Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers

Sfeir, Jad; Kittah, Nana Esi; Tamhane, Shrikant; Jasim, Sina; Chemaitilly, Wassim; Cohen, Laurie E.; Murad, M. Hassan

doi:10.1210/jc.2018-01204

Cited by 23 publications

(18 citation statements)

References 32 publications

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“…Testing with ITT, GHRH (with or without arginine), and glucagon has been recommended, in this order, for the diagnosis of GHD in adult survivors of childhood cancer (29), while no recommendations were provided for the diagnosis of GHD after adult height achievement in COGHD. In addition, a systematic review on the diagnosis of GHD as a late effect of radiotherapy in survivors of childhood cancer raises the question on how to interpret the GH response after GHRHarg in patients with primary hypothalamic dysfunction (8) with a recommendation against the use of GHRH alone or in combination with arginine after hypothalamic–pituitary axis radiation. Our study, the largest reported so far in cancer survivors retested after adult height achievement (8), confirms that patients with GHD and brain tumors have significantly lower responses of GH after GHRHarg, although some of them perform well above the recommended cut-offs (9–11, 15–17).…”

Section: Discussionmentioning

confidence: 99%

“…In a more recent study performed in a larger cohort of COGHD, ROC curve analysis indicated the best diagnostic accuracy for a GH peak after ITT of 5.62 μg/liter (7) confirming that the GH peak proposed by the Consensus was adequate for the definition of permanent GHD in young adults with COGHD (2). Finally, a systematic review from an Endocrine Society taskforce stated that insufficient data are available to assess the accuracy of serial GH testing in survivors of childhood cancers (8).…”

Section: Introductionmentioning

confidence: 99%

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Accuracy and Limitations of the Growth Hormone (GH) Releasing Hormone-Arginine Retesting in Young Adults With Childhood-Onset GH Deficiency

et al. 2019

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Background: Re-testing for GH secretion is needed to confirm the diagnosis of GH deficiency (GHD) after adult height achievement in childhood-onset GHD (COGHD). Aim: To define the cut-off of GH peak after retesting with GH-releasing hormone plus arginine (GHRHarg) in the diagnosis of permanent GHD in COGHD of different etiology. Patients and methods: Eighty-eight COGHD (median age 17.2 y), 29 idiopathic GHD (IGHD), 44 cancer survivors (TGHD) and 15 congenital GHD (CGHD) were enrolled in the study; 54 had isolated GHD (iGHD) and 34 had multiple pituitary hormone deficiencies (MPHD). All were tested with insulin tolerance test (ITT) and GHRHarg. IGHD with a GH response to ITT ≥6μg/L were considered true negatives and served as the control group, and patients with a GH response <6μg/L as true positives. Baseline IGF-I was also measured. The diagnostic accuracy of GHRHarg testing and of IGF-I SDS in patients with GHD of different etiologies was evaluated by ROC analysis. Results: Forty-six subjects with a GH peak to ITT ≥6μg/L and 42 with GH peak <6 μg/L showed a GH peak after GHRHarg between 8.8–124μg/L and 0.3–26.3μg/L, respectively; 29 IGHD were true negatives, 42 were true positives and 17 with a high likelihood GHD showed a GH peak to ITT ≥6μg/L. ROC analysis based on the etiology indicated the best diagnostic accuracy for peak GH cutoffs after GHRHarg of 25.3 μg/L in CGHD, 15.7 in TGHD, and 13.8 in MPHD, and for IGF-1 SDS at −2.1 in CGHD, −1.5 in TGHD, and −1.9 in MPHD. Conclusions: Our findings indicate that the best cut-off for GH peak after retesting with GHRHarg changes according to the etiology of GHD during the transition age. Based on these results the diagnostic accuracy of GHRHarg remains questionable.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Accuracy and Limitations of the Growth Hormone (GH) Releasing Hormone-Arginine Retesting in Young Adults With Childhood-Onset GH Deficiency

et al. 2019

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“…Importantly, children with prior exposure to CRT may have concomitant GHD and precocious puberty, with the latter masking the usual decline in growth seen with isolated GHD. CCS should undergo formal GH stimulation testing for confirmation of the diagnosis of GHD [15, 77], as is the recommendation for the non-CCS population [78]. Important caveats in GH stimulation testing in the CCS population include: (1) avoiding the use of GH-releasing hormone as a single agent for testing given the possibility of false positives due to the cause of GHD being hypothalamic rather than pituitary in origin [79, 80], and (2) avoiding formal provocative testing for GHD in CCS with established deficits in 3 other anterior pituitary hormones [78].…”

Section: Evaluation Of Growth Impairment and Ghdmentioning

confidence: 99%

Growth Disturbances in Childhood Cancer Survivors

Antal

Balachandar

2019

Horm Res Paediatr

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Survival from childhood cancer has improved dramatically over the last few decades, resulting in an increased need to address the long-term follow-up and care of childhood cancer survivors. Appropriate linear growth is an important measure of health, with alterations of growth in children and short adult height in those who have completed growth serving as potential indicators of the sequelae of the underlying diagnosis or the cancer treatments. It is therefore critical that clinicians, particularly endocrinologists, be familiar with the patterns of altered growth which may be seen following diagnosis and treatment for childhood cancer. In this article, we will review the growth alterations seen in childhood cancer survivors, focusing on risk factors and considerations in evaluation and care.

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“…GHD is more common after radiotherapy for treatment of childhood cancer ( Sfeir et al, 2018 ). Radiotherapy for childhood cancer usually includes two irradiation methods.…”

Section: Role Of Gh-igf1 Signaling Pathways On Therapy Resistance In Cancer Radiotherapymentioning

confidence: 99%

Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers

Cheng

Gui

et al. 2021

Front. Cell Dev. Biol.

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Radiotherapy remains one of the most important cancer treatment modalities. In the course of radiotherapy for tumor treatment, the incidental irradiation of adjacent tissues could not be completely avoided. DNA damage is one of the main factors of cell death caused by ionizing radiation, including single-strand (SSBs) and double-strand breaks (DSBs). The growth hormone-Insulin-like growth factor 1 (GH-IGF1) axis plays numerous roles in various systems by promoting cell proliferation and inhibiting apoptosis, supporting its effects in inducing the development of multiple cancers. Meanwhile, the GH-IGF1 signaling involved in DNA damage response (DDR) and DNA damage repair determines the radio-resistance of cancer cells subjected to radiotherapy and repair of adjacent tissues damaged by radiotherapy. In the present review, we firstly summarized the studies on GH-IGF1 signaling in the development of cancers. Then we discussed the adverse effect of GH-IGF1 signaling in radiotherapy to cancer cells and the favorable impact of GH-IGF1 signaling on radiation damage repair to adjacent tissues after irradiation. This review further summarized recent advances on research into the molecular mechanism of GH-IGF1 signaling pathway in these effects, expecting to specify the dual characters of GH-IGF1 signaling pathways in radiotherapy and post-radiotherapy repair of cancers, subsequently providing theoretical basis of their roles in increasing radiation sensitivity during cancer radiotherapy and repairing damage after radiotherapy.

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Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers

Abstract: The diagnostic accuracy of various dynamic tests for GHD in CCSs appears to follow the same patterns as those in non-CCSs. Interpreting GHRH stimulation is a challenge given the primarily hypothalamic dysfunction in CCSs. IGF-1 and IGFBP-3 perform poorly in this population.

Cited by 23 publications

References 32 publications

Accuracy and Limitations of the Growth Hormone (GH) Releasing Hormone-Arginine Retesting in Young Adults With Childhood-Onset GH Deficiency

Accuracy and Limitations of the Growth Hormone (GH) Releasing Hormone-Arginine Retesting in Young Adults With Childhood-Onset GH Deficiency

Growth Disturbances in Childhood Cancer Survivors

Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers

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