Prolactin-secreting Pituitary Microadenoma Research Articles

Features of the course of somatolactotrophic tumors of the pituitary gland. Description of clinical case

A patient aged 32 with complaints of primary infertility based on additional examination data (increased blood prolactin level, presence of pituitary gland formation according to magnetic resonance imaging of the brain) was diagnosed with prolactin-secreting pituitary microadenoma. At the same time, galactorrhea and menstrual disorders were not noted. Against the background of cabergoline treatment, a pregnancy occurred, which ended with the birth of a full-term healthy child. After delivery, the patient resumed dosing cabergoline 0.5 mg 1 once every two weeks, against the background of which a pronounced decrease in prolactin levels was observed, but there was a progression in the growth of pituitary adenoma (macroadenoma). No acromegaly traits were observed in the patient.Against the background of withdrawal of cabergoline, the patient underwent a study of tropical pituitary hormones, which revealed an increase in the level of growth hormone and insulin-like growth factor-1. During the oral glucose tolerance test with 75 grams of glucose, the somatotropin-producing activity of the pituitary macroadenoma was confirmed. At the age of 43, the patient underwent transsphenoidal adenomectomy, after which she experienced persistent remission for past 6 years.The purpose of this work is to focus the attention of practitioners on the manifestation of possible mixed hormonal activity of pituitary microadenomas.

Ectopic Cavernous Sinus Microprolactinoma Treated Medically.

Ectopic prolactin-secreting microadenomas are rare and management is often surgical in contrast to intrasellar pituitary prolactin-secreting microadenomas. We present a case of ectopic dopamine-resistant microprolactinoma treated with cabergoline which led to symptom resolution, hormonal remission, and cystic degeneration of the tumor. A 30-year-old active duty male presented with a chief complaint of inability to maintain an erection for 6 months. Initial workup revealed suppressed serum testosterone of 128.60 ng/ml with an elevated prolactin level at 275.10 ng/ml. Pituitary magnetic resonance imaging showed a small mass measuring 9 mm in the left cavernous sinus. Medical management was initiated with cabergoline, which was titrated over the course of a year from 0.5 mg a week to 3.5 mg a week at its peak before being weaned off completely at 54 months. After treatment, the patient's symptoms resolved, his prolactin decreased to 29.5 ng/ml, near-normal, and his tumor had decreased size with cystic degeneration. Management for any prolactinoma has three primary goals: remittance of symptoms, decrease in prolactin levels, and decrease in tumor size. These are achieved through primarily medical management or surgery. Even though ectopic microprolactinomas are still frequently addressed surgically, this case shows that medical therapy can successfully treat ectopic prolactin-secreting pituitary microadenomas even in cases of dopamine resistance.

Application of Contrast-Enhanced 3-Dimensional T2-Weighted Volume Isotropic Turbo Spin Echo Acquisition Sequence in the Diagnosis of Prolactin-Secreting Pituitary Microadenomas

This study aimed to investigate the value of contrast-enhanced 3-dimensional (3D) T2-weighted (T2W) Volume Isotropic Turbo Spin Echo Acquisition (VISTA) sequence in prolactin-secreting pituitary adenoma diagnosis. We enrolled 158 patients with hyperprolactinemia. Coronal dynamic contrast-enhanced (DCE) T1 spin echo and T2W VISTA sequences were performed. The detection of pituitary microadenomas in 3 imaging groups (DCE magnetic resonance imaging [MRI], VISTA, and DCE MRI + VISTA) were compared using McNemar test and χ2 test. The DCE MRI + VISTA group detected 28 more pituitary microlesions than DCE MRI alone. Among these, 20 lesions were clearly observed on VISTA images but were negative on DCE MRI. The combined sequences showed higher sensitivity (85.3%) and diagnostic accuracy (89.2%) for adenoma detection than any of the sequences alone (P < 0.01). We noted that in 65.7% of the patients with adenoma (46 of 70), a "hypointense rim" was present around the lesion on the VISTA images. Of them, 11 patients underwent surgery. Histopathology confirmed that the "hypointense rim" was a pseudocapsular structure at the edge of the adenoma. For patients with hyperprolactinemia, the 3D T2W VISTA sequence is an important supplement to DCE MRI, because it could improve the detection rate of pituitary microadenomas.

Changes in Options for Management for Prolactin Secreting Pituitary Microadenomas

Changes in Options for Management for Prolactin Secreting Pituitary Microadenomas

SAT-484 Pituitary Microadenoma and Cerebral Venous Thrombosis in a Patient with Transient Adipsic Diabetes Insipidus after Treatment for Craniopharyngioma

Background Craniopharyngioma is a rare embryonic sellar malformation, that can present with headache, motor and cranial nerve palsies. Treatment of large masses involves surgical excision followed by radiation therapy. Hypopituitarism and diabetes insipidus are some of the post-operative complications. Rarely, patients may develop inability to appreciate fluid losses, resulting in marked hypernatremia and dehydration associated with life-threatening lower extremity thrombosis and pulmonary embolism. We present a patient developing cerebral venous thrombosis resulting from transient adipsic diabetes insipidus accompanied by new-onset pituitary microadenoma. Clinical A 39-year-old female post-excision and radiation therapy for craniopharyngioma developed hypopituitarism and diabetes insipidus. Three months after initiating radiotherapy, she presented with headache and inability to sense thirst. She took desmopressin 100 mcg tablet only three times for the past month. There was hypernatremia at 154 meq/L (Normal Value 135-145 meq/L) and hyperprolactinemia at 235 ng/mL (NV 5.11-26.19 ng/ml). Contrast-enhanced MRI revealed cerebral venous thrombosis and a pituitary microadenoma. Thrombosis has been attributed to plasma volume contraction and consequent plasma hyperviscosity. She was started on enoxaparin, hydration with hypotonic solution, desmopressin 100 mcg tablet and bromocriptine 2.5 mg tablet for the possibility of new-onset prolactin secreting pituitary microadenoma. There was decrease in headache severity and normalization of sodium level. She was discharged on apixaban 2.5 mg tablet twice a day, bromocriptine, levothyroxine 100 mcg tab daily, desmopressin daily or at least twice a week and hydrocortisone 20 mg tab daily. After three months, she had increased ability to sense thirst but still had occasional headaches. Imaging showed partial resolution of thrombosis. Prolactin decreased to 0.925 ng/mL (NV 3-20 ng/ml). In general, prolactinomas have serum prolactin that parallel tumor size. Rarely, minimal prolactin elevations may be consistent with a prolactinoma, but a non-prolactin secreting mass should first be considered in the presence of a microadenoma. The initially elevated prolactin has been attributed to disruption of dopamine inhibition to the pituitary lactotrophs. Serial imaging of the pituitary microadenoma appears to be a reasonable follow-up. Prompt evaluation must be done should there be any signs and symptoms of hormonal hypersecretion or if there is increase in size of the microadenoma. Conclusion This is the first case to demonstrate cerebral venous thrombosis and new-onset pituitary microadenoma in a patient developing transient adipsic diabetes insipidus after treatment for craniopharyngioma. These entities must be included in the workup of patients presenting with headache. No relevant disclosures.

GAL3 Protein Expression is Related to Clinical Features of Prolactin-Secreting Pituitary Microadenoma and Predicts its Recurrence after Surgical Treatment

Background: Previous in vitro study showed that Galectin-3 (Gal-3) protein plays an important role in pituitary tumorigenesis, however, the association of Gal-3 expression with the clinical feature and prognosis of pituitary tumor in a clinical setting remains unknown. Methods: We enrolled 220 patients with prolactin-secreting pituitary adenomas (PA) who previously had transsphenoidal pituitary surgery. The Gal-3 expression was detected in the patients' PA samples using immunohistochemistry and those patients were followed up. A prolactin-secreting PA cell line, the MMQ cell line, was used to study the in vitro effect of Gal-3 on proliferation, migration and invasion of PA cells using small interfering RNA (siRNA) transfecton technique. The in vivo tumorgenesis in nude mice was also studied. Results: We found that Gal-3 expression was not related to age and sex, but positively associated with tumor invasion (P<0.001), tumor sizes (P<0.001) and pre-operative prolactin levels (P<0.001). The multivariate Cox analysis showed that the Gal-3 expression was closely associated with the recurrence of PA after the surgical treatment (HR =3.15, P=0.002). The in vitro studies showed that Gal-3 knock-down by the siRNA technique significantly inhibited the proliferation, migration and invasion ability of the MMQ cells, whereas Gal-3 siRNA transfection induced apoptosis of the MMQ cells. The in vivo tumorgenesis assay showed that Gal-3 siRNA transfection significantly inhibited the tumor volume in vivo compared to transfection of the control siRNA (P<0.001). Conclusion: Gal-3 regulates proliferation, apoptosis, migration and invasion of the MMQ cells. Gal-3 may be used as a tissue marker to evaluate the clinical feature and prognosis of PA patients.

Magnetic Resonance Imaging of Cutis Verticis Gyrata

To describe the magnetic resonance imaging (MRI) findings in cutis verticis gyrata (CVG) and familiarize the interpreters of neuroimaging studies with its characteristic appearance and intracranial and systemic associations. The MRI examinations of 12 patients (7 men and 5 women; age range, 16 to 66 years; mean, 40.3 years) with CVG were retrospectively evaluated for distribution, orientation, number of folds, and the associated intracranial or calvarial abnormalities. Eleven patients had bilateral involvement. The number of folds was 3 to 8 (average, 6), and the direction was anterior-posterior (longitudinal) in 9 patients. Transverse and longitudinal folds coexisted in 3 patients. The subcutaneous tissues underneath CVG were thickened in all patients, whereas skin was thickened in 7. Intracranial abnormalities identified included meningioma, schwannoma, glioma, and prolactin-secreting pituitary microadenoma. There were no skull abnormalities. Cutis verticis gyrata CVG has a typical appearance on MRI characterized by scalp undulations due to thickening of the skin and subcutaneous tissues.

Patients with macroprolactinaemia: clinical and radiological features

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. 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 </= 40% after polyethylene glycol precipitation were indicative of macroprolactinaemia. Macroprolactin, entirely explaining biochemical hyperprolactinaemia, was found in 42.2% of patients, a third of whom presented with signs and symptoms of hyperprolactinaemia. Determination of macroprolactin changed the initial diagnosis in a consistent proportion of patients. In particular, idiopathic hyperprolactinaemia, initially diagnosed in 41 patients, was then excluded in 28 of them. Diagnosis of prolactin-secreting pituitary microadenoma shifted to non-secreting pituitary microadenoma in 10 of 49 patients, while in all patients with prolactin-secreting pituitary macroadenoma or hyperprolactinaemia due to stalk deafferentation the presence of macroprolactin was excluded and the initial diagnosis confirmed. Finally, macroprolactin was present in the majority of patients with magnetic resonance imaging (MRI) scans suggestive for primary empty sella (4 of 5 women) or pituitary hyperplasia (12 of 17 women, 3 of 3 men). Collectively, about half of subjects with macroprolactinaemia showed variable MRI abnormalities. The presence of macroprolactin was a relevant cause of misdiagnosis in patients with hyperprolactinaemia. However, due to the unexpected high frequency of pituitary abnormalities observed in the present series, we suggest that the diagnostic algorithm of hyperprolactinaemic states should include both polyethylene glycol precipitation test and MRI imaging.

Morphology Predicts Oncology: A Commentary on Vezina and Sutton's Article, “Prolactin-Secreting Pituitary Microadenomas: Roentgenologic Diagnosis”

Morphology Predicts Oncology: A Commentary on Vezina and Sutton's Article, “Prolactin-Secreting Pituitary Microadenomas: Roentgenologic Diagnosis”

Successful treatment of refractory schizophrenia with combined olanzapine and quetiapine in a patient with a prolactin secreting pituitary microadenoma

Treatment-resistant schizophrenia presents a particular problem in patients who, for whatever reason, cannot be treated with clozapine. Pharmacological strategies for the further management of such individuals usually involve the coadministration of two or more antipsychotic drugs, leading to an increased potential for adverse effects. Hyperprolactinaemia (elevation of serum prolactin levels) is a common side-effect of antipsychotics and one that it is especially important to minimize in patients with primary pituitary pathology. We present a patient with treatment resistant schizophrenia and a prolactin-secreting microadenoma of the pituitary who was intolerant of clozapine therapy. She was prescribed a combination of olanzapine and quetiapine and experienced almost complete resolution of her psychosis, with no elevation of serum prolactin levels. We suggest that this may be a strategy worthy of consideration in patients for whom conventional treatment methods have failed, particularly those who are sensitive to the prolactinogenic effects of many antipsychotic medications.

Complete remission of hyperprolactinemia and erythrocytosis after hysterectomy for a uterine fibroid in a woman with a previous diagnosis of prolactin-secreting pituitary microadenoma

A 44-year-old woman who had been suffering for 10 years from amenorrhea and hyperprolactinemia resistant to high doses of bromocriptine was hospitalized with erythrocytosis, normal serum erythropoietin (sEpo) levels, and hypertension. Erythrocytosis secondary to uterine myoma and a prolactin-secreting pituitary microadenoma were initially diagnosed. The hyperprolactinemia was bromocriptine resistant, despite gradual increase of the dosage to 30 mg/day. Both hyperprolactinemia and erythrocytosis unexpectedly regressed completely after the patient underwent hysterectomy for a uterine fibroid 9 months after the erythrocytosis was first disclosed. Given the well-known effects of prolactin on hematopoietic cells, we hypothesize that--in this very unusual case--the two main, apparently unrelated abnormalities (erythrocytosis with normal sEpo levels and hyperprolactinemia) may have been the clinical consequence of the functional redundancy and pleiotropy of the "pituitary" hormone prolactin, inappropriately secreted by a uterine fibroid for more than 10 years.

Prolactin-secreting pituitary microadenomas: inaccuracy of high-resolution CT imaging.

Computed tomographic (CT) and surgical findings were correlated retrospectively in 51 patients with preoperative diagnoses of prolactin-secreting pituitary microadenomas. Thirty-nine had microadenomas at surgery. Twenty-three had identifiable discrete lesions. Of these, 21 had microadenomas and two did not; these two groups could not be distinguished reliably. Six patients with proven microadenomas had normal CT scans. Focal hypodense lesions, sellar floor erosion, infundibulum displacement, gland height greater than 8 mm, and an abnormal diaphragma sellae configuration are neither sensitive nor specific findings of microadenoma. A significant number of patients with proven microadenomas had few or none of these abnormalities. Thus, recognition of prolactin microadenoma may not be possible by CT alone, even with high-resolution direct coronal imaging.

Dopaminergic mechanisms regulating prolactin secretion in patients with prolactin-secreting pituitary adenoma. Long-term studies after selective transsphenoidal surgery

Twenty-seven female patients with prolactin-secreting pituitary microadenoma, were studied at different intervals following selective transsphenoidal removal of the tumor. Postoperatively, all patients had normal prolactin (PRL) levels and regular menstrual cycles were restored. Sixteen of 27 patients showed positive responses to TRH and metoclopramide (MCP) within 1 mo after surgery. On the contrary, 9 patients showed extremely low PRL levels and exhibited negative responses to provocative stimuli immediately after surgery. The long-term evaluation of these patients demonstrated that normal neuroendocrine relationships were restored after several months since positive PRL responses to TRH and MCP could be elicited in such patients. The remaining 2 patients who showed basal PRL levels in the upper range of normal, exhibited negative responses to TRH and MCP. These patients had progressively increasing basal PRL levels, with negative responses to provocative stimuli. In addition, 8 patients with normal responses to TRH and MCP exhibited 10–20 mo after surgery a normal decrease in PRL levels following administration of carbidopa plus L-Dopa. Negative responses to carbidopa plus L-Dopa were instead obtained in 6 postoperative patients with elevated PRL levels and negative responses to TRH and MCP. These results suggest that: 1) Hyperprolactinemia induced by “autonomous” pituitary adenomas increases hypothalamic dopamine (DA) secretion, which in turn inhibits PRL secretion by nonadenomatous lactotropes. 2) Total selective removal of the microadenoma acutely decreases PRL concentration, but a functional inhibition of the normal lactotrope can persist for a period of few months following surgery in a certain number of patients. 3) Prolonged reduction of PRL concentration is accompanied to a normal DA tone with reestablishment of normal neuroendocrine relationships.

Sella ‘erosions’ in a series of 50 normal women: The place of tomography in the diagnosis of prolactin secreting pituitary microadenoma

The following paper assesses the results of pluridirectional tomograms in 50 normal females of reproductive age, as reflected by the opinions given by 4 different radiologists with major interest in the pituitary fossa. Only 16 of the 50 tomograms were uniformly read as normal. The study has merit in highlighting the ‘abnormalities’ of the pituitary fossa in what appear to be a group of normal controls, and to stress the phenomenon of observer variations. It is suggested, therefore, that sella tomograms alone are incapable of diagnosing with sufficient accuracy the presence of pituitary microadenoma in a young woman and, therefore, should not be performed as a routine in the evaluation of patients suspected of prolactin secreting microadenoma.

Enlargement of a prolactin‐secreting pituitary microadenoma during bromocriptine treatment

A patient with prolactin-secreting pituitary microadenoma was treated with bromocriptine, 5 mg daily for 1 year. Despite normalization of prolactin levels throughout the treatment period, partial destruction of the sellar floor with growth of the adenoma into sphenoidal sinus were evident in a control tomography performed at the end of the treatment.

The reliability of radiology in detecting prolactin-secreting pituitary microadenomas

Radiological findings in 30 patients with proven prolactin-secreting pituitary adenomas, originally diagnosed exclusively by endocrine criteria, have been reviewed. Conventional tomography was the examination most often abnormal (50%), and changes or lack of changes corresponded to the state of the pituitary fossa as noted at operation in 93%. Tomographic abnormalities indicated the site of the tumour in 86%. Plain films were less sensitive (27% abnormal) although the changes reported were all confirmed during the surgical procedures. Although cavernous sinography and CT rarely yielded positive information unless either plain films or tomograms were abnormal, each may have a place in the assessment of a patient before operation: sinography to ensure that there is no significant anomaly of the carotid artery at the level of the pituitary fossa; CT scan to exclude a hypothalamic lesion or to detect an associated suprasellar tumour extension or intrasellar cisternal herniation. Strategies for the radiological investigation of patients suspected of having a prolactin-secreting pituitary tumour are proposed.

Prolactin-secreting pituitary microadenomas. II. Evaluation of surgical treatment

The authors evaluated results of surgical treatment for 12 cases of prolactin-secreting pituitary microadenomas with respect to the effect on the endocrinological status and compared these results with those for 10 cases of macroadenomas. The cases of microadenomas were all female; 10 cases with amenorrhea and galactorrhea, a case with oligomenorrhea and galactorrhea and a case with only amenorrhea. Both microadenomas and macroadenomas were operated on through the transsphenoidal route. Microadenomas were considered to have been removed completely but macroadenomas were not always removed completely because of their larger size. The relation between operative findings of microadenomas and basal serum PRL levels was analysed. Two elastic and firm adenomas showed elevated serum PRL levels (p<0.001) exceeding 400 ng/ml and two eosinophilic and two mixed adenomas showed higher serum PRL levels than the chromophobes (p<0.01). Adenomas with serum PRL levels around or over 200 ng/ml were all peripheral types. Localization within the sella turcica or size of the tumors had little relation to serum PRL levels. In microadenomas, serum PRL levels fell to the normal level in nine cases (75.0%) within a month after the operation. Three cases with normal PRL levels, however, gradually returned to elevated levels in the follow-up after a month. Conversely, no drop to the normal level was observed in cases of macroadenomas. Surgical impacts on HGH, TSH, LH, FSH and ACTH reserves were examined. Only four out of 18 cases (22.2%) among the microadenomas and macroadenomas had impaired hormonal reserves after transsphenoidal surgery which was considered to be a safe procedure. Regular menses were restored in nine out of 12 cases (75.0%) of microadenomas after a mean interval of a month and a half after the operation. Six cases showed ovulatory menses. One case experienced normal delivery and two cases became pregnant among the six patients. Galactorrhea disappeared in nine out of 11 cases (81.8%) of microadenomas after a mean interval of 2 months and a half after the operation and another case showed a remarkable decrease in lactation. However, none of the seven cases of macroadenomas showed restored menses, only one out of six cases had cessation of lactation and another two cases showed a decrease in lactation after the operation. Transsphenoidal removal of prolactin-secreting microadenomas was a safe and satisfactory treatment of choice.

Evaluation and treatment of patients with prolactin-secreting pituitary tumors.

Six women with secondary amenorrhea and hyperprolactinemia, four of whom had associated galactorrhea, were studied. Four were found to have prolactin-secreting pituitary microadenomas and two had macroadenomas. Suppression of prolactin secretion and stimulation of prolactin, serum growth hormone and thyroid-stimulating hormone secretion were studied, and gonadotropin and adrenocorticotropic hormone reserves were evaluated. The most sensitive techniques available for the diagnosis of pituitary adenomas in patients with amenorrhea and hyperprolactinemia appear to be the measurement of the magnitude of plasma prolactin elevation and hypocycloidal tomography of the sella turcica. The dynamic function tests proved to be of little diagnostic, but of great prognostic, value for patients with small pituitary tumors.

Restoration of Cyclic Ovarian Function by Metergoline Treatment in a Patient with a Prolactin-Secreting Pituitary Microadenoma

A patient with amenorrhea due to a prolactin-secreting pituitary microadenoma was treated with the antiserotoninergic drug metergoline for 8 months. The first menstruation occurred after 1 month of therapy, and it was followed by regular menses by the 3rd month. Presumptive evidence of ovulation was obtained in at least some instances by serum progesterone and gonadotropin determination. Serum prolactin was only slightly lowered by treatment. The patient had menses and possibly ovulation in the 2 months following drug withdrawal. Metergoline might restore ovarian function in hyperprolactinemic amenorrhea either by prolactin suppression or perhaps by direct stimulation of gonadotropin release.

Prolactin-Secreting Pituitary Microadenoma: Detection and Evaluation

Eleven women with secondary amenorrhea associated with hyperprolactinemia were studied. Base line evaluations, visual field determinations, and routine sella turcica x-rays were normal. Prolactin-secreting pituitary microadenomas were found in all of the patients only after further diagnostic studies were carried out. These studies included polytomography of the sella turcica; dynamic pituitary testing of growth hormone reserve, adrenocorticotropic hormone reserve, and gonadotropin reserve; and prolactin suppression with L-dopa. The early diagnosis of a small prolactin-secreting adenoma may be possible if several diagnostic criteria are utilized. The most sensitive diagnostic indices available are (1) polytomography, (2) the magnitude of the plasma prolactin elevation, and (3) the failure to suppress prolactin secretion with L-dopa. Our findings emphasize the importance of an extensive evaluation of all women with amenorrhea associated with hyperprolactinemia.