PMC8020339_01
(A, B) In thyroid echography, both lobes of the thyroid gland were swelling although increase of blood flow was not observed. (C, D). In brain magnetic resonance imaging, there was a giant tumor (51 x 34 x 22 mm) around pituitary fossa, pressuring on optic chiasm from the middle. Bilateral internal carotid arteries were surrounded by the tumor, and infiltration into the cavernous sinus was observed.
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In thyroid echography, both lobes of the thyroid gland were swelling although increase of blood flow was not observed ( Figures 1A, B  ). In brain magnetic resonance imaging (MRI), there was a giant tumor (51 x 34 x 22 mm) around pituitary fossa, pressuring on optic chiasm from the middle ( Figures 1C, D  ).
(A) In hematoxylin and eosin (HE) staining, solid proliferation of chromophobe cells was observed. (B) In CAM5.2 staining, many cytokeratin-producing cells were observed. (C) In MIB1 staining, percentage of MIB1-positive cells was about 3%, indicating that the proliferative activity was relatively low. (D-F) In GH staining, many GH-positive cells were observed, and in TSH staining, many TSH-positive cells were observed, whereas in prolactin staining, prolactin-positive cells were not detected at all.
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In hematoxylin and eosin (HE) staining of the resected pituitary adenoma, solid proliferation of chromophobe cells was observed ( Figure 2A ). In CAM5.2 staining, many cytokeratin-producing cells were observed ( Figure 2B ). In MIB1 staining, percentage of MIB1-positive cells was about 3%, indicating that the proliferative activity was relatively low ( Figure 2C ). TSH staining, many TSH-producing cells were observed ( Figure 2E ), whereas in prolactin staining, prolactin-producing cells were not detected at all ( Figure 2F ). These findings further confirmed our diagnosis that this subject had pituitary adenoma producing GH and TSH simultaneously.
(A) Time course of GH and IGF-1 levels for 6 years. After the diagnosis of GHoma and TSHoma, pituitary tumor resection was performed. After about 1 year later, cyber knife therapy was performed together with the treatment with somatostatin analog and GH receptor antagonist. After these therapies, GH and IGF-1 levels were suppressed for a long period of time. (B) Time course of TSH, FT3 and FT4 levels for 6 years. After the operation, since thyroid function was not sufficiently suppressed, we started the treatment with anti-thyroid drug thiamazole. Since thyroid function was normalized after about 3 years later, we stopped the treatment with thiamazole. After then TSH, FT3 and FT4 levels were not increased for a long period of time.
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After the surgery, IGF-1 level was also markedly decreased and became within normal range (reference range in our institution: 141-328 ng/ml) ( Figure 3A ). After the cyber knife therapy together with octreotide, IGF-1 was marked decreased and became within normal range ( Figure 3A ). After then, GH and IGF-1 levels did not increase at least for 6 years ( Figure 3A ). But TSH, FT3 and FT4 levels did not increase at least for 6 years ( Figure 3B ).
There were no particular abnormalities in brain MRI taken 1 month after operation (A), 1 year after operation (half year after cyber knife therapy) (B) and 4 years after operation (C).
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In addition, there were no particular abnormalities in brain MRI taken 1 month after operation ( Figure 4A ), 1 year after operation (half year after cyber knife therapy) ( Figure 4B ) and 4 years after operation ( Figure 4C ).