Assessment of the performance of the Brazilian Portuguese Nottingham Health Profile in adult growth hormone deficiency and pulmonary hypertension

Background: The Nottingham Health Profile (NHP) is a generic measure of perceived distress that has been used widely as an outcome measure in clinical practice and trials. The availability of two Brazilian datasets provided the opportunity to assess the psychometric performance of the NHP in different populations - adult growth hormone deficiency (GHD) and pulmonary hypertension (PH). The purpose of the study was to see how valuable the NHP could be in assessing outcomes in diseases where no disease-specific measures are available. Methods: Secondary analyses were performed with NHP data. Patients diagnosed with adult GHD or PH were administered the NHP during clinic visits on two occasions, two weeks apart. A disease-specific measure of quality of life (QoL) was also administered to the relevant sample of patients on each occasion. Results: The psychometric properties of the NHP were good for both disease groups. As expected, both samples reported high scores on energy level, the PH sample scored high on physical functioning and the GHD sample on emotional reactions. For both samples, most of the NHP sections were able to distinguish between groups of respondents with different ratings of perceived general health. While most sections of the NHP were relatively highly correlated with the QoL measures, pain and sleep did not seem to be important predictors of QoL in either of the samples. Conclusions: The use of the NHP in adult GHD and PH populations in Brazil is not recommended as there are high-quality disease-specific measures available for each disease. However, where no disease-specific measures are available, the NHP can provide good descriptive information of the impact of disease on different patient populations.

Circulating LEAP-2 Levels in Adult Growth Hormone Deficiency and Their Relationship With IGF-1

Liver enriched antimicrobial peptide-2 (LEAP-2) is an endogenous antagonist of ghrelin, which acts as an allosteric modulator of growth hormone secretagogue receptors. It is expressed predominantly in liver, followed by kidney, jejunum, duodenum and stomach. Its expression in conditions of metabolic impairment, obesity for instance, may be upregulated, usually pairing with a concomitant reduction in ghrelin secretion. Weight gain and hyperglycaemia seem to be the main trigger factors for LEAP-2 production. Adult growth hormone deficiency (aGHD) is known as a pathological condition characterized by metabolic impairment (insulin resistance, weight gain, increased fat mass, decreased lean mass). To the best of our knowledge, no study in literature deals with the problem of circulating LEAP-2 levels in GHD. Therefore, the primary endpoint of this cross-sectional observational study was to evaluate circulating LEAP-2 levels in GHD in comparison to healthy controls whether the secondary endpoint was to evaluate any possible correlation with IGF-1 and metabolic parameters in such condition. 30 patients were included in the study. Group A included adult GHD: 15 patients, 7 females and 8 males, mean±standard error of the mean (SEM) age 54.6±3.51 years, BMI 29,95±1.63 kg/m2). The etiologies of GHD were empty sella (n=6), idiopathic (n=6), post-surgical hypopituitarism (n=2), pineal cyst (n=1). Group B was formed by controls: 15 patients, 11 females and 4 males, mean±SEM age 40.33±2.61 years, BMI 24.19±1.33 kg/m2. They were evaluated for: serum glucose and insulin, HOMA-index, QUICKI-index, Total/LDL/HDL cholesterol, triglycerides, IGF-1 and LEAP-2 (measured using Human LEAP-2 ELISA kit, Phoenix Pharmaceuticals Inc, according to manufacturer’s instructions). Circulating LEAP-2 is significantly higher in GHD than in control group (26.98±3.12 vs 18.7±1.9 ng/ml, p=0.03). LEAP-2 levels in our cohort was not influenced by BMI, while a significant direct correlation between LEAP-2 and age was detected in aGHD group. A strong significative inverse correlation between LEAP-2 and IGF-1 was evidenced in aGHD (r2=0.5). Finally, in this group, LEAP-2 inversely correlates with total cholesterol (r2=0.45). As expected circulating LEAP-2 levels, in a condition of metabolic impairment such as GHD, were higher than controls even if no correlation with BMI was evidenced in our cohort. The inverse correlation between LEAP-2 and IGF-1 in GHD patients may suggest a body adjustment in a worse clinical condition. LEAP-2 may act as a brake for ghrelin production, thus preventing further weight gain and fat mass increase, although losing its secretagogue effect.

3D DXA Hip Differences in Patients with Acromegaly or Adult Growth Hormone Deficiency

The skeleton is regulated by and responds to pituitary hormones, especially when the circulating levels are perturbed in disease. This study aims to analyse the between-group differences in 3D dual-energy X-ray absorptiometry (DXA) parameters at the hip site among patients with acromegaly or adult growth hormone deficiency (AGHD) and a healthy control group. The current cross-sectional study includes data for 67 adults, 20 with acromegaly, 14 with AGHD and 33 healthy controls. We obtained the areal bone mineral density (aBMD) outcomes using DXA and cortical and trabecular parameters using 3D-DXA software (3D-SHAPER). The mean-adjusted 3D-DXA parameters did not differ between acromegaly patients and the controls (p > 0.05); however, we found cortical bone impairment (−7.3% to −8.4%; effect size (ES) = 0.78) in AGHD patients (p < 0.05). Differences in the cortical bone parameters were more evident when comparing AGHD patients (−8.5% to −16.2%; ES = 1.22 to 1.24) with acromegaly patients (p < 0.05). In brief, the 3D mapping highlighted the trochanter as the site with greater cortical bone differences between acromegaly patients and the controls. Overall, AGHD patients displayed lower cortical parameters at the trochanter, femoral neck and intertrochanter compared to the controls and acromegaly patients. To sum up, 3D-DXA provided useful information about the characteristics of bone involvement in growth hormone (GH)-related disorders. Patients with AGHD showed distinct involvement of the cortical structure.

Adult growth hormone deficiency guidelines: more difficult than it seems to incorporate into clinical practice universally

Adult growth hormone deficiency (GHD) is a syndrome characterized by adverse phenotypic, metabolic, and quality-of-life features. Over the past 2 decades, there is accumulating evidence demonstrating improvement of most of these parameters when GH is optimally replaced. Appropriate selection of patients at risk of GHD is crucial when considering and performing appropriate testing to establish the diagnosis. While generally safe, GH replacement requires careful dose initiation and monitoring to assure effectiveness and tolerance in treated patients. Several consensus clinical practice guidelines recommend evaluation of adults presenting with pituitary disorders for GHD. However, the clinical practice of managing such patients varies among countries largely due to lack of recognition of the condition, lack of GH availability, and lack of reimbursement of the drug, as demonstrated from a large online survey prepared by the European Society of Endocrinology involving 2148 patients from Europe and Australia. These data reinforce the notion of the large variability of disease recognition, clinical practice and education of adult GHD amongst healthcare professionals, and the lack of availability and reimbursement of the drug contributing to the under-utilization of GH replacement therapy in several countries. This commentary article highlights the fact that despite the publication of several guideline recommendations and positive long-term safety and efficacy data of GH replacement, there is still a need for increased education to enhance the awareness in the general population and improve the knowledge of healthcare professionals and administrators of adult GHD as a disease state to allow for early identification and treatment optimization.