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prolactinoma

Prolactinoma

Epidemiology

Prolactinomas are the most common functioning pituitary adenomas.

They account for approximately 40 % of all pituitary adenomas. Over 95 % of prolactinomas are microadenomas (< 10 mm diameter).

Types

Current classification systems rely on phenotypic elements and have few molecular markers for complementary classification.

Giant prolactinoma

Macroprolactinoma

Microprolactinoma (At the time of diagnosis , 90 % of prolactinomas in women are microadenomas, vs. 60 % for males probably due to gender specific differences in symptoms resulting in earlier presentation in females).

Cystic prolactinoma

Etiology

Neoplastic transformation of lactotrophs.

Gene and protein expression

Seltzer et al. aimed to summarize prior research exploring gene and protein expression in prolactinomas in order to highlight molecular variations associated with tumor development, growth, and prolactin secretion. A PubMed search of select MeSH terms was performed to identify all studies reporting gene and protein expression findings in prolactinomas from 1990 to 2014.

1392 abstracts were screened and 51 manuscripts were included in the analysis, yielding 54 upregulated and 95 downregulated genes measured by various direct and indirect analytical methods. Of the many genes identified, three upregulated (HMGA2, HST, SNAP25), and three downregulated (UGT2B7, Let7, miR-493) genes were selected for further analysis based on our subjective identification of strong potential targets.

Many significant genes have been identified and validated in prolactinomas and most have not been fully analyzed for therapeutic and diagnostic potential. These genes could become candidate molecular targets for biomarker development and precision drug targeting as well as catalyze deeper research efforts utilizing next generation profiling/sequencing techniques, particularly genome scale expression and epigenomic analyses 1).

A total of 52 genes were identified as being significantly different between prolactinomas and normal samples which were classified into 29 COG functional categories. Three TFs, ZIC3 (Zic family member 3), NGFIC (nerve growth factor-induced protein C) and SP1 (Specificity Protein 1) were screened out, which can regulate part of DEGs. Two down-regulated genes, FSHB (follicle stimulating hormone β subunit) and LHB (luteinizing hormone β subunit) were involved in GnRH (gonadotropin releasing hormone) signaling pathway 2).

Clinical features

Some tumors secrete both PRL and GH.

see Prolactinoma Clinical Features

Management

Books

MRI of the Pituitary Gland By Jean-François Bonneville, Fabrice Bonneville, Françoise Cattin, Sonia Nagi

This clinically oriented book will familiarize the reader with all aspects of the diagnosis of tumors and other disorders of the pituitary gland by means of magnetic resonance imaging (MRI). The coverage includes acromegaly, Cushing’s disease, Rathke cleft cysts, prolactinomas, incidentalomas, Clinically nonfunctioning pituitary adenomas, other lesions of the sellar region, hypophysitis, and central diabetes insipidus. Normal radiologic anatomy and the numerous normal variants are described, and guidance is also provided on difficulties, artifacts, and other pitfalls. The book combines concise text and high-quality images with a question and answer format geared toward the needs of the practitioner. MRI is today considered the cornerstone in the diagnosis of diseases of the hypophyseal-hypothalamic region but the relatively small size of the pituitary gland, its deep location, the many normal anatomic variants, and the often tiny size of lesions can hinder precise evaluation of the anatomic structures and particularly the pituitary gland itself. Radiologists and endocrinologists will find MRI of the Pituitary Gland to be full of helpful information on this essential examination, and the book will also be of interest to internists and neurosurgeons.

Literature review

A systematic literature review was performed utilizing the PRISMA guidelines. Seltzer et al. aimed to summarize prior research exploring gene and protein expression in prolactinomas in order to highlight molecular variations associated with tumor development, growth, and prolactin secretion. A PubMed search of select MeSH terms was performed to identify all studies reporting gene and protein expression findings in prolactinomas from 1990 to 2014.

1392 abstracts were screened and 51 manuscripts were included in the analysis, yielding 54 upregulated and 95 downregulated genes measured by various direct and indirect analytical methods. Of the many genes identified, three upregulated (HMGA2, HST, SNAP25), and three downregulated (UGT2B7, Let7, miR-493) genes were selected for further analysis based on our subjective identification of strong potential targets.

Many significant genes have been identified and validated in prolactinomas and most have not been fully analyzed for therapeutic and diagnostic potential. These genes could become candidate molecular targets for biomarker development and precision drug targeting as well as catalyze deeper research efforts utilizing next generation profiling/sequencing techniques, particularly genome scale expression and epigenomic analyses 3).

Case series

Sixty-three consecutive female patients with a mean age of 29.5 ± 1.1 years. Based on magnetic resonance imaging findings before surgery, 31 (49.2%) patients had microadenoma, and the remaining 32 (50.8%) had macroadenoma. The median follow-up after transsphenoidal surgery was 53 (33-74) months, and long-term surgical remission was achieved in 50 (79.37%) patients with 28 (90.32%) microadenomas and 22 (68.75%) macroadenomas. No meningitis or persistent cerebrospinal fluid leaks occurred. Only one case suffered from persistent diabetes insipidus at follow-up. No severe pituitary dysfunction was observed in microprolactinoma patients. Of patients with menstrual disorders, 85% regained regular menstrual cycles after surgery. Nineteen patients in this cohort desired pregnancy and 15 of them successfully gave birth after surgery. All 17 microadenoma patients with modern surgical indications achieved normal prolactin levels and regular menstrual cycles with only one patient on drug therapy at follow-up.

Long-term follow-up showed a high remission rate in female prolactinoma patients, especially in microadenoma patients, after surgery. Transsphenoidal surgery performed by experienced neurosurgeons may offer a valuable approach to treat female microprolactinoma patients of child-bearing age with modern indications for surgery 4).

2016

Akin et al report herein a retrospective analysis of the results of 142 consecutive prolactinoma cases operated upon using an endoscopic endonasal trans-sphenoidal approach over a period of 6 years.

Medical records of 142 cases were analysed with respect to indications for surgery, duration of hospital stay, early remission rates, failures and recurrence rates during a median follow-up of 36 months.

On the basis of magnetic resonance imaging (MRI) data, 19 patients (13.4 %) had microadenoma, 113 (79.6 %) had macroadenoma, and the remaining 10 (7.0 %) had giant adenomas. Cavernous sinus invasion was identified in 25 patients by MRI and confirmed during surgery. Atypical adenoma was diagnosed in 16 patients. Sparsely granulated prolactin adenoma was identified in 99 patients (69.7 %). Our results demonstrate that male sex and higher preoperative prolactin levels are independent factors predicting persistent disease. The post-surgical complications are as follows: 2.8 % patients had meningitis, 2.1 % patients had postoperative cerebrospinal fluid leak and 2.1 % patients had panhypopituitarism. At the end of follow-up, 74.6 % patients went into remission. During follow-up period, five patients who had initial remission developed recurrence.

This series together with literature data suggest that an endoscopic endonasal trans-sphenoidal approach in the treatment of proloctinomas has a favourable rate of remission. According to the findings of this study, endoscopic endonasal trans-sphenoidal surgery might be an appropriate therapy choice for patients with prolactinoma who could not have been managed with recommended therapeutic modalities 5).

2002

Between 1979 and 1991, 241 patients with prolactinomas underwent transsphenoidal resection. Nineteen patients were lost to follow-up review, whereas the remaining 222 patients underwent measurement of their prolactin levels on postoperative Day 1 (POD 1), at 6 and 12 weeks, and every 6 months thereafter for a minimum of 5 years. On POD 1, prolactin levels in 133 patients (Group 1) were lower than 10 ng/ml, in 43 patients (Group 2) between 10 and 20 ng/ml, and in 46 patients (Group 3) higher than 20 ng/ml. At 6 and 12 weeks, normal prolactin levels (< or = 20 ng/ml) were measured in 132 (99%) of the 133 patients in Group 1 but only in 32 (74%) of the 43 patients in Group 2. By 5 years postoperatively, normal levels of prolactin were still measured in 130 patients (98%) in Group 1 compared with only five patients (12%) in Group 2. No patient with a prolactin level lower than 3 ng/ml on POD 1 was found to have an elevated hormone level at 5 years. The likelihood of a long-term chemical cure was greater for patients with microadenomas (91% cure rate) than for those with macroadenomas (33%). Preoperative prolactin levels also correlated with hormonal outcome.

Prolactin levels lower than 10 ng/ml on POD 1 predict a long-term chemical cure in patients with microadenomas (100% cure rate) and those with macroadenomas (93% cure rate). In contrast, a cure is not likely to be obtained in patients with normal levels ranging between 10 and 20 ng/ml on POD 1 if they harbor macroadenomas (0% cure rate). A recurrence reported several years after surgery probably represents the presence of persistent tumor that was not originally removed. If the initial operation was performed by an experienced surgeon, however, reoperation is not likely to yield a chemical cure 6).

Case reports

2016

Two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10-20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma.

Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists.The interval between prolactinoma and acromegaly diagnoses can be several decades.Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can 
lead to an early diagnosis of acromegaly before the development of complications 7).

2014

A case of sarcomatous transformation of a prolactin (PRL)-producing pituitary adenoma in a 27-year-old man, originally presented with bitemporal visual disturbance, headache, and hyperprolactinemia 8 years earlier. Tumor shrinkage was confirmed by magnetic resonance imaging (MRI) during treatment with dopamine-receptor agonist. However, 3 years later transsphenoidal surgery had to be performed because of tumor re-growth. Histopathological examination revealed a PRL-producing adenoma with fibrotic changes. One year later, he presented with right-sided visual disturbance, and tumor re-growth was confirmed using MRI. He underwent transcranial surgery, followed by radiation therapy (50 Gy in 25 fractions). The histological and immunostaining features were similar in both specimens obtained from the two operations. Four years later, he presented with left-sided visual disturbance, and tumor re-growth was confirmed using MRI. The mass lesion dramatically increased in size within 2 months, and partial removal of the tumor by craniotomy was performed. The specimen was histologically diagnosed as malignant fibrous histiocytoma (MFH). Regardless of aggressive chemotherapy, his clinical symptoms and imaging findings worsened rapidly. He died 7 months after the diagnosis of MFH. Because patients with pituitary tumor undergoing radiotherapy face the possibility of developing such neoplasm, long-term follow-up is required 8).

1) , 3)
Seltzer J, Scotton TC, Kang K, Zada G, Carmichael JD. Gene expression in prolactinomas: a systematic review. Pituitary. 2015 Aug 4. [Epub ahead of print] PubMed PMID: 26238304.
2)
Zhao L, Lin M, Wang S. Identification of human prolactinoma related genes by DNA microarray. J Cancer Res Ther. 2014 July-September;10(3):544-548. doi: 10.4103/0973-1482.137962. PubMed PMID: 25313736.
4)
Yi N, Ji L, Zhang Q, Zhang S, Liu X, Shou X, Lu B. Long-term follow-up of female prolactinoma patients at child-bearing age after transsphenoidal surgery. Endocrine. 2018 Jun 22. doi: 10.1007/s12020-018-1652-y. [Epub ahead of print] PubMed PMID: 29934876.
5)
Akin S, Isikay I, Soylemezoglu F, Yucel T, Gurlek A, Berker M. Reasons and results of endoscopic surgery for prolactinomas: 142 surgical cases. Acta Neurochir (Wien). 2016 May;158(5):933-42. doi: 10.1007/s00701-016-2762-z. Epub 2016 Mar 12. PubMed PMID: 26970763.
6)
Amar AP, Couldwell WT, Chen JC, Weiss MH. Predictive value of serum prolactin levels measured immediately after transsphenoidal surgery. J Neurosurg. 2002 Aug;97(2):307-14. PubMed PMID: 12186458.
7)
Manuylova E, Calvi LM, Hastings C, Vates GE, Johnson MD, Cave WT Jr, Shafiq I. Late presentation of acromegaly in medically controlled prolactinoma patients. Endocrinol Diabetes Metab Case Rep. 2016;2016. pii: 16-0069. PubMed PMID: 27855229.
8)
Kurosaki M, Kambe A, Ishibashi M, Watanabe T, Horie Y. A case report of sarcoma of the sella caused by postoperative radiotherapy for a prolactin-producing pituitary adenoma. Brain Tumor Pathol. 2014 Jan 21. [Epub ahead of print] PubMed PMID: 24446079.
prolactinoma.txt · Last modified: 2018/06/25 10:37 by administrador