Alterations in diurnal rhythmicity in patients treated for nonfunctioning pituitary macroadenoma: a controlled study and literature review.
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 >3 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 (P=0.006). 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 (≥2.0 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.


CONCLUSIONS
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.
Center for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The Netherlands SDJoustra@lumc.nl.
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Joustra
Center for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The NetherlandsCenter for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The Netherlands.
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Thijs
Center for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The Netherlands.
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van den Berg
Center for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The Netherlands.
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van Dijk
Center for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The Netherlands.
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Pereira
Center for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The NetherlandsCenter for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The Netherlands.
G J
GJ
Lammers
Center for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The NetherlandsCenter for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The Netherlands.
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van Someren
Center for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The Netherlands.
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Romijn
Center for Endocrine Tumors LeidenDepartment of Endocrinology and MetabolismDepartment of NeurologyLeiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The NetherlandsStichting Epilepsie Instellingen Nederland (SEIN)Achterweg 5, 2103SW Heemstede, The NetherlandsDepartment of Sleep and CognitionNetherlands Institute for Neuroscience, Meibergdreef 47, 1105BA Amsterdam, The NetherlandsNeuroscience Campus AmsterdamDepartments of Integrative Neurophysiology and Medical Psychology, VU University and Medical Center, De Boelelaan 1117, 1081HZ Amsterdam, The Netherlands.
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Biermasz
D000328:Adult; D000368:Aged; D001794:Blood Pressure; D001831:Body Temperature; D002940:Circadian Rhythm / Q000502:physiology*; D003397:Craniopharyngioma / Q000503:physiopathology; D005221:Fatigue; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000378:metabolism; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000503:physiopathology* / Q000601:surgery; D012463:Saliva / Q000737:chemistry; D012881:Skin Temperature; D012893:Sleep Wake Disorders / Q000209:etiology; D013493:Suprachiasmatic Nucleus / Q000503:physiopathology
D008550:Melatonin