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About Insulin Sensitivity, CRP Levels, and Metabolic Syndrome Endocrine Care Castillo AlejandroRosell et al. Panhypopituitarism Without GH Replacement:. Horm Metab Res 2018; 00: 00–00 Panhypopituitarism Without GH Replacement: About Insulin Sensitivity, CRP Levels, and Metabolic Syndrome Authors Alejandro Rosell Castillo1, Denise Engelbrecht Zantut-Wittmann1, Arnaldo Moura Neto1, Rodrigo Menezes Jales2, Heraldo Mendes Garmes1 Affiliations ABSTracT 1 Endocrinology Division, Department of Clinical Medicine, A complete deficiency of anterior pituitary hormones from University of Campinas, Campinas, São Paulo, Brazil several etiologies characterizes Panhypopituitarism (PH). De- 2 Imaging Division, Department of Obstetrics and spite advances in treatment, patients with PH maintain high Gynecology, University of Campinas, Campinas, rates of morbidity and mortality, a reason to investigate some São Paulo, Brazil insulin sensitivity, metabolic and inflammatory parameters that could be related to the increase of these indicators. This Key words was a cross-sectional study comprising 41 PH patients under insulin resistance, hypopituitarism, inflammatory activity, hormonal replacement, except for growth hormone, and 37 dyslipidemia individuals in a control group (CG) with similar age, gender and received 22.03.2018 body mass index (BMI). We assessed clinical data as age, sex, accepted 19.06.2018 BMI, waist circumference, waist/hip ratio (WHR), history of hypertension, diabetes mellitus and dyslipidemia as well as Bibliography fasting glycaemia, insulin, HOMA-IR, HbA1c, high-sensitivity DOI https://doi.org/10.1055/a-0649-8010 CRP (hs-CRP), and lipid profile. PH patients presents lower val- Horm Metab Res 2018; 50: 690–695 ues of glycaemia, insulin, HOMA-IR (0.88 vs 2.1) and WHR, but © Georg Thieme Verlag KG Stuttgart · New York higher levels of hs-CRP (0.38 vs 0.16mg/dl) when compared ISSN 0018-5043 with the CG. Although the occurrence of dyslipidemia was high- er in patients with PH, the frequency of metabolic syndrome Correspondence was similar between the groups. In multivariate linear regres- Heraldo Mendes Garmes, MD, PhD sion analysis, the PH group independently predicted lower Faculdade de Ciências Médicas HOMA-IR and WHR values. In conclusion, this study demon- Departamento de Clínica Médica strated that patients with PH without GH replacement have Disciplina de Endocrinologia lower HOMA-IR and WHR values and higher levels of hs-CRP Universidade Estadual de Campinas than a CG paired by age, gender and BMI. The diagnosis of Rua Tessália Vieira de Camargo dyslipidemia was more frequent in patients with PH, but the 126, Barão Geraldo occurrence of MS was similar to CG. Further studies are needed CEP 13083-887, Campinas, São Paulo, Brazil to confirm our findings and to better understand the metabol- Tel.: + 55/19/35217 703, Fax: + 55/19/35217 408 ic characteristics of patients with PH. [email protected] This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Introduction The assessment of insulin sensitivity in patients with PH with- Panhypopituitarism (PH) is characterized by a complete deficiency out GH replacement is controversial. Although some studies show of anterior pituitary hormones resulting from several etiologies decrease in insulin sensitivity [4, 5], other studies did not [6, 7]. These patients need replacement of thyroid hormones, glucocor- Although some authors demonstrated increased markers of car- ticoids, sex hormones, and growth hormone (GH) [1, 2]. These het- diovascular disease in PH under hormonal replacement, except for erogeneous characteristics regarding etiologies and therapeutic growth hormone [8–11], it is still debatable whether cardiovascu- diversity make it difficult to interpret the results of clinical studies lar mortality is actually increased in these patients and the true im- in patients with PH. The increase in PH prevalence due to advanc- portance of each hormonal deficiency in this outcome [12–16]. es in the treatment of hypothalamic-pituitary region diseases [3] It is known that adult patients with growth hormone deficiency justifies new studies for the better understanding of the pathophys- have cardiovascular risk factors, such as adverse lipid profiles [17– iology of increased morbidity and mortality rates present in these 19], abnormal body composition [20, 21], and increased body patients. weight [22, 23]; however, the increased prevalence of metabolic 690 Castillo AR et al. Panhypopituitarism and Insulin Sensitivity... Horm Metab Res 2018; 50: 690–695 syndrome (MS) in PH patients under hormonal replacement, hormone levels were within the recommended values [29]. Li- except for growth hormone is not well established. In spite of pid-lowering, antihypertensive and antidiabetic drugs were start- some studies show an increase in the rates of MS [24, 25], interest- ed at the discretion of the treating physicians. The diagnosis of MS ingly, a study has shown an increase in the prevalence of metabol- was confirmed based on the IDF-AHA/NHLBI criteria 2009 [30]. ic syndrome in women, but not in men with PH [23]. Some authors Exclusion criteria were acutely infirm patients, malignant tum- verified that patients with hypopituitarism have a higher BMI ors, active inflammatory disease, class III/IV heart failure (NYHA than the general population [26–28], a factor that is closely classification), severe hepatic disease (low albumin or increased related to MS. IRN), advanced kidney disease (stage 4 or 5), patients under hemo- Despite the existence of several studies evaluating the metabol- dialysis, those with psychiatric diseases or with HIV, and/or hepa- ic, inflammatory and insulin sensitivity characteristics in patients titis C infection. with PH without GH replacement, the results are still contradicto- ry. With the hypothesis that the BMI could influence these results, Control group it's necessary to make adjustments for BMI to investigate if PH is Forty-one individuals without pituitary disease and with normal pi- associated with insulin resistance independently of elevated BMI. tuitary function, paired by age, gender and BMI, were recruited as For this reason, we assessed insulin sensitivity as measured by a control group in the same period and following the same criteria HOMA-IR index in patients with PH without GH replacement and for exclusion applied to patients with PH. The individuals were re- compared to a control group paired by BMI, gender, and age. Ad- cruited among the relatives of patients from the outpatient neu- ditionally, we evaluated some related factors as the inflammatory roendocrinology clinic. Four individuals withdrew consent before activity, the frequency of MS, and dyslipidemia diagnosis. exams, leaving our control group with 37 individuals for analysis. The same clinical and laboratory parameters evaluated in the group of patients with PH were assessed in the control group. Patients and Methods Clinical parameters Study design Clinical data were recorded consisting of age, sex, BMI, waist This was a cross-sectional study. We evaluated patients with pre- circumference, waist/hip ratio (WHR), and presence of hyperten- vious diagnosis of PH, all followed in the tertiary Service of Neu- sion (blood pressure > 130/80 mmHg or treatment for this condi- roendocrinology of the clinics hospital of the University of Campi- tion), type 2 diabetes mellitus (fasting glycemia > 126 mg/dl on nas between the years 2013 and 2015. All patients were on levothy- more than two occasions or treatment of the condition) and dys- roxine, prednisone, estrogen and progesterone or testosterone lipidemia diagnosis (abnormal lipid profile or treatment for this replacement and none on GH therapy. We assessed clinical and ep- condition). idemiological data and fasting blood samples were drawn for glu- cose, insulin, HbA1c, hs-CRP, and lipid profile. HOMA-IR was calcu- Laboratory measurements lated as an insulin resistance parameter. Clinical and laboratory Total cholesterol, HDL and LDL-cholesterol and triglycerides were characteristics of PH patients were compared with the control sub- measured by automated enzymatic method). Hs-CRP was meas- jects. The control group consisted of individuals with normal pitu- ured by ELISA (Cusabio Biotech Co, Ltd; Wuban, Hubei, China). Sen- itary function, paired by age, gender and BMI. The study was ap- sitivity is the least amount that can be differentiated from zero, no proved by the local Research Ethics Committee. Written informed known cross-reactivity. Relative value (RV) > 0.1 mg/dl for inflam- consent was obtained from all the participants after full explana- matory conditions. Insulin was measured by immunoassay-chemi- tion of the study. luminescence (Siemens medical solutions diagnostics, USA), RV: 2.0–28.4 μU/ml. HbA1c was measured by high performance liquid Patients chromatography method (RV: 4–5.6 %) and fasting glycemia by the Fifty-four patients older than 18 years with deficiency of all hor- hexoquinase method (RV: 70–100 mg/dl). HOMA-IR was calculat- mone axes of anterior pituitary were included. Thirteen patients ed by the formula insulin × glucose/22.5, considering as insulin re- This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. did not show up for the exams, leaving 41 patients for analysis. Data sistance values ≥ 2.7. regarding age, sex, height, weight, waist and hip measures, diag- nosis of hypertension, type 2 diabetes mellitus, and dyslipidemia Statistical analysis were assessed. The diagnosis of
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