Association of Soy and Exclusive Breastfeeding With Central Precocious Puberty: A Case-Control Study.

Introduction: While soy is suggested as a possible risk factor, exclusive breastfeeding (EBF) has a likely protective effect in precocious puberty. Our aim was to evaluate the association between both of these variables with central precocious puberty (CPP). Methods: We performed a retrospective, case-control study. A total of 161 girls were divided into two groups: 84 patients diagnosed with CPP composed the case group and 77 patients without the diagnosis of CPP (had gone through normal onset of puberty) were the control group. Results: Our control group had a higher presence of EBF >6 months, which was an important protective factor for CPP (OR: 0.5; IC 95%: 0.3-0.9, p = 0.05) and also correlated negatively with the presence of it (r = -0.2; p < 0.05). Oppositely, the use of soy was significantly higher in the CPP group, (OR: 3.8; IC 95%: 1.5-6, p < 0.05) and positively correlating (r = 0.2; p < 0.01) with the presence of CPP. Duration of soy intake (years) correlated with bone age (r = 0.415; p < 0.05). A logistic regression was performed to evaluate the effects of EBF duration and soy on CPP. The model was significant (x² (2) = 20,715, p = <0.001) and explained 12.2% (Nagelkerke R2) of the variance, correctly classifying 62.5% of cases. EBF was associated with a reduction of likelihood of having CPP [OR = 0,187 (CI = 0.055-0,635); Wald = 7,222, p = 0.007], while soy intake increased the risk [OR = 3.505 (CI) = 1,688-7,279, Wald = 11,319, p = 0.001]. Conclusion: Our data found the use of soy was associated with CPP. Additionally, EBF was pointed as a protective factor. However, future prospective studies are needed to clarify this issue.

One-year treatment with gonadotropin-releasing hormone analogues does not affect body mass index, insulin sensitivity or lipid profile in girls with central precocious puberty.

Background Puberty is associated with a physiological decline in insulin sensitivity (IS). Overweight (OW) and obesity (OB) are common among girls with central precocious puberty (CPP). CPP is considered a risk factor for metabolic diseases. The aim of this study was to assess surrogate measures of IS, body mass index (BMI) and other metabolic parameters in CPP girls at diagnosis and during treatment with gonadotropin-releasing hormone analogues (GnRHa). Methods We present a prospective longitudinal study of CPP girls. The standard oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR), whole-body IS index (ISI) and fasting lipid profiles were evaluated at diagnosis, and at 6 and 12 months of treatment. Results Nineteen CPP girls were included; 17 were evaluable. At baseline, seven patients had normal weight (NW), five were OW and five were OB. During GnRHa treatment no significant changes were observed in BMI, HOMA-IR or ISI when considering the whole group. Whereas, when we analyzed patients according to BMI status, in NW patients, BMI increased significantly with no changes in HOMA-IR or ISI along treatment. In the OW/OB group, no significant differences were observed in BMI, HOMA-IR or ISI. Conclusions Girls with CPP showed a high frequency of OW/OB and a high prevalence of IR. GnRHa did not affect BMI, IS or the lipid profile when considering the whole cohort of patients. However, there was an increase in BMI in NW girls but not in OW/OB patients.

High DHEAS Level in Girls Is Associated with Earlier Pubertal Maturation and Mild Increase in Androgens throughout Puberty without Affecting Postmenarche Ovarian Morphology.

OBJECTIVE: To assess whether the presence of high DHEAS (HD) at 7 years determines different timing, sequence, and rate of pubertal events, and whether it is associated with adrenal and/or ovarian hyperandrogenism and changes in ovarian morphology throughout puberty. METHODS: In a longitudinal study of 504 girls, clinical evaluation was performed every 6 months after 7 years of age to detect Tanner stages; hormonal and anthropometric measurements were conducted at thelarche (B2), breast Tanner 4 (B4), and 1 year after menarche; ultrasonographic evaluation was also performed after menarche. The girls were classified as HD if their DHEAS level was >42.1 µg/dL (>75th percentile) around 7 years. RESULTS: HD around 7 years is associated with a younger age at thelarche, pubarche, and menarche. Girls with HD had higher androstenedione and total testosterone levels, and a higher free androgen index (FAI), and lower levels of antimüllerian hormone (AMH) at B2, and higher levels of androstenedione and FAI at B4 and after menarche. All these results were significant even after adjusting for body mass index, age at first DHEAS determination, and birth weight. One year after menarche, polycystic ovarian morphology was detected in 7.6 and 7.3% of the HD and the normal DHEAS group, respectively. Ovarian volume was correlated with AMH, testosterone, androstenedione, and LH but not with DHEAS around 7 years. CONCLUSION: Prepubertal HD in normal girls was associated with earlier thelarche, pubarche, and menarche, and a mild androgen increase throughout puberty. We believe continuous follow-up of this cohort is important to prospectively address the interrelationships between biochemical adrenarche and early growth as determinants of ovarian function.

Hipertricosis cubital en una paciente con pubarquia precoz: Caso clmico / Hypertrichosis cubiti in a girl with precocious puberty: Case report

La hipertricosis cubital es un aumento localizado de la densidad, longitud y espesor del vello. Es una entidad benigna con muy escasos pacientes descritos en la literatura médica (alrededor de medio centenar). La mitad de los casos descritos asocian otros defectos o malformaciones, y la otra mitad son problemas puramente estéticos. La pubarquia precoz en niñas se define como el inicio del vello púbico antes de los 8 años de edad. Se presenta a una paciente de 6 años con la asociación no descrita previamente de hipertricosis cubital y pubarquia precoz.

Hypertrichosis cubiti is a localized increase in hair density, length and thickness. It is an uncommon and benign entity with very few patients described in the medical literature (more or less than half a hundred). Half of the described patients associate other defects or malformations and the other half are purely aesthetic cases. Early pubarche in girls is defined as the onset of pubic hair before 8 years of age. We present a six-year-old patient with the association not previously described of hypertrichosis cubiti and precocious pubarche.

[Hypertrichosis cubiti in a girl with precocious puberty: Case report]. / Hipertricosis cubital en una paciente con pubarquia precoz: Caso clmico.

Hypertrichosis cubiti is a localized increase in hair density, length and thickness. It is an uncommon and benign entity with very few patients described in the medical literature (more or less than half a hundred). Half of the described patients associate other defects or malformations and the other half are purely aesthetic cases. Early pubarche in girls is defined as the onset of pubic hair before 8 years of age. We present a six-year-old patient with the association not previously described of hypertrichosis cubiti and precocious pubarche.

La hipertricosis cubital es un aumento localizado de la densidad, longitud y espesor del vello. Es una entidad benigna con muy escasos pacientes descritos en la literatura médica (alrededor de medio centenar). La mitad de los casos descritos asocian otros defectos o malformaciones, y la otra mitad son problemas puramente estéticos. La pubarquia precoz en niñas se define como el inicio del vello púbico antes de los 8 años de edad. Se presenta a una paciente de 6 años con la asociación no descrita previamente de hipertricosis cubital y pubarquia precoz.

Pubertad precoz y temprana: evaluación y tratamiento / Early puberty: evaluation and treatment

El autor de este artículo repasa las características clínicas de la pubertad precoz y la pubertad temprana, las pruebas diagnósticas indicadas en la evaluación de los pacientes que la presentan y las recomendaciones actuales de tratamiento. (AU)

The author of this article reviews the clinical features of early puberty, the diagnostic tests for the patients ́ evaluation andthe current treatment recommendations. (AU)

Pubertad precoz: no solo una cuestión de edad / Precocious puberty: not only a matter of age

Se ha observado que el inicio de la pubertad en las niñas se viene produciendo cada vez a edad más temprana, motivando la preocupación de los padres y la búsqueda de atención ante la posibilidad de pubertad precoz. A la actualidad, el diagnóstico de pubertad precoz central y pubertad normal de inicio temprano mantiene puntos de corte cronológicos establecidos hace más de un lustro; esto, a pesar de los cambios seculares descritos en diversas poblaciones del orbe. La importancia de diferenciar un evento fisiológico de uno patológico es la necesidad de adoptar una decisión oportuna de tratamiento con la finalidad de evitar compromiso de la talla final, alteraciones en la vida reproductiva y riesgo de enfermedades a futuro, como las enfermedades cardiovasculares y cáncer de mama en la vida adulta. Por lo tanto, los límites para el inicio de la pubertad, basados en normalidad bioestadística poblacional, no deberían traducirse únicamente en el establecimiento de límites de edad cronológica, debido al riesgo de diagnósticos erróneos. En el presente artículo hacemos una revisión de los acontecimientos relacionados a la pubertad en sus formas fisiológicas y patológicas en niñas, presentando los acuerdos y controversias descritos en la literatura científica...

The onset of puberty in girls has been occurring each time at a younger age, generating concern among parents and seeking healthcare for possible precocious puberty. Nowadays diagnosis of central precocious puberty (CPP) and early puberty onset have chronological cutoff points established over five years ago and despite secular changes described in various populations of the world. The importance of differentiating a physiological event from a pathogenic one is mainly because of the need of timely decision to begin treatment in order to prevent height compromise, reproductive system alterations and risk of future diseases like cardiovascular disease and breast cancer in adulthood. Limits for puberty onset based on biostatistics in normal population should not be applied only to establish limits of chronological age because the risk of a wrong diagnosis. In this article physiological and pathological events of puberty in girls will be reviewed; agreements and disputes described in scientific literature will be presented...

Bone mineral density and body composition in girls with idiopathic central precocious puberty before and after treatment with a gonadotropin-releasing hormone agonist.

OBJECTIVES: Idiopathic central precocious puberty and its postponement with a (gonadotropin-releasing hormone) GnRH agonist are complex conditions, the final effects of which on bone mass are difficult to define. We evaluated bone mass, body composition, and bone remodeling in two groups of girls with idiopathic central precocious puberty, namely one group that was assessed at diagnosis and a second group that was assessed three years after GnRH agonist treatment. METHODS: The precocious puberty diagnosis and precocious puberty treatment groups consisted of 12 girls matched for age and weight to corresponding control groups of 12 (CD) and 14 (CT) girls, respectively. Bone mineral density and body composition were assessed by dual X-ray absorptiometry. Lumbar spine bone mineral density was estimated after correction for bone age and the mathematical calculation of volumetric bone mineral density. CONEP: CAAE-0311.0.004.000-06. RESULTS: Lumbar spine bone mineral density was slightly increased in individuals diagnosed with precocious puberty compared with controls; however, after correction for bone age, this tendency disappeared (CD = -0.74 + 0.9 vs. precocious puberty diagnosis = -1.73 + 1.2). The bone mineral density values of girls in the precocious puberty treatment group did not differ from those observed in the CT group. CONCLUSION: There is an increase in bone mineral density in girls diagnosed with idiopathic central precocious puberty. Our data indicate that the increase in bone mineral density in girls with idiopathic central precocious puberty is insufficient to compensate for the marked advancement in bone age observed at diagnosis. GnRH agonist treatment seems to have no detrimental effect on bone mineral density.

Bone mineral density and body composition in girls with idiopathic central precocious puberty before and after treatment with a gonadotropin-releasing hormone agonist

OBJECTIVES: Idiopathic central precocious puberty and its postponement with a (gonadotropin-releasing hormone) GnRH agonist are complex conditions, the final effects of which on bone mass are difficult to define. We evaluated bone mass, body composition, and bone remodeling in two groups of girls with idiopathic central precocious puberty, namely one group that was assessed at diagnosis and a second group that was assessed three years after GnRH agonist treatment. METHODS: The precocious puberty diagnosis and precocious puberty treatment groups consisted of 12 girls matched for age and weight to corresponding control groups of 12 (CD) and 14 (CT) girls, respectively. Bone mineral density and body composition were assessed by dual X-ray absorptiometry. Lumbar spine bone mineral density was estimated after correction for bone age and the mathematical calculation of volumetric bone mineral density. CONEP: CAAE-0311.0.004.000-06. RESULTS: Lumbar spine bone mineral density was slightly increased in individuals diagnosed with precocious puberty compared with controls; however, after correction for bone age, this tendency disappeared (CD = -0.74 + 0.9 vs. precocious puberty diagnosis = -1.73 + 1.2). The bone mineral density values of girls in the precocious puberty treatment group did not differ from those observed in the CT group. CONCLUSION: There is an increase in bone mineral density in girls diagnosed with idiopathic central precocious puberty. Our data indicate that the increase in bone mineral density in girls with idiopathic central precocious puberty is insufficient to compensate for the marked advancement in bone age observed at diagnosis. GnRH agonist treatment seems to have no detrimental effect on bone mineral density.

[Thelarche and nutritional status: an epidemiological study of two ethnic groups]. / Telarquia y estado nutricional: Estudio epidemiológico en dos grupos étnicos.

BACKGROUND: Improvements in environmental conditions may result in an earlier onset of thelarche. However, its onset is not homogeneous among different population groups. AIM: To assess the relationship between nutritional status, ethnicity and age of thelarche. MATERIAL AND METHODS: Cross-sectional study of girls in second through sixth grade, attending 165 schools located in Chile's Araucania region. Of these, 231 girls who presented thelarche (breast button) were selected. The girls' surnames were used to identify their ethnicity: indigenous had three or four last names of Mapuche indigenous origin (n =113), while non-indigenous were those who only had Chilean-Spanish last names (n =118). Weight, height, waist circumference and skinfold thicknesses were measured and socio-economic background information was collected through a home interview. RESULTS: The median age of thelarche was 10 years and 4 months, regardless of ethnic group. Multivariant models showed that an increase of one z score unit of body mass index (BMI) decreased the median age of thelarche by 5.6 months (CI: -7.24 to -3.90), controlling for the effect of different covariables. A decrease in one z score of height retards the median age of thelarche by 5.5 months (CI: 4.02 to 6.98). Ethnicity did not influence the age of thelarche. CONCLUSIONS: The age of thelarche found by us is similar to that reported in international studies, it comes earlier as weight increases, is delayed as height decreases and is not related to ethnicity.

Ultrassonografia pélvica em crianças e adolescentes: [revisão] / Pelvic ultrasonography in children and teenagers: [review]

O conhecimento das mudanças que ocorrem no útero e ovários durante a puberdade é fundamental ao investigar alterações da pelve feminina em crianças e adolescentes. O exame ultrassonográfico nestas pacientes é rotineiramente realizado por via abdominal usando o líquido da bexiga como uma janela ultrassônica, embora possa ser algumas vezes realizado pela via vaginal em adolescentes sexualmente ativas. As principais indicações para ultrassonografia pélvica em crianças e adolescentes são a puberdade precoce ou atrasada, dor ou massas pélvicas, genitália ambígua, sangramento vaginal em crianças e amenorreia primária. Neste artigo relatamos a técnica do exame, além de descrever os achados mais freqüentes.

The knowledge of uterine and ovarian changes in the puberty is essential in the investigation changes in the female pelvis of children and teenagers. In these patients, pelvic ultrasonography is routinely performed with a full bladder to produce an acoustic window, although this examination may also be performed with endovaginal approach in sexually active teenagers. Main indications for pelvic ultrasonography in children and teenagers are either early or delayed puberty, pelvic pain or tumors, ambiguous genitalia, vaginal bleeding in children, and primary amenorrhea. In the present paper, the authors describe the scanning technique and the most frequent sonographic findings.

Telarquia y estado nutricional: Estudio epidemiológico en dos grupos étnicos / Thelarche and nutritional status: An epidemiológical study of two ethnic groups

Background: Improvements in environmental conditions may result in an earlier onset of thelarche. However, its onset is not homogeneous among different population groups. Aim: To assess the relationship between nutritional status, ethnicity and age of thelarche. Material and methods: Cross-sectional study of girls in second through sixth grade, attending 165 schools located in Chile's Araucania region. Of these, 231 girls who presented thelarche (breast button) were selected. The girls' surnames were used to identify their ethncity: indigenous had three or four last names of Mapuche indigenous origin (n =113), while non-indigenous were those who only had Chilean-Spanish last names (n =118). Weight, height, waist circumference and skinfold thicknesses were measured and socio-economic background information was collected through a home interview. Results: The median age of thelarche was 10 years and 4 months, regardless of ethnic group. Multivariant models showed that an increase of one z score unit of body mass index (BMI) decreased the median age of thelarche by 5.6 months (CI: -7.24 to -3.90), controlling for the effect of different covariables. A decrease in one z score of height retards the median age of thelarche by 5.5 months (CI: 4.02 to 6.98). Ethnicity did not influence the age of thelarche. Conclusions: The age of thelarche found by us is similar to that reported in international studies, it comes earlier as weight increases, is delayed as height decreases and is not related to ethnicity.

Comparison of three doses of leuprolide acetate in the treatment of central precocious puberty: preliminary results.

OBJECTIVE: Depot luteinizing-hormone releasing hormone (LHRH) agonist have been widely used for the treatment of central precocious puberty (CPP), but the optimal doses to obtain hormonal suppression are still unknown, especially in patients with higher weights. The goal of our study was to compare the efficacy of three leuprolide acetate (LA) preparations, suppressing gonadotropin secretion in patients with CPP. DESIGN: In an open 12-month protocol, we evaluated LA 7.5 mg/month, 11.25 and 22.5 every 3 months. PATIENTS: Fourteen girls with CPP and weights over 30 kg. MEASUREMENTS: Clinical, radiological and laboratory follow-up: GnRH test plus LH, FSH 40 min post analogue was performed periodically. RESULTS: Pretreatment basal and LHRH stimulated LH levels between groups were not different. Basal and LHRH stimulated LH levels decreased significantly between baseline and from 3 up to 12 months of therapy in all groups (P = 0.001). GnRH stimulated LH peak <2 IU/l, the main efficacy criterion was met in 80, 75 and 100% of the children at 6 months in the 7.5, 11.25, 22.5 mg doses respectively. By 12 months, 100% of patients had LH suppressed to <2 IU/l. CONCLUSIONS: These results affirm that 3-month injections may be a satisfactory alternative for the therapy of children with CPP to avoid monthly injections. In addition, suppression of LH occurs sooner in the 3-month 22.5 mg LA dose compared to the 3-month 11.5 mg; therefore, adequate dosing may be important for optimal outcome. Further investigation is needed in more patients over 30 kg, with longer treatment duration, and ultimately final height consideration.

Leydig cell tumor of the testis with histological and immunohistochemical features of malignancy in a 1-year-old boy with isosexual pseudoprecocity.

The article reports the clinical, histopathological, and immunohistochemical findings of a 1-year-old boy presenting with isosexual pseudoprecocity attributable to a functioning Leydig cell tumor of the testis. The case appears to represent the youngest patient ever recognized with this well-known syndrome. Malignancy features were also for the first time initially assessed using criteria, retrospectively developed from the literature, for metastasizing Leydig cell tumor. All the following were found: infiltrative borders, cellular pleomorphism, high mitotic index (12-14/high-power field), high MIB-1 index (40%), P53 positivity in 50% of the cells, and bcl-2 positivity in 15% of the cells. Immunohistochemistry proved the cells of the tumor to be positive for inhibin, Melan-A, synaptophysin, cytokeratin, and calretinin and negative for S-100 and chromogranin A. Notably, lipochrome and crystals of Reinke were not found in the tumor cells. Although the neoplasm fulfilled the criteria for a potentially metastasizing Leydig cell tumor, there was no evidence of that event having occurred, perhaps as a result of early treatment or as indication that criteria developed for Leydig cell tumor of adults may not apply to children.

Hiperplasia supra-renal congênita por deficiência de 11-ß-hidroxilase / Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency

Este artigo tem o objetivo de relatar o diagnóstico e a evolução clínica de um paciente de 15 anos portador de uma disfunção congênita da esteroideogênese adrenal, que pode apresentar-se como hipertensão arterial de diagnóstico muitas vezes tardio (adolescência), virilização ou formas perdedoras de sal (nascimento e infância).

[Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency]. / Hiperplasia supra-renal congênita por deficiência de 11-beta-hidroxilase.

The objective of this article is to relate the diagnostic and clinical evolution of a 15 year old patient with a congenital adrenal steroidogenesis dysfunction that can present as hypertension diagnosed later in life (adolescence), virilization or salt wasting (birth and childhood).

[Peripheral precocious puberty caused by a juvenile granulosa cell ovarian tumor, with iso and heterosexual manifestations in a six years old girl]. / Pubertad precoz periférica por tumor ovárico de las células de la granulosa juvenil, con manifestaciones iso y heterosexuales en una niña de 6 años.

A six years old girl consulted due to mammary development. On physical examination, clitoris enlargement and a tumor localized in the abdominal-pelvic region were observed. Hormonal study disclosed elevated testosterone and estradiol levels. On exploratory laparotomy, a right ovarian tumor was observed and a right salpingooophorectomy was performed. The contemporary biopsy informed a disgerminoma, leading to a surgical staging of the tumor. The definitive pathological diagnosis was a juvenile granular cell tumor, limited to the ovary. In the postoperative period, estradiol and testosterone levels returned to normal values and the pseudopuberty reverted. The patient did not receive adjuvant treatment and after three years of follow up, there is no evidence of tumor recidivism.

The relationship between ovarian structure and serum insulin, insulin-like growth factor-I (IGF-I) and its binding protein (IGFBP-1 and IGFBP-3) levels in premature pubarche.

The aim of this study was to determine serum insulin, insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBP-1 and IGFBP-3) levels and their relationship with androgen levels and ovarian structure in 23 girls with premature pubarche (PP). Fasting levels of testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), androstenedione (delta4A), sex hormone binding globulin (SHBG), glucose (G), insulin (I), IGF-I, IGFBP-1, IGFBP-3 were measured. Androgens or steroid hormone levels > 3 SD of normal postpubertal levels were considered as an exaggerated response to the ACTH test. The fasting I to G ratio (FIGR) was calculated and FIGR > 22 was suggestive of insulin resistance (IR). A pelvic ultrasound (US) was carried out and the ovarian structure was divided into five classes (c): c1--homogeneous, c2--microcystic, c3--multicystic, c4--polycystic and c5--follicular. The girls with PP were divided into two groups according to the main ovarian classes observed: PPc1 (n = 6) and PPc2 (n = 15). The FIGR showed IR in 44% of patients. The androgens, SHBG, G, I, FIGR, IGF-I and IGFBP-1 levels were similar among the groups (PPc1 vs PPc2). An exaggerated response to ACTH was more common and IGFBP-3 levels were higher in the PPc2 than in the PPc1 group (p = 0.04). Regression analysis revealed that I was correlated with DHEAS (r = -0.43, p = 0.04) and IGFBP-1 (r = -0.51, p = 0.01); IGF-I was correlated with DHEA (r = -0.42, p = 0.05), delta4A (r = -0.47, p = 0.02), SHBG (r = -0.43, p = 0.04), IGFBP-1 (r = -0.61, p = 0.002) and IGFBP-3 (r = 0.56, p = 0.005); IGFBP-1 was correlated with SHBG (r = 0.56, p = 0.005). These findings suggest that there might be interactions between the insulin-IGF-I-IGFBPs system and hyperandrogenism. However, the possible causal role of adrenal androgen hypersecretion on the insulin-IGF-I-IGFBPs axis and ovarian structure in girls with PP remains to be established. Since studies reveal that IGFBP-3 levels could be a negative predictor for insulin sensitivity throughout puberty, we hypothesize that girls with PP and microcystic ovaries are at risk of developing IR in the course of normal puberty.

Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.

Primary adrenal insufficiency is a rare condition in pediatric age, and its association with precocious sexual development is very uncommon. We report a 2-yr-old Brazilian boy with DAX1 gene mutation whose first clinical manifestation was isosexual gonadotropin-independent precocious puberty. He presented with pubic hair, enlarged penis and testes, and advanced bone age. T levels were elevated, whereas basal and GnRH-stimulated LH levels were compatible with a prepubertal pattern. Chronic GnRH agonist therapy did not reduce T levels, supporting the diagnosis of gonadotropin-independent precocious puberty. Testotoxicosis was ruled out after normal sequencing of exon 11 of the LH receptor gene. At age 3 yr he developed clinical and hormonal features of severe primary adrenal insufficiency. The entire coding region of the DAX1 gene was analyzed through direct sequencing. A nucleotide G insertion between nucleotides 430 and 431 in exon 1, resulting in a novel frameshift mutation and a premature stop codon at position 71 of DAX-1, was identified. Surprisingly, steroid replacement therapy induced a clear decrease in testicular size and T levels to the prepubertal range. These findings suggest that chronic excessive ACTH levels resulting from adrenal insufficiency may stimulate Leydig cells and lead to gonadotropin-independent precocious puberty in some boys with DAX1 gene mutations.

Nodular Leydig cell hyperplasia in a boy with familial male-limited precocious puberty.

In boys with familial male-limited precocious puberty, an activating mutation of the luteinizing hormone receptor causes Leydig cell hyperplasia, resulting in excess testosterone production. There are no reports of Leydig cell masses in boys with familial male-limited precocious puberty. We describe a 10-year-old boy with familial male-limited precocious puberty who developed Leydig cell nodules.