline alone; 36 had been treated with bromocriptine alone; and 110 had received both drugs at some stage. The median cumulative dose for cabergoline was 152 mg (IQR, 50-348 mg), and for bromocriptine it was 7815 mg (IQR, 1764-20 477 mg). A total of 28 cases of moderate valvular stenosis or regurgitation were observed in 24 (3.2%) patients. No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION: This large UK cross-sectional study does not support a clinically concerning association between the use of dopamine agonists for the treatment of hyperprolactinemia and cardiac valvulopathy.

Approach to the patient with persistent hyperprolactinemia and negative sellar imaging.

Hyperprolactinemia is a common cause of menstrual disturbances affecting young women. There is a diversity of causes, from physiological, such as pregnancy, to pharmacological and pathological, such as hypothyroidism. Renal and hepatic failure, intercostal nerve stimulation by trauma or surgery, prolactinomas, other tumors in the hypothalamus-pituitary region, as well as macroprolactinemia can also be considered. Identifying the correct cause is important to establish the correct treatment. Should all these causes be ruled out and pituitary imaging revealed as negative, idiopathic hyperprolactinemia is therefore diagnosed. In symptomatic patients, treatment with dopaminergic agonists is indicated. As for the asymptomatic hyperprolactinemic individuals, macroprolactinemia should be screened, and once it is detected, there is no need for pituitary imaging study or for dopaminergic agonist use.

Positron emission tomography measurement of dopamine D2 receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia.

OBJECTIVE: Hyperprolactinemia is a common side effect of antipsychotic drugs used in the treatment of schizophrenia. However, the magnitude of hyperprolactinemia differs among antipsychotics, and there is no reliable mechanism-related marker for the risk of hyperprolactinemia that would allow us to characterize antipsychotics. METHOD: In this study, 11 healthy male subjects taking different doses of sulpiride and 24 male patients with DSM-IV-diagnosed schizophrenia taking different antipsychotic drugs (risperidone, olanzapine, haloperidol, and sulpiride) participated. Positron emission tomography scanning using [¹¹C]FLB 457 was performed on all subjects. The dopamine D2receptor occupancy of antipsychotics in the pituitary and temporal cortex was calculated. Correlations between plasma concentration of prolactin and dopamine D2receptor occupancies were evaluated. The ratio of drug concentration of cerebral receptor site to that of pituitary receptor site (brain/plasma concentration ratio; B/P ratio) was calculated from the receptor occupancies in the 2 regions. Data were collected between November 2001 and September 2007. RESULTS: Significant positive correlation was observed between the plasma concentration of prolactin and dopamine D2receptor occupancy in the pituitary by all 4 antipsychotics (P = .001). Dopamine D2receptor occupancies of sulpiride were markedly different between the pituitary and temporal cortex, and the B/P ratio for sulpiride (0.34) was significantly lower than for olanzapine (P = .007) and risperidone (P = .015). Olanzapine had a relatively high B/P ratio (2.70), followed by haloperidol (2.40) and risperidone (1.61). CONCLUSIONS: Dopamine D2receptor occupancy in the pituitary is a good indicator of hyperprolactinemia. B/P ratio, indicating the penetrating capability across the blood-brain barrier, seems to be a good characteristic biomarker of each antipsychotic drug for the risk of hyperprolactinemia at therapeutic dose.

Prevalence of hyperprolactinemia and abnormal magnetic resonance imaging findings in a population with infertility.

Hyperprolactinemia is rare among asymptomatic patients with infertility. Its prevalence and the mean PRL levels did not differ with [1] the infertility diagnosis, [2] the presence or absence of menstrual irregularities, or [3] the severity of menstrual dysregulation. Abnormal magnetic resonance imaging findings, though, are not uncommon among women with hyperprolactinemia despite the lack of symptoms and the mild PRL elevations.

Suprasellar tuberculoma presenting as panhypopituitarism.

Suprasellar tuberculomas are exceptionally rare. We present the case of a middle aged male who presented with generalised apathy and meningism of two weeks duration. Neuroimaging was suggestive of tuberculomas in suprasellar cistern, while endocrinological investigation showed panhypopituitarism manifesting as pituitary hypothyroidism, hypocortisolism, and hyperprolactinemia. Cerebrospinal fluid examination showed lymphocytic reaction with raised proteins. A diagnosis of suprasellar tuberculoma with panhypopituitarism was made. The patient was started on antituberculous treatment and hormone replacement which led to remarkable improvement in condition of patient and resolution of tuberculous granuloma in follow up imaging.

Gender effects on cardiac valvular function in hyperprolactinaemic patients receiving cabergoline: a retrospective study.

BACKGROUND: Ergot-derived dopamine agonists are associated with increased risk of valvular dysfunction in Parkinson's disease. The risk of valvular disease associated with lower doses of cabergoline used to treat prolactinomas remains controversial. OBJECTIVE: To determine whether there is an association of cabergoline and valvular function in patients with hyperprolactinaemia according to gender. DESIGN: Case-record retrospective study. SETTING: Outpatient neuroendocrine clinical centre at a tertiary care hospital. STUDY PARTICIPANTS: One hundred patients (48 men and 52 women) with hyperprolactinaemia who had an echocardiogram while receiving cabergoline for at least 6 months. CONTROLS: One hundred controls (48 men and 52 women) selected from Massachusetts general hospital (MGH) database of echocardiograms without clinically significant findings, matched to patients for age, gender, body mass index (BMI) and hypertension. MAIN OUTCOME MEASURE: Echocardiogram. RESULTS: There were no significant differences in valvular function in patients compared with controls. However, women patients had a higher prevalence of mild tricuspid regurgitation (TR) than female controls (15.4%vs. 1.9%, P = 0.03). Among men only, patients had more trace TR than controls (68.8%vs. 45.8%, P = 0.02). The mild valvular regurgitation in patients was not clinically significant and did not correlate with dose, duration or cumulative dose. CONCLUSIONS: Overall cabergoline was not associated with valvulopathy. However, subdivided by gender, hyperprolactinaemic men and women had higher prevalence of trace or mild TR, respectively, compared with gender matched controls. There may be gender differences in valvular dysfunction associated with cabergoline. Longer term, larger studies are necessary to evaluate definitively an effect of cabergoline on valvular function in hyperprolactinaemic patients.

Patients with macroprolactinaemia: clinical and radiological features.

BACKGROUND: Macroprolactinaemia may represent a relevant cause of misdiagnosis, unnecessary investigation and inappropriate treatment. The aim of this study was to investigate the clinical and neuroradiological characteristics of patients with and without macroprolactinaemia and to evaluate the impact of macroprolactin determination on the diagnostic work-up of hyperprolactinaemic patients. MATERIALS AND METHODS: Retrospective analysis in 135 consecutive hyperprolactinaemic patients (111 women and 24 men; mean age 37 +/- 11.6 years) whose archived sera were subsequently tested for macroprolactin. Recoveries

Hiperprolactinemia en niños y adolescentes, conceptos e interrogantes actuales / Hyperprolactinemia in children and adolescents, current questions and concepts

La hiperprolactinemia constituye la alteración endocrina más común del eje hipotálamo-hipofisario, aunque su prevalencia en la población infantojuvenil no está aún claramente definida. Además de la Prolactina (PRL) nativa (23Kda), se han descripto numerosas variantes moleculares (PRL glicosilada, fosforilada, sulfatada, deaminada, BIG PRL, BIG BIG PRL, etc.), algunas de ellas con menor o ausente actividad biológica. El recién nacido presenta inmadurez fisiológica del eje prolactínico, alcanzando niveles de hasta 800 ng/mL en las primeras horas de vida. Posteriormente, cualquier proceso que interrumpa la secreción de dopamina, interfiera con su liberación hacia los vasos portales hipofisarios o bloquee los receptores dopaminérgicos de las células lactotróficas, puede causar hiperprolactinemia. La patología tumoral constituye el diagnóstico de mayor relevancia. Los prolactinomas poco frecuentes tienen, por su presentación clínica en niños y adolescentes, algunas características destacables. De acuerdo a nuestra experiencia, el retraso puberal puede observarse en aproximadamente el 50 % de las pacientes de sexo femenino y en más del 25 % de los varones. La mayor prevalencia de macroadenomas en varones coincide con los hallazgos en adultos y no dependería de un mayor retraso en el diagnóstico. En pacientes con hiperprolactinemia asintomática debe evaluarse la presencia de proporciones alteradas de isoformas de PRL. La cromatografía en columna con sephadex G100, la precipitación con suspensión de proteína A o con PEG y la ultracentrifugación constituyen los métodos más frecuentemente empleados para la detección de las distintas isoformas de PRL. En nuestra experiencia la B PRL constituyó el 6,6 - 32,6 % de la PRL total y la BB PRL constituyó el 40 y el 72 % de la misma en este grupo de pacientes. Por su efectividad y tolerancia, los agonistas dopaminérgicos constituyen la terapia inicial de elección en pacientes en edad pediátrica. La bromocriptina y la cabergolina han sido empleadas y con resultados similares a los de los pacientes adultos. La adquisición de nuevos conceptos y la mejor comprensión de la fisiología y la fisiopatología de los estados hiperprolactinémicos en niños y adolescentes, han modificado las alternativas diagnósticas y terapéuticas

Hyperprolactinemia is the most common endocrine alteration of the pituitary-hypothalamic axis, although its prevalence in the pediatric and adolescent population is not clearly defined yet. Apart from native (23Kda) Prolactin (PRL), many molecular variants (glycosylated, phosphorilated, sulphated, deaminated PRL, BIG PRL, BIG BIG PRL, etc) have been described, some of them with less or no biological activity. Newborns have physiological immaturity of the prolactin axis, attaining levels of as much as 800 ng/mL during the first hours after birth. Subsequently, any process that discontinues dopamine secretion, interferes with its secretion to the pituitary portal vessels or blocks dopaminergic receptors of lactotrophic cells, may cause hyperprolactinemia. Tumor disease is the major diagnosis. Prolactinomas, though rare, have some noticeable features, given their clinical presentation in children and adolescents. Based on our experience, pubertal delay occurs in approximately 50 % of females and in over 25 % of males. The larger prevalence of macroadenomas in males is consistent with findings in adults and would not be related to a later diagnosis. In patients with asymptomatic hyperprolactinemia, the presence of altered proportions of PRL isoforms should be evaluated. G100 Sephadex column chromatography, precipitation with a protein A suspension or PEG and ultracentrifugation, are the most common methods for detection of PRL isoforms. In our experience, B PRL accounted for 6.6 - 32.6 % of total PRL and BB PRL accounted for 40 to 72 % of total PRL in this group of patients. Because of their effectiveness and tolerance, dopaminergic agonists are the initial therapy of choice in pediatric age patients. Bromocriptine and cabergoline have been used with similar results to those obtained in adults. The new concepts gained and the better insight into the physiology and pathophysiology of hyperprolactinemic conditions in children and adolescents have brought about a change in diagnostic and therapeutic alternatives

Drug treatment of hyperprolactinemia.

Medical treatment of hyperprolactinemia is based upon use of dopamine agonists (DA): bromocriptine, lisuride, quinagolide and cabergoline. In over 80% of cases, these drugs induce normal prolactinemia and ovulatory cycles. In resistant cases, the DA should be changed. Tolerance may occasionally be poor, particularly with bromocriptine, which appears less well-tolerated than quinagolide and than cabergoline above all. In the event of intolerance to a given DA, another should be tried. In patients with macroprolactinoma treated with DA, MRI monitoring should be carried out after 3 months of treatment to verify tumor size reduction, then after 1 year, yearly for the next 5 years and once every 5 years if adenoma size is stable. In cases of microprolactinoma, control under treatment is pointless. MRI may be performed after 1 year and then after 5 years. Once normal prolactin levels have been achieved, attempts may be made to stop the treatment. When a prolonged treatment is interrupted, especially with cabergoline, progressive increase in serum prolactin and return of hyperprolactinemia symptoms are seen in only around 20-30% of cases, particularly when residual adenoma exists after prolonged treatment. Nevertheless, prolactin levels should continue to be monitored after discontinuation of DA, possibly with MRI monitoring, since prolactin levels may rise again after a number of months or years. When normal prolactin levels have been achieved with DA, another solution consists in reducing the dose or dosing frequency of DA in steps to the lowest effective dose consistent with maintenance of normal prolactin levels and stable adenoma size. For drug-induced hyperprolactinemia, where the causative medication cannot be withdrawn, it is often pointless and possibly even dangerous to administer a DA. It is therefore necessary to check for absence of pituitary adenoma and where necessary, begin treatment with sex steroids so as to ensure satisfactory impregnation with sex steroids and avoid osteoporosis. For macroprolactinoma, the first-line treatment is drug therapy with DA. At present, there is no evidence to suggest that prior treatment with DA can modify the outcome of surgery. With microprolactinoma, DA treatment offers a good first-line therapeutic option but surgery may also be useful. DAs for microprolactinoma may be withdrawn after menopause.