SUN-291 Presence of Aberrant Adrenocorticotropic Hormone Precursors in Two Cases of McCune- Albright Syndrome

Abstract Background: McCune-Albright syndrome (MAS) is a rare disorder. MAS is caused by an activating postzygotic somatic mutation in the GNAS, and, is classically defined by the occurrence of fibrous dysplasia (FD), café-au-lait skin macules, and precocious puberty. Autonomous GH and/or PRL production in MAS has been reported. However, there have been no reports of ACTH excess in MAS. Method: Plasma ACTH and serum cortisol (F) levels were assessed using electrochemiluminescence immunoassays (Eclusys ACTHTM and Eclusys Cortisol IITM, respectively; Roche Diagnostics K.K., Tokyo, Japan).Clinical Cases: Case1; 42-year-old man showed craniofacial deformities and suffered from multiple bone fractures. He was diagnosed with FD at the age of 23 years. Café-au-lait macules were found on his back. He had slightly acromegaloid features. He showed no cushingoid features. Pituitary adenoma or hyperplasia was not detected by MRI. The diagnosis of GH excess was confirmed by no suppression of serum GH levels by a 75-g oral glucose tolerance test (nadir GH: 2.34 ng/mL) and an elevated serum IGF-I level (307 ng/mL; normal range: 92-257 ng/mL). The patient was treated with monthly subcutaneous lanreotide injection and then GH excess was well controlled. Basal ACTH and F levels in blood were 40.6-63.4 pg/mL and 8.0-10.5 μg/dL, respectively. The urinary free cortisol (UFC) level was 53 μg/day. Autonomous F excess was excluded by the level of midnight F (1.2 μg/dL) and the level of F (0.2 μg/dL) after a low-dose (1 mg) dexamethasone suppression test (DST). Case2; A 32-year-old man was diagnosed with MAS and gigantism at the Pediatrics Department at the age of 5 years. Treatment of GH excess was well controlled by monthly octreotide depot. He had no acromegaloid features and no cushingoid features. Café-au-lait macules were observed from the left flank to the back. Pituitary adenoma or hyperplasia was not detected by MRI. Basal ACTH and F levels in blood were 35.5-73.1 pg/mL and 7.0-11.7 μg/dL, respectively. The UFC level was 61 μg/day. Autonomous F excess was excluded by the level of F (<0.2 μg/dL) after a low-dose (0.5 mg) DST.Possibility of primary adrenal insufficiency was excluded by ACTH stimulation test and/or insulin tolerance test in both cases. The involvement of 11β-HSD1 by GH excess and PC1/3 deficiency were also excluded. Gel exclusion chromatography was then performed. POMC and pro-ACTH were detected and the aberrant ACTH/normal ACTH ratio was 42% in both cases. Conclusion: This is the first report of the presence of aberrant ACTH precursors, particularly POMC, in MAS. A high ratio of circulating ACTH to F may suggest secretion of inactive ACTH precursors in MAS. Further investigations are required to determine whether GNAS mutations or other mechanisms are involved in the presence of aberrant ACTH precursors in MAS.

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Transsphenoidal surgery in a patient with acromegaly and McCune–Albright syndrome: application of neuronavigation

Journal of Neurosurgery ◽

10.3171/jns/2008/108/01/0164 ◽

2008 ◽

Vol 108 (1) ◽

pp. 164-169 ◽

Cited By ~ 8

Author(s):

Wanchen Dou ◽

Ning Lin ◽

Wenbin Ma ◽

Yi Yang ◽

Huijuan Zhu ◽

...

Keyword(s):

Fibrous Dysplasia ◽

Transsphenoidal Surgery ◽

Tolerance Test ◽

Oral Glucose ◽

Mccune Albright Syndrome ◽

History Of ◽

Albright Syndrome ◽

Clinical Triad ◽

The Right ◽

Mccune Albright

✓The McCune–Albright syndrome (MAS) is characterized by a clinical triad of polyostotic fibrous dysplasia, café-au-lait hyperpigmented macules, and hypersecretory endocrinopathies. Acromegaly is an uncommon manifestation of the endocrine disturbance associated with MAS, and the role of surgery in managing these cases has been a topic of debate. The authors present the case of a 35-year-old man with MAS who was also diagnosed with acromegaly, hyperprolactinemia, and pituitary macroadenoma. The patient had an 18-year history of fibrous dysplasia involving the right frontal bone and ribs as well as multiple endocrinopathies, but no cutaneous hyperpigmented macules. An oral glucose tolerance test demonstrated partial suppression of plasma levels of growth hormone (GH). The patient underwent transsphenoidal resection of the pituitary tumor, performed with assistance of neuronavigation, and tolerated the procedure well. After the surgery, both prolactin and GH levels returned to normal. These results suggest that neuronavigation-assisted transsphenoidal surgery can safely remove pituitary adenomas associated with MAS and successfully treat the underlying endocrine abnormalities.

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McCune-albright syndrome and acromegaly: hormonal control with use of cabergoline and long-acting somatostatin - case report

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302009000100015 ◽

2009 ◽

Vol 53 (1) ◽

pp. 102-106 ◽

Cited By ~ 2

Author(s):

João Paulo C. Almeida ◽

Lucas Alverne F. Albuquerque ◽

Camila L. H. Ferraz ◽

Ítalo Mota ◽

Jackson Gondim ◽

...

Keyword(s):

Drug Therapy ◽

Bone Growth ◽

Tolerance Test ◽

Hormonal Control ◽

Oral Glucose ◽

Mccune Albright Syndrome ◽

Albright Syndrome ◽

Long Acting ◽

The Right ◽

Mccune Albright

OBJECTIVES: The use of drug therapy based on cabergoline, octreotide and long-acting release (LAR) octreotide has presented varying results in the treatment of GH excessive production in patients with McCune-Albright Syndrome. METHODS: We report the case of a 29 year-old female patient presenting McCune-Albright Syndrome and complaint of excessive bone growth. RESULTS: The patient presented a pituitary adenoma involving the right internal carotid artery and excessive secretion of growth hormone (no GH suppression was observed after the oral glucose tolerance test). Due to the presence of diffuse thickness in skull base bones, surgical approach was not considered effective and the patient was submitted to drug therapy with octreotide LAR and cabergoline. At the one year follow-up, GH and IGF-1 levels were normal and no adverse effects were present. CONCLUSION: The use of drug therapy based on the association of cabergoline and octreotide is safe and able to achieve complete hormonal control in the treatment of acromegaly for McCune-Albright patients.

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Modern views on the genetic determinism of GH-secreting pituitary adenomas (literature review and own data)

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY ◽

10.22141/2224-0721.17.1.2021.226425 ◽

2021 ◽

Vol 17 (1) ◽

pp. 11-19

Author(s):

R. Nikolaiev ◽

L. Rostomyan ◽

A. Beckers ◽

O. Khyzhnyak ◽

M. Mykytyuk ◽

...

Keyword(s):

Pituitary Adenoma ◽

Genetic Analysis ◽

Pituitary Adenomas ◽

Young Age ◽

Mccune Albright Syndrome ◽

Men1 Gene ◽

Men 1 ◽

Albright Syndrome ◽

Aip Gene ◽

Mccune Albright

Background. This article presents a review of the current literature on the role of the genetic component in the etiology and pathogenesis of hormone-active pituitary adenomas secreting growth hormone (GH) and clinically manifesting by acromegaly and/or gigantism (multiple endocrine neoplasia 1 (MEN-1), McCune-Albright syndrome, Carney complex, X-linked acrogigantism (X-LAG), familial isolated pituitary adenoma — FIPA). Materials and methods. To identify mutations in the AIP gene and to verify FIPA, 26 patients of the Ukrainian population (19 women and 7 men) were examined in whom acromegaly was diagnosed in adolescence or young age, and genetic analysis was performed. To determine the genetic determinism in the development of GH-secreting pituitary adenoma and differential diagnosis of FIPA and MEN-1 syndromes by sequencing method (MLPA — ligation-dependent probe amplification), the genes MLPA, P244-C1 were studied involving exons 1–6 MEN1 gene, (MLPA, P017-D1) AIP gene. Results. Among those examined, only two patients had AIP gene mutations. In one patient, genetic screening for MEN1 gene mutation was negative and no clinical symptoms suggestive of McCune-Albright syndrome were detected. A variant heterozygous missense c.714C>G (p.Cys238Trp) was found in the AIP gene. This AIP gene assay is compatible with a genetic predisposition to develop pituitary adenoma. The offspring of this patient has a 50% chance of inheriting this variant, acromegaly, hypersomatotropinemia, MEN-1 syndrome, familial isolated pituitary adenoma. Another patient was diagnosed with MEN syndrome type 1 (Wermer syndrome): insulinoma, parathyroid gland adenomas (2), primary hyperparathyroidism with a heterozygous c.134A>G variant (p.Glu45Gly) found in the MEN1 gene. The presence of the c.l34A>G (p.Glu45Gly) class variant 4 is likely to be pathogenic. The prevalence of this variant in the general population is unknown, so it is very rare. Conclusions. The genetic analysis is appropriate in pediatric and young patients or those with GH-secreting macro/giant pituitary adenoma diagnosed at a young age (under 35), regardless of family history. In patients with a history of a disease, genetic analysis is recommended in any case to identify FIPA and to predict the further course of the disease and the effectiveness of treatment with somatostatin analogues.

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A Case of McCune-Albright Syndrome Complicating Pituitary Adenoma and Fibrous Dysplasia

Orthopedics & Traumatology ◽

10.5035/nishiseisai.54.407 ◽

2005 ◽

Vol 54 (3) ◽

pp. 407-408

Author(s):

Yoshiyuki Masuda ◽

Fumihiro Miyaguchi ◽

Kyoji Hayashi ◽

Kazunori Yone ◽

Setsuro Komiya

Keyword(s):

Pituitary Adenoma ◽

Fibrous Dysplasia ◽

Mccune Albright Syndrome ◽

Albright Syndrome ◽

Mccune Albright

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Clinical characteristics and management of growth hormone excess in patients with McCune–Albright syndrome

Acta Endocrinologica ◽

10.1530/eje-16-0715 ◽

2017 ◽

Vol 176 (3) ◽

pp. 295-303 ◽

Cited By ~ 8

Author(s):

Yong Yao ◽

Yang Liu ◽

Linjie Wang ◽

Kan Deng ◽

Hongbo Yang ◽

...

Keyword(s):

Growth Hormone ◽

Complete Remission ◽

Clinical Manifestations ◽

Tolerance Test ◽

Oral Glucose ◽

Somatostatin Analogue ◽

Preoperative Treatment ◽

Retrospective Clinical Study ◽

Albright Syndrome ◽

Gh Excess

Objective McCune–Albright syndrome (MAS) is a sporadic, postzygotic disease presenting with fibrous dysplasia, cafe-au-lait spots and multiple endocrinopathies. Growth hormone (GH) excess is an uncommon but potentially severe complication of MAS. This study aims to describe the clinical manifestations of GH excess in the context of MAS and analyze the responses of these patients to treatments. Design Retrospective clinical study. Methods Clinical data from 52 MAS patients were analyzed. Serum GH and IGF1 levels, as well as nadir GH levels after an oral glucose tolerance test and alkaline phosphatase (ALP) levels were determined before and after the treatment. Results In total, 13 MAS patients (25%) had the complication of GH excess, including 10 males (76.9%). Among them, all had FD, and 6 patients had sphenoidal bone involvement. Visual deficits were present in 8 patients, and hearing deficits were present in 5. Olfactory dysfunction was observed in 3 patients. Evident pituitary adenomas were confirmed in 9 patients by MRI. These patients underwent surgery with or without pretreatment of long-acting somatostatin analogue octreotide, and 6 achieved complete remission. The serum ALP levels decreased significantly after treatment for GH excess. Conclusions MAS with GH excess is more common in male patients. GH excess can lead to more severe skeletal lesions in MAS patients involving more of the craniofacial bones. Complete trans-sphenoidal complete tumor excision with neuronavigational guidance is effective and could lower ALP levels. LAR is recommended as a preoperative treatment and when patients fail to achieve complete remission after surgery.

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