Acromegaly presenting with low insulin-like growth factor-1 levels and diabetes: a case report

Abstract

IntroductionAcromegaly is an endocrine disorder arising from excessive serum growth hormone levels in adulthood and is characterized by progressive somatic enlargement. Biochemical confirmation is achieved by demonstration of elevated baseline serum growth hormone levels which are not suppressed during an oral glucose tolerance test, and by increased levels of serum insulin-like growth factor-1. The serum insulin-like growth factor-1 level provides an assessment of integrated growth hormone secretion and is recommended for diagnosis, monitoring, and screening of acromegaly. We report a case of a patient with acromegaly secondary to a pituitary microadenoma who presented with low insulin-like growth factor-1.Case presentationAn 83-year-old Sinhalese woman presented to our hospital with an enlarging multinodular goiter. She was observed to have macroglossia, thickened coarse skin, acral enlargement, and newly detected, uncontrolled diabetes. A diagnosis of acromegaly was suspected. She did not complain of recent headaches, vomiting, visual difficulties, or galactorrhea and was clinically euthyroid. Her pulse rate was 84 beats/min, and her blood pressure was 150/90 mmHg. A visual field assessment did not reveal a defect. Her random growth hormone levels were 149 mU/L (<10 mU/L), and her oral glucose tolerance test was supportive of acromegaly with a paradoxical rise of growth hormone. Her serum age-specific insulin-like growth factor-1 level was below normal at 124.7 ng/ml (normal range 150–350 ng/ml). Her serum insulin-like growth factor-1 level, measured after glycemic control was achieved with metformin and insulin, was elevated, which is characteristic of acromegaly. Magnetic resonance imaging of her pituitary revealed a pituitary microadenoma. Acromegaly secondary to a growth hormone–secreting pituitary microadenoma was confirmed.ConclusionsSystemic illnesses, including catabolic states, hepatic or renal failure, malnutrition, and diabetes mellitus, are known to decrease insulin-like growth factor-1 levels and may result in false-negative values in patients with acromegaly A low insulin-like growth factor-1 level does not exclude acromegaly in a patient with supportive clinical features and poorly controlled diabetes.

Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly

“…In this study, normal IGF-1 level was not observed in any of the patients. This may be due to majority of the patients in our study presented with macroadenoma on the contrary to the case reports in the literature [17][18][19][20].…”

“…However, to the best of our knowledge this is the first comparative study investigating impact of hepatic insulin resistance on IGF-1 levels in patients with acromegaly. Only low or normal IGF-1 levels are reported in patients with acromegaly with unregulated type 2 DM as case reports [17][18][19][20]. Increase in IGF-1 levels are reported with the improvement of glycemic regulation in these patients.…”

“…reports. Improvement of glucose metabolism leads to increase in IGF-1 levels in all and decrease in GH levels in some of these patients [17][18][19][20][21][22][23]. Therefore, GH and IGF-1 levels may not reflect actual levels in patients with acromegaly accompanying DM or prediabetes.…”

The Biochemical Diagnosis of Acromegaly

“…In contrast to the variability of GH, IGF-1 is secreted continuously, has a longer halflife and exhibits more stable concentrations in blood, and levels are proportionate to the mean GH levels, although this correlation between GH with IGF-1 may be lost at higher GH values, possibly due to saturation of hepatic GH receptors [8,13]. Furthermore, IGF-I levels can be determined at any time of the day without the patient having to fast [14]. For these reasons, measuring IGF-1 level is the initial test recommended in patients with clinically suspected acromegaly and IGF-1 levels below normal upper range for age and sex can effectively exclude the diagnosis of acromegaly [1,9].…”

“…Porkajac and colleagues studied GH and IGF-1 assay performance close to cut-off values for active acromegaly and submitted serum samples known to give borderline results to 23 centers for IGF-1 assessment and reported more than a 2-fold variation in IGF-1 cut-off for the ULN range measured in different laboratories and the diagnosis of acromegaly was inaccurately excluded in 30% of samples assayed for IGF-1 [17]. Assays to determine IGF-1 and GH levels include electrochemiluminescence immunoassay (Roche Cobas) or chemiluminescence immunoassay (Siemens Immulite, IDS-iSYS, Diasorin Liaison), which introduce antibodies to bind and separate out target antigens, or liquid chromatography-mass spectrometry, which selects the target analyte based on mass and use an electric ion field to determine the values, and there could be notable discrepancies in IGF-1 test results between different assays [13,14]. Therefore, the recommendation is to use the same well-validated IGF-1 assay throughout patient follow-up [12].…”