The arginine and GHRP-2 tests as alternatives to the insulin tolerance test for the diagnosis of adult GH deficiency in Japanese patients: A comparison

Kinoshita, Yasuyuki; Tominaga, Atsushi; Usui, Satoshi; Arita, Kazunori; Sakoguchi, Tetsuhiko; Sakamoto, Kazuhiko; Kurisu, Kaoru

doi:10.1507/endocrj.ej12-0230

Cited by 12 publications

(8 citation statements)

References 31 publications

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“…A GH cutoff value of 9 ng/mL with GHRP-2 corresponded to a GH value of 1.8 ng/mL with the insulin tolerance test when the GH value was calibrated with recombinant World Health Organization 98/574 standard [ 22 ]. Although the GHRP-2 test is not included in the Endocrine Society Guidelines [ 23 ], the GHRP-2 test is considered to be safe [ 24 ] and widely used to diagnose SGHD in Japan because of its high sensitivity and specificity compared with the insulin tolerance test [ 25 ]. The peak GH concentration after GHRP-2 stimulation was ≥9 ng/mL in 40 patients (SGHD − ) and <9 ng/mL in 32 patients (SGHD + ).…”

Section: Methodsmentioning

confidence: 99%

Elevated (Pro)renin Receptor Expression Contributes to Maintaining Aerobic Metabolism in Growth Hormone Deficiency

Seki

Yatabe

Suda

et al. 2018

Journal of the Endocrine Society

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ContextGrowth hormone deficiency (GHD) leads to obesity and may induce tissue hypoxia. As (pro)renin receptor [(P)RR] is reported to contribute to the aerobic metabolism by stabilizing pyruvate dehydrogenase (PDH), it may play a substantial role in GHD.ObjectiveWe aimed to investigate serum soluble (P)RR [s(P)RR] concentration, the origin of s(P)RR, and significance of (P)RR in GHD.Design, Setting, and ParticipantsSerum s(P)RR concentration was examined in 72 patients with pituitary diseases, including 32 patients with severe GHD (SGHD) and after GH replacement in 16 SGHD patients. Leptin-deficient ob/ob obese mice were treated with pegvisomant, a GH receptor antagonist, to explore the source of elevated serum s(P)RR in GHD. Adipocytes were cultured with 5% O2 to examine the effects of hypoxia.ResultsSerum s(P)RR concentration was higher in patients with SGHD than in those without SGHD. Obesity was the important determinant of s(P)RR concentration. Serum s(P)RR concentration significantly decreased after GH replacement in SGHD patients. (P)RR mRNA expression was increased specifically in the adipose tissue (AT) of pegvisomant-treated obese mice compared with that of control obese mice. Hypoxia in cultured adipocytes increased (P)RR expression without affecting the PDH E1 β subunit (PDHB) expression; however, with (P)RR knockdown by small interfering RNA, hypoxia significantly decreased the expression of PDHB.ConclusionGHD patients showed increased serum s(P)RR concentration, possibly caused by obesity and hypoxia. (P)RR expression in AT of GHD patients may be elevated to help maintain aerobic metabolism under hypoxia. Thus, the elevated serum s(P)RR level may reflect hypoxia in ATs.

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Section: Methodsmentioning

confidence: 99%

Elevated (Pro)renin Receptor Expression Contributes to Maintaining Aerobic Metabolism in Growth Hormone Deficiency

Seki

Yatabe

Suda

et al. 2018

Journal of the Endocrine Society

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“…To further investigate the pituitary function, CRH (100 μg), TRH (200 μg), GnRH (100 μg) and GHRP-2 (100 μg) load tests were performed (Fig. 2) in the previously described manner [11][12][13][14] to confirm normality of not only basal, but also responsive secretion of pituitary hormones other than ACTH [11]. The adrenal response was markedly abnormal; the low baseline cortisol level of 0.2 μg/dl stayed at the same level at all the time points up to 120 min.…”

Section: Case Presentationmentioning

confidence: 99%

Isolated ACTH deficiency following immunization with the BNT162b2 SARS-CoV-2 vaccine: a case report

et al. 2022

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Background The global COVID-19 pandemic requires urgent development of new vaccines. Endocrinological adverse effects following the new mRNA vaccine against COVID-19 have been reported in several cases. Specific to the involvement of pituitary function; however, only a single case with hypophysis has been reported. This is the first case of isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) following mRNA vaccination against COVID-19. Case presentation A healthy 31-year-old man received the BNT162b2 SARS-CoV-2 mRNA vaccine. The first injection was uneventful. One day after the second injection, he noticed general fatigue and fever. In the following several days, he additionally developed headaches, nausea, and diarrhea. Four days after the vaccine injection, he visited a hospital with worsening of these symptoms. Physical examination revealed slight disorientation but no other deficits. Laboratory tests revealed hyponatremia, hypoglycemia, and extremely low plasma ACTH and serum cortisol levels (ACTH < 1.5 pg/ml, cortisol 1.6 μg/dl). He was diagnosed with adrenal crisis and was emergently treated with hydrocortisone. The symptoms responded well and he recovered within a few days. Magnetic resonance images after the replacement with hydrocortisone revealed an atrophic pituitary gland. The patient was referred to our tertiary hospital for further endocrinological examination. Pituitary endocrine load tests revealed isolated adrenocortical response deficiency. After other clinical assessments, he was diagnosed as having isolated ACTH deficiency. After initiation of hydrocortisone replacement, there has been no recurrence of symptoms related to adrenocortical insufficiency nor involvement of other pituitary functions. Conclusion This is the first reported case of IAD potentially associated with COVID-19 immunization. Recent reports have emphasized the importance of adjuvants in the mRNA vaccine that induce the endocrinological adverse effects through disturbance of the autoimmune system, but details are still unclear. Given the broad and rapid spread of vaccinations against COVID-19, it is clinically important to consider that there could be cases with a rare but emergent adrenal crisis even among those who present common symptoms of adverse effects following inactive SARS-CoV-2 mRNA vaccination.

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“…A GH cut-off value of 9 ng/mL with GHRP-2 corresponded to a GH value of 1.8 ng/mL with an ITT when the GH value was calibrated with the recombinant WHO 98/574 standard [13]. Although the GHRP-2 test was not included in the Endocrine Society Guidelines [14], the GHRP-2 test is considered safe [15] and is widely employed to diagnose severe GHD in Japan owing to its high sensitivity and specificity when compared to ITT [16].…”

Section: Gh-releasing Peptide-2 Testmentioning

confidence: 99%

Association between overweight and growth hormone secretion in patients with non-functioning pituitary tumors

Seki

Ichihara

2022

PLoS ONE

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Introduction Growth hormone (GH) deficiency (GHD) is often complicated by non-functioning pituitary tumors (NFPTs); however, its prevalence remains unclear because preoperative screening for GHD with provocative tests is not recommended. Accordingly, we attempted to clarify the characteristics of GHD in unoperated patients with NFPT. Materials and methods We retrospectively reviewed adult patients with non-functioning pituitary adenoma (NFPA) and Rathke’s cyst who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests from January 2013 to December 2016. We investigated the association between peak GH response to GHRP-2 and background characteristics. Results Among 104 patients (85 NFPA and 19 Rathke’s cysts), 45 (43%) presented severe GHD, as diagnosed using GHRP-2 tests. Body mass index (β = -0.210, P = 0.007), free thyroxine (β = 0.440, P < 0.001), and tumor height (β = -0.254, P < 0.001) were significant variables for determining the peak GH response to GHRP-2 in multiple regression analyses. Overweight (odds ratio, 3.86; 95% confidence interval, 1.02–14.66) was significantly associated with severe GHD after adjustment for age, sex, creatinine, free thyroxine, tumor height and clinical diagnosis. The regression slopes between tumor height and peak GH response to GHRP-2 significantly differed between overweight patients and non-overweight individuals, as determined by analysis of covariance (P = 0.040). In the 48 patients who underwent postoperative GHRP-2 tests, severe postoperative GHD was significantly more common in overweight patients than non-overweight individuals (100% vs. 48%, P < 0.001). Conclusion We observed a negative synergistic effect between overweight and tumor size on GH secretion in patients with NFPTs, indicating that GH provocation tests for diagnosing underestimated GHD could be considered in overweight unoperated patients with large NFPTs.

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The arginine and GHRP-2 tests as alternatives to the insulin tolerance test for the diagnosis of adult GH deficiency in Japanese patients: A comparison

Cited by 12 publications

References 31 publications

Elevated (Pro)renin Receptor Expression Contributes to Maintaining Aerobic Metabolism in Growth Hormone Deficiency

Elevated (Pro)renin Receptor Expression Contributes to Maintaining Aerobic Metabolism in Growth Hormone Deficiency

Isolated ACTH deficiency following immunization with the BNT162b2 SARS-CoV-2 vaccine: a case report

Association between overweight and growth hormone secretion in patients with non-functioning pituitary tumors

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