Clinical and molecular features of four Brazilian families with multiple endocrine neoplasia type 1.

Objective: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by its clinical variability and complexity in diagnosis and treatment. We performed both clinical and molecular descriptions of four families with MEN1 in a follow-up at a tertiary center in Brasília. Methods: From a preliminary review of approximately 500 medical records of patients with pituitary neuroendocrine tumor (PitNET) from the database of the Neuroendocrinology Outpatient Clinic of the University Hospital of Brasília, a total of 135 patients met the criteria of at least two affected family members. From this cohort, we have identified 34 families: only four with a phenotype of MEN1 and the other 30 families with the phenotype of familial isolated pituitary adenoma (FIPA). Eleven patients with a clinical diagnosis of MEN1 from these four families were selected. Results: Variants in MEN1 gene were identified in all families. One individual from each family underwent genetic testing using targeted high-throughput sequencing (HTS). All patients had primary hyperparathyroidism (PHPT), and the second most common manifestation was PitNET. One individual had well-differentiated liposarcoma, which has been previously reported in a single case of MEN1. Three variants previously described in the database and a novel variant in exon 2 have been found. Conclusions: The study allowed the genotypic and phenotypic characterization of families with MEN1 in a follow-up at a tertiary center in Brasília.

Giant cabergoline-resistant prolactinoma in a man who presented with a psychotic episode during treatment: a case report.

BACKGROUND: Prolactinomas are tumors of the pituitary gland that usually respond very well to treatment with cabergoline. Resistance to cabergoline is very rare, but when it occurs, it is a difficult problem to resolve if the tumor is inoperable. CASE PRESENTATION: A 62-year-old white man was treated for a giant macroprolactinoma detected during investigation of a subacute subdural hematoma of the left frontal lobe. The patient was treated with cabergoline for 17 years with a dose ranging from 1.0 mg to 3.5 mg per week. We were not able to normalize his prolactin level, which initially was 14,992 ng/ml and ultimately 1754 ng/ml. The tumor significantly shrank during the follow-up period but persisted. The patient had cardiac valvulopathies that did not worsen. He had an ischemic stroke and developed a psychotic condition that was successfully treated by lowering the cabergoline and administering quetiapine and mirtazapine together. This regimen led to a small increase in the patient's prolactin that returned to previous levels and remained as such until the last medical evaluation. The tumor continued to shrink and had a cystic degeneration in the last evaluation. CONCLUSIONS: Combined use of cabergoline with quetiapine and mirtazapine to treat a psychotic crisis may have contributed to shrinking the tumor in our patient because these antipsychotics have action mediated by growth factors that interfere with growth of pituitary tumors.

Prolactinomas Resistant to Treatment With Dopamine Agonists: Long-Term Follow-Up of Six Cases.

Introduction: Prolactinomas are preferentially treated with dopamine agonists. However, a few adenomas are resistant to this treatment. Objective: To evaluate the characteristics of patients with resistance to dopamine agonists in the long-term. Method: A retrospective study of six cases was made. Patients who did not achieve normalized prolactin blood concentrations and a reduction of more than 50% of the tumor volume with the minimum dose of 3.5 mg per week of cabergoline for 3 months or the maximum supported dose of bromocriptine for 6 months were considered resistant to dopamine agonists. Patients were followed up at the Clinic of Neurology and Endocrinology or the University Hospital of Brasilia. Results: Six patients were selected. Three patients were initially treated with bromocriptine prior to treatment with cabergoline. Four patients were men, and two were women. At the time of diagnosis, ages ranged from 9 to 62 years. Initial prolactin concentrations ranged from 430 to 14,992 ng/mL and in the last assessment ranged from 29.6 to 2,169 ng/mL. The tumor volume ranged from 0.77 to 24.0 mm3. Tumor regression occurred in all patients, ranging from 20 to 100%, but total disappearance of the adenoma with an empty sella occurred in one patient. The maximum weekly doses of cabergoline ranged from 3.0 to 4.5 mg. Follow-up time ranged from seven to 17 years. Normalization of prolactin concentrations occurred only in one woman after 17 years of treatment. Three patients also underwent surgery, but only one woman was cured of the disease. Conclusion: This study confirms that tumors resistant to dopamine agonists are more aggressive, since we did not have any microadenoma; treatment with high dose of cabergoline may reduce the size of the tumor without its disappearance, and that normalization of prolactin concentration rarely occurs. To our knowledge, this is the longest follow-up of a series of cases with resistance to dopamine agonists.

Beneficial Effects of High Doses of Cabergoline in the Treatment of Giant Prolactinoma Resistant to Dopamine Agonists: A Case Report with a 21-Year Follow-Up.

INTRODUCTION: Prolactinomas are pituitary tumors with a very low prevalence in childhood and adolescence compared to adulthood. This condition is preferentially treated with dopamine agonists. Resistance to these drugs is rare. CASE REPORT: We describe the case of a boy diagnosed with macroadenoma at the age of 9 and followed up for 21 years. He did not fully respond to treatment with dopamine agonists. His initial prolactin level was 2,400 ng/mL (in males, normal values are <16.0 ng/mL) and never normalized. At the last assessment, his prolactin level was 21.5 ng/mL, recorded after 21 years of treatment with the dopamine agonist cabergoline at a dose as high as 4.5 mg per week. Although the prolactin level remained elevated throughout the follow-up period, the patient never presented a low testosterone level and had normal pubertal development. An MRI of the sella turcica showed that the tumor became progressively cystic and disappeared, but a normal pituitary gland was observed. The pituitary gland retained its normal functions despite a partially empty sella. DISCUSSION: Long-term treatment with high doses of cabergoline may cause cystic degeneration of a prolactinoma considered to be resistant to this treatment, but we cannot rule out the possibility that this outcome represents the natural development of the tumor.