SYNCHRONOUS DOUBLE PITUITARY ADENOMA SECRETING PROLACTIN, LH, AND ALPHA SUBUNIT GLYCOPROTEIN: A NEW MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 (MEN1) PHENOTYPE.

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Delmar M. Lourenço-Jr, Flavia L. Coutinho, Rodrigo A. Toledo
Unidade de Endocrinologia Genetica, LlM-25, Endocrinologia, Hospital das Clinicas do Faculdade de Medicina do Un ivers ida de de Sao Paulo, Brazil.
Background: Co-secreting pituitary adenomas represent 1020% of pituitary tumors (PIT) in MEN1 (1). Positive immunohistochemistryfor LH or FSH may be present in 15% of MEN1-related non-functioning PITs, however, the clinical/hormonal status of LH/FSH excess was described in only one isolated case with FSH-secreting pituitary carcinoma (1,2). All PIT subtypes were reported in MEN1, except true LH-oma (1). Also, multiple or double pituitary adenomas in MEN1, documented by MRI, have rarely been reported (3).

Objectives: To investigate the occurrence of double and co-secreting PIT in 40 MEN1 cases from eight different MEN1 families, all harboring germ line MEN1 mutation.

Results: PIT was diagnosed in 20 out of the 40 MEN 1 cases. Prolacti noma-only was documented in 60% (12/20) of PIT cases, and non-functioning PIT was seen in 35%. We documented a case presenting a co-secreting PIT belonging to different adenoma types (GH-PRL-TSH and FSH/LH). and recognized by MRI as a double adenoma. This 49 year-old male (diagnosed with hyperparathyroidism, gastrinoma, nonfunctional pancreatic tumor and microprolactinoma) has been followed up for 10 years. Prolactin was high (55 ng/mL, normal levels: 2.0-10), showed no response to TRH, and went to normal ranges after bromoergocriptine (BEC) treatment. Total/free testosterone and FSH were normal and LH values were normal/high (9.7 UI/L; NL: 1-8.4). During the administration of BEC, testosterone (1390 ng/dL; NL, 271-965) and LH (16.9 UI/L) increased progressively. After BEC withdrawal, prolactin showed a striking increase whereas testosterone returned to normal levels. During the follow up, it was shown a) the patient showed a progressive LH hyper-responsiveness to GnRH (from 5.3 => 33.8 UI/L; to 12 => 70 UI/L; NL, peak after GnRH: 12-29.7) and b) the patient had mildly high basal levels of LH. Chromatographic LH analysis revealed no other molecular forms of LH. Alpha-subunit glycoprotein levels were excessively high (4211 ng/L; NL: 120 – 790). Double adenomas and the deviation of pituitary stalk were evident by pituitary MRI.

Conclusions: We described a new pituitary phenotype in MEN1 characterized by a synchronous double PIT secreting LH, prolactin, and alpha subunit. Treatment with BEC allowed us to reveal the diagnosis of LH-oma.

References:

1. Verges B, etal. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. Journal of Clinical Endocrinology and Metabolism 2002 87 457-465.
2. Benito M, et al. Gonadotroph tumor associated with multiple endocrine neoplasia type 1. Journal of Clinical Endocrinology and Metabolism 2005 90 570-574.
3. Sahdev A, Bilateral pituitary adenomas occurring with multiple endocrine neoplasia type one. American Journal ofNeuroradiology2000211067-1069.

Support: RAT. is recipient of Coordenaçao de Aperfeiçoamento de Pessoal de Nfvel Superior (CAPES) PhD fellowship. D.M.L is recipient of Fundac;ao Faculdade de Medicina (FFM) pos-doctoral fellowship.