Alteration of Hypothalamic–Pituitary–Thyroid Axis Function in Non-Small-Cell Lung Cancer Patients

Abstract

The aim of this study was to evaluate the hypothalamic-pituitary-thyroid (HPT) axis function in patients suffering from lung cancer. Thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free thyroxine (FT4), interleukin (IL)-2, and melatonin serum levels were measured in blood samples collected every 4 hours for 24 hours from 11 healthy participants (H; ages 35-53 years) and 9 patients suffering from non-small-cell lung cancer (C; ages 43-63 years). Relationships between hormone levels overall and over time of day were evaluated within and among groups. A prominent circadian rhythm with peaks near midnight was present for TSH and melatonin serum levels in both H and C, indicating similar synchronization of the main body clock to the 24-hour environmental light-dark cycle. As regards 24-hour means in H and C, TSH was lower in C, whereas TRH, FT4, and IL-2 were higher in C, with no difference in melatonin levels. Simple linear regression, FT4 versus TRH, showed a positive correlation in H and a negative correlation in C, whereas FT4 versus TSH showed a negative correlation in both groups. For FT4 versus IL-2, a negative correlation was found in C but not for H, whereas TSH versus TRH showed no correlation for either group. Both groups were found to be similarly synchronized to the 24-hour sleep-wake schedule, but HPT axis function was altered in patients suffering from lung cancer. When compared with healthy controls, cancer patients showed modifications of hormone serum levels overall and a negative correlation between individual TRH and FT4 levels.

The Intriguing Thyroid Hormones–Lung Cancer Association as Exemplification of the Thyroid Hormones–Cancer Association: Three Decades of Evolving Research

“…Assessment of the pattern of HPT axis function in the setting of a 24 h sleep-wake schedule in 11 healthy participants (age of 35–53 years-old) and 9 patients with NSCLC (age of 43–63 years-old) by Mazzoccoli et al demonstrated that, compared to healthy participants, NSCLC patients had lower 24 h means TSH levels, but higher 24 h means TRH and fT4 levels. Nevertheless, both groups of patients experienced similar synchronization of the main body clock to the 24 h environmental light-dark cycle, resulting in a prominent circadian rhythm of TSH with peaks near midnight [ 102 ].…”

Integration of Chronobiological Concepts for NSCLC Management

“…The melatonin/cortisol mean nocturnal level ratio was also decreased in LC patients [75,76]. Taken together, these results suggested that lung cancer is associated with alteration in the proportions and 24-h profiles of various lymphocyte subsets; this may be related to disease stage and probably altered immune function [73][74][75]76].…”

“…In LC patients, a progressive increase in GH and a steady decline of IGF-1 serum levels with loss of circadian rhythmicity were observed. This loss of diurnal rhythms could play a role in carcinogenesis and tumor growth regulation [71][72][73][74][75]. All profiles of time-related neuroendocrine-immune system components seemed to be the advancing stage of disease [71][72][73][74][75][76].…”

Small cell lung cancer starting with diabetes mellitus: Two case reports and literature review

“…They had the following common features: (1) middle age, smoking history and hypokalemia; (2) no significant clinical manifestations of Cushing’s syndrome, but increased ACTH and high level of cortisol in serum and urine; and (3) bronchoscopic biopsy confirmed SCLC. Changes in thyroid function in both patients were attributed to inhibition of the pituitary–thyroid axis by excess cortisol[16]. The condition of Patient 1 deteriorated rapidly, losing the best opportunity for treatment, whereas Patient 2 remained healthy for 2 years.…”