Hypothalamic Hamartoma Revealed by Precocious Puberty in Girls: About A New Case

Precocious puberty is a multifactorial process whose diagnosis is based, first of all, on the clinic but also on the realization of the bone age, the pelvic ultrasound and the cerebral IRM. Moreover, the GnRH test constitutes the cornerstone to highlight a premature activation of the Hypothalamo-hypophyseal axis. We report the case of a 3-year-old girl admitted for exploration of precocious puberty. The central origin was confirmed by a GnRH test with a peak reaching 45 mIU/L. A hypothalamohypophyseal MRI was performed, showing a mass consistent with a hypothalamic hamartoma. Treatment with GnRH analogues is the treatment of choice for central precocious puberty.

Download Full-text

Rapid progressive central precocious puberty: diagnostic and predictive value of basal sex hormone levels and pelvic ultrasound

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0577 ◽

2020 ◽

Vol 33 (6) ◽

pp. 785-791

Author(s):

Valeria Calcaterra ◽

Catherine Klersy ◽

Federica Vinci ◽

Corrado Regalbuto ◽

Giulia Dobbiani ◽

...

Keyword(s):

Precocious Puberty ◽

Tanner Stage ◽

Central Precocious Puberty ◽

Bone Age ◽

Diagnostic Value ◽

Sex Hormone ◽

Pelvic Ultrasound ◽

Predictive Values ◽

Hormone Levels ◽

Ultrasound Parameters

AbstractObjectivesData on the predictive values of parameters included in the diagnostic work-up for precocious puberty (PP) remain limited. We detected the diagnostic value of basal sex hormone levels, pelvic ultrasound parameters and bone age assessment for activation of the hypothalamic-pituitary-gonadal axis in girls with PP, in order to help in the decision to perform GnRH testing.Patients and methodsWe retrospectively considered 177 girls with PP. According to puberty evolution, the girls were divided into two groups: rapid progressive central precocious puberty (RP-CPP) and non/slowly progressive/transient forms (SP-PP). In all patients we considered Tanner stage, basal luteinizing hormone (LH) and estradiol (E2) values, bone age, and pelvis examination. We assessed the diagnostic value of each variable and identified the number of pathological parameters that best identify patients with RP-CPP.ResultsBasal LH ≥ 0.2IU/L, E2 level ≥ 50 pmol/L, uterine longitudinal diameter ≥ 3.5 cm, transverse uterine diameter ≥ 1.5 cm, endometrial echo and ovarian volume ≥ 2 cm3 were significantly associated with RP-CPP (p ≤ 0.01). The ability to diagnose RP-CPP was enhanced with increasing number of pathological hormonal and instrumental parameters (p < 0.001). With more than three parameters detected, sensitivity and specificity reached 58% (95%CI 48–67) and 85% (95%CI 74–92), respectively, with a PPV = 86% (95%CI 76–93) and PPN = 54% (95%CI 43–54); the area under the ROC curve was 0.71 (95%CI 0.65–0.78).ConclusionDespite the availability of different tests, diagnosing RP-CPP remains difficult. A diagnosis model including at least three hormonal and/or ultrasound parameters may serve as a useful preliminary step in selecting patients who require GnRH testing for early detection of RC-PP.

Download Full-text

Ovarian cysts and tumors as the cause of isosexual pseudoprecocious puberty

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0608305m ◽

2006 ◽

Vol 134 (7-8) ◽

pp. 305-309 ◽

Cited By ~ 4

Author(s):

Katarina Mitrovic ◽

Dragan Zdravkovic ◽

Tatjana Milenkovic ◽

Katarina Sedlecki ◽

Zoran Stankovic

Keyword(s):

Luteinizing Hormone ◽

Granulosa Cell ◽

Precocious Puberty ◽

Granulosa Cell Tumor ◽

Central Precocious Puberty ◽

Bone Age ◽

Cell Tumor ◽

Ovarian Cysts ◽

Pelvic Ultrasound ◽

Releasing Hormone

Introduction. Precocious puberty in girls is generally defined as appearance of secondary sexual characteristics before eight years of age. Menarche before the ninth birthday may serve as an additional criterion. Precocious puberty is divided in central precocious puberty and pseudoprecocious puberty. Central precocious puberty (GnRH dependent) occurs because of premature activation of hypothalamic-pituitarygonadal axis and activity of gonadotrophins. Pseudoprecocious puberty (GnRH independent) is caused by activity of sexual steroids that are not the result of gonadotrophin activity. Objective. Objective of our study was to examine the etiology, clinical and laboratory manifestations of isosexual pseudoprecocious puberty in girls. Method. In the period between 1995 and 2004, clinical and laboratory sings of 34 girls with precocious puberty were studied at the Endocrine Department of the Institute of Mother and Child Health Care of Serbia. Initial evaluations included height measurement, staging of puberty, bone age assessment and pelvic ultrasound. Important diagnostic sonographic parameters of precocious puberty were the volumes of ovaries and uterus as well as ovarian structure. The initial hormonal evaluation included measuring of plasma oestradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH). The luteinizing hormone releasing hormone (LHRH) stimulation test was used to evaluate LH and FSH responsiveness (60 ?g/m2 LHRH- Relefact LHRH?, Ferring). Blood samples were collected at 0, 20 and 60 minutes. Basal and GnRH stimulated LH and FSH were determined by immunoradiometric assay. Estradiol concentration was measured using the fluoroimmunometric assay. Results. Thirty-four girls aged 6 months to 9 years (mean age 4.5 years) with precocious puberty were studied during the period of 9 years. Eleven girls presented with breast development, six with vaginal bleeding and seventeen with signs of puberty. On the basis of clinical signs, bone age, estradiol levels and LHRH test, premature the larche was diagnosed in eleven patients (32.4%), premature menarche in six (17.6%) and central precocious puberty in ten girls (29.4%). Seven girls (20.6%) presented with pseudoprecocious puberty. Pelvic ultrasound examination revealed unilateral ovarian cysts in six patients and granulosa cell tumor in one. Elevated estrogen serum levels and failure of gonadotropin responses after gonadotropin releasing hormone were the classical findings in patients with isosexual pseudoprecocious puberty during the acute period of disease. In four patients, the cyst decreased spontaneously after several months, while in two patients, the cyst was removed by laparotomy. Surgical treatment was performed in a patient with granulosa cell tumor. Conclusion. Our work demonstrates that autonomous functional ovarian follicle cyst is the most often cause of isosexual pseudoprecocious puberty. Short period of observation is suggested because the cyst can resolve spontaneously. On the other hand, juvenile granulosa cell tumor, as highly malignant tumor, should be removed as soon as diagnosis is established.

Download Full-text

Central Precocious Puberty in a Three-Year-Old Girl

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v27i3.1568 ◽

2021 ◽

Vol 27 (3) ◽

pp. 341

Author(s):

Suryani Jamal ◽

Liong Boy Kurniawan ◽

Suci Aprianti ◽

Ratna Dewi Artati ◽

Ruland DN Pakasi ◽

...

Keyword(s):

Physical Examination ◽

Precocious Puberty ◽

Tanner Stage ◽

Central Precocious Puberty ◽

Bone Age ◽

Breast Development ◽

Hypothalamic Hamartoma ◽

Secondary Sexual Characteristics ◽

Pelvic Ultrasonography ◽

Sexual Characteristics

Precocious puberty is defined as the onset of secondary sexual characteristics before 8 years of age in girls and 9 years in boys. Central Precocious Puberty (CPP) is caused by early activation of the hypothalamic-pituitary-gonadal axis. Laboratory test of LH, FSH, and Estradiol is recommended for monitoring suppressive effects from GnRHa therapy in the early three months and every six months. This study aimed to report a case of CPP in a 3-year and 3-month-old girl. A 3-year and 3-month-old girl went to the hospital with vaginal bleeding (menstruation), breast development, and pubic and axilla hair for 7-month-old. Physical examination found moderately ill with obesity, body weight 20 kg, height 98 cm. Tanner stage was A2M3P2, café au lait was found in the left forehead with size 7x3.5 cm. In March 2015 before GnRHa therapy, LH, FSH and Estradiol level increased with levels of 4.32 mlU/mL, 6.01 mlU/mL, and 67 pg/mL, and after 3 months of the treatment was 0.87 mlU/mL, 2.51 mlU/mL and <20 pg/mL. Pelvic ultrasonography showed suggestive precocious puberty, bone age 5-year and 9-month (Greulich and Pyle), CT-Scan of the brain showed hypothalamic tumor suspected hypothalamic hamartoma. This patient was treated with a GnRHa injection every 4 weeks. Leuprorelin is a synthetic non-peptide analogue of natural GnRH. The diagnosis was based on medical history, physical examination, laboratory, and radiological findings. The prognosis of the patient was good.

Download Full-text

Management of Central Precocious Puberty in Children with Hypothalamic Hamartoma

Children ◽

10.3390/children8080711 ◽

2021 ◽

Vol 8 (8) ◽

pp. 711

Author(s):

Junghwan Suh ◽

Youngha Choi ◽

Jun Suk Oh ◽

Kyungchul Song ◽

Han Saem Choi ◽

...

Keyword(s):

Developmental Delay ◽

Precocious Puberty ◽

Gnrh Agonist ◽

Clinical Symptoms ◽

Benign Lesion ◽

Standard Deviation Score ◽

Central Precocious Puberty ◽

Bone Age ◽

Hypothalamic Hamartoma ◽

Gelastic Seizure

Hypothalamic hamartoma (HH) is a rare, congenital, and benign lesion of the tuber cinereum, typically presenting with central precocious puberty (CPP), gelastic seizure, and developmental delay. This study aimed to investigate CPP in HH patients and compare clinical features between before and after gonadotropin-releasing hormone (GnRH) agonist treatment. A total of 30 HH patients under 18 years of age who visited Severance Children’s Hospital between January 2005 and May 2020 were retrospectively reviewed. Fourteen patients were male (46.7%) and sixteen (53.3%) were female, with a mean age at diagnosis was4.2 ± 2.9 years. During follow-up, 24 patients (80.0%) were diagnosed with CPP, 15 patients (50.0%) had gelastic seizure, and 13 patients (43.3%) had developmental delay. The gelastic seizure was significantly associated with sessile type HH rather than pedunculated type HH (85.7% vs. 18.8%, p = 0.001). After GnRH agonist treatment, discrepancies between bone age and chronological age decreased (3.3 ± 1.3 years to 2.0 ± 1.7 years, p = 0.002). Additionally, height standard deviation score for bone age was increased, and predicted adult height increased significantly in females, while males showed an increasing trend. Clinical symptoms of HH were closely associated with the location of HH, and GnRH agonist treatment was safe and effective in the management of CPP caused by HH.

Download Full-text

Assessment of gonadotropin concentrations stimulated by gonadotropin-releasing hormone analog by electrochemiluminescence (ECLIA) in girls with precocious puberty and premature thelarche

Hormone Research in Paediatrics ◽

10.1159/000521593 ◽

2021 ◽

Author(s):

Kamila Botelho Fernandes de Souza ◽

Melyna Shayanne Pessôa Veiga ◽

Gabriela Ráina Ferreira Martins ◽

Adriana Paula da Silva ◽

Lívia Grimaldi Abud Fujita ◽

...

Keyword(s):

Precocious Puberty ◽

Central Precocious Puberty ◽

Bone Age ◽

Gonadotropin Releasing Hormone ◽

Assay Method ◽

Premature Thelarche ◽

Releasing Hormone ◽

Cutoff Values ◽

Hormone Analog ◽

Hormone Analogs

Objective: The aim of this study is to determine the cutoff values of gonadotropin response to gonadotropin-releasing hormone analogs (GnRHas) corresponding to the activation of the hypothalamic–pituitary–gonadal axis that could differentiate central precocious puberty (CPP) from premature thelarche (PT) and using the electrochemiluminescence assay method. Methods: A total of 49 girls underwent the stimulation test with the intramuscular injection of 3.75 mg leuprolide acetate. Based on the clinical and laboratory characteristics, they were divided into two groups: CPP (n = 22) and PT (n = 27). Baseline estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were collected before GnRHa administration, and LH and FSH at 60 and 120 min, respectively, after GnRHa administration. Results: The girls with CPP presented an increased height Z-score, advanced bone age, and higher baseline LH, FSH, estradiol, and LH/FSH ratio in relation to PT (p < 0.001). Stimulated LH differed significantly between the two groups, and the LH cutoff values were ≥4.29 IU/L (p < 0.001) and ≥3.95 IU/L at 60 and 120 min, respectively (p < 0.001). LH peak was found at 60 min after stimulation. Conclusions: The GnRHa test is effective in distinguishing CPP from PT, and a single sampling, at 60 min, with LH concentrations above 4.29 may be the parameter of choice with the advantage of greater convenience and practicality.

Download Full-text

Central precocious puberty due to hypothalamic hamartoma in neurofibromatosis type 1

HORMONES ◽

10.1007/bf03401416 ◽

2016 ◽

Vol 15 (1) ◽

pp. 144-146 ◽

Cited By ~ 1

Author(s):

Emanuele Bartolini ◽

Stefano Stagi ◽

Perla Scalini ◽

Andrea Bianchi ◽

Antonio Ciccarone ◽

...

Keyword(s):

Precocious Puberty ◽

Neurofibromatosis Type 1 ◽

Central Precocious Puberty ◽

Neurofibromatosis Type ◽

Hypothalamic Hamartoma

Download Full-text

Anthropometric, metabolic, and reproductive outcomes of patients with central precocious puberty treated with leuprorelin acetate 3-month depot (11.25 mg)

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0142 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Carolina O. Ramos ◽

Ana P M Canton ◽

Carlos Eduardo Seraphim ◽

Aline Guimarães Faria ◽

Flavia Rezende Tinano ◽

...

Keyword(s):

Precocious Puberty ◽

Adult Height ◽

Central Precocious Puberty ◽

Bone Age ◽

Overweight And Obesity ◽

Leuprorelin Acetate ◽

The Mean ◽

Hormone Analogs

Abstract Objectives Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Methods Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). Results At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p<0.05). The mean AH was 163.2 ± 6.2 cm (mean SDS: 0.1 ± 1). All patients were within their target height (TH) range. There was a decrease in the percentage of overweight and obesity from the diagnosis until AH (39–19% p>0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Conclusions Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes.

Download Full-text

A diagnostic model of idiopathic central precocious puberty based on transrectal pelvic ultrasound and basal gonadotropin levels

Journal of International Medical Research ◽

10.1177/0300060520935278 ◽

2020 ◽

Vol 48 (8) ◽

pp. 030006052093527

Author(s):

Bo Yuan ◽

Ya-Lei Pi ◽

Ya-Nan Zhang ◽

Peng Xing ◽

He-Meng Chong ◽

...

Keyword(s):

Luteinizing Hormone ◽

Precocious Puberty ◽

Endometrial Thickness ◽

Central Precocious Puberty ◽

Diagnostic Model ◽

Transverse Diameter ◽

Pelvic Ultrasound ◽

Ovarian Volume ◽

Idiopathic Central Precocious Puberty ◽

Anterior Posterior

Objective To establish a diagnostic model of idiopathic central precocious puberty on the basis of transrectal pelvic ultrasound and basal gonadotropin. Methods A total of 669 girls with Tanner breast development stage II were enrolled in this study from January 2015 to December 2018. The participants were divided into the ICPP group and the premature thelarche group. We analyzed various variables, including age at initial diagnosis, basal luteinizing hormone levels, the long diameter of the uterus, the transverse diameter of the uterus, the anterior–posterior diameter of the uterus, the volume of the uterus, maximum ovarian diameter, average ovarian volume, maximum ovarian volume, number of follicles (≥4 mm), maximum follicular diameter, endometrial thickness, and vaginal wall thickness. Results The following diagnostic model was established: Y=−14.123 + 0.630 × age at initial diagnosis + 1.119 × transverse diameter of the uterus + 1.278 × anterior–posterior diameter of the uterus + 0.637 × average ovarian volume + 1.316 × maximum ovarian diameter + 0.146 ×number of follicles ≥4 mm + 2.925 × endometrial thickness + 0.559 × basal luteinizing hormone value. The area under curve was 0.922, sensitivity was 84.9%, and specificity was 86.2%. Conclusion Basal LH levels and transrectal pelvic ultrasound should be applied together to improve the accuracy of diagnosis in ICPP.

Download Full-text