Discordant GH and IGF-1 Results in Treated Acromegaly: Impact of GH Cutoffs and Mean Values Assessment

Campana, Claudia
Cocchiara, Francesco
Corica, Giuliana
Nista, Federica
Arvigo, Marica
Amarù, Jessica
Rossi, Diego Criminelli
Zona, Gianluigi
Ferone, Diego
Gatto, Federico

¹ Endocrinology Unit, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
² Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
³ Division of Neurosurgery, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

Correspondence: Diego Ferone, MD, PhD, Endocrinology Unit, Department of Internal Medicine & Medical Specialties (DIMI), IRCCS Ospedale Policlinico San Martino, University of Genoa, Largo Rosanna Benzi, 10, 16132, Genoa, Italy. E-mail [email protected].

Received: 19 August 2020; Editorial Decision: 14 November 2020; First Published Online: 25 November 2020; Corrected and Typeset: 22 December 2020.

Journal of Clinical Endocrinology & Metabolism 106(3):p 789-801, March 2021. | DOI: 10.1210/clinem/dgaa859

Abstract

Context:

Discordant growth hormone (GH) and insulin-like growth factor-1 (IGF-1) values are frequent in acromegaly.

Objective:

To evaluate the impact of different GH cutoffs on discordance rate. To investigate whether the mean of consecutive GH measurements impacts discordance rate when matched to the last available IGF-1 value.

Design:

Retrospective study.

Setting:

Referral center for pituitary diseases.

Patients:

Ninety acromegaly patients with at least 3 consecutive evaluations for GH and IGF-1 using the same assay in the same laboratory (median follow-up 13 years).

Interventions:

Multimodal treatment of acromegaly.

Main Outcome Measures:

Single fasting GH (GH_f) and IGF-1 (IGF-1_f). Mean of 3 GH measurements (GH_m), collected during consecutive routine patients' evaluations.

Results:

At last evaluation GH_f values were 1.99 ± 2.79 μg/L and age-adjusted IGF-1_f was 0.86 ± 0.44 × upper limit of normality (mean ± SD). The discordance rate using GH_f was 52.2% (cutoff 1 μg/L) and 35.6% (cutoff 2.5 μg/L) (P = 0.025). “High GH” discordance was more common for GH_f <1.0 μg/L, while “high IGF-1” was predominant for GH_f <2.5 μg/L (P < 0.0001). Using GH_m mitigated the impact of GH cutoffs on discordance (GH_m <1.0 μg/L: 43.3%; GH_m <2.5 μg/L: 38.9%; P = 0.265). At receiver-operator characteristic curve (ROC) analysis, both GH_f and GH_m were poor predictors of IGF-1_f normalization (area under the curve [AUC] = 0.611 and AUC = 0.645, respectively). The prevalence of disease-related comorbidities did not significantly differ between controlled, discordant, and active disease patients.

Discussion:

GH/IGF-1 discordance strongly depends on GH cutoffs. The use of GH_m lessen the impact of GH cutoffs. Measurement of fasting GH levels (both GH_f and GH_m) is a poor predictor of IGF-1_f normalization in our cohort.