ENDOCRINE DISORDERS AND DENTISTRY

I Made Siswadi Semadi

Division of Endocrinology and Metabolism, Department of Internal Medicine,

Faculty of Medicine, Udayana University
 dr. I Made Siswadi Semadi, M.Biomed, Sp.PD, KEMD, FINASIM
Place/DOB : Denpasar, 6th Dec

Office : Division of Endocrinology and Metabolism Department of Internal

Medicine Faculty of Medicine Udayana University/Prof. Ngoerah Hospital

Education : Medical Doctor - Faculty of Medicine Udayana University 2008

Internal Medicine Specialist - Faculty of Medicine Udayana University 2016
Endocrinology, Metabolism, and Diabetes Consultant 2022
 ENDOCRINOLOGY

• Branch of biologic science that is concerned with

the actions of hormones and the organs in which
the hormone are formed
• Its boundaries included study of the anatomy and
physiological function of the major endocrine
organs, the secretory products of these organs,
the mechanisms of hormone action, and the
clinical manifestations of hormone dysfunction
 Endocrine Organs
Adipocytes
Leptin
Adiponectin
etc.

Traditional GI Tract
Endocrine Ghrelin
Organs CCK
GIP
Non- GLP-1,2
Traditional etc.
Endocrine
Organ Kidney
Renin
• Are ductless & secrete hormones into bloodstream Erythropoietin
• Hormones go to target cells that contain receptor
proteins for it Heart
• Neurohormones are secreted into blood by Natriuretic
specialized neurons peptide
• Hormones affect metabolism of targets
Hormone’s Functions

Reproduction

Growth and Development

Energy production, utilization, and

storage

Maintenance of internal environment

Endocrine Pathology

1. Subnormal hormone production

2. Hormone overproduction
3. Production of abnormal hormone
4. Disorder of hormone receptors
5. Abnormalities of hormone transport or metabolism
6. Multiple hormone abnormalities
7. Benign or malignant tumors that produce hormone
 COMMON ENDOCRINE
DISORDER

 DIABETES MELLITUS

 THYROID DISORDER
 HYPOTHYROIDISM
 HYPERTHYROIDISM

 CUSHING SYNDROME
DIABETES MELLITUS
 Outline:

 Epidemiology
 Pathophysiology
 Risk factors
 Clinical features
 Diagnosis
 Management
DEFINITION

 Diabetes mellitus is a group of

metabolic diseases characterized by
hyperglycemia resulting from defects
in insulin secretion, insulin action, or
both.
Epidemiology
 Epidemiology of Diabetes (IDF Atlas, 2019)

Number of people (20-79 years) with Top 10 countries or territories for number of adults
diabetes globally and by IDF Region (20–79 years) with diabetes in 2019, 2030 and 2045
 Diabetes in Indonesia: Prevalence
Basic Health Research, Ministry of Health, 2007, 2013, 2018

94.3 94.3 89.1

DM DM DM

Non-DM Non-DM Non-DM

5.7 6.9 10.9

26.3 34.7 13.8

D-DM D-DM D-DM

UD-DM UD-DM UD-DM

73.7 65.3 86.2

2007 2013 2018

40 36.6
29.9 30.8
30 26.3
>2/3
20
10.2 Undiagnosed
10 DM
0
0
IFG IGT
2007 2013 2018
 Classification of diabetes
Diabetes can be classified into the following general categories
• Type 1 diabetes (due to autoimmune b-cell destruction, usually leading to
absolute insulin deficiency)
• Type 2 diabetes (due to a progressive loss of adequate b-cell insulin
secretion frequently on the background of insulin resistance)
• Gestational diabetes mellitus (diabetes diagnosed in the second or third
trimester of pregnancy that was not clearly overt diabetes prior to
gestation)
• Specific types of diabetes due to other causes, e.g., monogenic
diabetes syndromes (such as neonatal diabetes and maturity-onset
diabetes of the young), diseases of the exocrine pancreas (such as cystic
fibrosis and pancreatitis), and drug- or chemical-induced diabetes (such
as with glucocorticoid use, in the treatment of HIV/AIDS, or after organ
transplantation)

Perkeni 2019; ADA, 2020. Diabetes Care 2020;43(Suppl. 1):S14–S31

Patophysiology
 Pathogenesis of T2DM
Beta cells centric construct: Egregious eleven
The beta cell is a FINAL COMMON DENOMINATOR of beta cell damage

Schwartz SS et al. Diabetes Care 2016;39:179–186

Risk Factors
 Criteria for testing for diabetes or prediabetes
in asymptomatic adults
1. Testing should be considered in overweight or obese (BMI >25 kg/m2 or >23 kg/m2 in Asian
Americans) adults who have one or more of the following risk factors:
• First-degree relative with diabetes
• High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American,
Pacific Islander)
• History of CVD
• Hypertension (>140/90 mmHg or on therapy for hypertension)
• HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL
(2.82 mmol/L)
• Women with polycystic ovary syndrome
• Physical inactivity
• Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis
nigricans)
2. Patients with prediabetes (A1C >5.7% [39 mmol/mol], IGT, or IFG) should be tested yearly.

3. Women who were diagnosed with GDM should have lifelong testing at least every 3 years.

4. For all other patients, testing should begin at age 45 years.

5. If results are normal, testing should be repeated at a minimum of 3-year intervals, with
consideration of more frequent testing depending on initial results and risk status.

Perkeni 2019; ADA, 2020. Diabetes Care 2020;43(Suppl. 1):S14–S31

 Clinical
Features
 Symptoms of DM

Weakness Polyuria Polyphagia

Thirsty Weight loss

Ichy, numbness, blurred vision, impotence

Konsensus Perkeni, 2019
Diagnosis
 Criteria for the diagnosis of diabetes
PG >126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at
least 8 h.*
OR
2-h PG >200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed
as described by the WHO, using a glucose load containing the equivalent of 75
g anhydrous glucose dissolved in water.*
OR
A1C >6.5% (48 mmol/mol). The test should be performed in a laboratory using
a method that is NGSP certified and standardized to the DCCT assay.*
OR
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a
random plasma glucose >200 mg/dL (11.1 mmol/L).
DCCT, Diabetes Control and Complications Trial; FPG, fasting plasma glucose; OGTT, oral glucose tolerance test;
WHO, World Health Organization; 2-h PG, 2-h plasma glucose. *In the absence of unequivocal hyperglycemia, diagnosis
requires two abnormal test results from the same sample or in two separate test samples.

Perkeni 2019; ADA, 2020. Diabetes Care 2020;43(Suppl. 1):S14–S31

 Criteria for the diagnosis of prediabetes

FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (IFG)
OR
2-h PG during 75-g OGTT 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0
mmol/L) (IGT)
OR
A1C 5.7–6.4% (39–47 mmol/mol)

FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired
glucose tolerance; OGTT, oral glucose tolerance test; 2-h PG, 2-h plasma
glucose. *For all three tests, risk is continuous, extending below the lower
limit of the range and becoming disproportionately greater at the higher end
of the range.

Perkeni 2019; ADA, 2020. Diabetes Care 2020;43(Suppl. 1):S14–S31

 Criteria for the Diagnosis of
Diabetes

A1C ≥6.5%

The test should be performed in a laboratory

using an NGSP-certified method standardized
to the DCCT assay*

*In the absence of unequivocal hyperglycemia, result should be confirmed by repeat testing
NGSP : National Glycohemoglobin Standardization Program

ADA, Diabetes Care 2012;35(suppl 1):S11-S63.

Management
Type 2 diabetes is a progressive disease

HOMA: homeostasis model assessment

Lebovitz. Diabetes Reviews 1999;7:139–53 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:1249–58)
 Aim of treatment:
to prevent the complications of diabetes

Non-vascular complications:
❖ Cancer
DIABETES ❖ Infections
❖ Degenerative diseases
❖ Depression
❖ Cognitive disorders
MICROVASCULAR MACROVASCULAR ❖…
COMPLICATIONS COMPLICATIONS*
Diabetes is more
• Coronary heart disease
• Ischaemic stroke than a vascular disease
• Congestive heart failure

Diabetic Diabetic Diabetic Limb

retinopathy nephropathy neuropathy amputation
* The most common cause of
death in patients with
diabetes

Adapted from Grobbee DE. Metabolism 2003; 52: 24–28.

Management of diabetes
Diabetes self-management
education and support (DMSE/S)

Medical nutrition therapy

Physical activity

Medication

Self blood glucose

monitoring
 Medical Nutrition Therapy
Basal calories need: 25-30 kcal/ideal BW
Ideal BW: 90% (height in cm -100) x 1kg

• Carbohydrate 45-60%
• Protein 10-20%
• Fat 20 – 25%
• saturated fat <7%
• Polyunsaturated fat <10%
• Sufficient vitamin & minerals
• Na : <2300 mg/day

Perkeni 2019, ADA, 2020. Diabetes Care 2020;43(Suppl. 1):S14–S31

 Portion of healthy meal for patients
with diabetes
Example from Steno Diabetic Center

Protein
Charbo-
hydrate
Vegeta-
bles Charbo- Vegeta-
Protein hydrate bles

T Form, for Y Form, for

reducing body maintaining body
weight weight

Pedersen DE et al. Arch Intern Med. 2007; 167

Carbohydrate

White sugar, chocolate sugar, Fruits, low fat milk, brown rice,
white brerad, white rice yoghurt, wheat bread
 Protein

Sousage and processed meat,

shrimp, shellfish, red meat Chicken, fish, tofu
Fat

Coconut, margarine, cheese, Avocado, nut, olive oil, unsaturated

coconut oil, rich saturated fat fat
 Physical activity
 Calories or energy expenditure
mostly come from physical
activity
 Adjusted to age and time
availability
 Benefit if done routinely
 Regular, 3-5x/week, 30-45
min/day, total 150 min/week
Behavioral changes
Medications
 Pathophysiology of Type 2 Diabetes:
Therapies
GLP-1s DPP-
4s Insulin β
secretion
Insulin Sulfonylureas

Metformin
Glucose
production
TZDs TZDs Glucose
Insulin uptake
Metformin

α Glucagon GLP-1s
Normoglycemia
secretion GLP-1s
DPP-4s Incretin
effect
DPP-4s

Lipolysis TZDs
Neutransmitter
GLP-1s
function

Glucose
reabsorption
SGLT2s
 Current Antihyperglycemic Medications
TZDs
Glinides Sulfonylureas
alpha- Reduce peripheral Biguanide
Glucosidase Restore postprandial Generalized insulin
secretagogue
insulin
inhibitors insulin patterns Reduces hepatic
resistance
insulin
Delay CHO resistance
absorption

DPP-4 SGLT-2
Inhibitors 12 Different groups with different Inhibitors
mechanisms of action Block renal glucose
Restore GLP-1
reabsorption
Level

GLP-1
Analogs Bromocriptine
Colesevelam
Stimulate beta-cells Insulin Amylin Hypothalamic
Suppress Replacement pituitary reset
Analog Bile acid
glucagon Therapy sequestrant
Suppresses
glucagon
 OAD’s – a quick summary of the different
mechanism of actions

Incretins :GLP-1 analogue (exen-

atide)/DPP-4 inhibitors Improves Thiazolidinediones
glucose-dependent insulin secretion Increase glucose uptake in
from pancreatic β-cells, suppresses skeletal muscle and
glucagon secretion from -cells, slows decrease lipolysis in
gastric emptying adipose tissue

Meglitinides
Increase insulin secretion
from pancreatic -cells

Sulfonylureas
Increase insulin secretion
from pancreatic -cells
-Glucosidase inhibitors
Delay intestinal
carbohydrate absorption

GLP = glucagon-like peptide.

Adapted from Cheng and Fantus. CMAJ. 2005;172:213–226.
 Properties of available glucose-lowering agents that
may guide treatment choice in Type 2 Diabetes

Class Compounds(s) Cellular Primary Advantages Disadvantages

mechanism Physiological
action(s)
Biguanides Metformin Activates Hepatic Glucose Extensive Gastrointestinal side
AMP-kinase Production  Experience effects
No weight gain Lactic acidosis risk
No hypoglycemia (rare)
Likely CVD Events  Vitamin B12
deficiency
Multiple
contraindications:
CKD, acidosis,
hypoxia,
dehydration etc.
Sulfonylureas Glibenclamide / Closes KATP Insulin secretion  Extensive Hypoglycemia
glyburide channels on experience Weight gain
Glipizide beta cell Microvascular Risk  Blunts myocardial
Gliclazide plasme (UKPDS) ischaemic
Glimepiride membranes preconditioning ?
Low durability
Meglitinides Repaglinide Closes KATP Insulin secretion  Postprandial Hypoglycemia
Nateglinide channels on glucose excursions  Weight gain
beta cell Dosing flexibility Blunts myocardial
plasme ischaemic
membranes preconditioning ?
Frequent dosing
schedule

Inzucci SE, et al. Diabetologia. 2012

 Properties of available glucose-lowering agents that
may guide treatment choice in Type 2 Diabetes
Class Compounds(s) Cellular Primary Advantages Disadvantages
mechanism Physiological
action(s)
Thiazolidinedi Pioglitazone Activates the Insulin Sensitivity  No hypoglycemia Weight Gain
ones Rosiglitazone nuclear Durability Oedema / Heart
transcription HDL-C  Failure
factor PPAR-y Triacylglycerols  Bone Fractures
(pioglitazone) LDL-C 
CVD Events ? (rosiglitazone)
Mn  (meta-
analyses,
rosiglitazone)
Bladder Cancer ?
(pioglitazone)
a-Glucosidase Acarbose Inhibits Slows intestinal No hypoglycemia Modest HbA1c
Inhibitors Migitol intestinal a- carbohydrate Postprandial efficacy
Voglibose glucosidase digestions / glucose Gastrointestinal side
absorption excursions  effects (flatulence,
CVD Events  diarrhoea)
Non-systemic Frequent dosing
schedule
DPP-4 Sitagliptin Inhibits DPP-4 Insulin secretion  No hypoglycemia Modest HbA1c
Inhibitors Vildagliptin activity, (glucose-dependent) Well tolerated efficacy
Saxagliptin increasing Glucagon secretion  Urticardia/Angio-
Linagliptin postprandial (glucose-dependent) oedema
Alogliptin active incretin Pancreatitis ?
(GLP-1, GIP)
concentrations

Inzucci SE, et al. Diabetologia. 2012

 Properties of available glucose-lowering agents that
may guide treatment choice in Type 2 Diabetes

Class Compounds(s) Cellular Primary Advantages Disadvantages

mechanism Physiological
action(s)
GLP-1 Exenatide Activates GLP- Insulin secretion  No hypoglycemia Gastrointestinal side
Receptor Liraglutide 1 receptors (glucose-dependent) Weight reduction effects (nausea /
Agents Glucagon secretion  Improved beta vomiting)
(glucose-dependent) cell mass / Acute pancreatitis ?
Slows gastric function ? C cell hyperplasia /
emptying Cardiovascular medullary thyroid
Satiety  protective tumours
actions ? Injectable
Training
Requirements

Insulin Human NPH Activates Glucose disposal  Universally Hypoglycemia

Human Regular insulin Hepatic glucose effective Weight gain
Lispro receptors production  Theoretically Mitogenic effects ?
Aspart unlimited Injectable
Gluisine efficacy Training
Glargine Microvascular Requirements
Determir Risk  (UKPDS) ‘Stigma’ for
Pre-mixed patients
(several types)

Inzucci SE, et al. Diabetologia. 2012

Evaluating a dental patient with known diabetes and undiagnosed diabetes
Managing a patient with diabetes and acute oral infection
DIABETES AND SURGERY
 As indicated by data for general surgery procedures, if the
fasting blood glucose level is below 206 mg/100 mL,
increased risk is not predicted.
 However, if the fasting blood glucose level is between 207
and 229 mg/100 mL, the risk is predicted to be increased by
20% if surgical procedures are being performed.
 Additionally, if the fasting blood glucose level rises to above
230 mg/100 mL, an 80% increased risk of infection
postoperatively has been reported
 What is good glycemic control?
• Overall aim to achieve glucose levels as close to normal as
possible
• Minimise development and progression of microvascular and
macrovascular complications

ADA1 FPG HbA1c PPG

<130 mg/dL < 7.0% <180 mg/dL

IDF2 FPG HbA1c PPG

<110 mg/dl < 6.5% <145 mg/dL

PERKENI3 FPG HbA1c PPG

<100 mg/dl < 7% <140 mg/dl

1. American Diabetes Association Diabetes Care 2009;32 (Suppl 1):S1-S97

2. IDF Clinical Guidelines Task Force. International Diabetes Federation 2005. 3. PERKENI 2011 Konsensus .
 The benefits of good
blood glucose control are clear
Myocardial
Good control is ≤ infarction
7.0% HbA1c
-14%
HbA1c measures the
average
blood glucose level
over the Microvascular
last three months HbA1c complications
-1% -37%

Deaths related
to diabetes

-21%

Source: UKPDS = United Kingdom Prospective Diabetes Study. Stratton IM et al. BMJ. 2000;321(7258):405-412.
THYROID DISORDER
HYPOTHYROIDISM
 Hypothyroidism is an underproduction of
thyroid hormones.
 SIGN & SYMPTOMPS
 fatigue,  dry skin,
 constipation,  periorbital edema,
 Cold intolerance,  prolonged
 muscle cramps, relaxation of deep
 insomnia,
tendon reflexes.
 presence of thyroid
 weight gain,
enlargement is
 carpal tunnel
variable.
syndrome,
 hair loss,
 voice changes, and
slowed thinking.
ORAL MANIFESTATION OF HYPOTHYROIDISM
CAUSE OF HYPOTHYROIDSM
 Primary hypothyroidism
 Thyroiditis
 Hashimotio thyroiditis
 Subacute thyroiditis
 Iodine Deficiency

 Secondary Hypothyroidism: damage to the

hypothalamus or pituitary from tumor,
surgery, radiation, Sheehan syndrome,
and lymphocytic hypophysitis.
DIAGNOSIS & MANAGEMENT
HYPERTHYROIDISM
 Hyperthyroidism is the result of
an excess of thyroid hormones

 Complicates less than 1% of

pregnancies.
 SIGN & SYMPTOMS
 nausea and  weight loss or failed
vomiting, weight gain despite
 increased appetite, increased dietary
 heat intolerance, intake,
 insomnia,  resting tachycardia,
 changes in bowel  hypertension,
habits,  tremor,
 fatigue,  eye stare,
 irritable or anxious  eyelid lag,
mood.  proptosis,
 thyroid enlargement
or nodule.
 CAUSE OF
HYPERTHYROIDISM
 Graves disease  gestational
 hyperemesis trophoblastic disease,
gravidarum/gestational  metastatic thyroid
 transient thyrotoxicosis, cancer,
 solitary hyperfunctioning  struma ovarii,
nodule,  pituitary tumor,
 thyroiditis. In addition,  iodine induced,
 toxic multinodular goiter,  medication
 exogenous thyroid associated.
hormone (iatrogenic or
factitious),
ORAL MANIFESTATION OF HYPERTHYROIDISM
DIAGNOSIS & MANAGEMENT
ROLE OF DENTIST
 Obtaining an understanding of thyroid dysfunction is of
significant importance to the dentist for two reasons.
 First, the dentist may be the first to suspect a serious thyroid
disorder and aid in early diagnosis. The dentist plays an
important role in detecting thyroid abnormalities.
 The second reason is to avoid possible dental complications
resulting from treating patients with the thyroid disorders.
Modifications of dental care must be considered when
treating patients who have thyroid disease.
 One way the dental professional can protect the thyroid
gland is to use a thyroid collar while taking patient X-rays.
The thyroid is extremely sensitive to radiation, and excessive
radiation exposure is a known risk factor for various thyroid
conditions.
 The main complications of patients with hyperthyroidism and
hypothyroidism are associated with cardiac comorbidity.
 Under or over activity of the thyroid gland can cause life-
threatening cardiac events. Consequently, the dental
practitioner must be knowledgeable about thyroid
pathophysiology and the treatment of thyroid conditions
CUSHING SYNDROME
Cushing’s Syndrome
Definitions

❖ Cushing’ Syndrome:
A state of chronic glucocorticoid excess
leading to constellation of symptoms and signs
of hypercortisolism regardless of the cause.

❖Cushing’s Disease:
The specific type of Cushing’s syndrome due to
excessive ACTH secretion from a pituitary
tumor.

❖ Ectopic ACTH syndrome:

type of Cushing’s syndrome due to ACTH
secretion by nonpituitary tumor.
Differential Diagnosis

ACTH-dependent
➢ pituitary adenoma (Cushing’s disease)
➢ non-pituitary neoplasm (ectopic ACTH)

ACTH-independent
➢ Iatrogenic (glucocorticoid, megestrol acetate)
➢ Adrenal neoplasm (adenoma, carcinoma)
➢ Nodular adrenal hyperplasia
• primary pigmented nodular adrenal disease.

• massive macronodular adrenonodular hyperplasia

• food-dependent (GIP-mediated)

➢ Factitious
CLINICAL SYMPTOMS AND SIGNS
OF CUSHING’S SYNDROME
General:
 Central obesity
Endocrine and
 Proximal muscle weakness Metabolic
 Hypertension Derangements:
 Headaches  Hypokalemic alkalosis
 Psychiatric disorders  Osteopenia
 Delayed bone age in
Skin: children
 Wide(>1cm), purple striae  Menstrual disorders,
 Spontaneous echymoses decreased libido,
 Facial plethora
impotence
 Hyperpigmentation  Glucose intolerance,
 Acne diabetes mellitus
 Hirsutism  Kidney stones
 Fungal skin infections  Polyurea
Therapy
Surgery by source Medical
Adrenalectomy Adrenalectomy -
Transphenoidal resection Mitotane
Tumor Resection Glucocorticoid
Antagonists -
Adrenal Enzyme Mifepristone
Inhibitors Somatostatin
Ketoconazole – first line Analogues -
Aminoglutethimide Octreotide
Metyrapone
Etomidate
ROLE OF DENTIST
 Prolonged use and/or high doses of systemic steroids (implicated
in causation of iatrogenic CS) may predispose the patient/client to
secondary adrenal insufficiency, particularly in the context of
abrupt exogenous steroid withdrawal or peri-procedure stress →
using steroid carefuly
 For patients/clients at risk of immunosuppression and hence
infection (e.g., incompletely treated Cushing disease, or prolonged
use and/or high doses of systemic steroids for underlying disease
management) → risk of infection → antibiotics
 Dental/dental hygiene management includes prevention of
infections and prevention of pathologic fractures during chair
transfers and during dental surgery.
Regular communication of dentist with
endocrinologist is a critical component
of safe and optimal treatment of dental
patient with endocrine disorders
Matur Suksma!!