Comparative evaluation of several parameters of glycemic homeostasis in patients with functional pituitary adenomas

Aim.
To investigate glycemic homeostasis in patients with acromegaly and hyperprolactinaemia due to functional pituitary adenoma.
Materials and Methods.
We enrolled 48 patients with somatotropinoma (Group 1), 19 patients with somatomammotropinoma (Group 2) and 24 patients with prolactinoma (Group 3) with no history of glycemic disorders. Median age was 48.63?9.98 years; median disease duration was 13.1?6.9 years. The comparison group was composed of overweight or obese patients (n=75). We conducted a comparative analysis of glycemic parameters (Glc₀, immunoreactive insulin, HOMA2_S%, HOMA2_B% и HOMA2_IR, S_sum and S under isolated segments of the glycemic curve). We also tested their correlation with plasma levels of growth hormone, prolactin and IGF-1.
Results.
We detected hyperinsulinemia (>20 ?U/mL) in 35.1% of participants from Group 1, 33.3% and 25% from groups 2 and 3, respectively. There was no statistically significant difference between glycemic parameters of the study groups, though patients were mildly insulin resistant (HOMA2_IR 1.88 to 2.38 units) independantly from tumour secretory activity. Groups 1 and 2 were characterized by significantly higher fasting blood glucose levels vs. comparison group (though still within the reference values), and glucose homeostasis was maintained with lower activity of pancreatic ?-cells. Average S_sumanalysis showed lower glucose tolerance in groups 1 and 2 vs. Group 3. Median S values under isolated glycemic curve segments were significantly higher than in comparison group. Plasma levels of growth hormone did not correlate with S_sum and S parameters in groups 1 and 2. There was a linear correlation between S_sum and plasma IGF-1 levels in patients from Group 1 (r=0.45; p=0.006). We also noted that S_sum had a non-linear correlation with plasma prolactin levels in patients from Group 3 (r=0.41; p<0.05).
Conclusion.
Postprandial area under the glycemic curve has positive linear association with plasma IGF-1 (but not growth hormone) in patients with somatotropinoma.

pituitary adenoma, acromegaly, prolactinoma, insulin resistance, glycemic homeostasis

1. Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. Journal of Clinical Endocrinology & Metabolism 2004;89(2):667-674. doi: 10.1210/jc.2003-031199.

2. Bex M, Abs R, T'Sjoen G, Mockel J, Velkeniers B, Muermans K, et al. AcroBel--the Belgian registry on acromegaly: a survey of the 'real-life' outcome in 418 acromegalic subjects.. Eur J Endocrinol 2007;157(4):399-409. Available from: http://eje-online.org/cgi/pmidlookup?view=long&pmid=17893253 PubMed PMID: 17893253. doi: 10.1530/EJE-07-0358.

3. Mestron A, Webb S, Astorga R, Benito P, Catala M, Gaztambide S, et al. Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA. European Journal of Endocrinology 2004;151(4):439-446. Available from: http://www.eje-online.org/cgi/doi/10.1530/eje.0.1510439 PubMed PMID: 15476442. doi: 10.1530/eje.0.1510439.

4. Микитюк МР, Хижняк ОО, Сулима ТН. Особенности нарушений углеводного обмена у больных акромегалией. Ендокринологія. 2012; 15 (3): 248-254. [Mikityuk MR, Khizhnyak OO, Sulima TN. Osobennosti narusheniy uglevodnogo obmena u bol'nykh akromegaliey. Endokrinologіya 2012;15(3):248-254.]

5. Дедов ИИ, Молитвословова НН, Марова ЕИ. Акромегалия: патогенез, клиника, диагностика, дифференциальная диагностика, методы лечения. Пособие для врачей. Тверь:«Триада»; 2003. [Dedov II, Molitvoslovova NN, Marova EI. Acromegaly: pathogenesis, clinical manifestations, diagnosis, differential diagnosis, treatment methods. Manual for physicians. Tver':«Triada»; 2003.]

6. Марова ЕИ. Нейроэндокринология: клинические очерки. Ярославль: "ДИА-пресс"; 1999. 506 с. [Marova EI. Neuroendocrinology: clinical essays. Yaroslavl': "DIA-press""; 1999. 506 p.]

7. Giustina A, Barkan A, Casanueva F, Cavagnini F, Frohman L, Ho K. Criteria for Cure of Acromegaly: A Consensus Statement. Journal of Clinical Endocrinology & Metabolism 2000;85(2):526-529. doi: 10.1210/jcem.85.2.636.

8. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism 2011;96(2):273-288. doi: 10.1210/jc.2010-1692.

9. Seltzer HS, Allen EW, Herron AL, Brennan MT. Insulin Secretion in Response to Glycemic Stimulus: Relation of Delayed Initial Release to Carbohydrate intolerance in Mild Diabetes Mellitus*. J. Clin. Invest 1967;46(3):323-335. Available from: http://www.jci.org/articles/view/105534 doi: 10.1172/JCI105534.

10. Available from: www.dtu.ox.ac.uk/homacalculator/index.php

11. Микитюк МР, Хижняк ОО, Сулима ТН. Особенности нарушений углеводного обмена у больных акромегалией. Ендокринологія. 2012; 15 (3): 248-254. [Mikityuk MR, Khizhnyak OO, Sulima TN. Osobennosti narusheniy uglevodnogo obmena u bol'nykh akromegaliey. Endokrinologіya. 2012; 15 (3): 248-254.]