Insulin Sensitivity Is Not Decreased in Adult Patients With Hypopituitarism Without Growth Hormone Replacement

Abstract

Decreased insulin sensitivity in patients with hypopituitarism without GH replacement (pHP-WGHR) remains conflicting in literature. It is known that these patients present a decrease in free fat mass and an increase in fat mass. Typically, these kinds of alterations in body composition are associated with a decrease in insulin sensitivity; however, there is no consensus if this association is found in pHP-WGHR. Thus, we investigated pHP-WGHR regarding insulin sensitivity by euglycemic hyperinsulinemic clamp, the gold standard method, and body composition. In a cross-sectional study, we evaluated 15 pHP-WGHR followed up in a Service of Neuroendocrinology and 15 individuals with normal pituitary function as a control group with similar age, gender and body mass index. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp and homeostatic model assessment insulin resistance (HOMA-IR). Kappa coefficient evaluated the agreement between these two methods. Percentage of fat mass, percentage of free fat mass, fat mass weight and free fat mass weight were assessed by electrical bioimpedance. The pHP-WGHR presented similar insulin sensitivity to control group by euglycemic hyperinsulinemic clamp, both by the M-value, ( p = 0.0913) and by the area under the glucose infusion rate curve, ( p = 0.0628). These patients showed lower levels of fasting glycemia ( p = 0.0128), insulin ( p = 0.0007), HOMA-IR ( p = 0.009). HOMA-IR shows poor concordance with euglycemic hyperinsulinemic clamp (Kappa = 0.16) in pHP-WGHR, while in the control group the agreement was good (Kappa = 0.53). The pHP-WGHR presented higher values of percentage of fat mass ( p = 0.0381) and lower values of percentage of free fat mass ( p = 0.0464) and free fat mass weight (0.0421) than the control group. This study demonstrated that the insulin sensitivity evaluated by euglycemic hyperinsulinemic clamp in pHP-WGHR was similar to individuals with normal pituitary function, despite the pHP-WGHR presenting higher fat mass percentage. HOMA-IR was not a good method for assessing insulin sensitivity in pHP-WGHR.

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity

“…In this sense, in a previous study, our group showed that, unlike what was observed in individuals with normal pituitary function, the agreement between the assessment of IS by the homeostatic model assessment for insulin resistance (HOMA-IR) and the euglycemic hyperinsulinemic clamp (EHC) was poor in patients with hypopituitarism [13]. This was also reported in another study where it is suggested that standard minimal homeostatic models to assess IS, such as HOMA-IR, could not adequately identify IS in syndromes of severe short stature [14].These findings highlighted the relevance of EHC in the investigation of IS, since the EHC does not suffer interference from the insulin counter-regulatory hormones, which are altered in patients with hypopituitarism [13]. On the other hand, the stage of the disease onset, childhood or adulthood, could influence IS in patients with GHD.…”

Insulin signaling in the whole spectrum of GH deficiency

“…As shown in Table 2, the literature is controversial regarding the results of IS in patients with GHD. Some studies show that these patients have insulin resistance (86)(87)(88)(89)(90) and others show that IS is similar to the gender, age and BMI matched controls (41,42,88,(90)(91)(92).…”

“…It only evaluates insulin-dependent glucose uptake, faithfully representing the sensitivity to insulin action in these patients. In this regard, studies in humans have already demonstrated the lack of correlation between EHC and other methods used to assess IS in patients with GHD (41,42) suggesting that using other methods may induce controversial results. Therefore, in this review we considered only scientific studies that used HEC as a method for assessing IS in patients with GHD.…”

“…This review has already discussed the reasons why EHC is the most reliable method for assessing IS in patients with disorders in the production of counterregulatory hormones such as hypopituitarism. As an example we can cite studies from our group, we showed increased insulin sensitivity in patients with GHD compared to control group paired by age, gender and BMI using HOMA-IR (97), but the IS was similar in both groups using EHC (42). However, performing EHC and evaluating its results requires special care, it is noteworthy the importance of similar serum levels of hyperinsulinemia during clamp between the patient group and the control, making the blockade of tissue glucose production similar in both groups avoiding possible interference in the results from the action of counterregulating hormones, which is present only in the control group.…”

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism

“…Two recent metaanalyses involving observational studies have confirmed such increased mortality, with higher rates observed especially in women and in patients of younger age at diagnosis (5,6). Nevertheless, new concepts in the pathophysiology of hormonal deficiencies, recent advances in diagnostic tools, and the emergence of new formulations for hormone replacement have significantly contributed to a reduction in morbidity and mortality rates in these patients (7)(8)(9)(10). This narrative review provides a guide for the management of patients with hypopituitarism in Brazil, considering as much as possible regional differences and health care disparities.…”