McCune-Albright Syndrome

McCune-Albright Syndrome

No Results

No Results


McCune-Albright syndrome (MAS) consists of at least two of the following three features: (1) polyostotic fibrous dysplasia (PFD), (2) café-au-lait skin pigmentation (see the image below), and (3) autonomous endocrine hyperfunction (eg, gonadotropin-independent precocious puberty). Other endocrine syndromes may be present, including hyperthyroidism, acromegaly, and Cushing syndrome. Mazabraud syndrome, which can also exist in association with MAS, involves the occurrence of myxomas and usually PFD. [1, 2, 3, 4]

The clinical presentation of MAS is highly variable, depending on which of the various potential components of the syndrome predominate. Major manifestations include the following:

Precocious puberty (typically gonadotropin-independent) – This includes breast development, genital maturation (with or without pubic hair growth), increased height velocity, and macroorchidism [5]

Café-au-lait pigmentation – This consists of spots ranging from light brown to dark brown in color, often displaying a segmental distribution, and frequently predominating on one side of the body without crossing the midline; these spots must be differentiated from those characteristic of neurofibromatosis (NF)

PFD – Multiple pathologic fractures may be prominent early in the history; in many cases, bony involvement is found to predominate clinically on 1 side; potential presenting features include gait anomalies, visible bony deformities (including abnormal bone growths of the skull), bone pain, and joint stiffness with pain

Hyperthyroidism (rare without several other features of MAS also being present) – Findings may include tachycardia, arrhythmias (mostly supraventricular), hypertension, hyperthermia, tremor, sleeplessness, weight loss, or (in infants) failure to thrive

Other possible manifestations include the following:

Cushing syndrome

Growth hormone (GH) excess (gigantism and acromegaly)


Ovarian cysts

Pituitary tumors

Thyroid tumors

Hypophosphatemia (hypophosphatemic rickets)

Hypogonadotropic hypogonadism, particularly in the setting of hyperprolactinemia

See Clinical Presentation for more detail.

Full endocrine studies should be performed. Testicular or ovarian hyperfunction is the most common abnormality. Laboratory studies that may be helpful include the following:

Gonadotropin (luteinizing hormone [LH], follicle-stimulating hormone [FSH]) and sex hormone levels

Blood and urinary chemistries

Thyroid testing (thyroid-stimulating hormone [TSH], thyroxine [T4], antithyroid antibodies)

Adrenocorticotropic hormone (ACTH) levels

Serum prolactin (PRL)

Dexamethasone suppression testing (standard or low-dose/high-dose)

Urine collection assayed for free cortisol (urinary free cortisol [UFC])

Growth hormone (GH) and insulinlike growth factor 1 (IGF-1) levels

Polymerase chain reaction (PCR) assay

Diagnostic imaging modalities that may be considered include the following:

Plain radiography (mainly skull and mandibles [craniofacial survey], pelvis, femurs; as clinically indicated)

Ultrasonography (neck and thyroid; ovarian and pelvic; as clinically indicated)

Computed tomography (CT); as clinically pertinent

Magnetic resonance imaging (MRI); as clinically pertinent

Radionuclide bone scanning

Other studies that may be considered include the following:

Arterial blood gas determination (for suspected acidosis)

Electrocardiography (ECG; (for suspected arrhythmia)

Gastrointestinal (GI) endoscopy can be performed to evaluate (for suspected polyposis)

Biopsy (bone, muscle, soft tissue, thyroid); as clinically pertinent

See Workup for more detail.

There is no specific treatment for MAS per se. Pharmacologic agents that have been used to treat precocious puberty in MAS include the following:

Aromatase inhibitors

Gonadotropin-releasing hormone (GnRH) analogues (as adjuncts to aromatase inhibitors)

Ketoconazole [6]

Estrogen receptor agonists (eg, tamoxifen)


Cyproterone acetate

Medroxyprogesterone acetate

Currently, no clinically proven medical therapies are available for PFD associated with MAS. Oral and intravenous (IV) bisphosphonates (eg, pamidronate, alendronate, zoledronate) may be beneficial to prevent disease progression, although data are conflicting. Important: bisphosphonates are very effective at relieving pain in the majority of cases.

Pharmacologic agents that have been used to treat hyperthyroidism in MAS include the following:

Thionamides (eg, propylthiouracil)


Radioiodine (for tissue ablation)

No long-term effective medical treatment for ACTH-independent Cushing syndrome is available.

Pharmacologic agents that have been used to treat GH excess in MAS include the following:


Dopamine agonists (eg, bromocriptine and cabergoline), typically in conjunction with octreotide

GH receptor antagonists (eg, pegvisomant), probably best not used as monotherapy in this setting

Pharmacologic treatment of other manifestations of MAS is as follows:

Hypogonadism – Appropriate hormone replacement therapy

Hypophosphatemia with hyperphosphaturia – Aggressive oral phosphorus replacement

Hypophosphatemic rickets – Appropriate calcitriol therapy with calcium and phosphate repletion

Surgical interventions that may be considered include the following:

Precocious puberty – Oophorectomy or ovarian cystectomy, when medical therapy fails

PFD – Traction or fixation for fractures; for most PFD lesions, routine removal is not warranted

Hyperthyroidism – Thyroidectomy (partial near-total, or total)

Infantile Cushing syndrome – Bilateral adrenalectomy

Gigantism or acromegaly – Surgical removal of the offending lesion (pituitary adenoma) is rarely curative and is considered only if the tumor is threatening vision (in consultation with an experienced base-of-skull neurosurgeon)

See Treatment and Medication for more detail.

McCune-Albright syndrome (MAS) in its classic form consists of at least 2 of the following triad of features [7, 8, 9] :

Polyostotic fibrous dysplasia (PFD)

Café-au-lait skin pigmentation

Autonomous endocrine hyperfunction – The most common form of autonomous endocrine hyperfunction in this syndrome is precocious puberty, which is typically gonadotropin-independent [10, 11]

Other endocrine syndromes described in association with MAS include the following [12, 13] :


Acromegaly or gigantism (due to GH-producing pituitary adenoma)



Cushing syndrome



Hypophosphatemic rickets

Some severely affected patients may present with associated hepatic, cardiac, and gastrointestinal (GI) dysfunction (ie, elevated hepatic transaminases, GI polyposis, and cardiomyopathy). [14]

MAS has been shown to be due to a postzygotic activating mutation of the GNAS gene, coding for the G protein subunit Gs alpha in the affected tissues (see Pathophysiology and Etiology). For semantic reasons, it is important to differentiate MAS from Albright hereditary osteodystrophy (AHO). AHO, which also is caused by a GNAS1 gene defect, [15] results in pseudohypoparathyroidism or pseudopseudohypoparathyroidism. [16]

The clinical presentation of MAS is highly variable, depending on which of the various potential components of the syndrome predominate (see Presentation). Diagnosis of MAS depends on finding at least 2 of the phenotypic features associated with activating GNAS1 mutations.

Early recognition is vital. In typical cases, the diagnosis of MAS is not in doubt. However, in atypical cases, the combination of cutaneous pigmentation, bony lesions, and soft-tissue masses may suggest other conditions (eg, systemic mastocytosis and neurofibromatosis [NF]) (see DDx).

Full endocrine studies should be performed under the care of an endocrinologist. Testicular or ovarian hyperfunction is the most common abnormality. Diagnostic imaging modalities that may be considered include plain radiography, ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and radionuclide bone scanning (as clinically indicated) (see Workup).

Because MAS is a multisystemic condition with a host of variable presentations, management often is challenging and requires a multidisciplinary approach. For most physicians who are not endocrinologists, the crucial points in management are recognition of MAS and referral of the patient to an endocrinologist who is experienced in its management. The endocrinologist, in turn, offers other referrals as indicated (eg, neurosurgeon) (see Treatment).

Most of the clinical features of MAS are caused by a noninherited postzygotic activating mutation of the GNAS1 gene that results in overproduction of a variety of protein products in a fashion independent from normal feedback control mechanisms (see Etiology). [8]

Precocious puberty, the most common endocrine feature of MAS, is a result of gonadotropin-independent autonomous ovarian or testicular function. [5] Precocious puberty caused by this condition is far more common in girls than in boys. In girls, it is the result of estrogen excess from ovarian follicular cysts. [17] Because the sexual precocity associated with MAS is gonadotropin-independent, it is more accurately described as pseudoprecocious puberty.

The café-au-lait spots in MAS are large melanotic macules, sometimes referred to as café-au-lait macules (CALMs). Except for hyperpigmentation of the basal layer, no abnormal pathology is seen.

Fewer than 10 cases of MAS associated with Cushing syndrome have been well documented. This syndrome is distinct, unlike all other endocrinopathies of MAS, which are slowly progressive and persistent without treatment. Several cases of Cushing syndrome in the context of MAS have regressed within the first few years following onset.

Cushing syndrome associated with MAS is predominantly due to adrenocortical hyperfunction. Most of these cases have been described in infants or children. The adrenal glands are bilaterally enlarged and contain multiple small nodules in the cortex. In some cases, Cushing syndrome is transitory. Pituitary-based (ACTH-dependent) Cushing disease in the setting of MAS is far less common.

Hyperthyroidism typically occurs later in childhood, though it can occur within the first year of life. Like Cushing syndrome and precocious puberty, hyperthyroidism associated with MAS is a result of 1 or more autonomous hyperfunctioning thyroid nodules.

Growth hormone (GH) excess from somatotroph adenomas in the pituitary can occur at any age, resulting in gigantism or acromegaly. The GH excess among patients with MAS has been noted to be as high as 21%. The basis of GH hypersecretion in MAS remains incompletely understood, but it appears to have a different basis from that of acromegaly or gigantism in non-MAS patients. [18]  A study by Yao et al suggested that growth hormone excess in MAS occurs more frequently in males than in females; the investigators determined that of 52 patients with MAS, 13 (25.0%) had growth hormone excess, including 10 males (76.9%). The study also found an association between growth hormone excess in MAS and greater severity of skeletal lesions, with more craniofacial bone involvement. [19]

Fibrous dysplasia (FD) in MAS can involve any bone but most commonly affects the long bones, ribs, and skull. It may range from small asymptomatic areas detectable only by bone scan to markedly disfiguring lesions that can result in frequent pathologic fractures and impingement on vital nerves.

Approximately 30 cases of FD associated with single or multiple intramuscular or juxtamuscular myxomas (Mazabraud syndrome) have been documented. [2, 3] This syndrome has been associated with precocious puberty and café-au-lait spots and occurs in association with MAS. The myxomas associated with this condition can occur in virtually any location in the muscular system. The exact etiopathogenesis of the syndrome is unclear, because no activating mutations of the GNAS1 gene have been demonstrated in this clinical variant.

Simple myxomas typically are benign and solitary, with peak incidence in the sixth and seventh decades. The age of peak incidence for this syndrome is young adulthood, and the tumors commonly are multiple. The main sites of involvement are the large muscles of the thighs, buttocks, and shoulders. They often are located close to FD lesions but typically remain separate from them. They commonly recur, even after attempts at surgical resection.

Hypophosphatemic rickets is a potential complication that may worsen the bone disease associated with PFD. It is due to a tubulopathy and characterized by hyperphosphaturia. In patients with MAS, hyperphosphaturia may be due to a phosphatonin similar to that seen in patients with tumor-induced osteomalacia, which appears to be fibroblast growth factor 23 (FGF-23). While MAS patients with hypophosphatemic rickets are typically managed with calcitriol and phosphorus supplements, they must be monitored closely for hypercalcemia, excessive hypercalciuria, nephrocalcinosis, and progressive loss of renal function, as well as the development of secondary hyperparathyroidism.

Hepatic abnormalities range from mild elevation of hepatic transaminases to severe neonatal jaundice and chronic cholestasis. Although some liver biopsies appear normal, others reveal mild biliary abnormalities or fatty liver. One case report described fatty liver in an infant with Cushing syndrome, suggesting that the fatty liver may have been secondary to glucocorticoid excess. Elevated transaminases in this infant, however, persisted long after the glucocorticoid excess had been corrected with adrenalectomy.

A study by Wood et al indicated that a wide range of gastrointestinal (GI) tract and pancreatic abnormalities occur in patients with MAS, with the investigators pointing out that GNAS mutations are not only responsible for MAS but are also found in association with several GI and pancreatic neoplasms. GI abnormalities in the study’s seven patients included gastric heterotopia/metaplasia, gastric hyperplastic polyps, fundic gland polyps, and a hamartomatous polyp, with endoscopic ultrasonographic findings in the pancreas suggesting the presence of intraductal papillary mucinous neoplasms (IPMNs). [20]

In a cross-sectional study of 54 patients with MAS, Robinson et al found radiographic GI abnormalities in 30 (56%) of them. IPMNs occurred in 25 (46%) patients, with 14 individuals having IPMNs alone and 11 also having abnormal hepatobiliary imaging. In addition, the investigators reported that, compared with the rest of the cohort, more fibrous dysplasia (as evaluated using skeletal burden scores), as well as a greater prevalence of acute pancreatitis and diabetes mellitus, was present in the patients with MAS-associated GI pathology. [21]

Many case reports describe sudden deaths, mostly occurring in patients with multiple endocrine and nonendocrine manifestations of MAS. Persistent tachycardia has been observed in addition to mild-to-moderate cardiomegaly, even in the absence of hyperthyroidism. Although the cause of death in these patients is unclear, it is presumed to be secondary to cardiac arrhythmia.

Only a few cases of malignant transformation of skeletal lesions have been described in the setting of MAS, most frequently in the setting of therapeutic irradiation. This occurs in probably less than 1% of MAS cases. The tendency for malignant transformation to occur may be greater in patients who have concomitant GH excess or those with Mazabraud syndrome. Observed malignancies include the following:

Osteosarcomas (most common)




Females appear to be at greater risk for breast cancer, probably as a consequence of prolonged exposure to elevated estrogen and/or GH levels. The underlying GNAS1 mutation also may play a role. For the same reasons, these patients also appear to be at increased risk for thyroid malignancies and testicular cancer (a novel finding by the National Institutes of Health [NIH]).

MAS is caused by a sporadic, early postzygotic somatic mutation in the GNAS1 gene at locus 20q13.1-13.2, coding for the G protein subunit Gs alpha. [22] This genetic finding has been noted and confirmed in various tissue specimens from patients with MAS. [23] Researchers have isolated activating mutations of GNAS1 in pituitary adenomas, thyroid adenomas, ovarian cysts, monostotic bone dysplasia, and the adrenal glands. [24] GNAS1 gene abnormality in pseudohypoparathyroidism I-a has also been noted. [25]

G proteins couple cell surface receptors to intracellular proteins to activate or inactivate signaling cascades. The stimulatory G protein is normally activated when a hormone or other ligand binds to the cell surface receptor (see the image below). The activated Gs alpha disassociates from the receptor, binds to adenylyl cyclase, and stimulates an increase in intracellular cyclic adenosine monophosphate (cAMP) levels. Gs alpha then is inactivated, reassociates with the receptor, and is again available for hormone-mediated reactivation.

The mutations that cause MAS occur at a site in the protein that mediates inactivation of Gs alpha (see the image below). Once activated, the mutated Gs alpha subunit remains activated for a prolonged period despite the absence of hormone (GPCR ligand) stimulation. This results in constitutive activation of Gs alpha, constant stimulation of adenylyl cyclase, and persistently high levels of intracellular cAMP. Increased cAMP levels can mediate mitogenesis and increased cell function. The specific phenotype depends on the cell type containing the mutation.

The classic triad of features in MAS—PFD, autonomous endocrine hyperfunction, and café-au-lait skin pigmentation—can all be explained by activation of the Gs alpha subunit and increased intracellular cAMP levels.

Eumelanogenesis (formation of brown/black pigment) is normally stimulated by melanocyte-stimulating hormone (MSH) binding to the MSH receptor, a classic G protein receptor coupled to Gs alpha. Constitutive activation of the Gs alpha subunit in melanocytes results in the increase in brown pigmentation characteristic of the café-au-lait spots seen in the syndrome. Likewise, both the luteinizing hormone (LH) and the follicle-stimulating hormone (FSH) receptors are Gs alpha−coupled receptors.

Constitutive activation of the postreceptor cAMP signaling cascade in ovarian follicular cells results in cyst formation, estrogen production, and gonadotropin-independent precocious puberty. Similar mechanisms of increased intracellular cAMP likely explain essentially all of the other endocrine and nonendocrine features of MAS.

Because MAS results from a postzygotic somatic mutation, all the daughter cells of the embryonic cell in which the initial mutation occurred also contain the mutation. The earlier the mutation occurs in embryogenesis, the more widespread the tissue involvement.

Mutations late in embryogenesis are more focused and account for those mild cases in which only 2 or 3 of the classic phenotypic features of the syndrome are present. If the mutation occurs very late in tissue development after differentiation into a specific cell line, then a single adenoma may result. Gs alpha−activating mutations have been reported in isolated hyperfunctioning thyroid nodules and in somatotroph adenomas.

Although GNAS1 mutations could occur in germ cells (either oocytes or spermatocytes), the resulting zygote and all daughter cells then would contain the mutation. Activating GNAS1 mutations are likely lethal if they occur very early in embryogenesis. This accounts for the lack of autosomal dominant transmission of this syndrome.

The exact incidence of MAS in the United States and internationally is unknown, but its prevalence is probably between 1 case in 100,000 population and 1 case in 1 million population, rendering it a very rare, sporadically occurring disorder. [8] In a review of radiographs from 82,000 patients, only 23 cases of PFD were found. Polyostotic variants of FD are uncommon, and MAS is even less common. The relative incidence of monostotic FD (MFD) is 70%, whereas that of PFD is 30% and that of MAS is less than 3%.

Severe cases of MAS involving multiple endocrine tissues may be recognized shortly after birth. Cases of infantile Cushing syndrome and hyperthyroidism have also been reported in the neonatal period. Additionally, FD, café-au-lait pigmentation, liver disease, and hypophosphatemia can initially be seen in infancy.

Less severe findings of MAS can occur at almost any time during childhood. Most commonly, the onset of MAS occurs in early childhood (mean age, 4.9 years; range, 0.3-9 years), typically earlier in girls than in boys. Precocious puberty in girls can be seen in infants as young as 4 months, though it more frequently occurs in girls older than 1 year. Café-au-lait pigmentation is more likely to become apparent later in the progression of the syndrome.

GH-producing pituitary tumors and functional-thyroid adenomas secondary to activating GNAS1 mutations can occur in individuals at any age. Disease with a later onset (ie, in the early to late teenage years) tends to be associated with clinically attenuated phenotypes.

Both sexes are affected by MAS, but the syndrome has been reported to be about twice as common in females as in males. That girls develop precocious puberty far more frequently than boys (9:1 female-to-male ratio) probably explains why this autosomal mutation is recognized more frequently in girls than in boys. Other manifestations of MAS probably occur with approximately equal frequency in females and males.

MAS has no ethnic predilection.

Apart from the small subgroup of patients with increased perioperative mortality and those patients who develop malignancies, MAS is not associated with a significantly increased mortality. In general, patients achieve a normal life span. Mortality and morbidity related to MAS result from the fractures, malignancies, endocrine disorders, and other conditions associated with this syndrome. The symptom and disability burden of MAS can be quite high, owing to the associated chronic pain and deformities, as well as the sequelae of chronic multihormonal endocrinopathies. Thus, the prognosis varies according to the manifestations of MAS.

With precocious puberty, the prognosis depends on the duration of premature estrogen exposure. Early puberty is not a life-threatening condition and does not seem to lead to problems after true, centrally mediated puberty begins at an appropriate age. Early breast development and vaginal bleeding can be accompanied by loss of adult height potential. Reduction of height potential depends on the degree of bone age advancement that occurs during the periods of early estrogen exposure.

A study of 16 girls and 10 boys with MAS found (1) that MAS occurs slightly more frequently in girls than in boys, (2) that peripheral precocious puberty (PPP) in MAS occurs significantly more frequently and at a younger age in girls than in boys, (3) that PPP in boys with MAS correlates with bilateral testicular enlargement, (4) that unilateral macroorchidism can occur, and (5) that testicular microlithiasis might function as another marker for MAS in males. [26]

Moreover, a literature review by Aversa et al indicated that at presentation, macroorchidism is the most common testicular abnormality related to MAS. In addition, the study found that in MAS, an association does not always exist between macroorchidism and clinical and biochemical evidence of peripheral precocious puberty. [27]

FD may have severe effects, including pathologic fractures, facial disfigurement, and vision and hearing problems. It is difficult to treat effectively. Current therapies focus on treating complications of FD, rather than on preventing it from developing. Current studies using bisphosphonates are promising, though it is unclear whether bisphosphonates significantly reduce the morbidity associated with these lesions.

Hyperthyroidism can cause severe failure to thrive in infants and young children, decreased attention span, and osteoporosis. Tachycardia resulting from severe hyperthyroidism may complicate or trigger a cardiac event. Radioiodine (131 I) ablation or thyroidectomy treats hyperthyroidism effectively. The long-term prognosis is excellent with adequate thyroid hormone replacement.

Infantile Cushing syndrome can cause severe growth failure, poor muscle tone, and hypertension. Permanent effect on growth potential is also possible. Comorbid heart and liver disease are poor prognostic markers and may indicate the need for prompt adrenalectomy. [28]

The long-term prognosis for infantile Cushing syndrome depends on adequate replacement of both mineralocorticoids and glucocorticoids. Individuals remain at risk for significant morbidity or mortality due to adrenal insufficiency during times of severe stress and should receive stress doses of hydrocortisone on an emergency basis.

Hypophosphatemia causes rickets and short stature; the pathophysiology of hypophosphatemic rickets, as well as the need for long-term therapy with calcitriol and phosphorus supplementation in these cases, increases the risk of nephrocalcinosis and loss of renal function over time.

Gigantism or acromegaly can occur, carrying a risk of glucose intolerance, hypertriglyceridemia, hypertension, and mild myopathy. GH secretion in MAS is difficult to treat effectively. Octreotide acetate or pegvisomant has proved effective in many cases, but not all. Furthermore, radiation treatment of the adenoma increases the risk of malignant change in areas of FD in the radiation field. The long-term prognosis in refractory cases of acromegaly is poor.

Although 2 long-term follow-up studies have shown no increased risk of premature death, several authors have noted unexplained sudden death in patients with a severe phenotype. Patients may have multiple endocrine, cardiac, GI, central nervous system (CNS), hematopoietic, and hepatic manifestations, all of which can contribute to significant morbidity. Although no arrhythmias have been detected in individuals with MAS, this is the presumed mechanism of sudden death.

Educational requirements depend on the phenotypic expression of MAS. Individuals with FD in critical weight-bearing areas should be instructed to avoid activities (eg, contact sports) that put the skeleton at risk for pathologic fracture.

Patients who have undergone bilateral adrenalectomy for Cushing syndrome should be given clear instructions on changing steroid dosing for febrile illnesses. Furthermore, these individuals need to wear medic alert identification bracelets or necklaces so that if severe illness or trauma occurs, medical personnel will be aware of the requirement for stress doses of hydrocortisone.

Patients should also be informed MAS is not hereditary and that offspring of affected patients are not at increased risk for the syndrome.

For patient education resources, see the Thyroid and Metabolism Center, as well as Thyroid Problems.

Ramirez Mejia AR, Moreno Casado MJ, Ahumada Pavez NR, Rojas Soldado MA. Mazabraud’s syndrome. New clinical case and review of findings. Reumatol Clin. 2015 Dec 16. [Medline].

Faivre L, Nivelon-Chevallier A, Kottler ML, Robinet C, Khau Van Kien P, Lorcerie B, et al. Mazabraud syndrome in two patients: clinical overlap with McCune-Albright syndrome. Am J Med Genet. 2001 Mar 1. 99(2):132-6. [Medline].

Thomachot B, Daumen-Legre V, Pham T, Acquaviva PC, Lafforgue P. Fibrous dysplasia with intramuscular myxoma (Mazabraud’s syndrome). Report of a case and review of the literature. Rev Rhum Engl Ed. 1999 Mar. 66(3):180-3. [Medline].

Boyce AM, Florenzano P, de Castro LF, et al. Fibrous Dysplasia/McCune-Albright Syndrome. 2015 Feb 26 [updated 2018 Aug 16]. [Medline]. [Full Text].

Corica D, Aversa T, Pepe G, De Luca F, Wasniewska M. Peculiarities of Precocious Puberty in Boys and Girls With McCune-Albright Syndrome. Front Endocrinol (Lausanne). 2018. 9:337. [Medline]. [Full Text].

Messina MF, Aversa T, de Sanctis L, Wasniewska M, Valenzise M, Pajno GB, et al. Adult height following a combined treatment of ketoconazole – cyproterone acetate – leuprolide depot in a boy with atypical McCune-Albright syndrome. Hormones (Athens). 2014 Nov 5. [Medline].

Medina YN, Rapaport R. Evolving diagnosis of McCune-Albright syndrome. atypical presentation and follow up. J Pediatr Endocrinol Metab. 2009 Apr. 22(4):373-7. [Medline].

Dumitrescu CE, Collins MT. McCune-Albright syndrome. Orphanet J Rare Dis. 2008 May 19. 3:12. [Medline]. [Full Text].

Weinstein LS. Bilezikian JP, Raisz LG, Rodan GA, eds. Principles of Bone Biology. San Diego, Calif: Academic Press: Other skeletal diseases resulting from G protein defects–fibrous dysplasia and McCune Albright syndrome.; 1996. 877-87.

Rosen D, Kelch RP. Precocious and delayed puberty. Becker KL, Bilezikian JP, Hung W, et al, eds. Principles and Practice of Endocrinology and Metabolism. 2nd ed. Philadelphia, Pa: JB Lippincott; 1995. 830-42.

Bercaw-Pratt JL, Moorjani TP, Santos XM, Karaviti L, Dietrich JE. Diagnosis and management of precocious puberty in atypical presentations of McCune-Albright syndrome: a case series review. J Pediatr Adolesc Gynecol. 2012 Feb. 25(1):e9-e13. [Medline].

Cavanah SF, Dons RF. McCune-Albright syndrome: how many endocrinopathies can one patient have?. South Med J. 1993 Mar. 86(3):364-7. [Medline].

Elhaï M, Meunier M, Kahan A, Cormier C. McCune-Albright syndrome revealed by hyperthyroidism at advanced age. Ann Endocrinol (Paris). 2011 Dec. 72(6):526-9. [Medline].

Zacharin M, Bajpai A, Chow CW, Catto-Smith A, Stratakis C, Wong MW, et al. Gastrointestinal polyps in McCune Albright syndrome. J Med Genet. 2011 Jul. 48(7):458-61. [Medline].

Weinstein LS, Liu J, Sakamoto A, Xie T, Chen M. Minireview: GNAS: normal and abnormal functions. Endocrinology. 2004 Dec. 145(12):5459-64. [Medline].

Kapoor S, Gogia S, Paul R, Banerjee S. Albright’s hereditary osteodystrophy. Indian J Pediatr. 2006 Feb. 73(2):153-6. [Medline].

Sotomayor K, Iñiguez G, Ugarte F, Villarroel C, López P, Avila A, et al. Ovarian function in adolescents with McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2011. 24(7-8):525-8. [Medline].

Christoforidis A, Maniadaki I, Stanhope R. McCune-Albright syndrome: growth hormone and prolactin hypersecretion. J Pediatr Endocrinol Metab. 2006 May. 19 Suppl 2:623-5. [Medline].

Yao Y, Liu Y, Wang L, et al. Clinical characteristics and management of growth hormone excess in patients with McCune-Albright syndrome. Eur J Endocrinol. 2017 Mar. 176 (3):295-303. [Medline].

Wood LD, Noe M, Hackeng W, et al. Patients with McCune-Albright syndrome have a broad spectrum of abnormalities in the gastrointestinal tract and pancreas. Virchows Arch. 2017 Apr. 470 (4):391-400. [Medline].

Robinson C, Estrada A, Zaheer A, et al. Clinical and Radiographic Gastrointestinal Abnormalities in McCune-Albright Syndrome. J Clin Endocrinol Metab. 2018 Aug 15. [Medline].

Chapurlat RD, Orcel P. Fibrous dysplasia of bone and McCune-Albright syndrome. Best Pract Res Clin Rheumatol. 2008 Mar. 22(1):55-69. [Medline].

Cohen MM Jr, Howell RE. Etiology of fibrous dysplasia and McCune-Albright syndrome. Int J Oral Maxillofac Surg. 1999 Oct. 28(5):366-71. [Medline].

Diaz A, Danon M, Crawford J. McCune-Albright syndrome and disorders due to activating mutations of GNAS1. J Pediatr Endocrinol Metab. 2007 Aug. 20(8):853-80. [Medline].

Ozono K. [GNAS1 gene abnormality in pseudohypoparathyroidism I a]. Clin Calcium. 2007 Aug. 17(8):1214-9. [Medline].

Wasniewska M, Matarazzo P, Weber G, Russo G, Zampolli M, Salzano G, et al. Clinical presentation of McCune-Albright syndrome in males. J Pediatr Endocrinol Metab. 2006 May. 19 Suppl 2:619-22. [Medline].

Aversa T, Zirilli G, Corica D, De Luca F, Wasniewska M. Phenotypic testicular abnormalities and pubertal development in boys with McCune-Albright syndrome. Ital J Pediatr. 2018 Nov 19. 44 (1):136. [Medline]. [Full Text].

Brown RJ, Kelly MH, Collins MT. Cushing syndrome in the McCune-Albright syndrome. J Clin Endocrinol Metab. 2010 Apr. 95(4):1508-15. [Medline]. [Full Text].

de Sanctis C, Lala R, Matarazzo P, Balsamo A, Bergamaschi R, Cappa M, et al. McCune-Albright syndrome: a longitudinal clinical study of 32 patients. J Pediatr Endocrinol Metab. 1999 Nov-Dec. 12(6):817-26. [Medline].

Demos TC, Lomasney LM, Martin-Carreras T, Sanchez E, Bancroft LW. Polyostotic fibrous dysplasia. Orthopedics. 2014 Nov 1. 37(11):722-82. [Medline].

Arrigo T, Pirazzoli P, De Sanctis L, Leone O, Wasniewska M, Messina MF, et al. McCune-Albright syndrome in a boy may present with a monolateral macroorchidism as an early and isolated clinical manifestation. Horm Res. 2006. 65(3):114-9. [Medline].

Jung AJ, Soskin S, Paris F, Lipsker D. [McCune-Albright syndrome revealed by Blaschko-linear café-au-lait spots on the back]. Ann Dermatol Venereol. 2016 Jan. 143 (1):21-6. [Medline].

Medow JE, Agrawal BM, Resnick DK. Polyostotic fibrous dysplasia of the cervical spine: case report and review of the literature. Spine J. 2007 Nov-Dec. 7(6):712-5. [Medline].

de Araújo PI, Soares VY, Queiroz AL, dos Santos AM, Nascimento LA. Sarcomatous transformation in the McCune-Albright syndrome. Oral Maxillofac Surg. 2012 Jun. 16(2):217-20. [Medline].

Noh JH, Kong DS, Seol HJ, Shin HJ. Endoscopic Decompression for Optic Neuropathy in McCune-Albright Syndrome. J Korean Neurosurg Soc. 2014 Sep. 56(3):281-3. [Medline]. [Full Text].

de Sanctis L, Delmastro L, Russo MC, Matarazzo P, Lala R, de Sanctis C. Genetics of McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2006 May. 19 Suppl 2:577-82. [Medline].

Celi FS, Coppotelli G, Chidakel A, Kelly M, Brillante BA, Shawker T, et al. The role of type 1 and type 2 5′-deiodinase in the pathophysiology of the 3,5,3′-triiodothyronine toxicosis of McCune-Albright syndrome. J Clin Endocrinol Metab. 2008 Jun. 93(6):2383-9. [Medline]. [Full Text].

Lietman SA, Ding C, Levine MA. A highly sensitive polymerase chain reaction method detects activating mutations of the GNAS gene in peripheral blood cells in McCune-Albright syndrome or isolated fibrous dysplasia. J Bone Joint Surg Am. 2005 Nov. 87(11):2489-94. [Medline].

Narumi S, Matsuo K, Ishii T, Tanahashi Y, Hasegawa T. Quantitative and Sensitive Detection of GNAS Mutations Causing McCune-Albright Syndrome with Next Generation Sequencing. PLoS One. 2013. 8(3):e60525. [Medline]. [Full Text].

Randazzo WT, Franco A, Hoossainy S, Lewis KN. Daughter cyst sign. J Radiol Case Rep. 2012 Nov. 6(11):43-7. [Medline]. [Full Text].

Bulakbasi N, Bozlar U, Karademir I, Kocaoglu M, Somuncu I. CT and MRI in the evaluation of craniospinal involvement with polyostotic fibrous dysplasia in McCune-Albright syndrome. Diagn Interv Radiol. 2008 Dec. 14(4):177-81. [Medline].

Esmaili J, Chavoshi M, Noorani MH, Eftekhari M, Assadi M. Late diagnosed polyostotic fibrous dysplasia. Bone scan, radiography and magnetic resonance imaging findings. Hell J Nucl Med. 2010 Jan-Apr. 13(1):65-6. [Medline].

Defilippi C, Chiappetta D, Marzari D, Mussa A, Lala R. Image diagnosis in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2006 May. 19 Suppl 2:561-70. [Medline].

Riminucci M, Robey PG, Bianco P. The pathology of fibrous dysplasia and the McCune-Albright syndrome. Pediatr Endocrinol Rev. 2007 Aug. 4 Suppl 4:401-11. [Medline].

Dunkel L. Use of aromatase inhibitors to increase final height. Mol Cell Endocrinol. 2006 Jul 25. 254-255:207-16. [Medline].

Mieszczak J, Lowe ES, Plourde P, Eugster EA. The aromatase inhibitor anastrozole is ineffective in the treatment of precocious puberty in girls with McCune-Albright syndrome. J Clin Endocrinol Metab. 2008 Jul. 93(7):2751-4. [Medline].

Wit JM, Hero M, Nunez SB. Aromatase inhibitors in pediatrics. Nat Rev Endocrinol. 2011 Oct 25. 8(3):135-47. [Medline].

Alves C, Silva SF. Partial benefit of anastrozole in the long-term treatment of precocious puberty in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2012. 25(3-4):323-5. [Medline].

Feuillan P, Calis K, Hill S, Shawker T, Robey PG, Collins MT. Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome: a pilot study. J Clin Endocrinol Metab. 2007 Jun. 92(6):2100-6. [Medline].

Syed FA, Chalew SA. Ketoconazole treatment of gonadotropin independent precocious puberty in girls with McCune-Albright syndrome: a preliminary report. J Pediatr Endocrinol Metab. 1999 Jan-Feb. 12(1):81-3. [Medline].

Eugster EA, Rubin SD, Reiter EO, Plourde P, Jou HC, Pescovitz OH. Tamoxifen treatment for precocious puberty in McCune-Albright syndrome: a multicenter trial. J Pediatr. 2003 Jul. 143(1):60-6. [Medline].

Messina MF, Arrigo T, Wasniewska M, Lombardo F, Crisafulli G, Salzano G, et al. Combined treatment with ketoconazole and cyproterone acetate in a boy with McCune-Albright syndrome and peripheral precocious puberty. J Endocrinol Invest. 2008 Sep. 31(9):839-40. [Medline].

DiMeglio LA. Bisphosphonate therapy for fibrous dysplasia. Pediatr Endocrinol Rev. 2007 Aug. 4 Suppl 4:440-5. [Medline].

Lala R, Matarazzo P, Andreo M, Marzari D, Bellone J, Corrias A, et al. Bisphosphonate treatment of bone fibrous dysplasia in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2006 May. 19 Suppl 2:583-93. [Medline].

Mansoori LS, Catel CP, Rothman MS. Bisphosphonate treatment in polyostotic fibrous dysplasia of the cranium: case report and literature review. Endocr Pract. 2010 Sep-Oct. 16(5):851-4. [Medline].

Li GD, Ogose A, Hotta T, Kawashima H, Ariizumi T, Xu Y, et al. Long-term efficacy of oral alendronate therapy in an elderly patient with polyostotic fibrous dysplasia: A case report. Oncol Lett. 2011 Nov. 2(6):1239-1242. [Medline]. [Full Text].

Chan B, Zacharin M. Maternal and infant outcome after pamidronate treatment of polyostotic fibrous dysplasia and osteogenesis imperfecta before conception: a report of four cases. J Clin Endocrinol Metab. 2006 Jun. 91(6):2017-20. [Medline].

Florenzano P, Pan KS, Brown SM, et al. Age-Related Changes and Effects of Bisphosphonates on Bone Turnover and Disease Progression in Fibrous Dysplasia of Bone. J Bone Miner Res. 2019 Jan 15. [Medline].

de Boysson H, Johnson A, Hablani N, Hajlaoui W, Auzary C, Geffray L. Tocilizumab in the treatment of a polyostotic variant of fibrous dysplasia of bone. Rheumatology (Oxford). 2015 Sep. 54 (9):1747-9. [Medline].

Akintoye SO, Chebli C, Booher S, Feuillan P, Kushner H, Leroith D, et al. Characterization of gsp-mediated growth hormone excess in the context of McCune-Albright syndrome. J Clin Endocrinol Metab. 2002 Nov. 87(11):5104-12. [Medline].

Chanson P, Salenave S, Orcel P. McCune-Albright syndrome in adulthood. Pediatr Endocrinol Rev. 2007 Aug. 4 Suppl 4:453-62. [Medline].

Gesmundo R, Guanà R, Valfrè L, De Sanctis L, Matarazzo P, Marzari D, et al. Laparoscopic management of ovarian cysts in peripheral precocious puberty of McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2006 May. 19 Suppl 2:571-5. [Medline].

Majoor BCJ, Leithner A, van de Sande MAJ, Appelman-Dijkstra NM, Hamdy NAT, Dijkstra PDS. Individualized approach to the surgical management of fibrous dysplasia of the proximal femur. Orphanet J Rare Dis. 2018 May 2. 13 (1):72. [Medline]. [Full Text].

Verma RR, Paul A. Fibrous dysplasia of the fourth metacarpal: en-bloc resection and free metatarsal transfer. Orthopedics. 2006 Apr. 29(4):371-2. [Medline].

Boyce AM, Kelly MH, Brillante BA, Kushner H, Wientroub S, Riminucci M, et al. A randomized, double blind, placebo-controlled trial of alendronate treatment for fibrous dysplasia of bone. J Clin Endocrinol Metab. 2014 Nov. 99(11):4133-40. [Medline].

Wu D, Ma J, Bao S, Guan H. Continuous effect with long-term safety in zoledronic acid therapy for polyostotic fibrous dysplasia with severe bone destruction. Rheumatol Int. 2014 Sep 18. [Medline].

Messina MF, Aversa T, de Sanctis L, Wasniewska M, Valenzise M, Pajno GB, et al. Adult height following a combined treatment of ketoconazole – cyproterone acetate – leuprolide depot in a boy with atypical McCune-Albright syndrome. Hormones (Athens). 2014 Nov 5. [Medline].

Hatano H, Morita T, Ariizumi T, Kawashima H, Ogose A. Malignant transformation of fibrous dysplasia: A case report. Oncol Lett. 2014 Jul. 8(1):384-386. [Medline].

Gabriel I Uwaifo, MD Associate Professor, Section of Endocrinology, Diabetes and Metabolism, Louisiana State University School of Medicine in New Orleans; Adjunct Professor, Joint Program on Diabetes, Endocrinology and Metabolism, Pennington Biomedical Research Center in Baton Rouge

Gabriel I Uwaifo, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Society of Hypertension, Endocrine Society

Disclosure: Nothing to disclose.

Nicholas J Sarlis, MD, PhD, FACP Vice President, Head of Medical Affairs, Incyte Corporation

Nicholas J Sarlis, MD, PhD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American Association of Clinical Endocrinologists, American College of Physicians, American Federation for Medical Research, American Head and Neck Society, American Medical Association, American Society for Radiation Oncology, American Thyroid Association, Endocrine Society, New York Academy of Sciences, Royal Society of Medicine, Association for Psychological Science, American College of Endocrinology, European Society for Medical Oncology, American Society of Clinical Oncology

Disclosure: Received salary from Incyte Corporation for employment; Received ownership interest from Sanofi-Aventis for previous employment; Received ownership interest/ stock & stock option (incl. rsu) holder from Incyte Corporation for employment.

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke’s Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Bruce A Boston, MD Chief, Division of Pediatric Endocrinology, Director, Pediatric Endocrine Training Program, Doernbecher Children’s Hospital; Professor, Department of Pediatrics, Division of Pediatric Endocrinology, Oregon Health and Science University School of Medicine

Bruce A Boston, MD is a member of the following medical societies: Alpha Omega Alpha, American Diabetes Association, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children’s Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Marcie K Drury Brown, MD Fellow in Pediatric Endocrinology, Department of Pediatrics, Oregon Health and Science University

Marcie K Drury Brown, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Oregon Medical Association

Disclosure: Nothing to disclose.

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Sherry L Franklin, MD, FAAP Medical Director, Pediatric Endocrinology of San Diego Medical Group, Inc

Sherry L Franklin is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Pediatric Endocrine Society, and The Endocrine Society.

Disclosure: Nothing to disclose.

Stephen Kemp, MD, PhD Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children’s Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Arlan L Rosenbloom, MD Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida College of Medicine; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology

Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Florida Pediatric Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Eleanor E Sahn, MD Director, Division of Pediatric Dermatology, Associate Professor, Departments of Dermatology and Pediatrics, Medical University of South Carolina

Eleanor E Sahn, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

D Stanton Whittaker Jr, MD Consulting Staff, Boone Dermatology Clinic

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

McCune-Albright Syndrome

Research & References of McCune-Albright Syndrome|A&C Accounting And Tax Services