A calcitonin-secreting medullary thyroid carcinoma associated with mucosal neuromas, marfanoid features, myopathy and pigmentation

doi:10.1016/0002-9343(70)90106-3

The American Journal of Medicine

Volume 48, Issue 1, January 1970, Pages 120-126

https://doi.org/10.1016/0002-9343(70)90106-3 Get rights and content

Abstract

A patient with a medullary carcinoma of the thyroid secreting calcitonin is described. This patient showed many clinical features of the medullary carcinoma syndrome including neuromas of the tongue and eyelid, prominence of the lips and stigmata of Marfan's syndrome as well as two hitherto undescribed features, skin pigmentation and a congenital myopathy. The skin pigmentation was melanin, possibly accumulated as the result of a humoral agent produced by the tumour since the pigmentation disappeared after thyroidectomy. The myopathy involved particularly the proximal muscles, and a muscle biopsy specimen showed scattered foci of myopathic degeneration. Histochemical and ultrastructural studies revealed absence of normal differentiation of the muscle fibers into two types on the basis of oxidative enzyme activity and mitochondrial population, together with an apparent increase in sarcoplasmic glycogen.

References (29)

ED Williams et al.
Prostaglandin secretion by medullary carcinoma of the thyroid
Lancet
(1968)
WJ Cunliffe et al.
Calcitonin-secreting thyroid carcinoma
Lancet
(1968)
ED Williams
Medullary carcinoma of the thyroid
J Clin Path
(1967)
ED Williams
A review of 17 cases of carcinoma of the thyroid and phaechromocytoma
J Clin Path
(1966)
G Milhaud et al.
Epithélioma de la thyroide secrétant de la thyrocalcitonine
CR Acad Sci [D] (Paris)
(1968)
KEW Melvin et al.
Syndrome of excessive thyrocalcitonin produced by medullary carcinoma of thyroid
JS Meyer et al.
Granules and thyrocalcitonin-like activity in medullary carcinoma of the thyroid gland
New Eng J Med
(1968)
M Tubiana et al.
Medullary carcinoma and thyrocalcitonin
Brit Med J
(1968)
K Engleman et al.
Further evaluation of the tyramine test for phaechromocytoma
New Eng J Med
(1968)
GE Palade
A study of fixation for electron microscopy
J Exp Med
(1952)

DD Sabatini et al.

Cytochemistry and electron microscopy: the preservation of cellular ultrastructure and enzymatic activity by aldehyde fixation

J Cell Biol

(1963)

JR Venable et al.

A simplified lead citrate stain for use in electron microscopy

J Cell Biol

(1965)

P Hudgson et al.

Adult myopathy from glycogen storage disease due to acid maltase deficiency

Brain

(1968)

Taylor SF, Williams ED: Personal communication....

Cited by (49)

Multiple endocrine neoplasia type 2B: Maxillofacial significance in 5 cases
2014, Journal of Oral and Maxillofacial Surgery
This paper intends to review for the oral and maxillofacial surgery community the MEN abnormalities generally, to emphasize the maxillofacial abnormalities peculiar to the MEN2B variant particularly, and to demonstrate the importance of early recognition of its most important component, medullary thyroid carcinoma.
The findings in five individuals with confirmed diagnoses of MEN2B are arranged to demonstrate the various manifestations of the disorder, and together represent the largest single group in the oral and maxillofacial surgery literature to date.
Tabulation of the patients' individual findings demonstrates the variants and severity of the disorder, discloses findings not previously emphasized in the literature, and stresses the significance of early recognition of medullary thyroid carcinoma.
The evidence in this study group suggests that the oral mucosal lesions are more commonly neurofibromas than neuromas as previously reported, that the characteristic dental central diastemas may occur independent of tongue size or the presence of oral soft tissue lesions, and that the characteristic apertognathia potentially requires surgical correction.
Endocrine myopathies
2007, Handbook of Clinical Neurology
Citation Excerpt :
There was no evidence of the myocarditis that may be associated with phaeochromocytoma (Van Vilet et al., 1966). A myopathy has been associated with medullary carcinoma of the thyroid with hypercalcitoninemia (Cunliffe et al., 1970). The clinical features of a 19‐year‐old girl with a medullary carcinoma of the thyroid secreting calcitonin were described.
This chapter discusses rarer myopathies that are associated with growth hormone, insulin, parathormone, epinephrine, insulin, and testosterone. Most endocrine disorders are now detected and treated at an early stage, and muscle abnormalities are more rarely troublesome or severe. Muscle weakness in hyperthyroidism is well-recognized, with clinical evidence of weakness in up to around 75% of patients. It is more common in females than males. Up to 40% of patients with hypothyroidism have been claimed to have clinical evidence of muscle weakness. Typical symptoms include muscle stiffness, pain, and cramps, especially related to exercise or cold weather. In adults, an extreme presentation of hypothyroidism is Hoffmann's syndrome. The periodic paralysis of thyrotoxicosis is clinically similar to hypokalemic periodic paralysis. Cushing's disease, ectopic production of adrenocorticotrophic hormone (ACTH), and corticosteroid administration, all produced similar myopathic features in patients. The clinical features are typically a painless symmetrical proximal myopathy. This usually affects the legs more than the arms. There may be additional marked muscle wasting, and the more general systemic features of glucocorticoid excess. Around 50% of patients with increased growth hormones and acromegaly have proximal muscle weakness with pain and reduced exercise tolerance. Diabetic amyotrophy is primarily a neuropathy. Ischemic infarction of the thigh muscles may occur in poorly controlled diabetes mellitus. A myopathy has been associated with medullary carcinoma of the thyroid with hypercalcitoninemia.
The MEN II syndromes and the role of the ret proto-oncogene
1996, Advances in Cancer Research
This chapter focuses on genetic and biological aspects of the multiple endocrine neoplasia type II (MEN II) syndromes and of ret mutations. The discussion of clinical and pathological aspects is limited for providing the background to the biological problem and indicating the application of the genetic results. The MEN II syndromes are dominantly inherited syndromes of tumor formation and disordered development that involve principally four tissues: the “C” cells of the thyroid, the adrenal medulla, the parathyroid, and the intestinal autonomic nerve plexuses. There are distinct clinical subtypes of the syndromes, depending on the combination of tissues affected and the presence or absence of specific developmental abnormalities. The chapter discusses the ret proto-oncogene, the development of the tissues involved in Men II, and the patterns of ret expression. At least two sets of observations must be accounted for in any scheme of inherited and sporadic tumorigenesis in C cells. These are (1) the comparative rarity of cysteine codon mutations, compared with the MEN IIB codon 918 mutation, in sporadic tumors and (2) the apparently contradictory reports that differentiation of C cells and related neuroectodermal cells is induced by yet overexpression or is accompanied by silencing of yet expression. There is still little information about the molecular events in tumor progression in MEN II-related tumors. Studies using X chromosome markers show that the established tumors are clonal. Thyroid C cell tumors and pheochromocytomas have been reported in certain Wistar-derived and other strains of rat.
Centronuclear myopathy with type I fibre hypotrophy and "Fingerprint" inclusions associated with Marfan's syndrome
1980, Journal of the Neurological Sciences
The authors present results of histological and electron-microscopical investigations of muscular tissue obtained by biopsy from a 20-year-old man, who showed typical features of Marfan's syndrome associated with slowly progressive muscular weakness. The muscle showed a peculiar combination of centronuclear myopathy with hypotrophy of type I fibres and the so called “fingerprint myopathy”. The combination of such myopathic phenomena with Marfan's syndrome presents a unique and hitherto undescribed condition.
Brief report: RET genetic screening in patients with medullary thyroid cancer and their relatives: Experience with 807 individuals at one center
2007, Journal of Clinical Endocrinology and Metabolism
Germline RET gene mutations are causative of multiple endocrine neoplasia (MEN) 2 and may be identified by genetic screening. Three different syndromes are distinguished: MEN 2A, when medullary thyroid carcinoma (MTC) is associated with pheochromocytoma and/or parathyroid adenomas; MEN 2B, when accompanied by a marfanoid habitus and/or pheochromocytoma; and familial medullary thyroid carcinoma (FMTC), when only MTC is present.
During the last 13 yr, we performed RET genetic screening in 807 subjects: 481 with apparently sporadic MTC, 37 with clinical evidence of MEN 2, and 289 relatives. Genomic DNA was extracted from the blood of all subjects, and exons 10, 11, 13, 14, 15, and 16 were analyzed by direct sequencing after PCR.
We unexpectedly discovered a germline RET mutation in 35 of 481 (7.3%) apparently sporadic MTC patients. A germline RET mutation was also found in 36 of 37 patients with clinical evidence of hereditary MTC. The distribution of RET mutations in cysteine and noncysteine encoding codons was significantly different in the two groups of patients, with the prevalence of RET mutations in noncysteine codons being higher in MTC that presented as apparently sporadic (P < 0.0001). A total of 34 FMTCs (75.5% of all FMTC) arrived with apparent sporadic MTC, with no familial history of other MTC cases. According to genetic screening and clinical data, our 72 families were classified as follows: 45 FMTC (62.5%), 22 MEN 2A (30.5%), and five MEN 2B (7%).
In this large series of MTC, hereditary forms, mainly FMTC, were clinically unsuspected in 7.3% of apparently sporadic cases. As a consequence, the prevalence of FMTC in our series is higher than that previously reported (60 vs. 10%). In these cases, RET mutations were more prevalently located in noncysteine codons. Data derived from our series helped elucidate the role of RET genetic screening for the identification of all forms of MEN 2, and especially for FMTC, which are frequently clinically misdiagnosed as nonheritable, sporadic cases.
INTESTINAL GANGLIONEUROMATOSIS AS AN EARLY EXTRA-ENDOCRINE MANIFESTATION OF TYPE 2B MULTIPLE ENDOCRINE NEOPLASIA
2023, Problemy Endokrinologii

View all citing articles on Scopus

^†: Present address: Leeds General Infirmary, Great George Street, Leeds, 1, England.

¹: From the University Departments of Dermatology, Medicine and Surgery, Royal Victoria Infirmary, Newcastle Upon Tyne, NE1 4LP, England.

View full text

Case reportA calcitonin-secreting medullary thyroid carcinoma associated with mucosal neuromas, marfanoid features, myopathy and pigmentation

Abstract

Lancet

Lancet

Medullary carcinoma of the thyroid

J Clin Path

A review of 17 cases of carcinoma of the thyroid and phaechromocytoma

J Clin Path

Epithélioma de la thyroide secrétant de la thyrocalcitonine

CR Acad Sci [D] (Paris)

Syndrome of excessive thyrocalcitonin produced by medullary carcinoma of thyroid

Granules and thyrocalcitonin-like activity in medullary carcinoma of the thyroid gland

New Eng J Med

Medullary carcinoma and thyrocalcitonin

Brit Med J

Further evaluation of the tyramine test for phaechromocytoma

New Eng J Med

A study of fixation for electron microscopy

J Exp Med

Cytochemistry and electron microscopy: the preservation of cellular ultrastructure and enzymatic activity by aldehyde fixation

J Cell Biol

A simplified lead citrate stain for use in electron microscopy

J Cell Biol

Adult myopathy from glycogen storage disease due to acid maltase deficiency

Brain

Case report
A calcitonin-secreting medullary thyroid carcinoma associated with mucosal neuromas, marfanoid features, myopathy and pigmentation