Prolactin-secreting Pituitary Tumors Research Articles

8744 Genomic Variant Landscape In Aggressive & Treatment Resistant Prolactin-Secreting Tumors

Abstract Disclosure: D. Marrero-Rodríguez: None. K. Taniguchi-Ponciano: None. F. Martinez-Mendoza: None. E. Peña-Martinez: None. S. Vela-Patiño: None. S. Hinojosa-Alvarez: None. J. Hernandez-Perez: None. R. Chavez-Santoscoy: None. E. Sosa-Eroza: None. P.E. Espinosa Cardenas: None. M. Mercado: None. Pituitary tumors (PT) represent the second most frequent intracranial tumor and this neoplasm arises from adenohypophyseal cells. Prolactin-secreting tumor (PRL-tumors) are the most commonly neoplasm of the pituitary gland and arises from lactotrophs, and account for 50% of all pituitary tumors. Pituitary tumors are highly heterogeneous lesions and many of them are invasive in up to 45%, with up to 15% being clinically aggressive. Aggressive PRL-tumors are defined as invasive tumors with unusually rapid growth rate despite maximal tolerated dopamine agonist dose and requiring additional therapy and presenting multirecurrent potential. Predicting pituitary tumor behavior remains a challenge, therefore we performed whole exome sequencing to identify genomic variant landscape from aggressive and treatment-resistant prolactin-secreting pituitary tumors. Interestingly one tumor showed one hotspot mutation in splicing factor gene SF3B1 (c.C1873T:p.R625C), a second tumor showed an stop codon in SF3B1 (c.C496T:p.R166*). We then evaluated known hereditary-related pituitary tumor genes, identifying three patients with two different GNAS allelic variants the first one showed c.A3059G:p.N1020S and two tumors with c.C1307A:p.A436D variants. PRKAR1A gene did not showed any allelic variants in our cohort, while all tumors presented c.A1636G:p.T546A variant in MEN1 gene, in AIP gene allelic variant c.C682A:p.Q228K was present in all tumors. PAX6 gene is related to pituitary gland development and function, we found a deletion (c.980delA:p.K327Rfs*29) causing frameshift present in all tumors. The target coding-gene for cabergoline, first line of treatment, DRD2 di not showed any allelic variant. Also XRCC1 and ABCB1 genes, which are related to drug and therapy response showed c.A1196G:p.Q399R and c.T2887G:p.S963A allelic variants in 100% and 88% of tumors, respectively. Together this genomic landscape could represent higher risk to harbor aggressive non-responsive PRL secreting tumor. Presentation: 6/1/2024

Evaluation of Treatment Strategies for Male Prolactin-Secreting Pituitary Neuroendocrine Tumors.

Prolactin-secreting pituitary neuroendocrine tumors (PitNETs) are more common in women. Male patients may also have few symptoms and have macroadenomas extending outside the sella turcica. This study aimed to report the results of cabergoline treatment in male patients with prolactin-secreting PitNET. The study included nine male patients aged 26-65 years (median, 46 years) diagnosed with prolactin-secreting PitNETs. The age at onset, prolactin values, tumor size, symptoms, and treatment were assessed. The mean prolactin value at the initial presentation was 2734.6 ng/mL, and the mean maximum tumor diameter was 40.4 mm. Visual field disturbance was the most common symptom (44.4%), followed by headaches (33.3%), asymptomatic symptoms (11.1%), and galactorrhea (11.1%). Eight patients responded to cabergoline treatment with normalization of prolactin levels and tumor shrinkage. One patient did not respond to the cabergoline treatment and required surgical intervention. There were no cases of cerebrospinal fluid leakage. Cabergoline was found to be an effective treatment for male prolactin-secreting PitNETs.

THU079 Danio Rerio (Zebrafish): A New Model Of AIP Loss Of Function

Abstract Disclosure: X. Wang: None. A. Leggieri: None. S. Anagianni: None. C.H. Brennan: None. M. Korbonits: None. Background: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene account for 10% of cases with familial isolated pituitary adenoma (FIPA). The main features of patients carrying heterozygous AIP mutations include young-onset, large and invasive growth hormone and/or prolactin-secreting pituitary tumours, although a milder spectrum of presentation has been also described. In several animal models (mouse, fruit fly, round worm), homozygous deletion of AIP results in embryonic mortality. In mice abnormal cardiac development has been observed. Objective: The aim of this study was to generate a zebrafish loss-of-function model to explore the cellular biological processes affected by heterozygous or homozygous aip mutations. Methods: Zebrafish homologue of human AIP was identified by EMBOSS Needle program. We used CRISPR/Cas9 to generate a line of fish carrying loss-of-function mutations targeting zebrafish aip exon 2. aip RNA expression was examined using in situ hybridisation. The growth rate and cardiac function were assessed using a stereo microscope with an integrated camera. The videos and pictures were analysed in ImageJ. Antisense in situ hybridisation with probes to growth hormone 1 (gh1), prolactin (prl) and proopiomelanocortin a (pomca) was used to assess pituitary phenotypes. Results: Zebrafish aip shows 78.8% of homology to human AIP. aip mRNA is expressed throughout the developing zebrafish embryo until 28 hours post fertilisation (hpf) stage when it becomes more strongly expressed in the head. We generated a 29 bp deletion in exon 2 of the zebrafish aip gene. These mutant animals showed reduced aip expression. No significant gross morphology differences were observed at 3 to 7 days post fertilisation (dpf) between wildtype (WT) and heterozygote (Het) animals. At 5dpf, WTs showed an increased heart rate than Hets (P=0.033). Conclusion: We have generated an aip loss of function zebrafish line that provides an ideal opportunity to analyse the role of aip in development. Presentation: Thursday, June 15, 2023

Prognostic Models in Growth-Hormone- and Prolactin-Secreting Pituitary Neuroendocrine Tumors: A Systematic Review.

Growth-hormone (GH)- and prolactin (PRL)-secreting PitNETs (pituitary neuroendocrine tumors) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Proliferation markers alone have a questionable degree of prediction, so we try to identify validated prognostic models as accurately as possible. (1) Background: The data available so far show that the use of staging and clinical-pathological classification of PitNETs, along with imaging, are useful in predicting the evolution of these tumors. So far, there is no consensus for certain markers that could predict tumor evolution. The application of the WHO (World Health Organisation) classification in practice needs to be further evaluated and validated. (2) Methods: We performed the CRD42023401959 protocol in Prospero with a systematic literature search in PubMed and Web of Science databases and included original full-text articles (randomized control trials and clinical trials) from the last 10 years, published in English, and the search used the following keywords: (i) pituitary adenoma AND (prognosis OR outcome OR prediction), (ii) growth hormone pituitary adenoma AND (prognosis OR outcome OR prediction), (iii) prolactin pituitary adenoma AND (prognosis OR outcome OR prediction); (iv) mammosomatotroph adenoma AND (prognosis OR outcome OR prediction). (3) Results: Two researchers extracted the articles of interest and if any disagreements occurred in the selection process, these were settled by a third reviewer. The articles were then assessed using the ROBIS bias assessment and 75 articles were included. (4) Conclusions: the clinical-pathological classification along with factors such as GH, IGF-1, prolactin levels both preoperatively and postoperatively offer valuable information.

Current and Emerging Medical Therapies in Pituitary Tumors.

Pituitary tumors (PT) represent in, the majority of cases, benign tumors for which surgical treatment still remains, except for prolactin-secreting PT, the first-line therapeutic option. Nonetheless, the role played by medical therapies for the management of such tumors, before or after surgery, has evolved considerably, due in part to the recent development of well-tolerated and highly efficient molecules. In this review, our aim was to present a state-of-the-art of the current medical therapies used in the field of PT and the benefits and caveats for each of them, and further specify their positioning in the therapeutic algorithm of each phenotype. Finally, we discuss the future of PT medical therapies, based on the most recent studies published in this field.

Prolactinoma and cardiovascular diseases – an interdisciplinary problem

Prolactin-secreting pituitary tumour is a rare disease, in which excess prolactin causes significant functional and constitutional disorders of the whole body. Hyperprolactinaemia is associated with changes in body composition and metabolic disorders. The long-term prognosis and quality of life in patients with prolactinoma are mainly influenced by cardiovascular disorders, which, if left untreated, increase the cardiovascular risk and limit the treatment options for secondary organ complications. Cardiovascular mortality in patients with prolactinoma is several times higher than in the general population. Early diagnosis of prolactin-releasing pituitary tumour and a thorough morphological and functional cardiovascular assessment at each stage of the disease are necessary for risk stratification. Patients with prolactinoma should be put on combined treatment based on both serum prolactin control, and reduction of cardiovascular risk factors. Normalisation of prolactin levels and reduction of the tumour mass, achieved mainly through effective pharmacotherapy, reduce mortality and the risk of cardiovascular complications; therefore, the earliest possible diagnosis of prolactin pituitary tumour and implementation of appropriate treatment as well as active diagnosis and therapy of coexisting organ complications should be set as a goal in these patients. It seems that a thorough cardiological assessment of patients with prolactinoma should be obligatory, regardless of their age or the time of diagnosis. The aim of this study was to present the complexity of clinical problems in patients with prolactin secreting pituitary tumours, who require special interdisciplinary care.

Reappraising the Role of Trans-Sphenoidal Surgery in Prolactin-Secreting Pituitary Tumors.

Simple SummaryProlactinomas constitute a subgroup of pituitary adenomas for which there are several treatment options. Dopamine agonists (DA), since their introduction, have shown a strong efficacy both in the control of hyperprolactinemia and of the significant volumetric reduction of prolactinomas, leading, in some cases, to a definitive cure. Trans-sphenoidal surgery (TSS) has been traditionally confined to a failure of medical therapy, pituitary apoplexy with neurological worsening, and prolactinomas with wide cystic components. Moreover, the recent technical innovations introduced in TSS and increasing experience of surgeons have allowed to achieve better results, such as complete tumor resection with lower complication rates. On these grounds, the authors reviewed the extensive institutional Prolactinomas case series over the last 25 years to analyze the role of TSS in the management of Prolactinomas, particularly in terms of the cure rate.Background: Prolactinomas represent a unique challenge for endocrinologists and neurosurgeons. Considering recent innovations in surgical practice, the authors aimed to investigate the best management for prolactinomas. Methods: A retrospective, cross-sectional and monocentric study was designed. Consecutive patients affected by prolactinomas were enrolled if treated with a first-line treatment with a dopamine agonist (DA) or trans-sphenoidal surgery (TSS). Patients carried giant prolactinomas, and those with a follow-up <12 months were excluded. Results: Two hundred and fifty-nine patients were enrolled. The first treatment was DA for 140 patients and TS for 119 cases. One hundred and forty-six of 249 patients (58.6%) needed a second therapy. The mean follow-up was 102.2 months (12–438 months). Surgery highly impacted on the cure rate—in particular, in females (p = 0.0021) and in microprolactinomas (p = 0.0020). Considering the multivariate analysis, the female gender and surgical treatment in the course of the clinical history were the only independent positive predictors of a cure at the end of 5 years follow-up (p = 0.0016, p = 0.0005). The evaluation of serum prolactin (24 hours after TSS) revealed that 86.4% of patients with postoperative prolactin (PRL) ≤10 ng/mL were cured at the end of the follow-up (p < 0.0001). Conclusions: According to our experience, surgery allows a high cure rate of prolactinomas, particularly in females with microadenoma, with a good safety profile. TSS for prolactinomas should be considered as a concrete option, during the multidisciplinary evaluation, in centers of reference for pituitary diseases.

Psychotic Symptoms Subsequent to Chronic Untreated Prolactinoma: A Case Report

Prolactinomas are prolactin-secreting pituitary tumors originating from the lactotroph cells of the anterior pituitary gland. With hyperprolactinemia, prolactinoma patients may present symptoms of galactorrhea, amenorrhea, sexual dysfunction, and infertility, as well as symptoms due to tumor expansion. Moreover, high level of prolactin effects on mood and behavior thus may lead to depression, anxiety, and hostility through unknown mechanisms. A couple of previous case reports described psychotic disorders in patients with prolactinoma, but none of them came from Chinese population. The case presented here is a 24-year-old unmarried woman presenting psychotic symptoms and amenorrhea following menstrual irregularity. Her psychotic symptoms were intermittent and distressed her for 10 months. Her amenorrhea persisted for several years without a standardized therapy. A suspected prolactinoma was confirmed by a high level of serum prolactin and a brain MRI scanning showing a pituitary macroadenoma. Her psychotic symptoms were treated with olanzapine and psychotherapy during hospitalization. She has been maintained on aripiprazole, bromocriptine, and benzhexol after discharge. Olanzapine is effective and safe in treating psychotic symptoms resulting from hyperprolactinemia. Combination of aripiprazole and bromocriptine are a good option for the maintenance of patients with comorbid psychotic symptoms and prolactinoma.

Beta-Arrestin 2 Is Required for Dopamine Receptor Type 2 Inhibitory Effects on AKT Phosphorylation and Cell Proliferation in Pituitary Tumors

Dopamine receptor type 2 (DRD2) agonists are the first-choice treatment for prolactin-secreting pituitary tumors but are poorly effective in nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs). DRD2 reduces AKT phosphorylation in lactotrophs, but no data are available in NF-PitNETs. DRD2 effects on AKT are mediated by a β-arrestin 2-dependent mechanism in mouse striatum. The aim of this study was to investigate DRD2 effects on AKT phosphorylation and cell proliferation in human primary cultured NF-PitNET cells and in rat tumoral lactotroph cells MMQ, and to test β-arrestin 2 involvement. We found that the DRD2 agonist BIM53097 induced a reduction of the p-AKT/total-AKT ratio in MMQ (–32.8 ± 17.6%, p < 0.001 vs. basal) and in a subset (n = 15/41, 36.6%) of NF-PitNETs (subgroup 1). In the remaining NF-PitNETs (subgroup 2), BIM53097 induced an increase in p-AKT. The ability of BIM53097 to reduce p-AKT correlated with its antimitotic effect, since the majority of subgroup 1 NF-PitNETs was responsive to BIM53097, and nearly all subgroup 2 NF-PitNETs were resistant. β-Arrestin 2 was expressed in MMQ and in 80% of subgroup 1 NF-PitNETs, whereas it was undetectable in 77% of subgroup 2 NF-PitNETs. In MMQ, β-arrestin 2 silencing prevented DRD2 inhibitory effects on p-AKT and cell proliferation. Accordingly, β-arrestin 2 transfection in subgroup 2 NF-PitNETs conferred to BIM53097 the ability to inhibit both p-AKT and cell growth. In conclusion, we demonstrated that β-arrestin 2 is required for DRD2 inhibitory effects on AKT phosphorylation and cell proliferation in MMQ and NF-PitNETs, paving the way for a potential role of β-arrestin 2 as a biomarker predicting NF-PitNETs’ responsiveness to treatment with dopamine agonists.

MON-281 A Pilot Study: Comparing Prolactin Measurements Between Two Different Immunoassays

Hyperprolactinemia from a prolactin-secreting pituitary tumor is the most common endocrine disorder of the hypothalamic-pituitary axis. As suggested in the 2011 Endocrine Society Guidelines on Diagnosis and Treatment of Hyperprolactinemia, macroprolactin level should be assessed in patients with asymptomatic hyperprolactinemia. However, as discussed in prior studies comparing the performance of common prolactin immunoassays in a reference population of both males and females with and without known hyperprolactinemia or macroprolactinemia, there has been poor harmonization between assays and variable reactivity towards macroprolactin, resulting in significantly different normal ranges for total and monomeric prolactin between manufacturers. The goal of our analysis is to assess the concordance of the Roche and Siemens prolactin immunoassays using cases in which prolactin and macroprolactin testing was ordered on clinical indication. We hope to educate clinicians regarding potential variability between assays that may not be fully accounted for by using established, assay-specific reference ranges. We reviewed patients 18 years and older from any gender who underwent evaluation of prolactin levels as clinically indicated and had elevated serum prolactin on a Roche assay with a subsequent normal prolactin on a Siemens assay. Seven out of 18 patients had an elevated prolactin on the Roche assay and a normal prolactin on the subsequent Siemens assay that also tests for the presence of macroprolactin. The reasons for testing prolactin in the 7 patients were: secondary hypogonadism (4), pituitary microadenoma (1), oligomenorrhea (1) and baseline labs in a transgender female starting estrogen (1). Of the 7 cases we observed with discordant Roche and Siemens prolactin results, one of our 2 female patients and one of our 4 male patients would have shown concordant hyperprolactinemia results on both assays if the Siemens reference range was narrowed to align with published studies. This study demonstrates significant analytical discordance between prolactin immunoassays, leading to variable clinical interpretation regarding the presence of hyperprolactinemia. We suggest using a single prolactin immunoassay for routine measurement of prolactin as well as investigation of macroprolactin measurement to ensure comparable reactivity towards all forms of prolactin.

Hyperprolactinaemia in a patient with kidney failure

Hyperprolactinaemia is a common endocrine abnormality in patients with kidney failure. A 43-year-old female, known with kidney failure on maintenance haemodialysis, was referred with symptomatic hyperprolactinaemia. Biochemical investigations revealed a markedly elevated serum prolactin level. Magnetic resonance imaging of the brain (without gadolinium) demonstrated a pituitary macroadenoma. The patient was started on cabergoline therapy. This case discusses hyperprolactinaemia in kidney failure and highlights the importance of investigating markedly elevated prolactin levels. In cases where patients have galactorrhoea, headaches and/or visual disturbances, clinicians should be alert to the possibility of a prolactin-secreting pituitary tumour.

Impact of Prolactin Hipersecrey on Glucid and Lipid Metabolisms

Pituitary is a common terrain for the appearance of tumoral changes, representing the origin of about 15% of all intracranial tumors [13]. These tumors are, for the most part, histologically benign, as they arise from hormone secreting cells in the anterior lobe. Therefore, the aim of the paper is to specify the clinical and paraclinical clinical onset characteristics, the evolutionary peculiarities, as well as the metabolic complications secondary to the prolactin hypersecretion. The effects of prolactin-secreting pituitary tumors may occur as a result of mass effects of tumors or even hyperprolactinaemia. Because microadenomas are intrathecal, visual defects may not occur, but headaches occur more often (50%) than normal (27%) [1, 6]. A large tumor that extends beyond the limbs of the turkey can cause headaches and vision defects. The classical presentation is bitemporal hemianopsia due to the compression of the optic chiasm from a tumor that extends to the upper level. If chiasma is prefixed or if the tumor extends posteriorly, compression of a single optical system results in visual field defects similar. The lateral extension in the cavernous sinus can lead to the illness of the oculomotor function involving the cranial nerves III, IV and VI and the branches V1 and V2 of the cranial nerve V, alone or in combinations.

Tamoxifen in patients with dopamine agonist-resistant prolactinomas

Aim — to assess the efficacy and safety of tamoxifen in patients with prolactin-secreting pituitary tumors resistant to treatment with dopamine agonists.&#x0D; Material and methods. The study included 6 females aged 23—38 years. All patients received cabergoline for a prolonged time without normalization of prolactin levels and reversal of secondary hypogonadism. The cabergoline dose was 1—7 mg/week. Cabergoline administration was combined with tamoxifen at a dose of 20 mg per day, with a subsequent increase to 40 mg per day after 4 weeks of treatment. Patients received this combination therapy for 3 months.&#x0D; Results. Combined cabergoline and tamoxifen therapy resulted in a significant reduction in prolactin levels in all treated patients, which amounted to 22—66% of the baseline value. However, none of the patients achieved complete normalization of prolactin levels. Despite this fact, 2 patients developed normalization of the menstrual cycle. One of these got pregnant 1.5 months after discontinuation of tamoxifen and gave birth to a child. The second patient had amenorrhea recurrence after tamoxifen discontinuation. After tamoxifen discontinuation, two patients with amenorrhea were treated with dydrogesterone to prevent endometrial hyperplasia. One patient who had a normal menstrual function before tamoxifen developed endometrial hyperplasia, which was the cause for separate diagnostic curettage and a reduction in the tamoxifen dose to 20 mg per day. One month after tamoxifen discontinuation, the patient naturally conceived and subsequently gave birth to twins. One patient underwent placement of an intrauterine system containing levonorgestrel 2 months before the start of tamoxifen.&#x0D; Conclusion. Tamoxifen in combination with cabergoline provides an additional decrease in prolactin levels in patients with initial resistance to dopamine agonists. In patients with dopamine agonist-resistant prolactinomas and hypoestrogenemia, tamoxifen leads to normalization of the menstrual cycle.

A combined opiate agonist and antagonist treatment reduces prolactin secreting pituitary tumor growth

Prolactin secreting pituitary adenomas (prolactinomas) is the most common pituitary tumors in humans. Animal studies have identified aggressive prolactinoma development in fetal alcohol exposed rats. We have recently identified a combination treatment of a μ opioid receptor antagonist naltrexone and a δ opioid receptor agonist D-Ala2-,N-Me-Phe4,Gly-ol Enkephalin (DPDPE) increases innate immune function. In this study, we tested whether naltrexone and DPDPE combination therapy is useful to control pituitary tumor growth. Fetal alcohol exposed and control Fischer 344 female rats at 60days of age were ovariectomized and received an estrogen implant to induce prolactinomas. Six weeks after the estrogen implant, these animals received treatments of naltrexone and DPDPE or saline. The growth of the pituitary tumor prior to and after opioidergic agent treatments was visualized using magnetic resonance imaging (MRI). At the end of the treatment, pituitary weights, plasma prolactin and splenic levels of cytotoxic factors were determined. Both imaging data and weight data indicated that the volume and the weight of the pituitary were increased more after estrogen treatment in animals exposed to fetal alcohol than control. Naltrexone and DPDPE treatment reduced the weight and volume of the pituitary gland and plasma levels of prolactin in both fetal alcohol exposed and control-fed animals. The treatment of opioidergic agents also increased the levels of cytotoxic factors in the spleen. These data provide a novel possibility in treating pituitary tumors using a combination therapy of naltrexone and DPDPE.

Differential Effects of PI3K and Dual PI3K/mTOR Inhibition in Rat Prolactin-Secreting Pituitary Tumors.

Aggressive pituitary tumors are rare but difficult to manage, as there is no effective chemotherapy to restrict their growth and cause their shrinkage. Within these tumors, growth-promoting cascades, like the PI3K/mTOR pathway, appear to be activated. We tested the efficacy of two inhibitors of this pathway, NVP-BKM120 (Buparlisib; pan-PI3K) and NVP-BEZ235 (dual PI3K/mTOR), both in vitro on immortalized pituitary tumor cells (GH3) and on primary cell cultures of human pituitary tumors and in vivo on a rat model of prolactin (PRL) tumors (SMtTW3). In vitro, NVP-BEZ235 had a potent apoptotic and cytostatic effect that was characterized by decreased cyclin D/E and Cdk4/2 protein levels and subsequent accumulation of cells in G1 In vivo, the effect was transient, with a decrease in mitotic index and increase in apoptosis; long-term treatment had no significant inhibitory effect on tumor growth. In contrast, while NVP-BKM120 had little effect in vitro, it dramatically limited tumor growth in vivo Increased Akt phosphorylation observed only in the NVP-BEZ235-treated tumors may explain the differential response to the two inhibitors. Primary cell cultures of human PRL pituitary tumors responded to NVP-BEZ235 with reduced cell viability and decreased hormone secretion, whereas NVP-BKM120 had little effect. Altogether, these results show a potential for PI3K inhibitors in the management of aggressive pituitary tumors. Mol Cancer Ther; 15(6); 1261-70. ©2016 AACR.

Radioterapia nos tumores da hipófise – atualizações e controvérsias

IntroductionRadiotherapy is an effective treatment for residual or recurrent pituitary tumors with tumor volume control and decrease or normalization of excess hormone secretion in the clinically functioning adenomas. The risks of long-term toxicity, being the hypopituitarism the most frequent, make radiation therapy a rarely used second-line treatment. ObjectivesTo describe efficacy, safety and role of conventional external beam radiotherapy, as well as radiosurgery in the treatment of pituitary tumors. Material and MethodsSearch of original or review papers published until January 2012 with the following keywords“pituitary radiotherapy”, “radiotherapy for pituitary adenomas”, “stereotactic radiotherapy”, “pituitary radiosurgery”, “radiation therapy”, “radiotherapy for Cushing's Disease”, “radiotherapy for acromegaly”, “radiotherapy for non-functioning pituitary adenomas”, “radiotherapy for prolactin-secreting pituitary tumors”. ConclusionsRadiotherapy still has a complementary role to surgical resection, although it could be appropriate as a first-line treatment in selected cases. The new modalities of radiation treatment show promising results in the reduction of toxicity as well as in the latency of hormonal response; however more studies are necessary to prove long-term efficacy and safety.

Clinical manifestations of prolactin-secreting pituitary tumors in children and adolescents

Scarce clinical manifestations of prolactin-secreting pituitary tumors in children and adolescents make it difficult to timely diagnosis. Girls have more prevalence of microprolactinomas, manifests as a rule, menstrual irregularities. In males, the greater incidence of macroadenomas results in the presence of neuroophthalmologic signs. The diagnosis of prolactinomas requires both radiographic evidence of pituitary adenoma and laboratory analysis of sustained hyperprolactinemia.

DISORDERS OF BONE METABOLISM IN CHILDREN AND ADOLESCENTS WITH HYPERPROLACTINEMIA

Many patients with prolactin secreting pituitary tumors have a decreased bone mineral density. The bone loss is associated with an increase in bone resorption and is secondary to prolactin-induced hypogonadism. Normalization of prolactin increases the BMD but is not associated with its normalization. Despite low BMD hyperprolactinemic subjects do not demonstrate increase in fractures compared with the general population.

Radiotherapy for prolactin-secreting pituitary tumors

Review the medical and surgical management of patients with prolactinomas and provide an in-depth appraisal of the role of radiotherapy in the treatment of prolactinomas. A thorough review of the pertinent literature was carried out and relevant topics were identified. Topics covered in this comprehensive review include: indications for the use of radiotherapy, choice between conventional radiotherapy and stereotactic radiosurgery, as well as the benefits and potential complications associated with each modality. Due to the excellent response rates with medical management, and rapid symptom relief afforded by resection or debulking surgery in patients who do not respond or tolerate medical therapy, radiotherapy is reserved for patients who do not respond to dopamine agonists and surgery. Both external beam radiotherapy and stereotactic radiosurgery retain important roles in the treatment of refractory or recurrent prolactinomas. Choosing the optimal approach is crucial in maximizing tumor control outcomes and minimizing the risks associated with treatment. The primary determinants of optimal radiation approach are proximity of the tumor to the optic apparatus and tumor size, with radiosurgery being our recommended treatment of choice unless the tumor is larger than 3-4 cm or within 3 mm of the optic nerves, chiasm or tracts. Optimal multidisciplinary management requires the identification of appropriate candidates for radiotherapy in order to take full advantage of treatment options available for each patient.

Clinical significance of anaemia associated with prolactin-secreting pituitary tumours in men

An association between prolactin-secreting pituitary adenomas and anaemia in male patients has been recently reported. Our aim has been to evaluate the prevalence of anaemia in men with prolactinomas and to assess the relationships between haemoglobin concentrations and pituitary function at diagnosis in these patients. In a retrospective analysis, 26 male patients with prolactinomas (22 macroprolactinomas and 4 microprolactinomas) were studied. Blood haemoglobin concentration, haematocrit value and baseline hormonal levels were collected at the time of prolactinoma diagnosis. The presence or absence of partial or total hypopituitarism was also evaluated at diagnosis. Logistic regression analysis was used to assess the presence of anaemia as a function of serum hormone concentrations and pituitary dysfunction. Patient bearing macroprolactinomas showed significant lower haemoglobin concentrations than those found in patients with microprolactinomas (13.5 ± 1.2 g/dl vs. 15.1 ± 0.9 g/dl, p < 0.05). Anaemia (haemoglobin < 13 g/dl) was present in nine (34.6%) patients, all of them with macroprolactinomas. The degree of anaemia was mild (haemoglobin > 11 g/dl) in all patients. No correlation between haemoglobin and serum prolactin was found. Haemoglobin concentration was significantly lower in men with hypogonadism (n = 14) than in eugonadal men. Haemoglobin value was also significantly lower in patients with total hypopituitarism in comparison with patients with partial hypopituitarism (12.4 ± 1.0 g/dl, n = 7 vs. 14.0 ± 1.2 g/dl, n = 13, p = 0.007). The number of affected pituitary axes was found to be related with the presence of anaemia. Logistic regression analysis showed that anaemia was related with FT4 (OR 0.23; 95% CI 0.06-0.81, p = 0.02), cortisol (OR 0.81; 95% CI 0.68-0.96, p= 0.02) and the presence of hypopituitarism (OR 20.0; 95% CI 1.68-238.63, p = 0.02). Anaemia was found in about a third of men with prolactinomas. Our results also suggest that the presence of anaemia in these patients seems to be associated with panhypopituitarism.