Abstract
Graphical abstract
Abstract
Background
A high prevalence (40–75%) of organic brain lesions in boys with central precocious puberty (CPP) has been reported.
Objectives
To evaluate the causes of CPP in a large cohort of males and to identify the possible predictive factors for organic brain lesions in males.
Design
An observational study was conducted in 102 otherwise healthy boys with CPP diagnosed from 1998 to 2023 in a single tertiary center.
Methods
All boys underwent a thorough clinical, endocrine and neuroimaging assessment with a detailed evaluation of the pituitary region.
Results
Organic CPP was found in only 8/102 children (7.8%). Children with brain tumors were younger than 8 years, had no family history positive for precocious puberty and maternal menarche occurred at an age significantly more advanced than in children with idiopathic CPP. Headache was reported at diagnosis in 7/8 children with brain tumors. A progressive increase in the occurrence of idiopathic CPP in males has been observed in the last two decades with a peak of new diagnoses during the pandemic lockdown.
Conclusions
Our findings indicate that the prevalence of pathological brain lesions in boys with CPP is considerably lower than previously reported, thus making the diagnosis less alarming. Age younger than 8 years, presence of neurological symptoms, family history negative for precocious puberty in the first-degree relatives and age of maternal menarche older than 11 years raise suspicion of organic CPP and should lead to prompt neuroimaging.
Significance statement
Differently from what has been reported in most previous studies, our study has shown a low incidence of brain tumors in male children with precocious puberty, thus making the diagnosis less alarming for parents and physicians. Some criteria for a high index of suspicion of brain tumors in boys with precocious puberty have been identified. Finally, a progressive increase in the occurrence of idiopathic CPP in boys has been observed over the past two decades with a peak of new diagnoses during the pandemic lockdown, as previously reported in girls.
Introduction
Precocious puberty (PP) is characterized by the development of secondary sexual characteristics before the age of 9 years in boys and 8 years in girls (1). In boys, PP is clinically defined as 4 milliliters or more in testicular volume, measured by Prader orchidometer, before the age of 9 years (2, 3) PP is classified in central precocious puberty (CPP), also known as gonadotropin-dependent PP, and peripheral precocious puberty (PPP) or gonadotropin-independent PP. CPP is characterized by the early activation of the hypothalamic–pituitary–gonadal axis (4, 5).
The incidence of CPP is estimated to be 10 times higher in girls than in boys, with an incidence of 0.2–26.28 per 10,000 in girls and 0.023–0.9 per 10,000 in boys (6, 7). CPP is classified into idiopathic and organic forms. Organic CPP is associated with lesions in the central nervous system (CNS), including hamartomas, gliomas and other brain tumors (8).
The prevalence of CNS lesions differs significantly between females and males, varying from 8% to 33% in girls and 30% to 70% in boys (9, 10, 11). A progressive increase in the incidence of idiopathic CPP has been reported in females over the past two decades and multiple factors, such as environmental cues, endocrine disruptors, nutritional status, adoption and prematurity, have been suggested to play a role in this phenomenon (12, 13). In studies carried out before 2000, the reported prevalence of intracranial lesions reached 70–90% in male children (14, 15). Due to the reported high prevalence of CNS lesions, the consensus published in 2009 recommended to perform brain MRI with detailed imaging of the hypothalamic–pituitary region in all boys with CPP (16). However, recent studies emphasize a possible overestimation of the phenomenon, reporting an incidence of 6–20% of brain tumors among boys with CPP (17, 18, 19, 20).
The objectives of this study were to assess the prevalence of organic CPP in a large cohort of otherwise healthy boys with CPP referred to our center over the past 25 years and to identify the clinical and biochemical predictors of CNS tumors.
Study population
This observational study included all boys diagnosed with CPP at the tertiary pediatric endocrinology referral center in ‘Bambino Gesù’ Children’s Hospital (Rome, Italy) from January 1998 to December 2023.
Informed consent was obtained from the respective parents.
The diagnosis of CPP was based on the presence of testicular volume ≥4 mL before 9 years of age, LH (luteinizing hormone) peak ≥5 IU/L during gonadotropin-releasing hormone (GnRH) stimulation test and LH/FSH (follicle-stimulating hormone) ratio >1. Patients with the age at pubertal onset >9 years, with already known CNS abnormalities, associated endocrine disorders, previous hormonal therapies, malformations, neurofibromatosis or other inherited conditions including congenital adrenal hyperplasia were excluded from the study. 131 boys with CPP were initially included in the study. 29 children were excluded because they did not meet the criteria. A total of 102 children were included in the final analysis (Fig. 1).
Patient selection. *PPP, peripheral precocious puberty; CAH, congenital adrenal hyperplasia. **RT, radiotherapy; CT, chemotherapy. ***NF1, neurofibromatosis type 1.
Citation: Endocrine Connections 14, 2; 10.1530/EC-24-0405
Methods
At diagnosis, a detailed history was collected, focusing on family history of precocious/early puberty, history of periconceptional period, gestational age, auxological parameters at birth, history of international adoption, comorbidities and neurological symptoms (vomiting, headache and visual disturbances). Clinical evaluation comprised the assessment of auxological parameters and pubertal status.
Weight was assessed by a digital scale. Standing height was measured by using a Harpenden stadiometer (model AYRTON S100 Stadiometer) in children older than 2 years of age. The height SD score (SDS) was calculated using CDC growth charts as not all patients were of Italian descent (21). Height velocity SDS was calculated using Tanner’s growth charts (3). Target height (TH o MPH) was calculated using Tanner’s method ((maternal height + 13) + father’s height)/2.
Pubertal stage was assessed by physical examination according to Tanner’s criteria. The following signs were considered suggestive of PP: growth acceleration with height velocity above 1 SDS and Tanner stage 2 with testicular volume equal or greater than 4 mL assessed with Prader orchidometer (2). Diagnostic workup included left hand and wrist X-rays for assessing bone age by the method of Greulich & Pyle (22). Fasting venous blood samples were obtained to determine LH, FSH, testosterone, B-hCG using electrochemiluminescence assay (ECLIA). Testosterone levels greater than 20 ng/dL (0.7 nmol/L) were considered suggestive of pubertal activation.
GnRH was administered intravenously (Lutrelef-Ferring) at a dosage of 100 mcg for LHRH (luteinizing hormone-releasing hormone) test. FSH and LH were measured at 0, +30, +60, +90 and +120 min after the injection. An LH peak response after GnRH infusion greater than 5 mIU/mL was considered suggestive of pubertal response (23). This threshold has been reported to represent +2 SD for normal prepubertal subjects when using the immunochemiluminometric assay.
All boys with a diagnosis of CPP underwent brain MRI scan, performed before and after gadolinium-enhanced T1- and T2-weighted images in axial, coronal and sagittal sections. The MRI finding of pituitary microadenoma was considered when there was an intraglandular focal area <10 mm, with a gradual enhancement or rapid enhancement on the dynamic contrast-enhanced magnetic resonance images or an intraglandular focal area <10 mm of low- or high-signal intensity after injection of the contrast media (24).
Statistical analysis
All results are reported as mean ± SD. Differences among means in the different groups were assessed using one-way ANOVA and Bonferroni’s post hoc test. Differences in laboratory parameters not normally distributed in each MRI groups were assessed by the Kruskal–Wallis test.
Pearson’s chi-square test was used to analyze differences between MRI groups and non-continuous variables. Student’s t-test was used to analyze differences between the two groups and continues variables.
To evaluate the association between potential predictors and PP, a binary logistic regression model was performed. Significance was assigned for P value <0.05. Statistical analysis was performed using SPSS (version 17.0; SPSS, Inc., USA).
Ethics committee approval
Data are anonymized by the removal of any identifying marks and patient details. Retrospective clinical, laboratory and radiological data of patients were obtained and processed in conformity to the independent Ethics Committee of Bambino Gesù Children’s Hospital of Rome after a signed informed consent and conducted in accordance with the Declaration of Helsinki. The study was conducted in accordance with the current approved international guidelines and regulations.
Results
A progressive increase in the number of new diagnoses of PP in boys was observed from the year 2000, with a peak of incidence during the years 2012–2016 and 2020–2022 (Fig. 2). In the first decade, since 1998 to 2008, 13 new diagnosis were established (cumulative incidence of 12%), and in the second decade 2008–2018, 65 new diagnosis were made (61% increase). Moreover, a peak of incidence with 21 new cases was observed during the pandemic period in Italy (2020–2022), amounting to 20.6% of all the diagnoses made over the observation time. Among these cases, only one pathological MRI lesion was found (one hamartoma).
Study population stratified for the year of diagnosis (number of cases/year).
Citation: Endocrine Connections 14, 2; 10.1530/EC-24-0405
Based on the MRI findings, 76 patients (74.5%) showed normal brain MRI and were classified as idiopathic CPP, 18 (17.6%) reported incidental alterations of hypothalamic–pituitary area unrelated to PP, and 8 (7.8%) showed a pathological brain lesion. Pathological brain lesions were four hypothalamic hamartomas (one case <2 years of age and three patients aged 6–8 years), two diencephalic gangliogliomas aged 6–8 years, one diencephalic low-grade astrocytoma aged 2–6 years and one germinoma aged 2–6 years. The details of the brain MRI findings are summarized in Table 1.
Brain MRI findings.
| Type of lesion | Number of patients | |
|---|---|---|
| Pathological lesions | Hypothalamic hamartomas | 4 |
| Diencephalic gangliogliomas | 2 | |
| Diencephalic low-grade astrocytoma | 1 | |
| Pineal gland germinoma | 1 | |
| Mild alterations of hypothalamic–pituitary region | MRI suggestive of pituitary microadenomas (non-secreting) | 4 |
| Other alterations | ||
| Suprasellar-arachnoid cysts | 3 | |
| Tuber cinereum lipoma | 1 | |
| Pituitary pars intermedia cysts | 3 | |
| Empty sella | 1 | |
| Pituitary hypoplasia or pituitary stalk slight deviation | 4 | |
| Ectopic neurohypophysis | 2 | |
| Normal brain MRI or no alteration of hypothalamic–pituitary region | Pineal millimetric cysts | 5 |
| Millimetric arachnoid cysts in pericerebellar region | 2 | |
| Arnold-Chiari I | 1 | |
| Gliosis | 1 | |
| Frontal cysts | 3 | |
| Ventricular asymmetry | 3 | |
| Non-relevant findings | 61 | |
By stratifying children according to different age groups at the onset of symptoms, we found no pathological brain lesions in children aged >8 years (0/69, 0%), four cases in children aged 0–6 years (4/9, 44%) and four cases in children aged 7–8 years (4/24, 17%) (Fig. 3). Bone age was significantly lower in the pathological group compared to the other two groups (mean 7.3 ± 2.2 years in the pathological group versus 9.9 ± 2.2 years and 9.8 ± 1.9 years in the normal and mild/incidental alteration groups, respectively; ANOVA, P value = 0.027).
Brain MRI findings and percentage of pathological lesions according to the age groups.
Citation: Endocrine Connections 14, 2; 10.1530/EC-24-0405
Comparing the three MRI groups, a statistically significant difference was found in the age at the onset of puberty, which was 8.2 ± 1.4, 7.9 ± 1.3 and 5.5 ± 2.3 in normal, mild and pathological group, respectively (ANOVA, P value = 0.000); no significant difference was found between normal MRI and mild alteration MRI groups.
A pituitary microadenoma was identified in four children, ranging from 2 to 5 mm in diameter. Pituitary function tests yielded normal results. Brain MRI was repeated in the four children after 1 year, and no enlargement of the lesions was seen; in one case, the finding suggestive of microadenoma was not confirmed.
The age of maternal menarche was different in the groups, being higher in children with pathological lesions and lower in children with mild/incidental anomalies and normal MRI, with the mean values of 13 ± 0.4, 10.7 ± 1.4 and 11 ± 1.6 years in pathological, mild and normal MRI group (ANOVA, P value = 0.035), respectively.
Family history positive for early/PP was present in 94% (71/76) of children with normal brain MRI, whereas it was negative in all children with pathological brain MRI (chi-square test, P value = 0.001). No significant differences in the basal LH, basal FSH, FSH peak, LH peak, LH/FSH ratio and testosterone levels among MRI groups were found.
Nine children reported headache at diagnosis, including 7/8 children with pathological MRI (87%), one with arachnoid cyst of the suprasellar region and one with Arnold-Chiari malformation.
The study population included 10 (9.8%) adopted boys and 7 (6.8%) preterm boys with no brain lesions at MRI scan.
The hormonal levels and clinical data at the time of diagnosis of the study cohort according to the MRI groups are shown in Table 2.
Main clinical and laboratory findings stratified according to MRI findings at diagnosis.
| MRI groups | ||||||
|---|---|---|---|---|---|---|
| Normal | Pathological | Mild alterations | ||||
| Mean | SD | Mean | SD | Mean | SD | |
| Age at pubertal onset (years) | 8.2 | 1.4 | 5.5 | 2.3 | 7.9 | 1.3 |
| Age at maternal menarche (years) | 11.0 | 1.6 | 13.0 | 0.4 | 10.7 | 1.4 |
| Testicular volume (mL) | 6.4 | 2.5 | 6.2 | 2.0 | 6.1 | 2.4 |
| Pubarche (Tanner stage) | 1.8 | 0.7 | 1.9 | 0.6 | 1.9 | 0.8 |
| Gonadarche (Tanner stage) | 2 | 0.5 | 2.2 | 0.3 | 2.0 | 0.6 |
| Stature (SDS) | 0.9 | 1.3 | 1.2 | 0.7 | 0.9 | 1.5 |
| Growth velocity (cm/year) | 9.8 | 5.1 | 9.7 | - | 7.9 | 2.8 |
| BMI (kg/m2) | 0.3 | 4.0 | 0.3 | 0.9 | 1.0 | 1.5 |
| Bone age (years) | 10.2 | 2.0 | 7.4 | 2.2 | 9.8 | 2.1 |
| FSH (UI/L) | 2.4 | 1.9 | 3.0 | 4.0 | 2.1 | 1.4 |
| FSH peak (UI/L) | 5.8 | 4.3 | 9.1 | 13.8 | 5.3 | 3.5 |
| LH (UI/L) | 1.3 | 1.2 | 1.6 | 1.1 | 1.2 | 1.6 |
| LH peak (UI/L) | 16.3 | 10.2 | 16.4 | 11.2 | 17.3 | 11.8 |
| LH/FSH ratio | 4.6 | 7.7 | 3.1 | 2.2 | 4.2 | 2.7 |
| Testosterone (ng/dL) | 138.6 | 137.6 | 203.1 | 201.5 | 100.2 | 92.7 |
No statistically significant differences were found in hormone levels between MRI groups or between children with hamartoma and children with other brain tumors.
The logistic regression between the dichotomous outcome pathological MRI versus non-pathological MRI showed the following results:
- -For the variable ‘age at pubertal onset,’ we found the odds ratio (ExpB) of 0.566, confidence interval (CI) of 1.1–6.2, percentage of correctness of 91.2%, significance (P value) of 0.001 and predictive probability (ExpB/1 + ExpB) of 36%. As the age of pubertal onset increases, the probability of finding pathological brain lesions on MRI decreases by 36% per each year of age.
- -For the variable ‘maternal age at menarche,’ we found the odds ratio (ExpB) of 2.65, CI of 0.4–0.8, percentage of correctness of 92.8%, significance (P value) of 0.027 and predictive probability (ExpB/1 + ExpB) of 72.6%. As the age of maternal menarche increases, the probability of finding pathological brain lesions on MRI increases by 72% per each year of age.
Discussion
The results of our study conducted in a large Italian cohort of male patients with isolated CPP, stratified into different risk groups according to brain MRI findings, show a prevalence of pathological brain lesions in 7.8% of patients.
Several factors could contribute to the observed low-incidence of CNS lesions in comparison with most of the previous reports, such as the strict patient selection, the exclusion of possible confounding factors, the stratification according to MRI findings and the increasing trend of idiopathic CPP incidence in boys likewise reported in girls over the past two decades.
A significant increase in the incidence of idiopathic CPP in girls has been reported worldwide and, in particular, during SARS-CoV2 pandemic (25, 26). Similarly to the studies in girls, an increase in the incidence of new diagnoses of idiopathic CPP was observed in our cohort of boys during the 2020–2022 pandemic years (27, 28, 29). In particular, a vast majority of the new diagnoses were made from April to September 2020, corresponding to phases 2–4 of the first Italian lockdown, characterized by a relaxation of containment measures and an overall increase in admissions to hospital and outpatient clinics (30).
Up until now, this is the first study reporting the incidence of CPP in males according to the year of diagnosis and, in particular, to the different phases of SARS-CoV2 pandemic in Italy. The potential causes of the increased incidence of idiopathic PP in boys during the SARS-Cov2 pandemic are probably the same of those proposed for girls: sedentary lifestyle and consequent increase in body mass index, overuse of electronic devices, stress and anxiety, social isolation, changes in circadian rhythms and sleep patterns (31, 32, 33, 34, 35).
The increasing incidence of CPP in both girls and boys may also be explained by a progressive higher exposure to endocrine disruptor chemicals. Biomonitoring studies have reported the rising exposure to bisphenol-A and phthalates, which can affect various components of the GnRH network, particularly targeting kisspeptin neurons (36, 37, 38). Up until now, few and not consistent results have been reported in males. A recent study has shown that prenatal exposure to polychlorinated biphenyls (PCBs), a persistent environmental pollutant, is linked to altered concentrations of LH and testosterone (39). A reduction in testosterone levels and an increase in the FSH levels were found in Chinese boys whose mothers had been inadvertently exposed to high doses of PCBs and polychlorinated dibenzofurans through the consumption of contaminated rice oil (40).
In comparison with our results, previous studies reported a significant higher prevalence of CNS lesions in boys with CPP probably related to the inclusion of children with risk factors for brain tumors or to the trend of a progressive younger age at puberty onset in both sexes over the years.
Relevant previous studies reporting the occurrence of CNS lesions in boys with CPP are summarized in Table 3.
Previous studies in the literature reporting the occurrence of CNS lesions in boys with CPP from 2000 to 2024.
| Studies | Number of patients | Cases with CNS lesions | Type of lesions (tumors versus others)* |
|---|---|---|---|
| De Sanctis et al. 2000 (9), Italy | 45 | 18 (40%) revealed through CT or MRI | 6 hamartomas of the tuber cinereum, craniopharyngioma 5 neurofibromatosis, post-RT ependymoma Post-meningitis After CMV-related meningoencephalitis Post-CT |
| Chemaitilly et al. 2001 (4), France | 26 | 19 (73%) | 14 previously treated CNS lesions (surgery, RT and CT) 5 new lesions (3 hamartomas and 2 optic gliomas) |
| Alikasifoglu et al. 2015 (11), Turkey | 100 | 26 (26%) | 5 hamartoma 3 microadenoma 2 optic glioma 1 craniopharyngioma 1 pineal germinoma 14 other findings (cysts and neurodevelopmental anomalies) |
| Topor et al. 2018 (41), USA | 50 | 32/50 (64%) | 10 neurofibromatosis type 1 4 optic glioma 3 hypothalamic hamartoma 3 other CNS tumor 12 genetic syndromes/after brain injury |
| Lee et al. 2018 (42),*South Korea | 71 | 27/71 (38%) | 9 astrocytoma 2 hamartoma 2 neuroblastoma 1 germinoma 1 retinoblastoma 1 d/dx astrocytoma/hamartoma 1 pituitary macroadenoma Other findings including: Lipofuscinosis Epilepsy Ewing’s sarcoma Burkitt lymphoma |
| Yoon et al. 2018 (20), South Korea | 138 | 10/138 (7%) | 6 pineal or arachnoid or Rathke cysts 3 pituitary hyperplasia 1 thick pituitary sta |
| Vurallı et al. 2020 (43), Turkey | 120 | 26 (21.7%) | 16 new lesions with 6 hamartomas 4 arachnoid cyst 2 glioma 1 craniopharyngioma 1 germonima 1 pinealoblastoma 1 hemorragic adenoma 10 (8.3%) with previous developmental anomaly of CNS (parenchymal injury, necrotic lesions and hydrocephalus) |
| Wang et al. 2021 (19), China | 129 | 21/129 (16.3%) | 1 non-secreting pineal germinoma 1 hypothalamic hamartoma 18 others (8 Rathke or arachnoid or pineal cysts 7 pituitary hyperplasia and 4 pituitary hypoplasia) |
| Kendirci et al. 2022 (44), Turkey | 9 | 5 (55%) | 1 microadenoma 4 other findings (altered pituitary enhancement, demyelination area, corpus callosum dysgenesis, cavum septum pellucidum alteration) |
| Bajpai et al. 2022 (45), India | 26 (18 CPP, 8 PPP) | 10/18 (55%) | 4 hamartomas 2 craniopharyngioma 1 dysgerminoma Others: neurotuberculosis, hydrocephalus, postRT, holoprosencephaly |
| Hansen et al. 2023 (17), Denmark | 24 | 3/24 (10.3%) | Hamartomas and other lesions not specified |
| Cassio et al. 2024 (18), Italy | 193 | 11/193 (5.7%) | 5 hypothalamic hamartoma 3 optic glioma 1 germinoma non-hCG secreting 1 pilocytic astrocytoma craniopharyngioma |
| Present study, 2024, Italy | 102 | 8/102 (7.8%) | 4 hypothalamic hamartomas 2 diencephalic gangliogliomas 1 diencephalic low-grade-astrocytoma 1 pineal gland germinoma |
CT, chemotherapy; RT, radiotherapy.
Kendirci et al. reported pathological findings in 55.5% of cases aged 7.4 ± 1.7 years but only one patient with a pituitary abnormality (one case of microadenoma), whereas the other patients showed nonspecific findings such as congenital malformations or a simple altered enhancement at the brain MRI scan (44). Chemaitilly et al. reported in a cohort of 26 boys with CPP, 19 children with brain lesions, most of them (14/19, 74%) with a previous diagnosis of CNS lesion or positive history for cranial radiotherapy and chemotherapy (4). Vuralli et al. evaluated a cohort of 120 boys with CPP, reporting 26 patients with brain lesions (21%). However, 10/26 boys with organic CPP had a history positive for CNS anomalies, such as parenchymal injury, necrotic lesions and hydrocephalus (43). Topor et al. reported a prevalence of 64% of brain lesions in boys with CPP, but a high percentage of patients were affected by neurofibromatosis type 1, a well-known risk factor for optic gliomas and other CNS tumors (41). Similar heterogenous study cohorts, including both healthy boys and patients with known risk factors (previous tumors, cranial radiotherapy, chemotherapy, NF1 and epilepsy) were described in both recent and dated studies (9). In a cohort of Indian boys with PP enrolled from 1990 to 2000, eight boys with PPP, eight idiopathic CPP and ten (55%) with organic CPP were reported (45). However, children with known predisposing factors such as CNS malformations, epilepsy, PPP, congenital adrenal hyperplasia, previous radiotherapy and neurotuberculosis were included.
Two recent studies have investigated the prevalence of CNS alterations in boys with CPP (19, 20). Consistent with our results, they found an increased prevalence of the idiopathic form of CPP in comparison with the previously published data. A prevalence ranging from 7–16% of organic CPP was reported. However, patients aged more than 9 years were included in the cohorts, thus making the diagnostic criteria for PP less stringent. Interestingly, the study of Hansen et al. found a prevalence of 10% (3/24) of organic CPP, all occurring in children younger than 6.1 years of age (17).
Similarly, a recent Italian multicenter retrospective study collecting prepandemic data from 193 otherwise normal healthy boys with a strict diagnosis of CPP reported the presence of brain tumors in only 5.7% of the study sample (18). Brain tumors included gliomas, hamartomas, germinomas, pilocytic astrocytoma and craniopharyngiomas. The authors also showed that the age of pubertal onset was significantly lower in the brain tumor group (6.5 ± 2.8 years versus 8.2 ± 0.8 of the normal MRI group), consistent with our results. Differently from our study, they found increased basal LH concentrations in the pathological group. A positive family history was clearly reported in 19% of the cases in the normal MRI group, without detailed information about maternal menarche or first-degree relatives’ inheritance.
An important strength of the present study is the strict inclusion criteria used for the diagnosis of CPP. Indeed, only boys aged 9 years or less at the onset of symptoms were included and 33/102 (32.3%) of patients were diagnosed under the age of 8 years. Moreover, only boys with isolated PP without other potential risk factors for CNS lesions were included as the purpose of this study was to shed light on the real risk of finding a brain tumor in boys referred with the suspicion of PP in the absence of other comorbidities and potential risk factors.
The finding of no brain tumors in boys older than 8 years casts doubt on the need of routine brain MRI in boys with CPP aged more than 8 years without risk factors, family history positive for CPP, no rapidly progressing puberty and no neurological symptoms. This clinical-based guidance may be particularly useful for the management of patients living in remote and disadvantaged areas, with limited access to neuroimaging.
The age of maternal menarche equal or younger than 11 years and a family history positive for precocious/early puberty in a first-degree relative were present in a high percentage of boys with idiopathic CPP, highlighting the pivotal role played by genetic predisposition to CPP in males as previously reported in girls (46, 47, 48, 49). Our results suggest that family history should be systematically and accurately investigated and may become a key component of a clinical score for assessing the risk of brain tumors in male patients with CPP.
Conclusions
The results of this study show that the prevalence of organic brain lesions in boys with CPP, when the diagnosis is made on the basis of well-defined criteria, is considerably lower than previously reported, thus making the diagnosis less alarming. In a cohort of 102 Italian male patients with CPP, only 7.8% presented brain lesions responsible for CPP. Risk factors for organic brain lesions were as follows: I) the age of puberty onset lower than 8 years, II) neurological symptoms such as headache and III) absence of a family history for PP in the first-degree relative, in particular, the age of maternal menarche higher than 11 years.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the work reported.
Funding
This work was supported by the Italian Ministry of Health with “Current Research funds”.
Data availability statement
Data that support the findings of this study are available from the corresponding author upon reasonable request.
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