3. CONTENTS
• Introduction
• Endocrine system
• Central endocrine glands
• Effect of peripheral endocrine gland
hormones on periodontium
1. thyroid gland
2. parathyroid gland
3. pancreas
4. adrenal gland
5. sex steroids
• Conclusion
• References
4. INTRODUCTION
• “Periodontitis” is a type of chronic inflammatory disease affecting
people world wide, which is characterized by the loss of periodontal
connective tissue and alveolar bone, eventually leading to tooth loss.
The homeostasis of the periodontium involves complex multifactorial
relationships, in which the endocrine system plays an important role
5. HORMONES
• The word “hormone” is derived from the Greek word means
“Hormaein” which means to ‘execute or to arouse’.
Starling, 1905
• Hormone secreted by the endocrine system play an important role in
periodontitis
Hormones are specific regulatory molecules and secretory product of ductless
gland which are released in catalytic amounts into blood stream and
transported to specific target cells that modulate reproduction, growth and
development and the maintenance of internal environments as well as energy
production, utilization and storage.
6. ENDOCRINE SYSTEM
• The endocrine system collection of glands secrete hormones
circulatory system distant target organs.
• The phenomenon of biochemical processes serving to regulate distant
tissues by means of secretions directly into the circulatory system is
called endocrine signaling
11. • Triiodothyronine (T3) and thyroxine (T4) : role in normal growth,
development, skeletal maturation and bone turnover.
Ganong 2001, Bland 2000
• Hypothyroidism: the bone turnover is slow, bone growth and maturation
are retarded, osteosclerosis, bone fracture
Allain et al 1995, Vestergaard 2002.
• Hyperthyroidism: accelerated bone maturation with reduced bone
mineral density, high bone turnover and a negative Ca balance
Allain et al 1995, Vestergaard 2002
• Alveolar bone resorption is the most important clinical parameter used
to assess the severity of periodontal disease
12. • Limited evidence till now
Thyroid diseases may affect the status of the periodontal diseases, especially in
the hypothyroid condition
13. IL-6 & TNF-α (Major proinflammatory cytokines)
Enters systemic circulation including periodontal tissues
Stimulate resident cells of the periodontium to produce
higher concentration of metalloproteinases
Periodontal breakdown
Combined with endotoxins produced by germs in dental plaque
lead to higher local inflammatory mediator concentrations,
including cytokines and PG
osteoporosis
mediate connective tissue destruction and induce the
differentiation and activation of osteoclasts
14. Results point to the fact that thyroid hormones, in lower or higher
concentrations than normal, might co-induce periodontal disease, by
raising serum and salivary cytokine levels, which activate different
pathways determining alveolar bone and conjunctive tissue
destruction
15. Shaila Kothiwale, Vishal Panjwani
This case report presents a patient with periodontal destruction that is
associated and influenced by hypothyroidism
The report emphasizes the need for frequent professional evaluations,
patient education, and consistent educational reinforcement by health care
providers in patients with hypothyroidism
16. RESULT: thyroid hormones may significantly affect cortical bone healing around
titanium implants. Hyperthyroidism significantly increased the area of newly
formed bone in cortical zone, whereas hypothyroidism significantly decreased
the area of newly formed bone and bone density around the implant in cortical
zone
18. • Parathyroid hormone (PTH): product of chief cells of parathyroid
glands.
• PTH exerts both direct and indirect effects primarily on bone, kidney
and intestine and constantly helps in the maintenance of an optimum
level of endogenous calcium ion concentration in the bloodstream.
• Parathyroid hormone exerts both anabolic and catabolic action on the
bone.
19. An increase in bone
formation via increased
numbers of osteoblasts
Short-term intermittent
exposure to PTH shifts the
osteogenic progenitor cells
from the proliferation to
differentiation
Osteogenic growth factors
and cytokines indirectly help
in the process of
differentiation of
osteoblasts and osteoclasts
and help in the process of
bone anabolism
Insulin like growth factor 1:
stimulate the differentiation
of precursor cells into
mature osteoblasts,
stimulate bone apposition,
and inhibit osteoblast
apoptosis
Fibroblast growth factor:
proliferation of
osteoblast progenitors
and help in bone
apposition
Mechanism of PTH
action on bone at
cellular level
20. Effect of PTH on periodontium
• Primary hyperparathyroidism: adenomas
• Secondary hyperparathyroidism: chronic renal failure, have implicated in
alveolar bone destruction.
• Increased tooth loss and poor oral hygiene
• Brown tumours: diagnosed in primary hyperparathyroidism, cause
dislocation of teeth
• Secondary hyperparathyroidism associated with destructive periodontal
disease.
Frankenthal S, 2002
21.
22. Identical single defects (2 mm diameter) were created in the maxilla and
mandible treated with calcitriol soaked collagen in 60 rats
RESULT: Bone formation rate significantly increased within the
observation period in all groups. Bone regeneration was higher in the
maxilla than in the mandible.
23. The purpose of this study was to examine the effect of secondary HPT
on the periodontium of patients on hemodialysis
CONCLUSION: secondary HPT does not have an appreciable effect on
periodontal indices and radiographic bone height
25. Pancreas secretes 2 hormones:
1. Insulin
2. Glucagon
3. Other hormones: amylin, somatostatin and pancreatic
polypeptide.
2 major type of tissues:
1. Acini: secretes digestive juices into duodenum
2. Islets of Langerhans: secretes insulin & glucagon into the
blood
26. Insulin
• Insulin was first isolated from the pancreas in 1922 by
Banting & Best
• Associated with blood sugar
• Effect on carbohydrate metabolism
• Affects fat and protein metabolism
27. The metabolic disturbances and the resulting disease of
Diabetes mellitus are ultimately the result of a complete or
partial reduction in insulin secretion from the β cells,
impaired insulin action or the destruction of the cells.
DIABETES MELLITUS
29. • Results from cellular mediated
autoimmune destruction of pancreatic β
cells, usually leading to total loss of
insulin secretion
• usually present in children and
adolescents
• ‘‘Insulin-dependent diabetes.’’
• Ketoacidosis, a life-threatening
condition
Type 1
Diabetes
• “Non–insulin dependent diabetes”
• Have altered insulin production however,
autoimmune destruction of β-cells does
not occur and patients retain the
capacity for some insulin production
• The incidence of ketoacidosis is very low
Type 2
Diabetes
32. Association between diabetes
and periodontitis
• Diabetes has been unequivocally confirmed as a major risk factor for
periodontitis
• It was reported that the risk of periodontitis increases to almost
threefold in diabetic patients when compared to healthy individuals.
• NHANES III, adults with an HbA1c level of >9% had a significantly higher
prevalence of severe periodontitis than those without diabetes
33. Mechanism of diabetes influence
on periodontium
These are primarily related to the changes in:
Alterations in subgingival microbiota and GCF
Collagen metabolism, advanced glycation end products (AGEs),
and wound healing
Changes in host immunoinflammatory response
34. Alterations in subgingival microbiota
and GCF
Deepening of periodontal pockets and a shift to a flora
predominated by gram-negative rods and filaments
In type 1 DM subjects, Mashimo et al. reported an increase in
proportions of Capnocytophaga species, while Fusobacterium and
Bacteroides species remained at low levels
Type 2 DM subjects with periodontitis have a fairly similar
microbiota to non-diabetes mellitus periodontitis patients
Zambon et al. demonstrated a different serotype of P. gingivalis in
DM subjects
Nishimura et al. showed decreased chemotaxis of PDL fibroblasts
in response to PDGF when cultured in a hyperglycemic
environment, compared to normoglycemic conditions
Elevated glucose levels in the GCF of individuals with diabetes may, thus, adversely
affect periodontal wound healing and the local host response to microbial
challenge
35. Collagen metabolism
Changes in collagen
synthesis, maturation,
and turnover
Contribute to alterations in
wound healing and to
periodontal disease initiation
and progression
Newly formed collagen is susceptible
to degradation by collagenase, a MMP
which is elevated in diabetic tissues,
including the periodontium
decreased collagen production
and increased collagenase
activity, collagen metabolism is
altered by accumulation of
AGEs in the periodontium
36. Formation of AGEs
• AGEs are proteins or lipids that become glycated as a result of exposure
to sugars
• Constitute a heterogenous group of molecules formed by the non-
enzymatic reaction of reducing sugars, ascorbate and other
carbohydrates with amino acids, lipids peroxidation as well.
• Although this process take place continuously within the body during
aging, it is extremely accelerated in DIABETES
38. Once formed AGEs cause increased collagen cross-linking resulting in the
formation of highly stable collagen macromolecules that are resistance
to normal enzymatic degradation and tissue turn over.
This causes the accumulation of protein at the affected site. In the
blood vessel wall, AGE modified collagen accumulates, thickening the
vessel wall and narrowing the lumen.
Elevated oxidant stress has been suggested as the probable mechanism
responsible for the widespread vascular injury associated with diabetes
39. Wound healing
Wound Healing is Affected as cumulative effect of:
•Altered cellular activity
•Decreased collagen synthesis
•Glycosylation of existing collagen
•Increase collagenase production
Readily degrade newly
synthesized, less completely
cross linked collagen
•Reduced Collagen solubility
•Delayed remodelling of wound
site
Defective Healing
40. Changes in host
immunoinflammatory response
• In DM: reduction in PMN leukocyte function, including chemotaxis,
adherence and phagocytosis
• DM patients with severe periodontitis have depressed PMN leukocyte
chemotaxis compared to DM patients with mild to moderate periodontitis
• Another critical cell line in the periodontal immunoinflammatory
response to pathogens is the monocyte/macrophage line
• Diabetic patients possess a hyper-responsive monocyte/macrophage
phenotype in which stimulation by bacterial antigens such as LPS results
in increased pro-inflammatory cytokine production
• Production of PGE2 and IL-1β is also significantly higher
41. Accumulation of AGEs in the periodontium stimulates migration of monocytes
to the site
In the tissue, AGEs interact with receptors for AGEs (RAGE) on the cell
surfaces of monocytes
AGE–RAGE interaction results in immobilization of monocytes at the local site
Induces a change in monocyte phenotype, upregulating the cell and
significantly increasing pro-inflammatory cytokine production
Increased GCF production of TNF-α, PGE2 and IL-1β
Increases oxidant stress within the tissue, resulting in tissue destruction
AGE formation plays an important role in upregulation of the
monocyte/macrophage cell line
44. DM enhanced bone loss in the presence of OT combined with EP, but did not
increase bone loss in teeth subjected to OT alone. EP caused greater bone loss
when associated with OT
. NIDDM was positively associated with the probability of a change in bone score.
WBS result suggest that NIDDM-associated increased rate of alveolar bone loss
progression
47. • Stress increases circulating cortisol levels through stimulation of the
adrenal gland.(Hypothalamus –pituitary axis)
• The increased exposure to endogenous cortisol may have adverse effect
on the periodontium by diminishing the immune response to periodontal
bacteria.
49. Potential psycho-neuro-immunologic
mechanism
Negative emotions
Polypeptides from sympathetic nor-adrenaline transmitting & sensory
nerve fibres and from endocrine glands
regulate immune responses triggered by bacterial antigens
Corticotropic releasing hormone
ACTH from the pituitary
cortisol
hypothalamus
stimulates
Adrenal cortex release
50. Short-term elevations reduce inflammation and
mobilize immune components
the long-term, may reduce immunocompetency
through inhibition of IgA, IgG, and neutrophil function.
associated with chronic inflammation because the
glucocorticoid loses its ability to inhibit inflammatory
responses initiated by the immune system
inflammation and more destructive periodontitis
51. Potential behavioral mechanism
Stress and depression increase at-risk health
behaviours
Higher cortisol & β endorphin concentrations significantly up regulates
expression of MMP 1,2,7,11 in human gingival fibroblasts
Increased periodontal breakdown
Periodontitis Patricia et al, 2007
54. 7 subjects of different age group and profession were selected.
Unstimulated whole saliva was collected and GCF was sampled on filter disks.
The samples were analysed by a modified RIA method for serum
RESULTS: Higher values were obtained in samples from participants with
periodontitis which included smokers.
55. The frequency and severity of periodontal disease was assessed in a
group of patients with multiple sclerosis receiving corticosteroid
hormone therapy for neurological disease
It was concluded that corticosteroid therapy maintained over 1-4 years
had no obvious influence on clinical parameters of periodontal disease
in patients suffering from neurological disease.
58. Androgens
All natural androgens are derived from a 19-carbon tetracyclic
hydrocarbon nucleus, known as androstane.
One of the most potent androgenic hormones:
testosterone(17-hydroxy-androst-4-en-3-one),
synthesized by testicular Leydig cells,
the thecal cells of the ovary & the adrenal cortex.
59. • Androgens may play a significant role in the maintenance of bone mass
and inhibit osteoclastic function, inhibit PG synthesis and reduce IL-6
production during inflammation.
• Stimulates bone cell proliferation and differentiation and therefore has a
positive effect on bone metabolism
• Testosterone receptors are found in the periodontal tissues and the
number of receptors on fibroblasts tends to increase in inflamed or
overgrown gingiva where it increases matrix synthesis
60. In response to IL-1, chronically inflamed human gingival tissues and
periodontal ligament tissues showed an increase in androgen
metabolic activity and insulin like growth factor stimulated DHT
synthesis in gingiva and cultured fibroblasts
Increasing DHT concentrations progressively reduced IL-6 production
by gingival cells isolated from normal individuals and patients with
gingival inflammation and gingival hyperplasia
Testosterone has inhibitory effects in the cyclooxygenase pathway
of arachidonic acid metabolism in the gingiva by inhibiting
prostaglandin secretion
Kasasa and Soory
Parkar et al
Gornstein et al
These results showed that testosterone may have anti-inflammatory effects
on the periodontium
61. Estrogen
• The naturally occurring estrogens, estrone (3-hydroxyestra-1,3,5[10]-
triene-17-one), estradiol (estra-1, 3,5[10]-triene-3,17-diol) and estriol
(estra-1,3,5[10]triene-3,16,17-triol), are characterized by an aromatic
A ring, a hydroxyl group at C-3 and either hydroxyl groups (C-16 and C-
17) or a ketone group (C-17) on the D ring.
62. • Estradiol : most potent estrogen and is secreted by the ovary, testis and
placenta, as well as by peripheral tissues
• In premenopausal women, the most significant physiologic estrogen is
estradiol
• In both men and postmenopausal women, the most significant plasma
estrogen is estrone.
64. Progesterone
• The natural progestins, or steroids that have progestational activity, are
derived from a 21-carbon saturated steroid hydrocarbon known as
“pregnane”
• The principal progestational hormone secreted
into the bloodstream is progesterone
(pregn4-ene-3,20-dione), which is
synthesized and secreted by the
corpus luteum and placenta
65. • The biological activities of progestins are manifest during the luteal
phase of the menstrual cycle and pregnancy
• Plays a critical role in the maintenance of pregnancy by stimulating
endometrial glandular structure and function, decreasing the
contractility of the myometrium and suppressing the immune system to
prevent rejection of the developing foetus
• It is active in bone metabolism and has significant effect in the coupling
of bone resorption and bone formation by engaging osteoblast receptors
directly
70. Puberty
• Puberty occurs between the average ages of 11 to 14 in most women.
• The production of sex hormones (estrogen and progesterone) increases,
then remains relatively constant during the remainder of the
reproductive phase
71. Clinical & microbial changes
Periodontal tissues may have an exaggerated response to local factors.
A hyperplastic reaction of the gingiva may occur in areas where food debris,
materia alba, plaque, and calculus are deposited.
The inflamed tissues become erythematous, lobulated, and retractable.
Bleeding may occur easily with mechanical debridement of the gingival
tissues.
Histologically, the appearance is consistent with inflammatory hyperplasia
72. • There is chronic regurgitation of gastric contents on intraoral tissues
• This age group also is susceptible to eating disorders, namely, bulimia
and anorexia nervosa
“Perimylosis” (smooth erosion of enamel and dentin): typically on
the lingual surfaces of maxillary anterior teeth, varies with the
duration and frequency of the behavior
73. Menses
The monthly reproductive cycle has two phases:
Follicular phase
• Levels of FSH are elevated
• Estradiol peaks approximately 2 days before ovulation. The effect of
estrogen stimulates the egg to move down the fallopian tubules and
stimulates proliferation of the stroma cells, blood vessels, and glands
of the endometrium
Luteal phase
• Corpus luteum: estradiol and progesterone
• Estrogen peaks at 0.2 ng/mL and progesterone at 10.0 ng/mL to
complete the rebuilding of the endometrium for implantation of the
fertilized egg
• The corpus luteum involutes, ovarian hormone levels drop, and
menstruation ensues
74. Clinical changes in the
periodontal tissue
Ovarian hormones may increase inflammation in gingival tissues and
exaggerate the response to local irritants
Edematous during menses and erythematous before the onset of menses
When the progesterone level is highest, intraoral recurrent aphthous
ulcers, herpes labialis lesions and candidal infections occur
Because the esophageal sphincter is relaxed by progesterone, women
may be more susceptible to GERD
TNF-α, which fluctuates during the menstrual cycle elevated PGE2 synthesis
and angiogenetic factors, endothelial growth factors, and receptors may be
modulated by progesterone and estrogen, contributing to increases in gingival
inflammation during certain stages of the menstrual cycle
75.
76. Premenstrual syndrome (PMS)
• During the peak level of progesterone ( 7-10 days before menstruation)
• Lower levels of certain neurotransmitters such as enkephalins,
endorphins, GABA & serotonin
• Depression, irritability, mood swings, and difficulty with memory and
concentration
• More sensitive and less tolerant of procedures, heightened gag reflex,
exaggerated response to pain
77. Pregnancy
• The link between pregnancy and periodontal inflammation has been
known for many years.
• In 1778, Vermeeren discussed “toothpains” in pregnancy.
• In 1818, Pitcarin described gingival hyperplasia in pregnancy.
• Current research implies periodontal disease may alter the systemic
health of the patient and adversely affect the well-being of the fetus by
elevating the risk for low-birth-weight, preterm infants
78. Periodontal diseases
• The occurrence is extremely common, 30% to 100% of all pregnant women.
• It is characterized by: erythema, edema, hyperplasia,
and increased bleeding
• The anterior region, and interproximal sites
• Pyogenic granulomas (“pregnancy tumors,” pregnancy epulis) occur in 0.2% to 9.6%
of pregnancies
• 2nd or 3rd month of pregnancy
• Bleed easily and become hyperplastic and nodular.
• Sessile or pedunculated and ulcerated, ranging in colour from purplish red to deep
blue, depending on the vascularity of the lesion and degree of venous stasis.
• Occurs in an area of gingivitis and is associated with poor oral hygiene and calculus.
• Alveolar bone loss is usually not associated with pyogenic granulomas of pregnancy
In 1877, Pinard recorded the first case of “pregnancy gingivitis.”
79. Role of pregnancy hormones
SUBGINGIVAL PLAQUE COMPOSITION
Bacterial anaerobic/aerobic ratios increased, in addition to proportions
of Bacteroides melaninogenicus and P. intermedia
Estradiol or progesterone can substitute for menadione (vitamin K) as an
essential growth factor for P. intermedia
An increase in P. gingivalis during the 21st through 27th weeks of
gestation, but this was not statistically significant
Kornman and Loesche
80. PERIODONTAL DISEASE & PRETERM, LOW BIRTH WEIGHT INFANTS
• Untreated periodontal disease in pregnant women may be a significant
risk factor for preterm (<37 weeks’ gestation), low-birth-weight (<2500
g) infants. Offenbacher et al
• The correlation of periodontal disease to PLBW births may occur as a
result of infection and is mediated indirectly, principally by the
translocation of bacterial products such as endotoxin and the action of
maternally produced inflammatory mediators
• PGE2 and TNF-α, are raised to artificially high levels by the infection
process, which may foster premature labor
• Han et al: hematogenous spread of oral bacteria to the amnion
• Madianos et al: oral bacteria crosses the placental barrier and triggered
an immune response by the foetus.
81. Four organisms associated with mature plaque and progressing
periodontitis—T. forsythia, P. gingivalis, A. actinomycetemcomitans,
and Treponema denticola—were detected at higher levels in PLBW
mothers compared with normal-birthweight controls
Preeclampsia: preeclampsia and periodontitis indicated an
increased risk during pregnancy. Preeclampsia is a life-
threatening condition in late pregnancy characterized by
high blood pressure and excess urine protein. High C-
reactive protein levels also are associated with
preeclampsia in this population.
82. The maternal immune system is thought to be suppressed during pregnancy
immunosuppressive factors in the sera of pregnant women can be noted by
marked increase of monocytes
Pregnancy-specific βl-glycoproteins contribute to diminished lymphocyte
responsiveness to mitogens and antigens
a decrease in the ratio of peripheral T helper cells to T suppressor cells
(CD4/ CD8) has been reported to occur throughout pregnancy.
increased susceptibility to developing gingival inflammation
ovarian hormone stimulates the production of PGE1 and PGE2, which are
potent mediators of the inflammatory response
Kinnby et al found that high progesterone levels during pregnancy influenced
plasminogen activator inhibitor type 2 (PAI-2) and disturbed the balance of the
fibrinolytic system.
MATERNAL IMMUNORESPONSE
84. Oral contraceptives
• Mullally et al: current users of OCs had poorer periodontal
health
• When OCP taken for more than 1.5 year it increases
periodontal destruction
86. Menopause
• Menopause is associated with symptoms of estrogen deficiency
• Estradiol levels falls gradually in the years before menopause
• Levels of FSH & LH begin to rise, and levels of sex hormones begin to
fluctuate
• This stage of perimenopause is characterized by increasing ovarian
unresponsiveness, and thus sporadic ovulation ensues
87. Clinical changes in periodontal
tissue
Osteopenia and osteoporosis have been associated with the menopausal
patient
Osteopenia: is a reduction in bone mass caused by an imbalance between bone
resorption and formation, favoring resorption and resulting in demineralization
Osteoporosis: is a disease characterized by low bone mass and fragility and a
consequent increase in fracture risk
88. CONCLUSION
• It is evident that multifactorial mechanisms involving the endocrine
system are involved to a significant degree in the homeostasis of the
periodontium during each of the life stages of the human
• The influence of endocrine hormones in health and in disease is colossal
• Ironically, still there is limited evidence & our understanding of the
effect of these hormones on periodontium is still incomplete
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