Endocrine Disorders

Causes of endocrine disorders

1. Primary causes

• Originate in the gland responsible for producing the hormone

1. Secondary causes

• Caused by defective levels of stimulating hormones from pituitary gland but normal endocrine gland function

1. Tertiary causes

• Result from hypothalamic dysfunction, affecting pituitary function

All forms of endocrine disturbances can impact oral health and the safe management of dental patients

Pituitary disorders

Growth hormone deficiency

In children:

• Short stature and immature facial features due to lack of growth

• Particularly impacts linear bone growth before epiphyseal fusion

• Delayed puberty and hampered sexual development but normal intelligence

• Impacts mandibular and maxillary growth

• Malocclusion associated with smaller dental arches

• Retarded tooth root and supporting structures development

• Delays in normal eruption and shedding

In adults:

• Primarily affects metabolism

• Destruction of bone cells - fractures and osteoporosis

Growth hormone excess

Pituitary gigantism

• Serious condition that is nearly always caused by adenoma, a tumour of the pituitary gland - secretes GH

• Abnormally large height and weight but normal body proportions

• Abnormal enlargement of the hands and fee (similar to acromegaly)

• Changes in facial features, which can be quite prominent: enlarged forehead and jaw, pronounced underbite, spreading teeth, enlarged tongue, nose and lips

• Hyperglycaemia and overactive beta cells in pancreas - type 2 diabetes

• Death in early adulthood

Acromegaly - ‘enlarged extremities’

• Person cannot grow taller, but bones become thicker or deformed

• Especially marked in bones of hands and feet in membranous bones

• Lower jaw protrusion, slanting forehead, hunchback

• Enlarged soft tissue organs including tongue, liver, heart and kidneys

• Increased risk of bronchitis, diabetes, and heart failure

Characteristic Carnaval changes in acromegaly

• Mandibular prognathism and thickening

• Increased thickness and height of alveolar process

• Spacing and flaring of anterior teeth, with associated malocclusion, enlargement of tongue

• Spiky exostosis-like growths in the alveolar bone as an early sign of acromegaly

• Dentists are well-placed to detect the insidious onset of these craniofacial changes

Antidiuretic hormone deficiency

ADH stimulates water reabsorption in kidneys in response to increased plasma osmolarity

ADH deficiency causes diabetes insipidus - excessive water loss

Xerostomia is the leading oral issue

Thyroid disorders

Hyperthyroidism

Causes:

• Graves’ disease - autoimmune disorder associated with thyroid-stimulating antibodies

• Overactive thyroid nodules or thyroiditis

• Too much iodine

• Non-cancerous tumour of the pituitary

Common signs and symptoms

• Increased skin temperature and excessive sweating

• Tachycardia or irregular heart rate

• Tiredness and muscle weakness but difficulty sleeping

• Twitching or trembling

• Nervousness, anxiety, irritability

• Exophthalmos (protruding eyes with lid retraction)

• Increased sensitivity to catecholamines

Hypothyroidism (acquired)

• Caused by surgery, drugs such as lithium, excessive amounts, or lack, of iodine

• Hashimoto’s thyroiditis most common cause - autoimmune disease where an autoimmune reaction may be completely destroyed with the thyroid gland - more common in women

• Impact related to hypometabolism (fatigue, weight gain despite loss of appetite, cold intolerance etc.) - affects almost all organ systems

• Severely advanced form - myxoedema (‘puffy’ appearance) can lead to myxoedema crisis

Hypothyroidism (congenital)

• Previously known as cretinism

• Partial or complete loss of thyroid gland function in infants

• Most common cause is shortage of iodine in mother’s diet; 15-20% genetic causes

• If untreated, can lead to impaired neurological function, stunted growth, and physical deformities

• Thickening of lips and macroglossia due to increased accumulation of subcutaneous mucopolysaccharides

• In older children and adults: slowing metabolic processes and myxoedema - ranges from being mild to life-threatening

Parathyroid glands

Hyperparathyroidism

• Usually caused by a tumour or hyperplasia of the gland

• Key sign is bone lesions associated with excessive osteoclast activity

• Malocclusion due to drifting with definite spacing of teeth may be one of the first signs

• Higher risk of bone structure

Hypoparathyroidism

• Mainly affects nerve and muscle activity

• Enamel hypoplasia, delayed eruption, and there may be multiple unregulated teeth

• More prone to dental caries

Adrenal disorders

Addison disease

• Primary adrenal cortical insufficiency

• Caused by autoimmune disorder, infection (TB), trauma, cancer or haemorrhage

• Glucocorticoid deficiency - poor stress tolerance, hypoglycaemia, lethargy, weakness, nausea, vomiting

• Mineralocorticoid deficiency - dehydration, low blood pressure, fatigue

• High ACTH levels in primary adrenal insufficiency - skin hyperpigmentation (darkening)

• Hyperpigmentation in the palate and depapillation of the tongue

Treatment

• Relies on hormone replacement

• BUT: long-term corticosteroid therapy (>14 days) can suppress adrenal function (secondary adrenal insufficiency - very common)

• Limited ability of adrenal cortex to deal with stress - predisposing factor of acute adrenal insufficiency (Addison/adrenal crisis)

• Stress reduction protocol, effective anaesthesia and postoperative analgesia are very important in these situations

• Supplemental doses of corticosteroids can be used to help the body cope with stress

Cushing syndrome

Disorder resulting from long term excess cortisol

ACTH-dependent hypercortisolism from

• Hypersecretion of ACTH by the pituitary gland due to pituitary adenoma (Cushing disease)

• Secretion of ACTH by a nonpituitary tumour, such as small cell lung carcinoma or carcinoid tumour (ectopic ACTH syndrome)

ACTH-independent hypercortisolism

• Therapeutic administration of exogenous corticosteroids (e.g. prednisone) for treatment of inflammatory diseases (most common)

• Adrenocortical adenomas or carcinomas

Signs are basically exaggerated actions of cortisol

• Altered fat metabolism and abnormal fat distribution

• Rounding and puffiness of the face (moon face)

• Protein breakdown and muscle wasting

• Thin and easily bruising skin

• Osteoporosis due to calcium resorption

• Deranged glucose metabolism- hyperglycaemia and increased insulin requirement - may lead to diabetes

• Immune suppression - increased susceptibility to infection

• Increased gastric acid secretion - gastric ulceration

• Emotional and sleep disturbances (depression-like)

Dental concerns

• Immune suppression and increased risk of infection, as well as alveolar bone loss and impaired wound healing

• Comorbidities such as obesity, osteoporosis, and diabetes may influence periodontal attachment apparatus

Diabetes mellitus

• Metabolic condition from imbalance between the body’s need for glucose and the availability/effectiveness of insulin

• Lack of secretion or reduced activity of insulin - compromised transport of glucose into fat and muscles cells —>blood sugar remains high

• Increased fat and protein breakdown to compensate and provide an energy source for these cells

• Discovery of insulin in 1922 transformed it from being fatal disease into a manageable condition

Type 1 Diabetes

• Characterised by destruction of insulin-producing pancreatic beta cells

• Type 1A: immune-mediated - autoimmune destruction of pancreatic beta cells with a total lack of insulin, elevated blood glucose levels, and breakdown of body fat and proteins

• Antibodies to insulin and pancreatic beta cells even before onset disease

• Type 1B: idiopathic - arises spontaneously with causes unknown but strong inheritance link

• Type 1 diabetes prone to ketoacidosis

• Free fatty acids converted to ketones in the liver

• Insulin normally inhibits lipolysis and release of free fatty acids from adipocytes

• Without insulin, ketone conversion happens in an uncontrolled manner, leading to ketoacidosis

• Need insulin replacement to stop fat and protein catabolism and prevent ketoacidosis

Type 2 Diabetes

• Heterogenous condition primarily considered a lifestyle disease - not associated with autoantibodies

• Disorder of both insulin levels (beta cell dysfunction) and insulin function (insulin resistance) —> hyperglycaemia and wide-ranging complications

• Glucosuria

• Polyuria due to osmotic pull of glucose in urine and/or diuretic effect of certain medications

• Inflammatory processes in dysfunctional visceral adipose tissue - systemic inflammation and insulin resistance

• Unregulated insulin production in beta cells to overcome diminished insulin action

• Over time, increasing beta cell dysfunction and exhaustion

• Some develop absolute insulin deficiency and require insulin therapy

Other specific types of diabetes

• Formerly as secondary diabetes and describes diabetes associated with other conditions and syndromes

• May occur with

  • Pancreatic disease

  • Endocrine disorders, such as GH excess

  • Environmental agents, including viruses (e.g. mumps) and chemical toxins (e.g. nitrosamines)

  • Various drugs, including diuretics and antiretroviral therapy

  • Polycystic ovarian syndrome

  • Pregnancy (gestational diabetes)

Diabetes Diagnosis and Treatment

Diagnostic tests

• Blood tests based on fasting or casual plasma glucose levels or a glucose challenge test

• Capillary blood tests valuable for near-patient testing in diabetic patients - used in the dental clinic

  • Normal: 4 to 6 mmol/L

• Glycated haemoglobin test (HbA1c) - how much glucose is bound to red blood cells (6.5+% = diabetes, 5.7-6.4% = prediabetes, below 5.7% = normal)

• Indirect measure of average blood sugar level over last 2 to 3 months - lifespan of RBCs app. 120 days

• Assesses long-term glycemic control

Lifestyle management

Desired outcome for both type 1 and 2 diabetes - normalise blood glucose levels.

Type 1

• Food intake assessed and used as a basis for adjusting insulin replacement therapy

• Good routine required for balance between insulin administration, carbohydrate intake, and glucose levels

Type 2

• Type 2 diabetics need to target glucose, lipid and blood pressure goals, as well as weight loss if required

Drug management

Metformin

First line therapy where residual insulin is present

• Increases glucose uptake in muscle, inhibits hepatic glucose output, and decreases GI absorption

• Can cause anorexia and encourage weight loss

• Low risk hypoglycaemia

SGLT2i

Sodium glucose co transporter 2 inhibitors

• Increases renal excretion of glucose - osmotic effect can cause hypovolaemia, thirst and xerostomia

• Good cardiovascular protective effect

Sulfonylureas

E.g. tolbutamide

• Stimulate insulin secretion and appetite - may cause hypoglycaemia and weight gain

Insulin replacement therapy

• Mixtures of different formed of insulin are available in fixed proportions, e.g. mixture of short-and intermediate-acting insulin twice daily

• Problem: potential for hypoglycaemia

• Too much insulin relative to carbohydrate intake - blood glucose levels drop too low - brain deprived of its energy source —> insulin coma and permanent brain damage if severe

• Treatment: a sweet drink or snack; IV glucose or IM glucagon if unconscious

GLP-1 receptor agonists (semaglutide, ozempic)

• Mimics glucose-lowering action of incretins reduces body mass

GLP-1/GIP dual agonist (tirzepatide)

• Synergistic effects of GLP-1 and GIP agonists outperform GLP-1R mono agonism

DPP-4i (gliptins) - dipeptidyl peptidase-4 inhibitor

• Inhibit the enzyme that metabolises incretin hormones - elevate endogenous incretins

• Incretins - gastrointestinal peptides with blood glucose-lowering effects - reduced levels in diabetics

• Glucagon-like peptide-1 (GLP-1) and glucose-dependent insukinotropic polypeptide (GIP)

• Stimulate insulin secretion, slow gastric emptying, and reduce appetite and energy intake

Osteoporosis and PCOS

Osteoporosis

• Oestrogens normally promote apoptosis (death) of osteoclasts

• Decrease in bone mass with diminishing hormone levels, particularly after menopause

• Bone resorption by osteoclasts outpaces bone deposition by osteoblasts

• Demineralisation can begin at 30 in females and 60 in males

• Other contributing factors

  • Poor diet

  • Lack of exercise

  • Smoking

  • Diabetes

• Osteoporosis medications, including bisphosphonates (e.g. alendronate) and RANK ligand inhibitors (e.g. Denosumab) decrease osteoclast activity/bone resorption

• Potential problem of medication- related osteonecrosis of the jaw (MRONJ) associated with the use of these medications

• Osteonecrosis: non-healing exposed bone in the maxillofacial region, which may occur following oral surgery

• MRONJ pathophysiology not completely elucidated

• Tooth extraction a ‘common’ factor but teeth commonly had existing periodontal or periapical disease

• Greater risk with the IV antiresorptive medications as opposed to oral and chronic use

Polycystic ovarian syndrome (PCOS)

• PCOS is most common endocrine disorder among women of reproductive age - up to 26% in western societies

• Substantial negative effects on metabolic, psychologic, and cardiovascular health

• Irregular or absent menstrual periods, infertility, and symptoms like acne and excess hair growth, and/or unintended weight gain

• Associated with other comorbidities (insulin resistance, obesity, cardiovascular disease, and periodontal disease)

• Mechanisms include altered secretion of GnRH, defect in androgen synthesis, and development of insulin resistance

• Presence of many small, fluid filled sacs or cysts inside the ovaries in the case of PCOS

WRAP UP

Thyroid disorders - oral manifestations

Hypothyroidism in dental practices

Considerations for dental practice

• Generally tolerate dental treatment well

• Poor cardiovascular health may be primary consideration

• Delayed wound healing due to decreased fibroblast activity - susceptibility to infections

• Sedatives (benzodiazepines) and opioids to be used with caution - increased sensitivity to their action

• Patients more prone to caries and periodontal disease, as well as other oral problems, such as burning mouth syndrome

• Patients very sensitive to adrenaline-containing products - hypertensive crisis

• Increased levels of anxiety - stressful dental procedures can elicit life-threatening thyrotoxic crisis (syndrome caused by high levels of thyroid hormone)

• Particularly for invasive dental therapy, best to liaise with physician to see how well controlled the condition is

Parathyroid glands - oral manifestations

Pregnancy - Oral health

• Pregnancy gingivitis most common - mainly due to oestrogen and progesterone enhancing the inflammatory response

• Possible painless tumour like growths - pregnancy granulomas (epulis gravidarum) - normally regress following parturition

• Increased risk of caries - mainly due to

  • Food cravings and snacking

  • Reduced oral hygiene (increased gag reflex, fatigue etc.)

  • Morning sickness

  • Hormone induced xerostomia

Avoidance of dental visits mostly due to concerns about baby’s health

Pregnancy considerations

• Routine dental care is not only safe but likely to benefit both mother and child

• Weeks 14-20 most comfortable times for dental visits

• Drug use always a concern - exercise caution, particularly during first trimester

• Good safety records for lignocaine and mepivacaine have

• A few antibiotics (e.g. amoxicillin) and antifungals (e.g. nystatin) may be used

• Paracetamol is preferred analgesic - if required nitrous oxide may be used with medical consultation

Menopause

Declining levels of oestrogen and progesterone impact oral health

Use of hormone replacement therapy is controversial

Good oral hygiene practices are essential

• Thinning of oral mucosa

  • Increased risk of burning mouth syndrome

  • Hyposalivation and xerostomia

• Periodontium more prone to inflammation

  • Increased prevalence and severity of periodontitis

• Increased osteoclast activity

  • Risk of osteoporosis and exacerbated alveolar bone reabsorption

PCOS - dental concerns

• Low grade chronic systemic inflammation - possible link to periodontal disease

• Gingivitis difficult to treat due to underlying inflammation —> gum sensitivity, bleeding gums, halitosis (bad breath), receding gums, bone loss around teeth, tooth loss

• Altered sex hormones may impair epithelial barrier to bacterial injury or compromise collagen maintenance and repair

•  Decline of oestrogen with aging - risk of bone loss density

• Suspect PCOS  if patients struggle with receding gums, difficult chewing and tooth loss despite good oral hygiene

• Good oral hygiene important in managing symptoms of PCOS

• Prevention includes special care of teeth and gums, brushing, flossing, antiseptic mouthwash, and bi-annual dentist visits

Diabetes in the dental practice

Oral signs of diabetes

• Xerostomia due to polyuria and associated dehydration

• Increased rates (~3 fold) and severity of periodontal disease in type 1 and 2 diabetes

• Increased incidence of root caries - possibly due to increased root exposure from periodontitis combined with xerostomia

• Xerostomia + high salivary glucose levels + impaired immune function - more prone to oral infections and mucosal disorders e.g. lichen planus and burning mouth syndromes

• Vascular and immune dysfunction - poor wound healing

• Good oral health management essential and may improve diabetic control

Diabetes and dentistry

Periodontitis as a formal complication of diabetes?

Two way link between periodontal disease and diabetic control

Diabetic patients more prone to oral infections and caries

Delayed wound healing in diabetic patients

Need to be able to manage diabetic emergencies

AGEs and periodontal disease in diabetes

• Advanced glycation end products (AGE): proteins or lipids that become glycated after exposure to sugars - pro- inflammatory mediators and link diabetes to periodontal disease - excessive formation in diabetes

• AGEs bind to receptors and accumulate in periodontal tissue —> accumulation of inflammatory mediators

• Cascade of cytokine up-regulation, further increasing levels of pro-inflammatory cytokines

• Inflammation-mediated activation of osteoclasts and destruction of oral tissues

• Uncontrolled diabetes strongly correlated to increased alveolar bone loss

• Main element responsible for the development of micro and macro vascular complications in DM