Comment on “A somatotropin-producing pituitary adenoma with an isolated adrenocorticotropin-producing pituitary adenoma in a female patient with acromegaly, subclinical Cushing’s disease and a left adrenal tumor” [Letter to the Editor]

Abstract

I read with interest the case report by Kobayashi et al. entitled "A somatotropin-producing pituitary adenoma with an isolated adrenocorticotropin-producing pituitary adenoma in a female patient with acromegaly, subclinical Cushing's disease and a left adrenal tumor" published in Endocrine Journal. The authors reported a rare case of a 67-year-old Japanese woman with double independent pituitary adenomas, and simultaneous evidence of a left adrenal incidentaloma, causing appearance of signs and symptoms of acromegaly, but without Cushingoid features, and discussed literature regarding double pituitary adenomas [1].In a manuscript published in 1999 [2], we described the first case diagnosed in vivo up to that time of simultaneous occurrence of triple non-functioning pituitary adenomas in a 37-year-old woman who was referred to our outpatient clinic reporting oligomenorrhea, weight gain and persistent frontal and retroocular headache for several years. On admission to our Unit, clinical examination revealed moderate hirsutism and "moon face" while no hypothalamic pituitary dysfunction was demonstrated by basal and dynamic endocrine investigation. Preoperative MRI revealed three distinct hypointense areas measuring less than 5 mm in diameter in the left, medium and right side of the pituitary gland, respectively.In the case report by Kobayashi et al., basal and dynamic endocrine evaluation confirmed the diagnosis of acromegaly with a concomitant condition of subclinical Cushing's disease. Preoperative MRI showed two separated and well demarcated tumors with a low intensity on both T2-weighted and T1-weighted images. The left adenoma measured 5×7×6 mm and the right one 6×4×8 mm in diameter, and neither invaded the surrounding structures. In addition, a well demarcated left adrenal nodule (23×16 mm in diameter), not invading the surrounding tissues, was detected by abdominal CT and MRI. The patient underwent transsphenoidal neurosurgery and presence of two separated, totally resected, masses was confirmed. Immunostaining was ACTH-positive and GH-negative in the left adenoma and, on the contrary, GH-positive and ACTH-negative in the right one.Also in our case, not cited by Kobayashi, the preoperative MRI identification of three well defined adenomas was supported by transsphenoidal surgery, confirming MRI as the most sensitive neuroimaging technique in the evaluation of pituitary masses.The occurrence of multiple pituitary adenomas supports the role played by abnormal extrahypophiseal regulatory mechanisms in the pathogenesis of pituitary tumors [3]. Genetic and molecular mechanisms of tumorigenesis may be involved in the pathogenesis of concomitant pituitary adenomas, and the coexistence of multiple adenomas in the same pituitary gland strongly emphasizes the pathogenic role of abnormal stimulatory and/or inhibitory extrapituitary factors. These latter could play a role in the recurrence of pituitary tumors by promoting growth and clonal expansion of genetically altered cells [4].In conclusion, although several combi...