scholarly journals Cushing’s Syndrome Due to Medullary Thyroid Carcinoma: Diagnosis by Proopiomelanocortin Messenger Ribonucleic Acid in Situ Hybridization

2003 ◽  
Vol 88 (10) ◽  
pp. 4565-4568 ◽  
Author(s):  
R. C. Smallridge ◽  
K. Bourne ◽  
B. W. Pearson ◽  
J. A. van Heerden ◽  
P. C. Carpenter ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Thyroid Carcinoma ◽  
Neck Dissection ◽  
Medullary Thyroid Carcinoma ◽  
Cushing's Syndrome ◽  
Plasma Acth ◽  
Mri Scan ◽  
Ectopic Acth ◽  
Medullary Thyroid

Abstract Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 μg/d), epinephrine (66 μg/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 μg/dl and decreased to 12.9 and 4.5 μg/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. Bone density t-score was −4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 μg/d), epinephrine (0 μg/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing’s syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.

Quantification of intracellular calcitonin gene transcripts in human medullary thyroid carcinoma (MTC) by in situ hybridization

1990 ◽  
Vol 13 (7) ◽  
pp. 567-573 ◽  
Author(s):  
Michèle Noel ◽  
A. Gavoille ◽  
F. Lasmoles ◽  
E. Kahn ◽  
B. Caillou ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Medullary Thyroid ◽  
Calcitonin Gene ◽  
Gene Transcripts

scholarly journals An efficient method to detect calcitonin mRNA in normal and neoplastic rat C-cells (medullary thyroid carcinoma) by in situ hybridization using a digoxigenin-labeled synthetic oligodeoxyribonucleotide probe.

1993 ◽  
Vol 41 (3) ◽  
pp. 389-395 ◽  
Author(s):  
P Le Guellec ◽  
S Dumas ◽  
G E Volle ◽  
E Pidoux ◽  
M S Moukhtar ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Thyroid Carcinoma ◽  
Tumor Cells ◽  
Medullary Thyroid Carcinoma ◽  
Secretory Process ◽  
Blue Color ◽  
C Cells ◽  
Mature Peptide ◽  
Medullary Thyroid

We report here an efficient and rapid method for the specific detection of calcitonin in tumor C-cells of medullary thyroid carcinoma (MTC). This occasionally aggressive tumor arises from the endocrine thyroid C-cells. Its principal marker is calcitonin, the predominant C-cell secretion, which is detected in patients and in our animal model by radioimmunoassay of the plasma, as well as by immunohistochemistry of thyroid tissues. Although calcitonin is easily detectable in normal C-cells, its content is greatly reduced in tumor cells owing to the disappearance of the secretory granules that store the mature peptide. This finding suggests cell dedifferentiation correlated with an increasing aggressivity of the tumor. We therefore developed a rapid detection of calcitonin mRNA by in situ hybridization on routine paraffin sections, using a synthetic oligodeoxyribonucleotide probe labeled with digoxigenin-dUTP. The reaction was detected with an anti-digoxigenin antibody conjugated with alkaline phosphatase, and the enzyme catalyzed the appearance of a dark blue color. The signal was exclusively restricted to the normal, hyperplastic, and tumor C-cells. It was specific, as increasing concentrations of the unlabeled oligonucleotide led to progressive disappearance of the reaction. Its sensitivity was slightly diminished as compared with corresponding frozen sections, but the intensity of the signal was quite acceptable. High levels of calcitonin mRNA were found in all normal and hyperplastic C-cells. They were increased in most of the tumor MTC cells, which did not correlate with the amount of intracellular peptide stores but explained the abnormally high basal levels of circulating calcitonin of the tumor-bearing rats. ISH is therefore of greater value than ICC for an early anatomopathological detection of this tumor. Our data show that the tumor cells are not "dedifferentiated." They only lack the granular compartment storing the mature peptide before exocytosis, but CT biosynthesis and the rest of the secretory process seem to be complete. Our results suggest that factors expressed in malignant C-cells affect basic cell mechanisms involved in the storage of the mature calcitonin, rather than the expression of the CALC gene.

Presentation of a Medullary Endocrine Neoplasia 2A Kindred with Cushing's Syndrome

2008 ◽  
Vol 74 (7) ◽  
pp. 659-661
Author(s):  
Victor Zaydfudim ◽  
Daniel G. Stover ◽  
Susan W. Caro ◽  
John E. Phay
Keyword(s):  
Genetic Testing ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Ectopic Acth ◽  
Medullary Thyroid ◽  
Endocrine Neoplasia ◽  
Ectopic Acth Production ◽  
Men 2A

Although medullary thyroid cancer (MTC) can produce adrenocorticotropic hormone (ACTH) in up to 40 per cent of cases as determined by immunohistochemistry, clinical hypercortisolism is rarely seen. We report a medullary endocrine neoplasia 2A (MEN 2A) kindred whose proband case presented with Cushing's syndrome (CS). This 51-year-old woman presented with debilitating weakness, exertional dyspnea, 50 pound weight gain, moon facies, worsening hypertension, striae, and hirsutism. A comprehensive evaluation diagnosed ectopic ACTH production from unresectable metastatic MTC to the liver. Genetic testing revealed a germline RET proto-oncogene mutation at codon 609. Further genetic testing identified six family members with the same mutation. The patient underwent palliative bilateral laparoscopic adrenalectomies with significant improvement in major comorbidities. Overall CS resulting from ectopic ACTH overproduction by MTC is rare, occurring in 0.6 per cent of all patients with medullary thyroid carcinoma. About 50 cases have been previously reported in the literature, but only three in families with MEN 2A. We describe the first case of a MEN 2A kindred presenting with CS from ectopic ACTH production by metastatic medullary thyroid carcinoma. We advocate consideration of early bilateral laparoscopic adrenalectomies in patients with symptomatic hypercortisolism from unresectable metastatic medullary thyroid carcinoma.

ECTOPIC ACTH SYNDROME AND MEDULLARY THYROID CARCINOMA

1977 ◽  
Vol 86 (2) ◽  
pp. 306-316 ◽  
Author(s):  
G. Keusch ◽  
U. Binswanger ◽  
M. A. Dambacher ◽  
J. A. Fischer
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Cushing’S Syndrome ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Medullary Thyroid ◽  
Ectopic Cushing’S Syndrome ◽  
Normal Pituitary Gland

ABSTRACT A 40 year old patient with medullary thyroid carcinoma subsequently developed Cushing's syndrome with presumably ectopic ACTH formation. The immunoreactive calcitonin in the plasma was greatly and ACTH slightly increased. Despite the excessively high calcitonin concentration the patient finally developed a serious osteoporosis which presumably resulted from Cushing's syndrome. In this case at least, a raised endogenous plasma calcitonin level did not prevent an osteoporosis caused by hypercortisolism. The autopsy revealed a bilateral hyperplasia of the adrenal cortex and a normal pituitary gland suggesting that Cushing's syndrome was probably caused by an ectopic ACTH source. Twenty-two additional cases of medullary thyroid carcinoma with Cusing's syndrome reported in the literature have been reviewed. Eighteen out of 23 patients were alkalotic which is typical of an ectopic ACTH production. In these patients the characteristic clinical signs of hypercortisolism were nearly as frequently observed (70 %) as in patients with non-ectopic Cushing's syndrome (91 %). An ectopic Cushing's syndrome occurs only in 2–4 % of advanced cases of medullary thyroid carcinoma and is a serious complication. Among the 23 patients 18 died with an average survival time of only 4.5 months after the diagnosis of Cushing's syndrome was established.

scholarly journals A Case of Medullary Thyroid Carcinoma with Ectopic ACTH Syndrome

1977 ◽  
Vol 53 (11) ◽  
pp. 1279-1291 ◽  
Author(s):  
Shin-ichiro TAKAI ◽  
Toshio OGIHARA ◽  
Akira MIYAUCHI ◽  
Hiromu HIGASHI ◽  
Tsuyoshi NISHIMURA ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Medullary Thyroid

Prophylactic Lateral Neck Dissection for Medullary Thyroid Carcinoma is not Associated with Improved Survival

2021 ◽  
Author(s):  
Philip M. Spanheimer ◽  
Ian Ganly ◽  
Joanne F. Chou ◽  
Marinela Capanu ◽  
Aradhya Nigam ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Neck Dissection ◽  
Medullary Thyroid Carcinoma ◽  
Lateral Neck ◽  
Lateral Neck Dissection ◽  
Medullary Thyroid

Cushing’s syndrome in medullary thyroid carcinoma

1995 ◽  
Vol 18 (3) ◽  
pp. 180-185 ◽  
Author(s):  
A. Mure ◽  
C. Gicquel ◽  
N. Abdelmoumene ◽  
F. Tenenbaum ◽  
C. Francese ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Medullary Thyroid

MEN 2A with double mutation in RET gene: Ectopic ACTH production in medullary thyroid carcinoma

2016 ◽  
Vol 146 (9) ◽  
pp. 419-420
Author(s):  
Jessica Ares ◽  
Lucía Díaz-Naya ◽  
Alicia Martín-Nieto ◽  
Joaquín Pertierra
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Ectopic Acth ◽  
Double Mutation ◽  
Medullary Thyroid ◽  
Ret Gene ◽  
Ectopic Acth Production ◽  
Men 2A
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