Growth Hormone Hypersecretion Research Articles

A Potent Neutralizing Monoclonal Antibody to Human Growth Hormone Suppresses Insulin-Like Growth Factor-1 in Female Rats.

Acromegaly and gigantism are disorders caused by hypersecretion of growth hormone (GH), usually from pituitary adenomas. Although somatostatin analogues (SSA), dopamine agonists, and GH receptor antagonists are important therapeutic agents, all of these have issues with their effectiveness, safety, and/or convenience of use. To overcome these, we developed a GH-specific potent neutralizing a mouse monoclonal antibody (mAb) named 13H02. 13H02 selectively bound both to human and monkey GH with high affinity, and strongly inhibited the biological activity of GH in the Nb2 rat lymphoma cell proliferation assay. In hypophysectomized/GH-supplemented rats, a single subcutaneous administration of 13H02 significantly and dose-dependently lowered the serum insulin-like growth factor-1 levels. To pursue the therapeutic potential of this antibody for acromegaly and gigantism, we humanized 13H02 to reduce its immunogenicity and applied a single amino acid mutation in the Fc region to extend its serum half-life. The resulting antibody, Hu-13H02m, also showed GH-specific neutralizing activity, similar to the parental 13H02, and showed improved binding affinity to human FcRn.

Challenges Confounding Biochemical Diagnosis of Acromegaly.

Abstract:
 Acromegaly is a disorder caused by growth hormone (GH) hypersecretion resulting in excessive release of insulin like growth factor-1 (IGF-1). Both GH and IGF-1 measurements are crucial in its accurate diagnosis and in differentiating it from pseudoacromegaly. Early diagnosis is frequently restricted by its subtle, unnoticeable pathological changes; hence, clinical presentation is often late. Therefore, biochemical diagnosis is critical. However, the straightforward interpretation of these markers are hindered by factors that contribute to GH – IGF-1 discordance observed both in static and in dynamic function tests. These factors include both markers biological variation and their analytical assay limitations, which lead to false positive and negative results. This review is describing the pitfalls and challenges confounding the biochemical diagnosis of acromegaly. Despite these interpretive challenges, we strongly believe that interpretation of these results could be facilitated by effective clinician-laboratory professional communications which is the highlight of this review.
 
 Keywords: Acromegaly, growth hormone (GH), insulin like growth factor-1 (IGF-1), IGF-binding proteins (IGFBP)

Plurihormonal Pituitary Neuroendocrine Tumors: Clinical Relevance of Immunohistochemical Analysis.

Plurihormonal pituitary neuroendocrine tumors (PitNETs) are rare forms of tumors that express more than one hormone. The most common association is between growth hormone (GH) and prolactin (PRL), but other unusual combinations have been reported, such as GH and ACTH. Usually, the clinical dominance in these cases is related to GH hypersecretion. In these cases, immunohistochemistry (IHC) of transcription factors (TFs) is very useful for an accurate diagnosis. We included 42 patients diagnosed with pituitary neuroendocrine tumors (PitNETs): 37 patients with a confirmed diagnosis of acromegaly, and 5 patients with prolactinomas. All patients underwent transsphenoidal surgical intervention. We correlated the immunohistochemical features of plurihormonal PitNETs with clinical, hormonal, and imaging data. Tumor specimens were histologically and immunohistochemically examined. Based on the 2022 WHO classification, using IHC, 13 patients exhibited positive staining for more than one hormone, while unusual combinations like GH + ACTH and PRL + ACTH were also identified in other cases. Unusual cell combinations that produce hormones unrelated histogenetically, biochemically, or through regulatory mechanisms can appear and may display aggressive behavior, persistent disease, and high recurrence. We have not identified a clear correlation with the prognosis of these rare PitNETs.

The direct impact of pegvisomant on osteoblast functions and bone development.

Acromegaly is a chronic disease characterized by growth hormone (GH) hypersecretion, usually caused by a pituitary adenoma, resulting in elevated circulating levels of insulin-like growth factor type I (IGF-I). Pegvisomant (PEG), the GH-receptor (GHR) antagonist, is used in treating acromegaly to normalize IGF-I hypersecretion. Exposure to increased levels of GH and IGF-I can cause profound alterations in bone structure that are not completely reverted by treatment of GH hypersecretion. Indeed, there is evidence that drugs used for the treatment of acromegaly might induce direct effects on skeletal health regardless of biochemical control of acromegaly. We investigated, for the first time, the effect of PEG on cell proliferation, differentiation, and mineralization in the osteoblast cell lines MC3T3-E1 and hFOB 1.19 and its potential impact on bone development in zebrafish larvae. We observed that PEG did not affect osteoblast proliferation, apoptosis, alkaline phosphatase (ALP) activity, and mineralization. After PEG treatment, the analysis of genes related to osteoblast differentiation showed no difference in Alp, Runx2, or Opg mRNA levels in MC3T3-E1 cells. GH significantly decreased cell apoptosis (-30 ± 11%, p < 0.001) and increased STAT3 phosphorylation; these effects were suppressed by the addition of PEG in MC3T3-E1 cells. GH and PEG did not affect Igf-I, Igfbp2, and Igfbp4 mRNA levels in MC3T3-E1 cells. Finally, PEG did not affect bone development in zebrafish larvae at 5days post-fertilization. This study provides a first evidence of the impact of PEG on osteoblast functions both in vitro and in vivo. These findings may have clinically relevant implications for the management of skeletal health in subjects with acromegaly.

Double pituitary neuroendocrine tumors in a patient with normal growth hormone level acromegaly: A case report and review of the literature

Background: Acromegaly is a rare disease caused by growth hormone (GH) hypersecretion caused by a pituitary neuroendocrine tumor (PitNET). However, some acromegaly patients show normal GH levels, and they can be a pitfall in clinical diagnosis. Moreover, rarely, synchronous true double or multiple PitNETs are encountered. Moreover, these PitNETs increase the risk of a left lesion during surgical exploration. Case Description: The patient, who was a 73-year-old female, was referred to our hospital with a chief complaint of headache. Assessment of basal anterior pituitary function revealed a slightly high level of insulin-like growth factor-1 (IGF-1) (standard deviation, 2.4), and her physical findings exhibited mild acromegalic features. The endocrine evaluation confirmed acromegaly and magnetic resonance imaging (MRI) showed a macro PitNET with suprasellar extension. Endoscopic endonasal surgery (EES) was performed to remove the macro PitNET. Although postoperative MRI showed complete removal of the macro PitNET, endocrinological testing indicated no improvement in GH or IGF-1 excess. Pathological examination of the surgical specimen revealed a gonadotropic PitNET. Therefore, we repeated the MRI scan and found a micro PitNET in the thin left normal pituitary gland. A second EES was successfully performed to remove the micro PitNET completely, and both endocrinological and pathological examinations confirmed that the disease was cured. Conclusion: Diagnosing acromegaly with low GH levels requires close monitoring. Double PitNETs are relatively rare and can cause incomplete remission of functional PitNETs.

Serum Phosphorus and Calcium as Biomarkers of Disease Status in Acromegaly.

Acromegaly is a chronic disease caused by the hypersecretion of growth hormone (GH), leading to changes in the growth of visceral tissues and glucose impairment. Serum biomarkers that correlate with disease status are still unclear. This study aims to assess the potential of phosphorus and calcium as biomarkers in the clinical evaluation of patients with acromegaly and clarify their relationship with SAGIT and other common biomarkers. We retrospectively analyzed data from 306 medical records of patients with acromegaly hospitalized between 2015 and 2020. Factors such as patient biometrics, duration of disease, SAGIT score, tumor size, GH, insulin-like growth factor 1 (IGF-1), calcium, phosphorus, parathormone, and vitamin D were analyzed concerning current disease status (naïve, non-remission, remission). The results showed that serum phosphorus significantly correlated with IGF-1 and SAGIT scores for patients with active acromegaly. Specifically, the best predictor for the remission of acromegaly was a phosphorus level < 3.98 mg/dL and serum calcium levels < 9.88 mg/dL. Based on logistic regression, the higher the serum phosphorus level, the lower the odds of achieving remission (an increase in one unit leads to a decrease in the chance of about 80%). In conclusion, phosphorus and calcium can be effective biochemical markers for predicting disease status in acromegaly.

Changing faces: A case-based review of acromegaly

Acromegaly is a rare and underdiagnosed acquired disorder. It is commonly caused by an underlying pituitary adenoma that often requires surgical excision. Diagnosis is normally preceded by ~5–10 years of excessive growth owing to hypersecretion of growth hormone. This can have long-term medical complications and result in a reduced life expectancy. Acromegalic patients present to a number of healthcare professionals prior to diagnosis, including general dental practitioners. As changes in occlusion are often a patient's primary concern prior to acromegaly diagnosis, it is important that all dentists are aware of the presentation and differential diagnoses of such disorders. CPD/Clinical Relevance: Dentists should be aware of the initial presentation of acromegaly to facilitate early diagnosis.

Myocardial, Valvular, and Vascular Structural and Functional Properties in Acromegaly.

Acromegaly is an uncommon systematic endocrine disease caused by the hypersecretion of human growth hormone and, consequently, of insulin-like growth factor-1 during adulthood. Acromegaly could cause a typical cardiomyopathy characterized by left ventricular hypertrophy associated with diastolic dysfunction, which later could progress to systolic dysfunction. Moreover, some valvular and vascular abnormalities are also associated with acromegaly. This present review aims to summarize available information regarding acromegaly-associated abnormalities in myocardial, valvular, and vascular structural and functional properties and their relationship to disease activity and treatment options.

THU483 Role Of Excess GH On Breast Cancer Aggressiveness And Metastasis In Acromegaly

Abstract Disclosure: J. Oh: None. C. Kang: None. E. Wang: None. S. Lee: None. J. Nam: None. C. Ku: None. E. Lee: None. Introduction Acromegaly is a rare disease characterized by chronic growth hormone (GH) and insulin-like growth factor-1 hypersecretion. In previous studies, it is known that the incidence of breast cancer increases in patients with acromegaly. For breast cancers, autocrine GH and GHR are expressed in primary lesion, which is significantly increased in metastatic one. To date, however, the precise mechanism of endocrine GH in breast cancer metastasis has not been defined. This study aimed to investigate the role of endocrine excess GH facilitating breast cancer metastasis in acromegaly mice model. Method We used Aiplox/lox (Con) and rGHp-Cretg/+; Aiplox/lox mice (Acro), which was previously established to model the phenotype of human acromegaly. To generate orthotopic xenograft model, we used C57BL/6 female mouse derived breast cancer cell line Py230 cells. Py230 cells were injected into mammary gland and tumor volumes were measured every 2 days. Tumor growth and metastasis were confirmed by bioluminescent in vivo imaging system (IVIS). Also, we investigated the effects of GH on triple negative breast cancer cell lines, which have the higher expression of GHR. To define GH induced pathway, we performed RT2 array. Cell proliferation was investigated with MTT assay and cell migration was investigated with wound healing assay and transwell invasion assay. Results In mouse orthotopic xenograft studies, tumor volumes of Acro mice were higher than that of Con mice (increase of 310%, 846.04±290.7 vs. 205.97±33.7 mm3, p=0.001). The tumor volume and serum GH level showed positive correlation (R2= 0.4739, p=0.027). After 14 weeks, the Acro mice showed significantly increased bioluminescence activity in the lung (increase of 1023%, 494666.7±104668.2 vs. 44037.7±6641.9 AU, p=0.0127). When GHR antagonist was treated, tumor growth and lung metastasis were decreased. We excised primary tumor and lung metastatic foci and performed RT2 array. We found Tcf-20 gene, which is upregulated in both primary tumor and lung metastatic burden (increase of 216%, p=0.0153). We confirmed GH induced Tcf-20 gene induction (increase of 57% (p=0.043), 41% (p=0.05), 67% (p=0.0021) in Hs578T, Py230 (p=0.05), and Hcc1806 cells each). We knocked down Ghr or Tcf-20 genes and observed decrease of invasion and migration compared to GH treated siCON HCC1806 (decrease of 64.5% in siGHR, decrease of 83.3% in siTCF-20, compared to siCON cells, p=0.000819977) and Py230 cells (decrease of 47.3% in siGHR transfected, decrese of 49.3% in siTCF-20 transfected, compared to siCON cells, p=0.0012). Conclusion Excess GH in acromegaly possess a strong potential to promotes tumor development and metastasis. We identified a molecular mechanism by which GH-induced TCF-20 promote tumor aggression and metastasis. These findings can aid in the development of improved strategies for managing cancer in acromegalic patients. Presentation: Thursday, June 15, 2023

THU028 Novel Approach To Management Of Acromegaly With De Novo Oral Octreotide Or Combination Therapy With Cabergoline: A Case Series

Abstract Disclosure: A. Halstrom: None. G.A. Dobri: None. Acromegaly is a rare disorder characterized by tumoral hypersecretion of growth hormone (GH) leading to overproduction of insulin-like growth factor 1 (IGF-1). Patients present with physical changes, and systemic complications. Treatment involves surgery and medical therapy with the goal of normalizing IGF-1. First line medical therapy consists of first-generation injectable somatostatin receptor ligands (SRL) (octreotide LAR, lanreotide autogel). Dopamine agonists (cabergoline) can be used in patients with mild IGF-1 elevation. If IGF-1 levels do not normalize, pasireotide or pegvisomant can be tried. Until recently, SRLs were administered only as a deep tissue injection. Patients have reported injection site reactions, frustration, and breakthrough acromegaly symptoms between doses. Two trials were conducted which showed that oral octreotide is an effective alternative for patients after achieving biochemical control with the injectable formulation. Two cases are presented below in which patients with acromegaly were treated with de novo oral octreotide either or as combination therapy with cabergoline, after a significant time lapse since injection SRL. Our first case is a 24 year old female with a 19mm mammosomatotroph adenoma, resected 8 years prior, with questionable remnant on postoperative MRI and biochemically active acromegaly. She was started on octreotide LAR 20mg which was titrated up to 30mg. However, she had not achieved biochemical control, with lowest IGF-1 543ng/mL (83-456ng/mL), Z-score 2.4, and GH 5.8ng/mL (&amp;lt;= 7.1ng/mL). She wanted a break from medical therapy and discontinued octreotide LAR. She was later started on pegvisomant 15mg but stopped after 10 days due to an allergic reaction and was switched to cabergoline. Cabergoline was up titrated to 3.5mg weekly, still without biochemical control, IGF-1 417ng/mL (103-326ng/mL), Z-score 2.5, GH 7.69ng/mL (0.05-8ng/mL), at which time oral octreotide 20mg twice daily was started and cabergoline decreased to 2.5mg weekly. Oral octreotide was increased to 60mg daily and IGF-1 levels normalized to 294ng/mL (83-456ng/mL), Z-score 1. The second case is a 70 year old female with type 2 diabetes, arthritis, left ventricular hypertrophy, obstructive sleep apnea and colon polyps found to have a 10mm pituitary adenoma with IGF-1 481ng/mL (32-238ng/mL), Z-score 3.1, GH 1.28ng/mL (0.05-8ng/mL). She declined surgical resection and opted for medical management. Oral octreotide 20mg twice daily was started and further increased to 60mg daily IGF-1 went as low as 327ng/mL (28-231ng/mL), Z-score 2.5 and GH 0.4ng/mL (0.05-8ng/mL). The dose was increased to 80 mg daily are lab results are pending. These are the first two published cases describing a novel approach to treating acromegaly in which patients were found to have a biochemical response to de novo oral octreotide either alone or combined with cabergoline. Presentation: Thursday, June 15, 2023

Regos nervo glioma

Optic nerve glioma (ONG) is usually a low-grade tumor of the optic nerve. ONG can affect not only the optic nerve, but also the optic nerve chiasma and optic nerve tract. ONG can be classified as associated with neurofibromatosis type 1 (NF1) or sporadic ONG. Sporadic gliomas are more commonly diagnosed in adults, have an aggressive course, and are known to have a poor outcome. The disease can be asymptomatic. ONG often causes visual disturbances such as reduced visual acuity, visual field defects, and impaired color vision; due to the tumor mass effect, proptosis, strabismus, and diplopia are possible. As the disease progresses, various neurological symptoms can appear, including headache, hemiplegia, and endocrine disorders such as early maturation, growth hormone hypersecretion, or deficiency. A presumed diagnosis is based on clinical presentation and neuroimaging findings. Meanwhile, biopsy should be avoided due to the high probability of optic nerve damage. Treatment is individual for each patient, but remains controversial to this day. Thus, in this article, we review the prevalence, clinic, diagnostic and treatment options of ONG.

Skeletal complications in acromegaly.

Hypersecretion of growth hormone (GH) is rare and typically results from a pituitary functional tumor - somatotropinoma. It leads to excessive linear bone growth and manifests as gigantism if occurring in childhood and adolescence, before the closure of epiphyses or as a acromegaly in adulthood. The excess of GH impacts bone metabolism directly as well as indirectly through increased insulin-like growth factor 1 (IGF-1). In acromegaly as a consequence of overproduction of GH and IFG-1 and the influence of these hormones on bone osteoblasts, bone metabolism, growth and density increase. However, bone turnover is accelerated causing impaired bone microstructure and strength, which may lead to increased risk of vertebral fractures irrespective of normal bone mineral density. Apart from the changes in bone architecture, acromegaly also results in a degenerative joint disease of a different nature than primary osteoarthritis. Moreover, acromegaly leads to cardiovascular, metabolic and respiratory complications, and thus significantly impairs the quality of life. In this review, authors summarize the pathophysiology, diagnosis, and treatment of bone and joint disease in acromegaly.

Long-term Efficacy and Safety of Pasireotide in Patients With Acromegaly: 14 Years of Single-Center Real-World Experience.

Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I (IGF-I). Medical therapies, including the somatostatin receptor ligand (SRL) pasireotide, are frequently used to restore biochemical control. As patients often receive therapy over prolonged periods, long-term data from real-life settings are needed. A retrospective analysis was performed using a prospectively maintained database of all patients with acromegaly from our primary care center who were enrolled in clinical studies with pasireotide (first visit November 2008). The main outcome measures were safety and biochemical control (age-adjusted IGF-I ≤ upper limit of normal). Patients (n = 50) entered 4 parental studies and 30 continued in the rollover; at data cutoff (June 2022), 27 were still receiving pasireotide. Overall, median (range) exposure was 58 (3-137) months. Normal IGF-I was achieved in 54%, and acromegaly symptoms and quality of life were improved with treatment. No predictors of pasireotide response were identified; however, controlled patients had smaller tumors and lower GH at baseline. Tumor volume reduction occurred in 63% of evaluable patients (n = 10/16). Most patients presented hyperglycemic events, including 63.2% of patients with normal glucose before treatment. Older patients and those with higher IGF-I, glucose, and HbA1c at baseline had higher glucose and HbA1c during pasireotide treatment. Pasireotide provided clinical benefit and was well tolerated for more than 11 years of treatment in acromegaly patients, most of whom were resistant to first-generation SRLs.

Efficacy of long-term octreotide therapy of acromegaly as the first-line medical treatment

Acromegaly is a severe neuroendocrine disease characterized by hypersecretion of growth hormone (GH) caused in 95% of cases by pituitary adenoma, which leads to the development of pathology of various organs and systems. The severity of the condition is due not only to the direct effect of somatotropic hormone on the body and the effect of the adenoma on the surrounding structures, but also to the age of the patient and complications associated with the disease. Improvement in treatment methods allows for a personalized approach to patient management, taking into account various aspects of the clinical case. It is important for a specialist to take into account comorbidity in acromegaly, both in terms of pathological disorders and the impact on the patient’s psycho-emotional state. We present a clinical case of successful treatment with somatostatin analogues (ASS) in a patient who is afraid of surgery and has cardiovascular complications of acromegaly. Since the onset of acromegaly, confirmed by an elevated level of insulin-like growth factor-1 (IGF-1) and an endosellar pituitary macroadenoma measuring 11x9.5x8 mm, ASS therapy was initiated in the patient. The choice in favor of conservative treatment was due to a burdened cardiovascular history and the patient’s fear of surgery. Within three years from the start of drug therapy, there was a significant improvement in overall well-being, a tendency to reduce the size of the pituitary adenoma, and biochemical remission was achieved. The clinical case described by us confirms the possibility of successful primary treatment of ASS in a patient with acromegaly, taking into account all individual characteristics.

Abstract #1398813: A Rare Case of Acromegaly with Negative Immunohistochemical Staining for Growth Hormone

We are presenting a case of mixed prolactin and growth hormone (GH)-pituitary tumor with negative immunostaining for GH. 81-year-old male with history of type 2 diabetes mellitus, hypertension, obstructive sleep apnea, and colon polyps was found to have a pituitary macroadenoma during evaluation of his visual disturbances. Years before the presentation, he noticed his shoe size had increased and his wife observed his jaw becoming more prominent. Physical exam was notable for enlarged nose, mandibular prognathism, and enlarged hands. Pre-operative laboratory results were remarkable for significantly elevated levels of insulin-like growth factor-1 (IGF-1), GH, and prolactin. He underwent transsphenoidal resection (TSPR) of the mass and pathology demonstrated a lactotroph adenoma, negative for GH immunostaining. After surgery he was started on cabergoline 0.5mg PO twice weekly. Three months afterwards his IGF-1 level remained elevated at 415 ng/mL. Acromegaly was confirmed by an elevated GH level of 13.8 ng/mL 2-hours after oral glucose challenge, then a long-acting somatostatin analogue depot was initiated for treatment. In the first year of therapy, he had weight loss and hypoglycemia that required discontinuation of insulin therapy. His IGF-1 and GH levels decreased to within age-appropriate ranges. His prolactin level returned to normal and cabergoline was stopped after a successful discontinuation trial. Clinical suspicion for acromegaly is confirmed by elevated IGF-1 and GH levels. When a GH-secreting pituitary adenoma is resected, immunocytochemistry with GH staining typically supports the diagnosis. It is not common for these tumors to stain negative for GH in the presence of clinical and biochemical acromegaly. The opposite—termed silent somatotroph— is more common and may represent an early stage in the development of a somatotroph adenoma. Failure to provide adequate diagnostic tissue, histopathology misread, or loss of antigenicity during fixation or embedding may be reasons for false negatives. However, it has been suggested that sparse cytoplasmic stores of GH do not parallel the hypersecretion of GH and may reduce staining capacity. Thus, a diagnosis of acromegaly should be made in patients with clinical and biochemical findings, even in the absence of GH immunostaining.

Chromosomal microdeletion leading to pituitary gigantism through hormone-gene overexpression.

Pituitary gigantism is a rare endocrinopathy characterized by tall stature due to growth hormone (GH) hypersecretion. This condition is generally linked to a genetic predisposition to tumors that produce GH or GH-releasing hormone (GHRH). Here, we report a Japanese woman who exhibited prominent body growth from infancy to reach an adult height of 197.4cm (+7.4 standard deviation). Her blood GH levels were markedly elevated. She carried no pathogenic variants in known growth-controlling genes but had a hitherto unreported 752 kb heterozygous deletion at 20q11.23. The microdeletion was located 8.9 kb upstream of GHRH and encompassed exons 2-9 of a ubiquitously expressed gene TTI1 together with 12 other genes, pseudogenes and non-coding RNAs. Transcript analyses of the patient's leukocytes showed that the microdeletion produced chimeric mRNAs consisting of exon 1 of TTI1 and all coding exons of GHRH. In silico analysis detected promoter-associated genomic features around TTI1 exon 1. Genome-edited mice carrying the same microdeletion recapitulated accelerated body growth from a few weeks after birth. The mutant mice developed pituitary hyperplasia and exhibited ectopic Ghrh expression in all tissues examined. Thus, the extreme phenotype of pituitary gigantism in the patient likely reflects GHRH overexpression driven by an acquired promoter. The results of this study indicate that germline submicroscopic deletions have the potential to cause conspicuous developmental abnormalities due to gene overexpression. Furthermore, this study provides evidence that constitutive expression of a hormone-encoding gene can result in congenital disease.

Autonomous growth hormone secretion due to McCune Albright syndrome in paediatric age group: an ominous triad.

The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to elucidate challenges and intricacies in its diagnosis and management. It was a single centre study carried out in individuals with MAS and autonomous GH secretion (AGHS). In addition, a systematic search of literature across three databases (PubMed, Scopus and EMBASE) was performed from inception until May 31, 2021 to identify cases of MAS with AGHS in the pediatric age group (<18 years). Three cases from authors centre and 42 cases identified from systematic literature review were analysed. Precocious puberty was the most common presenting endocrinopathy seen in 56.8% (25/44) cases, followed by hyperthyroidism (10/45), hypophosphatemia (4/45), and hypercortisolism (2/45). Cranio-facial fibrous dysplasia (CFFD) was seen in all while polyostotic fibrous dysplasia and Café au lait macule was seen in 40/45 (88.9%) and 35/45 (77.8%), respectively. Pituitary adenoma (58.3% microadenoma) was localized in 53.3% (24/45) cases on pituitary imaging. Biochemical and clinical remission of AGHS was achieved in 61.5% (24/45) cases with medical therapy. Diagnosing AGHS in MAS is challenging because of concomitant presence of CFFD, non-GH endocrinopathies associated height spurt and elevated serum IGF-1. GH-GTT should be performed in presence of elevated growth velocity and serum IGF-1 (>1 X ULN) despite adequate control of non-GH endocrinopathies. Medical management can lead to disease control in substantial number of cases and often entails use of multiple agents.

Acromegaly: The Impacts of HGH Release on Patient Progression

Hypersecretion of human Growth Hormone (hGH) is the primary mechanism driving Acromegaly, a disease characterised by abnormal growth of extremities and disfigured facial features. This article will discuss hGH secretion, its effect on Acromegaly, and potential treatments for the disease, among other key topics.

ОСОБЕННОСТИ ПРАКТИЧЕСКОГО ИСПОЛЬЗОВАНИЯ СПЕЦИАЛИЗИРОВАННЫХ РЕФЕРЕНТНЫХ ИНТЕРВАЛОВ ГОРМОНАЛЬНЫХ ПОКАЗАТЕЛЕЙ У НЕСОВЕРШЕННОЛЕТНИХ СПОРТСМЕНОВ ДЛЯ ДИАГНОСТИКИ ЭНДОКРИННОЙ ПАТОЛОГИИ

Results of hormonal tests of highly qualified athletes can differ significantly from the general population standards, which makes their interpretation difficult. The purpose of this research was to compare the prevalence of hormonal changes in adolescent athletes according to both the standard and the specialized reference intervals (RI). Materials and methods used: 2550 adolescent athletes, of which 1483 (58.1%) boys and 1067 (41.9%) girls from 28 kinds of sport aged 14 years to 17 years and 11 months old (ME: 16.1±1.1 y/o). All the young athletes have undergone the study of thyroid-stimulating hormone (TSH), free thyroxine (T4 test), cortisol, somatotropic hormone (STH) and total testosterone (chemiluminescent method with Lazurite automatic analyzer by Dynex Technologies Inc., USA) as part of an in-depth medical checkup of athletes in accordance with the Order of the Ministry of Healthcare of Russia No. 134n dated March 01, 2016, on the basis of the Federal Scientific and Practical Center for Children and Adolescents of the Federal Medical and Biological Agency of Russia (Moscow, Russia). The assessment of the hormonal profile was carried out according to both the standard RI and the specialized RI for young athletes. Results: when assessing the endocrine status of young athletes according to the standard RI, the frequency of hormonal changes was 30.6%, and 22.1% according to the specialized RI. When using specialized RI in male athletes, an increase in TSH and cortisol is recorded 2 times less often (p&lt;0.001 for both parameters), an increase and decrease in total testosterone is determined in isolated cases, and hypersecretion of growth hormone is detected 6.5 times more often (p&lt;0.0001). An increase in TSH when assessed using specialized RI in female athletes occurs 2 times less often (p&lt;0.001). Hypersecretion of cortisol and growth hormone is recorded 20% (p=0.34) and 51% (p=0.02) less frequently, respectively. Conclusion: the use of the new RI does allow reducing of the frequency of detection of hormonal changes in adolescent athletes by 8.5% (p=0.03). The use of specialized RI of hormonal parameters in adolescent athletes to interpret TSH levels does not contradict with the modern clinical guidelines when deciding about the appointment of hormone replacement therapy for young athletes with subclinical hypothyroidism. The level of total testosterone, equal to 2.84 nmol/l, in young male athletes aged 16 to 17 y/o cannot be considered as a variant of the norm. The diagnostic value of determining growth hormone and cortisol in highly qualified athletes in adolescence is doubtful due to the high variability of the studied parameters and the complexity of interpreting the results obtained for practical use by a pediatric endocrinologist.

Development and evaluation of the Acromegaly Symptom Diary

BackgroundPatient-reported outcome (PRO) measures are important to consider when evaluating treatments, yet there are no PRO measures for patients with acromegaly that have been developed in accordance with US Food and Drug Administration guidance. Acromegaly is a rare, chronic condition caused by hypersecretion of growth hormone. Disease activity is monitored by measurement in serum of growth hormone and insulin-like growth factor-I. The objectives of this research were to develop the Acromegaly Symptom Diary (ASD), establish a scoring algorithm, and evaluate the psychometric measurement properties of the ASD.MethodsSemistructured interviews consisting of concept elicitation and cognitive debriefing components were conducted with 16 adult participants with acromegaly. The concept elicitation component identified symptoms important to individuals with acromegaly. The cognitive debriefing component gathered information about the participants’ experience with each proposed item of the ASD, their thought process for answering each question, and their interpretation of the items. The psychometric properties of the draft ASD were then evaluated using data from the ACROBAT Evolve (NCT03792555; n = 13) and ACROBAT Edge (NCT03789656; n = 47) clinical trials.ResultsThe 16 participants from the interviews described ongoing symptoms, with the most frequently reported being joint pain (n = 13) and fatigue (n = 12), followed by swelling (n = 8), headache (n = 7), and mood swings (n = 6), and were able to interpret and understand the ASD items and had no issues with the 24-hour recall period. From data collected in the clinical studies, the psychometric properties of internal consistency (0.91 − 0.80), test-retest reliability with item-level and total ASD scores (> 0.70), baseline construct validity (r ≥ |0.38|) across scales, and responsiveness to change (r = 0.52–0.56) were supported for the ASD. The proposed preliminary threshold range to characterize a meaningful change from the patients’ perspective for the ASD total is a 4- to 6-point change for improvement or worsening out of a total score of 70.ConclusionThese findings provide qualitative and quantitative evidence to support the ASD as fit for the purpose of evaluating the symptom experience of patients with acromegaly in clinical trials.