Diagnosis Of Growth Hormone Deficiency Research Articles

Consensus and controversies on the diagnosis of GH-deficiency in children and adults - A Delphi survey by the GH research society

Consensus and controversies on the diagnosis of GH-deficiency in children and adults - A Delphi survey by the GH research society

Metabolic Characteristics and Discriminative Diagnosis of Growth Hormone Deficiency and Idiopathic Short Stature in Preadolescents and Adolescents.

Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are the most common types of short stature (SS), but little is known about their pathogenesis, and even less is known about the study of adolescent SS. In this study, nuclear magnetic resonance (NMR)-based metabolomic analysis combined with least absolute shrinkage and selection operator (LASSO) were performed to identify the biomarkers of different types of SS (including 94 preadolescent GHD (PAG), 61 preadolescent ISS (PAI), 43 adolescent GHD (ADG), and 19 adolescent ISS (ADI)), and the receiver operating characteristic curve (ROC) was further used to evaluate the predictive power of potential biomarkers. The results showed that fourteen, eleven, nine, and fifteen metabolites were identified as the potential biomarkers of PAG, PAI, ADG, and ADI compared with their corresponding controls, respectively. The disturbed metabolic pathways in preadolescent SS were mainly carbohydrate metabolism and lipid metabolism, while disorders of amino acid metabolism played an important role in adolescent SS. The combination of aspartate, ethanolamine, phosphocholine, and trimethylamine was screened out to identify PAI from PAG, and alanine, histidine, isobutyrate, methanol, and phosphocholine gave a high classification accuracy for ADI and ADC. The differences in metabolic characteristics between GHD and ISS in preadolescents and adolescents will contribute to the development of individualized clinical treatments in short stature.

Tackling access and payer barriers for growth hormone therapy in Saudi Arabia: a consensus statement for the Saudi Working Group for Pediatric Endocrinology.

Prompt diagnosis and early treatment are key goals to optimize the outcomes of children with growth hormone deficiency (GHD) and attain the genetically expected adult height. Nonetheless, several barriers can hinder prompt diagnosis and treatment of GHD, including payer-related issues. In Saudi Arabia, moderate-to-severe short stature was reported in 13.1 and 11.7 % of healthy boys and girls, respectively. Several access and payer barriers can face pediatric endocrinologists during the diagnosis and treatment of GHD in Saudi Arabia. Insurance coverage policies can restrict access to diagnostic tests for GHD and recombinant human growth hormone (rhGH) due to their high costs and lack of gold-standard criteria. Some insurance policies may limit the duration of treatment with rhGH or the amount of medication covered per month. This consensus article gathered the insights of pediatric endocrinologists from Saudi Arabia to reflect the access and payer barriers to the diagnostic tests and treatment options of children with short stature. We also discussed the current payer-related challenges endocrinologists face during the investigations of children with short stature. The consensus identified potential strategies to overcome these challenges and optimize patient management.

Very low serum IGF-1 levels are associated with vertebral fractures in adult males with beta-thalassemia major.

Patients with beta-thalassemia major (BTM) often develop several endocrine disorders due to chronic iron overload. They are also prone to osteoporosis and vertebral fractures. Plasmatic insulin-like growth factor-1 (IGF-1) levels are often low in subjects with BTM, which origin is multifactorial. The aim of this study was to evaluate a possible relationship between serum IGF-1 levels and the presence of osteoporosis and/or vertebral fractures. We retrospectively evaluated the occurrence of vertebral fractures in 30 adult male patients affected by BTM (mean age 43.3 ± 7.9years) with low serum IGF-1 (median value 52.4ng/ml, 38.5-83.4). Only 6 of them (20.0%) were diagnosed with GH deficiency (GHD) after GHRH/arginine stimulation test, while 23 (76.7%) had osteoporosis and 12 (40.0%) had known vertebral fractures. All patients except one also showed at least one endocrine disorder. Serum IGF-1 was significantly lower in BTM patients with vertebral fractures compared to patients without vertebral fractures (U = 41.0, p = 0.005) while it was not significantly different between patients with low bone mass compared to patients without low bone mass. The diagnosis of GHD was significantly associated with lower serum IGF-1 (p = 0.001) and vertebral fractures (p = 0.002) but not with low bone mass. After ROC analysis, we found that very low IGF-1 (≤ 50.0ng/dl) was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and was also predictive of GHD (sensitivity 75.0%, specificity 100.0%). Our study shows that, in male patients with BTM, serum IGF-1 ≤ 50.0ng/dl is a marker of vertebral fractures and it is predictive of a diagnosis of GHD.

Issues of prevalence, pathogenesis, clinical features, diagnosis and treatment of the associated course of non-alcoholic fatty liver disease and diagnosis of growth hormone deficiency: Brief overview of articles

Growth hormone deficiency (GHD) is associated with insulin resistance, visceral obesity, type 2 diabetes, dyslipidemia, and NAFLD. The diagnosis of GHD should be suspected in all patients with hypothalamic-pituitary axis disorders. If GHD is not adequately treated before or after transplantation, the presence of NAFLD can lead to rapid progression of NASH to cirrhosis. Future research should focus on developing early detection strategies as well as biochemical and imaging techniques to monitor patients with PG for progression of NAFLD and NASH. Randomized controlled trials should evaluate optimal treatment strategies in this cohort and balance the effects on NAFLD, glucose metabolism, and diabetes risk, as well as the long-term effects on fibrosis and cancer risk. The potential of GH therapy in patients with NAFLD without GH deficiency needs to be further studied with long-term follow-up. It is important to note that the standard treatment for these patients should be a multidisciplinary approach with close collaboration between hepatologists and endocrinologists, focused on the needs of the individual patient.

Evaluation of growth hormone deficiency in women with unexplained infertility

PurposeGrowth hormone (GH) has been recognized to play a regulatory role in female reproduction. It has been reported that infertile GH deficient patients regained fertility after GH replacement. The frequency of GH deficiency is not established in patients diagnosed with unexplained infertility. Here, we aim to present the prevalence of GH deficieny in this patient group. MethodsWe included patients diagnosed with unexplained infertility throughout 18 months. Insulin tolerance test (ITT) and glucagon stimulation tests (GST) were performed and insufficient response to both tests was required for the diagnosis of GH deficiency. ResultsTwenty-five patients were included in the study, the mean age was 27.4 ± 4.5 years and the median duration of infertility was 60 months (min:14, max:120). Two patients were GH deficient according to GST and 14 to ITT. Two patients (8%) showed lack of response on both tests and were diagnosed with GH deficiency. ConclusionThe rate of GH deficiency among women with unexplained infertility was 8% in this preliminary study. There is need for further studies with larger patient groups to verify the results.

Blood pressure response to clonidine in children with short stature is correlated with postural characteristics: a retrospective cross-sectional study

BackgroundClonidine stimulation test has been widely used in the diagnosis of growth hormone deficiency in children with short stature with a high level of reliability. However, it may cause hypotension, which usually appears as headache, dizziness, bradycardia, and even syncope. It is well known that elevating the beds to make patients’ feet above their cardiac level might relieve this discomfort. However, the real efficiency of this method remains to be proved while the best angle for the elevated bed is still unclear.MethodsA total of 1200 children with short stature were enrolled in this retrospective cross-sectional study. Age, gender, weight, and basic systolic and diastolic blood pressure were collected. Blood pressure at 1, 2, 3, and 4 h after stimulation tests were recorded. The participants were divided into 3 groups based on the angles of the elevated foot of their beds named 0°, 20°, and 40° groups.ResultsAt one hour after the commencement of the tests, participants lying on the elevated beds showed a higher mean increase on the change of pulse pressure. The difference in the angles of the elevated beds did not show statistical significance compared with those who did not elevate their beds (0.13 vs. 2.83, P = 0.001; 0.13 vs. 2.18, P = 0.005; 2.83 vs. 2.18, P = 0.369). When it came to 4 h after the tests began, participants whose beds were elevated at an angle around 20° had a significantly higher mean increase in the change of pulse pressure values compared with those whose beds were elevated at an angle around 40° (1.46 vs. -0.05, P = 0.042).ConclusionElevating the foot of the beds of the patients who are undergoing clonidine stimulation tests at an angle of 20°might be a good choice to alleviate the hypotension caused by the tests.

Postoperative Craniopharyngioma in a 10-Year-Old Girl Presenting with Central Precocious Puberty, Central Diabetes Insipidus, and Growth Hormone Deficiency

Background: Hypopituitarism is the most common endocrinology complication of postoperative craniopharyngioma. However, we found a 10-year-old girl with a history of postoperative craniopharyngioma presenting with central precocious puberty (CPP), central diabetes insipidus (CDI), and growth hormone deficiency (GHD).
 Case presentation: A 5-year-old girl experienced breast growth followed by menstruation six months later. The patient's weight was 19 kg (weight-for-age: P25-P50), height was 109 cm (height-for-age: P10-P25), and good nutritional status (Waterlow 90%). The stage of pubertal development was M2P2. There was a history of craniopharyngioma, and it was resected at the age of 2 years. After surgery, the patient developed CDI and has received desmopressin. No new tumour growth was found from evaluation with periodic MRIs every three years. After CPP was established, with increased serum levels of LH, FSH, and estradiol, GnRH agonist therapy was given at 100 mcg/kg BW every month. During five years of follow-up, the patient experienced clinical and laboratory improvement. However, the growth is only 3-4 cm/year (<P3) with short stature (height-for-age: <P3) and overweight. Low levels of IGF1 and GH were found in the stimulation test results, so the diagnosis of GHD was confirmed. The patient will receive growth hormone therapy and is expected to reach her potential genetic height (148.5 - 165.5 cm).
 Conclusion: Even though the craniopharyngioma tumour has been resected and no recurrence has occurred, it is crucial to evaluate the hormones produced by the pituitary thoroughly.

Diagnostic significance and considerations of growth hormone stimulation testing and insulin-like growth factor 1 in growth hormone deficiency

The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.

Attenuation of gadolinium enhancement in pituitary gland on magnetic resonance imaging of patients with pediatric growth hormone deficiency

BackgroundAlthough it is generally thought that disturbance of perfusion in the anterior lobe of the pituitary gland leads to complete or partial hypopituitarism, the gadolinium (Gd) enhancement findings on Magnetic Resonance Imaging (MRI) of patients with growth hormone deficiency (GHD) remain unknown. The purpose of this study was to compare Gd enhancement of the pituitary gland on MRI of patients with GHD to that of healthy subjects.MethodsIn this retrospective study, we analyzed the data of 10 patients with clinically diagnosed GHD who underwent Gd-enhanced MRI of their pituitaries (age 8.3pm3.5 year, female 1, males 9), together with data of 5 patients with clinically normal growth hormone (GH) dynamics who also underwent Gd-enhanced pituitary MRI (age 6.2pm3.4 year, female 4, males 1). In each subject, a maximum-diameter region of interest (ROI) was drawn on the anterior pituitary gland of post Gd-enhanced coronal T1-weighted images, and the signal intensity ratio of the anterior pituitary gland to the white matter on the right temporal lobe of the same cross section was assessed.ResultsThe mean area of the ROI in the anterior pituitary gland and white matter of temporal lobe on the same cross section showed no significant differences between patients with GHD and those with normal GH (pituitary, 17.43 mm2pm8.24 vs. 21.08 mm2pm10.40, p = 1.00; white matter, 74.47mm2pm24.19 and 62.50 mm2pm17.90, p = 0.37), suggesting that the sizes of the pituitary glands were comparable. The ratios of Gd enhancement in the anterior pituitary gland showed significant differences between GHD and normal-GH subjects (pm0.716pm0.68pm0.26 vs.0.72pm0.16, p= 0.04).ConclusionsThese results suggested that the contrast effect on Gd-enhanced MRI is attenuated in the pituitary glands of patients with GHD compared to those with normal GH. These new clinical findings regarding Gd-enhanced MRI can assist the diagnosis of pediatric GHD.

Identifying patient-related predictors of permanent growth hormone deficiency.

Isolated childhood growth hormone deficiency (GHD) can persist into adulthood, and re-testing at the transition period is needed to determine whether continued growth hormone therapy is indicated. Here, our objective was to identify predictors of permanent GHD. Retrospective single-centre study of patients with childhood-onset GHD who were re-tested after adult height attainment. Auxological, clinical, laboratory, and MRI data throughout follow-up were collected. We included 101 patients. At GH treatment initiation, age was 8.1 ± 0.4 years, height -2.25 ± 0.8, and BMI -0.27 ± 0.1 SDS. The 29 (28.7%) patients with persistent GHD had lower height SDS (-2.57 ± 0.1 vs. -2.11 ± 0.1, p<0.001) and mean GH peaks (8.4 ± 1.0 vs.13.2 ± 0.5 mIU/L, p<0.001) at GHD diagnosis; at adult height, they had lower IGF1 (232 ± 19.9 vs. 331 ± 9.1 ng/mL, p<0.001) and higher BMI SDS (-0.15 ± 0.27 vs. -0.73 ± 0.13, p<0.005). By multivariate analysis, the best predictive model included height and BMI SDS, both GH peaks, and MRI findings at diagnosis. Patients with height at diagnosis <-3 SDS had a 7.7 (95% IC 1.4-43.1, p=0.02) fold higher risk of persistent GHD after adjustment on BMI SDS. An abnormal pituitary region by MRI was the strongest single predictor (7.2 times, 95% CI 2.7-19.8) and after multivariate analysis adjustment for GH peaks and height SDS at diagnosis, the risk increased to 10.6 (1.8 - 61.3) times. Height <-3 SDS at GHD diagnosis and pituitary MRI abnormalities should lead to a high index of suspicion for persistent GHD.

THU172 Accuracy Of The Glucagon Testing In The Diagnosis Of Growth Hormone Deficiency During Transition

Abstract Disclosure: N. Di Iorgi: None. D. Guglielmi: None. N. Flavia: None. A. Allegri: None. D. Fava: None. E. Casalini: None. G. Patti: None. M. Maghnie: None. Objectives: To evaluate the accuracy of the Glucagon test (GST) compared with the Insulin Tolerance test (ITT) as the gold standard in the diagnosis of Growth Hormone deficiency (GHD) in young adults with childhood-onset GHD (COGHD). Methods: Eighty-six subjects with COGHD (33F, 55M) were evaluated by ITT and GST stimulation tests and IGF-1 SDS at adult height achievement (median age of 17.5; IQR 13.9-18.4 years). Subjects were recruited from a single Center and based on the AACE 2019 Guidelines [1] classified as 1. idiopathic isolated GHD (I-GHD n=40 with normal brain MRI); 2. organic moderate GHD (omGHD with less than 3 pituitary deficiencies-PD and IGF-1&amp;lt;0 SDS, total n=40; n=12 midline defects, n=2 ALL, n=26 CNS tumors); 3. congenital/genetic defects/organic severe GHD (osGHD ≥3 PD and IGF-1 &amp;lt;-2 SDS, total n=6; n=1 midline defect, n=5 CNS tumors). ROC analyses were performed in order to analyze the Sensitivity (Se) and Specificity (Sp) of the GH peak after GST and of IGF-1 SDS compared to ITT. A peak GH value &amp;lt;6μg/L after ITT was suggestive of permanent GHD [2]. Results: Median GH peak to ITT (0.2; IQR 0.01-0.7 μg/L) and GST (0.1; IQR 0.01-1.4μg/L) were lower in osGHD compared to I-GHD subjects (15.0; IQR 8.6-21.9 to ITT and 12.6; IQR 10.5-18.8 μg/L to GST, P’s &amp;lt;0.0001); similarly, GH peak to ITT (2.1; IQR 1.1-6.8 μg/L) and GL (2.7; IQR 1.2-5.8) were lower in omGHD compared to I-GHD subjects (P’s &amp;lt;0.0001). Mean IGF-1 were also lower in osGHD (-3.2 SDS; IQR -7.4- -2.9, P&amp;lt;0.0001) and in omGHD (-2.0 SDS; IQR -2.8 - -0.7; P&amp;lt;0.0001) compared to I-GHD subjects (0,1; IQR -0.6-1.1SDS). A GH peak value to GST of 7.59 mcg/L (Se 92.3%, Sp of 87.2%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 89.5% of the entire cohort while an IGF-1 cut-off of -1.45 SDS (Se 73%; Sp 93.5%; AUC=0.84; 95% CI, 0.75 - 0.94) correctly classified 83,1%. A GH peak value to GST of 5.81 mcg/L (Se 96.6%, Sp of 81.8%; AUC=0.95; 95% CI, 0.88-1.02) correctly classified 92.5% of omGHD patients while an IGF-1 cut-off of -1.64 SDS (Se 72.3%, Sp of 90.9%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 77.5% omGHD patients. Median BMI SDS was higher in patients with osGHD (1.8; IQR 1,6- 2.2, P&amp;lt;0.001) and omGHD (0.6; IQR 0.1- 1.8, P&amp;lt;0.001) compared to I-GHD (0.2; IQR -0.7- 1.1). GH peak to GST correlated with BMI SDS only in the total cohort (r -0.313, P=0.0031). Conclusions: Our results suggest that a peak value &amp;lt;6 μg/L after GST is accurate in detecting permanent GHD during transition in a cohort of patients with organic GHD with less than 3 pituitary defects and IGF-1 values &amp;lt;0 SDS; the GH response to GST could be affected by BMI SDS, but further studies are needed. [1] Yuen KCJ et al. Endocr Pract 2019; 25 (11):1191-1232. [2] Maghnie M et al, EJE 2005; 152:589-596. Presentation: Thursday, June 15, 2023

FRI340 Growth Hormone Deficiency Post Carbon Monoxide Poisoning

Abstract Disclosure: A.Y. Ghamlouche: None. O. Alzohaili: None. A.H. Elkadry: None. Carbon monoxide (CO) is the poisonous byproduct of combustion of fossil fuels, that is odorless and tasteless. In toxic levels CO leads to the impaired functioning of red blood cell’s ability to transport oxygen to tissues.1 Following CO toxicity, white matter demyelination and necrosis of the Globus pallidus that further results in other neurologic disorders, is common.2 A novel and underrecognized consequence of CO poisoning is growth hormone deficiency (GHD). GHD is the most common pituitary hormone deficiency following a traumatic brain injury.3 Four cases of GHD were described following an event of CO poisoning. Recommended GHD diagnosis criteria of less than 5.0 ng/mL was used with these patients. The Insulin Tolerance Test (ITT) and Glucagon stimulation test (GST) were administered. All patients had no causes of GHD in their medical history prior to their encounters with CO poisoning. A 44-year-old male with exposure in 2020, came for an evaluation in January of 2022 complaining of memory impairment, brain fog, mental fatigue, cognitive decline, anxiety, poor libido, and neuropathy. showed a GH peak of 1.1 ng/mL during the ITT a peak of 1.0 ng/mL during the GST. A 51-year-old male with exposure in 2016, came for an evaluation in December of 2020 complaining of memory impairment, blurry vision, fatigue, physical weakness, mood changes, and stuttered speech. Results showed a GH peak of 4.4 ng/mL during ITT and a GH peak of 0.157 ng/mL during the GST.A 43-year-old female with exposure in 2017, came for an evaluation in January of 2022 complaining of memory loss, attention issues, anxiety, depression, fatigue, weight gain and neuropathy. Results showed a GH peak of 1.7 ng/mL during ITT and a GH peak of 2.6 ng/mL during the GST. A 42-year-old male with exposure in 2018, came for an evaluation in November of 2019 complaining of memory impairment, headaches, tremors, fatigue, anxiety, depression, declining cognition, insomnia, poor libido, lack of concentration, and poor vision. Results showed a GH peak of 3.6 ng/mL during ITT and a GH peak of 0.109 ng/mL during the GST. All 4 patients were started on GH replacement therapy following their tests. All patients responded well, and showed significant improvements in quality of life. A possible connection can be drawn between pituitary gland damage and hypoxia from CO poisoning.

The consequences of growth hormone deficiency in adults

Adult growth hormone deficiency (GHD) is a result of the decreased growth hormone (GH) production and secretion from the anterior pituitary gland in adulthood, that cannot be explained by the physiological ageing process. GHD is associated with numerous deleterious consequences such as adverse changes in body composition, carbohydrate and lipid metabolism, alterations in the cardiovascular system, and deterioration in the quality of life (QoL). Most of these complications are at least partially reversible during recombinant human growth hormone (rhGH) replacement therapy. Thus, physicians and particularly endocrinologists, should consider GHD diagnosis and select patients who could benefit from rhGH therapy.

Reliability of Agreement between Insulin, Clonidine, and Glucagon Stimulation Tests for the Diagnosis of Growth Hormone Deficiency in Children: A Retrospective Cohort Study.

Growth hormone (GH) deficiency (GHD) is a rare disorder. The diagnosis of GHD requires a combination of two provocative GH tests. This study aimed to find agreement between commonly used medications to determine which combined tests have high reliability of agreement. This retrospective cohort included 201 children who underwent GH provocation testing from January 2012 to December 2022. The insulin tolerance test (ITT) with the clonidine stimulation test (CST) or glucagon stimulation test (GST) with the CST were performed. We calculated Cohen's kappa to determine the agreement between the test medications by considering the post-stimulation peak GH level with a cut-off value of 10 ng/mL as the primary outcome. A total of 151 patients underwent the two provocative tests and were included in the analysis. Of these patients, 119 underwent the ITT and CST and 54 (45.3%) were diagnosed with GHD. However, 32 patients underwent the GST and CST and 18 (56.2%) were diagnosed with GHD. The kappa value for ITT and CST was 0.258 (25.8%), indicating fair agreement between clonidine and insulin (p = 0.005). However, the kappa value for CST and GST was 0.178 (17.8%), representing slight agreement. The correlation coefficient revealed a very strong relationship between ITT and CST. Clonidine has fair agreement and a very strong correlation coefficient with ITT when used to diagnose GHD in children. Among the commonly used pharmacological tests for GH provocation in our unit, the CST was considered the best pharmacological test in terms of safety and reduced parental anxiety.

A rare case of SCHMID metaphyseal chondrodysplasia associated with hypothyroidism,growth hormone deficiency and celiac disease: case report.

The authors present a rare case of 4-year-2-month-old boy referred to our Unit for harmonious short stature, he had a waddling gait, subtle micromelia, and hyperlordosis, no special facies. The skeletal scan made the diagnosis of SCHMID metaphyseal chondrodysplasia. The first laboratory workup showed elevated thyroid stimulating hormone and anti-tissue transglutaminase immunoglobulin A. The duodenal biopsies confirmed the diagnosis of coeliac disease. Treatment of levothyroxine was initiated with a gluten-free diet .6 years later, his re-evaluation showed a low insulin-like growth factor 1 and low growth hormone peaks confirming the diagnosis of growth hormone deficiency, Growth hormone therapy was initiated with an adjusted dose of levothyroxine. Other causes of short stature should not be missed when diagnosing chondrodysplasia, and further investigations should be carried out to detect other concomitant disorders since metaphyseal chondrodysplasia is a rare cause for short stature while hypothyroidism and coeliac disease are relatively common.

Combined growth hormone stimulation testing: Could the tests be shortened?

IntroductionGrowth hormone stimulation tests (GHST) remain the cornerstone for diagnosing growth hormone deficiency (GHD), yet they can be lengthy and costly. We aimed to examine whether the combined clonidine and glucagon stimulation test (CGST) and l-dopa and glucagon stimulation test (LDGST) can be shortened without compromising the test's specificity. Material and methodsWe retrospectively analyzed the baseline characteristics, auxological and laboratory data of children with short stature who had undergone a CGST and an LDGST for GHD. We compared the diagnostic accuracy for the standard test and shortened test, eliminating time points of 0 and 210 min. ResultsWe reviewed 830 charts (8.17 ± 2.92 years old; 56.27% males), with 431 (57.0%) children in the CGST group, and 38 (51.35%) in the LDGST group who tested negative for GHD. The peak and maximum GH levels occurred at the 60-min time point for both the CGST and LDGST. Eliminating the 0-min time point was the only time that did not affect the specificity of the CGST, with a false-positive rate of 2 (2.99%), specificity of 0.99 (0.99–0.99), and p value of 0.25. Eliminating the 0- and 210-min time points did not affect the specificity of the LDGST, with a false-positive rate of 2 (5.26%), specificity of 0.95 (0.95–0.95), and p value of 0.24. ConclusionsWe concluded that 0-min time point could be eliminated without compromising the combined GHST diagnostic value, thus resulting in cost reduction. Larger studies are needed for the combined LDGST to explore whether the 30- and 210-min time points could be eliminated, thus resulting in cost and time savings.

Quality of life in children and adolescents with growth hormone deficiency and their caregivers: an Italian survey

PurposeThe aim of this study was to produce evidence on quality of life (QoL) among Italian growth hormone deficiency (GHD) children and adolescents treated with growth hormone (GH) and their parents.MethodsA survey was conducted among Italian children and adolescents aged 4–18 with a confirmed diagnosis of GHD and treated with GH therapy and their parents. The European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) and the Quality of Life in Short Stature Youth (QoLISSY) questionnaires were administered between May and October 2021 through the Computer-Assisted Personal Interview (CAPI) method. Results were compared with national and international reference values.ResultsThe survey included 142 GHD children/adolescents and their parents. The mean EQ-5D-3L score was 0.95 [standard deviation (SD) 0.09], while the mean visual analogue scale (VAS) score was 86.2 (SD 14.2); the scores are similar to those of a reference Italian population aged 18–24 of healthy subjects. As for the QoLISSY child-version, compared to the international reference values for GHD/ idiopathic short stature (ISS) patients, we found a significantly higher score for the physical domain, and lower scores for coping and treatment; compared to the specific reference values for GHD patients, our mean scores were significantly lower for all domains except the physical one. As for the parents, we found a significantly higher score for the physical domain, and a lower score for treatment; compared to reference values GHD-specific, we found lower score in the social, emotional, treatment, parental effects, and total score domains.ConclusionsOur results suggest that the generic health-related quality of life (HRQoL) in treated GHD patients is high, comparable to that of healthy people. The QoL elicited by a disease specific questionnaire is also good, and comparable with that of international reference values of GHD/ISS patients.

GHRH + arginine test and body mass index: do we need to review diagnostic criteria for GH deficiency?

IntroductionThe proportion of patients with low GH response to provocative tests increases with the number of other pituitary hormone deficiencies, reason why in panhypopituitary patients GH stimulation tests may be unnecessary to diagnose GH deficiency (GHD)PurposeTo re-evaluate the diagnostic cut-offs of GH response to GHRH + arginine (ARG) test related to BMI, considering the patients’ pituitary function as the gold standard for the diagnosis of GHD.MethodsThe GH responses to GHRH + ARG were studied in 358 patients with history of hypothalamic-pituitary disease. GHD was defined by the presence of at least 3 other pituitary deficits (n = 223), while a preserved somatotropic function was defined by the lack of other pituitary deficits and an IGF-I SDS ≥ 0 (n = 135). The cut-off with the best sensitivity (SE) and specificity (SP), was identified for each BMI category using the ROC curve analysis. To avoid over-diagnosis of GHD we subsequently searched for the cut-offs with a SP ≥ 95%.ResultsThe best GH cut-off was 8.0 μg/l (SE 95%, SP 100%) in lean, 7.0 μg/l (SE 97.3%, SP 82.8%) in overweight, and 2.8 μg/l (SE 84.3%, SP 91.7%) in obese subjects. The cut-off with a SP ≥ 95% was 2.6 μg/l (SE 68.5%, SP 96.6%) in overweight and 1.75 μg/l (SE 70.0%, SP 97.2%) in obese subjects.ConclusionsThis is the first study that evaluates the diagnostic cut-offs of GH response to GHRH + ARG related to BMI using a clinical definition of GHD as gold standard. Our results suggest that with this new approach, the GHRH + ARG cut-offs should be revised to avoid GHD over-diagnosis.

Diagnosis and testing for growth hormone deficiency across the ages: a global view of the accuracy, caveats, and cut-offs for diagnosis.

Growth hormone deficiency (GHD) is a clinical syndrome that can manifest either as isolated or associated with additional pituitary hormone deficiencies. Although diminished height velocity and short stature are useful and important clinical markers to consider testing for GHD in children, the signs and symptoms of GHD are not always so apparent in adults. Quality of life and metabolic health are often impacted in patients with GHD; thus, making an accurate diagnosis is important so that appropriate growth hormone (GH) replacement therapy can be offered to these patients. Screening and testing for GHD require sound clinical judgment that follows after obtaining a complete medical history of patients with a hypothalamic-pituitary disorder and a thorough physical examination with specific features for each period of life, while targeted biochemical testing and imaging are required to confirm the diagnosis. Random measurements of serum GH levels are not recommended to screen for GHD (except in neonates) as endogenous GH secretion is episodic and pulsatile throughout the lifespan. One or more GH stimulation tests may be required, but existing methods of testing might be inaccurate, difficult to perform, and can be imprecise. Furthermore, there are multiple caveats when interpreting test results including individual patient factors, differences in peak GH cut-offs (by age and test), testing time points, and heterogeneity of GH and insulin-like growth factor 1 assays. In this article, we provide a global overview of the accuracy and cut-offs for diagnosis of GHD in children and adults and discuss the caveats in conducting and interpreting these tests.