ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P252 | DOI: 10.1530/endoabs.63.P252

A case of 'micromegaly': need for revision of oral glucose tolerance test (OGTT) cut-offs with modern growth hormone assays in acromegaly

Katharina Schilbach, Sylvère Störmann, Martin Bidlingmaier & Jochen Schopohl

Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.

The OGTT is the gold standard for confirmation or exclusion of acromegaly in treatment-naïve patients as well as after surgery. According to former guidelines, acromegaly is ruled out if the growth hormone (GH) nadir lies below 1.0 μg/l and 0.4 μg/l pre- and postoperatively, respectively. We present the case of a 40-year-old man who presented to the outpatient clinic in 2014 for endocrinological evaluation after an elevated IGF-I concentration had occasionally been detected within the scope of a clinical study. GH and IGF-I were measured using a modern, monoclonal antibody based assay adhering to recent guidelines (IDS iSYS). At that time, a GH nadir of 0.3 μg/l formally ruled out acromegaly. However, due to the clinical presentation and comorbidities (typical physiognomy, sleep apnea, arterial hypertension, impaired glucose tolerance, hypogonadotropic hypogonadism, and obesity) the patient was scheduled for follow-up consultations. IGF-I was persistently elevated (IGF-I SDS between 3.1 and 5), but GH nadir remained below 0.4 μg/l in two repeated OGTTs (0.36 and 0.24 μg/l in 2015 and 2016, respectively). In 2015, MRI revealed a pituitary microadenoma (9×4 mm) but the patient refused surgery. Tumour size was unchanged in annual follow-up MRIs. In November 2018, over 4 years of initial observation of elevated IGF-I, the patient finally agreed to transsphenoidal tumour resection. Neuropathological examination confirmed GH-secreting pituitary adenoma. Postoperatively, IGF-I concentration fell within the gender- and age-specific reference range (SDS 2, 10 weeks after surgery), and GH was suppressible to <0.05 μg/l after oral glucose load. The case also supports our recent observation in a larger cohort of healthy subjects: Using the same modern GH assay, GH nadir concentration fall below 0.4 μg/l in lean (BMI <25 kg/m2) and below 0.2 μg/l in obese (BMI >25 kg/m2) subjects. In the present case the BMI was >38 kg/m2 at all times. This case suggests that mild or early acromegaly might be missed when the commonly used cut-off of 0.4 μg/l is applied for all patients, particularly if modern, highly sensitive and specific GH assays are used.

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