Sex hormone binding globulin decrease as potential pathogenetic factor for hirsutism in adolescent girls / Disminución de la globulina transportadora de hormonas sexuales como factor patogénico de hirsutismo en la adolescencia

We investigated 252 non-obese female subjects aged 13-39 years to evaluate if an exaggerated descent of sex hormone binding globulin (SHBG) levels during adolescence can play a role in the development of hirsutism. Body hair was assessed according to Ferriman and Gallwey (FG), with a stringent criterion of normality of < 4. In 13-14 years girls, SHBG and free testosterone (FT) levels were similar in "hirsute" girls (FG > 4) and controls (FG < 4, regular menstrual cycles, no acne). In 15-18 years girls, SHBG values were lower in "hirsute" girls, FT levels were similar in both groups, FG correlated inversely with SHBG. In 19-39 yr women, FT levels were higher in "hirsute" subjects, SHBG values were similar in both groups, FG correlated positively with FT. Lowest SHBG values were observed at 15-18 years, but the slope of the decrease from 1314 years values was greater in the "hirsute" group. FT values increased progressively with age, but the increase was greater in the "hirsute" group. Those results suggest an important role of SHBG decrease in adolescence vs. a more accentuated testosterone increase in adults, as factors conditioning the development of hirsutism in these two different periods of life.

Se investigaron 252 mujeres con peso normal, de 13 a 39 años de edad, para evaluar si un descenso exagerado en los niveles de la globulina transportadora de hormonas sexuales ("sex hormone binding globulin"; SHBG) puede tener un rol en el desarrollo de hirsutismo. Este signo fue evaluado con la escala de Ferriman y Gallwey (FG), empleando un criterio riguroso de normalidad < 4. En niñas de 13-14 años, tanto SHBG como la testosterona libre ("free testosterone"; FT) fueron similares en niñas "hirsutas" (FG > 4) y controles (FG < 4, ciclos menstruales regulares, sin acné). En adolescentes de 15-18 años, los valores de SHBG fueron menores en las "hirsutas", los niveles de FT fueron similares en ambos grupos y el índice de FG correlacionó inversamente con SHBG. En las mujeres de 19-39 años, los niveles de FT fueron mayores en las "hirsutas", los valores de SHBG fueron similares en ambos grupos y FG correlacionó positivamente con FT. Los valores más bajos de SHBG se observaron entre 15 y 18 años, pero la pendiente de disminución a partir de los valores de 13-14 años fue mayor en el grupo de "hirsutas". Los valores de FT se incrementaron progresivamente con la edad, pero el aumento fue mayor en el grupo de "hirsutas". Estos resultados sugieren un rol importante del descenso de SHBG en la adolescencia vs. un incremento más acentuado de los niveles de testosterona en las adultas, como factores que condicionan el desarrollo del hirsutismo en esos dos diferentes periodos de la vida.

Association of ovarian volume and serum LH levels in adolescent patients with menstrual disorders and/or hirsutism

Pelvic ultrasonography was performed on 25 adolescent patients with menstrual disorders and/or hirsutism. Clinical and endocrinologic state was evaluated by history, physical examination and assays of serum LH, FSH, prolactin, testosterone and androstenedione levels in order to determine a possible association between hormonal levels and ovarian volume in the etiologic investigation of these adolescent girls. Patients aged 12 to 19 years, mean 14.92 years (menarche at 12 to 16 years; mean, 12.32 years) were divided into three groups according to ovarian size at ultrasonography: group I, N = 13, both ovaries 2-10 cm3; group II, N = 5, one of the ovaries > 10 cm3; group III, N = 7, both ovaries > 10 cm3. A strong correlation between serum LH levels and ovarian volume (r = 0.647, P < 0.0001) was observed. Moreover, when comparing the hormonal levels of all three groups, serum LH levels were significantly higher in group III (group I, 3.92 +/- 3.49; group II, 5.25 +/- 2.71; group III, 9.77 +/- 3.11 mIU/ml; mean +/- SD, P < 0.003) while testosterone and androstenedione levels showed a tendency to also be higher, but this difference was not significant. This hormonal pattern is suggestive of polycystic ovary syndrome (PCOS). The present results suggest that ovarian size of more than 10 cm3 at pelvic ultrasound in adolescent girls with menstrual disorders and/or hirsutism might be predictive of PCOS and emphasize the importance of careful assessment of ovarian volume by ultrasound

Serum LH levels in the differential diagnosis of hirsute anovulatory women

Polycystic ovarian syndrome (PCO) occurs frequently in hirsute patients. A dissociated explosive response of LH to LHRH administration has been associated with the diagnosis of PCO. Twenty-four of 58 women seen because of hirsutism were found to have ovarian dysfunction based on clinical signs such as anovulation and irregular menstrual cycles. Plasma androgen levels were elevated in the patient group. The LHRH test (200 micrograms, iv) was applied to the 24 patients and compared with 13 normal ovulatory controls. Serum FSH levels before and after the LHRH test were normal in all patients. Two patterns of LH response to LHRH stimulation were observed: an explosive response in 17 patients (delta LH: 39.4 +/- 21.8 IU/l, control group: 7.35 +/- 4.4 IU/l, P < 0.01) and a normal response in 7 patients (delta LH: 7.53 +/- 2.41 IU/l). There was a significant correlation (r = 0.63, P < 0.05) between basal LH levels and LH response to LHRH. Sensitivity and specificity calculated for basal LH levels higher than 6.0 IU/l, considering the LHRH test as reference, were 58 per cent and 85 per cent , respectively. The positive predictive value measuring the possibility of LH higher than 6.0 IU/l to be from a patient with PCO (explosive response to LHRH) was 92 per cent . These data suggest that, in hirsute anovulatory patients, basal LH levels may be a good predictor in the diagnosis of polycystic ovarian syndrome

Congenital adrenal hyperplasia among peripubertal girls with hyperandrogenism.

Fifteen girls with severe hyperandrogenism were investigated by us during the last 6 years. Thirteen of these were cases of untreated congenital adrenal hyperplasia (CAH) and 2 were cases of tumoral (one sertoli leydig cell tumor of the ovary and one adrenal adenoma) hyperandrogenism. Here we present the clinical profile and laboratory data of those with congenital adrenal hyperplasia. All the girls had masculinization of genitalia (clitoromegaly alone 5, clitoromegaly with varying degree of posterior labial fusion 8). Eleven cases had hirsutism and 9 had short stature. Two patients underwent unilateral adrenelectomy with diagnosis of adrenal adenoma. Hormonal profile confirmed the diagnosis of CAH with 21 hydroxylase deficiency (elevated 17 OHP levels with exaggerated 17 OHP response to ACTH) in 12 cases and 3 beta hydroxy steroid dehydrogenase deficiency (elevated DHEAS and 17 pregnenelone levels and exaggerated DHEAS and 17 pregnenelone response to ACTH) in one case.

Importância do cateterismo venoso percutâneo na identificaçäo da origem do hiperandrogenismo / Importance of percutaneous venous catheterization in the identification of the hyperandrogenism origin

Cateterismo venoso percutâneo seletivo (CVPS) adrenal e ovariano foi empregado na tentativa de se identificar a origem do hiperandrogenismo em três mulheres (12, 50 e 58 anos) portadoras de síndromes de hirsutismo ou virilizaçäo, nas quais a investigaçäo hormonal e a radiológica näo invasiva (ultra-sonografia e tomografia computadorizada) näo localizaram a origem da produçäo do excesso androgênico. Em todas, os níveis elevados de testosterona (T: 385, 300 e 248ng/dl) näo responderam (326, 252 e 219ng/dl) à administraçäo de dexametasona (2mg x 2d), enquanto os níveis basais de sulfato de deidroepiandrosterona (S-DHEA) (38, 130 e 180 para 21, 53 e 98µg/dl) e cortisol (F: 11,5; 20,2 e 27,5 para 0,9; 2,2 e 2,2 µg/dl) suprimiram normalmente. CVPS com determinaçöes de T e F além da relaçäo T/F) foi realizado antes, em todas, e durante cirurgia na paciente 3. Relaçäo T/F de 152,4 e 71,8 (com um gradiente venoso entre ovário e periferia [GOP] de 637 e 1.173ng/gl) identificou os ovários, esquerdo (F) e direito (D) como as fontes do excesso de andrógenos, respectivamente nos casos 1 e 2, enquanto as relaçöes T/F (87,4 e 97,2) e os GOPs (749 e 1.162ng/dl) estavam elevados em ambos os ovários na paciente 3. Assim, a lateralizaçäo da produçäo androgênica foi evidente nos casos 1 (tumor de células de Leydig do ovário E) e 2) hemangioma do ovário D com luteinizaçäo estromal), enquanto a produçäo bilateral, no caso 3, foi confirmada pela biópsia (síndrome dos ovários policísticos). Localizaçäo pré-operatória da origem do excesso androgênico pelo CVPS é essencial para de definir um tratamento apropriado às pacientes suspeitas de neoplasia androgênica, quando os métodos radiológicos näo-invasivos falham em localizar a origem do hiperandrogenismo. O CVPS näo é um procedimento amplamente disponível, nem isento de riscos, devendo, assim, ser indicdo somente na paciente hirsuta ou virilizada, cujos níveis plasmáticos basais de T e S-DHEA forem considerados "tumorais" (maiores do que 150ng/dl e 700µg/dl, respectivamente)

Hirsutismo en mujeres chilenas: importancia de la deficiencia congénita de 21-hidroxilasa de manifestación tardía / Hirsutism in Chilean women: importance of 21-hydroxylase congenital deficiency of late onset

The prevalence of steroid 21-hydroxylase (21-O Hase) deficiency of late onset was investigated in a Chilean population of hirsute women. In 33 hirsute patients, not family related, plasma 17-alpha hydroxyprogesterone (170H-P) was measured under basal conditions and after ACTH stimulation. Three cases of complete deficiency of late onset or post menarchia type were found, a prevalence of 91% similar to that reported by others. Affected patients were indistinguishable from other hirsute women, except in 170H-P concentrations after ACTH. Plasma testosterone and dihydroepiandrosterone sulphate were significantly higher in hirsute women, either deficiet of without enzyme deficiency, compared with a control group of 19 normal women. The 170H-P post ACTH levels of hirsute women who did not comply with criteria for enzyme deficiency were similar to control's. However, in these patients there was a significant correlation between hirsutism and 170H-P post ACTH, suggesting the presence of patients with mild enzyme deficiency, perhaps heterozygous for the defective gene. In conclusion, measurement of basal and post ACTH 170H-P during diagnostic work up in hirsute patients allows the detection of a significant number of cases with enzyme deficiency

Screening for late onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Basal and post-ACTH levels of 17 alpha hydroxy-progesterone (17 OHP) were determined in 53 subjects with hirsutism. Late onset congenital adrenal hyperplasia (LOCAH) was detected in five (10.6%) on the basis of elevated basal and/or ACTH stimulated levels of 17 OHP. Of the five patients, two were considered to have a heterogygous state on account of a small rise in stimulated 17 alpha OHP. Screening tests for LOCAH are essential as the clinical diagnosis is not otherwise possible for this treatable and often familial disorder.

Circulating androgens in hirsutism.

The androgen status in fifty consecutive women with hirsutism in the reproductive age group referred to the endocrine clinic was studied. Mean BMI was 24.3 +/- 5.6 kg/M2, 42% had menstrual disturbances and 30%, had severe hirsutism. The hirsute patients had significantly higher estimates of testosterone (48%), dihydrotestosterone (38%) and androstenedione (86%). Based on clinical and hormonal data, polycystic ovarian disease was diagnosed in 20 patients, nonclassical 21 hydroxylase deficiency in one and idiopathic hirsutism in 29.

Changes in the distribution of testosterone and estradiol serum fractions in hirsute women after administration of L-Thyroxine

La concentración sérica de la globulina ligadora de hormonas sexuales (SHBG) es dependiente del medio hormonal. Los estrógenos y las hormonas tireoideas aumentan los niveles mientras que los andrógenos y la hormona de crecimiento los disminuyen. El hirsutismo se asocia frecuentemente con una disminución de la SHBC sérica y un aumento de las testosterona (T) libre (L) y de la T no unida a SHBG (T no-u-SHBG) o biodisponible. Dado que la hormona tiroidea aumenta los niveles séricos de la hormona SHBG, se estudió en 10 mujeres adultas sin sobrepeso corporal con hirsutismo el efecto del tratamiento con 1-tiroxina (L-T4). La edad cronológica fue 22 ñ 2,7 años (media + DS). Cuatro pacientes presentaron síndrome de poliquistosis ovárica, 6 hirsutismo idiopático de las cuales 2 tenían oligomenorrea. Los estudios hormonales fueron realizados antes y después de un mes de tratamiento con L-T4 a una dosis de 2 microng/Kg de peso corporal. Se midieron los niveles séricos de SHBG por análisis de saturación y la testosterona (T), estradiol (E2), androstenediona, dehidroepiandrosterona (DHAS), LH, FSH, PRL, T4, T3, TSH por RIA, y se calcularon las fracciones séricas de T y E2 utilizando una ecuación matemática derivada de la ley de acción de masas. Se observaron los siguientes cambios antes y después, respectivamente (X ñ ES); SHBG 30,3 ñ 3,8 y 45,3 ñ 4,6 nmol/l (P<0,001), T n-u-SHBG 25,7 ñ 8,1 y 18,8 ñ 6 ng/dl (P<0,001), T libre 1,09 ñ 0,2 y 0,8 ñ 0,5 ng/dl (P<0,01) (Fig. 1), E2 no-u-SHBG 40,9...

Ausência de correlaçäo entre o grau de hirsutismo e os níveis de androgênios circulantes / The absence of correlation between the grade of hirsutism and the levels of circulating androgens

Säo analisados aspectos clínicos e laboratoriais de 110 pacientes hirsutas. Houve 71% de hirsutismo leve e apenas 2,7% de hirsutismo severo, näo havendo correlaçäo entre o grau de hirsutismo e o grau de distúrbio menstrual. A Síndrome dos Ovários Policísticos (SOP) esteve presente em 48,2% dos casos, sendo o hirsutismo idiopático em 15,5% das pacientes. A testosterona total esteve elevada em 32,4% das pacientes, näo tendo correlaçäo com o grau de hirsutismo

Exploración hormonal en el hirsutismo / Hormonal research in hirsutism

En el presente trabajo se estudiaron 51 mujeres hirsutas, 16 de las cuales presentaban Síndrome de Ovarios Poliquísticos (SOP) y las restantes eran idiopáticos (IH). A cada una de ellas se le determinaron los niveles en suero de testosterona (T), cortisol, hormona luteinizante (LH), hormona folículo estimulante (FSH), prolactina (PRL), sulfato de dehidroepiandrosterona (DHEA(s)), adrenocorticotrofina (ACHT) y la capacidad de unión de la proteína transportadora de andrógenos y estradiol (SHBG), antes y después de la administración de dexametasona (DXM). Se estudiaron como grupo control 5 mujeres normales. En las mujeres con HI los resultados de ACTH, PRL y cortisol fueron normales, mientras que los de T fueron normales o elevados. En las pacientes con T normal (n = 13) se obtuvieron valores disminuidos de la capacidad de unión de la SHBG, mientras que en las pacientes con T elevada (n = 22) el test de inhibición suprarrenal con DXM demostró que el exceso de T puede no ser inhibible (n = 11), inhibible (n = 6) o parcialmente inhibible (n = 5). En las pacientes de estos 2 últimos subgrupos, la estimulación adrenal con ACTH fue similar a la observada en el grupo control para los diversos esteroides estudiados. Asimismo, la inhibición de PRL con bromoergocriptina no modificó los andrógenos circulantes. En el SOP se obtuvieron valores de T significativamente elevados, los cuales fueron también inhibibles (n = 4), no inhibibles (n = 8) o parcialmente inhibibles (n = 4) con DXM. Además, en 8 de las pacientes con SOP se obtuvieron valores elevados de DHEA(s), que correlacionaron directamente con valores elevados de PRL. Las restantes 8 pacientes mostraron niveles de DHEA(s) y PRL normales. Este estudio demuestra que en los HI los resultados de T son heterogéneos, pudiendo ser normales o elevados. En este último caso nuestros resultados sugieren que el hiperandrogenismo en algunos casos es de origen adrenal, en otros de origen ovárico y en otros de origen mixto. El hiperandrogenismo de origen adrenal no parece dependiente del ACTH ni de la PRL. Nuestros resultados también demuestran que en un grupo de pacientes con SOP existe un compromiso adrenal, que pudiera correlacionarse con niveles elevados de PRL