GMDC Endocrine Lecture 2021 PDF

Endocrine Pathophysiology and Dental Medicine Katherine Modzelewski, MD Boston University School of Medicine Section of Endocrinology, Diabetes and Nutrition August 9, 2021 GMDC Course Overview • • • Course objective: familiarize you with basic medical concepts that may be relevant to your denta...

Endocrine Pathophysiology and Dental Medicine Katherine Modzelewski, MD Boston University School of Medicine Section of Endocrinology, Diabetes and Nutrition August 9, 2021 GMDC Course Overview • • • Course objective: familiarize you with basic medical concepts that may be relevant to your dental practice Lectures from a variety of medical specialists Grading: 40% midterm, 60% final exam – – Midterm covers only first semester Final covers only second semester Learning Objectives 1. Review the normal physiology of the pituitary, thyroid gland, and the adrenals 2. Recognize the major diseases of the endocrine glands including hyperfunction, hypofunction, and tumors 3. Review common dental concerns related to endocrine disorders Overview of Endocrine Pathophysiology • Endocrinology is the study of hormone action and the organs in which hormones are formed • Hormones are secreted from endocrine cells and travel to receptors on the surface of target cell nuclei, and after binding the hormones then exert their effects Main Endocrine Systems • Pituitary • Thyroid Covered in this lecture • Adrenal • Bone/Calcium Metabolism Dr. Holick • Diabetes Mellitus Dr. Alexanian • Reproductive • Lipid Metabolism PITUITARY GLAND Anatomy of the Pituitary • Anterior pituitary: –Epithelial cells without direct connection to the brain –Communicates with the brain via a portal plexus of veins • Posterior pituitary: –Contains axon terminals of neurons that arise in the hypothalamus and end in the posterior pituitary Normal Pituitary Anatomy: Sagittal View on MRI CEREBRUM ANTERIOR PITUITARY CEREBELLUM ORO PHARYNX POSTERIOR PITUITARY “bright spot” TONGUE SPINAL CORD Anterior Pituitary Hormones “FLAT PEG” FSH = Follicle stimulating hormone LH = Luteinizing hormone ACTH = Adrenocorticotrophic hormone TSH = Thyroid stimulating hormone PRL = Prolactin GH = Growth hormone Posterior Pituitary Hormones ADH = Antidiuretic hormone (vasopression) Oxytocin Anterior Pituitary Hormones HORMONE FSH LH ACTH TSH TARGET TISSUE Ovaries, testes Ovaries, testes Adrenal cortex Thyroid FUNCTION Germ cell (gamete) production Androgens, estrogens production Corticosteroid production Thyroid hormone production Prolactin GH Breast All tissues via IGF-1 Lactation Growth, metabolism Posterior Pituitary HORMONE ADH (vasopressin) Oxytocin TARGET TISSUE Kidney tubules Breast, uterus ADH = antidiuretic hormone FUNCTION Water balance Lactation, uterine contraction How Hormones Exert Their Effects • Directly on target organs – • GH, prolactin, ADH Stimulating hormones act on endocrine gland receptors to release hormones that act on target organs – TSH, ACTH, LH, FSH Hypothalamic-Pituitary Axis Direct Effect on Target Organ ENVIRONMENT BRAIN SENSORY INPUT HYPOTHALAMUS + Releasing Inhibiting factors factors PIT GH, PRL ENDOCRINE HORMONE + OR ENDOCRINE GLAND Peptide Hormone Receptor TARGET ORGAN NUCLEUS SOME HORMONES ARE DIRECTLY SECRETED BY THE ANTERIOR PITUITARY TO ACT ON TARGET ORGANS Hypothalamic-Pituitary Axis Stimulating Hormones ENVIRONMENT BRAIN SENSORY INPUT HYPOTHALAMUS + Releasing factors Inhibiting factors PIT PERIPHERAL ENDOCRINE ORGANS REGULATED BY THE PITUITARY STIMULATING HORMONE TSH, ACTH, LH, FSH + Peptide Hormone Receptor ENDOCRINE GLAND TARGET ORGAN NUCLEUS Thyroid Adrenal Ovaries Testes Hypothalamic-Pituitary Axis Stimulating Hormones ENVIRONMENT BRAIN SENSORY INPUT HYPOTHALAMUS + Releasing Inhibiting factors factors PIT T4, T3 Cortisol Estradiol Testosterone TSH, ACTH, LH, FSH + ENDOCRINE HORMONE + THE TARGET ENDOCRINE ORGAN SECRETES A HORMONE THAT ACTS ON TARGET TISSUES Peptide Hormone Receptor ENDOCRINE GLAND OR TARGET ORGAN NUCLEUS Steroid Hormone Receptor Thyroid Adrenal Ovaries Testes Hypothalamic-Pituitary Axis Stimulating Hormones THE PERIPHERAL HORMONE FEEDS BACK TO INHIBIT HYPOTHALAMUS AND PITUITARY SECRETION OF THE PITUITARY RELEASING HORMONE ENVIRONMENT SENSORY INPUT HYPOTHALAMUS NEGATIVE FEEDBACK + Releasing Inhibiting factors factors PIT T4, T3 Cortisol Estradiol Testosterone ENDOCRINE HORMONE + TSH, ACTH, LH, FSH + Peptide Hormone Receptor ENDOCRINE GLAND OR TARGET ORGAN NUCLEUS Steroid Hormone Receptor Thyroid Adrenal Ovaries Testes Posterior Pituitary ENVIRONMENT BRAIN SENSORY INPUT HYPOTHALAMUS Antidiuretic Hormone (ADH) POST PIT v v ADH IS SECRETED FROM NEURONS IN THE HYPOTHALAMUS THAT END IN THE POSTERIOR PITUITARY ANT PIT ENDOCRINE GLAND TARGET ORGAN NUCLEUS Approach to Pituitary Disease • Mass effect from pituitary adenoma (tumor) • Pituitary hypofunction (under activity) •Example: hypogonadism, adrenal insufficiency • Pituitary hyperfunction (over activity) •Example: acromegaly, Cushing’s disease Pituitary Adenoma - Epidemiology • Prevalence 8.9/100,000 individuals • Autopsy studies - pituitary incidentaloma noted in 15-27% - likely underestimated prevalence • 10-15% of all intracranial tumors • Microadenoma < 1cm in diameter, macroadenoma > 1 cm Pituitary Mass Effect Clinical Symptoms of Pituitary Masses • Adjacent structures: hypothalamus, optic nerves, cavernous sinus, temporal lobes and sphenoid sinus Structures Near the Pituitary Direction of adenoma growth Upward Neighboring Structures Optic pathways Hypothalamus Symptoms Blindness Headache Pituitary hormone deficiency Lateral Cranial nerves Disconjugate gaze III, IV, V, VI Drooping eyelid Pupil abnormality Facial pain Down Sphenoid sinus Nosebleed, posterior pharyngeal mass Lateral Extension of Pituitary Adenoma X Large Pituitary Adenomas: Extend Down Through Sphenoid Sinus into the Oropharynx ANTERIOR PITUITARY SPHENOID SINUS ORO PHARYNX TONGUE Pituitary Adenoma Extending Into The Oropharynx PITUITARY ADENOMA Pituitary Hypofunction Posterior Pituitary Hypofunction • Caused by anything that destroys the neuron that extends from the hypothalamus to the posterior pituitary – – – – Large pituitary tumors – most common cause Acceleration-deceleration injury (trauma) Pituitary surgery Infection/Inflammation • Lack of ADH (antidiuretic hormone), also called vasopressin leads to diabetes insipidus Diabetes Insipidus • ADH allows renal tubules in the kidney to reabsorb water • Often after pituitary surgery, the posterior pituitary is injured, leading to ADH loss • Loss of ADH leads to: – Very dilute urine - 6-10 liters/day – Extreme thirst – Dehydration with high serum sodium if cannot keep up with water intake – Fatigue, headache, lethargy • Treatment – DDAVP (desmopression) – long acting form of vasopressin by injection, nasal spray or tablets Anterior Pituitary Hypofunction • Low levels of growth hormone, adrenal hormones, thyroid hormone, sex hormones • Causes – Congenital defects - often midline – Tumors • Primary: Large pituitary adenomas, craniopharyngiomas • Metastatic carcinoma – Apoplexy - ischemia and hemorrhage – Can be single or multiple affected hormones GH Deficiency • Congenital GH deficiency – Main feature is short stature – Fusion of central incisors in child and maxillary hypoplasia – May be caused by mid-line developmental defects – Treatment with supplemental growth hormone Pituitary Hyperfunction Pituitary Adenomas - Hyperfunction • Tumors of each of the anterior pituitary hormone cells can hypersecrete that particular hormone – Prolactin: amenorrhea/impotence, galactorrhea – ACTH: high cortisol (Cushing’s disease) – GH: gigantism before puberty, acromegaly after – TSH: high TSH with high T4, T3 levels (hyperthyroidism) – LH/FSH: rare, amenorrhea/impotence (hypogonadism) • Non-secreting pituitary adenomas also common Acromegaly: Excess Secretion of GH and IGF-1 GH Excess BEFORE Puberty: GIGANTISM Growth plates still open Robert Wadelow 8’11” 490# Gentle Giant Alton, Illinois Don Fermin Arrudi Urieta The Giant of Aragones 1870-1913 GH Excess AFTER Puberty: ACROMEGALY Acromegaly - Dental Concerns • Increased growth of membranous bones of the cranium –Growth of mandible and supraorbital ridge –Long bone epiphyses have fused and cannot grow longer • Malocclusion of teeth • Space between teeth • Increased growth of the retropharyngeal soft tissues, tongue, and lips • Hypercementosis on dental x-rays Increase in Supraorbital Ridge and Mandible in Acromegaly Acromegaly, Mandible Growth and Prognathia INTRADENTAL SEPARATION AND PROGNATHISM WITH ACROMEGALY Acromegaly and Teeth Separation Acromegaly and Hypercementosis • • Hypercementosis: Excessive build up of normal cementum in concentric layers leading to a bulge of the root of the tooth Can interfere with dental extractions by causing fusion of teeth and cause necrosis of the tooth pulp by blocking normal blood supply to the teeth Pituitary Gland Summary • • • Pituitary gland is master gland controlling many other hormones Concern for mass effect, hyperfunction and hypofunction of hormones Growth hormone abnormalities can be associated with dental complications THYROID GLAND Thyroid Hormone • Functions –Growth, development and metabolism in children –Metabolism in adults –Essential for life • Two types of peripheral thyroid hormones –T4: major circulating thyroid hormone –T3: more active thyroid hormone Thyroid Physiology • TSH is secreted from the pituitary gland, travels through the blood supply to the thyroid and stimulates production of thyroid hormones (T3 and T4) • T3 and T4 feed back to the pituitary to increase or decrease TSH secretion • Levels can be affected by medications, stress, age and pituitary abnormalities Neck Anatomy Thyroid Anatomical Abnormalities Lingual Thyroid Ectopic thyroid at the base of the tongue due to embryologic abnormality PHYSICAL EXAM SAGITTAL MRI Nodular Thyroid Disease • 6-8% of adults have palpable thyroid nodules – May be visible on exam • 50% of older adults have at least one nodule (often small and non-palpable) by ultrasound • Nodules can be benign, malignant, non-functional, and hyperfunctioning Goiter Obstruction of the Trachea •Goiter is an enlarged thyroid, sometimes with discrete nodules and sometimes without •Goiter can cause obstruction of trachea and vessels with extension of the neck during dental exam and treatment •Cough, SOB, strider •Facial plethora •Distended neck veins Goiter Obstruction of Blood Vessels Superficial blood vessels bring blood from head to heart to compensate for obstruction Thyroid Function Abnormalities Hypothyroidism • Low T4 and T3 levels • Loss of feedback leads to high TSH levels • Thyroid hormone necessary for normal growth and development, metabolic rate • Thyroid hormone needed for childhood skeletal and teeth development and calcification Hypothyroidism • 4 - 8 times more common in women • Affects 10 - 20% of women over 50 • More common with family history of autoimmune disease • Major symptoms: fatigue, weight gain, constipation, facial puffiness, cold intolerance • Often symptoms misdiagnosed as menopause, aging, depression Causes of Hypothyroidism • Autoimmune chronic lymphocytic thyroiditis – Hashimoto’s disease – Positive TPO antibody • • • • Surgery Head and neck radiation Radioactive iodine ablation Transient inflammation Treatment of Hypothyroidism • Goal is TSH in normal range (0.5-5uIU/mL) • Drug of choice: Levothyroxine (T4) – Half life 7-10 days – Dosed once per day • Other medications NOT typically recommended – Cytomel (T3) short half-life (8 hours) with twice daily dosing, erratic levels – Porcine thyroid extract (Armour) – levels of T3 too high compared to T4, erratic levels, difficult to monitor Hypothyroidism Before L-T4 After L-T4 Severe Hypothyroidism Dental Concerns in Children • Delayed tooth eruption • Retention of primary teeth • Dental enamel is thinned • Malocclusion • Gingival edema, periodontal disease • Macroglossia, thick lips CRETINISM Hypothyroidism and Macroglossia Affects 1 in 4000 Live Births in North America BEFORE T4 TREATMENT AFTER T4 TREATMENT Hypothyroidism - Dental Considerations Macroglossia Malocclusion Gingival edema, periodontal disease Low metabolic rate increases sensitivity to IV/PO sedation, opioids and general anesthesia • If hypothyroidism is untreated and severe, invasive procedures, anesthesia or stress can precipitate myxedema coma • • • • – Bradycardia, hypotension, hypothermia, depressed mental status – This is a medical emergency and ER evaluation is necessary Hyperthyroidism • High T4 and T3 levels • Feedback from high peripheral levels leads to low TSH – Except for TSH-secreting pituitary adenoma loss of feedback leads to high TSH, T4 and T3 • Increased metabolism, anxiety, rapid heart rate, tremor, weight loss, dehydration Hyperthyroidism • Hypermetabolism: weight loss, heat intolerance, palpitations, tremor, rapid heart rate, anxiety • Enlarged goiter, bruit • Graves’ disease: proptosis, stare – Can be diagnosed on general dental exam when looking at patient Common forms of hyperthyroidism • Graves’ Disease – Diffuse toxic goiter – Often in younger women – Autoimmune disease – Thyroid stimulating antibodies activate the TSH receptor • Toxic multinodular goiter – More common in older individuals from iodine deficient areas • Toxic adenoma – More common in older individuals from iodine deficient areas • Thyroiditis – Usually transient, can be followed by hypothyroidism Treatment of Hyperthyroidism • Oral antithyroid medications –Propylthiouracil (three times daily) –Methimazole (daily) • Thyroidectomy • Radioactive Iodine Treatment (I-131) –Delay any oral examination for 2 weeks because of radioactive saliva Hyperthyroidism Dental Considerations • Risk of thyrotoxic crisis (thyroid storm) with general anesthesia or surgical stress (20-30% risk of death) – Fever, tachycardia, shortness of breath, tremor, coma – This is a medical emergency and ER evaluation is necessary – Local anesthetics are generally safe, but may need higher doses • Avoid epinephrine use – can provoke life-threatening hypertension and arrhythmias • Can lead to osteoporosis of alveolar bone leading to rapid dental caries and periodontal disease Thyroid Gland Summary • • • • Thyroid anatomical abnormalities such as nodules or ectopic thyroid may be seen on dental exam Hypothyroidism can lead to abnormalities in tooth development in children Untreated hypothyroidism can lead to dental complications in adults and increase risk for adverse outcomes (myxedema coma) Hyperthyroidism should be treated before dental procedures to prevent thyroid storm ADRENAL GLANDS Adrenal Glands • Adrenal cortex – Glucocorticoids (cortisol) for protein, fat and carbohydrate metabolism - regulated by pituitary ACTH – Mineralocorticoids (aldosterone) for control of sodium and potassium - regulated by BP/renin-angiotensin from kidney – Adrenal androgens (weak male hormone) secondary role in sexual maturation • Adrenal medulla – Epinephrine and Norepinephrine • Blood vessel constriction • Increased heart rate – Causes “Fight or Flight” reactions – Regulated by nervous system Pituitary-Adrenocortex Axis *This only pertains to the adrenal cortex – the adrenal medulla is not controlled by the pituitary ACTH is co-secreted with MSH (melanocyte stimulating hormone) – responsible for pigmentation Dental procedures What Does Cortisol Do? • Maintains blood pressure and cardiovascular function • Reduces the immune system's inflammatory response • Balances the effects of insulin, which allows glucose into cells for energy • Regulates the metabolism of proteins, carbohydrates, and fats Adrenal Insufficiency • Results from insufficient cortisol secretion • Primary – Adrenal disease (autoimmune [Addison’s], TB, tumor, hemorrhage) • Secondary and Tertiary – Hypothalamic or Pituitary disease (tumor, injury, autoimmune) – Adrenal suppression by exogenous steroids SECONDARY TERTIARY PRIMARY Adrenal Insufficiency Etiology Adrenal disease (autoimmune, TB, tumor, hemorrhage) Adrenal suppression by exogenous steroids ACTH High Cortisol Low Low Low Hypothalamic or Pituitary Low disease (tumor, injury, autoimmune) Low Adrenal Insufficiency Clinical Presentation • Fatigue, anorexia, nausea, weight loss • Hyperpigmentation of oral mucosa and skin – Only in primary adrenal insufficiency (excess MSH with ACTH) • • • • • • Weakness and muscle loss Delayed healing Hypotension Anorexia and weight loss Fevers Adrenal Crisis - stress, pain, general anesthesia results in decompensation with hypotension and shock – This is a medical emergency Adrenal Insufficiency and Hyperpigmentation: Gums and Buccal Mucosa Adrenal Insufficiency Treatment • Steroid hormone replacement – Normally with physiologic dosing of glucocorticoids – In primary adrenal insufficiency, also need mineralocorticoid support – In the event of stress, treat with higher doses – Cortisol levels may be affected by medications and general anesthesia, necessitating even higher doses DO NOT MEMORIZE - FOR REFERENCE ONLY Daily Replacement Dose and Relative Potency of Glucocorticoids • Hydrocortisone • Cortisone • Prednisone • Methylprednisolone • Triamcinolone • Dexamethasone 20 mg 25 mg 5 mg 4 mg 4 mg 0.75 mg 1X 1X 4X 4X 5X 25X Adrenal Insufficiency – Dental Considerations • For routine dental treatment, rarely need supplemental steroids beyond usual dose – If unsure, contact PCP or endocrinologist for confirmation • For major surgeries, treat with supplemental steroids – Extraction of bony impaction, osteotomy, bone resection, cancer surgery • Increased risk of adrenal crisis is associated with severity of surgery, drugs used, overall health status of the patient, and pain control • Surgery should be scheduled in the morning close to the time when steroids are typically taken • If resolved and steroids have been stopped within one month, treat with normal daily maintenance dose • If resolved and steroids have been stopped for more than one month, no need for perioperative steroids Adrenal Insufficiency • Other dental management issues – Hyperpigmented mucosa after injury – Delayed healing – Increased risk of infection • Consider for any patient with history of adrenal insufficiency: – Any post-op malaise, nausea,vomiting, hypotension, dizziness needs to be evaluated for adrenal crisis Adrenal Cortical Excess • Too much cortisol – Cushing’s syndrome • Etiologies – Exogenous glucocorticoid medication treatment – Adrenal adenoma, hyperplasia, or carcinoma – Pituitary ACTH-secreting adenoma (Cushing’s Disease) – Ectopic ACTH from other tumors Cushing’s Disease – Excess ACTH production by a pituitary tumor – Can cause enlargement of adrenal glands Cushing's Syndrome Symptoms • Hypertension • Central obesity - round face, buffalo hump, purple striae • Diabetes mellitus - hyperglycemia • Acne, hirsutism, amenorrhea • Increased risk of infections – Prevents WBC migration to site of infection – Hyperglycemia reduces WBC function • Osteoporosis Cushing’s and Skin Problems • Excess cortisol inhibits fibroblast synthesis of collagen –Thin skin –Purple stretch marks (striae) –Poor wound healing –Fragile capillaries and easy bruising Cushing’s – Dental Concerns/Bone Disease • Excess cortisol inhibits osteoblasts that form bone, leading to bone loss • Bone loss –Osteoporosis –Tooth loss NORMAL OSTEOPOROSIS NORMAL OSTEOPOROSIS Cushing's Syndrome – Dental Concerns –Perioperative HTN –Poor healing and increased risk of infections –Increased risk of diabetes mellitus –Increased risk of candida albicans infection (thrush) –Increased risk of peptic ulcers – avoid NSAIDs PSEUDOMEMBRANOUS CANDIDIASIS (THRUSH) Adrenal Medullary Tumor: Pheochromocytoma • Catecholamine secreting tumors • Rare – occurs in 0.2% of adults with hypertension • Presents with episodic headache, sweating, and tachycardia – 50% will have paroxysmal hypertension – Spells of anxiety, palpitations, sweats, weakness, panic – Spells often induced by a stress, anesthesia, surgery Pheochromocytoma – Dental Concerns • If patient has history of pheochromocytoma that has not been treated, do not do any procedures unless it is an emergency • Even in the case of emergency, proceed with intervention only after the following has been done: – On medications with good blood pressure control (less than 120/80) • Phenoxybenzamine, prazosin, terazosin, alphamethyltyrosine – Only after you speak with their endocrinologist or endocrine surgeon – Only with continuous BP and pulse monitoring – Emergency treatment with IV nitroprusside or phentolamine NEVER with beta blockers alone to avoid provoking crisis Adrenal Gland Summary • • • • Adrenal insufficiency can come from the pituitary or adrenal gland itself If patients are using steroids, consider higher dosing around the time of procedures Cushing’s syndrome can have effects throughout the body that impact healing after dental procedures Pheochromocytomas are endocrine emergencies and should be treated before any dental procedures are performed Take Home Points • Endocrine hormones function throughout the body, including the oropharynx • Acromegaly has effects on teeth/mandible including prognathism, malocclusion and hypercementosis • Endocrine emergencies include myxedema coma, thyrotoxic crisis (thyroid storm), adrenal crisis and untreated pheochromocytoma • Always proceed with caution for untreated endocrine conditions and consider consultation with a patient’s endocrinologist before proceeding with procedures Questions?