INFLUENCE OF RESIDUAL C-PEPTIDE SECRETION ON NOCTURNAL SERUM TSH PEAKIN WELL-CONTROLLED DIABETIC-PATIENTS

OBJECTIVE Several alterations in hypothalamopituitary-thyroid (HPT) fu nction have been described in diabetes mellitus and have been attribut ed to metabolic decompensation. The present study was performed in ord er to establish whether residual endogenous insulin secretion in patie nts with insulin-dependent diabetes mellitus (IDDM) may play a role in the control of HPT function. DESIGN The nocturnal (2230 h-0200 h) ser um TSH surge, the TSH response to TRH (200 mu g as an i.v. bolus) and serum free thyroid hormone levels were evaluated in C-peptide positive (CpP) (subjects with residual detectable endogenous pancreatic beta-c ell activity) and C-peptide negative (CpN) patients both before and af ter optimization of metabolic status by 3 days of treatment with conti nuous subcutaneous insulin infusion, and in normal controls. TSH respo nse to TRH and serum free thyroid hormone levels were assessed in the morning. SUBJECTS Twenty male diabetic patients hospitalized to achiev e a better control of hyperglycaemia were subdivided into 10 CpP (age: 33 +/- 1.5 years (mean +/- SE); body mass index (BMI): 22.6 +/- 0.3) and 10 CpN (age: 32 +/- 1.7 years; BMI: 22.5 +/- 0.4) patients, Nine n ormal men (age: 34.0 +/- 1.2 years; BMI: 23.1 +/- 0.4) served as contr ols. MEASUREMENTS The nocturnal serum TSH peak was measured by dividin g the highest night-time TSH value by the next morning TSH value and t hen multiplying by 100. Serum TSH revels were measured in samples take n just before (time 0) and 30 minutes after TRH administration, Serum free thyroid hormone levels were measured in samples taken at time 0 o f the TRH test. RESULTS Before improvement of hyperglycaemia, CpP and CpN patients showed similar alterations in HPT function; i.e. serum fr ee T3 levels and TSH responses to TRH were lower than normal; the noct urnal TSH surge was absent. Correction of hyperglycaemia normalized al l examined HPT parameters in CpP diabetics, whereas normalization in s erum free T3 levels and pituitary TSH responsiveness to TRH in CPN pat ients was not accompanied by restoration of the nocturnal TSH peak. CO NCLUSIONS These data indicate that the absence of residual pancreatic beta-cell function in patients with insulin-dependent diabetes mellitu s is associated with neuroendocrine dysfunction in the regulation of c ircadian TSH secretion, which is not reversible after restoration of g ood glycaemic control.