Scientific letter
A hidden cause of virilization in postmenopausal women
Una causa oculta de virilización en mujeres postmenopaúsicas
Maria D. Ballesteros-Pomar
, Alfonso Vidal-Casariego
Corresponding author
Sección de Endocrinología y Nutrición, Complejo Asistencial Universitario de León, Spain
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Ballesteros-Pomar, Alfonso Vidal-Casariego" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Maria D." "apellidos" => "Ballesteros-Pomar" "email" => array:2 [ 0 => "Mdballesteros@telefonica.net" 1 => "dballesteros@saludcastillayleon.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Alfonso" "apellidos" => "Vidal-Casariego" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Sección de Endocrinología y Nutrición, Complejo Asistencial Universitario de León, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Una causa oculta de virilización en mujeres postmenopaúsicas" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Virilizing ovarian tumors are very infrequent, representing less than 0.2% of all cases of hyperandrogenism and less than 1% of ovarian tumors.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Two women with severe hyperandrogenism who turned out to have a Leydig cell tumor are reported.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Our first patient was a 50-year-old woman with a 5-year history of weight gain of 20<span class="elsevierStyleHsp" style=""></span>kg, secondary amenorrhea, acne, hirsutism and progressive virilization (male-pattern alopecia, clitoromegaly and deepening of the voice). On physical examination, she revealed moon facies, buffalo hump, thin and wrinkled skin and abdominal purple red striae. Ferriman–Gallwey hirsutism score was 18. Plasma ACTH and cortisol, and urinary free cortisol were increased. Hormonal assessment is summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Very high testosterone, slightly high androstenedione (4.59<span class="elsevierStyleHsp" style=""></span>ng/mL, normal 0.3–3.5) but normal dehydroepiandrosterone sulfate (DHEAS) levels (1.25<span class="elsevierStyleHsp" style=""></span>mcg/mL, normal 0.35–4.3) were detected. FSH and LH levels were 27.4 and 13.4<span class="elsevierStyleHsp" style=""></span>U/L respectively (normal range for postmenopause 20–100<span class="elsevierStyleHsp" style=""></span>IU/L). Dexamethasone suppression tests (1 and 8<span class="elsevierStyleHsp" style=""></span>mg) were diagnostic of Cushing's disease; magnetic resonance imaging (MRI) revealed a 7<span class="elsevierStyleHsp" style=""></span>mm microadenoma in the right lateral margin of the pituitary gland, which was resected by transsphenoidal surgery. One month after surgery, she complained of no improvement of her symptoms. Remarkably high testosterone levels, slightly elevated androstenedione (3.89<span class="elsevierStyleHsp" style=""></span>ng/mL) but normal DHEA-S (2.15<span class="elsevierStyleHsp" style=""></span>mcg/mL) were found (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). These findings could indicate either an ovarian origin of hyperandrogenism or persistence of Cushing's disease. Although other diagnoses, such as ovarian hyperthecosis, could not be excluded, the rapid onset and very high levels of androgens suggested an ovarian tumor. Pituitary MRI could match with either tumor persistence or postsurgical changes; neck, thorax and abdominal CT scan and pelvic transvaginal ultrasound failed to find any mass. Bilateral laparoscopic oophorectomy was performed. A pure Leydig cell tumor of 12<span class="elsevierStyleHsp" style=""></span>mm was found on histological examination of the left ovary. Alpha-inhibin immunohistochemical staining was found to be positive. Total and free testosterone levels returned to the normal range (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), and the patient referred improvement in her voice, hair loss, acne and hirsutism, together with development of hot flushes. As hormonal findings suggested persistent Cushing's disease, MRI was performed showing a focal area of low intensity signal on non-contrast T1 suggesting a remaining microadenoma. Some months later the patient finally agreed to a new transsphenoidal pituitary surgery; unfortunately, the adenoma was not found and hypercortisolism persisted (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). A new MRI revealed a 3<span class="elsevierStyleHsp" style=""></span>mm microadenoma in the posterolateral right area of the pituitary; Gamma Knife radiosurgery was then delivered, with a maximum irradiation dose of 33.33<span class="elsevierStyleHsp" style=""></span>Gy. Along the following months the patient lost 10<span class="elsevierStyleHsp" style=""></span>kg, her general condition improved and hormonal levels finally normalized (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The second patient was a 60-year-old woman referred to the Endocrinology clinic due to 5-year complaints of male pattern alopecia, hirsutism and deepened voice. Hormonal evaluation showed increased total (8.58 and 4.86<span class="elsevierStyleHsp" style=""></span>ng/mL) and free testosterone levels (16 and 13.7<span class="elsevierStyleHsp" style=""></span>pg/mL); gonadotropin levels were low for postmenopausal state (luteinizing hormone 2.5<span class="elsevierStyleHsp" style=""></span>IU/l, follicle-stimulating hormone 3.84<span class="elsevierStyleHsp" style=""></span>IU/l). Other androgens remained within the normal range: androstenedione 2.92<span class="elsevierStyleHsp" style=""></span>ng/mL, DHEAS 0.81<span class="elsevierStyleHsp" style=""></span>mcg/mL. A CT scan and transvaginal ultrasound revealed no enlargement or mass in abdomen or pelvis. Considering the differential diagnosis of ovarian hyperthecosis vs ovarian tumor both ovaries were removed. A Leydig cell tumor of 15<span class="elsevierStyleHsp" style=""></span>mm was found in the right ovary, with positive staining for alpha-inhibin. After surgery, free and total testosterone levels fell to 0.7<span class="elsevierStyleHsp" style=""></span>pg/mL and 0.22<span class="elsevierStyleHsp" style=""></span>ng/mL. The physical changes gradually reversed and she suffered hot flushes.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Virilizing ovarian tumors are an unusual cause of hyperandrogenism; however, rapidly worsening signs of virilization in a postmenopausal woman should prompt an urgent diagnostic work-up for an androgen-secreting tumor. Peripheral total testosterone higher than 2<span class="elsevierStyleHsp" style=""></span>ng/mL (>7<span class="elsevierStyleHsp" style=""></span>nmol/l), or 3–4 times higher than the upper limit of normal range may be a cut-off level for ovarian neoplasm suspicion.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> One study has shown that testosterone level >8.67<span class="elsevierStyleHsp" style=""></span>nmol/l (2.5<span class="elsevierStyleHsp" style=""></span>ng/mL) had 100% sensitivity for ovarian neoplasm, together with 98% specificity.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Our initial differential diagnosis also considered stromal hyperthecosis. Pure Leydig cell tumors typically occur in postmenopausal women, with hirsutism or virilization in 75% of cases. These tumors are typically small at presentation,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> so imaging studies are often not useful for the diagnosis,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> as happened in our cases. Less than 150 cases have been reported to date.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In our first case, differential diagnosis of hyperandrogenism was particularly challenging, as our patient also suffered from Cushing's disease with an awkward evolution. However, as adrenal glands produce up to 95% of DHEA-S, its normal levels ruled out an adrenal origin of hyperandrogenism, while high testosterone levels indicated a virilizing ovarian tumor. Coexistent adrenal and ovarian hyperandrogenism has been reported in other unusual settings.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Rare steroid cell ovarian tumors of adrenocortical type have also been reported to result in cortisol co-secretion.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Ovarian tumors may also be associated with Cushing's syndrome due to ectopic secretion of ACTH or corticotropin-releasing factor (CRF).<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Our patient showed an ACTH-dependent Cushing's syndrome, which ruled out the possibility of cortisol co-secretion. Besides, hyperandrogenism disappeared after tumor removal, while Cushing's disease persisted; therefore, an ectopic source of ACTH secretion could also be ruled out.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion, screening for virilizing ovarian tumors is mandatory in rapidly progressive virilization, with elevated testosterone levels, after ruling out other more frequent causes. In the unusual situation of coexisting hypercortisolism, DHEA-S can be useful for differential diagnosis, as normal levels are found when the androgen source is ovarian. Normal imaging does not rule out virilizing ovarian tumors.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">DXM, dexamethasone.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Initial levels (June 2005) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">1 month after first transsphenoidal surgery (February 2006) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">After ooforectomy (January 2007) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">1 month after second transsphenoidal surgery (March 2009) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">12 months after radiosurgery (March 2013) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Normal range \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACTH (pg/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.7 and 75<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52.3 and 48.2<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">123 and 80.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Plasma cortisol (μg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.6 and 32.5<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.6 and 15.6<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Morning plasma cortisol after DXM 1<span class="elsevierStyleHsp" style=""></span>mg 11 p.m. (μg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.31 and 9.13<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.8 and 9.8<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum cortisol<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>1.8<span class="elsevierStyleHsp" style=""></span>mcg/dL (<50<span class="elsevierStyleHsp" style=""></span>nmol/L) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Morning plasma cortisol after DXM 2<span class="elsevierStyleHsp" style=""></span>mg/6<span class="elsevierStyleHsp" style=""></span>h or 8<span class="elsevierStyleHsp" style=""></span>mg 11 p.m. (μg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.25 and 1.18<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum cortisol decrease >50% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Urinary free cortisol (μg/24<span class="elsevierStyleHsp" style=""></span>h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">122.6 and 345<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">135.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">335.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">215 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35–120 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total testosterone (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.35 and 3.99<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.2 and 6.12<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.221 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Women 0.2–0.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Free testosterone (pg/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.5 and 18<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 and 28<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.06–2.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab559585.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Two samples were obtained in different days to confirm these results.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hormonal levels in Patient 1 along evolution.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" 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Scully" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Gynecol Pathol" "fecha" => "1987" "volumen" => "6" "paginaInicial" => "40" "paginaFinal" => "48" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3570631" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cushing’ Syndrome associated with adenocarcinoma of the ovary" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "V. Parsons" 1 => "B. Rigby" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1958" "volumen" => "272" "paginaInicial" => "992" "paginaFinal" => "994" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13417661" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ACTH-like excretion from carcinoma of the ovary: the clinical effect of m,p′-DDD" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Nichols" 1 => "J.C. Warren" 2 => "F.A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 1 | 5 |
| 2024 October | 42 | 4 | 46 |
| 2024 September | 50 | 4 | 54 |
| 2024 August | 40 | 2 | 42 |
| 2024 July | 31 | 5 | 36 |
| 2024 June | 35 | 5 | 40 |
| 2024 May | 45 | 6 | 51 |
| 2024 April | 39 | 7 | 46 |
| 2024 March | 44 | 2 | 46 |
| 2024 February | 54 | 4 | 58 |
| 2024 January | 59 | 7 | 66 |
| 2023 December | 62 | 15 | 77 |
| 2023 November | 69 | 8 | 77 |
| 2023 October | 92 | 10 | 102 |
| 2023 September | 50 | 4 | 54 |
| 2023 August | 44 | 5 | 49 |
| 2023 July | 45 | 7 | 52 |
| 2023 June | 59 | 6 | 65 |
| 2023 May | 68 | 6 | 74 |
| 2023 April | 39 | 3 | 42 |
| 2023 March | 47 | 9 | 56 |
| 2023 February | 57 | 3 | 60 |
| 2023 January | 47 | 4 | 51 |
| 2022 December | 45 | 7 | 52 |
| 2022 November | 44 | 6 | 50 |
| 2022 October | 26 | 7 | 33 |
| 2022 September | 48 | 6 | 54 |
| 2022 August | 37 | 11 | 48 |
| 2022 July | 29 | 7 | 36 |
| 2022 June | 20 | 9 | 29 |
| 2022 May | 23 | 8 | 31 |
| 2022 April | 23 | 10 | 33 |
| 2022 March | 25 | 8 | 33 |
| 2022 February | 55 | 6 | 61 |
| 2022 January | 48 | 12 | 60 |
| 2021 December | 47 | 9 | 56 |
| 2021 November | 34 | 9 | 43 |
| 2021 October | 30 | 14 | 44 |
| 2021 September | 20 | 8 | 28 |
| 2021 August | 33 | 6 | 39 |
| 2021 July | 24 | 8 | 32 |
| 2021 June | 35 | 10 | 45 |
| 2021 May | 26 | 20 | 46 |
| 2021 April | 108 | 27 | 135 |
| 2021 March | 48 | 8 | 56 |
| 2021 February | 28 | 6 | 34 |
| 2021 January | 30 | 7 | 37 |
| 2020 December | 40 | 15 | 55 |
| 2020 November | 33 | 5 | 38 |
| 2020 October | 24 | 7 | 31 |
| 2020 September | 30 | 8 | 38 |
| 2020 August | 40 | 14 | 54 |
| 2020 July | 30 | 15 | 45 |
| 2020 June | 27 | 8 | 35 |
| 2020 May | 30 | 13 | 43 |
| 2020 April | 19 | 12 | 31 |
| 2020 March | 39 | 12 | 51 |
| 2020 February | 36 | 7 | 43 |
| 2020 January | 40 | 16 | 56 |
| 2019 December | 50 | 15 | 65 |
| 2019 November | 38 | 14 | 52 |
| 2019 October | 38 | 4 | 42 |
| 2019 September | 31 | 8 | 39 |
| 2019 August | 29 | 9 | 38 |
| 2019 July | 34 | 23 | 57 |
| 2019 June | 44 | 19 | 63 |
| 2019 May | 108 | 41 | 149 |
| 2019 April | 61 | 9 | 70 |
| 2019 March | 23 | 7 | 30 |
| 2019 February | 17 | 13 | 30 |
| 2019 January | 10 | 6 | 16 |
| 2018 December | 20 | 4 | 24 |
| 2018 November | 26 | 1 | 27 |
| 2018 October | 28 | 8 | 36 |
| 2018 September | 28 | 2 | 30 |
| 2018 August | 17 | 4 | 21 |
| 2018 July | 17 | 6 | 23 |
| 2018 June | 9 | 3 | 12 |
| 2018 May | 15 | 11 | 26 |
| 2018 April | 12 | 3 | 15 |
| 2018 March | 9 | 3 | 12 |
| 2018 February | 24 | 1 | 25 |
| 2018 January | 27 | 3 | 30 |
| 2017 December | 32 | 2 | 34 |
| 2017 November | 25 | 3 | 28 |
| 2017 October | 13 | 4 | 17 |
| 2017 September | 11 | 1 | 12 |
| 2017 August | 26 | 6 | 32 |
| 2017 July | 10 | 4 | 14 |
| 2017 June | 16 | 8 | 24 |
| 2017 May | 24 | 7 | 31 |
| 2017 April | 21 | 2 | 23 |
| 2017 March | 16 | 36 | 52 |
| 2017 February | 28 | 3 | 31 |
| 2017 January | 14 | 3 | 17 |
| 2016 December | 20 | 7 | 27 |
| 2016 November | 15 | 3 | 18 |
| 2016 October | 36 | 7 | 43 |
| 2016 September | 17 | 6 | 23 |
| 2016 August | 17 | 8 | 25 |
| 2016 July | 16 | 3 | 19 |
| 2016 June | 29 | 10 | 39 |
| 2016 May | 18 | 16 | 34 |
| 2016 April | 18 | 22 | 40 |
| 2016 March | 32 | 8 | 40 |
| 2016 February | 28 | 13 | 41 |
| 2016 January | 25 | 1 | 26 |
| 2015 December | 32 | 10 | 42 |
| 2015 November | 27 | 9 | 36 |
| 2015 September | 1 | 0 | 1 |
| 2015 June | 1 | 0 | 1 |
| 2015 May | 1 | 0 | 1 |
| 2015 April | 2 | 1 | 3 |
| 2015 March | 3 | 0 | 3 |
| 2015 February | 2 | 0 | 2 |
| 2015 January | 5 | 0 | 5 |
| 2014 December | 1 | 1 | 2 |
| 2014 November | 4 | 3 | 7 |
| 2014 October | 17 | 5 | 22 |
| 2014 September | 7 | 10 | 17 |
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