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BHDS prevalence is estimated at 1/200,000 and more than 100 families have been described as affected by the disease. The folliculin <span class="elsevierStyleItalic">(FLCN)</span> gene, located on the short arm of chromosome 17 (17p 11.2), is mutated in patients with BHDS. Genetic analysis of <span class="elsevierStyleItalic">FLCN</span> detects mutations in 88% of patients with BHDS.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> The first mutation of the <span class="elsevierStyleItalic">FLCN</span> gene was described in 2002, since then, over 120 mutations have been described. In a French series, nodules were detected in 65% of patients with BHDS undergoing thyroid ultrasound.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 42-year-old woman who was referred to Endocrinology for the study of a thyroid nodule. The patient was a heterozygous carrier of the c.1546 A<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>T (p.Lys516 *) change in the <span class="elsevierStyleItalic">FLCN</span> gene, previously identified in her cousin. The typical skin lesions of BHDS were not observed on physical examination. An abdominal magnetic resonance imaging (MRI) showed a 3<span class="elsevierStyleHsp" style=""></span>mm cyst in the right kidney (Bosniak I). Likewise, a chest computed tomography (CT) was performed, showing an 8<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>mm nodule in the left inferior lung lobe and an 18<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mm nodule in the right thyroid lobe (RTL). A thyroid ultrasound confirmed the presence of a hypoechoic nodule with well-defined contours was confirmed, 14<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>14<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>26<span class="elsevierStyleHsp" style=""></span>mm, suggesting a histological study of the same.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The patient had normal thyroid function (TSH 1.2<span class="elsevierStyleHsp" style=""></span>mcU/ml [0.35–4.94]) and did not complain of local compressive symptoms. A 2<span class="elsevierStyleHsp" style=""></span>cm nodule was noticed on cervical palpation in RTL, with no cervical lymphadenopathies. A fine needle puncture-aspiration of the RTL nodule was performed. The result was within the diagnostic category <span class="elsevierStyleSmallCaps">IV</span> of the Bethesda System: hurthle cell proliferation. The patient was referred to the Surgery Department, where a right hemithyroidectomy (surgical treatment of choice for solitary nodules with indeterminate cytology)<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> was performed. A pathologic examination of the surgical specimen showed the presence of a 2.2<span class="elsevierStyleHsp" style=""></span>cm medullary thyroid carcinoma (MTC) without vascular-lymphatic or thyroid capsule invasion or parafollicular cell hyperplasia. Laboratory tests were requested to complete the study for the presence of primary hyperparathyroidism and/or pheochromocytoma, finding calcium, PTH, metanephrines and urine catecholamines values within normal range. After surgery, calcitonin was <2.0<span class="elsevierStyleHsp" style=""></span>pg/ml and carcinoembryonic antigen was 1.5<span class="elsevierStyleHsp" style=""></span>ng/ml (normal up to 3.8). A posthemythroidectomy thyroid ultrasound confirmed the absence of pathological lymph nodes.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A sequencing study of the <span class="elsevierStyleItalic">RET</span> gene was performed (PCR and Sanger automated sequencing of 20 exons), there being no mutation compatible with multiple endocrine neoplasia type 2. Complete thyroidectomy is indicated in the MTC after hemithyroidectomy if the patient has a germline mutation of the <span class="elsevierStyleItalic">RET</span> gene, significant elevation of basal/stimulated calcitonin or evidence of residual disease in imaging studies.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> In this case, although the above criteria were not met, after a multidisciplinary approach, it was decided to perform a complete thyroidectomy in the absence of literature on the treatment of MTC in patients with BHDS. No remarkable histological alterations or parafollicular cell hyperplasia were observed in the left hemithyroidectomy specimen. The patient had hypocalcaemia as postoperative complication, resulting from the accidental removal of two parathyroid glands, requiring treatment with calcium carbonate and calcitriol.</p><p id="par0025" class="elsevierStylePara elsevierViewall">BHDS was discovered in 1977 while conducting a study of a family with hereditary MTC. Six of the 9 siblings had thyroid cancer; besides, 4 of them had skin lesions, which had not been previously associated with thyroid carcinoma. A thorough investigation of the remaining 70 family members found no more cases of thyroid cancer.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In this patient, in addition to the usual MTC follow-up, a regular assessment to rule out the occurrence of renal tumours is required (abdominal MRI, hybrid oncocytic tumours are found in 67% of cases), as their risk of kidney tumours is 7 times greater than their unaffected relatives. The onset of cutaneous lesions (90% fibrofolliculomas, 57% trichodiscomas) and lung lesions should be monitored (thoracic CT; 89% of cases have lung cysts).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Given the possibility that MTC is present in the other 2 relatives affected of BHDS, a thyroid ultrasound was performed to the patient's sister, which ruled out the presence of thyroid nodules. The same study was still pending in the case of her cousin. In conclusion, thyroid ultrasound should be considered in patients suffering from BHDS, given the possibility of thyroid nodules in these patients.</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: Pérez García L, Antón Miguel MÁ, Fuentes Gómez CR. Carcinoma medular de tiroides en un paciente con síndrome de Birt-Hogg-Dubé. Med Clin (Barc). 2017;148:528–529.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[Updated 07.08.17] 1993–2016. 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Journal Information
Vol. 148. Issue 11.
Pages 528-529 (June 2017)
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Vol. 148. Issue 11.
Pages 528-529 (June 2017)
Letter to the Editor
Medullary thyroid carcinoma in a patient with Birt-Hogg-Dube syndrome
Carcinoma medular de tiroides en un paciente con síndrome de Birt-Hogg-Dubé
Leire Pérez García
, María Ángeles Antón Miguel, Clara Rosario Fuentes Gómez
Corresponding author
Servicio de Endocrinología y Nutrición, Hospital Universitario Araba, Vitoria, Álava, Spain
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