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It represents less than 5% of thyroid carcinomas and has an intermediate prognosis between poorly differentiated and differentiated carcinomas.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1,2</span></a> Most MTCs are nonfunctional, but in some cases they secrete adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone, causing therefore ACTH ectopic secretion and thus Cushing's syndrome.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">3–5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Cushing's syndrome has been classified as ACTH dependent or independent. The first includes Cushing's disease (pituitary secretion) and ectopic ACTH secretion.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> In ectopic secretion, bronchial and lung carcinomas (oat cell) are the most common causes, but there are many other neoplasms that can secrete ACTH, as endocrine disorders such as MTC and pheochromocytoma.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We report the case of a 72-year-old male, diagnosed with hypertension 10 years ago, well controlled to date, only with salt-free diet. He had no known diabetes or dyslipidemia.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the last 6 months he had visited the emergency room on 5 occasions for hypertensive crisis without associated clinical symptoms. Thus, he is hospitalized for further studies. In the anamnesis, he referred pelvic girdle muscle weakness of one year of evolution associated with low-back pain, which prevented him from walking unaided. The patient had lost weight and showed loss of muscle mass and skin hyperpigmentation (specifically on facial region) as well as complete loss of body hair.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Physical examination revealed hypertension (blood pressure 220/140<span class="elsevierStyleHsp" style=""></span>mmHg), signs of capillary fragility and skin atrophy with bruises on the upper limbs. Initial imaging tests (abdominal and cranial CT, lumbar spine MRI) showed only sigmoid diverticulosis and L5/S1 disk prolapse.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The patient's clinical condition worsened, requiring subsequent admission to the Intensive Care Unit to tracheal intubation secondary to respiratory failure, as well as for correction of metabolic alkalosis (pH 7.58) and severe hypokalemia (1.8<span class="elsevierStyleHsp" style=""></span>mEq/L) in sustained hypertension. A toracocervical CT highlighted the finding of intrathoracic multinodular goiter with diffuse enlargement of the left lobe, causing tracheal deviation to the right, as well as multiple mediastinal adenopathies.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The hydroelectrolytic disorders and refractory hypertension led us to perform hormonal function test, reflecting elevated plasma cortisol both at 8 a. m. (51.6<span class="elsevierStyleHsp" style=""></span>mmol/l) and at 12 p.m. (45.3<span class="elsevierStyleHsp" style=""></span>mmol/l), and plasma ACTH at 8 a.m. (121.1<span class="elsevierStyleHsp" style=""></span>mmol/l). With these analytical data, the presumptive diagnosis was ACTH-dependent Cushing's syndrome, origin source to be confirmed.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Pituitary MRI was normal, and with the chest CT findings, we decided to perform FNA to the nodule. This showed increased cellularity with positive staining for calcitonin and TTF-1, showing origin in thyroid C cells. Subsequently, determination of plasma calcitonin was requested, with a level of 7330<span class="elsevierStyleHsp" style=""></span>pg/ml. Thereby, diagnosis was MTC as a source of ACTH secretion and therefore producer of Cushing's syndrome.</p><p id="par0045" class="elsevierStylePara elsevierViewall">To rule out common associations with MTC (pheochromocytoma and hyperparathyroidism) several analytical determinations were performed with normal results: plasma metanephrines were below 0.15<span class="elsevierStyleHsp" style=""></span>mmol/l, and the levels of plasma calcium were 8.74<span class="elsevierStyleHsp" style=""></span>mg/dl, consistent with PTH 54.6<span class="elsevierStyleHsp" style=""></span>ng/dL (normal 15–65<span class="elsevierStyleHsp" style=""></span>ng/dL).</p><p id="par0050" class="elsevierStylePara elsevierViewall">Then, treatment with ketoconazole 600<span class="elsevierStyleHsp" style=""></span>mg/day was initiated for adrenal lock to performing surgery (total thyroidectomy and bilateral neck dissection), where the diagnosis was confirmed.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The subsequent genetic test revealed 2 mutations in the RET proto-oncogene: p.C618Y (exon 10; widely described in the literature), and p.R844Q (exon 14, with uncertain meaning and only previously described in a Polish family). Therefore, the patient of type 2A multiple endocrine neoplasia (MEN) was diagnosed performing subsequent genetic test to his first-degree relatives. The carriers of the mutation with uncertain significance were performed close image monitoring; the known mutation carriers underwent total thyroidectomy.</p><p id="par0060" class="elsevierStylePara elsevierViewall">MEN 2A combines pheochromocytoma, MTC and hyperparathyroidism, with autosomal dominant inheritance. It is caused by a germline mutation in the RET protooncogene.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> The MTC is the most common manifestation and it usually occurs in the second or third decade of life.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Genetic test helps us obtain a more accurate diagnosis and an appropriate treatment in patients with MTC. The identification of pathological mutations in the RET gene helps select carrier families and indicate the completion of prophylactic thyroidectomy in asymptomatic carriers.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ares J, Díaz-Naya L, Martín-Nieto A, Pertierra J. MEN 2A con doble mutación en gen <span class="elsevierStyleItalic">RET:</span> carcinoma medular de tiroides secretor de ACTH. 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Journal Information
Vol. 146. Issue 9.
Pages 419-420 (May 2016)
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Vol. 146. Issue 9.
Pages 419-420 (May 2016)
Letter to the Editor
MEN 2A with double mutation in RET gene: Ectopic ACTH production in medullary thyroid carcinoma
MEN 2A con doble mutación en gen RET: carcinoma medular de tiroides secretor de ACTH
Jessica Ares
, Lucía Díaz-Naya, Alicia Martín-Nieto, Joaquín Pertierra
Corresponding author
Departamento de Endocrinología y Nutrición, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
Article information
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