Medullary Thyroid Carcinoma: Ectopic Production of Peptides With Acth-Like, Corticotrophin Releasing Factor-Like and Prolactin Production-Stimulating Activities

Abstract

A 45-year-old women had medullary thyroid carcinoma associated with Cushing's syndrome and galactorrhoea. Elevated plasma immunoreactive ACTH and cortisol were partially suppressed by intravenous dexamethasone, appreciably raised by lysine vasopressin, and urinary excretion of 17-oxogenic steroids slightly elevated by metyrapone. A large arterio-venous increase in plasma corticotrophin releasing factor-like activity across the thyroid gland was observed and tumour tissue contained corticotrophin releasing factor-like activity. Biologically active ACTH was not detected in tumour extracts before incubation with trypsin, but after trypsinization a value of 3.2 mU per gram was obtained. Arterial plasma contained biologically active ACTH (1.5 mU/100 ml) prior to trypsinization. Venous effluent from the thyroid gland contained biologically active (9.6 mU/100 ml) and immunoreactive ACTH (970 pg/ml) before trypsinization. Tumour extracts also contained prolactin production-stimulating activity. These findings can explain the Cushing's syndrome and the galactorrhoea both of which disappeared completely after thyroidectomy.

Shift from CRH to ACTH Production in a Thymic Carcinoid with Cushing’s Syndrome

“…There was no response of blood ACTH to metyrapone. In previous case reports of ectopic CRHinduced Cushing's syndrome, the patients showed a posi tive response to metyrapone [1][2][3][4]7,10,13]. The response of blood ACTH to exogenously administered CRH was fully inhibited after the recurrence of the tumor, whereas there was a blunted response before the resection of the primary tumor.…”

“…Many cases of ectopic CRH production have been associated with ACTH production by the same tumor [1][2][3][4][5][6][7][8][9][10][11]. Wc report a case of Cushing's syndrome due to an ACTH/CRH-producing thymic carcinoid in which the hormonal phenotype changed from CRH-dominant in the primary tumor to ACTH-dominant after tumor recur rence.…”

Characterization of neurotensin production by a line of rat medullary thyroid carcinoma cells.

“…Values give the mean + SEM of six samples. (6)(7)(8). From medium during the 16-day growth experiment (Fig.…”

“…These cells synthesize and secrete CT and respond with an increase in CT secretion during incubation with calcium, K+, and glucagon. In screening these cells for neuroendocrine peptides, some of which have previously been associated with medullary thyroid carcinoma (3)(4)(5)(6)(7)(8), we found that the rat medullary thyroid carcinoma (rMTC) 6-23 line also produced and secreted neurotensin (NT), a tridecapeptide, which was originally isolated from bovine hypothalamus by Carraway and Leeman (9) and from human intestine by Hammer et al (10). Although a possible neurohormonal or neurotransmitter role has been postulated for NT, it has no known effects on calcium metabolism or calcium-regulating hormones and has not previously been associated with C cells.…”

“…described (9,10 [6][7][8][9][10][11][12][13] of the COOH-terminal region of NT for effective displacement of 125I-labeled NT from antibody-binding sites, and TG-1, an antiserum with NH2-terminal specificity (10). The content of iNT in culture medium was measured by direct addition to the assay after it was determined that fresh modified Eagle's medium did not inhibit binding of 125I-labeled NT.…”