leuprolide and Adenoma

We report the case of a 60 year old male who complained of headache and blurry vision--that progressed to left ophthalmoplegia and ptosis--after receiving a dose of leuprolide for Prostate cancer therapy. Imaging showed a hemorrhagic sellar mass. The patient underwent transsphenoidal debulking, and the tissue obtained demonstrated immunohistochemical staining for LH. A literature review revealed nine previously reported cases of pituitary apoplexy after GnRH agonist therapy for prostate cancer. In most cases, the sellar tissues stained for LH, consistent with a gonadotropinoma. The pathophysiology of these events is unclear, but recent animal models suggest possible explanations. The predominance of gonadotropinomas is important because they do not usually present with hypersecretory symptoms. Particular attention to clinical findings suggestive of a non functioning pituitary tumor in patients receiving GnRH agonist therapy is critical as routine screening with MRI is not practical.

Topics: Adenoma; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Pituitary Neoplasms; Prostatic Neoplasms; Sella Turcica; Stroke

Gonadotropin-releasing hormone (GnRH) agonists are widely used in hormone therapy for prostate cancer. We report a patient with pituitary apoplexy following this therapy as a rare complication and review the related literature. A 62-year-old man presented with elevated prostate specific antigen. Transrectal ultrasound guided biopsy of the prostate gland revealed adenocarcinoma. Whole-body (18)F-fluorodeoxyglucose (FDG) positron emission tomography/CT scan showed FDG-uptake in the pituitary region. MRI also demonstrated a pituitary tumor, diagnosed as an incidental non-functioning adenoma. The patient received his first dose of GnRH agonist (leuprolide 11.25mg) against prostate cancer. He complained of a severe headache 10 minutes after leuprolide administration and suffered from right third nerve palsy in the next 48 hours. MRI demonstrated a high intensity area on T1-weighted images, diagnosed as pituitary apoplexy. The patient underwent transsphenoidal surgery. Pathology revealed predominantly necrotic tissue and a gonadotropin secreting pituitary adenoma. Overall, 15 patients, including ours, have been reported with pituitary apoplexy after GnRH agonists with pathologic gonadotropin secreting adenoma. Fourteen of 15 patients were male. Pituitary apoplexy developed within 4 hours after administration of the agents in 8/15 patients. The combined data suggest that GnRH agonists have the potential to precipitate pituitary apoplexy in men with gonadotropin secreting adenoma. Therefore, prior to GnRH agonist therapy for prostate cancer, a known pituitary adenoma should be treated. Otherwise, the patients should be cautiously observed for any symptomatic change following drug administration.

Topics: Adenocarcinoma; Adenoma; Antineoplastic Agents, Hormonal; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Apoplexy; Pituitary Neoplasms; Prostatic Neoplasms

Bioactive gonadotropin-secreting pituitary adenomas are very rare in fertile women and can cause an ovarian hyperstimulation syndrome (OHSS). A 31-year-old woman with oligo-amenorrhea, severe ovarian cystic swelling and high serum estradiol was submitted to the resection of ovarian cysts and then treated with long-acting leuprolide 11.25 mg. Two months later, the ovarian multicystic hyperplasia relapsed, thus a pituitary MRI was performed and a pituitary macroadenoma was detected. In January 2010, she was referred to our Endocrinology Department where her hormonal evaluation showed high serum estradiol, FSH, α-subunit and inhibin with low LH. In April 2010, she underwent a trans-sphenoidal pituitary adenomectomy, which rapidly regularized the hormonal profile, the ovary and pituitary morphology and the menses. The case presented confirms that gonadotrophinomas occurring in reproductive-aged women frequently produce symptoms of ovarian hyperstimulation and proves that the use of GnRH analogs is not indicated in this condition.

Topics: Adenoma; Adult; Age Factors; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Humans; Leuprolide; Ovarian Cysts; Ovarian Hyperstimulation Syndrome; Pituitary Neoplasms; Recurrence; Reproduction; Treatment Failure

We report the case of a T3 prostate cancer in a 70-year-old white man. Hormone therapy represents a prominent branch in the treatment of locally advanced and metastatic prostate cancer. Gonadotropin-releasing hormone agonists have been proven to have a double effect on androgen metabolism: an initially stimulating, followed by an inhibitory, effect on the pituitary gland. This phenomenon may be noxious in the case of gonadotroph adenoma, with subsequent symptoms of intracranial hypertension. Gonadotropin-releasing hormone antagonists (abarelix), by avoiding the flare-up reaction, might be used in such instances.

Topics: Adenocarcinoma; Adenoma; Aged; Antineoplastic Agents, Hormonal; Biopsy; Diagnosis, Differential; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prostatic Neoplasms; Tomography, X-Ray Computed

Gonadotropin-releasing hormone (GnRH) agonists have become the treatment of choice for locally advanced and metastatic prostate cancer. We report a case of prostate cancer in which this treatment led to severe symptoms of intracranial hypertension due to the concomitant presence of an asymptomatic functional pituitary adenoma. A 70-year-old white man was initially evaluated for a multifocal adenocarcinoma, Gleason score 6 (3+3) with perineural invasion suggesting an extracapsular extension. A conformational external beam radiation (74 Gy) with a concomitant GnRH agonist (leuprolide) was initiated. Almost 10 days after the administration of leuprolide the patient complained of visual disturbance, diplopia and other symptoms of intracranial hypertension. Magnetic resonance imaging (MRI) of the brain demonstrated a large sella mass lesion. To relieve the patient's symptoms, a transsphenoidal subtotal tumorectomy was necessary. The histopathological examination revealed an invasive gonadotroph pituitary adenoma. Two years later, there is no sign of progression either on his prostatic disease (prostate-specific antigen of 0.21 ng/mL) or on his pituitary disease (FSH, 4.7 UI/L, LH, 3.1 UI/L and total testosterone, 627 ng/dL) with values of the hypothalamic-pituitary axis in the normal range. We advocate that a high index of suspicion of pituitary tumor must be considered in any case of intracranial hypertension following the administration of GnRH agonist. Abarelix could have a place in such cases.

Topics: Adenocarcinoma; Adenoma; Aged; Antineoplastic Agents, Hormonal; Diagnosis, Differential; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Neoplasms, Multiple Primary; Pituitary Neoplasms; Prostatic Neoplasms; Tomography, X-Ray Computed

Clinically unsuspected pituitary adenomas are common among adults on autopsy and MRI survey. Acute pituitary hemorrhage is far more rare. We report a case of a 61-year-old male patient with locally advanced prostate cancer who presented with an acute picture of pituitary apoplexy after his first dose of leuprolide. He developed headache and neck pain within a few hours of treatment followed by nausea, vomiting, ptosis and diplopia. Pituitary apoplexy is a potentially life threatening medical emergency. Although the pathophysiology is poorly defined, various conditions and treatments have been reported to trigger apoplexy. Apoplexy has been reported in response to pituitary stimulation by GnRH or GnRH-agonists. Initial stimulatory effects of gonadotropin releasing hormone (GnRH) analogue may induce apoplexy in patients with asymptomatic gonadotroph adenomas.

Topics: Adenoma; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Humans; Hypophysectomy; Leuprolide; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Apoplexy; Pituitary Neoplasms; Prostatic Neoplasms; Risk Factors; Treatment Outcome

We report here two cases of pituitary apoplexy or pseudoapoplexy revealing a gonadotroph adenoma. A 69-year-old man, who had just started antiandrogen treatment (Gn-RH agonist) for prostatic cancer, was admitted to neurosurgery emergency because of increasing headache and visual impairment. The CT-scan disclosed the presence of a large pituitary mass with lateral invasion of the left cavernous sinus. Hormonel testing showed panhypopituitarism. A few days later, diabetes insipidus appeared. The patient first received corticosteroid therapy and underwent surgical adenomectomy. Immunostaining of the tumor tissue was positive for FSHbeta, confirming the diagnosis of gonadotroph adenoma. Three months after surgery, the endocrine evaluation showed pituitary insufficiency. An 81-year-old man complained of mnemonic disorders. The CT-scan revealed a pituitary mass without extension. The Ophthalmological examination showed left temporal upper quadranopsia. Endocrinological tests with administration of GN-HR triggered headache and vomiting. A second CT-scan was unchanged. Hormone testing revealed increased serum levels of FSH and decreased serum levels of LH. Surgical management of the primary tumor was undertaken due to the visual field alteration. Immunohistochemical studies confirmed the diagnosis of gonadotroph FSHbeta adenoma.

Topics: Adenoma; Aged; Aged, 80 and over; Follicle Stimulating Hormone; Follicle Stimulating Hormone, beta Subunit; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Male; Pituitary Apoplexy; Pituitary Neoplasms; Prostatic Neoplasms; Tomography, X-Ray Computed

To report a case of a gonadotroph adenoma diagnosed after a dramatic increase in estradiol level and ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist.. Case report.. Outpatient practice and university hospital.. A 35-year-old woman who presented with infertility, amenorrhea, and an elevated basal estradiol concentration.. Ultrasonography, laparoscopy, endocrinologic assays, magnetic resonance imaging, transsphenoidal surgery, and immunocytochemical staining.. Ultrasonography and laparoscopy demonstrated bilaterally enlarged ovaries containing multiple preovulatory follicles, similar in appearance in those women undergoing controlled ovarian hyperstimulation with exogenous FSH. The serum estradiol level was moderately elevated, the FSH level was within the normal range, and LH was suppressed. Administration of leuprolide acetate resulted in very elevated estradiol concentrations and even larger ovarian cysts. Magnetic resonance imaging demonstrated a sellar mass. Examination of the tissue excised by transsphenoidal excision of the mass showed a pituitary adenoma that stained strongly for FSH.. Regular menses resumed soon after excision of the gonadotroph adenoma, followed by a spontaneous pregnancy.. Gonadotroph adenoma should be suspected in a reproductive age woman with oligomenorrhea or amenorrhea, infertility, multiple preovulatory follicles, and a persistently elevated serum estradiol concentration. Exacerbation of the ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist in this setting also strongly suggests a gonadotroph adenoma but can be avoided by recognizing the presenting features of this condition.

Topics: Adenoma; Adult; Estradiol; Female; Fertility Agents, Female; Humans; Leuprolide; Ovarian Hyperstimulation Syndrome; Pituitary Gland, Anterior; Pituitary Neoplasms; Pregnancy

Topics: Adenocarcinoma; Adenoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Humans; Hypophysectomy; Leuprolide; Luteinizing Hormone; Male; Neoplasms, Multiple Primary; Pituitary Neoplasms; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Failure

Treatment of prostatic cancer with GnRH agonist is a medical alternative to surgical castration, although hyperstimulation of the tumor can occur. We describe an unusual unwanted effect of such a treatment which unmasked a clinically silent gonadotroph adenoma. A 62-year-old man developed after the first injection of leuprorelin-depot a sudden intracranial hypertension, which was related to apoplexy of an unknown pituitary adenoma. Its gonadotroph origin was recognized after surgery by immunocytochemistry. Retrospectively, the tumor was shown to secrete in vivo both FSH and LH when on therapy with the agonist, demonstrating the lack of desensitization. Testosterone levels were also markedly and sustainly high when on therapy, a particularly unwanted effect in prostatic cancer. As gonadotroph adenomas occur in men in the same age group as prostatic cancer, the question is raised whether hormonal testing and pituitary imaging should be performed before starting a therapy with GnRH agonist in men.

Topics: Adenoma; Delayed-Action Preparations; Follicle Stimulating Hormone; Humans; Leuprolide; Luteinizing Hormone; Magnetic Resonance Imaging; Male; Middle Aged; Orchiectomy; Pituitary Apoplexy; Pituitary Neoplasms; Prostatic Neoplasms; Testosterone

Topics: Adenoma; Aged; Humans; Leuprolide; Luteinizing Hormone; Male; Pituitary Neoplasms; Prostatic Neoplasms

As a preliminary step in searching for a pharmacological treatment for gonadotroph adenomas, we administered the GnRH antagonist analog Nal-Glu GnRH to five patients, four men and a woman, with FSH-secreting gonadotroph adenomas in order to determine its effect on FSH secretion. Administration of a single 10-mg dose of Nal-Glu GnRH to four of the patients produced a significant decrease in the serum FSH concentration in two patients and returned the FSH level to normal in only one. Administration of 5 mg Nal-Glu every 12 h for 7 days, however, produced a significant (P less than 0.001) decrease, and to within the normal range, in four of the five patients (mean +/- SEM, 32.7 +/- 5.6 IU/L during the 3 days before treatment and 9.8 +/- 1.4 IU/L during the last 3 days of treatment). Also, in response to the 7-day treatment, LH fell significantly in all five patients, alpha-subunit fell in three, and testosterone fell in all four men. Administration for 6 weeks of the GnRH agonist analog leuprolide did not decrease the serum FSH concentration of one of the patients whose serum FSH did decrease in response to Nal-Glu GnRH. We conclude that repetitive administration of Nal-Glu GnRH may often inhibit FSH secretion by gonadotroph adenomas and that FSH secretion by gonadotroph adenomas may be dependent on endogenous GnRH secretion.

Topics: Adenoma; Adult; Aged; Amino Acid Sequence; Dose-Response Relationship, Drug; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Molecular Sequence Data; Paraneoplastic Endocrine Syndromes; Pituitary Neoplasms; Testosterone; Time Factors; Tumor Cells, Cultured