Circadian variations of thyrotropin bioactivity in normal subjects and patients with primary hypothyroidism.

Abstract

Circadian rhythm of TSH secretion is characterized by a pronounced nocturnal increment that is not followed by the expected rise of circulating thyroid hormone levels. These findings suggest that the nocturnal TSH surge may be constituted by molecules with reduced bioactivity. We, therefore, investigated TSH bioactivity (measured as cAMP accumulation in FRTL-5 cells) and its carbohydrate structure (by Concanavalin A affinity chromatography) in different blood pools taken during the day and night from seven normal subjects and from one patient with mild (mPH) and five with severe primary hypothyroidism (sPH). Patients with sPH were also studied during low dose L-T4 treatment. Cosinor analysis showed a significant TSH circadian rhythm in the control group and in L-T4-treated sPH patients. The nocturnal TSH surge was not followed by any increase in free thyroid hormone levels. In normal subjects, the daytime ratio of TSH bioactivity to immunoreactivity (TSH B/I) was higher than the nocturnal one [1.4 +/- 0.6 (+/- SD) vs. 1.1 +/- 0.6; P < 0.02]. The same pattern was observed in the only mPH patient (1.0 +/- 0.2 vs. 0.7 +/- 0.1; P < 0.01), but not in the sPH patients (0.8 +/- 0.3 vs. 0.7 +/- 0.1; P = 0.3). L-T4 administration to sPH patients caused the daytime TSH B/I to increase and restored the day/night difference in the TSH B/I (1.0 +/- 0.3 vs. 0.8 +/- 0.3; P < 0.02). Concanavalin A chromatography showed that a higher percentage of less mature forms of TSH are secreted during the night. These data indicate that TSH molecules secreted during the night are less bioactive and differently glycosylated than those circulating in the same individual during the day, thus explaining why thyroid hormone levels do not rise after the nocturnal TSH surge. In sPH patients, the TSH circadian rhythm is restored during L-T4 administration, and day/night differences in TSH B/I similar to those recorded in normal subjects are observed.

Biochemical Testing of the Thyroid: TSH is the Best and, Oftentimes, Only Test Needed – A Review for Primary Care

“…12 While generally not resulting in TSH values outside the normal range, this circadian rhythm may cause a variation in TSH by a mean of between 0.95 mIU/mL to 2.0 mIU/mL, 13 which could affect treatment decisions. Also, this circadian rhythm appears to remain intact in patients with subclinical hypothyroidism, and in one small study 50% of patients with a mildly elevated TSH between 8:00-9:00 am had a normal TSH (< 4.0 mIU/mL) when assessed between 2:00-4:00 pm.…”

Thyrotropin Isoforms: Implications for Thyrotropin Analysis and Clinical Practice

“…In such cases, chronic TRH administration has been shown to increase TSH bioactivity and restore thyroid function (126). In patients with primary hypothyroidism and TSH-secreting pituitary adenomas, normal, reduced, and increased TSH bioactivities have all been reported (112,122,(128)(129)(130)(131).…”

Non-Thyroidal Illness in the ICU: A Syndrome with Different Faces

“…In addition, plasma TSH concentrations measured in a single sample can also be transiently elevated, as occurs during surgery (20), but most often plasma TSH concentrations are in the normal range in patients admitted to the ICU. However, by analyzing TSH time series, it has become clear that in this acute phase of illness, the normal nocturnal TSH surge is absent (21,22). The magnitude of the decrease in circulating T3 during the first 24 h after the onset of acute illness reflects the severity of illness and correlates with mortality (23)(24)(25)(26).…”