Abnormal circadian rhythm and increased non-pulsatile secretion of thyrotrophin in Sheehan's syndrome

It has previously been shown that patients with postpartum pituitary necrosis (Sheehan's syndrome, SS) have paradoxically increased TSH levels and loss of the nocturnal TSH surge. This study sought to determine the circadian and pulsatile characteristics of TSH secretion underlying those abnormalities.

Chronobiological and cluster analyses of 24-h TSH profiles were performed in nine SS patients (43-61 years, median = 52 years) and nine healthy female controls (33-47 years, median = 42 years).

Serum concentrations of T3, T4, free T4 (fT4) and cortisol were measured by radioimmunoassay; TSH, GH, PRL and LH were determined by immunometric assays.

All patients and controls showed significant circadian TSH rhythms, but the percentage amplitude was decreased (7.5% vs. 21.3%, P < 0.0001) and the acrophase was markedly displaced in SS patients, occurring between 0315 h and 1515 h in seven/nine patients and in two/nine controls (P = 0.057). Patients showed increased total 24-h TSH secretion (6054 +/- 2293 vs. 2193 +/- 340 mU/l/min, mean +/- SE, P = 0.04) due to increased non-pulsatile or tonic 24-h TSH secretion (5631 +/- 2105 vs. 1925 +/- 301 mU/l/min, P = 0.026), but no difference was detected in pulsatile secretion (424 +/- 191 vs. 268 +/- 41, P = 0.82). The contribution of non-pulsatile to total TSH secretion was also increased in SS patients (93.8% vs. 87.6%, P = 0. 002). No significant changes were found in TSH pulse frequency, amplitude, duration or interpeak interval. When cluster parameters were individually analysed in two distinctive 12-h periods corresponding to acrophase and nadir, patients showed increased non-pulsatile TSH secretion in both periods, but no differences were found in pulsatile TSH secretion, pulse frequency or amplitude. The increment of TSH secretion during the acrophase in SS patients was exclusively due to increased non-pulsatile TSH secretion, as opposed to controls who displayed significant increments in both non-pulsatile and pulsatile TSH secretions.

Sheehan's syndrome patients have increased total TSH secretion due to increased tonic TSH secretion. A circadian TSH rhythm is still present in these patients, but shows decreased magnitude and markedly displaced acrophase.