Scientific letter
Cushing's syndrome associated with an adrenocortical oncocytoma
Síndrome de Cushing asociado a oncocitoma adrenocortical
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Calderón Vicente, Araceli Ronquillo Rubio, Pedro Yunta Abarca, Rosa Quílez Toboso, Jaime Aranda Regules" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Dulce M." "apellidos" => "Calderón Vicente" "email" => array:1 [ 0 => "dmcv2000@yahoo.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Araceli" "apellidos" => "Ronquillo Rubio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Pedro" "apellidos" => "Yunta Abarca" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Rosa" "apellidos" => "Quílez Toboso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Jaime" "apellidos" => "Aranda Regules" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Sección de Endocrinología y Nutrición, Hospital Virgen de la Luz, Cuenca, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Virgen de la Luz, Cuenca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Cirugía General, Hospital Virgen de la Luz, Cuenca, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de Cushing asociado a oncocitoma adrenocortical" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 976 "Ancho" => 1300 "Tamanyo" => 367880 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Proliferation of tumor cells with large eosinophlic and granular cytoplasms, with a diffuse growth pattern, showing nuclear pleomorphism. (b–d) Tumor cell cytoplasm shows strong, diffuse staining with melan-A and alpha-inhibin, but no staining for chromogranin.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case report</span><p id="par0005" class="elsevierStylePara elsevierViewall">Oncocytic neoplasms or oncocytomas usually arise in organs such as the kidney, thyroid, parathyroid, salivary, or pituitary glands. Adrenal cortex oncocytomas are extremely rare and are usually discovered as incidental findings. The case of a female patient with Cushing's syndrome caused by a benign adrenal oncocytoma is reported.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 61-year-old woman referred to the endocrinology outpatient clinic for obesity in February 2014. When questioned, she reported a tendency to overweight since she was 30 years old, but this had exacerbated in the last year, in which her weight had increased by 10<span class="elsevierStyleHsp" style=""></span>kg for no apparent reason. The patient had also had HBP for the previous 8 years, and was being treated with five antihypertensive drugs (ARB, beta-blocker, alpha-blocker, thiazide, and calcium channel blocker).</p><p id="par0015" class="elsevierStylePara elsevierViewall">Her personal history included menopause at 50 years of age; she had no other remarkable personal or family history.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Physical examination findings included: 96.4<span class="elsevierStyleHsp" style=""></span>kg of weight with BMI of 38.6<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>, BP of 130/90<span class="elsevierStyleHsp" style=""></span>mmHg, facial plethora with slight “full moon” appearance, facial hirsutism, atrophic skin, increased posterior cervical and supraclavicular fat, increased abdominal circumference with fat redistribution, and muscle atrophy in her lower limbs.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The results of the laboratory tests initially requested included: hemoglobin 16.7<span class="elsevierStyleHsp" style=""></span>g/dL and hematocrit 51.8% in a complete blood count, which was otherwise normal. The chemistry results were normal except for a glucose level of 107<span class="elsevierStyleHsp" style=""></span>mg/dL. Oral glucose (75<span class="elsevierStyleHsp" style=""></span>g) tolerance test: 106–280<span class="elsevierStyleHsp" style=""></span>mg/dL; plasma cortisol 15.9<span class="elsevierStyleHsp" style=""></span>mcg/dL after 1<span class="elsevierStyleHsp" style=""></span>mg of dexamethasone, and urinary free cortisol 233.9<span class="elsevierStyleHsp" style=""></span>mcg/24<span class="elsevierStyleHsp" style=""></span>h (No.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0–100).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Cushing's syndrome was suspected, and the following measurements were performed, some of them repeated on two consecutive days: plasma cortisol at 8<span class="elsevierStyleHsp" style=""></span>h: 14.1 and 13.9<span class="elsevierStyleHsp" style=""></span>mcg/dL, plasma cortisol at 23<span class="elsevierStyleHsp" style=""></span>h: 12.3 and 10.9<span class="elsevierStyleHsp" style=""></span>mcg/dL, ACTH: <5 and <5<span class="elsevierStyleHsp" style=""></span>pg/mL. Weak suppression with dexamethasone (0.5<span class="elsevierStyleHsp" style=""></span>mg/6<span class="elsevierStyleHsp" style=""></span>h 2 days): plasma cortisol 13.7<span class="elsevierStyleHsp" style=""></span>mcg/dL, urinary free cortisol 160<span class="elsevierStyleHsp" style=""></span>mcg/24<span class="elsevierStyleHsp" style=""></span>h.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Catecholamine and metanephrine levels in 24<span class="elsevierStyleHsp" style=""></span>h urine were normal, as were all other androgen levels measured (testosterone 0.27<span class="elsevierStyleHsp" style=""></span>ng/mL, androstenedione 2.04<span class="elsevierStyleHsp" style=""></span>ng/mL, DHEAS 1.3<span class="elsevierStyleHsp" style=""></span>mcg/mL). Gonadotropin and estradiol levels were FSH 42.80<span class="elsevierStyleHsp" style=""></span>mIU/mL, LH 7.21<span class="elsevierStyleHsp" style=""></span>mIU/mL, and estradiol 13<span class="elsevierStyleHsp" style=""></span>pg/mL.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Abdominal CT with contrast revealed an oval lesion, well defined and homogeneous, dependent on the left adrenal gland, approximately 33<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mm in size. Hounsfield units (HU) were 23<span class="elsevierStyleHsp" style=""></span>HU without contrast; after intravenous contrast injection, 102<span class="elsevierStyleHsp" style=""></span>HU at 65<span class="elsevierStyleHsp" style=""></span>s and 40<span class="elsevierStyleHsp" style=""></span>HU at 10<span class="elsevierStyleHsp" style=""></span>min. This showed the lesion to be benign because washout was greater than 50%, despite showing low lipid content behavior and being denser than normal.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The patient underwent a left laparoscopic adrenalectomy. Intravenous hydrocortisone 100<span class="elsevierStyleHsp" style=""></span>mg was administered before surgery, which was uneventful. The postoperative course was favorable, with hospital discharge 6 days after surgery. Three months after surgery. BP values were normal without antihypertensive treatment, the patient had lost 4<span class="elsevierStyleHsp" style=""></span>kg of weight, and her facial plethora had clearly improved. At 11 months, the patient continues on replacement therapy with hydrocortisone 30<span class="elsevierStyleHsp" style=""></span>mg/day, because in the most recent laboratory tests, her cortisol level after ACTH had increased from 3.4 to 7.6<span class="elsevierStyleHsp" style=""></span>mcg/dL.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Gross pathological examination of the adrenalectomy specimen showed a round, well-circumscribed, encapsulated tumor that measured 3<span class="elsevierStyleHsp" style=""></span>cm in its longer axis and was mahogany brown in color upon sectioning. Microscopic examination showed a tumor population with a solid growth pattern; more than 50% of tumor cells had eosinophilic and granular cytoplasm. These oncocytic cells had nuclei with mild pleomorphism; no mitotic figures were found. Immunohistochemistry tests were positive for vimentin, alpha-inhibin, and melan-A, weakly positive for calretinin, and focally positive for synaptophysin, with no staining for chromogranin, S-100, EMA, and CD10. The cell proliferation index was less than 1% (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Oncocytoma is a tumor which is characterized by consisting only or predominantly of oncocytes, large cells with abundant eosinophilic and granular cytoplasm as a consequence of mitochodrial accumulation. Adrenocortical oncocytoma is extremely uncommon; since it was first reported in 1986, approximately 148 cases have been published in the literature,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> and most tumors were benign and non-functioning. Because of these characteristics, oncocytomas are usually diagnosed incidentally.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> These tumors have been reported at all ages, with no clear preference (mean age 47 years, range 3–77 years), and are more common in females (2.5:1) and in the left adrenal gland (3.5:1). However, approximately 20% of adrenal oncocytomas may show some degree of malignancy, and hormone hyperproduction is found in 17% of cases.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Cushing's syndrome associated with adrenal oncocytoma has been reported in very few cases.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5–8</span></a> The reported patient was diagnosed with Cushing's syndrome of adrenal origin, and therefore underwent surgery, which is the usually recommended therapeutic alternative<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> and achieved resolution of her hypercorticism. The surgical specimen was examined based on the description by Bisceglia et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> for oncocytc adrenal tumors, according to which, adrenal tumors with more than 90% oncocytic cells are considered pure oncocytic tumors (A), those with 50–90% oncocytic cells are considered as mixed oncocytic tumors (B), and those with less than 50% oncocytic cells are classified as conventional adrenocortical tumors with oncocytic differentiation (C). Our case belonged to category B. The immunohistochemical profile of the tumor reported is superimposable on that of oncocytic adrenocortical tumors. These tumors are typically positive for vimentin, melan-A, alpha-inhibin, synaptophysin, and calretinin, and negative for CK20, chromogranin, S-100, EMA, and CD10.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> There are several classifications for determining the behavior of oncocytic adrenal tumors, of which the most widely accepted is the Lin–Weiss–Bisceglia classification.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> This system proposes major and minor criteria, so that the presence of at least one of the three major criteria (mitotic index greater than 5 per 50 high-power fields, atypical mitoses, and venous invasion) suggests malignancy, at least one of the four minor criteria (size greater than 10<span class="elsevierStyleHsp" style=""></span>cm and/or weight greater than 200<span class="elsevierStyleHsp" style=""></span>g, microscopic necrosis, capsular invasion, and sinusoid invasion) involves an uncertain malignant potential, and the absence of major and minor criteria suggests a benign potential. No major or minor criteria were found in our patient, and a potentially benign tumor was therefore diagnosed.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Adrenal oncocytoma should be considered in differential diagnosis of Cushing's syndrome of adrenal origin, or even adrenal incidentaloma, because most oncocytomas are non-functioning.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case report" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Calderón Vicente DM, Ronquillo Rubio A, Yunta Abarca P, Quílez Toboso R, Aranda Regules J. Síndrome de Cushing asociado a oncocitoma adrenocortical. Endocrinol Nutr. 2015;62:416–418.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 976 "Ancho" => 1300 "Tamanyo" => 367880 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Proliferation of tumor cells with large eosinophlic and granular cytoplasms, with a diffuse growth pattern, showing nuclear pleomorphism. (b–d) Tumor cell cytoplasm shows strong, diffuse staining with melan-A and alpha-inhibin, but no staining for chromogranin.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adrenal oncocytic neoplasm: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L. Mearini" 1 => "R. del Sordo" 2 => "E. Costantini" 3 => "E. Nunzi" 4 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 6 | 2 | 8 |
| 2024 September | 55 | 9 | 64 |
| 2024 August | 32 | 0 | 32 |
| 2024 July | 16 | 6 | 22 |
| 2024 June | 13 | 5 | 18 |
| 2024 May | 19 | 7 | 26 |
| 2024 April | 18 | 5 | 23 |
| 2024 March | 19 | 2 | 21 |
| 2024 February | 17 | 6 | 23 |
| 2024 January | 13 | 2 | 15 |
| 2023 December | 23 | 9 | 32 |
| 2023 November | 12 | 4 | 16 |
| 2023 October | 12 | 5 | 17 |
| 2023 September | 15 | 3 | 18 |
| 2023 August | 19 | 3 | 22 |
| 2023 July | 28 | 7 | 35 |
| 2023 June | 17 | 3 | 20 |
| 2023 May | 33 | 5 | 38 |
| 2023 April | 18 | 1 | 19 |
| 2023 March | 18 | 4 | 22 |
| 2023 February | 15 | 4 | 19 |
| 2023 January | 10 | 7 | 17 |
| 2022 December | 22 | 5 | 27 |
| 2022 November | 22 | 7 | 29 |
| 2022 October | 17 | 4 | 21 |
| 2022 September | 23 | 35 | 58 |
| 2022 August | 13 | 12 | 25 |
| 2022 July | 24 | 5 | 29 |
| 2022 June | 12 | 5 | 17 |
| 2022 May | 22 | 7 | 29 |
| 2022 April | 15 | 13 | 28 |
| 2022 March | 21 | 6 | 27 |
| 2022 February | 15 | 6 | 21 |
| 2022 January | 29 | 7 | 36 |
| 2021 December | 19 | 7 | 26 |
| 2021 November | 8 | 4 | 12 |
| 2021 October | 32 | 14 | 46 |
| 2021 September | 38 | 9 | 47 |
| 2021 August | 21 | 4 | 25 |
| 2021 July | 27 | 5 | 32 |
| 2021 June | 23 | 10 | 33 |
| 2021 May | 28 | 10 | 38 |
| 2021 April | 43 | 9 | 52 |
| 2021 March | 34 | 16 | 50 |
| 2021 February | 21 | 5 | 26 |
| 2021 January | 21 | 9 | 30 |
| 2020 December | 24 | 2 | 26 |
| 2020 November | 12 | 6 | 18 |
| 2020 October | 7 | 5 | 12 |
| 2020 September | 17 | 9 | 26 |
| 2020 August | 19 | 4 | 23 |
| 2020 July | 17 | 15 | 32 |
| 2020 June | 23 | 11 | 34 |
| 2020 May | 18 | 4 | 22 |
| 2020 April | 11 | 5 | 16 |
| 2020 March | 11 | 6 | 17 |
| 2020 February | 12 | 7 | 19 |
| 2020 January | 15 | 4 | 19 |
| 2019 December | 16 | 9 | 25 |
| 2019 November | 15 | 6 | 21 |
| 2019 October | 11 | 0 | 11 |
| 2019 September | 22 | 4 | 26 |
| 2019 August | 11 | 1 | 12 |
| 2019 July | 20 | 9 | 29 |
| 2019 June | 16 | 15 | 31 |
| 2019 May | 98 | 10 | 108 |
| 2019 April | 43 | 6 | 49 |
| 2019 March | 15 | 2 | 17 |
| 2019 February | 15 | 5 | 20 |
| 2019 January | 17 | 4 | 21 |
| 2018 December | 23 | 3 | 26 |
| 2018 November | 20 | 7 | 27 |
| 2018 October | 11 | 7 | 18 |
| 2018 September | 8 | 2 | 10 |
| 2018 August | 2 | 1 | 3 |
| 2018 July | 6 | 0 | 6 |
| 2018 June | 8 | 2 | 10 |
| 2018 May | 5 | 0 | 5 |
| 2018 April | 0 | 1 | 1 |
| 2018 March | 2 | 0 | 2 |
| 2018 February | 8 | 2 | 10 |
| 2018 January | 2 | 2 | 4 |
| 2017 December | 8 | 0 | 8 |
| 2017 November | 7 | 0 | 7 |
| 2017 October | 10 | 1 | 11 |
| 2017 September | 7 | 5 | 12 |
| 2017 August | 9 | 3 | 12 |
| 2017 July | 5 | 0 | 5 |
| 2017 June | 15 | 5 | 20 |
| 2017 May | 24 | 10 | 34 |
| 2017 April | 30 | 4 | 34 |
| 2017 March | 24 | 29 | 53 |
| 2017 February | 35 | 6 | 41 |
| 2017 January | 18 | 2 | 20 |
| 2016 December | 23 | 3 | 26 |
| 2016 November | 17 | 4 | 21 |
| 2016 October | 17 | 3 | 20 |
| 2016 September | 19 | 4 | 23 |
| 2016 August | 8 | 7 | 15 |
| 2016 July | 15 | 1 | 16 |
| 2016 June | 31 | 6 | 37 |
| 2016 May | 22 | 12 | 34 |
| 2016 April | 15 | 4 | 19 |
| 2016 March | 1 | 0 | 1 |
| 2016 January | 0 | 1 | 1 |
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