Mccune Albright Syndrome and Polycystic Ovary Syndrome in a Single Individual

Abstract

BackgroundMcCune Albright Syndrome (MAS) is a genetic disease with autonomous endocrine hyperfunction (AEH) leading to peripheral precocious puberty (PP) in young females, while polycystic ovary syndrome (PCOS) is a disorder in women presenting with menstrual dysfunction (MD) and hyperandrogenism (HA). There are no reports in the literature of these two diagnoses in the same individual.CaseA 14 year old female with MAS presented to the Pediatric and Adolescent Gynecology Clinic for oligomenorrhea (OM). At age 7 she was diagnosed with obesity, premature adrenarche, and concern for PP due to early development of breasts and pubic hair. Work-up for PP with an ACTH and GnRH stimulation test (GnRH ST), sex hormone panel (HP), pelvic ultrasound (US), and bone age (BA) was negative. She developed accelerated growth velocity at age 8 and work-up showed enlarged follicular ovaries on US, advanced BA, normal HP, negative GnRH ST, two café-au-lait spots (CAL), and no fibrous dysplasia (FD) on bone scan. With these clinical features, the diagnosis peripheral PP secondary to MAS was given, and treatment with aromatase inhibitor (AI) and growth hormone (GH) due to short stature were initiated. Repeat GnRH ST showed central PP and Lupron was started at age 10, however all medications were stopped at age 11 due to discordant growth of her feet. She had appropriate pubertal progression, menarche at age 12, development of OM with only 4 menses in two years, and facial acne. PCOS was diagnosed by OM and clinical and biochemical signs of HA. Combined oral contraceptive pills (OCPs) were initiated with subsequent menstrual regulation and improvement in acne.DiscussionFeatures of MAS include AEH, bone FD, and CAL spots. A mutation in the GNAS gene causing persistent activation of the Gs protein in various endocrine glands and subsequent hormonal hypersecretion independent of the hypothalamic-pituitary (HP) hormone signaling leads to these features. Ovarian hyperfunction (OH) and thus hyperestrogenism (HE) can present as peripheral PP in infancy with early menses, breast development, and ovarian cysts. Studies show that persistent OH and HE causing ovarian cysts and menstrual abnormalities are common in adults with MAS and history of PP, which can lead to infertility and development of estrogen dependent disease.Young females with PCOS develop early HA influenced by fetal and/or postnatal events, disruption of the HP axis, and sustained HA. Diagnosis in adolescents includes a combination of OM for 2 years after menarche, clinical and/or biologic HA, insulin resistance (IR), and PCO. HA and IR increases risk of infertility and cardiometabolic disease, thus early recognition and treatment may reduce morbidity later in life. Treatment is directed at improving MD, HA, and metabolic abnormalities with lifestyle modifications and combined hormonal agents.Young females with a history of obesity and premature adrenarche have a 15-20% risk of developing PCOS, however long-term consequences of MAS, continued HE, and its association with PCOS has not been well documented. Ongoing surveillance of females with MAS is important to monitor for development and management of hormone dependent disease. BackgroundMcCune Albright Syndrome (MAS) is a genetic disease with autonomous endocrine hyperfunction (AEH) leading to peripheral precocious puberty (PP) in young females, while polycystic ovary syndrome (PCOS) is a disorder in women presenting with menstrual dysfunction (MD) and hyperandrogenism (HA). There are no reports in the literature of these two diagnoses in the same individual. McCune Albright Syndrome (MAS) is a genetic disease with autonomous endocrine hyperfunction (AEH) leading to peripheral precocious puberty (PP) in young females, while polycystic ovary syndrome (PCOS) is a disorder in women presenting with menstrual dysfunction (MD) and hyperandrogenism (HA). There are no reports in the literature of these two diagnoses in the same individual. CaseA 14 year old female with MAS presented to the Pediatric and Adolescent Gynecology Clinic for oligomenorrhea (OM). At age 7 she was diagnosed with obesity, premature adrenarche, and concern for PP due to early development of breasts and pubic hair. Work-up for PP with an ACTH and GnRH stimulation test (GnRH ST), sex hormone panel (HP), pelvic ultrasound (US), and bone age (BA) was negative. She developed accelerated growth velocity at age 8 and work-up showed enlarged follicular ovaries on US, advanced BA, normal HP, negative GnRH ST, two café-au-lait spots (CAL), and no fibrous dysplasia (FD) on bone scan. With these clinical features, the diagnosis peripheral PP secondary to MAS was given, and treatment with aromatase inhibitor (AI) and growth hormone (GH) due to short stature were initiated. Repeat GnRH ST showed central PP and Lupron was started at age 10, however all medications were stopped at age 11 due to discordant growth of her feet. She had appropriate pubertal progression, menarche at age 12, development of OM with only 4 menses in two years, and facial acne. PCOS was diagnosed by OM and clinical and biochemical signs of HA. Combined oral contraceptive pills (OCPs) were initiated with subsequent menstrual regulation and improvement in acne. A 14 year old female with MAS presented to the Pediatric and Adolescent Gynecology Clinic for oligomenorrhea (OM). At age 7 she was diagnosed with obesity, premature adrenarche, and concern for PP due to early development of breasts and pubic hair. Work-up for PP with an ACTH and GnRH stimulation test (GnRH ST), sex hormone panel (HP), pelvic ultrasound (US), and bone age (BA) was negative. She developed accelerated growth velocity at age 8 and work-up showed enlarged follicular ovaries on US, advanced BA, normal HP, negative GnRH ST, two café-au-lait spots (CAL), and no fibrous dysplasia (FD) on bone scan. With these clinical features, the diagnosis peripheral PP secondary to MAS was given, and treatment with aromatase inhibitor (AI) and growth hormone (GH) due to short stature were initiated. Repeat GnRH ST showed central PP and Lupron was started at age 10, however all medications were stopped at age 11 due to discordant growth of her feet. She had appropriate pubertal progression, menarche at age 12, development of OM with only 4 menses in two years, and facial acne. PCOS was diagnosed by OM and clinical and biochemical signs of HA. Combined oral contraceptive pills (OCPs) were initiated with subsequent menstrual regulation and improvement in acne. DiscussionFeatures of MAS include AEH, bone FD, and CAL spots. A mutation in the GNAS gene causing persistent activation of the Gs protein in various endocrine glands and subsequent hormonal hypersecretion independent of the hypothalamic-pituitary (HP) hormone signaling leads to these features. Ovarian hyperfunction (OH) and thus hyperestrogenism (HE) can present as peripheral PP in infancy with early menses, breast development, and ovarian cysts. Studies show that persistent OH and HE causing ovarian cysts and menstrual abnormalities are common in adults with MAS and history of PP, which can lead to infertility and development of estrogen dependent disease.Young females with PCOS develop early HA influenced by fetal and/or postnatal events, disruption of the HP axis, and sustained HA. Diagnosis in adolescents includes a combination of OM for 2 years after menarche, clinical and/or biologic HA, insulin resistance (IR), and PCO. HA and IR increases risk of infertility and cardiometabolic disease, thus early recognition and treatment may reduce morbidity later in life. Treatment is directed at improving MD, HA, and metabolic abnormalities with lifestyle modifications and combined hormonal agents.Young females with a history of obesity and premature adrenarche have a 15-20% risk of developing PCOS, however long-term consequences of MAS, continued HE, and its association with PCOS has not been well documented. Ongoing surveillance of females with MAS is important to monitor for development and management of hormone dependent disease. Features of MAS include AEH, bone FD, and CAL spots. A mutation in the GNAS gene causing persistent activation of the Gs protein in various endocrine glands and subsequent hormonal hypersecretion independent of the hypothalamic-pituitary (HP) hormone signaling leads to these features. Ovarian hyperfunction (OH) and thus hyperestrogenism (HE) can present as peripheral PP in infancy with early menses, breast development, and ovarian cysts. Studies show that persistent OH and HE causing ovarian cysts and menstrual abnormalities are common in adults with MAS and history of PP, which can lead to infertility and development of estrogen dependent disease. Young females with PCOS develop early HA influenced by fetal and/or postnatal events, disruption of the HP axis, and sustained HA. Diagnosis in adolescents includes a combination of OM for 2 years after menarche, clinical and/or biologic HA, insulin resistance (IR), and PCO. HA and IR increases risk of infertility and cardiometabolic disease, thus early recognition and treatment may reduce morbidity later in life. Treatment is directed at improving MD, HA, and metabolic abnormalities with lifestyle modifications and combined hormonal agents. Young females with a history of obesity and premature adrenarche have a 15-20% risk of developing PCOS, however long-term consequences of MAS, continued HE, and its association with PCOS has not been well documented. Ongoing surveillance of females with MAS is important to monitor for development and management of hormone dependent disease.