Alterations in diurnal rhythmicity in patients treated for nonfunctioning pituitary macroadenoma: a controlled study and literature review

Abstract

Objective: Patients treated for nonfunctioning pituitary macroadenomas (NFMAs) have fatigue and alterations in sleep characteristics and sleep-wake rhythmicity frequently. As NFMAs often compress the optic chiasm, these complaints might be related to dysfunction of the adjacent suprachiasmatic nucleus (SCN). We aimed to explore whether indirect indices of SCN functioning are altered in the long term after surgery for NFMAs. Methods: We studied 17 NFMA patients in long-term remission after transsphenoidal surgery, receiving adequate and stable hormone replacement for hypopituitarism, and 17 control subjects matched for age, gender, and BMI. Indirect indices of SCN function were assessed from 24-h ambulatory recordings of skin and core body temperatures, blood pressure, and salivary melatonin levels. Altered melatonin secretion was defined as an absence of evening rise, considerable irregularity, or daytime values O3 pg/ml. We additionally studied eight patients treated for craniopharyngioma. Results: Distal-proximal skin temperature gradient did not differ between NFMAs and control subjects, but proximal skin temperature was decreased during daytime (PZ0.006). Core body temperature and non-dipping of blood pressure did not differ, whereas melatonin secretion was often altered in NFMAs (OR 5.3, 95% CI 0.9-30.6). One or more abnormal parameters (R2.0 SDS of control subjects) were observed during nighttime in 12 NFMA patients and during daytime in seven NFMA patients. Similar patterns were observed in craniopharyngioma patients. Conclusion: Heterogeneous patterns of altered diurnal rhythmicity in skin temperature and melatonin secretion parameters were observed in the majority of patients treated for NFMAs. On a group level, both NFMA and craniopharyngioma patients showed a lower daytime proximal skin temperature than control subjects, but other group averages were not significantly different. The observations suggest altered function of central (or peripheral) clock machinery, possibly by disturbed entrainment or damage of the hypothalamic SCN by the suprasellar macroadenoma or its treatment.

Content and system development of a digital patient-provider communication tool to support shared decision making in chronic health care: InvolveMe

“…Data collection from patients and HCPs revealed a wide range of symptoms and needs experienced by the participating patient groups. This is in line with previous research addressing the impact of living with chronic health conditions [1][2][3][4][37][38][39][40][41][42]. Patients with chronic health conditions are characterized by large individual variations in symptoms, symptom frequency, symptom severity and the degree to which the patients are bothered by the symptoms, which makes it difficult to anticipate the type of care that may be in the patients' best interest.…”

“…They had to be ≥18 years old and able to read and speak Norwegian. Both patient groups frequently experience a long period of slow deterioration of their health status before undergoing surgery, and both groups do experience a variety of symptoms in the aftermath [36][37][38][39][40], which negatively impact HRQoL [41,42]. Renal replacement therapy through RTX is generally accepted as the preferred treatment for end-stage renal disease [36].…”

“…Patients may also experience symptoms' from medication side-effects and other co-morbid conditions [40]. NFPAs are benign pituitary tumors, and treatment is primarily surgery [37]. Patients face many challenges, included visual limitations, fear of recurrence, persisting distressing thoughts, loneliness and frustration [38,39].…”

Clock genes and cancer development in particular in endocrine tissues

“…In human autopsied pituitaries, PER1 mRNA expression showed daytimedependent differences according to time of death with decreased levels observed at evening, whereas the protein levels of PER1, CRY1 and CLOCK did not fluctuate with the time of day (Becquet et al 2014). In other studies, circadian rhythmicity has been indirectly studied through melatonin secretion and sleep disturbances (Joustra et al 2014). Altered melatonin secretion was found in 41% of patients with non-functional pituitary macroadenomas (NFPA) (Joustra et al 2014); those patients had high daytime levels, no evening rise or severe irregularity of melatonin secretion.…”

Non-24-Hour Sleep-Wake Rhythm Disorder and Melatonin Secretion Impairment in a Patient With Pineal Cyst

“…1 In sighted subjects, most cases remains idiopathic, but few studies reported CRSWD in patients with hypothalamic lesions, namely tumors, and postsurgical or actinic lesions. [2][3][4] The role of pineal gland lesions in causing FRD is controversial. 5,6 FRD is not listed among the pineal cyst-related symptoms, which encompass instead headache, visual disturbances, vertigo, vomiting, and other sleep-related complaints.…”