Cushing's syndrome caused by ACTH- and calcitonin-secreting medullary carcinoma of the thyroid

Melvin, Kenneth E. W.; Tashjian, Armen H.; Cassidy, Carl E.; Givens, James R.

doi:10.1016/0026-0495(70)90080-6

Cited by 70 publications

(9 citation statements)

References 11 publications

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“…In the present patient, the presence of subnormal responsiveness to ACTH, metyrapone and Pitressin@, absence of normal dexamethasone suppressability, absence of normal corticosteroid circadian periodicity, and initially markedly elevated plasma ACTH concentration, are in keeping with the majority of reports cited both for ACTH producing pituitary tumours (Krieger et al, 1964;Nelson et al, 1966) and ectopic ACTH producing tumours (Engel & Kehane, 1963;Liddle et al, 1963;O'Riordan et al, 1966;Friedman et al, 1966;Landon et al, 1967;Strott et al, 1968;Melvin et al, 1970;Marks et al, 1975).…”

Section: Discussionsupporting

confidence: 87%

The Characterization of the Acth Produced by a Primary Pituitary Tumour in a Patient With Cushing's Disease

Krienger

Choi

Anderson

1976

Clinical Endocrinology

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The nature of ACTH present in pituitary tumours associated with Cushing's disease has not been previously characterized nor correlated with the electron microscopic appearance. The present report describes the culture of tumour tissue obtained from a patient with a pituitary tumour associated with Cushing's disease, and the characterization of the ACTH content of tumour and media by bioassay, immunoassay, and Sephadex G-50 gel filtration. Electron microscopic studies were also performed. The pathological diagnosis was pituitary adenoma with basophilic PAS-positive granules. Electron microscopy showed uniformity of size and shape of the tumour cells, the presence of secretory granules of varying size and density, and disorganized tubular and vacuolar arrays of endoplasmic reticulum. The bioreactive ACTH content of the tumour was 0-29 mug/g, which is markedly below that seen in the normal pituitary, but within the range reported for ectopic ACTH-producing tumours. Immunoreactive ACTH when measured by a C-terminal antibody was five-fold higher than when measured by an N-terminal antibody; the latter gave a value of 1-24 mjg/g. On Sephadex G-50 gel filtration, 9% of the N-terminal immunoreactivity was present in the Vo fraction ('big' ACTH). This latter fraction had a greater percentage of bioreactivity (28%) than previously reported for this molecular species. Analysis of the tumour culture medium revealed a variation in molecular size similar to that seen in the tumour, although the percentage of ACTH of large molecular size was greater, suggesting increased secretion of a possible 'prohormone' by the tumour. Plasma ACTH was characterized by a 2:1 ratio of immunoreactivity (N-terminal) to bioreactivity, and a 4:1 ratio of C-terminal/N-terminal immunoreactivity. This report also appears to be the first of successful short-term tissue culture of a primary ACTH-producing tumour. The granule size was considerably larger than that reported for normal pituitary ACTH-containing cells.

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Section: Discussionsupporting

confidence: 87%

The Characterization of the Acth Produced by a Primary Pituitary Tumour in a Patient With Cushing's Disease

Krienger

Choi

Anderson

1976

Clinical Endocrinology

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“…Although Cushing's syndrome dependent on ACTH is a well-recognized occurrence in some patients with medullary thyroid carcinoma (Melvin et al, 1970;Howlett et a/., 1985) and phaeochromocytoma (Rees & Ratcliffe, 1974; Spark ef a]., 1979), plasma concentrations of immunoreactive ACTH were low in this instance. Although Cushing's syndrome dependent on ACTH is a well-recognized occurrence in some patients with medullary thyroid carcinoma (Melvin et al, 1970;Howlett et a/., 1985) and phaeochromocytoma (Rees & Ratcliffe, 1974; Spark ef a]., 1979), plasma concentrations of immunoreactive ACTH were low in this instance.…”

Section: Clinical Implications Of Np Y In Phaeochromocytomamentioning

confidence: 69%

Neuropeptide Y in Multiple Endocrine Neoplasia: Release During Surgery for Phaeochromocytoma

Connell

Corder

Asbury

et al. 1987

Clinical Endocrinology

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High plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal less than 3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak = 1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50-fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery.

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“…Six of the cases presented with typical manifestations of Cushing's syndrome, including "moon facies" and truncal obesity (1)(2)(3)(4)(5). Four of the cases presented with hypokalemic alkalosis (6)(7)(8)(9); in these cases, the Cushing's features were more subtle and consisted primarily of nonspecific muscle weakness and atrophy, which are more characteristic of the classical ectopic ACTH syndrome. Table 4 summarizes the duration of diagnosed thyroid carcinoma and of symptoms ascribable to hypercortisolism in these patients.…”

Section: Discussionmentioning

confidence: 91%

“…These include bronchial carcinoid tumors, epithelial thymomas, and certain cases of indolent medullary carcinomas of the thyroid. Table 3 summarizes the clinical data from 10 cases of ACTH-secreting medullary carcinoma of the thyroid in which detailed clinical and laboratory information have been reported (1)(2)(3)(4)(5)(6)(7)(8)(9). Six of the cases presented with typical manifestations of Cushing's syndrome, including "moon facies" and truncal obesity (1)(2)(3)(4)(5).…”

Section: Discussionmentioning

confidence: 96%

ACTH-Secreting Medullary Carcinoma of the Thyroid Presenting as Severe Idiopathic Osteoporosis and Senile Purpura: Report of a Case and Review of the Literature*

Rosenberg

Hahn

Orth

et al. 1978

The Journal of Clinical Endocrinology & Metabolism

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A 64-yr-old female presented with severe osteoporosis and easy bruisability of over 2-yr duration. Biopsy of a neck mass revealed medullary carcinoma of the thyroid. Subsequently, lymphangitic pulmonary metastases were demonstrated which had been present radiographically for at least 4 yr. Basal serum calcitonin was markedly elevated and increased during calcium infusion. The diagnosis of ectopic ACTH syndrome was first entertained when hypokalemic alkalosis was observed during evaluation of her carcinoma. Elevated urinary 17-hydroxycorticosteroids, 17-ketosteroids, plasma cortisol, and immunoreactive plasma ACTH levels were documented. Adrenal steroidogenesis seemed to suppress on high dose dexamethasone. The primary tumor and its metastases contained high concentrations of immunoreactive ACTH and beta-melanocyte-stimulating hormone. Hepatic metastases contained extremely high concentrations of calcitonin. In contrast to the usual presentation of the ectopic ACTH syndrome as primarily hypokalemic alkalosis and glucose intolerance, patients with relatively benign and indolent ACTH-secreting tumors, such as certain cases of medullary carcinoma of the thyroid, may present with more typical signs and symptoms of Cushing's syndrome. The more pronounced cushingoid features in this latter group presumably reflects a more prolonged period of exposure to elevated glucocorticoid levels. Ten cases of ACTH-secreting medullary carcinoma of the thyroid from the literature are discussed. Extopic ACTH production by such tumors should be considered in the evaluation of patients with Cushing's syndrome or unexplained severe osteopenia.

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Cushing's syndrome caused by ACTH- and calcitonin-secreting medullary carcinoma of the thyroid

Cited by 70 publications

References 11 publications

The Characterization of the Acth Produced by a Primary Pituitary Tumour in a Patient With Cushing's Disease

The Characterization of the Acth Produced by a Primary Pituitary Tumour in a Patient With Cushing's Disease

Neuropeptide Y in Multiple Endocrine Neoplasia: Release During Surgery for Phaeochromocytoma

ACTH-Secreting Medullary Carcinoma of the Thyroid Presenting as Severe Idiopathic Osteoporosis and Senile Purpura: Report of a Case and Review of the Literature*

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