McCune-Albright Research Articles

8479 A Challenging Case of Hypercortisolism in an Adult Patient With McCune Albright Syndrome

Abstract Disclosure: P. Kesavan Chary: None. S. Jasim: None. Background: McCune Albright Syndrome (MAS) is a rare genetic disorder that occurs due to a spontaneous post-zygotic missense mutation in the GNAS gene resulting in activating gain of function mutations in G-proteins. MAS classically presents as a triad of café-au-lait skin pigmentation, fibrous dysplasia of bone, and precocious puberty. However, continuous autonomous stimulation of endocrine glands can also result in various other endocrinopathies. We present a rare case of hypercortisolism due to bilateral multinodular adrenal hyperplasia (BMAH) in an adult patient with MAS. Case Report: A 38 year old female had MAS, clinically manifested by precocious puberty, renal phosphate wasting with rickets and osteomalacia, fibrous dysplasia of bone with history of multiple fractures, growth hormone excess, and multinodular thyroid status-post total thyroidectomy. A surveillance CT abdomen showed bilateral (right 3.8 x 1.3 cm and left 1.0 x 0.9 cm) adrenal adenomas with low intrinsic attenuation and washout. On diagnosis, the patient had an AM cortisol of 32.5 ug/dL (6.2-19.4 ug/dL) after a low-dose dexamethasone suppression test (DST), and an AM cortisol of 27.3 ug/dL after a high-dose DST. Late night salivary cortisol was 0.518 ug/dL (<0.010-0.090 ug/dL), 24-hour urine cortisol was 78 ug/24hrs (6-42 ug/24hrs), and ACTH was <1.5 pg/mL (7.2-63.3 pg/mL). The patient was initially asymptomatic and monitored for a few months, but subsequently developed easy bruising, recurrent skin infections, and irritability. The patient declined surgical intervention and was initiated on Osilodrostat. Shortly after medication initiation, she was hospitalized for perforated diverticulitis, hypokalemia, and hypomagnesemia. During hospitalization, AM Cortisol was 49 mcg/dL (4.8-19.5 mcg/dL) and 24-hour urine cortisol was 1023 mcg/24hrs (normal range 3.5-45 mcg/24hrs; the patient’s level prior to admission was 170-190 mcg/24hrs). Osilodrostat was held and the patient was initiated on Etomidate infusion. Once plasma cortisol levels normalized, she resumed Osilodrostat prior to discharge. The patient subsequently tried multiple medical therapy options before undergoing a bilateral adrenalectomy as a definitive treatment choice. Conclusion: The gain of function mutations in MAS result in autonomous endocrine gland function that can manifest clinically as various endocrinopathies. While the most common endocrinopathies in MAS are precocious puberty, hyperthyroidism, and pituitary dysfunction, active surveillance is critical to monitor for less common presentations such as hypercortisolism. This is the first report of adrenal Cushing’s in an adult patient with MAS. Presentation: 6/3/2024

7291 From Vaginal Bleeding to Genetic Complexity: McCune Albright Syndrome in a Toddler; Emphasizing Atypical Manifestations, Diagnostic Challenges, and Comprehensive Management

Abstract Disclosure: A.G. Martinez Sanchez: None. N. Fernandez: None. C.L. Bustamante Escobar: None. Background: McCune Albright Syndrome (MAS) is a rare genetic disorder characterized by a triad of peripheral precocious puberty, irregular café-au-lait spots, and bone fibrous dysplasia. It is often caused by post-zygotic somatic mutations in the GNAS1 gene. We present a case of a patient initially presenting with precocious puberty, whose diagnostic journey revealed MAS with atypical manifestations. Presentation: A 23-month-old girl was brought to the emergency department after her mother noticed vaginal bleeding during a diaper change; denied any trauma, fever, rash, or dysuria. Patient developed accelerated growth about six months earlier, followed by pubic hair three months prior and bilateral thelarche two weeks before presentation. The patient had no exposure to endocrine disruptors. The physical examination revealed a well-developed child, in the 92nd percentile for weight and 97th for height. Additionally, breast buds, fine hair on the labia, and minimal blood at the vaginal introitus, with no apparent signs of trauma. Initial laboratory findings showed prepubertal LH and FSH levels, elevated estradiol 120 pg/ml (prepubertal range <10) and advanced bone age (4.2 years). Normal levels of testosterone, 17-hydroxyprogesterone, and DHEA sulfate. Pelvic ultrasound demonstrated an enlarged uterus (5.6 x 1.8 x 2.4 cm) and a large cystic lesion (4.4 cm) on the right ovary. During a follow-up at the endocrinology department one week later, a meticulous examination identified an irregular café-au-lait spot measuring about 2cm over the occipital right side of her scalp. Further tests, including GnRH stimulation test, tumor markers (LDH, b-HCG, CEA, and Ca19-9), brain MRI and bone scan, yielded normal findings. Given the presentation consistent with Peripheral precocious puberty, Letrozole was initiated at 1.25 mg daily. Three months later, her growth velocity remained accelerated. However, there was a decrease in both breast tissue and uterus size (4.2 x 1.2 x 1.7 cm), and the ovarian cyst was resolved. Genetic testing in blood indicated no mutations. To conduct a thorough assessment, the insulin-like growth factor (IGF-1) level was measured and found to be 200 ng/mL (normal range 56-144 ng/mL). Unfortunately, obtaining prolactin levels was challenging due to difficult intravenous (IV) access. Conclusion: This case reveals the complexity of MAS in precocious puberty, emphasizing atypical features that add complexity to the diagnosis. Identifying an irregular café-au-lait spot served as a diagnostic indicator, revealing the diverse clinical presentations. The challenges of relying solely on genetic testing for diagnosis are evident due to the mosaic nature and tissue-specific distribution of the mutation, as highlighted by the absence of mutations in this patient. Long-term management requires ongoing monitoring and a multidisciplinary approach for optimal patient outcomes. Presentation: 6/1/2024

Unraveling the Mystery: McCune-Albright Syndrome as a Rare Cause of Fanconi Syndrome and Kidney Failure

Unraveling the Mystery: McCune-Albright Syndrome as a Rare Cause of Fanconi Syndrome and Kidney Failure

McCune-Albright syndrome: a case report

McCune-Albright syndrome: a case report

Radiological Features of McCune-Albright Syndrome with Acromegaly: A Case

Radiological Features of McCune-Albright Syndrome with Acromegaly: A Case

Long-Term Clinical Evolution of McCune-Albright syndrome: 15 years of follow-up

Mc Cune Albright syndrome is a rare, sporadic disorder manifested by the triad of fibrous bone dysplasia (FD), café-au-lait skin spots and precocious puberty (PP), which may be associated with other hormonal hyperfunctions. The broad spectrum of manifestations reflects the mosaicism of the activating somatic mutation of the GNAS gene in different tissues. Follow-up of patients with Mc Cune Albright syndrome in adulthood remains essential, and requires multidisciplinary management, as this population remains susceptible to sometimes serious complications related to the hyper-secretory nature of all possible endocrine conditions. We report the case of a 15-year-old female patient with complete Mc Cune Albright syndrome since the age of 9 months.

Diagnosis and management of pituitary adenomas in children and adolescents.

Pituitary adenomas (PAs)-also now called pituitary neuroendocrine tumours or Pit-NETS-are rare in children and adolescents and exceptional below the age of 10. Most evidence-based high-quality data are derived from larger studies in adult patients. We will review recent knowledge on the epidemiology, clinical features, diagnosis, and treatment modalities of the different types of pituitary adenomas diagnosed in children and adolescents, emphasizing the many reasons why these cases should be discussed within pituitary-specific multidisciplinary teams with experts from both paediatric and adult practice. Paediatric PA presents multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

Management Challenges of an Infant with Multiple Endocrinopathies with Mc Cune Albright Syndrome: A Case Report

Management Challenges of an Infant with Multiple Endocrinopathies with Mc Cune Albright Syndrome: A Case Report

Radiofrequency echographic multispectrometry (REMS) in rare bone conditions

In recent years there has been a growing interest in radiofrequency echographic multispectrometry (REMS), an innovative technology, free of ionized radiation, that is capable of providing important information on bone status. In particular, REMS has been shown to measure bone mineral density (BMD) at axial skeletal bones with a precision, repeatability and accuracy not inferior to those of dual-energy X-ray absorptiometry (DXA). Moreover, REMS may be useful in the assessment of impaired bone quality (e.g., in patients with type 2 diabetes mellitus) and to predict fragility fracture risk. Due to these characteristics, REMS could be usefully used in the diagnosis and follow up of rare bone diseases. In 41 adult subjects (mean age 40.5 ± 18.7 years) with osteogenesis imperfecta (OI), BMD values at all skeletal sites, obtained using both DXA and REMS, were significantly lower than in controls. BMD by REMS values were significantly lower in patients with types III and IV versus type I OI, whereas BMD by DXA did not differ significantly between the two groups. REMS has also demonstrated excellent diagnostic accuracy in some patients suffering from McCune-Albright or Ehlers-Danlos syndromes. Furthermore, with REMS it is to obtain the real BMD value in the presence of artifacts, and, being free of ionizing radiation, it could be particularly advantageous in children and in women of childbearing age or during pregnancy and breastfeeding. In conclusion, on the basis of these preliminary data, REMS can be considered a precise and reliable technique for the evaluation and monitoring of bone status in individuals with rare bone diseases. KEY WORDS: Rare bone diseases, bone mineral density (BMD), dual-energy X-ray absorptiometry (DXA), radiofrequency echographic multispectrometry (REMS), osteogenesis imperfecta.

Malignant transformation of craniofacial fibrous dysplasia: A clinicopathological, immunohistochemical and molecular analysis of 15 cases in one single institution

ObjectiveMalignant transformation of craniofacial fibrous dysplasia (FD) is not common and its clinicopathological as well as molecular characteristics remain largely unknown with limited literature reports. Study designPatients diagnosed with FD including McCune-Albright syndrome (MAS), polyostotic fibrous dysplasia (PFD), and monostotic fibrous dysplasia (MFD), accompanied by malignant transformation at our institution over the past 18 years (2005–2023) were retrospectively screened and analyzed to investigate the epidemiology and clinicopathological features of these tumors. ResultsThree hundred and five patients were diagnosed as FD in our hospital from 2005 to 2023, with 176 females (57.7 %) and 129 males (42.3 %). The average age at diagnosis was 28.35 years, ranging from 7 to 70 years. A total number of 15 (4. 9 %) cases of FD with malignant transformation were selected. Among these 15 patients, the age of the initial diagnosis of FD ranged from 6 to 54 years (mean age 28.87 ± 16.77), and the ages when malignant transformation occurred ranged from 18 to 57 years (mean age 38.53 ± 13.05). Among 15 patients, 12 patients were female (80 %) and 3 were male (20 %). Fifteen cases included MSA in 2 patients, PFD in 4 patients, and MFD in 9 patients. Of the anatomical sites in craniofacial bones, the most common site of the lesion was the maxilla, followed by the mandible. Malignant neoplasm arising in FD were osteosarcoma (12/15), chondrosarcoma (1/15) and high-grade sarcoma of uncertain differentiation (2/15). The 3- and 5-year overall survival rate was 33.3 % (5/15) and 20 % (3/15) respectively. In secondary osteosarcoma from FD, MDM2 and CDK4 positivity were 33.3 % and 41.7 % respectively, and only one case was MDM2-amplified and CDK4-amplified. ConclusionMalignant transformation in fibrous dysplasia was an exceedingly rare event and with a female predominance. The overall survival rate was poor. Osteosarcoma was the most common malignant neoplasm arising in FD. MDM2 and CDK4 expression may aid in the diagnosis of secondary osteosarcoma in FD.

Putting two and two together: a rare case of mccune-albright syndrome

Putting two and two together: a rare case of mccune-albright syndrome

Dissecting the heterogeneity of craniofacial lesions in patients with fibrous dysplasia/McCune–Albright Syndrome

Fibrous dysplasia/McCune–Albright Syndrome (FD/MAS) frequently involves the craniofacial skeleton. Craniofacial fibrous dysplasia lesions exhibit diverse imaging characteristics on multimodality evaluation, utilizing radiographs, computed tomography (CT), magnetic resonance imaging (MRI), and 18F-sodium fluoride positron emission tomography (18F-NaF PET). A multimodal imaging classification of craniofacial fibrous dysplasia lesions may offer clinical insights into the types of lesions that are (1) prone to progression, (2) amenable to intervention (i.e., pharmacological or surgical), or (3) associated with symptoms such as pain. In this prospective, preliminary single site study of 15 patients with FD/MAS, the heterogeneity of craniofacial lesions (N = 35) was assessed using a combination of 18F-NaF PET, MRI, and CT. A k-means clustering algorithm was used to categorize lesions based on imaging characteristics. Clustering analysis revealed three types of lesion based on the magnitude of the regional 18F-NaF standardized uptake values (SUV), signal intensities on T1-weighted and fluid-sensitive sequences, and appearance on CT (lucent, sclerotic, and/or ground glass). This preliminary study provides a foundation for future longitudinal natural history or treatment studies, where the prognostic value of baseline craniofacial fibrous dysplasia imaging characteristics and clinical symptomatology can be further evaluated.

Fertility journey of a patient with McCune-Albright syndrome associated with bilateral ovarian involvement

Fertility journey of a patient with McCune-Albright syndrome associated with bilateral ovarian involvement

Fibrous dysplasia of bone in McCune-Albright syndrome: pathophysiology, clinical aspects and treatment

Fibrous dysplasia of bone in McCune-Albright syndrome: pathophysiology, clinical aspects and treatment

Clinical characteristics and management of gonadotropin-independent precocious puberty in McCune–Albright syndrome in children – A case series from a tertiary care center, Sri Lanka

McCune–Albright syndrome (MAS) is characterized by the triad of monostotic/polyostotic fibrous dysplasia (FD), café-au-lait spots, and precocious puberty. Gonadotropin-independent precocious puberty (GIPP) is frequently the presenting feature among many hyperfunctioning endocrinopathies seen in MAS. We report the clinical profile and management of four cases of MAS who were being followed up in a children’s hospital in Sri Lanka. Patient 1 presented with GIPP along with growth hormone excess at the age of 7 years and was started on spironolactone. Patient 2 presented at the age of 4 years but developed GIPP after 2 years and was started on letrozole. Patient 3 initially presented with thyrotoxicosis and hypophosphatemic rickets at 2 years of age and, after 9 months, developed GIPP and a unilateral ovarian cyst and was started on letrozole. Patient 4 presented at the age of 3 years with GIPP with a unilateral ovarian cyst, and letrozole was started. MAS is a clinically heterogeneous entity with various clinical manifestations, with GIPP being one of the most common presentations. Management options are varied with aromatase inhibitors showing promising results. However, long-term studies are needed to comment on the final heights of children with MAS with GIPP.

Analysis of clinical features of 193 Chinese patients with McCune-Albright syndrome through a literature review

To retrospectively analyze the clinical characteristics of 193 Chinese patients with McCune-Albright syndrome (MAS). By using keywords "McCune-Albright syndrome", "Albright syndrome", or " fibrous dysplasia " as the search terms, 193 cases of MAS reported in China from January 1990 to November 2022 from the Wanfang data, CNKI, VIP, PubMed, and Embase databases were obtained, and their clinical data was retrospectively analyzed. Intergroup comparisons were carried out by using t test, Mann-Whitney U test, and X2 test. The 193 MAS patients had included 42 males and 151 females, with the median first-visit age of females being younger than males. The typical triad group had accounted for 46.1% of patients, and the middle first-visit and diagnosis age was younger than the atypical group. The primary reason for first-visit in males of MAS was fibrous dysplasia (FD), whilst that in females of MAS was peripheral precocious puberty (PPP). FD has occurred in 84.5% of the patients, with an average age of onset age being 6.1 years old, and 90% was ≤ 16 years of age. Endocrine hyperfunction was found in 79.3% of the patients, with a higher proportion in females compared with males (P < 0.05). Pituitary involvement was seen in 21.8% of the patients, and the incidence of craniofacial FD and cranial nerve compression was significantly higher in those with elevated growth hormone (GH) than without (P < 0.05). Café-au-Lait Spots were noted in 86.5% of the patients, and 28.3% (28/99) had located on the different side of FD. Most MAS patients had atypical manifestations and multi-systemic involvement. It is more common and occurs earlier in females. The most common reasons for initial diagnosis in male and female patients were FD and PPP, respectively. Patients with elevated GH should be examined for cranial nerve compression.

A Girl with McCune-Albright Syndrome: Case Study

A Girl with McCune-Albright Syndrome: Case Study

Multiple endocrine hyperfunction in McCune-Albright syndrome

Multiple endocrine hyperfunction in McCune-Albright syndrome

Managing endocrine neoplasia in mccune albright syndrome

Managing endocrine neoplasia in mccune albright syndrome

Pregnancy planning strategy in a patient with mccune-albright syndrome

Pregnancy planning strategy in a patient with mccune-albright syndrome