Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD). In the case of non-functioning pituitary adenomas (NFAs), pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.
Acromegaly ; Adenoma ; Comorbidity ; Drug Therapy ; Humans ; Patient Selection ; Pituitary ACTH Hypersecretion ; Pituitary Neoplasms* ; Prolactinoma ; Quality of Life

OBJECTIVEPituitary prolactinoma with severe erectile dysfunction (ED) as the initial symptom is often misdiagnosed. This article explores the diagnosis and treatment of severe ED caused by pituitary prolactinoma.

METHODSWe retrospectively analyzed the diagnosis and treatment of 4 cases of pituitary prolactinoma with severe ED (IIEF-5 score 5 - 7) as the initial clinical symptom confirmed by MRI.

RESULTSThe 4 cases of pituitary prolactinoma-induced severe ED, with serum prolactin 10 times above the maximum normal level, were misdiagnosed for 2 years. All failed to respond to the PDE5 inhibitor therapy, and then 3 of them underwent transnasal hypophysectomy. Twenty-four months of follow-up found the level of prolactin restored to normal in 1 case (IIEF-5 = 19), and reduced to 600 and 768 IU/L respectively (IIEF-5 = 15) in the other 2. Then administration of the PDE5 inhibitor was followed, which produced satisfactory efficacy. One case was treated with oral bromocriptine, which restored the prolactin level to normal at 12 months (IIEF-5 > 21).

CONCLUSIONProlactin detection and brain MRI can help to confirm pituitary prolactinoma with severe ED at the onset. As for its treatment, in case of an extremely high level of prolactin, simple administration of the PDE5 inhibitor is ineffective. When the prolactin level is reduced after surgery or medication, the symptom of ED can be improved and, in case of no obvious relief, administration of the PDE5 inhibitor can be followed, which may achieve satisfactory results.

Adult ; Erectile Dysfunction ; diagnosis ; etiology ; Humans ; Male ; Middle Aged ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Pituitary Neoplasms ; complications ; diagnosis ; drug therapy ; Prolactinoma ; complications ; diagnosis ; drug therapy ; Retrospective Studies

BACKGROUNDOur earlier studies indicate that melatonin inhibits the proliferation of prolactinoma and induces apoptosis of pituitary prolactin-secreting tumor in rats. Melatonin has also been shown to induce apoptosis and to reduce the production of ATP in breast tumor cells. This study analyzed the levels of the four mitochondrial respiratory complexes and the production of ATP and also the effects of melatonin treatment of prolactinoma.

METHODSIn the in vivo study, mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin- and 17-β-estradiol (E2)-treated male rats. In the in vitro study, prolactinoma cells mitochondria were harvested. Activities of the four mitochondrial respiratory complexes were assayed using fluorometer. ATP production of prolactinoma cells was estimated using bioluminescent methods.

RESULTSElevated levels of four mitochondrial respiratory complexes activities and ATP production were recorded in prolactinoma cells. Moreover, in both in vivo and in vitro studies, melatonin inhibited the activities of mitochondrial respiratory complexes and the production of ATP in prolactinoma cells.

CONCLUSIONSThere is a link between mitochondrial function increase and tumorigenesis. Melatonin induces apoptosis of pituitary prolactin-secreting tumor of rats via the induction of mitochondrial dysfunction and inhibition of energy metabolism.

Adenosine Triphosphate ; metabolism ; Animals ; Estradiol ; therapeutic use ; Male ; Melatonin ; therapeutic use ; Mitochondria ; drug effects ; metabolism ; Prolactin ; metabolism ; Prolactinoma ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe long-term outcomes of patients with invasive giant prolactinomas (IGPs) treated with bromocriptine followed by comprehensive treatments.

METHODSThirty-four patients met the criteria of IGPs were treated with bromocriptine initially. Among of them, 11 had radiotherapy at the same time. During the treatments, transsphenoidal surgery or/and Gamma Knife were considered to apply to the patients according to the location, shrinkage of residual tumors and resistance of bromocriptine. Small dosage of bromocriptine was kept after operation.

RESULTSThe average follow-up duration is 33.6 months. Thirty-three patients obtained significant improvement, but one failed recovery of vision due to side-injury by radiotherapy. Tumor volume on magnetic resonance imaging (MRI) was decreased on average by 91.4%, PRL by 97.1%. The number of patients with low testosterone level restored from 17 to 6 and hypoadrenalism from 10 to 6 after combined treatment with priority of medical therapy. Rhinorrhea occurred in 2 cases, 1 restored in two weeks, 1 had transsphenoidal combined with transcranial surgery to remove the tumor and repair the fistula.4 had resistance to bromocriptine to some extend.

CONCLUSIONSDopamine agonist medications are effective as a first-line therapy for IGPs. In some patients treated by bromocriptine only, the tumor may disappear on MRI. Combined with surgery and Gamma Knife, the duration of treatment could be shortened and the dosage may be minimized, but using radiotherapy should be cautions.

Adolescent ; Adult ; Aged ; Bromocriptine ; therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Hormone Antagonists ; therapeutic use ; Humans ; Hypophysectomy ; Male ; Middle Aged ; Pituitary Neoplasms ; drug therapy ; surgery ; Prolactinoma ; drug therapy ; surgery ; Radiosurgery ; Retrospective Studies ; Time Factors ; Treatment Outcome

Although cabergoline is effective in the treatment of micro- and macro-prolactinoma, little is known about its efficacy in the treatment of invasive giant prolactinoma. We investigated the efficacy and safety of cabergoline in 10 male patients with invasive giant prolactinoma. Before treatment, mean serum prolactin level was 11,426 ng/mL (range, 1,450-33,200 ng/mL) and mean maximum tumor diameter was 51 mm (range, 40-77 mm). Three months after initiation of cabergoline treatment, serum prolactin concentrations decreased more than 97% in 9 patients; at last follow-up (mean treatment duration, 19 months), the mean decrease in serum prolactin concentrations was 98%, with 5 patients having normal serum prolactin levels. At first MRI follow-up (3-12 months after initiation of cabergoline), the mean reduction in tumor size was 85+/-4% (range, 57-98%). Cabergoline treatment for more than 12 months caused a greater reduction in tumor size compared to the treatment for less than 12 months (97+/-1% vs. 78+/-7%, P<0.05). These findings indicate that cabergoline treatment led to a significant and rapid reduction in serum prolactin concentrations and tumor size in patients with giant prolactinoma. Therefore, cabergoline represents an effective and well-tolerated treatment for invasive giant prolactinoma.
Adult ; Antineoplastic Agents/adverse effects/*therapeutic use ; Ergolines/adverse effects/*therapeutic use ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pituitary Neoplasms/*drug therapy ; Prolactin/blood ; Prolactinoma/*drug therapy ; Retrospective Studies

ObjectiveTo analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment.

METHODSWe retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15).

RESULTSThe average diameter of the sellar space-occupying lesions was significantly longer in group A than in B (［2.35±0.71］ vs ［1.83±0.36］ cm, P<0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P<0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level (［0.78±0.40］ vs ［2.71±0.70］ ng/ml with Andriol; ［0.93±0.44］ vs ［3.07±0.67］ ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P<0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm (［11.5±2.3］ vs ［7.5±2.3］ ml, P<0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either.

CONCLUSIONSHypothyroidism might be attributed to surgery- or radiotherapy-induced damage to the pituitary tissue, space-occupying effect of sellar lesion, and hyperprolactinemia. Both Andriol and hCG can improve the T level and erectile function, but the former does not help spermatogenesis.

Adult ; Chorionic Gonadotropin ; therapeutic use ; Follicle Stimulating Hormone ; blood ; Humans ; Hypogonadism ; diagnosis ; etiology ; therapy ; Luteinizing Hormone ; blood ; Male ; Pituitary Neoplasms ; blood ; complications ; pathology ; therapy ; Prolactinoma ; blood ; complications ; pathology ; therapy ; Retrospective Studies ; Sella Turcica ; Spermatogenesis ; Spermatozoa ; Testis ; anatomy & histology ; drug effects ; Testosterone ; analogs & derivatives ; blood ; therapeutic use ; Tumor Burden