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

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2090 ◽

2008 ◽

Vol 93 (7) ◽

pp. 2751-2754 ◽

Cited By ~ 39

Author(s):

Jakub Mieszczak ◽

Elizabeth S. Lowe ◽

Paul Plourde ◽

Erica A. Eugster

Keyword(s):

Aromatase Inhibitor ◽

Precocious Puberty ◽

Growth Velocity ◽

Vaginal Bleeding ◽

Linear Growth ◽

Skeletal Maturation ◽

Average Growth ◽

Mccune Albright Syndrome ◽

Albright Syndrome ◽

Mccune Albright

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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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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Clinical Characteristics and Management of Patients With McCune-Albright Syndrome With GH Excess and Precocious Puberty: A Case Series and Literature Review

Frontiers in Endocrinology ◽

10.3389/fendo.2021.672394 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiao Zhai ◽

Lian Duan ◽

Yong Yao ◽

Bing Xing ◽

Kan Deng ◽

...

Keyword(s):

Growth Hormone ◽

Growth Velocity ◽

Bone Age ◽

Peking Union Medical College ◽

Z Score ◽

College Hospital ◽

Mccune Albright Syndrome ◽

Medical College ◽

Albright Syndrome ◽

Mccune Albright

BackgroundMcCune-Albright syndrome is a rare disorder characterized by fibrous dysplasia, café au lait skin spots, and hyperfunctioning endocrinopathies. The coexistence of precocious puberty and growth hormone excess in McCune-Albright syndrome is rare. Both conditions can manifest as accelerated growth, and treatments can be more challenging for such patients. This study aimed to describe the clinical manifestations of combined GH excess and PP in the context of McCune-Albright syndrome and analyze the clinical features and treatments of these patients.MethodClinical data from 60 McCune-Albright syndrome patients from Peking Union Medical College Hospital were obtained. The demographic characteristics, growth hormone, insulin-like growth factor-1, prolactin, alkaline phosphatase, and sex hormone levels; growth velocity; and bone age data were obtained. The growth velocity Z-score, bone age over chronological age ratio, and predicted adult height Z-score were calculated before and after treatment. Published studies and case reports were systemically searched, and data on demographic, clinical, and biochemical characteristics and treatment outcomes were obtained.ResultsWe reviewed seven patients among 60 McCune-Albright syndrome patients at Peking Union Medical College Hospital (5 female) and 39 patients (25 female) from the published literature. Six of the seven patients from Peking Union Medical College Hospital and half of the patients from the published studies were pediatric patients. These patients had increased growth velocity Z-scores and bone age over chronological age ratios. After good control of both conditions, the growth velocity Z-score and bone age over chronological age ratio decreased significantly, and the predicted adult height Z-score increased. The final heights and predicted adult height Z-scores were not impaired in patients with gigantism. All the patients had craniofacial fibrous dysplasia associated with optic and otologic complications.ConclusionMcCune-Albright syndrome with growth hormone excess and precocious puberty is more common in girls. Patients have accelerated linear growth and advanced skeletal age, and early and good control of both conditions leads to a reduced growth velocity and stabilized bone age. The predicted adult and final heights are not negatively affected when growth hormone excess is diagnosed in pediatric patients.

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Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune–Albright syndrome

Acta Endocrinologica ◽

10.1530/eje-16-0526 ◽

2016 ◽

Vol 175 (5) ◽

pp. 477-483 ◽

Cited By ~ 18

Author(s):

Andrea Estrada ◽

Alison M Boyce ◽

Beth A Brillante ◽

Lori C Guthrie ◽

Rachel I Gafni ◽

...

Keyword(s):

Growth Velocity ◽

Adult Height ◽

Bone Age ◽

Skeletal Maturation ◽

Mccune Albright Syndrome ◽

Letrozole Treatment ◽

Albright Syndrome ◽

Historical Controls

Objective McCune–Albright syndrome (MAS) is a rare disorder with a broad spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP. Design Retrospective cohort analysis. Methods Clinical data, including history and physical examination, bone age, and pelvic ultrasounds, were reviewed on 28 letrozole-treated girls. Adult height was reviewed for 42 historical controls. Outcomes included rate of skeletal maturation, growth velocity, predicted adult height and adult height. Results Twenty-eight girls received letrozole treatment. Treatment duration was 4.1 ± 2.6 years (mean ± 1 s.d.) (range: 0.5–10.9) and mean follow-up was 6.0 ± 3.3 years (range: 0.5–15.0), for a total of 135.9 person-years of follow-up. Letrozole treatment was highly effective at decreasing the rate of skeletal maturation, with a decline in change in bone age over change in chronological age (ΔBA/ΔCA) from 1.7 (IQR: 2.3) to 0.5 (IQR: 0.4) (P < 0.0001), and growth velocity Z-scores, which declined from 2.2 ± 2.3 to −0.6 ± 1.6 (P = 0.0004). Predicted adult height Z-scores increased significantly from −2.9 ± 3.2 to −0.8 ± 1.5 for subjects on treatment (P = 0.004). Four subjects who completed treatment reached adult height Z-scores ranging from −1.5 to 1.7 (median: −0.6), which were increased in comparison with untreated historical controls (P = 0.02). There was no change in uterine size or ovarian volumes, and no adverse events over the treatment period. Conclusions In this study with the longest follow-up to date, letrozole treatment resulted in sustained beneficial effects on skeletal maturation, growth velocity and predicted adult height.

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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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