Prolactin-producing Pituitary Tumor Research Articles

Reconsideration of Surgical Indication for Prolactin-producing Pituitary Tumor Focusing on Visual Impairment.

Prolactin-producing pituitary tumor (PRLoma) is the most prevalent functional pituitary tumor. If the tumor becomes large, vision can be impaired. In contrast to other pituitary tumors, cabergoline (CAB) is extremely effective for PRLoma and has become the first-line treatment. In this study, we examined our experience with the pharmacological and surgical management of PRLomas with visual impairment (VI) to determine whether VI could be a surgical indication. Further, we discussed the function of surgery in situations where the gold standard of PRLoma treatment was CAB administration. Of the 159 patients with PRLomas (age, 13-77 [mean = 36.3] years; men, 29; women, 130) at Tokyo Women's Medical University Hospital from 2009 to 2021, 18 (age, 15-67 [mean = 35.8] years; men, 12; woman, 6) had VI (subjectively, 12; objectively, 6). They started CAB treatment immediately (maximum dose: 0.5 to 6 mg/week; average: 2.17 mg/week). VI improved in 16 patients (88.9%) but did not improve in 2 (11.1%) requiring surgeries. One of the two patients had a parenchymal tumor resistant to CAB, and the other had a cystic tumor due to intratumoral bleeding. Consequently, CAB is the first-line treatment for PRLomas with VI because of its significantly high rate of improvement. However, close and rigorous surveillance is necessary for cases resistant to CAB, and the correct decision is required regarding surgical interventions at proper timing and appropriate surgical approaches considering the purpose of surgery.

Executive summary of the expert consensus document from the Spanish Society of Neurosurgery and the Spanish Society of Endocrinology and Nutrition: Clinical recommendations on the perioperative management of pituitary tumors

Pituitary tumors (PT) account for 15% of intracranial tumors affect 10.7%–14.4% of the population although the incidence of clinically relevant PT is 5.1 cases/100,000 inhabitants. Surgical treatment is indicated in PTs with hormone hypersecretion (except for prolactin-producing PTs) and those with local compressive or global neurological symptoms. Multidisciplinary care, is essential for patients with PTs, preferably delivered in a center of excellence and based on a well-defined care protocol. In order to facilitate and standardize the clinical procedures for this type of tumor, this document gathers the positioning of the Neuroendocrinology Knowledge Area of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Neurosurgery (SENEC) on the management of patients with PTs and their preoperative, surgical and postoperative follow-up.

Executive summary of the expert consensus document from the Spanish Society of Neurosurgery and the Spanish Society of Endocrinology and Nutrition: clinical recommendations on the perioperative management of pituitary tumors

Pituitary tumors (PT) account for 15% of intracranial tumors affect 10.7–14.4% of the population although the incidence of clinically relevant PT is 5.1 cases/100,000 inhabitants. Surgical treatment is indicated in PTs with hormone hypersecretion (except for prolactin-producing PTs) and those with local compressive or global neurological symptoms. Multidisciplinary care, is essential for patients with PTs, preferably delivered in a center of excellence and based on a well-defined care protocol. In order to facilitate and standardize the clinical procedures for this type of tumor, this document gathers the positioning of the Neuroendocrinology Knowledge Area of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Neurosurgery (SENEC) on the management of patients with PTs and their preoperative, surgical and postoperative follow-up.

Resumen ejecutivo del documento de consenso de expertos de la Sociedad Española de Neurocirugía y de la Sociedad Española de Endocrinología y Nutrición sobre: recomendaciones clínicas en el manejo perioperatorio de los tumores hipofisarios

Pituitary tumors (PT) account for 15% of intracranial tumors affect 10.7 to 14.4% of the population although the incidence of clinically relevant PT is 5.1 cases/100,000 inhabitants. Surgical treatment is indicated in PTs with hormone hypersecretion (except for prolactin-producing PTs) and those with local compressive or global neurological symptoms. Multidisciplinary care, is essential for patients with PTs, preferably delivered in a center of excellence and based on a well-defined care protocol. In order to facilitate and standardize the clinical procedures for this type of tumor, this document gathers the positioning of the Neuroendocrinology Knowledge Area of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Neurosurgery (SENEC) on the management of patients with PTs and their preoperative, surgical and postoperative follow-up.

Resumen ejecutivo del documento de consenso de expertos de la Sociedad Española de Neurocirugía y de la Sociedad Española de Endocrinología y Nutrición sobre: recomendaciones clínicas en el manejo perioperatorio de los tumores hipofisarios

Pituitary tumors (PT) account for 15% of intracranial tumors affect 10.7 to 14.4% of the population although the incidence of clinically relevant PT is 5.1 cases/100,000 inhabitants. Surgical treatment is indicated in PTs with hormone hypersecretion (except for prolactin-producing PTs) and those with local compressive or global neurological symptoms. Multidisciplinary care, is essential for patients with PTs, preferably delivered in a center of excellence and based on a well-defined care protocol. In order to facilitate and standardize the clinical procedures for this type of tumor, this document gathers the positioning of the Neuroendocrinology Knowledge Area of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Neurosurgery (SENEC) on the management of patients with PTs and their preoperative, surgical and postoperative follow-up.

Atypical presentation of a prolactin-producing pituitary neuroendocrine tumor that mimics the image of an adamantinomatous craniopharyngioma

Atypical presentation of a prolactin-producing pituitary neuroendocrine tumor that mimics the image of an adamantinomatous craniopharyngioma

Clinicopathological aspects of growth-hormone and prolactin-producing pituitary neuroendocrine tumors

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Prolactin-secreting Pituitary Macro-adenoma Presenting with Mass Effects, Hormonal Deficiencies, and Neurogenic Diabetes Insipidus: A Case Report and Review of Literature

To report and review a case of prolactin-producing pituitary tumor presenting with mass effects, hormonal deficiency, and neurogenic diabetes insipidus in a nulliparous woman of Afro-Caribbean descent. The patient presented with dull-aching headaches associated with worsening vision, nausea, and vomiting. The patient also complained of polyuria, nocturia, thirst, polydipsia, and weight gain. Physical examination showed bilateral visual field defects, while investigations revealed hypernatremia and elevated plasma osmolality but decreased urine sodium concentration, osmolality, and specific gravity.
 Results of the hormonal profile showed high plasma prolactin levels, a low plasma concentration of the antidiuretic hormone, and decreased levels of other anterior pituitary hormones. Imaging revealed a large, uncalcified, cystic pituitary mass extending into adjacent structures and compressing the optic chiasm and internal carotid artery. The outcome of the water deprivation and desmopressin administration tests were consistent with neurogenic diabetes insipidus, and a diagnosis of prolactin-producing pituitary macroadenoma with mass effects, hormonal deficiencies, and neurogenic diabetes insipidus was made. The patient was commenced on medical treatment and referred for histopathological diagnosis and definitive treatment. This report highlights the coexistence of neurogenic diabetes insipidus with a prolactin-producing pituitary macroadenoma presenting with mass effects.

Involvement of GPR4 in increased growth hormone and prolactin expressions by extracellular acidification in MtT/S cells.

Hormone-secreting pituitary adenomas show unregulated hormonal hypersecretion and cause hyperpituitarism. However, the mechanism of the unregulated hormone production and secretion has not yet been fully elucidated. Solid tumors show reduced extracellular pH, partly due to lactate secretion from anaerobic glycolysis. It is known that extracellular acidification affects hormone secretion. However, whether and how the extracellular acidification influences the unregulated hormone production and secretion remain unknown. In the present study, we found that GPR4, a proton-sensing G protein-coupled receptor, was highly expressed in MtT/S cells, a growth hormone-producing and prolactin-producing pituitary tumor cell line. When we reduced the extracellular pH, growth hormone and prolactin mRNA expressions increased in the cells. Both increased expressions were partially suppressed by a GPR4 antagonist. We also found that extracellular acidification enhanced growth hormone-releasing factor-induced growth hormone secretion from MtT/S cells. These results suggest that GPR4 may play a role in hypersecretion of the hormone from hormone-producing pituitary tumors. A GPR4 antagonist will be a useful tool for preventing the hypersecretion.

Macroprolactinemia associated with pituitary macroadenoma: treatment with quinagolide

According to current concept, macroprolactin is biologically inactive and, therefore, its accumulation in serum has little, if any, pathological significance. Authors present the history of a 80-year-old man who proved to have, among other associated disorders, an intra- and parasellar pituitary tumor measuring 21x12x12 mm in size which was revealed by pituitary MRI. His hormonal evaluation indicated a marked hyperprolactinemia mainly due to macroprolactinemia (total prolactin, 514 ng/ml; reference range, 1.6-10.7 ng/ml; macroprolactin 436 ng/ml, monomer prolactin 78.2 ng/ml). Tests for function of the pituitary-thyroid axis showed a mild subclinical primary hypothyroidism. The function of the pituitary-adrenal axis was normal, and other hormonal tests revealed low-normal serum gonadotropins and decreased testosterone level, whereas serum insulin-like growth factor I was normal. Although the majority of current guidelines state that dopamine-agonist treatment which is successfully used in prolactin-producing pituitary tumors and in other hyperprolactinemic disorders is unnecessary in patients with macroprolactinemia, the authors introduced a dopamine-agonist, quinagolide. During prolonged treatment, plasma prolactin returned close to the upper limit of normal (12.3 ng/ml) and 9 months after the beginning of treatment pituitary MRI showed a remarkable shrinkage of the pituitary tumor. Authors propose that in this patient the pituitary tumor secreted macroprolactin, and they recommend a treatment trial with dopamine-agonist in pituitary macroadenomas associated with macroprolactinemia.

Diagnostic and therapeutical approach in psychosis - pituitary adenoma comorbidity. Case report

Background:Among pituitary adenomas, prolactin-producing pituitary tumors are the most common type which are treated frequently with dopamine agonists in intrasellar types. The onset of a psychotic disorder concomitant with the tumor complicates the diagnostic algorithm of the psychiatric condition and the following therapeutical approach of both of them.The Aim:to elucidate on empirical basis the etiology of the psychotic disorder comorbid with pituitary adenoma in order to find an optimal therapeutical resolution to both conditions.Method:female patient, 25 years old, was hospitalized for psychotic and expansive symptoms which appeared six months after initiation of bromocriptine treatment for prolactin-producing pituitary microadenoma and had a fluctuated course. All investigations excluded the involvement of another organic factors. The difficulty of the case consisted in finding the differentiated etiology of the persistent psychiatric symptomatology: is it bromocriptine induced or is it a primary mental disorder?Results:the psychiatric symptoms were treated with antipsychotics – quetiapine1000mg/day, but the maintenance dose had to be reduced to half because the prolactin serum level raised. Three months later the patient relapsed and the antipsychotic dose was raised, which induced high prolactin serum level. Bromocriptine dose was raised as the psychiatric condition worsened and the antipsychotic dose was raised again. Finaly bromocriptine swiched to cabergoline 1,5mg/twice a week. The psychotic symptoms diminished and the remission was reached with prolactin serum level maintained within normal limits with cabergoline.Conclusion:empiric research found that the most probable cause of persistent psychosis is related to the dopamine agonist use.

Estrogen induction of prolactin‐producing pituitary tumors in the Fischer 344 rat: Modulation by dietary‐energy but not protein consumption

Our laboratory is examining the hypothesis that diet may modulate the ability of estrogens to regulate cell proliferation and survival, either of which could affect development of neoplasms in estrogen-responsive tissues. In this study, we examined whether the amount of energy and protein consumed in the diet modulates the ability of the synthetic estrogen diethylstilbestrol (DES) to induce development of prolactin-producing pituitary tumors in two strains of rat, Fischer 344 (F344) and Holtzman, that differ in their propensity to develop pituitary tumors when treated with estrogens. Male F344 rats treated with DES for 8 wk developed pituitary tumors (defined as grossly enlarged pituitary masses that displayed diffuse lactotroph hyperplasia but lacked adenomatous foci). In contrast, male Holtzman rats displayed only a modest increase in pituitary weight in response to DES. Energy consumption but not protein consumption modulated DES-induced pituitary tumorigenesis in the male F344 rat. Relative to that observed in untreated animals, pituitary weights in F344 rats treated with DES increased 11.2- and 9.2-fold in animals fed either the control diet or an equicaloric high-protein diet, respectively, but only 3.5-fold in animals fed an energy-restricted diet. In contrast, neither the amount of energy nor protein consumed in the diet affected the modest pituitary growth response of male Holtzman rats to administered DES. Energy restriction had no apparent effect on pituitary cell proliferation, either basal or DES stimulated, in these rat strains. We concluded that dietary energy restriction inhibits the ability of administered DES to induce pituitary tumor development in the F344 rat by acting at a step after induction of pituitary cell proliferation.

Dietary energy restriction abolishes development of prolactin-producing pituitary tumors in Fischer 344 rats treated with 17beta-estradiol.

Reduction in energy consumption is known to inhibit development of a variety of spontaneous, carcinogen-induced, and hormone-dependent cancers, but the mechanism or mechanisms by which this occurs remain unknown. We hypothesize that energy consumption may modulate development of estrogen-dependent neoplasms by altering the manner in which target cells respond to estrogens. To test this hypothesis, ovariectomized female Fischer 344 rats were fed diets that allowed consumption of different amounts of energy, and the ability of 17beta-estradiol (E2), administered for 10 wk from subcutaneous Silastic implants, to promote development of prolactin-producing pituitary tumors was examined. A 40% restriction of energy consumption virtually abolished the ability of E2 to promote development of pituitary tumors and associated hyperprolactinemia. A 25% restriction of energy consumption appeared to slightly inhibit E2-induced pituitary growth and hyperprolactinemia, but the observed degree of inhibition was not statistically significant. Interestingly, dietary energy restriction did not inhibit induction by E2 of pituitary cell proliferation and lactotroph hyperplasia. Furthermore, E2 treatment inhibited expression of testosterone-repressed prostate message-2 mRNA, a cellular marker of apoptosis, and this inhibitory effect of E2 was blocked by 40% energy restriction. These data suggest that dietary energy restriction virtually abolished E2-induced development of prolactin-producing pituitary tumors, not by blocking the ability of E2 to induce cell proliferation but rather by blocking the ability of E2 to enhance cell survival. This study and the accompanying paper provide the first indication that dietary energy consumption may modulate estrogen action at the level of the target cell.

Estrogen induction of prolactin-producing pituitary tumors in the Fischer 344 rat: Modulation by dietary-energy but not protein consumption

Estrogen induction of prolactin-producing pituitary tumors in the Fischer 344 rat: Modulation by dietary-energy but not protein consumption

Estrogen-induced tumorigenesis in the Copenhagen rat: disparate susceptibilities to development of prolactin-producing pituitary tumors and mammary carcinomas

The Copenhagen (COP) rat is unique among inbred rat strains in its high degree of resistance to spontaneously arising and induced mammary cancers. Hyperprolactinemia resulting from tumors of the anterior pituitary gland has been suggested to be the causative factor in the etiology of estrogen-induced mammary cancer in rats. Therefore, we have examined the ability of administered estrogens to induce development of PRL-producing pituitary tumors and mammary carcinomas in COP rats. Diethylstilbestrol (DES), administered to male COP rats for 12 weeks, beginning when the animals were 9 weeks of age, induced development of PRL-producing pituitary tumors, defined as grossly enlarged pituitary masses displaying lactotroph hyperplasia and associated hyperprolactinemia. When treated with 17 β-estradiol (E2), female COP rats developed pituitary tumors and hyperprolactinemia, but displayed a high degree of resistance to development of mammary carcinomas. These data indicate that E2-induced hyperprolactinemia is insufficient to induce development of mammary carcinomas in the female COP rat.

Plasma calcitonin, IGF-I levels and vertebral bone mineral density in hyperprolactinemic women during bromocriptine treatment

Hyperprolactinemia is associated with decreased bone mineral density, which may be caused by the hypogonadism and hypoestrogenicity noticed in patients with hyperprolactinemia. Since calcitonin inhibits the bone resorption, and insulin-like growth factor I (IGF-I) has important anabolic effects on the skeleton, lack of one or both peptides may contribute to the development of osteopenia. We therefore measured the plasma calcitonin and IGF-I levels in nine women with hyperprolactinemia caused by a prolactin-producing pituitary tumor. The calcium-stimulated C-cell reactivity was studied by measuring calcitonin in plasma during a calcium clamp before and after normalization of serum prolactin during treatment with bromocriptine. Basal CT levels were measurable but lower than in healthy controls. Basal IGF-I levels and calcium-stimulated plasma calcitonin were normal in the hyperprolactinemic state and similar to the calcitonin and IGF-I levels during bromocriptine treatment. The serum prolactin levels decreased (p < 0.001) and the serum estradiol levels increased (p < 0.001). The bone mineral density of the lumbar spine increased significantly during treatment. Thus, basal plasma CT levels are slightly reduced in hyperprolactinemic women. However, the reversible osteopenia in hyperprolactinemic women is less likely to be caused by inhibited IGF-I secretion or by deficient CT levels since the CT response to calcium is normal. In addition, bromocriptine treatment with normalization of prolactin levels is beneficial for the bone mineral content in this condition.

Reduction in the size of prolactin-producing pituitary tumor after Cabergoline administration

Different weekly doses (400 to 3,000 micrograms) of the new, long-acting dopamine agonist Cabergoline (Farmitalia Carlo Erba, Milan, Italy) were given to 11 hyperprolactinemic women with pituitary tumor. Pituitary computerized tomography (CT) scans were performed before the start of treatment and after 3 (n = 5), 6 (n = 3), and 9 (n = 3) months of Cabergoline administration. Plasma prolactin (PRL) was determined in blood samples collected before and at weekly intervals during Cabergoline administration. Cabergoline induced marked inhibition of PRL secretion in conjunction with a CT demonstration of reduction in the pituitary tumor size in all patients. The potent, long-lasting PRL inhibitory effect of Cabergoline and the absence of side effects typical of dopaminergic compounds suggest that the use of this drug is advantageous over others in the medical treatment of hyperprolactinemia.

Hyperprolactinemia, Infertility, and Hypothyroidism

A 30-year-old woman presented with infertility, hyperprolactinemia, and pituitary enlargement. Although relatively asymptomatic, she was found to have primary hypothyroidism. She became pregnant within a month following institution of levothyroxine replacement, and the pituitary enlargement resolved within one year. We discuss the relationship between hypothyroidism, hyperprolactinemia, and pituitary enlargement. This case emphasizes the need for thyroidal status evaluation in patients with presumptive prolactin-producing pituitary tumors before initiation of therapy for the hyperprolactinemia.

Combined Medical and Surgical Treatment of Prolactin-Producing Pituitary Tumors

Combined Medical and Surgical Treatment of Prolactin-Producing Pituitary Tumors

Thyroliberin receptor binding and adenylyl cyclase activation in cultured prolactin-producing rat pituitary tumor cells (GH cells).

A thyroliberin (TRH)-responsive particulate bound adenylyl cyclase is present in two rat anterior pituitary tumor cell strains (GH4C1 and GH3) which synthesize and secrete prolactin. At a given Mg2+ concentration, ATP and the guanyl nucleotides GTP and guanyl 5'-yl-imidodiphosphate (GMP-P(NH)P) caused a dose-dependent increase in adenylyl cyclase activity. The maximum response to thyroliberin occurred with ATP and GTP at concentrations above 0.30 mM and 2 microM, respectively. The maximal stimulatory effect of thyroliberin on adenylyl cyclase activity was 2-fold in the presence of GTP. GMP-P(NH)P increased the basal enzyme activity 4- to 10-fold over and above that of equimolar concentrations of GTP but supported poorly the TRH-induced response. Mg2+ caused a dose-dependent increase in the basal enzyme activity and reduced TRH and fluoride-induced responses. Also, Mn2+ and Co2+ stimulated the basal adenylyl cyclase activity while Zn2+, Ca2+, and Cu2+ inhibited the enzyme, and neither cations supported the TRH response. Half-maximal stimulation of the adenylyl cyclase by TRH and half-maximum binding of [3H]TRH to membranes at 35 degrees C were 102 and 56 nM, respectively. Pretreatment with TRH decreased the apparent Vmax of the enzyme and the maximal binding of [3H]TRH. Of 6 TRH analogs tested, only one was able to displace [3H]TRH from its receptor and to increase the adenylyl cyclase activity. We suggest that adenylyl cyclase activation is an early event in the stimulus secretion coupling between TRH and prolactin-producing GH cells.