Two case reports of X-linked acrogigantism and pathogenic gene detection / 中华内分泌代谢杂志

Objective:To report the clinical characteristics, diagnosis, and treatment of 2 cases of X-linked acrogigantism(X-LAG).Methods:The clinical information of two patients were retrospectively reported, and peripheral blood DNA was collected for copy number variations detection.Results:Both patients had onset at age of two, with common clinical characteristics including linear growth acceleration, mild facial coarsening, enlargement of hands and feet, increased appetite, and snoring, etc. The heights Z scores of the two patients before treatment were + 6.86 and + 6.53, respectively. Growth hormone(GH) glucose inhibition test showed that GH nadir values were over 1 ng/mL and insulin-like growth factor-Ⅰ(IGF-Ⅰ) were 586.0 ng/mL and 1 042.0 ng/mL, respectively. Patient 1 received three cycles of octreotide microspheres therapy followed by surgery, and achieved clinical and biochemical remission. Patient 2 had lanreotide for 5.5 years but failed biochemical remission. Microduplication of Xq26.3, which contained pathogenic gene G-protein coupled receptor 101(GPR101), was found in germline DNA of two patients through copy number variation detection, leading to the diagnosis of X-LAG.Conclusion:It should be cautious of X-LAG when children below 2 years old presents symptoms such as overgrowth and so on. Medication combined with surgery is effective.

Clinical Relevance and Immunohistochemical Patterns of Silent Pituitary Adenomas: 10 Years of Single-centre Experience.

BACKGROUND: Silent pituitary adenomas are clinically non-functional (i.e., without clinically evident pituitary hormone production). INTRODUCTION: The aim of this study was to investigate subjects with silent pituitary adenomas for possible variations in their clinical status. METHODS: A total of 102 patients who had undergone surgery for pituitary adenoma and had been diagnosed with silent pituitary adenoma was included in the study. The patients' preoperative and postoperative hormonal parameters and magnetic resonance imaging (MRI) features were collected, and pathological specimens were re-evaluated. RESULTS: Immunohistochemistry results of the 102 patients were as follows: hormone-negative adenomas (n=35) 35.5%; FSH+LH-positivity (n=32) 31.3%; ACTH-positivity (n=11) 10.7%; α-subunit- positivity (n= 9) 8.8%; prolactin-positivity (n=8) 7.8%; GH-positivity (n=6) 5.4%; and plurihormonal adenoma (n=1). The mean sizes of SGA, SGHA, and SCA were 28.0±12.7, 30.0±16.0, and 27.7±8.9mm (p>0.05), respectively. With the exception of silent gonadotroph adenomas (SGAs), female gender dominance was shown in patients with silent growth hormone adenoma (SGHA) and silent corticotroph adenoma (SCA). Although no clinical relevance was observed in relation to hormonal excess, preoperative GH (4.21±4.6, vs. 0.27±0.36 p=0.00) was slightly more elevated in SGHA than in GH-negative adenomas. Additionally, preoperative basal ACTH values (47.3±28.7 vs. 23.9±14.4, p=0.003) were also higher in SCA compared to the other types. Our findings revealed SCAs to be of more aggressive behaviour than SGHAs and SGAs due to invasiveness in radiological imaging, their elevated re-operation, and postoperative ACTH values. CONCLUSION: Silent pituitary adenomas represent a challenging diagnostic tumour group. Careful initial evaluation of patients with pituitary adenomas should consider any mild signs and symptoms of functionality, particularly in cases of GH- and ACTH-secreting adenomas.

An update on the genetics of pituitary growth hormone adenoma / 中华内分泌代谢杂志

Pituitary growth hormone adenoma is a benign tumor in sellar region, which presents clinical manifestations of acromegaly or gigantism due to excessive secretion of growth hormone. With the development of genetic technology, a variety of genetic variations are identified being involved in the pathogenesis of growth hormone adenoma and their clinical phenotypes as well as treatment responses, which promotes precise diagnosis and management of pituitary growth hormone adenomas. Among somatic mutations, activating somatic mutations of GNAS can be found in 40% of growth hormone adenomas. Mosaic mutations of GNAS lead to McCune-Albright syndrome, and the most common pituitary features is excessive secretion of growth hormone. Germline mutations of aryl hydrocarbon receptor interacting protein (AIP) can be found in familial and sporadic growth hormone adenomas. AIP-mutated adenomas usually are early-onset macroadenoma with poor response to somatostatin therapy. Xq26.3 microduplication involving the gene GPR101 causes X-linked acrogigantism. Growth hormone adenoma can present as a sporadic solitary pituitary adenoma, or as a part of syndromic disease such as multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4), Carney syndrome, etc. This article summarized the progress of genetic research on growth hormone adenoma, to increase understanding of solitary and syndromic pituitary growth hormone adenomas, and promote further exploration of mechanism and potential therapy targets of pituitary growth hormone adenomas.

A retrospective study on the clinical characteristics of patients with growth-hormone adenoma / 解放军医学杂志

Objective To evaluate the clinical characteristics of patients with growth-hormone adenoma (GHA) and summarize the diagnosis and treatment experience.Methods The clinical data of 338 GHA cases at the General Hospital of PLA from Jan. 1990 to Dec. 2016 were collected, of which 252 cases with more complete clinical data were retrospectively analyzed including their general situation, medical history, laboratory tests and auxiliary examinations, and treatment modalities and outcomes. Parts of the patients were followed up.Results The cases of hospitalized GHA patients have increased year by year since 1990, and the number of patients admitted in the last 3 years accounted for 56.2% of the total number of cases. The sex ratio for GHA patients was nearly 1:1. Age of visiting followed Gaussian distribution while the 41-50 age group occupied the largest part. The most typical sign is hand and foot enlargement (60.7%), followed by the hypertrophy of nasal ala. The most common symptoms are headache (42.5%), hypopsia, visual field defect and diplopia. More than half of GHA patients were complicated with prediabetes and diabetes (72.6%), sleep apnea (69.5%), goiter or thyroid nodularity (56.4%), cardiac insufficiency (57.0%) and colon polyp (54.1%); while the percentages of cases undergone the relevant examination in the total number of cases were as follows: 75g OGTT test (42.1%), polysomnography (23.4%), thyroid ultrasound (37.3%), echocardiogram (47.6%) and colonoscopy (14.7%); GHA was 23.37±1.42μg/L and IGF-1 was 804.28±273.93ng/ml on average; 85.0% of somatotroph tumors are macroadenoma. Surgery remains the mainstay of therapy to GHA, while medical therapy was selected by less patients. During the follow-up, only 38.0%of GHA patients can be contacted, among them the remission rate decreased to 40.5%. The positive rate of long-term remission evaluated by early postoperative GHA level was consistent with that confirmed by the long-term follow-up (χ2=3.368,P>0.05). Conclusions The number of hospitalized GHA patients have increased recent years. The common clinical signs and symptoms are somatic enlargement and nonspecific headache. Due to uncompleted screening, GHA associated complications are always misdiagnosed; It is essential to establish a sound model of follow-up to improve patients' quality of life. The early postoperative GHA levels may predict the prognosis of surgery.

Characterization of transsphenoidal complications in patients with acromegaly: an analysis of inpatient data in the United States from 2002 to 2010.

BACKGROUND: Transsphenoidal surgery (TSS) is a common procedure for a variety of pituitary lesions. This procedure can be associated with complications related to the surgery or specific pathology. In this study, we evaluate inpatient postoperative complications among patients who underwent TSS for growth hormone adenomas using a nationally representative database, and compare patient characteristics and complications to patients who underwent TSS for other benign pituitary neoplasms. METHODS: Analysis of the Nationwide Inpatient Sample revealed 13,070 TSS patients (including 892 with acromegaly) between 2002 and 2010. Complication rates, outcomes, patient demographics, hospital stay, and total charges were evaluated among TSS patients with and without acromegaly. RESULTS: There was an increase in TSS performed in both cohorts from 2002 to 2010. Acromegaly patients were younger, had shorter hospital stays, and incurred fewer charges. Acromegaly patients had a lower occurrence of postoperative urinary/renal complications (0.2% vs 1.1%), thromboembolic events (0% vs 0.4%), fluid/electrolyte abnormalities (5.7% vs 9.1%), and iatrogenic hypopituitarism (0.3% vs 1.1%) compared to other TSS patients (all p < 0.05). After adjusting for age, acromegalic patients maintained a statistically lower occurrence of fluid/electrolyte abnormalities (p = 0.007). Cerebrospinal fluid leak occurrence in acromegaly patients was 2.6% vs 1.7% in non-acromegaly patients, a result that did not reach significance (p = 0.054). CONCLUSION: Upon comparison of inpatient hospitalizations for patients undergoing TSS for growth hormone adenomas and other benign pituitary neoplasms, acromegaly patients had a significantly lower occurrence of postoperative fluid/electrolyte abnormalities. Acromegaly patients had shorter hospitalizations and subsequently fewer total charges.