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PubMed · 557387

[Primary hyperparathyroidism].

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Y Fujimoto. 1977. [Primary hyperparathyroidism].. https://pubmed.ncbi.nlm.nih.gov/557387/

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HMGA proteins up-regulate CCNB2 gene in mouse and human pituitary adenomas.

The high mobility group As (HMGAs) belong to a family of nonhistone nuclear proteins that orchestrate the assembly of nucleoprotein complexes. Through a complex network of protein-DNA and protein-protein interaction, they play important roles in gene transcription, recombination, and chromatin structure. This protein family is involved, through different mechanisms, in both benign and malignant neoplasias. We have recently reported that transgenic mice carrying the Hmga1 or Hmga2 genes under transcriptional control of the cytomegalovirus promoter develop pituitary adenomas secreting prolactin and growth hormone. We have shown that the mechanism of the HMGA2-induced pituitary adenoma is based on the increased E2F1 activity. The expression profile of mouse normal pituitary glands and adenomas induced in HMGA transgenic mice revealed an increased expression of the ccnb2 gene, coding for the cyclin B2 protein, in the neoplastic tissues compared with the normal pituitary gland. Here, we show, by electrophoretic mobility shift assay and chromatin immunoprecipitation, a direct binding of HMGA proteins to the promoter of ccnb2 gene, whereas luciferase assays showed that HMGAs are able to up-regulate ccnb2 promoter activity. Finally, we report an increased CCNB2 expression in human pituitary adenomas of different histotypes that is directly correlated with HMGA1 and HMGA2 expression. Because cyclin B2 is involved in the regulation of the cell cycle, these results taken together indicate that HMGA-induced cyclin B2 overexpression gives an important contribution to experimental and human pituitary tumorigenesis.

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[A case of Cushing's disease associated with a non-functioning adrenal tumor].

A 52-year-old woman was admitted to our hospital for further examination of central obesity, hypertension and hirsutism suggesting Cushing's syndrome. Hirsutism had been remarkable for two years, and muscle weakness of the lower extremities gradually developed during the past year. CT scan revealed a tumor in the left adrenal gland which was 1 cm in diameter, round, well-circumscribed, homogeneous and not enhanced. Endocrine data disclosed increased urinary 17-OHCS (11.5-16.4 mg/day) and elevated plasma ACTH (125 pg/ml) and cortisol (19 micrograms/dl) with a lack of diurnal rhythm. Administration of the single-dose dexamethasone (1mg) did not suppress plasma cortisol. However, consecutive administration of either 2mg or 8mg of dexamethasone for 2 days suppressed both plasma cortisol and urinary 17-OHCS. Administration of metyrapone raised both urinary 17-OHCS and plasma ACTH levels. Rapid ACTH test resulted in a hyperresponse of plasma cortisol. CRF injection raised plasma ACTH and cortisol. Bilateral adrenal glands were well demonstrated by 19-iodocholesterol (I-131) scintigraphy during the administration of dexamethasone. MRI with Gd-contrast revealed a microadenoma in the sella turcica. With the diagnosis of Cushing's disease, the microadenoma was removed by the transsphenoidal approach and adrenal function was normalized. However, the left adrenal tumor remained on CT scan but was not demonstrated by scintigraphy. These findings indicate that this is a very rare case of Cushing's disease which was associated with an unilateral non-functioning adrenal tumor.

Adenoma

[Subtraction scintigraphy with thallium-201 chloride and technetium-99m pertechnetate versus high resolution ultrasonography in the localization of the parathyroid glands in primary hyperparathyroidism].

BACKGROUND: The aim of this study was to evaluate the use of scintigraphy with thallium-201 chloride (201 Tl) and technetium-99m pertechnetate (99mTc) in the diagnosis of the localization of the pathological parathyroid glands in primary hyperparathyroidism and compare the results with those of high resolution ultrasonography. METHODS: Twelve patients of 56.1 +/- 7.8 years of age diagnosed with primary hyperparathyroidism were studied between March 1987 and June 1990. High resolution ultrasonography with a 7.5 MHz transducer and scintigraphy of digital subtraction with 201Tl-99mTc were carried out preoperatively in all the patients. None of the patients had had previous cervical surgery and diagnosis was proven following surgery by histopathologic study. RESULTS: Ultrasonography detected 9 out of 11 adenomas and 3 out of 4 hyperplastic glands. Scintigraphy identified 9 adenomas and only 2 of the hyperplastic glands. With this latter technique there was one false positive. The sensitivity of ultrasonography was 80% and that of scintigraphy was 73% with specificity being 100% vs 96.9%, respectively. CONCLUSIONS: Subtraction 201 Tl-99mTc scintigraphy is useful in the diagnosis of the localization of pathologic parathyroid glands in patients with no previous cervical surgery although in this series this technique did not surpass that of high resolution ultrasonography.

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