Unexpected effect of testosterone in hypergonadotropic hypogonadism and nodular Leydig cell hiperplasia. Report of one case

ABSTRACT We report a 27 -year-old male referred because of hypergonadotropic hypogonadism with low testosterone and azoospermia. At 23 years of age, he underwent an excision of a hypoechoic 0.7 cm nodule of the left testicle. The pathological diagnosis was a Leydig cell tumor. In the right testicle, there were three nodules at ultrasound, the biggest measuring 0.6 cm. Four years later, the nodules in the right testicle were still present and the larger nodule was excised. The biopsy showed tubules with only Sertoli cells in the perinodular zone. Diffuse and nodular hyperplasia of the Leydig cells was found in the interstitium. The pathological diagnosis was Sertoli syndrome with severe hyperplasia of the Leydig cells. With testosterone therapy, LH decreased, and the nodules disappeared. Thereafter, upon interrupting therapy, LH increased, and the nodules reappeared in two occasions. Resuming testosterone treatment, the nodules disappeared again, suggesting a Leydig cell hyperplasia dependent on chronic LH stimulation.

Presentamos un varón de 27 años referido por hipogonadismo hipergonadotrófico con testosterona baja y azoospermia. El paciente tenía el antecedente de un nódulo sólido hipoecogénico de 0,7 cm en el testículo izquierdo, extirpado los 23 años de edad en el año 2002 y diagnosticado patológicamente como tumor de células de Leydig. En ese año se encontraron tres nódulos en el testículo derecho por ultrasonografía, el mayor de 0,6 cm. Cuatro años después, en 2007, los micronódulos del testículo derecho seguían presentes. El mayor de ellos fue extirpado. En la biopsia, había túbulos con solo células de Sertoli en la zona perinodular. En el intersticio había hiperplasia difusa y nodular de las células de Leydig. El diagnóstico patológico fue un síndrome de Sertoli con severa hiperplasia de células de Leydig. La terapia con testosterona disminuyó la LH y los nódulos inesperadamente desaparecieron. En dos ocasiones, al interrumpir esta terapia, la LH aumentó y los nódulos reaparecieron. Este proceso revirtió nuevamente con el uso de testosterona, sugiriendo una hiperplasia de células de Leydig dependiente del estímulo crónico de LH.

Tratamiento hormonal de la pedofilia: ¿puede curar la pedofilia con la castración química? / Pedophilia hormonal therapy: can pedophilia be cured with chemical castration

Históricamente la sociedad ha rechazado el abuso sexual de menores de 13 años, dictándose leyes al respecto. La justicia luego de un debido proceso condenaba al victimario con reclusión incluso hasta la década del 70-80, con orquiectomía. Los adelantos en neurobiología, endocrinología, sicofarmacología y sicología se consideraron las bases para tratar al pedófilo y someterlo a libertad condicional, ahorrándose el costo financiero de la reclusión de por vida. Diversos países dictaron leyes contra la conducta pedófila. En dicha legislación ejerció gran influencia la promulgación en EE.UU. (estado de Washington "sobre el ofensor sexual" y el dictamen de la Corte Suprema en 1997 en el juicio de Kansas vs Hendricks). En Chile en los 90 el caso del pedófilo apodado "Zacarach" sacó a la luz pública el tema que no se quería ver. En esa fecha se presentó al parlamento un proyecto de Ley para "curar" la pedofilia con acetato de Medroxiprogesterona imitando legislación de EE.UU. Causó sorpresa en el medio endocrinológico que se usara terapia hormonal como "cura" de la pedofilia. Se ha utilizado en varios países la castración química producida por gestágenos o agonístas del GnRH más antiandrógenos (acetato de Ciproterona), para inhibir la secreción y acción de la testosterona disminuyendo líbido y erección. No se ha demostrado que exista curación de la orientación pedófila y existen dudas de la prevención primaria y secundaria de la pedofilia. Pese al adelanto tecnológico en neurociencias para estudio de las zonas vinculadas a la sexualidad, aún no existen marcadores que permitan diagnosticar o pronosticar futuros resultados de la terapia. El tratamiento médico de la pedofilia no garantiza curación ni prevención del delito pedofílico.

Historically, society has rejected sexual abuse of children under 13, with there having been laws enacted in this regard. The judicial system, after a due process, condemned the perpetrator with reclusion and even up until the decades of the 70s and 80s with orchiectomy. Advances in neurobiology, endocrinology, psychopharmacology and psychology were considered the basis for treating the pedophile and putting them on probation, saving the financial cost of imprisonment for life. Multiple countries have enacted laws against pedophilic behaviour. Such legislation was greatly influenced by the enactment in the USA (state of Washington "on the sex offender" and the ruling of the Supreme Court in 1997 in the trial of Kansas against Hendricks). In Chile in the 90s, the case of a pedophile nicknamed "Zacarach" brought to light an issue that nobody wanted to see. Around that time, a bill was presented to Parliament to try and "cure" pedophilia with Medroxyprogesterone acetate, imitating US legislation. It was a surprise in the endocrinological world that hormonal therapy would be used as a "cure" for pedophilia. Chemical castration produced by gestagens or GnRH agonists plus antiandrogens (Cyproterone acetate) has been used in several countries to inhibit the secretion and action of testosterone, reducing libido and erection. It has not been proven that there is a cure for pedophile orientation and there are doubts about the primary and secondary prevention of pedophilia. Despite technological advances in neurosciences for the study of the zones pertaining to sexuality, there are still no indicators that allow for diagnosis or prediction of future results of therapy. The medical treatment of pedophilia does not guarantee cure or prevention of pedophilic crime.

Visión personal del rol de SOCHED en la tramitación parlamentaria de la Ley de Identidad de Género (2013 - 2018) / Personal vision of the role of SOCHED in the parliamentary procedure of the Gender Identity Law (2013 - 2018)

SOCHED debe preocuparse del desarrollo profesional de sus miembros y de alzar su voz ante temas endocrinológicos relevantes para la sociedad chilena. La invisibilidad a todo nivel del tema trans nos encontró mal posicionados, pues la nula formación en este aspecto cerraba el ciclo de su desconocimiento en pre y post grado. Las solicitudes de muchos años para discutir el tema en nuestros congresos había sido sistematicamente rechazadas o ignoradas. El desconcierto y alarma produjeron las consultas de personas trans que nos solicitaban la fase endocrinológica de la readecuación corporal, revelando la falta de preparación para comprenderlos y tratarlos. El proyecto de ley de identidad de género puso en evidencia además la falta de estructura de SOCHED para actuar en el campo político y parlamentario. Reseñamos la actuación de SOCHED en este proceso y las medidas sugeridas sobre cambios a realizar y puntos débiles a corregir. Se debe evitar su repetición , por ejemplo si se propusiera el tratamiento hormonal de la pedofilia.

SOCHED must worry about the professional development of its members and to raise its voice before the endocrinological issues for the Chilean society. The invisibility at all levels of the trans aspect found us bad positioned, as the null formation in this aspect closed the cycle of its disconnection in pre-and post-grade. The request of many years to discuss this topic in our congresses had been systematically rejected or ignored. The alarm and disconcerate caused by the questions of trans persons who requested us the endocrinological phase of body readjustment, revealing the failure of preparation to understand and treat them. The gender identity law project put evidence also the lack of SOCHED structure to act in the political and parliamentary field. We review the action of SOCHED in this process and the measures suggested about changes to be implemented and the weaknesses points to correct. their repetition must be avoided, for example if the hormone treatment of the pedophilia is proposed.

Trastorno de identidad de género. Parte II: terapia endocrinológica en el proceso de readecuación corporal / Gender identity disorder. Part II: endocrine therapy in the process of body readjustment

Endocrinology step of transgender readjustment therapy is made according to previously published in the part 1 of article: “gender identity disorder in rev. chil. endocrinol. diabetes 2015, 8 (4): 167-173.During started puberty in Tanner stage 2-3, the persistence of the experience that their identity male or female gender is not coherent with its bodily, authorize to start the endocrinological therapy, as an important step of body readjusting. In the process of transition from male to female or female to male, should stop pubertal development, what we do with GNRH analogues: intramuscle leuprolideor triptorelin 11.25 mg. every 12 weeks or with medroxyprogesterone acetate 150 mg. monthly. This process continues until 16 years, adding antiandrogen, preferably spironolactone in the process of body readjusting of male to female. At 16 years old, starts the cross hormonal therapy to masculinizing or feminizing. Maintaining gonadotrophin suppression, female to male, testosterone undecanoate or other injectable testosterone esters is administered, customizing the date of administration and inMale to female, daily use of oral estradiol valerate or transdermal gel. Plasma levels of estradiol andtestosterone should not be located in high or supraphysiological range to avoid thromboembolism or polycythemia risk in those who receive testosterone. Should to be explained the time to obtain the bodily effects, achieving a realistic attitude of the goals and the need for regular checks. Attendance to emotional changes, mainly to meet the social gender role. The laboratory, metabolic, hormonal, hemogram and electrolytic changes are evaluated. To be indicated bone densitometry and study images of internal genitals and breasts are necesary...

Trastorno de identidad de género: Parte I. Definición, epidemiología, etiología, rol del endocrinólogo en diagnóstico y tratamiento / Gender identity disorders: definition, etiology,epidemiology and role of the endocrinologist in theirmanagement

Gender identity disorders (GID) or transsexuality have been a latent issue in Chile 20 years after the first sex reassignment treatment in 1973. Sexual minority groups have posed the problem and even present a bill for civil sexual change. Since the nineties, the number of consultants due to gender identity problems has increased steadily, including children and adolescents. The lack of medical expertise in the area, requires urgent training programs. The first part of this manuscript will deal with the definition, epidemiology, etiology and role of the endocrinologist in the process of sexual reassignment among patients with gender identity disorders. We review sexual differentiation, brain sexual dimorphism and Sexual Development Disorders (SDD) aiming to understand the neurobiological causes of GID and to perform a better differential diagnosis with Sexual Development Disorders. GID are not a psychiatric disease. However the suffering caused by stigmatization, exclusion andabuse generate emotional problems (gender dysphoria). SDD has a genetic and hormonal basis in most cases. Its clinical expression at birth can cause an erroneous civil sex assignation or a discordant civil sex with the sexual identity of the person when there is a surgical correction. GIS without gender dysphoria was excluded as a mental disease from DSM-V and it will also be excluded from the eleventh version of the international classification of diseases. It will maintained as a condition that should be differentiated from SDD and whose treatment should be financed by health systems.

Hiperprolactinemia y disfunción sexual en el varón / Hyperprolactinemia and sexual dysfunction among males

Hyperprolactinemic males usually have a hypoactive libido and less commonly, erectile dysfunction and disturbances of orgasm and ejaculation. Hyperprolactinemia alters the balance between neurotransmitters, neuropeptides and hormones involved in libido and erection, affecting dopaminergic tone. An imbalance between dopamine, that stimulates sexual function and serotonin that inhibits it, is generated. In the central nervous system, hyperprolactinemia inhibits centers controlling sexual desire and erection. At the neuroendocrine level, it decreases GnRH, LH and testosterone pulses, resulting in a hypogonadotrophic hypogonadism. Erection is also inhibited peripheral actions of low testosterone and high prolactin levels. There is a disturbance of penile smooth muscle relaxation and of the parasympathetic sacrum-penis reflex arch. In experimental animals, acute hyperprolactinemia hampers the central erection mechanism whereas in chronic conditions, peripheral disturbances also occur. Even correcting low testosterone levels, the adverse effects of hyperprolactinemia on sexual function persist. The use of dopaminergic agonists may achieve normal prolactin and testosterone levels resulting in normal sexual function. Chronic hyperprolactinemia results in progressive deterioration of sexual function and a higher hypothalamic damage that does not respond to clomiphene. In this situation and in the presence of sellar tumors that destroy gonadotrophic cells, there is indication of androgenic replacement maintaining the use of dopaminergic agonists...

Alteración de la fertilidad masculina por hiperplasia suprarrenal congénita: Azoospermia reversible con terapia de glucocorticoide / Congenital adrenal hyperplasia causing male infertility: Report of one case

In males, congenital adrenal hyperplasia due to 21 hydroxylase deficiency is associated to normal fertility or infertility caused by a hypogonadotrophic hypogonadism (HH) or gonadal damage caused by intratesticular adrenal remnants. We report a 29-year-old male with azoospermia, without any important personal or family background. Physical examination was normal, his height was 150 cm and his testicular volume was 10 ml (normal 15 to 25 ml). Laboratory showed a normal testosterone and FSH and LH in the low normal limit. These results discarded a HH, whose diagnostic requirements are a low testosterone and inadequately normal or low gonadotrophins. A testicular biopsy was informed as compatible with HH. A 21 hydroxylase deficiency was suspected and confirmed with extremely high levels of 17 hydroxyprogesterone at baseline and after stimulation with fast acting ACTH. Clomiphene citrate did not increase testosterone or gonatrophin levels. Testicular ultrasound discarded the presence of adrenal nodules. Betametasone therapy resulted in a normal testicular development, normalization of sperm count, reduction of 17 hydroxyprogesterone and testosterone levels with an ulterior rise of the latter. Spontaneous paternity was achieved twice. It must be remembered that in cases of azoospermia due to congenital adrenal hyperplasia, testosterone produced by adrenal glands hinders the laboratory diagnosis of HH.

Terapia médica de la ginecomastia con tamoxifeno. Influencia del volumen y duración de la ginecomastia en el resultado terapéutico / Influence of size and duration of gynecomastia on its response to treatment with tamoxifen

Background. Gynecomastia is treated when it is painful, there are psychosocial repercussions or it does not revert in less tan two years. It is treated with the antiestrogenic drug tamoxifen, but there are doubts about its effectiveness in high volume gynecomastias or in those lasting more than two years. Aim. To assess the effectiveness and safety of tamoxifen for gynecomastia and the influence of its volume and duration on the response to treatment. Patients and methods. Forty three patients with gynecomastia, aged 12 to 62 years, were studied. Twenty seven patients had a pubertal physiological gynecomastia, in eight it was caused by medications, in four it was secondary to hypogonadism, in three it was idiopathic and in one it was due to toxic exposure. Twenty patients had mastodynia and in 33, gynecomastia had a diameter over 4 cm. It lasted less than two years in 30 patients, more than two years in nine and four did not recall its duration. All were treated with tamoxifen 20 mg/dayfor 6 months. A follow up evaluation was performed at three and six months of treatment. Results. Mastodynia disappeared in all patients at three months. At six months gynecomastia disappeared in 26 patients (62 percent), but relapsed in 27 percent. All gynecomastias caused by drugs with antiandrogen activity disappeared. Fifty two percent of gynecomastias over 4 cm and 90 percent of those of less than 4 cm in diameter disappeared (p<0.05). Fifty six percent of gynecomastias lasting more than two years and 70 percent of those of a shorter duration disappeared (p=NS). Two patients had diarrhea or flushes associated to the therapy. Conclusions: Tamoxifen is safe and effective for the treatment of gynecomastia. Larger lesions have a lower response to treatment.

Etiología de la ginecomastía: Importancia de no subdiagnosticar una ginecomastia patológica / Etiological study of gynecomastia: Results of a prospective study and recommendations

Background : Gynecomastia can be physiological or pathological. A limited study of gynecomastia is recommended during puberty and in the elderly, ages in which gynecomastia is usually considered physiological. Other authors suggest that this condition should be studied when it is painful, rapidly growing, of recent onset, when its diameter is more than 4 cm and when is associated to testicular masses. Aim: To investigate the causes of gynecomastia and to evaluate the above mentioned criteria to exclude pathological conditions. Material and methods: Prospective study of 117 patients aged 10 to 83 years, consulting for gynecomastia. All were subjected to a standardized study including a clinical examination and measurement of plasma estradiol and testosterone levels. Results: Forty one percent of gynecomastias were considered pathological and the rest, physiological. Among pathological conditions, 18 patients had an endocrine etiology (hypogonadism in ten patients, estrogen secreting tumors in three, hyperestrogenism of unknown etiology in four and peripheral resistance to androgens in one), in 17 it was secondary to medications and in 13 it was secondary to other causes (idiopathic, pesticide exposure, alcoholism, diabetes or re feeding). In 79 percent of 86 patients of less than 20 years, the condition was physiological and in four of five elderly subjects, it was pathological. Thirty nine percent of pathological gynecomastias lacked the signs and symptoms that according to authors, should prompt a thorough study. Conclusions: All patients with gynecomastia should be studied with a complete medical history and the measurement of estradiol and testosterone levels. The criteria proposed to conduct minimal studies in gynecomastia, would miss a large volume of pathological conditions.

Actualización de la terapia del hirsutismo / Update in the treatment of hirsutism

El hirsutismo es un síntoma del hiperandrogenismo femenino a nivel dermatológico y constituye en sí mismo un problema estético y psicosocial para la mujer. Se analizan las drogas involucradas en el tratamiento, el mecanismo de acción y efectos colaterales. La eficiencia y seguridad de ciproterona, espironolactona y flutamida en 3 grupos de mujeres hirsutas se comparan con los datos de la literatura.

Eficacia de la flutamida en el tratamiento del hirsutismo: contribución del uso combinado con anticonceptivos orales en mujeres normoandrogénicas / Effectiveness of flutamide alone or combined with oral contraceptives in the treatment of hirsutism in women

Background: Flutamide is an antiandrogen devoid of other hormonal effects, except for a decrease in the secretion of adrenal androgens such as dehydroepidandrosterone sulphate (DHEA-s) and androstenedione. Aim: To assess the effectiveness of flutamide in the treatment of hirsutism, used as monotherapy or combined with oral contraceptives (OC). Patients and methods: Women with peripheral hirsutism (defined as the presence of normal serum androgen levels and normal ovulatory menstrual cycles) were assigned to receive flutamide alone (500 mg/day) or flutamide plus an OC (ethynylestradiol 0.03 mg and desogestrel 150 µg). Hirsute with hyperandrogenism (polycystic ovary syndrome) were assigned to receive flutamide plus an OC. The degree of hirsutism was assessed using a clinical score (Moncada) at three, six and twelve months of therapy. Results: Twenty five women with peripheral hirsutism received flutamide alone and 18 receive flutamide plus the contraceptive. Eighteen women with polycystic ovary syndrome were studied. At three months, the reduction in hirsutism was 11.2, 15.9 and 24.7 percent in women with peripheral hirsutism receiving flutamide alone or flutamide plus OC and in hyperandrogenic women receiving flutamide plus OC, respectively. At twelve months, the figures were 57.2, 57.3 and 52.5 percent respectively. In hyperandrogenic women, at baseline and three months, serum testosterone levels were 0.96 and 0.42 ng/ml and serum DHEA-s levels were 2,980 and 1,490 ng/ml respectively. No collateral effects of treatment or elevations in serum transaminase levels were observed. Conclusions: Flutamide is effective in the treatment of hirsutism in women with normal or elevated androgen levels. Adding OC did not improve the efficacy of the drug.

Hipogonadismo asociado a la senilidad en el varon (climaterio masculino - andropausia - Adam) / hypogonadism associated to male senescense (male climateric -andropause - ADAM

Actualmente se acepta que en hombres envejecidos sanos existe un descenso progresivo aunque no universal, de la testosterona total y libre, llegando un 20 a 30 por ciento a rango hipogonádico. El diagnóstico de hipogonadismo asociado a envejecimiento es de exclusión. Se requieren estudios para poder diferenciar si los síntomas compatibles con hipogonadismo se deben a falla testosterónica, envejecimiento o alteración de otros ejes endocrinos.

Evolución y pronostico de los trastornos menstruales en la adolescencia / Evolution and prognosis of menstrual disorders in adolescence

Los trastornos menstruales son muy frecuentes en los primeros 5 años de edad ginecológica, evolucionando desde un alto porcentaje de ciclos anovulatorios en el primer año postmenárquica a una mayoría de ciclos ovulatorios a los 6 años de edad ginecológica. Estas irregularidades menstruales pueden corresponder a un proceso de maduración del eje hipotálamo-hipófisis-gonadal, o señalar la aparición de cuadros como el síndrome de ovario poliquístico. Otra gran causa de amenorrea y oligoamenorrea desde la pubertad, es el trastorno funcional hipotalámico, en que excluidos todo otro trastorno endocrino, enfermedad sistémica y cuadro orgánico, una alteración funcional en las neuronas del GNRH produce insuficiencia o disfunción hipotalámica de acuerdo al grado de compromiso de la pulsatilidad del GNRH. Se presenta las características clínicas y evolución de un grupo de pacientes con disfunción hipotalámica diagnosticada en la adolescencia, y reevaluadas en la vida adulta.

Menstrual disturbances are very cycles frecuent during the first 5 years after menarche. High prevalence of anovulatory cycles occur in the first year. In contrast high prevalence of ovulatory cycles occur at 6 years postmenarchal. Menstrual disturbances have been associated with hypothalamic-pituitary-ovarian axis madurative phenomenon or pathology of pubertal root as polycystic ovary syndrome. Hypothalamic dysfunction is other cause of menstrual disturbances when other diseases have been discarded. This condition is caracterized by a alteration of the GNRH pulse generation system. We report the natural history of reproductive and menstrual evolution in women with hypothalamic dysfunction developed in adolescence.

Efectos del valerato de estradiol ciproterona sobre el síndrome climaterio y parámetros bioquímicos en mujeres chilenas / Effects of estradiol valerate and ciproterone acetate on climateric syndrome and biochemical parameters in Chilean women

La menopausia se asocia a un demostrado aumento del riesgo de enfermedad cardiovascular y de osteoporosis, lo que justifica el uso de terapia hormonal de reemplazo. Como ésta se plantea por tiempo prolongado, debe ser efectiva en prevenir las complicaciones y en suprimir el síndrome climatérico. Se estudió la eficacia de la asociación de valerato de estradiol (VE) y acetato de ciproterona (CPA) en la reducción de los síntomas asociados a menopausia. Se analizaron, prospectivamente, 342 mujeres durante 6 meses, consignando la intensidad de sus síntomas y los cambios en peso, presión arterial y parámetros bioquímicos. Las oleadas de calor, así como otros síntomas y signos, disminuyeron en intensidad. No hubo diferencia significativa en la evolución del peso ni de la presión arterial, aunque sí en algunos parámetros del perfil lipídico y hepático. Se concluye que la asociación VE y CPA reduce la intensidad de los síntomas climatéricos en el grupo estudiado

Remisión prolongada del hiperandrogenismo femenino después de suspender la terapia con glucocorticoides / Prolonged remission of female hyperandrogenism after discontinuing glucocorticoid therapy

Adrenal androgen hypersecretion either produced by genetic defects or reticular disfunction, is reduced by exogenous glucocorticoid administration and as with any suppression therapy, it should relapse when the therapy is discontinued. However, prolonged remissions of adrenal androgen hypersecretion after discontinuing glucocorticoids have been described. We report 15 patients with adrenal hyperandrogenism and elevated levels of dehydroepiandrosterone sulfate that received treatment with dexamethasone. After 1 month of treatment with dexamethasone 0.5 mg/day, dehydroepiandrosterone sulfate levels returned to normal and remained so during a mean of 19 months receiving dexamethasone 0.25 mg/day. One year after discontinuing therapy, hormone levels continued within normal range in all patients. It is concluded that a long remission period of adrenal hyperandrogenism was achieves after discontinuing glucocorticoid therapy

Amenorrea: análisis clínico y diagnóstico de 227 casos / Amenorrhea: clinical and diagnostic analysis

Se practicó una revisión analítica de 227 pacientes amenorreicas, primarias y secundarias, atendidas en el Consultorio Endocrino-Ginecológico de los hospitales San Francisco de Borja y Paula Jaraquemada entre los años 1974-1986 con los objetivos de: a) averiguar la frecuencia de cada una de ellas; b) determinar los diagnósticos y sus frecuencias, tanto en amenorreas primarias como en secundarias y c) conocer los diagnósticos más importantes en las asociaciones C1 = amenorrea e hirsutismo; C2 = amenorrea y galactorrea; C3 = amenorrea y baja de peso y C4 = amenorrea de inicio post-parto. Los resultados fueron: a) la amenorrea secundaria fue más frecuente que la primaria con una relación 6/1 en nuestro estudio; b) en las amenorreas primarias los principales diagnósticos fueron: falla ovárica por disgenesia gonodal y amenorrea de causa uterina, tanto agenesia como endometritis TBC en igual porcentaje, y en las secundarias el PCO seguido de hiperprolactinemia y difunción hipotalámica. Se realizó un análisis comparativo de estos hallazgos con otras series nacionales y extranjeras. c) C1 = la asociación de amenorrea con hirsutismo más virilización es causada básicamente por SAG, así como la misma, sin virilización, por el PCO. C2 = en amenorrea-galactorrea, la gran causa es la hiperprolactinemia; C3 = en amenorrea y baja de peso, tiene un papel preponderante la anorexia nerviosa y C4 = en amenorrea del inicio postparto, en nuestro universo, el principal diagnóstico es el síndrome de Sheehan