Clinically nonfunctioning pituitary adenomas are the most common types among pituitary adenomas. These tumors are usually diagnosed in their later stages due to the absence of clinical symptoms and detectable hormonal hypersecretion. Although these tumors are benign, they are hard to be completely removed during neurosurgery due to the massive invasion into the surrounding tissues at diagnosis. Furthermore, relapse is common. In recent years, medical treatment of pituitary adenomas has witnessed a rapid development. New medications have shown certain effectiveness in reducing the tumor size and improving the clinical symptoms.
Adenoma ; drug therapy ; Humans ; Pituitary Neoplasms ; drug therapy

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

Surgery, anticoagulation therapy, pregnancy, and hormone treatments, such as bromocriptine, are well-characterized precipitating factors for pituitary apoplexy. However, whether cytotoxic chemotherapy for systemic cancer could cause pituitary apoplexy has not been investigated. Here, we present a case of a 41-year-old woman who developed a severe headache with decreased visual acuity after intravenous cytotoxic chemotherapy to treat metastatic breast cancer. Preoperative neuroimaging revealed pituitary adenoma with necrosis. Operative findings and pathologic examination concluded extensive necrosis with a small intratumoral hemorrhage in a pre-existing pituitary adenoma. We reviewed two additional previously published cases of pituitary apoplexy after systemic chemotherapy and suggest that cytotoxic chemotherapy may induce pituitary apoplexy.
Adult ; Breast Neoplasms* ; Breast* ; Bromocriptine ; Drug Therapy* ; Female ; Headache ; Hemorrhage ; Humans ; Necrosis ; Neuroimaging ; Pituitary Apoplexy* ; Pituitary Neoplasms ; Precipitating Factors ; Pregnancy ; Visual Acuity

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

PURPOSE: This study is designed to find out the clinical characteristics, growth status, and response to growth hormone treatment in children with organic growth hormone deficiency(GHD) after treatment of brain tumors. METHODS: Fifty-three children with organic GHD were evaluated for pituitary function, serum insulin-like growth factor-1(IGF-1), and insulin-like growth factor binding protein-3(IGFBP-3) concentrations. We also observed their growth status and corresponding change with or without growth hormone treatment. RESULTS: The causes of organic GHD were craniopharyngioma(47%), germinoma (19%), and medulloblastoma(17%), and 18 children(35%), diagnosed with brain tumors, presented with symptoms suggesting hormonal deficit. Initial height was -2.5+/-.2 SDS in craniopharyngioma, -1.7+/-.1 SDS in germinoma, and -2.1+/-.6 SDS in medulloblastoma, and children with craniopharyngioma showed the highest obesity rate, at 21.4+/-9.3%. After treatment for brain tumors, children with craniopharyngioma had the lowest values of peak GH, IGF-1, and IGFBP-3 concentrations, which were 1.1+/-.3 ng/mL, 74.1+/-6.6 ng/mL(-1.7+/-.2 SDS), and 1.9+/-.0 mg/L(-2.0+/-.1 SDS) respectively. The numbers of deficient hormones increased from 2.4+/-.1 to 3.2+/-.2 after treatment of brain tumors(P<0.05). Nine children showed normal or accelerated growth velocity(growth velocity 7.0+/-.8 cm/yr) without GH replacement and they had higher body mass index(BMI), IGF-1 concentrations, and IGFBP-3 SDS(P<0.05) compared to the others(growth velocity 1.9+/-.9 cm/yr). Height SDS increased every year during the first three years of GH treatment(P<0.05), 0.5+/-.4 SDS(n=20) for the first year, 0.4+/-.4 SDS(n=14) for the second, and 0.3+/-.5 SDS(n=11) for the third, and it increased by 1.1+/-.9 SDS(n=11) in total. CONCLUSION: The numbers of deficient pituitary hormones were increased after operation, irradiation, and/or chemotherapy. Children with GHD showed good response to GH replacement. Some children grew normally in spite of growth hormone deficiency, and their BMI, serum levels of IGF-1 and IGFBP-3 SDS were increased compared to those of the decreased growth group. This study suggests that further studies are needed to determine the mechanism of growth with low GH concentrations.
Brain Neoplasms* ; Brain* ; Child* ; Craniopharyngioma ; Drug Therapy ; Germinoma ; Growth Hormone* ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Medulloblastoma ; Obesity ; Pituitary Hormones

BACKGROUNDThyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism. Somatostatin (SST) analogs work by interacting with somatostatin receptors (SSTRs). This study aimed to evaluate short-term preoperative octreotide (OCT) use in TSHoma patients and to investigate SSTR2 and SSTR5 expression and observe structural changes in tumor tissue.

METHODSWe reviewed records and samples from eight TSHoma patients treated between July 2012 and July 2015. We tested immunohistochemically for SSTR2/5 expression and examined TSHoma cells for morphological changes. Signed rank sum test was used to compare the efficacy of short-term preoperative OCT treatment.

RESULTSOCT treatment (median time: 7.9 days, range: 3-16 days; median total dose: 1.8 mg, range: 0.9-4.2 mg) led to significant decrease in all patients' thyroid hormone levels (FT3 [nmol/L]: 8.33 [7.02, 12.29] to 4.67 [3.52, 5.37] [P = 0.008]; FT4 [pmol/L]: 25.36 [21.34, 28.99] to 16.66 [14.88, 21.49] [P = 0.016]; and TSH [μU/ml]: 5.80 [4.37, 6.78] to 0.57 [0.19, 1.24] [P = 0.008]). All the eight tumor specimens expressed high SSTR2 protein levels; 5/8 expressed high SSTR5, but 3/8 that expressed low SSTR5 presented a significantly higher TSH suppression rate (P = 0.036). Electron microscopy showed subcellular level impairments, including clumped nuclear chromatin and reduced cytoplasmic volume. Golgi complexes were observed in the OCT-treated TSHoma specimens.

CONCLUSIONSOCT can control hormone levels and damage the ultrastructure of tumor cells and organelles. Short-term response to OCT may be related to SSTR5 expression. Preoperative SST analog treatment for TSHoma could be considered as a combination therapy.

Adult ; Female ; Humans ; Immunohistochemistry ; Male ; Microscopy, Electron ; Middle Aged ; Octreotide ; therapeutic use ; Pituitary Neoplasms ; drug therapy ; metabolism ; Receptors, Somatostatin ; metabolism ; Thyrotropin ; secretion

BACKGROUNDLittle information about the current management of patients with thyroid-stimulating hormone (TSH)-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was contained in the literature. This study aimed to report the efficacy and safety of the long-acting octreotide formulation in patients with TSH-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure.

METHODSFifteen patients with TSH-secreting pituitary adenomas (8 men and 7 women), who previously underwent incomplete surgical resection and/or adjuvant radiotherapy (n = 12) and failure of octreotide treatment (n = 15), followed between 2007 and 2010 in Beijing Tiantan Hospital were included in this study. All patients received 1- to 2-months of the long-acting octreotide formulation treatment after the above combination of treatment. Paired samples t-test was used to analysis the variables.

RESULTSAfter two-month duration of the long-acting octreotide formulation treatment, the mean serum free or unbound thyroxine (FT4) ((16.02 ± 1.72) pmol/L) and free triiodothyronine (FT3) ((2.87 ± 0.43) pmol/L) levels of 15 patients significantly decreased compared with those after octreotide-treatment (FT4, (35.36 ± 7.42) pmol/L, P < 0.001; FT3, (17.85 ± 7.22) pmol/L, P < 0.001). Mean TSH levels stayed in the normal range after the long-acting octreotide formulation treatment ((0.72 ± 0.21) mU/L) and were significantly lower than the pretreatment value ((5.27 ± 1.04) mU/L, P < 0.001), post-surgery value ((3.37 ± 0.31) mU/L, P < 0.001) and post-octreotide-treatment value ((4.52 ± 0.41) mU/L, P < 0.001). In these patients with TSH-secreting pituitary adenomas there was no evidence of tachyphylaxis.

CONCLUSIONThe long-acting octreotide formulation may be a useful and safe therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary adenomas in patients who underwent incomplete surgery or need long-term somatostatin analog therapy.

Adult ; Female ; Humans ; Male ; Middle Aged ; Octreotide ; therapeutic use ; Pituitary Neoplasms ; blood ; drug therapy ; secretion ; surgery ; Thyrotropin ; blood ; secretion ; Thyroxine ; blood ; Triiodothyronine ; blood

Pituitary metastasis from renal cell carcinoma is rare and has never been reported for renal cell carcinoma primarily treated with sorafenib. Herein, we present a case of an advanced clear-cell renal cell carcinoma in which pituitary metastasis progressed but extracerebral metastases showed partial response to sorafenib treatment.
Antineoplastic Agents ; therapeutic use ; Carcinoma, Renal Cell ; drug therapy ; pathology ; Humans ; Kidney Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Niacinamide ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; therapeutic use ; Pituitary Neoplasms ; radiotherapy ; secondary ; Radiotherapy, Conformal

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