Clinical Usefulness of the Growth Hormone–Releasing Peptide-2 Test for Hypothalamic-Pituitary Disorder

Suzuki, Shohachi; Ruike, Yutarou; Ishiwata, Kazuki; Naito, Kumiko; Igarashi, Katsushi; Ishida, Akiko; Fujimoto, Masanori; Koide, Hisashi; Horiguchi, Kentaro; Tatsuno, Ichiro; Yokote, Koutaro

doi:10.1210/jendso/bvac088

Cited by 4 publications

(5 citation statements)

References 24 publications

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“…Previous studies have assessed the GST in identifying GHD in adult patients with pituitary disorders and reported that GH cut-offs between 2.5 and 3 μg/L provided good sensitivity and specificity ( 54 , 55 , 56 ). There have also been other studies that suggest that using a GH cut-off of 3 μg/L overdiagnoses adult GHD in overweight/obese subjects ( 57 , 58 ).…”

Section: Growth Hormone Stimulation Testsmentioning

confidence: 99%

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

Yuen

Johannsson

Miller

et al. 2023

Endocrine Connections

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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 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 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 IGF-I 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.

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Section: Growth Hormone Stimulation Testsmentioning

confidence: 99%

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

Yuen

Johannsson

Miller

et al. 2023

Endocrine Connections

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“…The normal response of ACTH to the CRH test indicated hypothalamic-adrenal insufficiency. In addition, the low peak cortisol level with normal ACTH response after GHRP2 administration indicated hypothalamic-adrenal insufficiency [31]. This diagnosis was confirmed based on the absence of ACTH response and the peak cortisol level <18 μg/dL in the ITT.…”

Section: Discussionmentioning

confidence: 83%

A case of osteogenesis imperfecta caused by a <i>COL1A1</i> variant, coexisting with pituitary stalk interruption syndrome

et al. 2023

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Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder that affects 6-7 per 100,000 populations, and pituitary stalk interruption syndrome (PSIS) is a rare congenital defect with varying degrees of pituitary hormone deficiency, affecting approximately 0.5 in every 100,000 births. Currently, only two cases of these complications have been reported. A 46-year-old male who had experienced more than 20 fractures (peripheral and vertebral) during adolescence visited our hospital for close examination. He presented with blue sclerae and long bone deformations. We suspected OI because his mother and sister, who were being treated for osteoporosis, also had blue sclerae. Genetic testing identified a heterozygous variant (c.757C > T, p.Arg253Ter) in the COL1A1 gene, leading to the diagnosis of OI. His mother and sister also had the same variant. Considering that he underwent GH replacement therapy for his short stature during his childhood, his pituitary hormone levels were also evaluated to know if GH deficiency impacted low bone density; hypopituitarism was then suspected. The pituitary function test results led to the diagnoses of hypothalamic GH deficiency, hypogonadism, hypothyroidism, and hypoadrenocorticism. Furthermore, magnetic resonance imaging showed anterior pituitary atrophy, pituitary stalk loss, and ectopic posterior pituitary, leading to the diagnosis of PSIS. The combination of OI and hypopituitarism may have caused further bone fragility. Therefore, although rare, clinicians should keep in mind that patients with OI can possibly have concomitant pituitary insufficiency, which can lead to developmental and growth retardation.

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“…A total of 20 cases applied either the GHRP-2 test or the GRF test or both. Three cases reported a maximum GH concentration of <16 ng/ml, which was lower than the diagnosis criteria in the GHRP-2 test ( 8 ). The time to peak values usually occurred at 15 to 60 min.…”

Section: Resultsmentioning

confidence: 93%

“…GHRP-2 is available in Japan and widely used by Japanese researchers. The results of the GHRP-2 test are classified as non-GHD (peak GH > 16 ng/ml), moderate GHD (9 ng/ml < peak GH ≤ 16 ng/ml), and severe GHD (peak GH ≤ 9ng/ml) ( 8 ). Since most of the provocative tests were performed in Japan, the above diagnostic criteria apply to these patients in our review.…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency: a systematic review

Wang,

Shi,

et al. 2024

Front. Endocrinol.

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BackgroundImmune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency (IAD) is a rare but potentially fatal disease.MethodsWe comprehensively searched the PubMed database and made a systematic review of immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency. If the status of other anterior pituitary hormones was not mentioned, the case was excluded.ResultsWe identified 123 cases diagnosed as immune checkpoint inhibitor-induced IAD, consisting of 44 female and 79 male patients. The average age of these patients was 64.3 ± 12.6 years old, and 67.5% were 60 years old or above. The majority (78.9%) of these patients received anti-programmed cell death protein-1 (anti-PD-1) antibodies or anti-programmed cell death ligand 1 (anti-PD-L1) antibodies or both, and 19.5% received combined therapy, sequential therapy, or both. A total of 26 patients received anti-cytotoxic T lymphocyte antigen 4 antibodies (anti-CTLA-4). The median ICI treatment cycle before the diagnosis of adrenal insufficiency was 8 (6, 12), and the median ICI treatment duration before the diagnosis of adrenal insufficiency was 6 (4, 8) months. Eleven cases developed IAD 1 to 11 months after discontinuation of ICIs. Fatigue and appetite loss were the most common symptoms, and surprisingly, there were two asymptomatic cases of IAD. Most patients (88 cases) had normal pituitary magnetic resonance imaging, only 14 cases reported mild atrophy or swelling pituitary gland, and 21 cases reported no imaging results. Most diagnoses were made by basal hormone levels, and pituitary stimulation tests were performed in only a part of the cases. No cases had been reported of discontinuation of ICI use due to IAD nor had there been any deaths due to IAD.ConclusionIAD was predominant in elderly male patients mainly receiving anti-PD-1 or anti-PD-L1 antibodies. It was sometimes difficult to recognize IAD at first glance since non-specific symptoms were common and asymptomatic cases of IAD were also reported. Although IAD can be deadly, it usually does not affect the continued use of ICIs.

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Clinical Usefulness of the Growth Hormone–Releasing Peptide-2 Test for Hypothalamic-Pituitary Disorder

Cited by 4 publications

References 24 publications

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

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

A case of osteogenesis imperfecta caused by a <i>COL1A1</i> variant, coexisting with pituitary stalk interruption syndrome

Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency: a systematic review

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