ergoline and Hypopituitarism

Meningitis is an uncommon complication of an untreated pituitary macroadenoma. Meningitis may occur in patients with macroadenomas who have undergone transsphenoidal surgery and radiotherapy and is usually associated with rhinorrhea. Less commonly, cerebrospinal fluid rhinorrhea has been reported as a complication of treatment of prolactinomas by dopamine agonists. Cerebrospinal fluid rhinorrhea in cases of untreated pituitary macroadenoma is reported only in isolated cases. Acute bacterial meningitis without rhinorrhea in patients with an untreated pituitary macroadenoma is an exceptional finding with only three previously reported cases.. A 31-year-old male was urgently admitted for headache, fever and visual loss. Neuroimaging disclosed an invasive pituitary lesion. Cerebrospinal fluid leakage was not clinically detected. Lumbar puncture showed acute meningitis. Blood tests revealed increased inflammatory markers, a serum prolactin of 9000 ng/ml (2.5-11 ng/ml) and panhypopituitarism. Intravenous antibiotics and hydrocortisone replacement therapy were initiated, leading to a favorable clinical outcome. An endoscopic transsphenoidal debulking procedure was performed, it showed that the sphenoid floor was destroyed and the sinus occluded by a massive tumor.. Meningitis should be ruled out in patients with a pituitary mass who present with headache and increased inflammatory tests, even in the absence of rhinorrhea.

Topics: Adult; Anti-Bacterial Agents; Blindness; Cabergoline; Combined Modality Therapy; Ergolines; Fever; Headache; Hormone Replacement Therapy; Humans; Hydrocortisone; Hypophysectomy; Hypopituitarism; Male; Meningitis, Aseptic; Neoplasm Invasiveness; Pituitary Neoplasms; Prolactinoma; Sella Turcica; Third Ventricle; Thyroxine

The frequency and the degree of recovery of anterior pituitary hormone deficits in patients with macroprolactinoma responsive to cabergoline are not clear. Our aim was to evaluate pituitary function in these patients with particular reference to an assessment of the possible restoration of pituitary deficits.. The records of all subjects prospectively presenting to our Department with macroprolactinomas treated with cabergoline over a 2-year period were reviewed. Pituitary function was assessed at diagnosis and, if abnormal, for three consecutive years for the GH, FSH/LH and ACTH axes, and at 3 years for the TSH axis.. Twelve patients were included. Severe GH deficiency was found in 83% at diagnosis and did not resolve in any patient at last assessment. Gonadotrophin deficiency was found in 90% at diagnosis and in 50% at last evaluation (showing reversal in 44% of deficient patients, all achieved within 1 year). ACTH deficiency was found in 17% at diagnosis and it did not reverse in any patient at last assessment. TSH deficiency was found in 36% at diagnosis and in 27% at last assessment (reversal in 25% of deficient patients).. In our study, in a group of patients with macroprolactinoma systematically assessed at intervals, pituitary dysfunction in response to cabergoline was found to be mostly irreversible, except for the gonadotroph axis which showed restoration in a subset of subjects following achievement of normoprolactinaemia. It would appear that the reversibility of pituitary axes may be less common than previously thought.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hypopituitarism; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies

Hyperprolactinaemia frequently causes secondary hypogonadism through central suppression of gonadotropin secretion. Macroprolactinomas (> 1 cm diameter) are more common in males and may additionally cause more generalised hypopituitarism. Recovery of the thyrotropic and/or corticotropic axes is well described following selective adenomectomy, but remains poorly defined in relation to medical (dopamine-agonist) therapy of macroprolactinomas. We therefore performed a retrospective examination of case records of male patients who had received medical therapy alone for macroprolactinoma between 1980-2001 (n = 35) and in whom tumor shrinkage was documented by interval pituitary imaging (reported throughout by a single neuroradiologist). Mean prolactin level at baseline was 59,932 mU/L (median 31,400; range 3,215-332,000); mean period of follow up was 4.2 years (median 2.6; range: 1.0-15). Defects of the following axes were evident at diagnosis: LH/FSH-testosterone (n = 27; 77%), TSH-T4 (n = 14; 41%-not including one case with pre-existing 1 degress hypothyroidism), ACTH-cortisol (n = 8; 23%). Overall, 14 men (40%) were deficient in 1 axis, seven (20%) in 2 axes and seven (20%) in 3 axes. Growth hormone secretory status was not systematically evaluated. In all but 6 patients, prolactin levels fell to normal or near-normal levels (mean 764 mU/L; median 260; range: < 10-4,833). Of the patients in whom adequate reassessment had been performed, thyrotroph function recovered in 4/9, corticotroph function in 4/6 and gonadotroph function in 16/26 cases. In four cases (11%) previously described, development of visual impairment as a result of the chiasmal traction syndrome necessitated a dose reduction in medical therapy to allow a degree of controlled tumor re-expansion. The prevalence at diagnosis of TSH and ACTH deficiency in men with macroprolactinomas was 41% and 23%, respectively. Among eight patients with insufficiency of TSH and/or ACTH secretion who underwent complete interval reassessment over several years of treatment, recovery of at least one axis occurred in six cases (75%). This study highlights the importance of screening ACTH- and/or TSH-deficient men during dopamine agonist therapy in order to identify cases where hypopituitarism has resolved.

Topics: Adrenocorticotropic Hormone; Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Follicle Stimulating Hormone; Humans; Hypopituitarism; Luteinizing Hormone; Male; Middle Aged; Pergolide; Pituitary Function Tests; Pituitary Gland; Pituitary Neoplasms; Prolactin; Prolactinoma; Testosterone; Thyrotropin

To evaluate the prevalence of resistance to cabergoline treatment, we studied 120 consecutive de novo patients (56 macroadenoma, 60 microadenoma, 4 nontumoral hyperprolactinemia) treated with cabergoline (CAB) compared with 87 consecutive de novo patients (28 macroadenoma, 44 microadenoma, 15 nontumoral hyperprolactinemia) treated with bromocriptine (BRC) for 24 months. Resistance was evaluated as inability to normalize serum PRL levels (first end point) and to induce tumor shrinkage (second end point). After 24 months, PRL normalization and tumor shrinkage after CAB and BRC treatments, respectively, were obtained in 82.1% and 46.4% of macroprolactinomas (P < 0.001) and in 90% vs. 56.8% of microprolactinomas (P < 0.001). The median doses of CAB and BRC able to fulfill the two criteria of treatment success were 1 mg/wk and 7.5 mg/d in macroprolactinomas, 1 mg/wk and 5 mg/d in microprolactinomas, and 0.5 mg/wk and 3.75 mg/d in nontumoral hyperprolactinemia. Hyperprolactinemia persisted in 17.8% of macroprolactinomas, 10% of microprolactinomas, and after CAB at doses of 5-7 mg/wk and in 53.6% of macroprolactinomas, 43.2% of microprolactinomas, and 20% of nontumoral hyperprolactinemic patients, after BRC at doses of 15-20 mg/d. In these resistant macro- and microprolactinomas, the maximal tumor diameter was reduced by 43.7 +/- 3.6% and 22.1 +/- 3.7% and by 59.3 +/- 7.1% and 4.3 +/- 2.1% after CAB and BRC, respectively (P < 0.001). In conclusion, long-term CAB treatment induced the successful control of hyperprolactinemia associated with tumor shrinkage in a higher proportion of patients than did BRC treatment. In a small number of patients (i.e. 17.8% of macroprolactinomas and 10% of microprolactinomas), however, CAB treatment did not normalize serum PRL levels despite reducing tumor mass, even at very high doses. Therefore, an absence of tumor shrinkage cannot be considered as end point to indicate resistance to CAB, and increasing the dose of CAB higher than 3 mg/wk does not seem to be helpful in controlling PRL hypersecretion.

Topics: Adenoma; Adolescent; Adult; Aged; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance; Ergolines; Female; Hormone Antagonists; Humans; Hyperprolactinemia; Hypopituitarism; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Radioimmunoassay; Retrospective Studies

Management of macroprolactinomas has dramatically changed in recent decades, from surgical to medical treatment as first-line therapy, with the development of dopamine agonists (DA). But few data exist on the long-term outcome of these patients.. Retrospective descriptive multicenter study of patients with macroprolactinoma followed for at least 5 years between 1973 and 2008 at the University Hospitals of Strasbourg and Marseille.. Forty-eight patients were included with 27 men, hypopituitarism in 33.3% of all patients and mean serum prolactin (PRL) level at diagnosis 2218.2±4154.7μg/L. Among the patients, 58.3% received medical treatment, 25% had additional surgery and 12.5% surgery and radiotherapy. The mean follow-up duration was 196±100 months. At the end of follow-up, 10 patients (20.8%) were cured (i.e. normal PRL level and normal imaging, no symptoms and withdrawal of DA≥1 year), 33 (68.8%) were controlled (i.e. normal PRL level, normal or abnormal imaging, no symptoms, DA in progress) and 5 (10.4%) were uncontrolled. Uncontrolled patients had significant higher baseline PRL level (P=0.0412) and cabergoline cumulative dose (P=0.0065) compared to the controlled group. There was no increase in frequency of hypopituitarism. Clinically significant valvular heart disease was found in 2 patients but screening was not systematic.. Macroprolactinoma is currently most often a chronic disease controlled with DA. However, uncertainty about the adverse effects associated with high cumulative doses and the lack of data on the prognosis at very long-term should incite to revisit current strategies, including the role of surgery combined to medical treatment.

Topics: Adolescent; Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; France; Humans; Hyperprolactinemia; Hypopituitarism; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Treatment Outcome; Young Adult

Men with prolactin-secreting tumors usually harbor macroadenomas. The degree of pituitary dysfunction may vary among different adenoma size subgroups, as is recovery after treatment. Our study purpose was to characterize hypopituitarism and recovery after treatment in men with macroprolactinomas.. A retrospective study, including a consecutive group of 81 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (>7×ULN). Patients were divided into three categories according to adenoma size at presentation: 10-19 mm (group A), 20-39 mm (group B), and ≥40 mm (group C). We compared total testosterone, gonadotropins, cortisol, thyroid hormones and hemoglobin levels at presentation and after treatment.. Eighty-one patients were included; 24, 31 and 26 patients in groups A, B and C, respectively. Pretreatment hypogonadism prevalence was 75.0, 93.5 and 90.9% (p = 0.046; A vs B and C), central hypocortisolism - 0, 6.9 and 33.3% (p = 0.005), and central hypothyroidism - 6.7, 17.9 and 26.1% (NS) in groups A, B and C, respectively. Only 26.7% of all patients presented with hypocortisolism and/or hypothyroidism (42.9% in group C). Anemia (Hb < 13.5 g%) was detected in 31.3, 57.1 and 80.0% in groups A, B and C, respectively (p = 0.04). Larger adenoma diameter correlated strongly with lower FT4 levels following treatment (r = -0.42, p = 0.043).. Macroprolactinomas in men caused partial hypopituitarism, affecting testosterone in all adenoma size groups and cortisol more in patients with larger adenomas. However, most of the men did not have pituitary hormones affected, beside testosterone. Most patients recovered central hypocortisolism but not hypothyroidism following treatment.

Topics: Adult; Aged; Aged, 80 and over; Cabergoline; Ergolines; Humans; Hypopituitarism; Male; Middle Aged; Prevalence; Prolactinoma; Retrospective Studies; Testosterone; Young Adult

Topics: Anemia; Antineoplastic Agents; Biomarkers, Tumor; Cabergoline; Chronic Disease; Dopamine Agonists; Drug Therapy, Combination; Early Detection of Cancer; Ergolines; Hematocrit; Hemoglobins; Hormone Replacement Therapy; Humans; Hydrocortisone; Hypogonadism; Hypopituitarism; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Testosterone; Thyroxine; Treatment Outcome

To describe a patient who was misdiagnosed as having a nonfunctional pituitary tumor due to the hook effect on prolactin measurements.. A 45-year-old female was admitted with visual disturbances, panhypopituitarism and central diabetes insipidus due to pituitary tumor recurrence. She had been operated 4 times earlier and received cranial irradiation for a suspected nonfunctional pituitary adenoma. Serum prolactin was moderately elevated (164.5 ng/ml), but increased markedly after 1:100 dilution to 14,640 ng/ml. Diagnosis of a giant macroprolactinoma was made and cabergoline was started. Prolactin level normalized and a mild shrinkage of the tumor was achieved after 12 months of therapy.. The hook effect must be kept in mind while evaluating a giant pituitary adenoma with moderately elevated prolactin levels. This way unnecessary surgical procedures or irradiation may be avoided.

Topics: Antineoplastic Agents; Cabergoline; Diabetes Insipidus, Neurogenic; Diagnostic Errors; Ergolines; Female; Glucocorticoids; Humans; Hypopituitarism; Middle Aged; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prednisolone; Prolactin; Prolactinoma; Thyroxine

Pituitary adenomas are rare in young patients. Prolactinomas are the most common type of pituitary adenomas in children older than 12 years, occurring more often in girls, at a 4.5:1 female-to-male ratio. The clinical presentation may vary according to the age and sex of the patient. Pituitary apoplexy is a rare life-threatening condition caused by a sudden infarction or hemorrhagic necrosis of the pituitary containing an adenoma. A wide variety of conditions can trigger apoplexy such as pituitary irradiation, general anesthesia, traumatic head injury, pituitary stimulatory tests and a wide variety of medications including bromocriptine. We report a case of a 16-year-old male patient with puberty arrest harboring a macroprolactinoma, who developed a sudden clinical picture of pituitary apoplexy during the 12th month of treatment with cabergoline.

Topics: Adenoma; Adolescent; Antineoplastic Agents; Cabergoline; Ergolines; Humans; Hypopituitarism; Magnetic Resonance Imaging; Male; Pituitary Diseases; Pituitary Neoplasms; Prolactin; Prolactinoma; Stroke

To review clinical presentation, management and outcomes following different therapies in patients with pituitary apoplexy.. Retrospective analysis of case-records of patients with classical pituitary apoplexy treated in our hospitals between 1983-2004.. Forty-five patients (28 men; mean age 49 years, range 16-72 years) were identified. Only 8 (18%) were known to have pituitary adenomas at presentation. Thirty-four (81%) patients had hypopituitarism at presentation. CT and MRI identified pituitary apoplexy in 28% and 91% cases, respectively. Twenty-seven (60%) patients underwent surgical decompression, whilst 18 (40%) were managed conservatively. Median time from presentation to surgery was 6 days (range 1-121 days). Patients with visual field defects were more likely than those without these signs to be managed surgically (p = 0.01). Complete or near-complete resolution occurred in 93% (13/14), 94% (15/16) and 93% (13/14) of the surgically treated patients with reduced visual acuity, visual field deficit and ocular palsy, respectively. All patients with reduced visual acuity (4/4), visual field deficit (4/4) and ocular palsy (8/8) in the conservative group had complete or near-complete recovery. Only 5 (19%) patients in the surgical group and 2 (11%) in the conservative group had normal pituitary function at follow up. One (4%) patient in the surgical group and 4 (22%) in the conservative group had a recurrence of pituitary adenoma.. This large series suggests that the patients with classical pituitary apoplexy, who are without neuro-ophthalmic signs or exhibit mild and non-progressive signs, can be managed conservatively in the acute stage.

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Cabergoline; Combined Modality Therapy; Decompression, Surgical; Ergolines; Female; Humans; Hypopituitarism; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Apoplexy; Pituitary Gland; Pituitary Neoplasms; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Vision Disorders

Cabergoline therapy normalizes prolactin levels and reduces the size of macroprolactinomas. However there are no data indicating whether cabergoline can normalize growth hormone secretion in patients who were growth hormone deficient at the time of diagnosis of a macroprolactinoma.. We studied nine patients with biochemical and radiological evidence of a macroprolactinoma who were also growth hormone deficient (peak growth hormone response to insulin-induced hypoglycaemia < 10 mU/l). Patients were assessed before and after cabergoline therapy to assess their growth hormone secretory status, IGF-I levels, cortisol response and change in tumour size.. Treatment with cabergoline was associated with a significant reduction in prolactin concentration (74341 +/- 31939 mU/l vs. 265.9 +/- 86.3, P = 0.009). The mean change in peak growth hormone response to insulin-induced hypoglycaemia was significantly greater following cabergoline therapy compared with pretreatment levels (33.5 +/- 11.8 mU/l vs. 4. 34 +/- 1.21 mU/l, P = 0.022). However IGF-I levels were not different after treatment when compared with baseline although a nonsignificant trend towards improvement was noted (24.2 +/- 3.97 nmol/l vs. 18.4 +/- 4.94 nmol/l, P = 0.058). The mean peak cortisol concentration was 407.7 +/- 64.1 nmol/l before treatment with a nonsignificant rise to 477.4 +/- 84.8 nmol/l, P = 0.813 after treatment. These changes were associated with a significant reduction in mean maximal tumour diameter (21.2 +/- 2.9 mm vs. 29.1 +/- 2.8 mm, P = 0.009). There was no significant difference in either prolactin concentration or tumour size pre- or post-treatment between those who recovered growth hormone secretion and those that did not. Six of the nine (67%) patients recovered a normal growth hormone response (> 10 mU/l) after cabergoline therapy. Those that remained growth hormone deficient after treatment were all panhypopituitary at baseline while those that recovered showed only partial anterior hypopituitarism.. These data indicate that growth hormone secretion may recover following successful reduction of prolactin levels after cabergoline therapy for a mean of 22 months (range 6-28 months) in most but not all subjects with a macroprolactinoma. It is therefore advisable that individuals with a macroprolactinoma in whom growth hormone replacement therapy is being considered undergo repeat assessment of growth hormone secretion following medical treatment.

Topics: Adolescent; Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Human Growth Hormone; Humans; Hydrocortisone; Hypopituitarism; Insulin-Like Growth Factor I; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Recovery of Function; Treatment Outcome