The effects of abnormal sleep behaviors on hormones and its correlations with endocrine disorders.

1. METABOLIC AND ENDOCRINE
CONSEQUENCES
OF ABNORMAL HUMAN SLEEP
Dr.Ahmed Elshebiny, MD
Assistant Professor of Internal Medicine,
Diabetes and Endocrinology,KFU, KSA
Lecturer, Internal Medicine, Menoufia university , Egypt
Former Clinical Research Fellow,Joslin Diabetes Center, USA Image Credit: kanyanat wongsa/Shutterstock.com

2. HUMAN SLEEP AND
THE ENDOCRINE
SYSTEM
The body functions follow a circadian rhythm. Sleep is an
active process. Sleep pattern differs by age.
Sleep and hormones are interrelated
Short sleep durations were associated with obesity, insulin
resistance, diabetes mellitus, hypertension and dyslipidemia
Sleep deprivation was associated with increased CV disease
and increased mortality
GH, GHRH , prolactin & somatostatin promote sleep while
cortisol and androgen increase awareness or reduce sleep.
Sleep disorders can retard growth and treatment of these
disorders lead to growth catch-up
Screen patients for sleep disorders, insufficient sleep or OSA
as fatigue may result from both endocrine or sleep disorders

3. THE FIRST PART: UNDERSTANDING HUMAN SLEEP
 What is sleep medicine?
 Why we sleep?
 Is sleep a passive or an active process?
 What are the functions of sleep?
 What happened to our sleep?
 What is meant by abnormal sleep?
 How hormones affect sleep regulation?
 How hormones change during the day and night?
 Melatonin / Melatonin receptor agonists
 Do we take detailed sleep history from our patients?

4. THE SECOND PART: SLEEP AND HORMONES,
PHYSIOLOGICAL AND PATHOLOGICAL INSIGHTS
 Human sleep and the somatotropic axis
 Sleep , obesity and the metabolic syndrome
 Sleep , appetite and fasting
 Sleep , hyperglycemia and diabetes mellitus
 Sleep , hypertension, lipids and the cardiovascular disease
 Sleep and mortality
 Sleep and fertility
 Sleep and the cortisol axis
 Sleep / thyroid interrelationship
 Sleep and bone health

5. SEEP MEDICINE HISTORY

6. UNDERSTANDING HUMAN SLEEP
Sleep
• A state of unconsciousness in which the brain
is relatively more responsive to internal than
external stimuli
• Characterized by cycling and reversal of
relative external unresponsiveness
• Differentiated from other types of loss of
consciousness
• Homeostatic and circadian factors determine
the time and quality of sleep
• VLPO acts as sleep center or switch

7. SLEEP IS AN ACTIVE PROCESS
 Sleep is not merely the absence of waking.
 It is an active process in which metabolism, tissue
restoration, memory consolidation, and general
homeostatic balance is maintained

8. FUNCTIONS OF SLEEP
Sleep
Functions
Development
Energy conservation
Brain waste clearance
Modulation of immune response
Cognition and memory consolidation
Performance, vigilance
Psychological wellbeing

9. NORMAL SLEEP ARCHITECTURE
 4-6 cycles/night composed of NREM and REM
sleep
 NREM sleep is subdivided into stages
numbered 1 to 3.
 NREM accounts for approximately 75% to 80%
of total sleep, and REM accounts for the
remaining 20% to 25% of sleep.
 REM is the phase of sleep responsible for
dreaming. It is characterized by total body
voluntary muscle paralysis (except for the
extraocular muscles)
NREM (N1)
NREM (N2)
NREM
(N3)= SWS
REM sleep

10. SLEEP DURATION AND COMPOSITION DIFFER BY AGE

11. NEUROENDOCRINE REGULATION OF SLEEP
 Sleep Generation is initiated
within the ventrolateral
preoptic nucleus (VLPO) of the
anterior hypothalamus
 Arousal regions include the
tuberomammillary nucleus,
lateral hypothalamus, locus
coeruleus, dorsal raphe,
laterodorsal tegmental
nucleus, and
pedunculopontine tegmental
nucleus.
 Hypocretin (orexin) neurons
in the lateral hypothalamus
help to facilitate this process.
Arousal
system
The
sleep
center

12. OREXIN SYSTEM

13. THE CIRCADIAN RHYTHMICITY
 Circadian rhythm is the body’s cyclical nature .
 The hypothalamus controls it via the
suprachiasmatic nucleus
 The circadian rhythm is approximately 24.2
hours per cycle.
 Melatonin, has also been shown to be a
modulator of the circadian rhythm .
 Melatonin levels are greatest at night and
decrease during the daytime.

14. THE CIRCADIAN
GENE NETWORK

15. IMPLICATIONS
OF CIRCADIAN
RHYTHM
DISRUPTION

16. MCQ 1
Which hypothalamic nucleus is responsible for the circadian rhythm?
A. Paraventricular nucleus (PVN)
B. Suprachiasmatic nucleus(SCN)
C.Ventrolateral preoptic nucleus (VLPO)
D.Slow wave sleep

17. HOW HORMONES CHANGE DURING SLEEP?
Affected (increased) by sleep specially in SWS
Growth hormone and prolactin
AM surge, Circadian rhythmicity
Cortisol
AM surge, Circadian rhythmicity
Testosterone
Increased nocturnal pulses which increases with onset of puberty
LH
TSH is suppressed by sleep and reaches its nadir in the midafternoon. Sleep
deprivation increases nocturnal TSH
TSH
High at night.Affects the sleep duration and quality
Melatonin
Sleep deprivation increases ghrelin and decreases leptin
Ghrelin and Leptin
Glucose increases by 30% and Insulin by 60% during night
Glucose and insulin

18. SLEEP DISORDERS
Insomnia
Obstructive sleep
apnea
Central sleep apnea
Narcolepsy
Somnambulism

19. SLEEP LOSS AND SLEEP DEPRIVATION
Acute sleep
loss
Chronic sleep
deprivation

20. SLEEP APNEA
Obstructive
sleep apnea
Central
Sleep apnea
Mixed

21. OBSTRUCTIVE SLEEP APNEA
OSA is a common sleep disordered breathing characterized
by:
 Recurrent apneas or hypopneas
 Upper airway constriction, hypoxemia, hypercapnia,
autonomic activation,
 EEG arousal and sleep fragmentation, leading to
daytime fatigue and sleepiness
 Hypercortisolemia
 Decreased IGF-1
 Increased risk of CV disease and mortality
0%
5%
10%
15%
20%
25%
30%
Category 1
Prevalence of OSA in Men andWomen aged
30-60
Men women

22. ENDOCRINE DISEASES ASSOCIATED WITH OSA
 Obesity
 Type 2 DM
 PCOS
 Hypothyroidism ( Thyroid hormone deficiency)
 Acromegaly (GH excess)
 OSA is reversible after treatment in patients with hypothyroidism
 Insulin levels and glucose tolerance in patients with PCOs are associated with severity of OSA

23. OBSTRUCTIVE SLEEP APNEA AND HORMONES

24. OSA AND ALDOSTERONE SYSTEM

25. WHAT HAPPENED
TO OUR SLEEP?
Globally, insufficient sleep is prevalent
across various age groups, considered to
be a public health epidemic that is often
unrecognized, under-reported, and that
has rather high economic costs

26. THE COSTS OF SLEEP DEPRIVATION

27. SLEEP DISORDERS IN SAUDI ARABIA
Obstructive sleep apnea(OSA)
• In one study, 11.2 % in men and 4% in women ( age 30-60 years)
• OSAS was 4% and 1.8 % respectively
Parent –reported snoring during sleep
• 17.9% of elementary Saudi school children.
Narcolepsy with cataplexy
• 40 per 100,000 people

28. SLEEP MEDICINE FACILITIES IN KSA
Riyadh
(6 sleep
facilities)
Dammam (5
sleep facilities)
Jeddah (7
sleep facilities)
Bahammam AS,Alsaeed M,Alahmari M,Albalawi I, Sharif MM. Sleep medicine services in Saudi Arabia: the 2013 national survey.AnnThorac Med. 2014;9(1):45–47.

29. STUDYING SLEEP

30. MELATONIN
 Derived from tryptophan
 Acts on central and peripheral receptors
 Synthetic forms are available
 Melatonin receptor agonists are approved for
insomnia

31. SLEEP FOR GROWTH
Sleep is no less important than food for growth

32. MCQ 1
At which stage of sleep the growth hormone peaks?
A. REM Sleep
B. Stage one NREM
C.Stage 2 NREM
D.Slow wave sleep (SWS)

33. GROWTH HORMONE SECRETION DURING SLEEP

34. EFFECT OF SLEEP DEPRIVATION ON GH SECRETION
Van Cauter et al, 2000

35. SW SLEEP AND NOCTURNAL GH PATTERNSTHROUGH ADULT LIFE
Van Cauter et al, 1998 , American Academy of Sleep Medicine

36. GHRH
GH
SW sleep
BIDIRECTIONAL INTERACTIONS
BETWEEN GH &SLEEP
REM sleep
Ghrelin
Somatostatin

37. SLEEP DEPRIVATION AND OBESITY EPIDEMIC
 Obesity and sleep deprivation are two epidemics
 There is a bidirectional link between sleep
deprivation and obesity.
 Sleep deprivation may mediate increases in BMI.
 Obesity increases the risk for sleep disorders,
which may compromise sleep quality
 Experimental sleep restriction was associated
with increased levels of ghrelin, salt retention and
inflammatory markers.
 Additionally, Sleep deprivation was associated
decreased levels of leptin and insulin sensitivity.
6 months of insufficient
sleep may lead to gain of
10 lb in weight as
compared to rested
subjects

38. POSSIBLE LINKS BETWEEN LACK OF SLEEP AND OBESITY
 Increased ghrelin and decreased leptin which lead
to increased hunger
 Fatigue during the day decreases the exercise
activity
 Behavioral increased eating due to increased time
being awake

39. SLEEP DEPRIVATION AND OBESITY IN ADULTS
 Epidemiological studies linked sleep deprivation to
increased BMI and obesity
 Both short sleepers (less than 5 hours) and long
sleepers ( more than 8 hours) are more likely to be
obese
 Studies showed that there are interpersonal
variability to the sensitivity of sleep deprivation
 A recent metanalysis from 26 pooled studies has
shown consistent increased risk of obesity among
short sleepers
 No sufficient longitudinal studies to prove causality

40. SLEEP
DEPRIVATION
AND OBESITY IN
CHILDREN AND
ADOLESCENTS
• Sleep deprivation has detrimental effects on cognitive functioning
and neurobehavioral performance in children and adolescents.
• There is a global epidemic of obesity among children and
adolescents.
• There is significant correlation between shorter sleeping hours
among children and adolescents and the development of obesity.

41. SLEEP & APPETITE
 Acute sleep deprivation and fragmentation are associated with
increased hunger and reduced fullness.
 Short and fragmented sleep are associated with increased release of
the hunger hormone ghrelin and reduced release of satiety peptides in
laboratorial settings.
 A worse habitual sleep efficiency is associated with
lower cholecystokinin postprandial plasma concentrations.

42. SLEEP , FOOD AND FASTING
 There is evidence to suggest that dietary
patterns that favour HC intakes are associated
with reduced SOL and SWS and increased REM.
 Longer-term effects have not been examined in
randomized controlled studies.
 Some foods, such as milk products, fish, fruit,
and vegetables, also show sleep-promoting
effects, but studies have been too diverse, short,
and small to lead to firm conclusions.
 Intermittent fasting may affect the sleep
composition in certain studies.

43. SLEEP DEPRIVATION AND FOOD DESIRABILITY

44. SLEEP ,
HYPERTENSION
AND
CATECHOLAMINES
 Poor sleep quality was associated with increased hypertension
 Women could be at higher
 Alcoholics may be at higher risk
 Experimental sleep deprivation to an average of 3.6 hrs. per night led to
increase in the blood pressure, heart rate and the urinary excretion of
norepinephrine.
 Obstructive sleep apnea may result in increased catecholamines, and
caution should be taken when screening for pheochromocytoma

45. SLEEP
DEPRIVATION AND
DYSLIPIDEMIA
• Sleep deprivation may be associated with higher serum levels of
cholesterol and triglycerides.
• Women could be at a higher risk of developing dyslipidemia with
sleep deprivation.

46. SLEEP AND
IMMUNE
SYSTEM
INTERACTIONS

47. SLEEP , HYPERGLYCEMIA AND DIABETES
 Sleep duration of less than 6 hours or more than 8 hrs. increase the risk of type 2 DM
 Just snoring is associated with higher levels of HBA1c
 OSA is independently associated with abnormal glucose metabolism
 OSA is present in 60-80% of patients with type 2 DM
 Type 2 DM is present in 15-30% of patients with OSA
 Sleep fragmentation is associated with abnormal glucose metabolism
 Decrease SWS decreases insulin sensitivity
 Severity of OSA is associated with glucose control (HbA1c) ii patients with Type 2 DM
 Use of CPAP in patients with OSA improves glucose parameters.
 Use of CPAP may improve the GH secretion in these patients as it improves sleep pattern.

48. SLEEP , CARDIOVASCULAR DISEASE AND MORTALITY
Poor sleep, insomnia and short
sleep durations were associated
with increased CV disease risk by
29% and premature mortality in
different epidemiological studies

49. SLEEP, SEX AND FERTILITY IN MEN
 There is a distinct morning testosterone surge
 Sleep deprivation may lower AM testosterone by up
to 20%
 Sleep apnea has a distinct effect on testosterone
 Treatment of OSA improves androgen profile
 CPAP improved Nocturnal penile tumescence in a
study
 Investigation of sleep should be included in patients
with hypogonadism
 Androgen replacement worsens undiagnosed OSA
and shortens sleep duration
 Screen patients for OSA before androgen
replacement

50. SLEEP DEPRIVATION AND POSSIBLE LINKS TO MALE
FERTILITY

51. SLEEP, SEX AND FERTILITY IN WOMEN
 Sleep Deprivation in women alters sex steroids
 Sleep deprivation is associated with sexual
dysfunction in questionnaire study
 Decreased sleep among female shift workers
suppresses melatonin production as well as
excessive HPA activation which results in early
pregnancy loss, failed embryo implantation,
anovulation and amenorrhea.

52. SLEEP AND THE CORTISOL AXIS
 sleep loss activates HPA axis
 The HPA axis follows a distinct 24 h pattern.
 The nadir for cortisol occurs near midnight.
 The peak happens in the morning at about 9 a.m.
 Animal and human studies show that external cortisol can increase the time being awake
 In Cushing‫׳‬s syndrome, polysomnogram shows reduction of SWS, increased sleep latency, enhanced wake time,
shortened REM latency, and elevated REM density.

53. SLEEP /THYROID INTERRELATIONSHIP
 TSH follows a circadian rhythms in contrast to stable thyroxine
levels
 Thyroid dysfunctions impact sleep quality
 Both hyper and hyperthyroidism may be associated with
insomnia
 Hypothyroidism may be linked to OSA

54. SLEEP AND BONE HEALTH
 Night-shift work, which causes both sleep disruption and circadian
misalignment, has been associated with lower BMD and increased
fracture risk
 Sleep deficiency and/or circadian disruption may increase the risk
of falls due to reduced vigilance/balance
 Long and Short Sleep Duration Have Been Associated with Low
BMD
 Bone remodelling may follow a circadian rhythm and circadian
genes may have a role
 Melatonin may improve BMD

55. MELATONIN AND
BONE HEALTH

56. TAKE HOME
MESSAGE