Pituitary abscess: a report of two cases.

Pituitary abscess (PA) is an infrequent disease, which consists of an infection within the sella turcica that might be life-threatening. We present here two cases of this rare entity. Case 1: A 53-year-old woman was followed for an incidentally found pituitary cyst. Six years later the cyst enlarged and transsphenoidal surgery was performed. Two years later, the patient developed sudden onset of intense headache and nausea. The MRI showed a 2 by 2.5 cm sellar and suprasellar mass, that enhanced peripherally with gadolinium contrast and became hyperintense in T2-weighted images, suggesting a new-onset cystic lesion. During transsphenoidal surgery, large amounts of purulent material were drained from the sella. The cultures were positive for Klebsiella Ozaenae. Case 2: A 63-year-old woman, 4 years after transsphenoidal resection of a GH-secreting macroadenoma, developed a new sellar 2.6 cm cystic mass. On re-operation, purulent material was drained from the sella. The lesion persisted on the MRI and visual acuity worsened so a repeat pituitary decompression was carried out 6 months later, obtaining the same pathological results. Three years later, the MRI still shows the same mass. She feels well and her physical examination and clinical history are unremarkable. These cases illustrate the difficulties in the diagnosis and management of this rare entity.

Expression of p16(INK4A) gene in human pituitary tumours.

Pituitary adenomas comprise 10-15% of primary intracranial tumours but the mechanisms leading to tumour development are yet to be clearly established. The retinoblastoma pathway, which regulates the progression through the cell cycle, is often deregulated in different types of tumours. We studied the cyclin-dependent kinase inhibitor p16(INK4A) gene expression at mRNA level in human pituitary adenomas. Forty-six tumour specimens of different subtypes, 21 clinically non-functioning, 12 growth hormone-secreting, 6 prolactin-secreting, 6 adrenocorticotropin-secreting, and 1 thyrotropin-secreting tumours were studied. All clinically non-functioning and most of the hormone-secreting tumours were macroadenomas (38/46). The RT-PCR assay and electrophoresis of the PCR-products showed that p16(INK4A) mRNA was undetectable in: 62% of non-functioning, 8% of growth hormone-secreting, 17% of prolactin-secreting and 17% of adrenocorticotropin-secreting adenomas. Forty percent of all macroadenomas and 25% of microadenomas had negative p16(INK4A) mRNA, the latter results suggest that the absence of p16(INK4A) product might be an early event in tumours with no expression of this suppressor gene. Within the non-functioning adenomas 63% were "null cell" and 37% were positive for some hormone, both subgroups showed similar percentage of cases with absence of p16(INK4A) mRNA. Our results show that clinically non-functioning macroadenomas have impaired p16(INK4A) expression in a clearly higher proportion than any other pituitary tumour subtype investigated. Other regulatory pathways may be implicated in the development of tumours with positive p16(INK4A) expression.

Skin reaction and fever after treatment with pegvisomant in a patient with acromegaly.

BACKGROUND: Pegvisomant is a growth hormone receptor antagonist approved for the treatment of acromegaly. Documented adverse effects include headache, injection-site reactions, flulike syndrome, and reversible elevation of hepatic enzymes. Skin manifestations at the injection site are reported in approximately 11% of patients and are characterized as erythematous, self-limited reactions that neither require treatment nor lead to drug discontinuation. OBJECTIVE: This report describes a skin reaction and fever occurring after treatment with pegvisomant in a patient with acromegaly. CASE SUMMARY: The patient was a 54-year-old white woman with acromegaly (weight, 85 kg; height, 170 cm). At the time of consultation, her medication regimen was levothyroxine 150 microg/d for hypothyroidism and amlodipine 5 mg/d for hypertension. She started treatment with the somatostatin analogue octreotide acetate 20 mg every 4 weeks, which was then adjusted to 30 mg. Treatment was associated with only partial suppression of insulinlike growth factor-1 concentrations (from 980 ng/mL to 352, 632, and 480 ng/mL at 3, 6, and 9 months, respectively). At this point, octreotide was discontinued and treatment was initiated with pegvisomant 10 mg/d SC. This treatment was initially well tolerated, but after 11 days, she developed an intense erythematous pruriginous reaction at the injection site accompanied by fever (39 degrees C) for 48 hours and, simultaneously, similar lesions at each site of the previous injections. Pegvisomant was discontinued and methylprednisolone 40 mg/d was started, followed by complete disappearance of the lesions in 5 days. Based on the Naranjo algorithm, the adverse reaction observed was probably related to pegvisomant treatment (score = 6). CONCLUSIONS: We report a patient with acromegaly who developed a skin reaction and fever probably associated with pegvisomant administration. The reaction subsided 5 days after the drug was discontinued and methylprednisolone treatment was given.

Cabergoline monotherapy in the long-term treatment of Cushing's disease.

BACKGROUND: Cabergoline is a long-acting dopamine receptor agonist used to treat prolactinomas. Identification of D(2) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson's syndrome, ectopic ACTH-secreting tumors, and recently Cushing's disease (CD). OBJECTIVE: To evaluate the long-term efficacy of cabergoline monotherapy in patients with CD. METHODS: Retrospective analysis of non-randomized clinical therapy with cabergoline in 30 patients with CD treated in academic centers of Buenos Aires and Montreal. Cabergoline was initiated at 0.5-1.0 mg/week and adjusted up to a maximal dose of 6 mg/week based on urinary free cortisol (UFC) levels. Complete response to cabergoline was defined as a sustained normalization of UFC with at least two normal values measured at 1-3 months interval; partial response was defined as a decrease of UFC to <125% of the upper limit of normal, and treatment failure as UFC ≥ 125% of it. RESULTS: Within 3-6 months, complete response was achieved in 11 patients (36.6%) and partial response in 4 patients (13.3%). After long-term therapy, nine patients (30%) remain with a complete response after a mean of 37 months (range from 12 to 60 months) with a mean dose of 2.1 mg/week of cabergoline. Two patients escaped after 2 and 5 years of complete response, but one patient transiently renormalized UFC after an increase in cabergoline dosage. No long-term response was maintained in four initial partial responders. CONCLUSIONS: Cabergoline monotherapy can provide an effective long-term medical therapy for selected patients with CD, but requires close follow-up for dose adjustments.

Correction of cortisol overreplacement ameliorates morbidities in patients with hypopituitarism: a pilot study.

CONTEXT: Hypopituitarism in adults is known to be associated with deleterious effects on body composition, lipid profile and quality of life (QoL). This was attributed to GH deficiency. The potential role of glucocorticoid overreplacement had never been investigated. OBJECTIVE: To investigate whether reduction in glucocorticoid replacement dose to more physiological one could ameliorate the "AO-GHD"-attributed symptomatology in patients with hypopituitarism. Design Eleven patients with panhypopituitarism taking 20-30 mg/day of hydrocortisone, but on no GH replacement were switched to 10-15 mg of hydrocortisone daily. Both basally and 6-12 months later, their body mass index, body composition by dual-energy X-ray absorptiometry, lipid profile, and the score of quality of life, QOL-AGHDA were measured. RESULTS: Within 6-12 months of lower hydrocortisone dose, subjects lost an average of 7.1 kg of total body fat and 4.1 kg of abdominal fat. No changes were seen in lean body mass, bone mineral content and HOMA-IR. Plasma total cholesterol and triglyceride concentrations decreased significantly (< 0.05) and the QoL improved (P = 0.018). CONCLUSIONS: Our pilot study suggests that decreasing the glucocorticoid replacement dose to approximately 15 mg/day is beneficial in terms of patients' body composition, lipid profile and quality of life.

La corrección de la sustitución excesiva de cortisol mejora la morbilidad en pacientes con hipopituitarismo: un estudio piloto / Correction of Cortisol Overreplacement Ameliorates Morbidities in Patients with Hypopituitarism: A pilot study

Context: Hyporituitarism in adults is known to be associated with deleterious effects on body composition, lipid profile and quality of life (QoL). This was attributed to GH deficiency. The potential role of glucocorticoid overreplacement had never been investigated. Objective: To investigate whether reduction in glucocorticoid replacement dose to more physiological one could ameliorate the "AO-GHD"-attributed symptomatology in patients with hypopituitarism. Design: Eleven patients with panhypopituitarism taking 20-30 mg/day of hydrocortisone, but on no GH replacement were switched to 10 to 15 mg of hydrocortisone daily. Both basally and 6-12 months later, their body mass index, body composition by dual-energy x-ray absorptiometry, lipid profile, and the score of quality of life, QOL-AGHDA were measured. Results: Within 6-12 months of lower hydrocortisone dose, subjects lost an average of 7.1 kg of total body fat and 4.1 kg of abdominal fat. No changes were seen in lean body mass, bone mineral content and HOMA-IR Plasma total cholesterol and triglyceride concentrations decreased significantly (<0.05) and the QoL improved (p=0.018). Conclusions: Our pilot study suggests that decreasing the glucocorticoid replacement dose to ~ 15 mg/ day is beneficial in terms of patients' body composition, lipid profile and quality of life.