31/10/2025 1  Endocrine and Metabolic Disorders Dr Lalima Tiwari, Oral Medicine Specialist Learning Outcomes  Understanding of the oral manifestations of systemic disease and care of the medically compromised patient  Disorders affecting the  Pancreas – Diabetes Mellitus  Adrenal Glands – Cushing’s syndrome, Addison’s disease  Thyroid glands – Grave’s disease, Hashimoto’s thyroiditis  Pituitary glands – Gigantism, Acromegaly  Parathyroid glands – Hyperparathyroidism, Hypoparathyroidism  Pregnancy  Disorders of the Pancreas  Two essential functions:  Endocrine  Exocrine  Endocrine activity:  Insulin  Proinsulin  Amylin  C-peptide  Somatostatin  Pancreatic polypeptide  Glucagon  Exocrine activity:  Proteolytic pancreatic enzymes that support digestion of food in the intestine  Trypsin  Chymotrypsin  Carboxypeptidase  Elastase 1 2 3  #### Learning Outcomes - Understanding of the oral manifestations of systemic disease and care of the medically compromised patient - Disorders affecting the: - Pancreas – Diabetes Mellitus - Adrenal Glands – Cushing’s syndrome, Addison’s disease - Thyroid glands – Grave’s disease, Hashimoto’s thyroiditis - Pituitary glands – Gigantism, Acromegaly - Parathyroid glands – Hyperparathyroidism, Hypoparathyroidism - Pregnancy #### Disorders of the Pancreas The pancreas performs two essential functions: endocrine and exocrine activity. **Endocrine Activity** The endocrine system involves the secretion of: - Insulin - Proinsulin - Amylin - C-peptide - Somatostatin - Pancreatic polypeptide - Glucagon **Exocrine Activity** The exocrine system involves proteolytic pancreatic enzymes that support the digestion of food in the intestine: - Trypsin - Chymotrypsin - Carboxypeptidase - Elastase A diagram illustrating the anatomy of the pancreas, showing its position relative to surrounding organs like the duodenum, liver, and stomach. The diagram labels key structures such as the pancreatic duct, cystic duct, and various parts of the pancreas including the head, body, and tail, along with associated ducts like the common bile duct and accessory pancreatic duct. 31/10/2025 **Disorders affecting Pancreatic Functions** - **Inflammatory Diseases** - Chronic and acute pancreatitis - Exocrine pancreatic insufficiency - Enzymes produced by pancreas start working before they reach small intestine - Inflammation in the gland disrupts insulin production - **Neoplastic Diseases** - Pancreatic neuroendocrine tumours - Pancreatic cancer - **Cystic Fibrosis** - Damage to pancreatic ducts - Pancreatic gland cells breakdown and become fibrotic - Thickened mucus accumulates in the area of pancreatic ducts resulting in pancreatic exocrine and endocrine insufficiency - **Obesity** - Pathological accumulation of adipose tissue in the body - Associated with exocrine pancreatic insufficiency - Associated with increased risk of pancreatic cancer --- **Diabetes Mellitus** - Diabetes Mellitus (DM) is a metabolic disease commonly characterised by an elevation of the blood glucose levels - Pancreatic beta cells produce insulin which facilitates absorption of glucose into cells. - DM occurs due to lack of insulin production or insulin sensitivity - Most common types: - Type 1 DM: associated with failure in insulin production resulting from destruction of pancreatic beta cells by T-cell mediated autoimmunity - Type 2 DM: characterised by insulin resistance and reduction of insulin production - It is important that all forms of diabetes to be diagnosed and managed at early stage to prevent or slow down potential complications --- **Oral manifestations of Diabetes Mellitus** - More than 90% of diabetic patients suffered from oral complications - Possible mechanism that may be related to oral complications of diabetes include impaired neutrophil function, increased collagenase activity, reduction in collagen synthesis, microangiopathy and neuropathy **TABLE 1. Prevalence of Oral Manifestations in Controlled and Uncontrolled Diabetes (9)** | Oral Manifestation | Prevalence in Controlled Type 2 Diabetes (%) | Prevalence in Uncontrolled Type 2 Diabetes (%) | | --- | --- | --- | | Hyposalivation | 68 | 84 | | Halitosis | 52 | 76 | | Periodontitis | 32 | 48 | | Burning mouth sensation | 32 | 24 | | Candidiasis | 28 | 36 | | Taste alteration | 28 | 44 |   #### Inflammatory Diseases - Chronic and acute pancreatitis - Exocrine pancreatic insufficiency - Pathophysiology: Enzymes produced by the pancreas start working before they reach the small intestine - Inflammation in the gland disrupts insulin production #### Neoplastic Diseases - Pancreatic neuroendocrine tumours - Pancreatic cancer #### Cystic Fibrosis - Damage to pancreatic ducts - Pancreatic gland cells breakdown and become fibrotic - Thickened mucus accumulates in the area of pancreatic ducts resulting in pancreatic exocrine and endocrine insufficiency #### Obesity - Pathological accumulation of adipose tissue in the body - Associated with exocrine pancreatic insufficiency and increased risk of pancreatic cancer #### Diabetes Mellitus Overview - Metabolic disease characterized by an elevation of blood glucose levels. - Mechanism: Pancreatic beta cells produce insulin which facilitates absorption of glucose into cells. DM occurs due to lack of insulin production or insulin sensitivity. - Type 1 DM: Failure in insulin production resulting from destruction of pancreatic beta cells by T-cell mediated autoimmunity. - Type 2 DM: Characterized by insulin resistance and reduction of insulin production. - Clinical Importance: Early diagnosis and management are essential to prevent or slow down potential complications. #### Prevalence of Oral Manifestations More than 90% of diabetic patients suffer from oral complications. Mechanisms include impaired neutrophil function, increased collagenase activity, reduction in collagen synthesis, microangiopathy, and neuropathy. | Oral Manifestation | Prevalence in Controlled Type 2 Diabetes (%) | Prevalence in Uncontrolled Type 2 Diabetes (%) | | :--- | :---: | :---: | | Hyposalivation | 68 | 84 | | Halitosis | 52 | 76 | | Periodontitis | 32 | 48 | | Burning mouth sensation | 32 | 24 | | Candidiasis | 28 | 36 | | Taste alteration | 28 | 44 | A flowchart diagram illustrating the relationship between diabetes mellitus and various disorders affecting pancreatic functions, including inflammatory diseases, neoplastic diseases, cystic fibrosis, and obesity. The diagram categorizes these conditions and their impacts on pancreatic functions such as insulin production and exocrine insufficiency. A table titled 'TABLE 1. Prevalence of Oral Manifestations in Controlled and Uncontrolled Diabetes (9)' that lists various oral manifestations of diabetes mellitus, such as hyposalivation, halitosis, periodontitis, burning mouth sensation, candidiasis, and taste alteration, with their prevalence percentages in controlled and uncontrolled type 2 diabetes patients. 31/10/2025 **Oral manifestations of Diabetes Mellitus** - Dry mouth - Xerostomia (80%) and salivary gland hypofunction - Prevalence: 52-76% - Highest level of salivary gland hypofunction is observed in diabetics with poor glycaemic control - Reduced salivary flow as a result of polyuria and dehydration - Studies have found that urea and glucose levels in saliva were significantly higher in DM patients than healthy subjects - Salivary glucose promotes proliferation and colonization of bacteria in oral cavity - Glucose is basis for candida development and decrease in neutrophil activity - Results in dysgeusia, dental caries, oral pain, dysphagia, lower quality of life **Oral Manifestations of Diabetes Mellitus** - Dental Caries - Development of new and recurrent dental caries - Reduced cleansing and buffering capacity of saliva - Increase of carbohydrate in saliva - Increase level of oral yeast, streptococci mutans and lactobacilli - Lead to increase in incidence of tooth decay - Chronic hyperglycaemia may cause irreversible pulpitis - Periapical pathology - Higher prevalence of periapical lesions in patients with poorly controlled diabetes - DM patients have lower success rate of endodontic treatment **Oral manifestations of Diabetes Mellitus** - Periodontal disease - Most common oral manifestation - Poor glycaemic control associated with outbreak and progression of gingivitis, periodontitis, alveolar bone loss - Prevalence of severe periodontitis in diabetic patients compared to non-diabetic patients: 59.6% vs 39% - Possible mechanisms: - Alterations in host defence response (neutrophil dysfunction) - Subgingival microflora - Structure and metabolism of collagen - Vascularity and gingival crevicular fluid - Risk factors: poor oral hygiene, poor metabolic control, longer duration of diabetes, smoking - Elimination of pathogens by treatment leads to decrease of inflammation, which in turn reduces insulin resistance = reduction in glucose levels. - Two – way relationship    #### Salivary Gland Hypofunction and Xerostomia - Prevalence: 52-76% (Xerostomia observed in up to 80% of cases). - Highest level of hypofunction is observed in diabetics with poor glycaemic control. - Reduced salivary flow results from polyuria and dehydration. - Salivary Composition: Urea and glucose levels in saliva are significantly higher in DM patients. - Impact: Salivary glucose promotes bacterial colonization and candida development; results in dysgeusia, dental caries, oral pain, dysphagia, and lower quality of life. #### Dental Caries and Pulpal Pathology - Increased incidence of new and recurrent dental caries due to reduced cleansing/buffering capacity of saliva and increased carbohydrate/yeast levels (Streptococci mutans and lactobacilli). - Chronic hyperglycaemia may cause irreversible pulpitis. - Higher prevalence of periapical lesions in poorly controlled diabetes with lower success rates for endodontic treatment. #### Periodontal Disease - Most common oral manifestation. - Prevalence: Severe periodontitis in diabetic vs. non-diabetic patients is 59.6% vs. 39%. - Mechanisms: - Alterations in host defence (neutrophil dysfunction) - Changes in subgingival microflora - Altered collagen structure and metabolism - Vascularity changes and gingival crevicular fluid alterations - Two-way relationship: Elimination of pathogens reduces inflammation, which reduces insulin resistance and glucose levels. A close-up photo of teeth showing periodontal disease, illustrating alveolar bone loss and gingival inflammation. This image is used to visually represent the severe periodontitis prevalence in diabetic patients compared to non-diabetic patients. A photo showing dental caries, highlighting the development of new and recurrent cavities. This image supports the discussion on reduced salivary cleansing and buffering capacity in diabetic patients. A photo of a tongue with a dry, cracked appearance, illustrating xerostomia and salivary gland hypofunction. This visual aids in explaining the high prevalence of dry mouth in diabetic patients. ```markdown 31/10/2025 ## Oral Manifestations of Diabetes Mellitus ### Oral Infections - Fungal, bacterial infections - Decreased salivary flow rate, absence of antimicrobial effects in addition to impaired defence mechanism and poor metabolic control play important role in developing infection - Higher rates of candida colonization reported in T1DM compared to T2DM (84% vs 68%), 27% in non-diabetics - Candida related lesions: denture stomatitis, angular cheilitis, median rhomboid glossitis common - Most common in diabetic patients who smoke, wear dentures, have poor glycaemic control, and use steroids and broad-spectrum antibiotics --- ## Oral Manifestations of Diabetes Mellitus ### Burning Mouth - Attributed to poor glycaemic control, metabolic alterations in oral mucosa, angiopathy, candida infection and neuropathy ### Taste dysfunction - Seen in poorly controlled diabetes - Sweet or salty taste disorder - Salivary dysfunction can contribute to altered taste sensation --- ## Oral Manifestations of Diabetes Mellitus ### Oral mucosal alterations - Coated, fissured tongue - Recurrent aphthous stomatitis - Oral lichen planus/oral lichenoid dry reaction - Controversial ### Poor wound healing - Well-known complication during oral surgeries - Delayed vascularization, diminished blood flow and hypoxia, reduction in innate immunity, decreased growth factor production, psychological stress ```   #### Oral Infections - Fungal and bacterial infections are common due to decreased salivary flow, impaired defense mechanisms, and poor metabolic control. - Candida colonization: Higher in T1DM (84%) than T2DM (68%); non-diabetics at 27%. - Common lesions: Denture stomatitis, angular cheilitis, and median rhomboid glossitis. - Risk factors: Smoking, denture use, poor glycaemic control, steroids, and broad-spectrum antibiotics. #### Sensory and Mucosal Alterations - **Burning Mouth:** Attributed to poor glycaemic control, metabolic alterations in mucosa, angiopathy, candida infection, and neuropathy. - **Taste Dysfunction:** Sweet or salty taste disorders seen in poorly controlled diabetes; exacerbated by salivary dysfunction. - **Mucosal Changes:** Coated or fissured tongue, recurrent aphthous stomatitis, and oral lichen planus/lichenoid reactions (though controversial). #### Wound Healing - Delayed vascularization, diminished blood flow, and hypoxia. - Reduction in innate immunity and growth factor production. - Psychological stress also contributes to poor healing outcomes during oral surgeries. A photo showing three oral lesions, labeled A, B, and C, illustrating candida-related conditions such as denture stomatitis, angular cheilitis, and median rhomboid glossitis, with a caption indicating the image is from Rohani et al., 2019. A photo displaying two oral lesions, labeled A and B, depicting oral lichen planus or lichenoid reactions, with a caption referencing the image source as Rohani et al., 2019. 31/10/2025 **Dentists' role in caring for patients with Diabetes Mellitus** - Diabetes is a common disease with concomitant oral manifestations that can modify dental care needs - Be familiar with diagnosis and prevention techniques - Effective management of diabetic patients - Cooperation between patient, doctor, dentist - Regular check-ups will allow dentists to anticipate patient needs and interact competently with other health care professionals - Careful examination of oral cavity including mucosa, periodontal inflammation, bleeding and general state of teeth **Disorders of the Adrenal Glands** - Adrenal glands major regulators of body homeostasis and endocrine stress response - Three morphologically and functionally distinct compartments - Outer zona glomerulosa: produces aldosterone - Zona Fasciculata: glucocorticoid synthesis, production of cortisol - Zona reticularis: adrenal androgens: androstenedione, DHEA - Dysregulation of signalling pathways in adrenal cortex associated with development of adrenal tumours **Disorders of the Adrenal Glands** - Cushing syndrome - Prolonged elevation in plasma cortisol - Exogenous: glucocorticoid use - Endogenous: benign pituitary adenoma, benign or malignant adrenal tumours - Estimated prevalence: 2-3 per million to 8 per million persons, annually Image from: National Institute of Diabetes and Digestive and Kidney Disease <img src="https://i.imgur.com/7X5hL0l.png" alt="Adrenal gland anatomy diagram showing the adrenal gland, its relationship with the kidney, and its three zones: zona glomerulosa, zona fasciculata, and zona reticularis, along with the adrenal medulla. Labels point to the capsule, adrenal cortex, and adrenal medulla."> <img src="https://i.imgur.com/7X5hL0l.png" alt="Diagram illustrating the hypothalamic-pituitary-adrenal (HPA) axis. It shows the hypothalamus releasing CRH, which stimulates the pituitary gland to release ACTH, which in turn stimulates the adrenal gland to release cortisol. Arrows indicate the direction of hormone flow and feedback loops.">   #### Professional Responsibilities - Dentists must be familiar with diagnosis and prevention techniques for DM-related oral manifestations. - Management requires cooperation between the patient, physician, and dentist. - Regular check-ups facilitate anticipation of patient needs and inter-professional interaction. - Clinical focus: Examination of mucosa, periodontal inflammation, bleeding, and general tooth state. A diagram showing the adrenal gland anatomy, illustrating its relationship with the kidney and the three zones of the adrenal cortex: zona glomerulosa, zona fasciculata, and zona reticularis, along with the adrenal medulla. Labels point to the capsule, adrenal cortex, and adrenal medulla. A diagram illustrating the hypothalamic-pituitary-adrenal (HPA) axis, showing the hypothalamus releasing CRH, which stimulates the pituitary gland to release ACTH, which in turn stimulates the adrenal gland to release cortisol. Arrows indicate the direction of hormone flow and feedback loops. ```markdown 31/10/2025 --- **Cushing Syndrome** Image from: Reinke et al., 2023 --- **Oral manifestations of Cushing’s syndrome** - Increased risk of developing periodontal disease - Inhibit new bone formation - Delayed wound healing - Osteoporosis of jaw bone - Higher risk of oral candidiasis, recurrent aphthous ulcers --- **Dental considerations in Cushing’s syndrome** - Obtain comprehensive medical records in patients with CS, including the dosage and frequency of glucocorticoids. - OHCPs should avoid the abrupt discontinuation of corticosteroids and consult with the patients’ physicians. - Be aware of drug interactions with patients who are taking glucocorticoids. - Monitor vital signs at baseline and during dental procedures to avoid hypertensive episodes. - OHCPs should carefully evaluate pain management with aspirin and NSAIDs in patients with CS at risk of peptic ulcer. --- <img src="https://i.imgur.com/placeholder.png" alt="Cushing Syndrome Symptoms Diagram" /> --- ```    #### Pathophysiology and Prevalence - Characterized by prolonged elevation in plasma cortisol. - Exogenous cause: Glucocorticoid use. - Endogenous causes: Benign pituitary adenoma, or adrenal tumours (benign/malignant). - Estimated prevalence: 2-8 per million persons annually. #### Oral Manifestations - Increased risk of periodontal disease. - Inhibition of new bone formation leading to osteoporosis of the jaw bone. - Delayed wound healing. - Higher risk of oral candidiasis and recurrent aphthous ulcers. #### Dental Management Considerations - Obtain comprehensive medical records, including dosage and frequency of glucocorticoids. - Consult with physicians; avoid abrupt discontinuation of corticosteroids. - Monitor vital signs (baseline and during procedures) to avoid hypertensive episodes. - Exercise caution with drug interactions. - Evaluate pain management carefully; aspirin and NSAIDs pose a risk for peptic ulcers in these patients. A diagram illustrating the symptoms of Cushing's syndrome, including visual representations of clinical signs such as obesity, red round face, and muscle wasting, along with a table listing frequent and nonspecific symptoms and laboratory abnormalities. A slide summarizing the oral manifestations of Cushing's syndrome, highlighting increased risk of periodontal disease, inhibited bone formation, delayed wound healing, osteoporosis, and higher risk of oral candidiasis and aphthous ulcers. A slide outlining dental considerations for patients with Cushing's syndrome, emphasizing the need for comprehensive medical records, avoiding abrupt corticosteroid discontinuation, monitoring vital signs, and careful pain management with aspirin and NSAIDs. ```markdown 31/10/2025 7 Addison’s disease  Adrenal insufficiency characterised by adrenal hypofunction = inadequate production of glucocorticoids, especially cortisol  Primary: Addison’s disease  Secondary: disease of the pituitary or hypothalamus, chronic use of steroids  Tertiary: hypothalamic abnormalities or dysfunction  AD is a severe disease with a fatal outcome without adequate hormonal replacement. Hahner et al., 2021  Diagnostic tools Pathogenesis Aetiology 21-Hydroxylase autoantibodies T and B cell autoimmunity against adrenocortical cells Autoimmune Culture, QuantiFERON test, PCR, adrenal CT Mycobacteria, bacteria (e.g. Neisseria meningitidis, Haemophilus influenzae, Pseudomonas aeruginosa), viruses (e.g. human immunodeficiency virus, herpes simplex, cytomegalovirus) or fungi (e.g. Pneumocystis jirovecii) Infection Adrenal CT Primary tumour (bilateral), metastasis (bilateral), adrenal lymphoma (bilateral) Tumour Adrenal CT, phospholipid autoantibodies Anti-phospholipid syndrome, anticoagulant therapy, disseminated intravascular coagulation Bleeding Patient history Bilateral adrenalectomy Surgery Adrenal CT, subcutaneous fat biopsy Ferritin, HFE sequencing Adrenal imaging Amyloidosis Haemochromatosis Histiocytosis Infiltrative Sequence of relevant gene Congenital adrenal hyperplasia, congenital lipoid adrenal hyperplasia, adrenoleukodystrophy (X-linked), adrenal hypoplasia congenita, autoimmune polyglandular syndrome type 1 Genetic Medication and patient history Enzyme inhibition (ketoconazole, fluconazole, itraconazole, etomidate, aminoglutethimide, metyrapone, trilostane, osilodrostat); adrenolytic effect and increased cortisol metabolism (mitotane); inflammation (checkpoint inhibitors) Medication Causes of Addison’s disease Hahner et al., 2021 Clinical manifestations of Addison’s disease  Develop slowly  Weakness  Fatigue  Loss of appetite  Weight loss  Pigmentation of skin and oral mucosa  Clinical features more prominent in Addison’s disease than in secondary adrenal insufficiency  Can occur at any age – most often during 2nd and 3rd decade of life Hahner et al., 2021 19 20 21 ``` ```html <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"><tr><th>Aetiology</th><th>Pathogenesis</th><th>Diagnostic tools</th></tr><tr><td>Autoimmune</td><td>T and B cell autoimmunity against adrenocortical cells</td><td>21-Hydroxylase autoantibodies</td></tr><tr><td>Infection</td><td>Mycobacteria, bacteria (e.g. Neisseria meningitidis, Haemophilus influenzae, Pseudomonas aeruginosa), viruses (e.g. human immunodeficiency virus, herpes simplex, cytomegalovirus) or fungi (e.g. Pneumocystis jirovecii)</td><td>Culture, QuantiFERON test, PCR, adrenal CT</td></tr><tr><td>Tumour</td><td>Primary tumour (bilateral), metastasis (bilateral), adrenal lymphoma (bilateral)</td><td>Adrenal CT</td></tr><tr><td>Bleeding</td><td>Anti-phospholipid syndrome, anticoagulant therapy, disseminated intravascular coagulation</td><td>Adrenal CT, phospholipid autoantibodies</td></tr><tr><td>Surgery</td><td>Bilateral adrenalectomy</td><td>Patient history</td></tr><tr><td>Infiltrative</td><td>Amyloidosis<br>Haemochromatosis<br>Histiocytosis</td><td>Adrenal CT, subcutaneous fat biopsy<br>Ferritin, HFE sequencing<br>Adrenal imaging</td></tr><tr><td>Genetic</td><td>Congenital adrenal hyperplasia, congenital lipoid adrenal hyperplasia, adrenoleukodystrophy (X-linked), adrenal hypoplasia congenita, autoimmune polyglandular syndrome type 1</td><td>Sequence of relevant gene</td></tr><tr><td>Medication</td><td>Enzyme inhibition (ketoconazole, fluconazole, itraconazole, etomidate, aminoglutethimide, metyrapone, trilostane, osilodrostat); adrenolytic effect and increased cortisol metabolism (mitotane); inflammation (checkpoint inhibitors)</td><td>Medication and patient history</td></tr></table> ``` ```html <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"><tr><th>Central nervous system</th><td>• Anorexia<br>• Weight loss<br>• Fatigue<br>• Salt craving<br>• Depression</td></tr><tr><th>Neuropsychiatric system</th><td>• Depression<br>• Fatigue<br>• Reduced libido</td></tr><tr><th>Gastrointestinal system</th><td>• Diarrhoea<br>• Vomiting<br>• Abdominal pain</td></tr><tr><th>Dermatological system</th><td>• Dry skin<br>• Hyperpigmentation (PMS)<br>• Hyperpigmentation (DAB)<br>• Loss of public/axillary hair</td></tr><tr><th>Blood electrolytes</th><td>• Hypokalaemia<br>• Hypernatraemia<br>• Hyponatraemia</td></tr><tr><th>Musculoskeletal system</th><td>• Muscle pain<br>• Joint pain<br>• Weakness</td></tr></table> ``` ```html <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"><tr><th>Fig. 2: Types of adrenal insufficiency.</th></tr><tr><td><img src="https://i.imgur.com/placeholder.png" alt="The hypothalamic-pituitary-adrenal axis diagram showing Primary, Secondary, and Tertiary adrenal insufficiency."></td></tr></table> ```    #### Classification and Etiology Adrenal insufficiency characterized by inadequate production of glucocorticoids (especially cortisol). Without replacement, the disease can be fatal. - **Primary (Addison’s Disease):** Autoimmune (21-Hydroxylase autoantibodies), infection (TB, HIV, fungi), tumours, or genetic factors. - **Secondary:** Pituitary or hypothalamic disease, or chronic steroid use. - **Tertiary:** Hypothalamic dysfunction. | Aetiology | Pathogenesis | Diagnostic Tools | | :--- | :--- | :--- | | Autoimmune | T and B cell autoimmunity | 21-Hydroxylase autoantibodies | | Infection | Bacterial, viral, or fungal pathogens | Culture, PCR, Adrenal CT | | Tumour | Primary or metastatic | Adrenal CT | | Bleeding | Anti-phospholipid syndrome, anticoagulants | Adrenal CT, antibodies | | Infiltrative | Amyloidosis, Haemochromatosis | Biopsy, Adrenal imaging | | Genetic | Congenital adrenal hyperplasia, etc. | Gene sequencing | | Medication | Enzyme inhibition (e.g., ketoconazole) | History | #### Clinical Manifestations Symptoms develop slowly and are more prominent in primary disease: - Fatigue, weakness, and loss of appetite/weight. - Pigmentation of skin and oral mucosa. - Gastrointestinal issues: Diarrhoea, vomiting, abdominal pain. - Musculoskeletal: Muscle/joint pain. - Electrolyte imbalance: Hyponatremia, hyperkalemia. A diagram titled 'Fig. 2: Types of adrenal insufficiency' illustrating the three types of adrenal insufficiency: primary (Addison's disease), secondary, and tertiary. The diagram shows the hypothalamic-pituitary-adrenal axis with labels for cortisol, DHEA, ACTH, and CRH, and indicates the effects of each type of insufficiency on hormone levels. The image is from Hahner et al., 2021. A table titled 'Causes of Addison's disease' that lists various aetiologies, their pathogenesis, and diagnostic tools. The table includes categories such as Autoimmune, Infection, Tumour, Bleeding, Surgery, Infiltrative, Genetic, and Medication, with corresponding details for each. The table is from Hahner et al., 2021. A figure titled 'Clinical manifestations of Addison's disease' that lists symptoms such as weakness, fatigue, and weight loss, and includes a diagram of the human body with labels for various systems affected by the disease, including the central nervous system, gastrointestinal system, and musculoskeletal system. The image is from Hahner et al., 2021. 31/10/2025 --- **Slide 22** **Oral manifestations of Addison’s disease** - Mucosal pigmentation – gingiva, vermillion border of lip, buccal mucosa, palate, tongue - Patchy – macular-like or nodular-like - Dark brown – black - Asymptomatic - Usually occur before extra oral manifestations - Non-specific finding - Differential diagnosis: - Peutz-Jeghers syndrome - McCune-Albright syndrome - Elevated ACTH, low AM cortisol Bouguetzi et al., 2020 --- **Slide 23** **Management of Addison’s disease** - Immediate treatment as potentially life-threatening condition - Patients with adrenal crisis require intensive fluid resuscitation with IV saline, dextrose and hormone replacement to correct lack of glucocorticoid - Hydrocortisone --- **Slide 24** **Dental considerations in Addison's disease** - Adrenal crisis can be precipitated by stress (e.g. stress associated with surgical procedures or trauma) - Patients with primary adrenal insufficiency are at higher risk of experiencing adrenal crisis - Underlying cause is decrease in endogenous production of cortisol - Dentist must be alert to recognize the condition as early as possible - Risk factors associated with adrenal crisis in dental office - Unrecognized adrenal insufficiency - Poor health status - Stability at time of dental treatment - Pain - Infection - Invasive procedures - In presence of risk factors, patients undergoing minor to moderate oral surgery should receive supplementation of 25-75 mg hydrocortisone equivalent  #### Oral Pigmentation - Locations: Gingiva, vermillion border of lip, buccal mucosa, palate, and tongue. - Appearance: Patchy, macular-like or nodular-like; dark brown to black. - Clinical Significance: Usually occurs before extra-oral manifestations; asymptomatic. - Differential Diagnosis: Peutz-Jeghers syndrome, McCune-Albright syndrome. #### Management and Adrenal Crisis - Adrenal crisis is a life-threatening emergency requiring intensive fluid resuscitation (IV saline, dextrose) and hormone replacement (Hydrocortisone). - **Dental Risks:** Crisis can be precipitated by stress, pain, infection, or invasive procedures. - **Supplementation:** For minor to moderate oral surgery in at-risk patients, supplementation of 25-75 mg hydrocortisone equivalent may be required. - Dentists must recognize unrecognized adrenal insufficiency or poor health stability before treatment. A photo showing the presence of brown and black patches and plaques distributed in the oral cavity, specifically highlighting the left buccal mucosa and hard palate, illustrating mucosal pigmentation associated with Addison's disease. ```markdown 31/10/2025 ## Thyroid glands - Primary function of thyroid follicular cells is synthesis of thyroid hormones - Tetraiodothyronine (T4) = thyroxine - Triiodothyronine (T3) - Function - Growth - Basal metabolic rate control - Body temperature - Gluconeogenesis - Lipolysis - Proteolysis - Glucose absorption - Stimulated through hypothalamic-pituitary axis - Dysfunction of this system can result in potentially fatal conditions --- ## Grave’s disease - Hyperthyroidism - Enlarged and overactive thyroid gland - Most common in Caucasian and Asian women aged 20 – 40 years - Pathophysiology: autoimmune - Autoantibodies to the TSH receptors of the follicular cells lead to stimulation of thyroid hormone production - Due to negative feedback effect of thyroid hormone on anterior pituitary gland, TSH levels will be low --- ## Grave’s disease - Enlarged, overactive thyroid gland - Ocular abnormalities - Localised dermopathy - Extra thyroidal manifestations - Thymus - Pituitary glands - Testes - Kidney - Heart - Brain - Adipose tissue - Fibroblasts - Bone - Clinical presentation - Anxiety - Weight loss - Palpitations - Insomnia - Elderly patients can present with cardiovascular symptoms - Tachycardia - Atrial fibrillation - Distinct feature of Grave’s disease is sudden onset of symptoms ```    #### Thyroid Function Overview - Follicular cells synthesize T4 (thyroxine) and T3 (triiodothyronine). - Controls basal metabolic rate, growth, body temperature, and various metabolic processes (gluconeogenesis, lipolysis). #### Grave’s Disease Pathophysiology - Autoimmune hyperthyroidism where autoantibodies stimulate TSH receptors. - Results in low TSH levels due to negative feedback. - Most common in women aged 20–40. #### Clinical Presentation - Enlarged, overactive thyroid (goitre). - Ocular abnormalities and localized dermopathy. - Systemic symptoms: Anxiety, weight loss, palpitations, insomnia, tachycardia, and atrial fibrillation. - Characterized by a sudden onset of symptoms. A diagram illustrating the thyroid glands and their hormonal regulation, showing the hypothalamic-pituitary-thyroid axis with labeled components including the hypothalamus, pituitary gland, thyroid gland, and thyroid hormones (T3, T4). The diagram includes a feedback loop mechanism and highlights the primary function of thyroid follicular cells in synthesizing thyroid hormones. A diagram summarizing Grave's disease, highlighting its characteristics such as hyperthyroidism, an enlarged and overactive thyroid gland, and autoimmune pathophysiology involving autoantibodies to TSH receptors. The diagram also notes the low TSH levels due to negative feedback from thyroid hormones. A diagram detailing the clinical presentation and extra-thyroidal manifestations of Grave's disease, listing symptoms like anxiety, weight loss, and palpitations, and identifying affected organs such as the thymus, pituitary glands, and heart. It emphasizes the sudden onset of symptoms as a distinct feature. 31/10/2025 **Oral manifestations of Grave’s disease** - Increased susceptibility to caries, periodontal disease - Enlargement of extra glandular thyroid tissue - Maxillary or mandibular osteoporosis - Loss of taste - Accelerated dental eruption - Early primary tooth exfoliation - Oral burning - Thyroid may be enlarged or noticeable palpable - Development of connective tissue diseases like Sjogren’s syndrome or Systemic lupus erythematosus **Dental management for Grave’s disease** - Haemostasis: - Elevated blood pressure and heart rate - Longer duration to stop bleeding - Anti-thyroid drugs can cause hypoprothrombineamia and bleeding - Susceptibility to infections: inadequate woundn healing, oral infections - NSAIs should be used in caution - Patients have increased anxiety, and stress or surgery can trigger thyrotoxic crisis. Epinephrine contraindicated **Hashimoto’s Thyroiditis** - Decrease in thyroid hormone and thyroid gland function - Chronic thyroiditis (Hashimoto’s disease) - Symptoms: - Slower metabolic rate - Weight gain - Lethargy - Intolerance to cold - Dry and cool skin - Puffiness of the face and eyelids - Blood pressure normal, but heart rate slow    #### Oral Manifestations - Increased susceptibility to caries and periodontal disease. - Maxillary or mandibular osteoporosis. - Accelerated dental eruption and early primary tooth exfoliation. - Loss of taste and oral burning. - Enlargement of extra-glandular thyroid tissue. - Association with Sjogren’s syndrome or Systemic Lupus Erythematosus. #### Dental Management - **Haemostasis:** Elevated BP/heart rate and anti-thyroid drugs (causing hypoprothrombineamia) can prolong bleeding. - **Infection Risk:** Inadequate wound healing. - **Drug Precautions:** Epinephrine is contraindicated as stress/surgery can trigger a thyrotoxic crisis; use NSAIDs with caution. A slide titled 'Oral manifestations of Grave's disease' listing various oral symptoms such as increased caries susceptibility, periodontal disease, and thyroid enlargement, presented in a bulleted format. A slide titled 'Dental management for Grave's disease' detailing considerations like haemostasis, elevated blood pressure, and caution with NSAIDs, presented as a bulleted list. A slide titled 'Hashimoto's Thyroiditis' outlining the condition's characteristics, including decreased thyroid function and symptoms like weight gain and lethargy, presented in a bulleted list. 31/10/2025 11 **Oral manifestations of Hashimoto’s Thyroiditis** - Childhood hypothyroidism = cretinism - Thick lips - Large protruding tongue (Macroglossia) - Delayed eruption of teeth - Impacted mandibular second molars - Common oral findings: - Macroglossia - Dysgeusia - Delayed eruption - Poor periodontal health - Altered tooth morphology - Delayed wound healing **Dental considerations for hypothyroidism** - Haemostasis: longer time to achieve - Susceptibility to infection due to delayed wound healing - Drug interactions of l-thyroxine include increased metabolism of phenytoin, carbamazepine. It also increases effects of warfarin **Pituitary Gland** - The normal anterior pituitary secretes six main hormones from five separate cell lineages: - adrenocorticotrophic hormone (ACTH) from corticotroph cells - thyroid stimulating hormone (TSH) from thyrotroph cells - growth hormone (GH) from somatotroph cells - prolactin from lactotroph cells - follicle stimulating hormone (FSH) and luteinising hormone (LH) from gonadotroph cells. - The posterior pituitary releases two hormones, which are synthesised in the hypothalamus – arginine vasopressin (also known as antidiuretic hormone) and oxytocin.   #### Clinical Features - Characterized by decreased thyroid hormone and slower metabolic rate. - Symptoms: Weight gain, lethargy, cold intolerance, dry/cool skin, facial puffiness, and bradycardia. #### Oral Manifestations - **Cretinism (Childhood Hypothyroidism):** Thick lips and protruding tongue (macroglossia). - **General Findings:** - Delayed eruption of teeth and impacted mandibular second molars. - Dysgeusia. - Poor periodontal health and altered tooth morphology. - Delayed wound healing. #### Dental Considerations - **Haemostasis:** Longer time required to achieve. - **Infection:** Increased susceptibility due to delayed healing. - **Drug Interactions:** L-thyroxine increases the metabolism of phenytoin and carbamazepine and enhances the effects of warfarin. A diagram illustrating the pituitary gland, showing its location in the brain and the hormones it secretes. The diagram includes a cross-section of the brain highlighting the anterior and posterior pituitary, with labels indicating the hormones produced by different cell types, such as ACTH, TSH, GH, prolactin, FSH, and LH from the anterior pituitary, and vasopressin and oxytocin from the posterior pituitary. A photo showing oral manifestations of Hashimoto's Thyroiditis, including a close-up of a patient's mouth with thick lips and a large protruding tongue (macroglossia), and another image of the tongue being extended, highlighting the condition. 31/10/2025 **Pituitary Disorders** **Disorders of the Pituitary Gland: Acromegaly** **Oral manifestations of Acromegaly** --- **Table 2. Pituitary adenoma subtypes²⁷** | Clinically non-functioning pituitary tumours | • Silent gonadotroph adenoma<br>• Other non-secretory adenomas from corticotroph, lactotroph and somatotroph cell lineage<br>• Null cell adenoma | | --- | --- | | Functioning pituitary tumours | • Prolactinoma<br>• GH-secreting adenoma (acromegaly)<br>• ACTH-secreting adenoma (Cushing’s disease)<br>• Rare functioning tumours – thyrotropinoma, FSH-secreting pituitary adenoma | **ACTH: adrenocorticotropic hormone; FSH: follicle stimulating hormone; GH: growth hormone** --- **Acromegaly** - Enlargement of hands and feet - Frontal bossing - Splayed dentition - Mandibular enlargement – jaw malocclusion - Enlarged tongue - Skin tags - Oily skin - Sweating - Hirsutism (women) - Obstructive sleep apnoea - Osteoarthritis - Carpal tunnel syndrome - Hypertension - Cardiomyopathy - Goitre - Liver/spleen enlargement - Colonic polyps - Diabetes - Tall stature (prepubertal onset – gigantism) --- **Table 1** **Oral manifestations of Acromegaly** | Symptoms/Signs | Diagnosis | Possible Treatments | | --- | --- | --- | | Third-class malocclusion | Dental evaluation | No treatment or orthodontic treatment – if necessary, orthodontic surgical treatment – in the inactive phase of the disease | | Dental diastema | Dental evaluation | Possible conservative treatment in any phase of the disease or orthodontic treatment, preferably not in the active phase of the disease | | Macroglossia | Mallampati or Modified Mallampati evaluation | Medical therapy for the control of acromegaly syndrome; possible surgical or conservative treatment of OSA with special dental appliances | | Osseous tort or exostoses | Dental evaluation | No treatment; surgical treatment in the event that the exostoses hinder the insertion of dental prostheses | | Incongruity of mobile prosthesis or implant based prosthesis, and possible leakage | Dental evaluation | Adjustment of the prosthesis base or replacement of the same; in case of prosthesis fixed on implants, verification and possible adjustment of the intermaxillary pillars, preferably not in the active phase of the disease | | Frontal elements inclination | Orthodontic evaluation | No treatment or orthodontic treatment in the inactive phase of the disease | | Hypereruption | Periodontal evaluation, following routine radiographic examination | No treatment | | Circles and TMJ pain | Dental and gynecologic evaluation, radiographic deepening with RM | Functional treatment with genioplasty for the temporomandibular joint or application of a customized bite | | Thickening of gingival tissues | Dental evaluation | No treatment or surgical treatment in the inactive phase of the disease | --- <img src="https://i.imgur.com/placeholder.jpg" alt="Acromegaly symptoms and imaging" />    #### Pituitary Adenoma Subtypes - **Non-functioning:** Silent gonadotroph, null cell, or other non-secretory adenomas. - **Functioning:** Prolactinoma, GH-secreting (Acromegaly), ACTH-secreting (Cushing’s), and rare TSH/FSH-secreting tumours. #### Clinical Features of Acromegaly - Enlargement of hands, feet, and mandible (jaw malocclusion). - Frontal bossing and splayed dentition (diastema). - Macroglossia (enlarged tongue). - Systemic: Sleep apnoea, hypertension, cardiomyopathy, diabetes, and osteoarthritis. #### Oral Signs and Treatment Approaches | Symptoms/Signs | Diagnosis | Possible Treatments | | :--- | :--- | :--- | | Class III Malocclusion | Dental eval | Orthodontic/Surgical (in inactive phase) | | Dental Diastema | Dental eval | Conservative or Orthodontic | | Macroglossia | Mallampati eval | Medical control of GH; OSA appliances | | Osseous exostoses | Dental eval | Surgical only if hindering prostheses | | Gingival Thickening | Dental eval | No treatment or surgery (inactive phase) | | TMJ Pain | Dental/Radiographic | Functional treatment or customized bite | Table 2 titled 'Pituitary adenoma subtypes' categorizes pituitary adenomas into clinically non-functioning and functioning types, listing specific subtypes such as silent gonadotroph adenoma, prolactinoma, and GH-secreting adenoma (acromegaly), with explanations of associated hormones. Table 1 titled 'Oral manifestations of Acromegaly' details various oral symptoms, their diagnostic methods, and possible treatments, including conditions like third-class malocclusion, dental diastema, and macroglossia, with recommendations for dental and orthodontic interventions. A composite image showing clinical manifestations of acromegaly, including facial features (a), a sagittal MRI scan (b), hand deformities (c), a chest X-ray (d), and a frontal view of a patient (e), illustrating the systemic effects of the condition. 31/10/2025 13  Gigantism  Occurs when growth hormone hypersecretion occurs before fusion of the long bone epiphysis  Rare  Suspected when patient’s heigh is 3 standard deviations above normal mean height or 2 standard deviations above the adjusted mean parental height  Associated with various syndromes:  Neurofibromatosis  Carney complex  McCune Albright syndrome Oral Manifestations of Gigantism  Teeth size are proportional to generalised enlarged body size  Interdental spacing  Dental malocclusion  Hypercementosis of roots  Prognathic mandible  Frontal bossing 37 38 39    #### Overview - Occurs when GH hypersecretion happens before the fusion of long bone epiphyses. - Rare condition; suspected when height is >3 standard deviations above the mean. - Associated syndromes: Neurofibromatosis, Carney complex, and McCune Albright syndrome. #### Oral Manifestations - Teeth size proportional to generalized enlarged body size. - Interdental spacing and dental malocclusion. - Hypercementosis of roots. - Prognathic mandible and frontal bossing. A collage of seven photographs labeled A through G, showing various oral manifestations of gigantism, including dental malocclusion, interdental spacing, and prognathic mandible. A diagram illustrating gigantism, showing a normal human figure and a larger figure with a labeled pituitary gland, explaining that gigantism occurs when growth hormone hypersecretion happens before the fusion of long bone epiphyses. A table listing the oral manifestations of gigantism, including teeth size proportional to body size, interdental spacing, dental malocclusion, hypercementosis of roots, prognathic mandible, and frontal bossing. ```markdown 31/10/2025 14 **Role of Dentist in Acromegaly and Gigantism** - Early diagnosis can improve quality of life and reduce risk of mortality - Assessment of oro-facial disorders e.g. macroglossia, diastemas, prognathism can be assessed early - Role in diagnosis of co-morbidities: e.g. obstructive sleep apnoea **Disorders of Parathyroid Glands** - 4 small glands embedded in the posterior aspect of the thyroid gland - Main function is production and secretion of: - Parathyroid hormone (PTH) - Levels of PTH and serum calcium are inversely proportional - At low serum calcium levels, PTH in conjunction with vitamin D works to mobilize calcium stores and increase calcium absorption and reabsorption - Both calcium and vitamin D provide negative feedback to parathyroid glands - As levels of calcium and vitamin D increase, they bind receptors of Parathyroid glands and inhibit production and release of PTH Image from: Lofrese et al., 2023 **Disorders of Parathyroid Glands** - Rare conditions - Misregulation of calcium homeostasis due to alterations in secretion of PTH - Primary hyperparathyroidism is most common - Hypercalcaemia alongside increased serum PTH concentration - Hypoparathyroidism is less common - Low calcium levels in blood serum due to inadequately low PTH levels ```  #### Physiology of Parathyroid Hormone (PTH) - Four small glands that produce PTH to regulate calcium homeostasis. - PTH and serum calcium are inversely proportional: low calcium triggers PTH and Vitamin D to mobilize calcium stores and increase absorption. - Negative feedback: High calcium and Vitamin D inhibit PTH release. #### Classification of Disorders - **Primary Hyperparathyroidism:** Most common; hypercalcaemia with increased PTH. - **Hypoparathyroidism:** Less common; low serum calcium due to inadequately low PTH. #### Role of the Dentist - Early diagnosis of Acromegaly/Gigantism through assessment of macroglossia, diastemas, and prognathism. - Identification of co-morbidities like obstructive sleep apnoea. A diagram illustrating calcium regulation in the body, showing the role of parathyroid glands, PTH, and vitamin D in maintaining calcium homeostasis. It depicts processes such as calcium mobilization from bones, absorption in the intestines, and reabsorption in the kidneys, with text explaining the inverse relationship between PTH and serum calcium levels. 31/10/2025 **Hyperparathyroidism** - Dangerously elevated levels of calcium in blood - Clinical symptoms: - Nausea - Vomiting - Constipation - Kidney stones - Bone pain - Psychosis or altered mental status - Primary hyperparathyroidism: result of parathyroid adenoma, hyperplasia or carcinoma - Secondary hyperparathyroidism: chronic hypocalcaemic state - Chronic kidney disease or vitamin D deficiency - Tertiary hyperparathyroidism: long-term hyperparathyroidism - End stage renal disease - Leads to hyperplasia of parathyroid glands --- **Oral manifestations of hyperparathyroidism** From: Systematic review of oral manifestations related to hyperparathyroidism | Systemic symptoms | | | :--- | :--- | | General | Anemia (fatigue, weakness, dyspnea), weight loss, fever, polydipsia, edema | | Neurologic | Headaches, confusion, memory loss, insomnia, anxiety, depression, lethargy, suicide, coma | | Renal | Nephrocalcinosis, nephrolithiasis, polyuria/nocturia, hematuria | | Skeletal | Bone pain, arthralgia, osteoporosis, osteomalacia, brown tumors, fracture | | Digestive | Constipation, nausea, vomiting, peptic ulcers, cholelithiasis, pancreatitis | | Cardiac | Hypertension | | Oral symptoms | | | Expansile | Speaking difficulties, mastication difficulties, airway obstruction, malocclusion | | Oral pain | | | Neuropathy | | | Tooth mobility | | | Fracture | | | Tooth structure | Hypoplastic enamel, hypoplastic dentin, loss cementum, pulp calcification, periodontitis | | Soft tissue | Giant cell epulis, mucosal pallor (anemia) | | Radiographic findings | | | Cortical destruction | | | Tooth displacement | | | Loss LD | | | Root resorption | | | Obliteration IAN | | | Altered calcification | | ---    #### Clinical Types - **Primary:** Result of parathyroid adenoma, hyperplasia, or carcinoma. - **Secondary:** Chronic hypocalcaemic state (e.g., chronic kidney disease, Vitamin D deficiency). - **Tertiary:** Long-term hyperparathyroidism leading to autonomous hyperplasia (e.g., end-stage renal disease). #### Systemic and Oral Symptoms - **Systemic:** Nausea, kidney stones, bone pain ("brown tumors"), and altered mental status. - **Oral Symptoms:** - Mastication and speaking difficulties, malocclusion. - Tooth mobility and neuropathy. - Structural changes: Hypoplastic enamel/dentin, pulp calcification, and periodontitis. - Soft tissue: Giant cell epulis, mucosal pallor. - **Radiographic Findings:** Cortical destruction, loss of lamina dura (LD), root resorption, and altered calcification. A diagram illustrating the systemic effects of hyperparathyroidism, showing a human figure with labeled systems (Digestive, Nervous, Musculoskeletal, Urinary) and associated symptoms such as nausea, bone pain, and kidney stones. A table summarizing the oral manifestations of hyperparathyroidism, categorized by systemic symptoms, oral symptoms, tooth structure, soft tissue, and radiographic findings, sourced from a systematic review. A series of intraoral and radiographic images showing various oral manifestations of hyperparathyroidism, including tooth mobility, root resorption, and bone changes, sourced from Lajolo et al., 2020. ```markdown 31/10/2025 --- **Management of hyperparathyroidism** - Treatment must focus on identification and type of hyperparathyroidism - For all suspected patients: - Serum PTH - 24-h urinary calcium - 25-hydroxy vitamin D - Parathyroidectomy most commonly reported treatment - Treatment of underlying aetiology would lead to dissipation of oral bone involvement - Role of dentist: occasionally indication of illness might be a growth in the jaw - Oral manifestations and dental radiographs can recognise secondary HPT early --- **Hypoparathyroidism** - Rare disease that results in hypocalcaemia - Symptoms range from paraesthesias and muscle cramps to seizures and laryngospasms - Most common cause is injury to or removal of parathyroid gland during anterior neck surgery - Often associated with basal ganglia calcification, cataracts and neuropsychiatric symptoms - Goal of treatment is to maintain blood calcium level near the low end of normal range while preventing symptoms of hypocalcaemia - Oral calcium, active vitamin D --- ```  #### Management and Diagnosis - Diagnostic requirements: Serum PTH, 24-h urinary calcium, and 25-hydroxy vitamin D. - Primary treatment: Parathyroidectomy. - Dental Role: Recognition of jaw growths or radiographic changes can lead to early diagnosis of secondary hyperparathyroidism. #### Hypoparathyroidism Overview - Rare disease resulting in hypocalcaemia. - Causes: Most commonly injury to or removal of glands during neck surgery. - Symptoms: Paresthesias, muscle cramps, seizures, and laryngospasms. - Associated features: Basal ganglia calcification, cataracts, and neuropsychiatric symptoms. - Treatment: Oral calcium and active Vitamin D to maintain calcium at the low end of the normal range. A panoramic X-ray showing a 34-year-old female with secondary hyperparathyroidism, displaying radiolucent changes around the distal root of tooth #46 and sclerotic changes in the mandible, particularly in the posterior left region. 31/10/2025 17 --- **Hypocalcemia** **Definition** Mild hypocalcemia: total serum Ca²⁺ < 8.5 mg/dl, or ionized Ca²⁺ < 4.65 mg/dl. Severe hypocalcemia: total Ca²⁺ < 7.5 mg/dl, or ionized Ca²⁺ < 3.6 mg/dl. Facititous: decreased total Ca²⁺ with normal ionized Ca²⁺ (asymptomatic) **Etiology** With low PTH: hypoparathyroidism With high PTH: vitamin D deficiency, CKD, acute pancreatitis, hyperphosphatemia Other: medications (e.g., loop diuretics), multiple blood transfusions, hypomagnesemia **Diagnosis** Serum total and ionized Ca²⁺, electrolytes and kidney function, ABG/VBG, serum intact PTH, ECG (e.g., prolonged QT interval) **Treatment** Calcium supplementation Treatment of the underlying condition --- **Neurological** Seizure Tetany (increased neuromuscular excitability) Paresthesias (e.g., perioral) Spasms (e.g., carpopedal) Muscle cramps, stiffness, myalgia **Cardiovascular** Arrhythmias (palpitations, irregular pulse, syncope), hypertension, congestive heart failure **Chronic manifestations** Psychiatric: e.g., anxiety, depression Neurological: pseudotumor cerebri Ophthalmologic: papilledema, cataracts Dental changes: altered morphology, enamel hypoplasia **Note** Symptoms of tetany (e.g., spasms, cramps and paresthesia) are the most characteristic features of hypocalcemia. --- **Oral manifestations of hypoparathyroidism** - Dental abnormalities - Enamel hypoplasia - Delayed eruption - Hypodontia and microdontia - Poorly calcified dentine - Widened pulp chambers - Dental pulp calcifications - Shortened roots with blunt apex - Malformed roots - Delay or cessation of dental development - Ankylosis - Caries - Chronic candidiasis - Paresthesia of tongue or lips - Alterations in facial muscles Kelly et al., 2009 --- **Dental management of the patient with hypoparathyroidism** - Prevention of caries with periodic check up, diet and oral hygiene advice - Before performing dental treatment, serum calcium levels should be determined - > 8 mg/100 ml to prevent cardiac arrhythmias, seizures, laryngospasms, bronchospasms --- <figure> <img src="https://i.imgur.com/placeholder.png" alt="Radiograph showing dental abnormalities in hypoparathyroidism" /> <figcaption>Image showing dental abnormalities in hypoparathyroidism</figcaption> </figure>    #### Hypocalcemia Definitions and Etiology - **Mild:** Total serum Ca²⁺ < 8.5 mg/dl. - **Severe:** Total Ca²⁺ < 7.5 mg/dl. - **Etiology:** Hypoparathyroidism (low PTH); Vitamin D deficiency, CKD, or acute pancreatitis (high PTH). #### Clinical Manifestations of Hypoparathyroidism - **Neuromuscular:** Tetany (characteristic feature), seizures, perioral paresthesia, and muscle cramps. - **Chronic:** Anxiety, depression, cataracts, and dental changes. - **Oral/Dental Abnormalities:** - Enamel hypoplasia, hypodontia, and microdontia. - Delayed eruption and malformed/shortened roots with blunt apices. - Widened pulp chambers and pulp calcifications. - Chronic candidiasis and paresthesia of the tongue or lips. #### Dental Management - Focus on caries prevention (diet, hygiene, check-ups). - **Safety Threshold:** Serum calcium levels should be determined before treatment and should be > 8 mg/100 ml to prevent arrhythmias, seizures, and spasms. A diagram illustrating the clinical aspects of hypocalcemia, including definitions, etiology, diagnosis, treatment, and manifestations such as neurological, cardiovascular, and chronic effects. It features a central human figure with annotations pointing to areas affected by hypocalcemia, such as tetany and paresthesias. A radiograph showing dental abnormalities in hypoparathyroidism, including widened pulp chambers, poorly calcified dentine, and malformed roots. The image is accompanied by a list of oral manifestations of hypoparathyroidism. A slide detailing dental management for patients with hypoparathyroidism, emphasizing caries prevention and the importance of checking serum calcium levels before dental treatment to prevent complications like arrhythmias and seizures. 31/10/2025 18 **Pregnancy** - Increase in oestrogen and progesterone important for normal progression of pregnancy - Increased hormonal secretion and foetal growth induce several systemic changes - Cardiovascular - Haematologic - Respiratory - Renal - Gastrointestinal - Endocrine - Genitourinary - Local changes also occur in oral cavity **Oral manifestations of pregnancy** - Gingivitis - Gingival hyperplasia - Pyogenic granuloma - Salivary changes – reduced whole stimulated saliva flow rate - Increased facial pigmentation - Worsen pre-existing periodontal disease **Dental treatment during pregnancy** - Most dental treatment can be carried out safely during pregnancy - Elective treatment best performed in second trimester of pregnancy - Elective procedures requiring general anaesthesia, or IV sedation should be deferred until after the birth, and preferably after breastfeeding stopped - If unsure pregnancy status – defer treatment decisions until pregnancy status known - If intraoral radiographs are necessary for assessment or diagnosis in infection or trauma, there is no reason to defer them - Use leaded drape - Before prescribing consider general principles of dry use in pregnancy or breastfeeding  #### Systemic and Oral Changes - Increased oestrogen and progesterone induce cardiovascular, haematologic, and endocrine changes. - **Oral Manifestations:** - Gingivitis and gingival hyperplasia. - Pyogenic granuloma. - Reduced stimulated salivary flow rate. - Increased facial pigmentation. - Exacerbation of pre-existing periodontal disease. #### Dental Treatment Guidelines - **Timing:** Most treatment is safe; elective treatment is best performed in the second trimester. - **Sedation:** Defer elective procedures requiring GA or IV sedation until after birth/breastfeeding. - **Radiographs:** If necessary for infection or trauma, do not defer; use a leaded drape. - **Prescribing:** Follow general principles for drug use during pregnancy/breastfeeding; defer decisions if pregnancy status is unknown. A close-up clinical photograph showing a gingival lesion, likely a pyogenic granuloma, on the lower anterior teeth. The image is part of a slide discussing oral manifestations of pregnancy, specifically illustrating gingival hyperplasia or a pyogenic granuloma. ```markdown 31/10/2025 55  Thank you for listening!  lalima.tiwari@uwa.edu.au 56  References  Mauri-Obradors E, Estrugo-Devesa A, Jané-Salas E, Viñas M, López-López J. Oral manifestations of Diabetes Mellitus. A systematic review. Med Oral Patol Oral Cir Bucal. 2017 Sep 1;22(5):e586-e594. doi: 10.4317/medoral.21655. PMID: 28809366; PMCID: PMC5694181.  Rohani B. Oral manifestations in patients with diabetes mellitus. World J Diabetes. 2019 Sep 15;10(9):485-489. doi: 10.4239/wjd.v10.i9.485. PMID: 31558983; PMCID: PMC6748880.  Maya S. Indurkar, Arati S. Maurya, Sanjiv Indurkar; Oral Manifestations of Diabetes. Clin Diabetes 1 January 2016; 34 (1): 54–57. https://doi.org/10.2337/diaclin.34.1.54  Kumari M, Kumar T, Rai S, Rai A, Sultana R, Priya L. Evaluation of Dental Health in Terminally Ill Patients. J Med Life. 2020 Jul-Sep;13(3):321-328. doi: 10.25122/jml-2020-0023. PMID: 33072203; PMCID: PMC7550152.  Reincke M, Fleseriu M. Cushing Syndrome:A Review. JAMA. 2023;330(2):170–181. doi:10.1001/jama.2023.11305  Mirfarsi, Sahar, Dalia Seleem and Airani Sathananthan, “Dental Considerations and Precautions Associated with Oral Excisional Biopsy on a Patient with Cushing’s Syndrome (Hypercortisolism)” (2023) 67(4) The Dental clinics of North America 581  Hahner, S., Ross, R.J., Arlt, W. et al. Adrenal insufficiency.Nat Rev Dis Primers 7, 19 (2021). https://doi.org/10.1038/s41572-021-00252-7  Adel Bouguezzi, Hela Zouaghi. Oral Pigmentation as a Sign of Addison’s disease. On J Dent & Oral Health. 3(1): 2020. OJDOH. MS.ID.000551.  Bugălă NM, Carsote M, Stoica LE, Albulescu DM, Ţuculină MJ, Preda SA, BoiceaAR, Alexandru DO. New Approach to Addison Disease: Oral Manifestations Due to Endocrine Dysfunction and Comorbidity Burden. Diagnostics (Basel). 2022 Aug 28;12(9):2080. doi: 10.3390/diagnostics12092080. PMID: 36140482; PMCID: PMC9497746.  Chandna S, Bathla M. Oral manifestations of thyroid disorders and its management. Indian J Endocrinol Metab. 2011 Jul;15(Suppl 2):S113-6. doi: 10.4103/2230-8210.83343. PMID: 21966646; PMCID: PMC3169868.  Davies, T.F., Andersen, S., Latif, R. et al. Graves’ disease. Nat Rev Dis Primers 6, 52 (2020). https://doi.org/10.1038/s41572-020-0184-y  Preo, G., De Stefani, A., Dassie, F. et al. The role of the dentist and orthodontist in recognizing oro-facial manifestations of acromegaly: a questionnaire-based study. Pituitary 25, 159–166 (2022). https://doi.org/10.1007/s11102-021-01183-y  De Stefani A, Dassie F, Wennberg A, Preo G, Muneratto A, Fabris R, Maffei P, Gracco A, Bruno G. Oral Manifestations and Maxillo-Facial Features in the Acromegalic Patient: A Literature Review. Journal of Clinical Medicine. 2022; 11(4):1092. https://doi.org/10.3390/jcm11041092 57  Lajolo, Carlo et al, “Brown Tumors of the Oral Cavity: Presentation of 4 New Cases and a Systematic Literature Review” (2020) 129(6) ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY 575  Palla, B., Burian, E., Fliefel, R. et al. Systematic review of oral manifestations related to hyperparathyroidism. Clin Oral Invest 22, 1–27 (2018). https://doi.org/10.1007/s00784-017-2124-0  Letícia Martins Guimarães, Alline Teixeira Valeriano, Hélder Antônio Rebelo Pontes, Ricardo Santiago Gomez, Carolina Cavalieri Gomes, Manifestations of hyperparathyroidism in the jaws: Concepts, mechanisms, and clinical aspects, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 133, Issue 5, 2022, Pages 547-555,  Mittal, S., Gupta, D., Sekhri, S., & Goyal, S. (2014). Oral manifestations of parathyroid disorders and its dental management. J Dent Allied Sci, 3(1), 34-8.  Alice Kelly, Luciana Pomarico, Ivete Pomarico Ribeiro de Souza, Cessation of dental development in a child with idiopathic hypoparathyroidism: a 5-year follow-up, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, Volume 107, Issue 5, 2009, Pages 673-677,  Therapeutic guidelines: Dental treatment during pregnancy and breastfeeding; 2022  Vt H, T M, T S, Nisha V A, A A. Dental considerations in pregnancy-a critical review on the oral care. J Clin Diagn Res. 2013 May;7(5):948-53. doi: 10.7860/JCDR/2013/5405.2986. Epub 2013 Mar 21. PMID: 23814753; PMCID: PMC3681080. ```    #### Contact Information - **Email:** lalima.tiwari@uwa.edu.au #### Literature References - Mauri-Obradors E, Estrugo-Devesa A, Jané-Salas E, Viñas M, López-López J. Oral manifestations of Diabetes Mellitus. A systematic review. Med Oral Patol Oral Cir Bucal. 2017 Sep 1;22(5):e586-e594. doi: 10.4317/medoral.21655. PMID: 28809366; PMCID: PMC5694181. - Rohani B. Oral manifestations in patients with diabetes mellitus. World J Diabetes. 2019 Sep 15;10(9):485-489. doi: 10.4239/wjd.v10.i9.485. PMID: 31558983; PMCID: PMC6748880. - Maya S. Indurkar, Arati S. Maurya, Sanjiv Indurkar; Oral Manifestations of Diabetes. Clin Diabetes 1 January 2016; 34 (1): 54–57. https://doi.org/10.2337/diaclin.34.1.54 - Kumari M, Kumar T, Rai S, Rai A, Sultana R, Priya L. Evaluation of Dental Health in Terminally Ill Patients. J Med Life. 2020 Jul-Sep;13(3):321-328. doi: 10.25122/jml-2020-0023. PMID: 33072203; PMCID: PMC7550152. - Reincke M, Fleseriu M. Cushing Syndrome: A Review. JAMA. 2023;330(2):170–181. doi:10.1001/jama.2023.11305 - Mirfarsi, Sahar, Dalia Seleem and Airani Sathananthan, “Dental Considerations and Precautions Associated with Oral Excisional Biopsy on a Patient with Cushing’s Syndrome (Hypercortisolism)” (2023) 67(4) The Dental clinics of North America 581 - Hahner, S., Ross, R.J., Arlt, W. et al. Adrenal insufficiency. Nat Rev Dis Primers 7, 19 (2021). https://doi.org/10.1038/s41572-021-00252-7 - Adel Bouguezzi, Hela Zouaghi. Oral Pigmentation as a Sign of Addison’s disease. On J Dent & Oral Health. 3(1): 2020. OJDOH. MS.ID.000551. - Bugălă NM, Carsote M, Stoica LE, Albulescu DM, Ţuculină MJ, Preda SA, Boicea AR, Alexandru DO. New Approach to Addison Disease: Oral Manifestations Due to Endocrine Dysfunction and Comorbidity Burden. Diagnostics (Basel). 2022 Aug 28;12(9):2080. doi: 10.3390/diagnostics12092080. PMID: 36140482; PMCID: PMC9497746. - Chandna S, Bathla M. Oral manifestations of thyroid disorders and its management. Indian J Endocrinol Metab. 2011 Jul;15(Suppl 2):S113-6. doi: 10.4103/2230-8210.83343. PMID: 21966646; PMCID: PMC3169868. - Davies, T.F., Andersen, S., Latif, R. et al. Graves’ disease. Nat Rev Dis Primers 6, 52 (2020). https://doi.org/10.1038/s41572-020-0184-y - Preo, G., De Stefani, A., Dassie, F. et al. The role of the dentist and orthodontist in recognizing oro-facial manifestations of acromegaly: a questionnaire-based study. Pituitary 25, 159–166 (2022). https://doi.org/10.1007/s11102-021-01183-y - De Stefani A, Dassie F, Wennberg A, Preo G, Muneratto A, Fabris R, Maffei P, Gracco A, Bruno G. Oral Manifestations and Maxillo-Facial Features in the Acromegalic Patient: A Literature Review. 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A table titled 'References' listing various academic articles related to oral manifestations of systemic diseases, including diabetes, Cushing's syndrome, and thyroid disorders, with details such as authors, titles, journals, publication dates, and DOIs. The table is organized in a structured format with bullet points for each reference. A table titled 'References' listing academic articles related to oral manifestations of systemic conditions such as hyperparathyroidism, hypoparathyroidism, and dental considerations during pregnancy, with details including authors, titles, journals, publication dates, and DOIs. The table is formatted with bullet points for each reference. 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