Clonidine Test Research Articles

8517 Low Peak GH in Stimulation Tests Among Obese Children; Is it Clinically Meaningful?

Abstract Disclosure: D. Strich: None. C. Meirman: None. S. Edri: None. D.J. Gillis: None. Background: Peak growth hormone (GH) levels in stimulation tests are lower in obese subjects. The clinical significance of this finding is unclear. It has been suggested that results of tests should be adjusted for body mass index (BMI). Aims: A. To evaluate the association between GH peak levels and body mass index (BMI ) in a single center. B. To discuss the biological and clinical significance of the findings and make recommendations based on this study and other data from the medical literature. Methods: Peak GH levels and BMI standard deviation scores (BMI-SDS) for a total of 988 tests (Clonidine - 694, Glucagon - 198, Arginine - 96) performed in one center were analyzed. Studies referring to the biology of growth hormone and to the evaluation of GH deficiency were reviewed. Results: In the testing center studied, mean peak GH levels were significantly lower in arginine (p=0.015) and clonidine tests (p=0.018) starting at BMI standard deviation score over 1 compared to below 1 BMI-SDS. The differences still remained significant for a subgroup with peaks below 7.5 ng/dl (p=0.003 and p=0.042 respectively). The proportion of overweight and obese children in our cohort and in similar cohorts of children undergoing stimulation tests was about tenfold lower than in the corresponding general population. In other studies, short obese patients responded better than non-obese to GH treatment and had greater increases both in height and IGF-1. Obese adult patients with low GH peaks had high carotid intima-media thickness compared with non GH deficient obese. Conclusion: Obese children are generally tall and therefore are not referred for testing. Those who are short, tend to have lower peaks than their lean peers in GH stimulation tests and respond better to GH therapy. These patients have biologically significant GH deficiency. We do not recommend "correcting" GH test results for BMI in the decision algorithm for GH therapy. Presentation: 6/3/2024

A-072 Growth hormone stimulation tests: experience of a large cohort from a Brazilian diagnostic medical center

Abstract Background Growth hormone (GH) stimulation tests are used to diagnose short stature in children and to assess hypothalamic-pituitary axis in adults. The most frequently stimulation tests are: oral clonidine (CLO), insulin-induced hypoglycemia (ITT), glucagon (GLU) and exercise (EXE). Well-known side effects are hypotension, nausea and vomiting. The aim of this study was to evaluate side effects and intercurrences observed during the performance of GH stimulation tests and to identify their possible predisposing factors. Methods From April/2022 to May/2023, in a large private laboratory located in 8 different sites, 3,006 GH stimulation tests were performed, with 266 patients with two or more GH stimulation tests. Results Considering only patients aged < 18 years (95% of the tests), the mean age was 10.3 ± 2.7 years (median 10.6 years), with 62.5% being male. GH stimulation test was distributed as follows: 64% CLO, 27.6% ITT, 7% GLU and 1.4% EXE. Patients with a history of asthma, allergies, seizure and heart disease were reported in 3%, 1.7%, 0.9% and 0.6%, respectively. More than 2 punctures for venous access were necessary in 9.3% of the cases, particularly in CLO test. The age of patients submitted to GLU was significantly lower compared to CLO and ITT (9.5 ± 3.3 years vs 10.3 ± 2.7 years and 10.6 ± 2.6 years, p < 0.001). Side effects were noted in only 5.1% of the total tests (145/2,863 tests), most frequent in the GLU (50/197 tests, 25%) and none observed in the EXE. There was no correlation of reported side effects with age and weight. As expected, hypotension was more frequent in CLO (27%), not associated with the oral clonidine administered dose (0.1 or 0.150 mg/SC). Nausea and vomiting occurred in 23% of the GLU tests. Symptomatic hypoglycemia that needed glucose administration (oral or parenteral) occurred in 8% of the ITT. Cough was observed in 6 patients during CLO, with no previous history of asthma or allergies. There were no occurrences that hospital transfer was need. Conclusions GH stimulation tests are safe and rarely cause serious side effects, certainly due to the presence of a prepared team for promptly support.

Evaluation of Clinical Characteristics and Growth Hormone Response in a Rare Skeletal Dysplasia: Pycnodysostosis.

Introduction Pycnodysostosis is a rare osteosclerotic skeletal dysplasia; its clinical features include short stature, characteristic facial features, increased bone fragility, and acro-osteolysis of the distal phalanx. Lack of clear guidelines for treatment and follow-up in rare diseases such as pycnodysostosis with growth hormone (GH) deficiency poses a difficulty for the clinician. This study aims to identify clinical, radiological, and endocrine findings of patients with pycnodysostosis focusing on the first year of recombinant human growth hormone (rhGH) treatment response. The eminence of this study is that it presents clinical experience with rhGH, providing an approach for future similar cases. Methods Three girls and two boys from three different families diagnosed with pycnodysostosis via clinical, radiological, and genetic evaluation followed up in the pediatric endocrinology clinic between 2022 and 2023 were enrolled in this study. Clinical findings, anthropometric measurements (weight, height, body mass index [BMI]), and laboratory, radiological, and genetic examinations were evaluated retrospectively. Participants were evaluated for GH deficiency using L-DOPA and clonidine tests if growth rate was below -2 standard deviation score (SDS) for gender and age after one-year follow-up. Results Complaints on admission were short stature (80%) and recurrent bone fractures (20%). Characteristic facial features and brachydactyly were seen in all the patients. Median height SDS on admission was -3.0 (range: -1.9 to -3.8). Median height SDS on last clinic visit was -3.2 (range: -1.7 to -4.2) at a median age of 8 years (range: 3.5-14 years). BMI was normal in four patients, while one was overweight. Bone mineral densitometry z-score was high, and two patients had bone fractures following minor trauma, while one had recurrent fractures. Two siblings (first and second cases) and the third case were diagnosed with GH deficiency, and anterior pituitary hormones were normal otherwise. One had partial empty sella in hypophyseal magnetic resonance imaging. rhGH (33 mcg/kg/day, subcutaneously) was started. Growth rate of the first, second, and third cases increased from 3.3, 3.1, 3.9 to 5, 4.3, 7.2 cm/year, respectively. Prior to rhGH, two had adenoid hypertrophy which was stable following rhGH. Growth rate follow-up of the fourth case continues, while the fifth case, the only participant who has reached adult height, has normal height according to age and gender normative. Conclusion Although rare, pycnodysostosis should not be overlooked in a patient with characteristic facial features, disproportionate short stature, and recurrent fractures. GH deficiency should be evaluated early if growth rate is declining. rhGH may restore growth rate and the possibility of catch-up in growth in patients with pycnodysostosis and GH deficiency. Hence, after first year of rhGH, growth rate of patients with pycnodysostosis is lower when compared to other etiologies of GH deficiency.

Biochemical Assessment of Pheochromocytoma and Paraganglioma.

Pheochromocytoma and paraganglioma (PPGL) require prompt consideration and efficient diagnosis and treatment to minimize associated morbidity and mortality. Once considered, appropriate biochemical testing is key to diagnosis. Advances in understanding catecholamine metabolism have clarified why measurements of the O-methylated catecholamine metabolites rather than the catecholamines themselves are important for effective diagnosis. These metabolites, normetanephrine and metanephrine, produced respectively from norepinephrine and epinephrine, can be measured in plasma or urine, with choice according to available methods or presentation of patients. For patients with signs and symptoms of catecholamine excess, either test will invariably establish the diagnosis, whereas the plasma test provides higher sensitivity than urinary metanephrines for patients screened due to an incidentaloma or genetic predisposition, particularly for small tumors or in patients with an asymptomatic presentation. Additional measurements of plasma methoxytyramine can be important for some tumors, such as paragangliomas, and for surveillance of patients at risk of metastatic disease. Avoidance of false-positive test results is best achieved by plasma measurements with appropriate reference intervals and preanalytical precautions, including sampling blood in the fully supine position. Follow-up of positive results, including optimization of preanalytics for repeat tests or whether to proceed directly to anatomic imaging or confirmatory clonidine tests, depends on the test results, which can also suggest likely size, adrenal vs extra-adrenal location, underlying biology, or even metastatic involvement of a suspected tumor. Modern biochemical testing now makes diagnosis of PPGL relatively simple. Integration of artificial intelligence into the process should make it possible to fine-tune these advances.

Pheochromocytoma and Extraadrenal Paraganglioma: Case Report and Review of the Laparoscopic Approach

The reported percentage of catecholamine-producing tumors is around 80-85% in pheochromocytomas and 15- 20% in paragangliomas. The case of a 34-year-old female patient with a clinical, imaging and histopathological diagnosis of pheochromocytoma with paraganglioma with successful laparoscopic surgical resolution with a retroperitoneal approach is described. The cardinal symptom is uncontrolled hypertension despite medical management with multiple antihypertensives. The initial diagnostic approach is with the measurement of metanephrines in plasma and urine, if this is not conclusive, the clonidine test can be performed. With a positive laboratory result, an imaging study should be performed for localization and finally surgical resolution with a preference for the laparoscopic approach, with less risk of post-surgical complications.

Constitutional delay of growth and puberty – features of the clinic and diagnosis: Prospective study

Aim. To assess clinical, hormonal and metabolic characteristics of adolescent boys with constitutional delay of growth and puberty.
 Materials and methods. One hundred teenage boys aged 15 were examined. The main group (n=70) patients with constitutional delay of growth and puberty (inclusion criteria: height SDS -2.0 and below, Tanner 1); comparison group (n=30) healthy adolescents of the same age. Objective examination: height SDS score, BMI SDS, puberty score. Laboratory diagnostics: IGF-1, testosterone, luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-Mullerian hormone; stimulating tests: clonidine test, triptorelin test. Instrumental methods: radiography of the bones of the wrist of the left hand with the wrist joint to assess bone age using the GreulichPyle method, ultrasound examination of the scrotum, assessment of the component composition of the body by bioimpedancemetry. Statistical data processing: XL Statistics version 7.0, Microsoft Excel, 2010. Nonparametric statistical methods were used. Data are presented as a median indicating the values of the 1st and 3rd quartiles ([Q1; Q3]), the MannWhitney test was used.
 Results. Patients with constitutional delay of growth and puberty had significantly lower rates of physical development compared with healthy peers (p=0.003). Most patients of the main group were found to be underweight, accompanied by a persistent decrease in the proportion of active tissues and a significant, paradoxical increase in the proportion of fat mass according to bioimpedancemetry. The identified deviations indicated metabolic disorders and indicated the formation of sarcopenia syndrome in adolescents with CIGR. The level of sex hormones corresponded to the degree of biological immaturity of the patients, low values of inhibin B in combination with an increased level of AMH indicated Sertoli cell deficiency.
 Conclusion. The pronounced deviations in the clinical, hormonal and metabolic status of patients with constitutional delay of growth and puberty obtained during the study were traced in the clinical picture of most adolescents, which is a significant deviation in the child's health and requires medical correction.

A COMPARISON OF L-DOPA AND CLONIDINE GROWTH HORMONE STIMULATION TESTS IN CHILDREN WITH SHORT STATURE

Aim: The purpose of this study was to compare the results of L-dopa and clonidine GH stimulation tests applied in children with short stature and to identify which of these tests should be primarily selected. Materials and Methods: The records of 68 patients aged between 2.5 and 16.6 years presenting to the pediatric endocrinology clinic with short stature and undergoing GH stimulation tests between September 2016 and February 2021 were evaluated retrospectively. Cases with GH levels <10 ng/dl following the first GH stimulation test then underwent the other GH stimulation test. Thirty-four (50%) of the cases in the study consisted of individuals beginning with the clonidine test, while the other 34 (50%) started with the L-dopa test. Results: Thirty-five patients (51.5%) were girls and 33 (48.5%) were boys. Twenty-seven (79.4%) of the individuals in whom L-dopa was employed as the first test had insufficient GH responses, while a sufficient GH response could not be achieved in 18 cases (66.7%) with the clonidine test. Insufficient growth hormone responses were observed in 17 (50%) of the patients undergoing the clonidine test as the first test, and sufficient growth hormone response was also not achieved at the L-dopa test performed as the second test in 15 (88.2%) of these cases (p< 0.001). A cut-off point of 8.9 ng/dl was determined for 50% sensitivity and 100% specificity for the L-dopa test, and a cut-off point of 9.76 for 88% sensitivity and 94% specificity for the clonidine test. Conclusion: GH stimulation tests performed to investigate GHD are laborious and time-consuming. The first stimulation test to be applied to differentiate GHD from ISS must therefore be well selected. The clonidine stimulation test, with higher sensitivity than but similar specificity to the L-dopa test, can be employed as the first test.

Оцінка соматотропної функції в дітей із синдромом біологічно неактивного гормонa росту на основі проведення стимуляційних тестів iз клонідином та інсуліном

Мета дослідження: оцінити ефективність фармакологічних тестів iз клонідином та інсуліном для стимуляції соматотропного гормона (СТГ) при діагностиці синдрому біологічно неактивного гормонa росту (СБНГР). Матеріали та методи. Обстежено 158 хворих на СБНГР — 47 дівчаток і 111 хлопчиків, середній вік яких становив 8,30 ± 0,24 року. У дослідження включені пацієнти з відставанням у рості понад 2 стандартнi вiдхилення. Визначали базальний та стимульований рівні СТГ із застосуванням тестів з інсуліном та клонідином. Обов’язково проводили чотириденну пробу на чутливість до гормонa росту (ГР) з визначенням рівнів інсуліноподібного фактора росту­1 до першої ін’єкції ГР і наступного дня після завершення проби. Результати. Максимальне підвищення рiвня СТГ на тлі тестів з інсуліном та клонідином в усіх пацієнтів iз СБНГР становило понад 10 нг/мл. Максимальне збільшення показників СТГ було вірогідно вищим (р < 0,01) при проведенні стимуляційного тесту з клонідином, ніж з інсуліном. Це доведено як у дітей з СБНГР — 17,79 ± 0,51 нг/мл та 13,83 ± 0,92 нг/мл відповідно, так і в контрольній групі — 16,81 ± 1,60 нг/мл і 11,18 ± 0,70 нг/мл. Зафіксовано, що індекс стандартного відхилення інсуліноподібного фактора росту­1 у хворих дітей вірогідно нижчий (р < 0,001), ніж у контрольнiй групi. Більш вираженими зміни були в пацієнтів препубертатного віку. Висновки. Фармакологічний тест iз клонідином є більш інформативним, ніж з інсуліном, і викликає вірогiдно вищий стимуляційний максимальний викид ГР. Рекомендовано розпочинати дослідження функції СТГ з проведення проби з клонідином, що є більш безпечною завдяки відсутності ризику тяжких гіпоглікемічних станів.

Оцінка ефективності лікування пацієнтів з ознаками затримки внутрішньоутробного розвитку при оптимізації дози препаратів рекомбінантного гормону росту

Актуальність. Згідно зі світовими статистичними даними, близько 5–10 % новонароджених мають затримку внутрішньоутробного розвитку (ЗВУР) — народжуються з малою масою та/або низькою довжиною тіла щодо свого гестаційного віку. Внаслідок неадекватних темпів постнатального росту у таких дітей до 2-річного віку відзначається відставання в рості. Цей дефіцит прискорення росту спостерігається протягом усього дитинства і підліткового періоду, що у кінцевому підсумку призводить до низькорослості у дорослому віці. Мета: проаналізувати ефективність терапії різних дозових рівнів препаратів рекомбінантного гормону росту (рГР) з метою корекції росту у дітей допубертатного віку з ознаками затримки внутрішньоутробного розвитку. Матеріали та методи. Обстежені 50 дітей (16 дівчаток і 34 хлопчики) з відставанням у рості (середній вік — 6,82 ± 0,36 року), які народилися з ознаками ЗВУР. За результатами тестів із клонідином та інсуліном, пацієнтів з ознаками ЗВУР було розподілено на дві групи: група А — діти без соматотропної недостатності (n = 34; 68 %), група Б — пацієнти з дефіцитом гормону росту (n = 16; 32 %). Група контролю включала 34 пацієнтів (середній вік — 6,58 ± 0,38 року) із соматотропною недостатністю — 13 дівчаток і 21 хлопчика. Усі пацієнти отримували лікування рекомбінантним гормоном росту, починаючи з дози 0,03 мг/кг/добу згідно з протоколом для гіпофізарного нанізму; у разі незадовільної швидкості росту дозу поступово збільшували до 0,05 мг/кг/добу у пацієнтів групи Б. Результати. Вірогідне сповільнення прискорення росту в перші 6 місяців лікування рГР у дозі 0,033 мг/кг/добу було виявлено у пацієнтів з ознаками ЗВУР без соматотропної недостатності (р < 0,05). При лікуванні рГР у дозі 0,05 мг/кг/добу протягом наступних 6 місяців відбулося статистично значуще збільшення коефіцієнта стандартного відхилення SDS (Standard Deviation Score) росту пацієнтів з ознаками ЗВУР без соматотропної недостатності (–2,0 ± 0,14 SDS проти –2,58 ± 0,15 SDS перших 6 місяців з дозою рГР 0,033 мг/кг/добу) (р < 0,05). Висновки. Оптимальною дозою рГР для лікування дітей з ознаками ЗВУР із соматотропною недостатністю є 0,033 мг/кг/добу, а у пацієнтів з ознаками ЗВУР без дефіциту гормону росту — 0,05 мг/кг/добу.

ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.

1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD. On-line survey in endocrine centres throughout Europe. Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018. Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved. Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.

SUN-939 Case Report: Malignant Pheochromocytoma

Introduction: The concept of malignancy for pheochromocytoma is complex and the best definition is the presence of metastases, according to WHO. Anatomopathological scoring systems are not effective in predicting metastases. Malignancy should be considered when tumors larger than 8cm (> 80g), paragangliomas (especially retroperitoneal), dopamine / methoxythyramine increase, Ki67> 6% and SDHB mutation. At 5 years, survival ranges from 50-69%. Metastases may appear 20-40 years after initial treatment of pheochromocytoma. We describe a case that metastasis was identified 33 years after pheochromocytoma excision Case report: A 57-year-old female patient with a postoperative history of 33 years of right adrenal pheochromocytoma was discharged from the endocrinologist after 10 years of follow-up. At diagnosis 33 years ago, she had symptoms of hypertension with paroxysms and weight loss that disappeared after tumor removal. 2 years investigating weight loss with general practitioner without another celebratory. On physical examination, orthostatic hypotension was highlighted. Plasma methanephrine 0.8 nmol / L (VR <0.5) and plasma normetanephrine 1.8 nmol / L (VR <0.9), chromogranin A 5.7 nmol / L (VR <3 nmol / L) and clonidine test with 36.6% suppression of metanephrines, suggesting tumor recurrence. MRI localized recurrence of the adrenals and MIBG scintigraphy with I131 that showed, respectively, in the topography next to the paracaval and retroportal right diaphragmatic crura, isointense T1 and slightly hyperintense T2 at 1.8 cm and radiopharmaceutical hypercaptation in right adrenal topography. Genetic panel by NGS did not identify germline mutation in 22 pheochromocytoma-related genes. FDG PETCT was consistent with MRI and MIBG images. Gallium PETCT68 DOTATOC detected the lesions already described, in addition to a lytic lesion in the left femoral intertrochanteric medulla. Anatomopathological approached abdominal lesion confirming pheochromocytoma metastasis in lymph node conglomerate. Currently has a negative methanephrine plasma, however chromogranin A 142 ng / mL (VR <93), and was chosen by the observant approach. Conclusion: The case of the patient illustrates that pheochromocytoma should be followed indefinitely, as metastases may appear many years later and may present different aggressiveness potentials.

Cortisol Levels in Glucagon Stimulation Test in Children Assessed for Short Stature: Clinical and Laboratorial Correlations.

To assess total cortisol levels in children being evaluating for short stature with normal cortisol reserve and to correlate this response to clinical and laboratory data. Children assessed with glucagon test in our department were recruited in this study retrospectively. Inclusion criteria were: i) age>1 year, ii) absence of chronic illness or medication interfering with ACTH-cortisol axis, iii) GH stimulation levels>3ng/mL at least in one provocation test (glucagon or clonidine), iv) absence of multiple pituitary growth hormone deficiencies, v) normal short Synacthen test in cases of low cortisol response in glucagon test.Two hundred and thirty-seven subjects (160 males, 67.5%) with a mean age of 9.02±3.19 years, were finally included in the analysis. Cortisol peak levels but not cortisol AUC were significantly increased in females compared to males (26.83±7.31 μg/dl vs. 24.04±7.20 μg/dl). When linear correlations were studied, both cortisol peak levels and cortisol AUC were linearly but inversely correlated to age (r=-0.234, p<0.001 and r=-0.315, p<0.001, respectively). Finally, cortisol AUC was inversely correlated to weight Z-scores (r=-0.160, p=0.014). When our analysis was limited only to subjects with intact GH response (GH peak> 7 ng/mL), age was still inversely correlated to cortisol AUC (r=-0.312, p<0.001), and cortisol AUC was linearly correlated to GH AUC assessed with clonidine test (r=0.223, p=0.013). Girls, younger and thinner children exhibit higher cortisol response to glucagon test.

Impact of BMI on peak growth hormone responses to provocative tests and therapeutic outcome in children with growth hormone deficiency

This study investigated the relationship between peak stimulated growth hormone (GH) and body mass index (BMI), as well as the impact of BMI on therapeutic response in patients with GH deficiency (GHD). A total of 460 patients were enrolled in the study. The patients were divided into four groups as per the etiology and peak GH values: idiopathic (n = 439), organic (n = 21), complete (n = 114), and partial (n = 325) GHD groups. Subsequently, they were classified as normal, overweight, or obese based on their BMI. There was no difference in BMI between complete and partial GHD. A significant negative relationship between peak GH and BMI were found. Moreover, obese GHD children had a considerably better therapeutic response in height increase and BMI decrease during 2 years of GH treatment compared to non-obese children with GHD. There was no difference between peak GH and type of GH stimulation test (GHST), except the clonidine test, which showed a much lower peak GH in obese GHD children. In conclusion, BMI had a negative impact on peak GH response, and therapeutic outcome was more favorable in the obese group. Despite no difference in GH response by type of GHST, the degree of obesity differentially affected the results.

Diagnosis of Idiopathic GHD in Children Based on Response to rhGH Treatment: The Importance of GH Provocative Tests and IGF-1.

Purpose: Serum IGF-1 (Insulin like growth factor 1) and Growth Hormone (GH) provocative tests are reasonable tools for screening and diagnosis of idiopathic GH Deficiency (IGHD). However, the average cut-off points applied on these tests have a lower level of evidence and produce large amounts of false results. The aim of this study is to evaluate the sensitivity, specificity, and accuracy of IGF-1 and GH stimulation tests as diagnostic tools for IGHD, using clinical response to recombinant human GH (rhGH) treatment as diagnostic standard [increase of at least 0.3 in height standard deviation (H-SD) in 1 year].Methods: We performed a prospective study with 115 children and adolescents presenting short stature (SS), without secondary SS etiologies such as organic lesions, genetic syndromes, thyroid disorders. They were separated into Group 1 [patients with familial SS or constitutional delay of growth and puberty (CDGP), not treated with rhGH], Group 2 (patients with suspicion of IGHD with clinical response to rhGH treatment), and Group 3 (patients with suspicion of IGHD without growth response to rhGH treatment). Then, they were assessed for diagnostic performance of IGF-1, Insulin Tolerance Test (ITT) and clonidine test (CT) alone and combined at different cut-off points.Results: Based on the ROC curve, the best cut-off points found for IGF-1, ITT, and CT when they were used isolated were −0.492 SDS (sensitivity: 50%; specificity: 53.8%; accuracy: 46.5%), 4.515 μg/L (sensitivity: 75.5%; specificity: 45.5%; accuracy: 52.7%), and 4.095 μg/L (sensitivity: 54.5%; specificity: 52.6%; accuracy: 56.9%), respectively. When we had combined IGF-1 with−2SD as cut-off alongside ITT or CT, we found 7 μg/L as the best cut-off point. In this situation, ITT had sensitivity, specificity and accuracy of 93.9, 81.8, and 90.1%, while CT had 93.2, 68.4, and 85.7%, respectively.Conclusion: Our data suggest that diagnosis of IGHD should be established based on a combination of clinical expertise, auxologic, radiologic, and laboratorial data, using IGF-1 at the −2SD threshold combined, with ITT or CT at the cut-off point of 7 μg/L. Additional studies, similar to ours, are imperative to establish cut-off points based on therapeutic response to rhGH in IGHD, which would be directly related to a better treatment outcome.

Timing of GH Peak in Both Glucagon and Clonidine Tests is of Major Clinical Importance

Objective: To detect a possible correlation between timing of the peak value of growth hormone (GH) during stimulatory tests (STs) and the effectiveness of treatment with recombinant human growth hormone (rhGH) in children with idiopathic GH deficiency (iGHD). Methods: We retrospectively studied 92 patients with iGHD (57 boys; mean age at diagnosis: 9.93 years). Diagnosis was confirmed by 2 different STs, glucagon stimulation test (GST), and clonidine stimulation test (CST). Auxologic parameters were recorded, while observed and predicted (according to KIGS Prediction Model) height velocity during the first year of treatment and the index of responsiveness (IoR) were calculated for the prepubertal children (n = 65). Results: Atypical GST was defined as that with peak GH value at time 0 minutes, 30 minutes, 60 minutes, or 180 minutes, whereas atypical CST was defined as that with peak timing at 0 minutes, 30 minutes, or 120 minutes. Atypical GST was detected in 18 patients (19.57%). IoR was lower in the prepubertal children with atypical GST (-1.81 ± 0.67 versus -1.34 ± 0.85; P = .051). In the CST, the 18 children who had atypical timing, had significantly lower IoR (-1.86 ± 0.66 versus -1.35 ± 0.84; P = .047). When the patients were categorized according to the number of atypical tests, significant differences in the IoR were detected (-2.09 ± 0.68 with 2 atypical STs [n = 6], -1.64 ± 0.61 with 1 atypical ST [n = 16], and -1.29 ± 0.87 with no atypical ST [n = 43], P = .045). Conclusion: The presence of atypical peak GH timing during ST may be a factor that predicts lower growth hormone velocity during the first year of rhGH treatment in prepubertal children with iGHD. Abbreviations: CST = clonidine stimulation test; GH = growth hormone; GHD = growth hormone deficiency; GST = glucagon stimulation test; iGHD = idiopathic growth hormone deficiency; IoR = index of responsiveness; rhGH = recombinant human growth hormone; SDS = standard deviation scores; ST = stimulatory test.

Pheochromocytoma presenting with severe hyperglycemia and metabolic acidosis following intra-articular glucocorticoid administration: a case report

BackgroundThere are several reports of pheochromocytoma crisis triggered by systemic glucocorticoid administration. However, pheochromocytoma crisis after intra-articular glucocorticoid administration has been rarely reported.Case presentationA 45-year-old Japanese man presented to our hospital with a sudden, severe headache. He had no history of diabetes. He had received an intra-articular injection of betamethasone (2 mg) for joint pain, 2 days prior to his admission. On examination, his blood pressure was 240/126 mmHg and pulse was 120 beats/minute. The possibility of cerebrovascular events was ruled out by imaging studies and lumbar puncture. Blood tests revealed severe hyperglycemia (523 mg/dL) and metabolic acidosis (pH 7.21, anion gap 26.2 mEq/L, lactate 11.75 mmol/L) with a glycosylated hemoglobin level of 5.7%. Although a urine sample could not be obtained, fulminant type 1 diabetes mellitus and diabetic ketoacidosis were suspected based on these findings. However, after the initial treatment for diabetic ketoacidosis, his insulin secretion was found to be normal and the plasma levels of ketones were not elevated. This excluded the possibility of fulminant type 1 diabetes mellitus and diabetic ketoacidosis. Subsequently, a left adrenal gland tumor and elevated levels of serum catecholamine and urinary catecholamine metabolites were detected, while his other hormone levels were normal. Serum catecholamine levels did not decrease following the clonidine test, and a functional scintigraphy using iodine-131 metaiodobenzylguanidine showed strong uptake in the region of the left adrenal gland. Although no signs of pheochromocytoma crisis, such as paroxysmal hyperglycemia and hypertension, had been observed since admission, a pheochromocytoma was diagnosed based on the investigations. After controlling his blood pressure, a left adrenalectomy was performed.ConclusionsThis case illustrates that intra-articular glucocorticoid administration can induce a pheochromocytoma crisis and an increase in hyperglycemia, and that pheochromocytoma crisis can resemble the clinical picture of fulminant type 1 diabetes mellitus owing to severe hyperglycemia with metabolic acidosis and normal glycosylated hemoglobin levels, especially under the influence of glucocorticoid.

New Insights in Growth Hormone Stimulation Tests Protocols

Abstract Objective: The objective of this study was to analyze the performance of 2 stimulation tests used in the diagnosis of growth hormone deficiency. Method: A retrospective study was conducted on a non-random sample of 310 patients, between 2 and 20 years old, who were hospitalized in the Mureș County Hospital’s Endocrinology Department and in the National Institute of Endocrinology C.I. Parhon with short stature between 2009-2015. Inclusion criteria: all subjects who underwent growth hormone stimulation tests in accordance with the national protocol. Microsoft Office Excel was used for data collection and MedCalc v 12.5 was used for statistical analysis. Results: From the total of 310 patients, 102 were diagnosed in Târgu Mureș and 208 in Bucharest. Sex ratio favored boys (boys:girls 1.64:1). In 173 subjects growth hormone deficiency was confirmed. For both tests the percentage of maximum response was the highest for the 60 minutes blood sample regardless if the test were positive or not. Both tests have 100% sensitivity and negative predictive value, with the highest specificity for the 60 minutes clonidine and 30 minutes insulin. The false positive rate was 60% for the insulin test and 27.2% for clonidine for Târgu Mureș sample and 86.9% for the insulin test and 62.5% for clonidine for Bucharest sample. The concordance of the 2 tests was 49.36%. Conclusions: Stimulating growth hormone testing has a number of limitations but is still needed in some auxological circumstances. We recommend performing the clonidine test first to exclude idiopathic short stature and then the insulin tolerance test for the diagnosis of growth hormone deficiency.

Reliability of clonidine testing for the diagnosis of growth hormone deficiency in children and adolescents.

The diagnosis of growth hormone deficiency (GHD) is currently based on clinical, auxological, biochemical and neuro-radiological investigation. Provocative tests of GH secretion using physiological/pharmacological stimuli are required to confirm GHD. The clonidine test (CT) is widely used to assess GH secretory status. In this retrospective study, we analyzed the reliability of CT and the effect of puberty in a large number of children with short stature who had been evaluated for suspected GHD. Data were collected retrospectively from 327 children and adolescents with short stature (204 boys and 123 girls, median age 10.5years (IQR 7.90-12.40) followed in four Italian Paediatric Endocrine Units (Cagliari, Genova, Napoli and Roma) between 2005 and 2013. All children underwent CT as the first GH stimulation test after exclusion of other known cause of their short stature. In 73 prepubertal children and 25 pubertal children, the GH peak after CT was <7μg/L. GHD was confirmed in 87 (37 organic, 50 idiopathic). Six prepubertal and five pubertal patients showed false positive responses. The median BMI-SDS in these children was similar to that of children with GH peak ≥7μg/L, and none were obese. Overall, the prevalence of false-positive responses was 3.3%. The median (IQR) peak GH after CT was similar between prepubertal and pubertal GHD (3.80μg/L [1.7-6.00] vs 3.51μg/L [0.76-5.74]) and non-GHD (13.70μg/L [10.70-18.40] vs 12.40μg/L [9.90-19.25]) children. Our results show that CT is a reliable and safe GH-releasing agent in both prepubertal and pubertal children.

Combined simultaneous arginine clonidine stimulation test: Timing of peak growth hormone (GH) concentration and correlation with clinical indices of GH status

BackgroundThe aims of this study were to determine if it is possible to truncate a combined simultaneous arginine clonidine stimulation test, and to correlate the outcome of the test with clinical indices of GH status. MethodsCharts of subjects who underwent a combined simultaneous arginine clonidine stimulation test between January 1, 2007 and August 31, 2016 were reviewed. Results131/203 (64.5%) tests performed in children with growth failure demonstrated a peak GH ≥ 10 ng/ml. 6/7 (85.7%) tests performed in adolescents at the end of GH treatment had a peak GH ≥ 5 ng/ml. Among these negative tests, 97.8% had a passing GH by 120 min. 58/98 (59.1%) tests that had a sample at 150 min were negative. 3/58 (5.2%) had a passing GH level only at 150 min. Therefore, if the test were shortened to 120 min, 5.2% of normal responders would be missed. There was a weak correlation of peak GH with baseline growth velocity and serum IGF-1 z-score. A trend towards an inverse correlation between peak GH level and change in growth velocity pre- and post-GH was seen. ConclusionsIf the combined simultaneous arginine clonidine test were shortened to 120 min, 5.2% of normal responders would be missed. Although this test has not been compared to any “gold standard” GH stimulation test, the outcome of this test does correlate weakly with clinical indices of GH status and spares patients the inconvenience of sequential testing.

Tratamiento con hormona de crecimiento y craneofaringioma: presentación de caso

El craneofaringioma es el tumor más frecuente de la edad pediátrica. Se localiza frecuentemente en el área supraselar; histológicamente benigno, pero con carácter expansivo que provoca manifestaciones clínicas secundarias a la afectación de estructuras vecinas. El tratamiento es quirúrgico y, en la mayoría de los casos, trae como consecuencia un panhipopituitarismo. El tratamiento con hormona de crecimiento (GH) en estos casos es un tema de debate. A nivel internacional se ha realizado en situaciones excepcionales, obteniendo resultados favorables. En Cuba, este es el primer caso dentro de una casuística de 813 pacientes tratados con GH, en 12 años de experiencia.Describimos el caso clínico de una paciente con diagnóstico de craneofaringioma, operada, que recibió tratamiento con hormona de crecimiento. Se trata de una fémina que a los 9 años de edad inicia sus estudios por presentar talla baja. Se le realizó test de clonidina que reveló déficit de GH. En la tomografía computarizada de cráneo se observó lesión hipofisaria de 2 cm de diámetro que ocupa cisterna supraselar, con lo que se llega al diagnóstico de un craneofaringioma. Se lleva a cabo la intervención quirúrgica con resección total macroscópica del tumor. Posteriormente, se instaura un panhipopituitarismo, por lo que se realiza sustitución del eje tiroideo, adrenal, gonadal y hormona antidiurética. Se evalúa alteración del crecimiento, ausencia de recidiva tumoral y, con el consentimiento de la familia, se inicia tratamiento con GH, con lo que se obtiene ganancia de talla favorable de 39 cm/5años, sin evidencia de recidiva tumoral.