Primary hyperparathyroidism presenting as a brown tumor with hypercalcemia crisis in a second-trimester pregnant woman: A case report.

INTRODUCTION: Primary hyperparathyroidism (PHPT) in pregnancy is rare and unrecognized because the maternal physiological adaptations blurs the symptoms. There is no standard treatment strategy for maternal PHPT. Early diagnosis and interventions can prevent catastrophic consequences to the mother and fetus. PATIENT CONCERNS: A 31-year-old Chinese woman was admitted, due to a lump on the left lower leg for 4 months. The patient complained of mild pain in the left lower leg following exercise that could be relieved after a short rest. The patient was at 18 weeks of gestation, and the growth of the fetus was normal. The patient has a 3-year history of hypercalcemia and a 2-year history of nephrolithiasis. No family history of hypercalcemia and endocrine tumors were present. DIAGNOSIS: Laboratory tests demonstrated high serum calcium level of 3.84 mmol/L, parathyroid hormone 1393 pg/mL, alkaline phosphatase 488 µ/L. Ultrasound showed a 22.4 mm × 7.8 mm solid nodule in the left lower lobe of the thyroid gland. Based on these findings, the patient was diagnosed with PHPT. INTERVENTIONS: The patient accepted continuous renal replacement to reduce ironized calcium level. Parathyroidectomy was performed at the 19th week of gestation. Threatened abortion occurred 2 days after the surgery, and magnesium sulfate was used to prevent the abortion. Calcium gluconate, calcium carbonate and vitamin D3 were used to treat the hypocalcemia that occurred 5 days after the surgery. OUTCOMES: Pathology examination demonstrated the parathyroid adenoma. Abortion was prevented using magnesium sulfate and hypocalcemia was cured with calcium gluconate, calcium carbonate and vitamin D3. At 38-week of gestation, the patient (ionized calcium level: 2.16 mmol/L) delivered a healthy female baby weighing 2700 g with 10/10 Apgar. Till now, both the mother and infant showed no complications. CONCLUSION: Maternal PHPT is rare and challenging to diagnose, causing life-threatening complications to mother and fetus. Any decision regarding surgery for a pregnant woman with primary hyperparathyroidism is more complex than in men or nonpregnant women. The decision should be made based on the severity of hypercalcemia and symptoms.

Medulloblastoma during pregnancy: Hormone-mediated association? Report of 2 cases.

OBJECTIVE: To report two rare cases of medulloblastoma in pregnant patients and a review of the literature. MATERIAL AND METHODS: Report of patients diagnosed with medulloblastoma during their pregnancies, who were treated with surgery and adjuvant therapy. We also reviewed other cases reported in the literature and the association made with hormonal receptors. RESULTS: Brain tumors in coincidence with pregnancy are unusual, and the incidence of medulloblastoma in pregnancy is still rarer. We found 8 cases of medulloblastomas diagnosed during pregnancy. Reports suggest that hormonal changes and increases in the levels of growth factors and angiogenic factors during pregnancy influence the rate of growth of brain tumors (not only medulloblastomas but also meningiomas or glial tumors). CONCLUSIONS: The uniqueness of these cases is their rarity. The symptoms are usually masked by the symptoms of pregnancy. At present, there is still little evidence regarding the pathogenesis and treatment of medulloblastoma in pregnancy.

The effect of prednisolone on endometrial VGEF concentrations, Gene polymorphisms and pregnancy outcome in women with polycystic ovary syndrome: A retrospective cohort study.

PCOS (Polycystic Ovary Syndrome) occurs due to hyperandrogenism, excessive androgen, abnormal growth, steroidogenesis and seems to be associated with abnormal Vascular endothelial growth factor (VEGF) level in serum. The treatment is provided on the basis of body symptoms to mute the excess production of hormone. The study assessed the effect of prednisolone treatment on the concentration of VEGF, pregnancy outcomes and variants of VEGF SNPs. In the current retrospective study, the samples were collected from PCOS female patients who received prednisolone and those who did not received it, were compared along with control, in terms of pregnancy results and the association complications. The results inferred that the prednisolone made the concentration of VEGF significantly to normal levels along with other pregnancy-related and growth-related hormones. But the reduced normal limits were achieved only among few patients whereas no significant improvement found in the women who received prednisolone and control, in terms of pregnancy outcomes or complications. Further, there were no relations between the impact of treatment and the variants of VEGF SNPs. To conclude, there is no solid evidence found in the current study with regards to notable beneficial effect when the patients were treated with prednisolone, either in pregnancy outcomes or VEGF SNPs. The current study results should be considered only as a preliminary one since the genetic polymorphisms tend to exhibit different results based on population, ethnic groups etc. The results yielded may not be generalized due to differences in genetic background.

Hyperparathyroidism during pregnancy. Is it a diagnostic and therapeutic challenge?

BACKGROUND: Primary hyperparathyroidism (PHPT) is characterized by an increase in parathyroid hormone (PTH) and hypercalcemia, which, when present during pregnancy, increases both maternal and fetal morbidity and mortality. OBJECTIVE: Emphasize the importance of surgical intervention in primary hyperparathyroidism during pregnancy. CLINICAL CASE: A 27-year-old female with a pregnancy of 27.2 weeks of gestation, with a diagnosis of symptomatic primary hyperparathyroidism secondary to parathyroid adenoma, a history of nephrolithiasis and severe acute pancreatitis, surgery was decided upon finding intrathyroid right parathyroid adenoma, post-surgical course with adequate evolution and remission of hyperparathyroidism. CONCLUSIONS: Parathyroidectomy in primary hyperparathyroidism during pregnancy is safe.

INTRODUCCIÓN: El hiperparatiroidismo primario (HPTP) se caracteriza por un aumento de la hormona paratiroidea (PTH) e hipercalcemia, que aumenta la morbimortalidad materna y fetal cuando se presenta durante el embarazo. OBJETIVO: Enfatizar la importancia de la intervención quirúrgica en el hiperparatiroidismo primario durante el embarazo. CASO CLÍNICO: Paciente femenino de 27 años de edad con embarazo de 27.2 semanas de gestación, con diagnóstico de hiperparatiroidismo primario sintomático secundario a adenoma paratiroideo, antecedentes de nefrolitiasis y pancreatitis aguda grave; al decidir realizar un procedimiento quirúrgico se identificó un adenoma paratiroideo derecho intratiroideo; el curso posquirúrgico mostró adecuada evolución y remisión del hiperparatiroidismo. CONCLUSIÓN: La paratiroidectomía en el hiperparatiroidismo primario durante el embarazo es segura.

Serum vascular endothelial growth factor-D as a diagnostic and therapeutic biomarker for lymphangioleiomyomatosis.

BACKGROUND: In lymphangioleiomyomatosis (LAM), tuberous sclerosis gene mutations activate the mechanistic target of the rapamycin pathway, resulting in vascular endothelial growth factor-D (VEGF-D) overproduction. While the utility of serum VEGF-D testing for the diagnosis of LAM is outlined in ATS/JRS LAM Guidelines, the assay has not been fully validated for Asian populations. Our aims were to validate serum VEGF-D testing in Japan, by directly comparing measurements in Japan and the U.S., determining the diagnostic cut-off for serum VEGF-D levels among the Japanese women with typical thin walled cystic change on CT, and determining the performance of VEGF-D as a prognostic biomarker. SUBJECTS AND METHODS: We determined serum VEGF-D levels from 108 LAM patients, 14 disease controls, and 51 healthy volunteers from the Japanese population. Measurements of 61 LAM patients were compared to those from the principal VEGF-D laboratory in the U.S at Cincinnati Children's Hospital Medical Center. We correlated baseline serum VEGF-D levels with baseline and longitudinal clinical data to determine how pregnancy, sirolimus or gonadotrophin-releasing hormone (GnRH) agonists influence serum VEGF-D levels. RESULTS: Serum VEGF-D measurements in Japan and the U.S. were very similar. Baseline serum VEGF-D levels effectively distinguished LAM from other diseases and healthy volunteers at a cut-off level of 645 pg/ml and were diagnostically specific at 800 pg/ml, consistent with the recommendations of the ATS/JRS LAM Guidelines. Baseline serum VEGF-D correlated negatively with the DLco baseline % predicted and with the annual decrease in DLco % predicted. There was no significant association between baseline serum VEGF-D level and the outcomes of death or transplant. Serum VEGF-D levels markedly decreased during treatment with sirolimus, but not with GnRH analogues. Serum VEGF-D levels of most LAM patients did not increase over time, and neither pregnancy nor menopause significantly modulated serum VEGF-D levels. CONCLUSIONS: Serum VEGF-D is a useful diagnostic and therapeutic biomarker for LAM. Satisfactory precision and international inter-laboratory agreement of the clinical assay support VEGF-D recommendations in the ATS/JRS LAM Guidelines for the Japanese population.

Prolactin, prolactin disorders, and dopamine agonists during pregnancy.

Pituitary disorders, and especially prolactinomas, are not common among pregnant women, though they tend to occur during a woman's years of fertility. The majority of prolactinoma patients present with infertility and menstruation dysfunction; however, prolactinomas are associated with potentially significant morbidity if they remain unrecognized and untreated. Herein, we survey the role of prolactin and prolactinomas in pregnancy while also outlining the therapeutic approach to prolactinoma during pregnancy. The current literature on the impact of dopamine agonists during pregnancy is also reviewed.

Accelerated growth of hemangioblastoma in pregnancy: the role of proangiogenic factors and upregulation of hypoxia-inducible factor (HIF) in a non-oxygen-dependent pathway.

Hemangioblastomas (HBs) are benign, highly vascular tumors, often characterized by loss of function of the von Hippel-Lindau (vHL) gene. They are the most common central nervous system tumor observed in vHL syndrome. Loss of function of the vHL gene creates a "pseudo-hypoxic" state, causing overactivation of hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF)-related pathways. In some cases, HBs can rapidly increase in size during pregnancy to then present acutely, which most frequently occurs after the 20th gestational week. These changes in size usually occur from enlargement of the cystic component of the HB. Due to their preferred location in the posterior fossa near critical structures as well as along the spinal cord, such cases can present with severe neurological deficits, requiring urgent surgical intervention in a multidisciplinary setting. However, the reasons for this acute flare-up during pregnancy remain poorly understood, as are the reasons why this occurs in only a subset of tumors. Unveiling the etiology for this clinical scenario can affect the treatment of HBs, as it will contribute to the understanding of the pathophysiology of such a transformation from a quiescent lesion to a symptomatic one, not only in the setting of pregnancy. Identifying the correct triggers and the conditions initiating and mediating this switch will enable us to develop preventive medications which should allow us to keep the tumor in its quiescent phase. In this pathophysiological review, we investigate the association between HB growth and pregnancy based on an analysis > 40 such published cases. We suggest that the proangiogenic state of pregnancy is the leading etiology for this striking association, and to support the argument, we discuss its potential impact on HIF overexpression in a non-hypoxic manner through activation of the PI3K/Akt/mTOR pathway by proangiogenic factors. Specifically, we discuss the involvement of placental growth factor (PlGF) and its receptor vascular endothelial growth factor receptor 1 (VEGFR-1) in various pathologic processes that can lead to the formation and growth of peritumoral edema and cysts, which are the primary causes for the development of any symptoms in HB. Both PlGF and VEGFR-1 are expressed at increased levels during pregnancy, and both have been reported as part of various pathological processes, including angiogenesis and tumorigenesis. The unique feature that both do essentially not show any significant negative impact on regular physiological processes makes them attractive therapeutic targets since very little side effects are expected. Further research into the effects of anti-PlGF or anti-VEGFR-1 therapy in HB is therefore recommended.

Significance of Serum Human Epididymis Protein 4 and Cancer Antigen 125 in Distinguishing Type I and Type II Epithelial Ovarian Cancers.

OBJECTIVE: The objective of this study was to assess the effectiveness of human epididymis protein 4 (HE4) and cancer antigen 125 (CA125), and risk of ovarian malignancy algorithm (ROMA) in identifying type I and type II epithelial ovarian cancers (EOCs). METHODS: A cross-sectional diagnostic study was conducted of 499 Thai women older than 18 years who had clinically diagnosed pelvic masses and underwent elective surgery at our hospital between July 2012 and July 2014. Preoperative serum HE4 and CA125 levels were measured, and postoperative pathologic slides were reviewed. RESULTS: Of 499 Thai women enrolled in this study, 357 were noncancerous (NC), 79 had type I EOCs (EOCs-I) and 63 had type II (EOCs-II). Risk of ovarian malignancy algorithm revealed significantly better performance than HE4 and CA125 in discriminating between NC and EOCs-I (receiver operating characteristic curve and area under the curve [ROC-AUC]: ROMA, 0.86; HE4, 0.80; and CA125, 0.77), and NC and EOCs-II (ROC-AUC: ROMA, 0.97; HE4, 0.95; and CA125, 0.93). In differentiation between EOCs-I and EOCs-II (setting EOC-II as reference), ROMA yielded a better performance than HE4 and CA125 (ROC-AUC: ROMA, 0.83; HE4, 0.82; and CA125, 0.77); however, CA125 and HE4 showed higher sensitivity (CA125, 77.8%; HE4, 76.2%), whereas ROMA had the highest specificity (79.8%). CONCLUSIONS: In women who present with pelvic masses, ROMA performed very well in distinguishing between noncancer lesions and EOCs but the combined HE4 and CA125 test was more effective in predicting EOC types.

Hypercalcemic crisis in third trimenon: evaluating the optimal treatment strategy.

Hypercalcemia due to primary hyperparathyroidism during pregnancy is a rare condition and associated with increased morbidity and mortality for the mother and the unborn child. Whereas parathyroidectomy is favored during the second trimester, no clear recommendations exist for its management during the third trimenon. We here report the case of a 26-year-old woman in the 29th week of her first pregnancy, who was admitted to our clinic with hypertension, intra-uterine growth retardation and polyhydramnios. Severe hypercalcemia due to primary hyperparathyroidism was diagnosed (total calcium 3.34 mmol/l; PTH 216 pg/ml), but no enlarged parathyroid gland could be localized by ultrasound. Treatment with calcitonin and cinacalcet could not control hypercalcemia. Therefore explorative surgery was performed and a single parathyroid adenoma was resected, resulting in normalization of serum calcium levels. The surgical procedure was tolerated well by the mother and fetus. Hypercalcemia-induced hypertension and polyhydramnios ameliorated before C-section was performed two weeks later and unrelated to the intervention. This case report underlines the importance of early diagnosis and treatment of primary hyperparathyroidism during pregnancy. If diagnosed in the third trimenon, an interdisciplinary approach is crucial. If medical treatment fails to sufficiently control hypercalcemia, surgical parathyroid exploration should be considered even in cases of unsuccessful localization of adenomatous parathyroid glands.

Cross-reactivity between MUC1 antigen and MCA: false elevation of serum CA 15-3 level in pregnant and lactating women by Ma695-Ma552-based assay.

PURPOSE: Cancer antigen 153 (CA 15-3) is one of the most commonly used biomarkers of breast cancer. However, elevated CA 15-3 is reported in pregnant and lactating women more frequently on Beckman DxI 800 immunoassay system (Ma695-Ma552 antibody pair) than on Abbott ARCHITECT system (115D8-DF3 antibody pair) in laboratory methodological evaluation. We conducted this study in order to figure out the reason behind this phenomenon. METHODS: Serum CA 15-3 concentration was analyzed in 426 subjects, including 180 patients with breast cancer, 121 patients with benign breast disease, and 125 healthy volunteers (45 pregnant and 80 non-pregnant women). CA 15-3 assay was further validated using another cohort of 112 pregnant or postpartum women. Immunological cross reaction was analyzed by Western blotting and immunoprecipitation. RESULTS: The serum CA 15-3 level was abnormally higher in almost 95% of the pregnant and lactating women detected using Ma695-Ma552 antibody pair (median: 71.4 U/mL) than that detected using 115D8-DF3 antibody pair (median: 16.5 U/mL). Western blotting and immunoprecipitation indicated that such a significant difference was mainly due to the cross reaction between monoclonal antibody Ma552 and mucin-like carcinoma-associated antigen (MCA). CONCLUSIONS: The CA 15-3 assay using 115D8-DF3 antibody pair is more suitable for monitoring therapy in pregnancy-associated breast cancer.

Maternal Malignancy Evaluation After Discordant Cell-Free DNA Results.

Cell-free DNA screening for fetal aneuploidy is a commonly used testing strategy in pregnancies at high risk for fetal aneuploidy. The use of cell-free DNA screening is expanding to the low-risk population, because the detection rate for trisomy 21 surpasses that of traditional screening modalities. Although the sensitivity and specificity of cell-free DNA are superior to traditional screening, false-positive results do occur and may indicate an adverse maternal health condition, including maternal mosaicism or, rarely, malignancy. The risk of maternal cancer is significantly elevated when more than one aneuploidy is detected that is discordant from fetal karyotype. Given this risk as well as the rising incidence of cancer in pregnancy, patient counseling and malignancy evaluation should be considered in women when more than one aneuploidy is detected. We reviewed the published literature and developed an algorithm to evaluate women when these results are identified.

Unique features of pregnancy-related meningiomas: lessons learned from 148 reported cases and theoretical implications of a prolactin modulated pathogenesis.

Meningiomas are some of the most frequently encountered adult intracranial tumors. Dramatic flare ups in size may occasionally be observed during pregnancy, leading to complicated clinical scenarios, with profound effects and substantial risks for both the mother's and the fetus's well-being. Despite the fact that such changes have largely been attributed to progesterone-based mechanisms, recent studies have put this theory into question or defied it. In order to assess these particular tumors carefully and to try and clarify the pathophysiology of such pregnancy-related meningioma growth, an in-depth review of the pertinent literature was undertaken. Based on clinical, radiographic, and pathological data gathered from 148 reported cases, we have found several unique features characterizing these pregnancy-related meningiomas. The presence of such observed features was found to be of high statistical significance when compared to their expected prevalence in the general population and included the following: (1) parasellar location, (2) anterior circulation blood supply, (3) visual symptoms at presentation, (4) high rate of clear-cell and chordoid morphology. A hypothesis is developed that these features are related to hormonal influences of the pituitary gland, and we discuss that this may be due to elevated prolactin levels. We encourage further research to test this exciting new theory.

How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey.

OBJECTIVE: Data regarding pregnancies in relation to pituitary tumors are limited. The effects of pregnancy on pituitary adenomas and the effects of adenoma itself (hormonal activity, mass effects and pituitary insufficiency) and/or treatment on the ongoing gestation and developing fetus were evaluated. METHODS: The study was a retrospective study. A questionnaire involving questions regarding medical history before index gestation, history of related pregnancy, result of index gestation and postpartum follow-up of the patients was filled by the investigator in one of the eight Referral Endocrinology Centers from Turkey. RESULTS: One hundred and thirteen (83 prolactinoma, 21 acromegaly, 8 NFPA and 1 plurihormonal pituitary adenoma) pregnancies of 87 (60 prolactinoma, 19 acromegaly, 7 NFPA and 1 plurihormonal pituitary adenoma) patients were reviewed. The clinically important pregnancy-related tumor growth of pituitary adenomas was found to be low in previously treated adenomas. Prolactinomas were more likely to increase in size during pregnancy especially if effective prior treatment was lacking. The risk of hypopituitarism is also minimal due to pituitary adenomas during pregnancy. The results of pregnancies did not differ in patients who were on medical treatment or not for prolactinomas and acromegaly during gestation. Neural tube defect and microcephaly associated with maternal cabergoline use; Down syndrome and corpus callosum agenesis associated with maternal bromocriptine use; unilateral congenital cataract, craniosynostosis and microcephaly associated with maternal acromegaly were detected for the first time. CONCLUSION: Medical treatment can be safely done stopped in patients with prolactinoma and acromegaly when pregnancy is confirmed and reinstituted when necessary. Prospective studies may help to determine the effects of medical treatment during gestation on the mother and fetus.

Incidental Detection of Maternal Neoplasia in Noninvasive Prenatal Testing.

BACKGROUND: Noninvasive prenatal testing (NIPT) uses cell-free DNA (cfDNA) as an analyte to detect copy-number alterations in the fetal genome. Because maternal and fetal cfDNA contributions are comingled, changes in the maternal genome can manifest as abnormal NIPT results. Circulating tumor DNA (ctDNA) present in cases of maternal neoplasia has the potential to distort the NIPT readout to a degree that prevents interpretation, resulting in a nonreportable test result for fetal aneuploidy. METHODS: NIPT cases that showed a distortion from normal euploid genomic representation were communicated to the caregiving physician as nonreportable for fetal aneuploidy. Follow-up information was subsequently collected for these cases. More than 450000 pregnant patients who submitted samples for clinical laboratory testing >3 years are summarized. Additionally, in-depth analysis was performed for >79000 research-consented samples. RESULTS: In total, 55 nonreportable NIPT cases with altered genomic profiles were cataloged. Of these, 43 had additional information available to enable follow-up. A maternal neoplasm was confirmed in 40 of these cases: 18 malignant, 20 benign uterine fibroids, and 2 with radiological confirmation but without pathological classification. CONCLUSIONS: In a population of pregnant women who submitted a blood sample for cfDNA testing, an abnormal genomic profile not consistent with fetal abnormalities was detected in about 10 out of 100000 cases. A subset of these observations (18 of 43; 41.9%) was attributed to maternal malignant neoplasms. These observational results suggest the need for a controlled trial to evaluate the potential of using cfDNA as an early biomarker of cancer.

Management of chronic myeloid leukemia in the setting of pregnancy: when is leukocytapheresis appropriate? A case report and review of the literature.

BACKGROUND: Chronic myeloid leukemia (CML) is a common hematologic malignancy; however, its occurrence during pregnancy is unusual due to its low prevalence in females of childbearing age. There are conflicting reports of how to best manage CML in pregnancy, particularly in the setting of leukocytosis. HEMAPHERESIS: A 30-year-old female was diagnosed with CML at 18 weeks' estimated gestational age. On initial presentation she reported fatigue, night sweats, and early satiety, and was found to have a white blood cell (WBC) count of 69.3 × 109 /L and platelet count of 366 × 109 /L. Her disease was managed during pregnancy using interferon-α alone despite persistent leukocytosis. CONCLUSION: CML may be effectively managed during pregnancy, even in the setting of leukocytosis, without the application of leukocytapheresis. Management relies not only upon the coordination of drug therapy and fetal monitoring, but requires close communication between multiple medical disciplines. Leukocytapheresis has been safely performed during pregnancy and may be a suitable adjunct management strategy in pregnant patients diagnosed with CML with specific clinical presentations, such as hyperleukocytosis (WBC count > 150 × 109 /L) and/or symptomatic leukostasis.

Prospective evaluation of serum anti-Müllerian hormone dynamics in 250 women of reproductive age treated with chemotherapy for breast cancer.

AIM: Women of reproductive age with breast cancer generally receive gonadotoxic chemotherapy. Fertility issues are of great concern for them. However, little is known on ovarian damage during chemotherapy and its evolution during long-term follow-up. The aim of this study was to provide a detailed description of serum anti-Müllerian hormone (AMH) evolution during chemotherapy and 24-month follow-up. METHODS: This prospective cohort study was conducted in 250 patients, aged 18-39 years, diagnosed with breast cancer and treated with adjuvant/neoadjuvant chemotherapy. Each patient underwent blood AMH measurement at each chemotherapy cycle, and at 6, 12 and 24 months after chemotherapy. Menses occurrence was also recorded. RESULTS: Mean basal AMH level was 4.19 ± 4.84 ng/mL, and was negatively correlated with age. Serum AMH level rapidly decreased in all patients after each chemotherapy cycle to undetectable levels in most of them, and slowly increased in 45% of the patients during the 24-month follow-up. AMH decrease was significantly associated with age and basal AMH level, but not with cyclophosphamide dose and tamoxifen use. The prevalence of chemotherapy-related amenorrhoea was 92.4% at the end of chemotherapy; women with amenorrhoea being significantly older and having lower basal AMH than women who resumed menses. CONCLUSIONS: Our study confirms rapid and deep ovarian reserve alteration in young women receiving chemotherapy for breast cancer, and shows moderate AMH recovery in some patients. Although AMH cannot alone predict fertility potential, these new data emphasise the need for post-treatment ovarian insufficiency follow-up, strongly support the use of fertility preservation strategies and may provide new tools for improved counselling.

Maternal, Fetal, and Neonatal Imatinib Levels With Treatment of Chronic Myeloid Leukemia in Pregnancy.

BACKGROUND: Pregnant women with chronic myeloid leukemia (CML) can be treated effectively with the tyrosine-kinase inhibitor imatinib, but data regarding fetal and neonatal exposure and safety are limited. CASE: We present a patient with newly diagnosed CML in early pregnancy. Leukapheresis and interferon-α were initiated in the second trimester with limited benefit. Imatinib was subsequently started at 28 weeks of gestation with complete hematologic response within 4 weeks. No significant maternal or neonatal adverse effects were noted, but imatinib and its primary active metabolite concentrated in maternal breast milk and neonatal urine. CONCLUSION: Imatinib is effective for CML in pregnancy, but caution is warranted in light of potentially unrecognized fetal and neonatal effects.

Prolactin Secreting Pituitary Microadenoma: Results of Transsphenoidal Surgery After Medical Therapy With Dopamine Agonist.

Medical therapy with dopamine agonist is very effective in controlling prolactin serum levels and it usually represents the first therapeutic choice for prolactin secreting pituitary adenomas. However, many patients present increase of prolactinemia after withdrawal of medical therapy which consequently should be taken for long time; other present intolerance to medical therapy; women with pregnancy need to withdraw dopamine agonists with consequent potential related problems: in these patients transsphenoidal surgery can be requested. The presented study concerns the efficacy of transsphenoidal surgery in patients affected by microprolactinoma after treatment with medical therapy for different periods of time. Different postsurgical results were achieved in 2 groups of 24 (group 1) and 25 (group 2) patients affected by microprolactinoma who had taken medical therapy for a period of time respectively longer or shorter than 1 year. In summary, the authors observed in group 1 a rate of hormonal remission of 33.3% and an overall prolactinemia improvement with possibility of medical therapy withdrawal in 49.9% of patients. In group 2, the authors observed a rate of hormonal remission of 84% and an overall rate of improvement with no necessity of medical therapy of 92%. Therefore, the authors' experience showed that the surgical option for the therapy of microprolactinomas should be indicated within 1 year from the beginning of medical therapy with dopamine agonist, to achieve a high rate of hormonal remission and possibility to withdraw medical therapy. The authors' protocol for microprolactinoma treatment is presented.