Thyroid carcinoma and Cushing's syndrome

Abstract

SYNOPSIS Two cases of thyroid carcinoma and Cushing's syndrome are reported. Nine other previously published cases of this association are reviewed: in one the thyroid tumour was described as medullary, in two as papillary, and in the other six as anaplastic, undifferentiated, atypical, or solid carcinoma. Both of our own cases were medullary carcinomas of the thyroid, and on reviewing the histology of five of the other cases all proved to be medullary carcinoma with identifiable amyloid in the stroma. A consideration of the temporal relationships of the development of the carcinoma and of Cushing's syndrome suggested that in the two cases with papillary carcinoma these conditions could have been unrelated, but that in eight of the nine cases with medullary carcinoma there was evidence that thyroid carcinoma was present at the time of diagnosis of Cushing's syndrome.The other main groups of the so-called 'non-endocrine' tumours associated with Cushing's syndrome are briefly reviewed, and evidence that a surprising number of these cases are related to carcinoid tumours is put forward. Medullary carcinoma of the thyroid is also probably related to this group of tumours. It is suggested that the great majority of the tumours associated with Cushing's syndrome are derived from cells of foregut origin which are endocrine in nature. In neoplasms derived from these cells the polypeptide hormone may well be imperfectly formed, and possess an amino-acid sequence in common with ACTH or other biologically active polypeptides.The association of 'non-endocrine' tumours with Cushing's syndrome is a subject that has expanded considerably since 1928 when Hurst Brown described a case of diabetes and hirsutism in a woman with an oat-cell carcinoma of the lung. For some years after Thorne's review (1952) it seemed as if this association was confined to tumours of the thymus, lung, and pancreas, but over the last 10 years or so tumours of widely diverse origins have been reported with Cushing's syndrome. The work of Meador, Liddle, Island, Nicholson, Lucas, Nuckton, and Luetscher (1962) has suggested that the mechanism of this association is the production of an ACTH-like substance by the tumour, but although this is a logical explanation it still leaves unanswered the problem as to why such a multiplicity of tumours should be able to produce a substance with an ACTH-like activity.We would like to report two cases of thyroid carcinoma and Cushing's syndrome. While there Received for publication 20 July 1967. 129 are some complex aspects to this relationship it does provide a clue to the understanding of the association of 'non-endocrine' tumours with Cushing's syndrome. Taken together with a review of other published cases of thyroid and non-thyroidal carcinomas with Cushing's syndrome, we can put forward a possible explanation for the production of ACTH by such widely differing tumours.

Medullary carcinoma of the thyroid with parathyroid adenoma and hypercalcaemia

“…Williams, Morales, and Horn (1968) stress the close relationship between medullary carcinoma, certain thymic tumours, oat cell carcinoma, and carcinoid tumours, all of which may produce a variety of peptide hormones. Weichert (1970) suggests that cells in these tumours with the capacity to form peptide hormones have a neural crest origin in common with similar neuroendocrine cells which migrate into the endocrine glands.…”

Diagnostic and Therapeutic Problems in Cushing’s Syndrome Series of 7 Cases

“…Adrenal venography and the hormone deter minations at different levels of the inferior vena cava have further contributed to the differential diagnosis of the adrenal tumors (15,23). Thus, small or multiple tumors can be revealed and the surgeon is able to decide on the most suitable sur gical method.…”

Diagnostik des medullären Schilddrüsenkarzinoms

“…Das klinische Bild wird natürlich auch durch die hormonellen und enzymatischen Abweichungen dieses Syndroms bestimmt. Außer Calcitonin kann das medulläre Schilddrüsenkarzinom noch Histaminase (4,5), Dopa-Decarboxylase (2, 22), Prostaglandin (11, 50), Serotonin (25,42), ACTH (12,27,51), CRF (»corticotropin-releasing factor«) und »PRF« (»prolactin releasing factor«) ( 7) produzieren oder enthalten.…”