The Aromatase Inhibitor Anastrozole Is Ineffective in the Treatment of Precocious Puberty in Girls with McCune-Albright Syndrome

Abstract Context: Precocious puberty (PP) in girls with McCune-Albright syndrome (MAS) is characterized by episodic development of large unilateral ovarian cysts followed by sudden onset of vaginal bleeding. Some patients experience frequent bleeding as well as accelerated linear growth and advanced skeletal maturation. The use of anastrozole for the treatment of PP in this condition has not been well studied. Objective: The objective of the study was to determine the safety and efficacy of the aromatase inhibitor anastrozole for the treatment of PP in girls with MAS. Design and Settings: This was a prospective international multicenter study in which subjects received anastrozole 1 mg daily for 1 yr. Patients: Twenty-eight girls 10 years of age or younger with MAS and progressive PP were enrolled. Main Outcome Measures: Vaginal bleeding, rate of skeletal maturation (change in bone age over change in chronological age), growth velocity, and uterine/ovarian volumes were measured. These indices were compared with a 6-month pretreatment interval. Results: No difference in vaginal bleeding (mean number of days per year) was noted. Mean change in ΔBA/ΔCA, which was 1.25 ± 0.77 at baseline, was −0.25 ± 1.02 at study end (P = 0.22). Average growth velocity z score was 1.40 ± 3.15 at study entry and 0.26 ± 2.71 at 12 months (P = 0.10). Mean ovarian/uterine volumes were unaffected by anastrozole, and no significant adverse events occurred. Conclusions: Although it appears safe, anastrozole for 1 yr was ineffective in halting vaginal bleeding, attenuating rates of skeletal maturation, and linear growth in girls with MAS. Pharmacological strategies other than anastrozole should be pursued for the treatment of PP in this population.

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Management of precocious puberty in girls with McCune–Albright syndrome using letrozole

Endocrine Connections ◽

10.1530/ec-18-0344 ◽

2018 ◽

Vol 7 (12) ◽

pp. 1424-1431 ◽

Cited By ~ 1

Author(s):

Xi Wang ◽

Qi Yu

Keyword(s):

Precocious Puberty ◽

Growth Velocity ◽

Adult Height ◽

Skeletal Maturation ◽

College Hospital ◽

Cross Sectional ◽

Mccune Albright Syndrome ◽

The Mean ◽

Albright Syndrome ◽

Mccune Albright

Objective To evaluate the safety and efficacy of letrozole in girls with progressive precocious puberty (PP) associated with McCune–Albright syndrome (MAS). Design Monocentric retrospective cross-sectional and longitudinal study of consecutive patients. Patients Ten MAS patients treated at Peking Union Medical College Hospital between September 1999 and December 2017 were retrospectively reviewed; those with complications due to PP were followed. Results The mean age at letrozole initiation was 4.5 ± 2.6 years, while the mean duration of treatment was 3.3 ± 2.4 years. Letrozole was highly effective at decreasing the rate of skeletal maturation, with a significant decrease in the bone age-to-chronological age (BA/CA) ratio from 1.9 ± 1.1 pre-treatment to 1.5 ± 1.2 on letrozole treatment (P = 0.016). Moreover, growth velocity Z-scores declined from 0.41 ± 0.5 to −0.2 ± 0.31 with treatment (P < 0.001). Predicted adult height Z-scores increased significantly from −2.03 ± 2.33 at baseline to 1.13 ± 0.84 following treatment initiation (P = 0.029). Moreover, vaginal bleeding declined significantly on letrozole. Conclusions Our findings suggest that letrozole may be an effective therapy in some girls with MAS, as treatment results in improved BA/CA ratio, growth velocity and predicted adult height. Possible adverse effects include nettle rash.

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SUN-061 Anthropometric and Reproductive Outcomes of Patients with Gonadotropin-Independent Precocious Puberty Due to McCune-Albright Syndrome After Treatment with Distinct Therapeutic Agents

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1730 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Aline Guimarães de Faria ◽

Priscila Sales Barroso ◽

Carolina Ramos ◽

Ana Pinheiro Machado Canton ◽

Marina Cunha Silva ◽

...

Keyword(s):

Aromatase Inhibitors ◽

Precocious Puberty ◽

Vaginal Bleeding ◽

Adult Height ◽

Therapeutic Agents ◽

Chronological Age ◽

Mccune Albright Syndrome ◽

First Choice ◽

Albright Syndrome ◽

Mccune Albright

Abstract Ovarian estrogen-secreting cysts leading to peripheral precocious puberty (PPP) are some of the major clinical manifestations of the McCune-Albright syndrome (MAS). Therapeutic options for PPP of MAS include tamoxifen, progestational agents, aromatase inhibitors (AI) and anti-androgens that aiming to block sex steroid synthesis or action. Here, we described the anthropometric and reproductive follow-up of patients with PPP of MAS treated with distinct therapeutic agents. Thirteen unrelated girls with MAS were studied. They had PPP combined with café-au-lait spots or/and fibrous dysplasia. All patients were treated with one or more of the following agents: tamoxifen, medroxyprogesterone acetate, aromatase inhibitors (anastrozole or letrozole) and anti-androgens (cyproterone), and, in cases with secondary gonadotropic axis activation, depot GnRHa was used. Patients were evaluated every three months, when height, weight, and Tanner pubertal stage were determined. Vaginal bleeding or other adverse effects were also reviewed. The chronological age (CA) at the diagnosis of PPP was 5.9 ± 2.35 (2.4 to 10.2 years). Thelarche and vaginal bleeding were the first manifestations in 76.9% and 53%, respectively. The first choice of treatment was tamoxifen in 30.7% of the patients, followed by aromatase inhibitors (23%) and medroxyprogesterone acetate in 23% of them. Tamoxifen plus medroxyprogesterone, or cyproterone, or leuprorelin were used (each one) as the first choice in 1 patient (7.6%). Eight patients (61%) presented secondary central precocious puberty and were treated with depot GnRHa. Vaginal bleeding was recurrent in 70% of patients, during treatment. Progression of breast Tanner stage during treatment occurred in 78% of the patients. The great majority (80%) of girls presented bone age (BA) advancement at the diagnosis of PPP (mean Δ BA - CA of 3.2±1.3 yr), which was normalized for chronological age in all except one patient. The mean duration of treatment was 5.8 ± 3.4 yr (ranging from 1 to 12 yr). Three patients are still under medical treatment. Hypertrichosis and uterine enlargement were the main side effects of tamoxifen in 3 and 5 patients, respectively. One patient treated with letrozole presented laboratory hyperandrogenism. Ten patients reached their adult height (149.9 ± 7.9 cm), 60% of them were below their target height. Menarche occurred at a median age of 11.8 yr (10.4 to 14 y), and all but one patient presented regular menstrual cycles. One patient spontaneously became pregnant. Despite a reasonable number of treatment options for peripheral PP in MAS, none of them showed proven effective results in stopping vaginal bleeding, reduce pubertal progression and preserving potential genetic adult height. Therefore, due to the extremely heterogeneous nature of PPP of MAS, the clinical treatment remains a challenge.

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A case of McCune Albright syndrome in the context of an ovarian mass and late development of café-au-lait macules

International Journal of Integrative Pediatrics and Environmental Medicine ◽

10.36013/ijipem.v6i.85 ◽

2020 ◽

Vol 6 ◽

pp. 2-4

Author(s):

Prisca Pungwe ◽

Dirin Ukwade ◽

Ganesh Maniam ◽

Ryan Dean ◽

Abigail Batson ◽

...

Keyword(s):

Precocious Puberty ◽

Ovarian Cyst ◽

Vaginal Bleeding ◽

Late Development ◽

Ovarian Mass ◽

Polyostotic Fibrous Dysplasia ◽

Pelvic Mri ◽

Mccune Albright Syndrome ◽

Albright Syndrome ◽

Mccune Albright

McCune-Albright syndrome (MAS) is a genetic disorder characterized by polyostotic fibrous dysplasia, precocious puberty, and café-au-lait spots. In this case, a patient presented with precocious puberty in the setting of an ovarian mass and late development of café-au-lait macules, confounding the final diagnosis of MAS. A 3-year-old girl presented with vaginal bleeding. She had a previous episode of vaginal bleeding, breast budding, and a right ovarian cyst at 5 months of age. Work-up at that time showed no abnormal findings, though past medical history was notable for two fractures. Physical exam was significant for increased height (89th percentile), increased weight (99th percentile), bilaterally elevated breast mounds with palpable breast tissue and darkened areolae (Tanner stage 3), and residual blood in the vaginal introitus. Notable labs included low FSH and high ultrasensitive estradiol. Pelvic MRI showed a right ovarian cyst, which, in the context of precocious puberty, raised the suspicion for a juvenile granulosa cell tumor. Follow-up pelvic MRI demonstrated features that instead suggested an ovarian response to hormonal stimulation. On a subsequent visit several months later, the patient had small café-au-lait macules on the chest and right buttock, which were not present on the initial evaluation. Further workup revealed advanced bone age on an x-ray at 6 years 10 months, and multifocal polyostotic fibrous dysplasia involving bilateral femurs and right tibia. Failure to include MAS in the differential had led to unnecessary oophorectomy. It is crucial to identify MAS as a cause of peripheral precocious puberty to guide proper management.

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Aromatase Inhibitor, Anastrozole, Therapy for Precocious Puberty in 3-year-old Girl with the McCune-Albright Syndrome

Clinical Pediatric Endocrinology ◽

10.1297/cpe.12.75 ◽

2003 ◽

Vol 12 (2) ◽

pp. 75-79 ◽

Cited By ~ 1

Author(s):

Yumiko Kinoshita ◽

Zenro Kizaki ◽

Yasunori Ishihara ◽

Hisakazu Nakajima ◽

Shinsuke Adachi ◽

...

Keyword(s):

Aromatase Inhibitor ◽

Precocious Puberty ◽

Mccune Albright Syndrome ◽

Albright Syndrome ◽

Mccune Albright

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Treatment of Precocious Puberty in the McCune–Albright Syndrome with the Aromatase Inhibitor Testolactone

New England Journal of Medicine ◽

10.1056/nejm198610303151802 ◽

1986 ◽

Vol 315 (18) ◽

pp. 1115-1119 ◽

Cited By ~ 63

Author(s):

Penelope P. Feuillan ◽

Carol M. Foster ◽

Ora H. Pescovitz ◽

Karen D. Hench ◽

Thomas Shawker ◽

...

Keyword(s):

Aromatase Inhibitor ◽

Precocious Puberty ◽

Mccune Albright Syndrome ◽

Albright Syndrome ◽

Mccune Albright

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McCune-Albright syndrome onset with vaginal bleeding

BMJ Case Reports ◽

10.1136/bcr-2021-243401 ◽

2021 ◽

Vol 14 (7) ◽

pp. e243401

Author(s):

Ngo Van Doan ◽

Nguyen Minh Duc ◽

Vuong Kim Ngan ◽

Nguyen Van Anh

Keyword(s):

Precocious Puberty ◽

Vaginal Bleeding ◽

Genetic Disorder ◽

Brain Mri ◽

Clinical Signs ◽

Bone Lesions ◽

Mccune Albright Syndrome ◽

Multiple Organs ◽

Albright Syndrome ◽

Mccune Albright

McCune-Albright syndrome (MAS), a rare genetic disorder, affects multiple organs and classically presents with the triad of polyostotic fibrous dysplasia (FD), skin hyperpigmentation (café-au-lait spots) and precocious puberty. Diagnosis occurs when patients manifest at least two of these three symptoms. We describe a 4-year-old girl who was admitted to our hospital due to recurrent vaginal bleeding, initially diagnosed as precocious puberty. On brain MRI, abnormalities in the maxillary and occipital bones were compatible with FD. Clinical examination after craniofacial bone lesions and clinical signs indicated MAS revealed abnormally pigmented macules on the neck and back, which were initially overlooked. No abnormal hormone tests were observed. Precocious puberty is the most common MAS-associated symptom that results in the admission to the hospital, whereas the clinical manifestation of FD in the first years of life is usually equivocal and probably has not been discovered by parents. Thus, comprehensive medical examinations are necessary to obtain a prompt and proper diagnosis.

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Treatment of precocious puberty in a McCune–Albright syndrome patient using Chinese medicinal herbs combined with megestrol acetate: A case report

Traditional Medicine and Modern Medicine ◽

10.1142/s2575900018720011 ◽

2018 ◽

Vol 01 (01) ◽

pp. 69-74

Author(s):

Wen Sun ◽

Yonghong Wang ◽

Jian Yu ◽

Min Ji

Keyword(s):

Precocious Puberty ◽

Bone Dysplasia ◽

Medicinal Herbs ◽

Megestrol Acetate ◽

Chinese Medicinal Herbs ◽

Gene Encoding ◽

Mccune Albright Syndrome ◽

Activating Mutation ◽

Albright Syndrome ◽

Mccune Albright

Introduction: McCune–Albright Syndrome (MAS) is a rare congenital sporadic disorder characterized by fibrous bone dysplasia, café-au-lait pigmented spots on the skin, and non-gonadotropin dependent precocious puberty (PP), which is caused by a postzygotic somatic activating mutation in the GNAS gene encoding the alpha subunit of Gs protein. In our case study, we recorded a girl with the onset of MAS and treated her with Chinese medicinal herbs combined with megestrol acetate. We aim to provide a method for the treatment of children with this rare form of precocious puberty. Case Presention: A 4-year-old girl presented with vaginal bleeding and enlarged breasts. The activating mutation of GNAS was not detected in the patient’s peripheral blood samples, as some had reported. Because of peripheral PP and fibrous dysplasia of the diagnosed bone, the patient was considered as MAS. We chose the Chinese medicinal herbs combined with megestrol acetate for treatment, and the patient was effectively treated. Conclusion: The combination therapy of Chinese medicinal herbs plus megestrol acetate in managing PP in an MAS is one of the useful treatments.

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McCune Albright Syndrome: A Case Report

Journal of Nepal Paediatric Society ◽

10.3126/jnps.v40i2.29099 ◽

2020 ◽

Vol 40 (2) ◽

pp. 134-137

Author(s):

Subhana Thapa Karki ◽

Vandana Jain

Keyword(s):

Case Report ◽

Fibrous Dysplasia ◽

Precocious Puberty ◽

Genetic Disease ◽

Clinical Presentation ◽

Endocrine Disorders ◽

Mccune Albright Syndrome ◽

Café Au Lait Spots ◽

Albright Syndrome ◽

Mccune Albright

McCune Albright syndrome (MAS) is a very rare genetic disease characterised by any two of the following three findings: café au lait spots, polyosteotic fibrous dysplasia and endocrine disorders. The clinical presentation of MAS may vary depending on which of the various components of the syndrome predominate. Here, we report one case of MAS presenting with precocious puberty.

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