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Diminished and Irregular Thyrotropin Secretion with Preserved Diurnal Rhythm in Patients with Active Acromegaly

Department of Endocrinology and Metabolic Diseases (F.R., N.R.B., M.F., J.A.R.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Department of Statistics (D.M.K.), University of Virginia, Charlottesville, Virginia 22904; and Endocrine Research Unit (J.D.V.), Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Ferdinand Roelfsema, Leiden University Medical Center, Department of Endocrinology and Metabolic Diseases, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: f.roelfsema{at}lumc.nl.

Context: The hypothalamo-pituitary-thyroid axis in acromegaly may be altered. Previous studies report diminished serum TSH concentrations in patients with active acromegaly and decreased response to TRH. On the other hand, most patients have normal thyroid hormone concentrations.

Objective: Our aim was to analyze serum TSH profiles in relation to GH profiles in patients with untreated acromegaly, in order to delineate aberrations in the hypothalamo-pituitary-thyroid system.

Intervention: Twenty-one patients with active acromegaly and matched controls underwent a 24-h, 10-min blood sampling study. GH and TSH data were analyzed with a newly developed automated deconvolution program, approximate entropy, and cosinor regression.

Results: Basal (10.4 ± 2.0 vs. 13.8 ± 1.4 mU/liter · 24 h; P = 0.02) and pulsatile (11.4 ± 1.7 vs. 18.6 ± 1.6 mU/liter · 24 h; P = 0.002) TSH secretion was decreased in patients. TSH secretory regularity was diminished with loss of pattern synchrony between TSH and GH. Total TSH secretion correlated with TSH increase after TRH (R = 0.75; P = 0.0001), negatively with the log-transformed GH secretion rate (R = –0.52; P = 0.001), but not with adenoma size. The diurnal TSH rhythm was preserved. Total and free T₄ concentrations were similar in patients and controls.

Conclusion: Basal and pulsatile TSH secretion is decreased in active acromegaly, although T₄ levels are unaffected. Diminished TSH secretion is compatible with enhanced restraint by tumoral GH feedback-driven somatostatin outflow, explaining also the reduced regularity of TSH secretion. Unchanged T₄ concentrations might reflect decreased sympathetic function in GH excess states, heightening responsiveness of the thyroid gland to TSH.

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				F. Roelfsema, A. M Pereira, N. R Biermasz, M. Frolich, D. M Keenan, J. D Veldhuis, and J. A Romijn Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome Eur. J. Endocrinol., November 1, 2009; 161(5): 695 - 703. [Abstract] [Full Text] [PDF]