Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination

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The increase in the incidental detection of asymptomatic pituitary adenomas, known as “pituitary inciden-talomas,” led the authors to conduct a survey of the natural course of these lesions.


Forty-two patients with clinically nonfunctioning pituitary adenomas who had manifested no neurological or endocrinological disorders were monitored with magnetic resonance imaging studies. The follow-up period ranged from 10.8 to 168.2 months (mean ± standard deviation, 61.9 ± 38.2 months). The mean initial tumor size was 18.3 ± 7 mm.

In 21 patients, the tumor increased by at least 10% of its measured size on detection. This increase was first detected between 8.4 and 58.8 months (mean 31.8 ± 17.6 months) after diagnosis. There was no correlation between the original tumor size, patient age, or the presence of intratumoral cysts and tumor growth. Symptoms were noted in 10 patients during follow up; in four, extensive tumor necrosis accompanied hemorrhage, leading to severe headache, acute ophthalmological symptoms, and panhypopituitarism, which was indicative of pituitary apoplexy. Transsphenoidal surgery was performed in 12 patients with enlarged tumors, including three with apoplexy. With the exception of one apoplectic patient, visual function was recovered in all who underwent surgery. All apoplectic patients continue to manifest hypopituitarism.


In the course of 4 years, the size of the incidentalomas increased in 40% of 42 patients and became symptomatic in 20%. During the 5-year follow up, pituitary apoplexy developed in 9.5%. These findings may justify early intervention, especially in young individuals with incidentally found macroadenoma.

Abbreviations used in this paper:LHRH = luteinizing hormone–releasing hormone; MR = magnetic resonance; TSS = transsphenoidal surgery.

Article Information

Address reprint requests to: Kazunori Arita, M.D., Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragoaka, Kagoshima, 890-8520, Japan. email:

© AANS, except where prohibited by US copyright law.



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    Images obtained in a 46-year-old man with chronic headache. Coronal (a) and sagittal (b) MR images demonstrating an asymptomatic pituitary adenoma with a height of 17 mm. Perimetry maps showing normal visual fields in both the left (c) and right (d) eyes. Follow-up MR images obtained 28 months postdiagnosis showed an increase in tumor height to 22 mm. Coronal (e) and sagittal (f) MR images obtained 71 months postdiagnosis revealing a tumor height of 25 mm. Perimetry maps demonstrating the appearance of visual field defects in the left (g) and right (h) eyes.

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    Kaplan–Meier survival curve demonstrating tumor enlargement–free survival in 42 patients with incidentally found pituitary adenoma.

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    Graph showing the percentage changes in the height of 21 enlarged adenomas. The tumor height measured at the latest follow-up examination was 110 to 180% of the height measured on initial diagnosis.

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    Kaplan–Meier survival curve demonstrating symptom-free survival in patients with incidentally found pituitary adenomas. The solid line represents all 42 patients. Open circles indicate cases with pituitary apoplexy. The thin dotted line indicates 28 patients with adenomas whose initial size was larger than 15 mm, whereas the bold dotted and dashed line represents 14 patients with adenomas whose initial size was 15 mm or smaller. The risk for symptomatic tumor enlargement was significantly greater with tumors whose height on detection exceeded 15 mm compared with those whose height was less than 15 mm (Cox–Mantel test, p = 0.007).

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    Coronal (a) and sagittal (b) MR images obtained in a 52-year old man, revealing a pituitary adenoma with slight suprasellar extension. Coronal (c) and sagittal (d) follow-up MR images obtained 16 months postdiagnosis and 2 days after his apoplectic attack, showing hemorrhagic infarction in the tumor and parasellar dural enhancement. These findings are compatible with pituitary apoplexy. This case was previously reported in Arita, et al., 2001.

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    Coronal (a) and sagittal (b) MR images obtained in a 74-year-old man, demonstrating a pituitary adenoma measuring 18 mm in height with slight compression of the chiasm. Follow-up coronal (c) and sagittal (d) MR images were obtained 26 months postdiagnosis, 1 day after injection of an LHRH analog, which elicited severe headache, showing an increase in tumor size and intratumoral hemorrhagic infarction.

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    Coronal (a) and sagittal (b) MR images obtained in a 60-year-old woman, revealing a pituitary adenoma measuring 20 mm in height without suprasellar extension. Coronal (c) and sagittal (d) MR images obtained 20 months postdiagnosis because of acute deterioration in left-sided eyesight, showing that the tumor size had increased. Note compression of the chiasm and an intratumoral fluid hematoma.

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    Coronal (a) and sagittal (b) MR images obtained in a 61-year-old man, revealing a pituitary adenoma measuring 18 mm in height. Coronal (c) and sagittal (d) MR images obtained 56 months postdiagnosis and 4 days after an apoplectic attack, showing tumor enlargement, peritumoral dural enhancement, and mucosal thickening of the sphenoid sinus.


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