Endocrine Pathology Flashcards
Describe the pituitary gland
-Small bean-shaped gland at base of brain within sella turcica
-Composed of two distinct lobes:
1. Anterior pituitary = “Adenohyphysis”
2. Posterior pituitary = “Neurohypophysis”
Describe the two lobes of the pituitary gland
- Anterior pituitary =
Adenohypophysis”
-Develops from epithelial cells derived embryologically from oral cavity (posterior pharynx) - Posterior pituitary = “Neurohypophysis”
-Develops from the floor of the diencephalon
What is the function of the pituitary gland?
Regulation of most endocrine glands via hormones (hypothalamus controls the release of hormones from pituitary gland)
List the anterior pituitary hormones
- TSH - thyroid stimulating hormone
- FSH - follicle stimulating hormone
- LH - luteinizing hormone
- GH - growth hormone
- ACTH - adrenocorticotrophic hormone
- PRL - prolactin
*produced in anterior pituitary cells –> Hypothalamic control
Describe TSH
Thyroid stimulating hormone –> thyroid gland
-stimulatory; controlled by TRH thyrotropin releasing hormone
Describe FSH
Follicle stimulating hormone –> ovaries/testes
-stimulatory; controlled by GnRH gonadotropin releasing hormone
Describe LH
Luteinizing hormone –> ovaries/testes
-stimulatory; controlled by GnRH gonadotropin releasing hormone
Describe GH
Growth hormone –> fat/muscle/bones/liver
-stimulatory; controlled by GHRH growth hormone releasing hormone
-inhibitory; controlled by GIH growth hormone inhibitory hormone
Describe ACTH
Adrenocorticotrophic hormone –> adrenal cortex
-stimulatory; controlled by CRH corticotropin releasing hormone
Describe PRL
Prolactin –> mammary glands
-inhibitory; controlled by PIF prolactin inhibitory hormone/dopamine
List the posterior pituitary hormone
- ADH
- Oxytocin
*Produced in hypothalamic neurons and stored in posterior pituitary –> hypothalamic control
Describe ADH
Anti-diuretic hormone –> kidney
-promotes resorption of water in collecting tubules of kidney
Describe Oxytocin
Oxytocin hormone –> uterus
-promotes contraction of smooth muscle in pregnant uterus
What is the most common cause of hyperpituitarism?
Functional Adenoma
What is the pathogenesis and histology of Adenomas?
Pathogenesis: G-protein mutations (most common)
Histology: Single cell type - producing single hormone
Describe Craniopharyngioma
Most common pituitary tumor of CHILDHOOD (rare)
What is the pathogenesis of Craniopharyngioma? The histology? The clinical/oral signs?
Pathogenesis: Neoplasia
Histology: resembles odontogenic tumors
Clinical/Oral:
-usually in children*
-trouble walking*
-loss of balance
-slow growth
-fatigue
-vomiting
Describe Giantism
Enormous growth in stature before bone epipyhses close
What is the pathogenesis of Giantism? The histology? The clinical/oral signs?
Pathogenesis: Functioning adenoma in CHILDHOOD
Histology:
-pituitary cell type = somatotroph
-hormone produced = increased GH
Clinical/Oral:
-short lifespan (increased cardiac output/heart failure)*
-height usually over 7ft*
-proportionally large
Describe Acromegaly
Increase in appositional bone growth and organ growth (changes occur very slowly - bony epiphyses are closed)
What is the pathogenesis of Acromegaly? The histology? The clinical/oral signs?
Pathogenesis: Functioning adenoma in ADULTHOOD
Histology:
-pituitary cell type = somatotroph
-hormone produced = increased growth hormone
Clinical/Oral:
-mandibular prognathism*
-macroglossia*
-new diastema develops*
-large hands/feet - normal height*
-patients develop hypertension and CHF
Describe Pituitary Dwarfism
Proportionate decrease in height when bony epiphyses are open
(Don’t confuse this with achondroplastic dwarfs (genetic))
What is the pathogenesis of Pituitary Dwarfism? The histology? The oral/clinical signs?
Pathogenesis: Pituitary hyposecretion of GH in CHILDREN (trauma; autoimmune; congenital; tumor)
Histology: decreased hormone produced = decreased growth hormone
Oral/Clinical:
-small teeth and jaws *
-proportionate small stature *
Describe Simmond Disease
Atrophy or decreased function of pituitary gland target organs
What is the pathogenesis of Simmond Disease? The histology? Clinical/Oral signs?
Pathogenesis: Anterior pituitary failure
Histology: Decreased GH, LH, FSH, TSH, ACTH, PRL
Clinical/Oral:
-anorexia and muscle weakness*
-hypotension; hypoglycemia; anemia*
-dry skin and loss of pubic/axillary hair*
-atrophy of genitalia and breasts*
-premature senility*
Describe Sheehan Postpartum Necrosis
Atrophy or decreased function of pituitary gland target organs after birth
*most common form of anterior pituitary necrosis
(progresses to symptoms of simmond disease is not treated)
What is the pathogenesis of Postpartum Necrosis? The histology? The clinical/oral signs?
Pathogenesis: excessive blood loss during delivery –> ischemia = necrosis of anterior pituitary
Histology: Decreased GH, LH, FSH, TSH, ACTH, PRL
Oral/Clinical:
-no lactation*
-amenorrhea*
-weakness and lethargy*
-anemia*
Describe Diabetes Insipidus
Imbalance of fluids with defect in urine concentration (nothing to do with blood sugar!)
What are the oral/clinical signs of Diabetes Insipidus? The histology?
Clinical/Oral:
-Polyuria* (increased urination - 5 L/day vs 2 L/day)
-Polydipsia* (increased thirst)
-Hypotension
Histology: Decreased ADH secretion or decreased kidney response
What is Diabetes Insipidus associated with? (4)
1) Craniopharyngioma
2) Langerhans cell disease
3) Head trauma
4) Idiopathic
What are the 3 distinct cell types seen in the anterior pituitary
1) Cells with basophilic cytoplasm
2) Cells with eosinophilic cytoplasm
3) Cells with chromophobic cytoplasm
Describe the histology of the posterior pituitary
-Modified glial cells = pituicytes
-Axon processes extending from hypothalamus
Describe Thyroid Gland development
-Located below and anterior to larynx
-Develops from tubular evagination of pharyngeal epithelium descending from foramen cecum
-Thyroglossal duct disappears or may remain as a central pyramidal lobe
-Ectopic thyroid tissue is most often located at base of tongue = lingual thyroid
What is the function of the thyroid gland?
-Regulation of metabolism and basic body functions
-Controlled by hypothalamus and anterior pituitary gland
Describe the histology of the thyroid gland
-Thyroid is developed into lobules –> each with 20-40 follicles
-Follicular cells produce and store thyroglobulin as a colloid
-Clusters of C-cells are between follicles and produce calcitonin
Thyroid follicles are filled with ______ and lined with _______
colloid; simple cuboidal epithelial cells (follicular cells)
Describe the thyroid hormones produced by follicular cells and stored as Thyroglobulin
1) T4 - Thyroxine –> brain, bone, heart, muscles
-Hypothalamus releases TRH = stimulates anterior pituitary to release TSH = activates G-protein –> cAMP released –> stimulates thyroglobulin conversion to T4 (iodine is needed!)
2) T3 - Triiodothyronine –> brain, bone, heart, muscles
-Hypothalamus releases TRH = stimulates anterior pituitary to release TSH = activates G-protein –> cAMP released –> stimulates thyroglobulin conversion to T3 (iodine is needed!)
*Negative feedback control
Describe the thyroid hormones produced by parafollicular C-cells
Calcitonin –> bone
-Controlled by increase in blood calcium
*Negative feedback control
What are the functions of T3 and T4?
Increased:
-Metabolic rate
-Heat production
-Appetite
-GH secretion
-Alterness/reflexes
-After release –> most free T4 is de-iodinated to T3
-T3 binds to receptors in target tissues with 10x greater affinity
What are the functions of Calcitonin
-Increased bone formation
-Stimulates osteoblastic activity
-Produced and released when blood calcium levels are high
Describe Thyroglossal Duct Cyst
Developmental cyst located anterior and superior to larynx
What is the pathogenesis of a Thyroglossal Duct Cyst? The histology? The oral/clinical signs?
Pathogenesis: Remnants of thyroglossal duct form cyst
Histology: Thyroid follicle is cyst wall
Oral/Clinical:
-soft/fluctuant mass at midline
-elevates when swallowing
-elevates when tongue protruded
-usually in children; under 20 yrs
Describe diagnostic thyroglossal duct cyst
Thyroid follicles in cyst wall
Describe a Lingual Thyroid
Ectopic thyroid tissue at base of tongue near foramen cecum
What is the pathogenesis of lingual thyroid? The histology? The oral/clinical signs?
Pathology: possible hypothyroidism
Histology: normal thyroid tissue
Oral/Clinical:
-vascular swelling near foramen cecum
-women (4:1) - any age
-dysphasia, sore throat
-bleeding possible
**Must refer for testing before biopsy
Describe Cretinism
Hypothyroidism in infants/children
What is the histology of Cretinism? The oral/clinical signs?
Histology: Decreased T3 and T4
Oral/Clinical:
-macroglossia
-delayed tooth eruption
-short stature; round face
-wide-spaced eyes; flat nasal bridge
** causes permanent mental retardation if not treated
What is Cretinism associated with?
-Iodine deficiency
-Aplasia
-Genetic mutation
Describe Myxedema
Hypothyroidism in adults
What is the histology of Myxedema? Oral/clinical signs?
Histology: Decreased T3 and T4 or decreased TSH
Oral/Clinical:
-macroglossia
-decreased metabolic rate - decreased RR and HR
-weight gain; cold intolerance; dry skin
**Causes reversible mental sluggishness and apathy
What is Myxedema associated with?
-Hashimoto disease
-Iodine deficiency
-Goiter
-Surgical ablation
Describe Hashimoto Disease
Progressive hypothyroidism in adults
What is the pathogenesis of Hashimoto disease? The histology? The oral/clinical signs?
Pathogenesis: Autoimmune disease –> auto-antibodies induce T-cells to destroy thyroid tissue = loss of follicular cells
Histology:
-Lymphocytic infiltrate; loss of follicular cells
- Decreased T3/T4 levels
Oral/Clinical:
-Symmetrical enlargement of thyroid
-Females (10:1) - 45-65yrs
-Genetic predisposition
**Associated with other auto-immune diseases
Describe Adenoma
Benign, encapsulated neoplasm of follicular epithelium
**Most are non-functional (don’t produce hormone)
*Toxic adenoma produces increased T3/T4 (rare)
What is the pathogenesis of adenoma? The histology? The oral/clinical signs?
Pathogenesis: neoplasia
Histology: resembles normal thyroid parenchyma
Oral/Clinical:
-usually solitary tumor
-rarely turns malignant
*Difficult to distinguish adenoma from goiter or malignancy
Describe Papillary Carcinoma
-Most common thyroid malignancy
-Grows slowly
-Spreads to cervical nodes
What is the pathogenesis of Papillary Carcinoma? Histology? Oral/clinical signs?
Pathogenesis: non-functional malignant neoplasia
Histology: Orphan Annie nuclei (clear nuclei, well formed papillae)
Oral/Clinical:
-painless mass in thyroid
-painless cervical node swelling
-any age
-history of previous radiation exposure
*good prognosis –> 95% 10yr survival
Describe Medullary Carcinoma
Thyroid malignancy of C-cells
What is the pathogenesis of Medullary Carcinoma? Histology? Oral/Clinical signs?
Pathogenesis: Functional malignant neoplasia, secretes calcitonin
Histology: Amyloid deposits
Oral/Clinical:
-painless mass in neck
-dysphagia; hoarseness
-adults 50-60yrs
**children/young adults if MEN 2A/2B (an inherited syndrome)
What is Medullary Carcinoma associated with?
Hereditary –> MEN 2A/MEN 2B
Describe Multinodular Goiter
Nodular enlargement of thyroid gland
*Can present as: euthyroid - hypothyroid - hyperthyroid
What is the pathogenesis of Multinodular Goiter? Histology? Oral/Clinical signs?
Pathogenesis: Increased TSH secretion
Histology: Follicular cell hypertrophy
Oral/Clinical:
-asymmetrical large mass on thyroid
-dysphasia
-possible airway obstruction
Describes Graves Disease
Most common form of hyperthyroidism
What is the pathogenesis of Graves Disease? Histology? Oral/Clinical signs?
Pathology: Autoimmune disease –> auto-antibodies mimic TSH = increased T3 and T4
Histology: Hyperplastic follicular cells - watery colloid
Oral/Clinical:
-symmetric enlargement of thyroid
-females (7:1) - 20-40yrs
-exophthalmos
-increased metabolism - increased HR, RR and BP, weight loss
-nervousness, diarrhea; sweating
Describe Goiter
Refers to any enlargement of thyroid tissue. Associated with:
-hypothyroidism
-hyperthyroidism
-normal thyroid function
Describe Aplasia
Developmental failure of thyroid to form associated with hypothyroidism
Describe Atrophy
Shrinkage of thyroid gland. Associated with:
-Simmond disease
-surgery
-hypothyroidism
Describe parathyroid gland development
-Developmentally derived from pharyngeal pouches
-Typically, 4 tiny tan glands located near left and right thyroid lobes
Describe parathyroid gland function
-Regulation of calcium homeostasis
-Controlled by blood levels of free (ionized) calcium
**Not controlled by hypothalamus/pituitary hormones
Describe parathyroid gland histology
-Primarily composed of chief cells with secretory granules containing PTH (parathyroid hormone)
-Adipocytes are found throughout the disease
Describe parathyroid hormone (PTH)
*Produced and secreted by chief cells
PTH –> kidneys and bone
-Decreased free calcium levels in the blood stimulate the chief cells to produce and secrete PTH
-Increased free calcium levels in the blood inhibit the secretion of PTH
PTH functions by:
Increased…
-calcium reabsorption in kidney
-active Vit D conversion in kidney
-calcium absorption in GI
-phosphate excretion in kidney
-osteoclastic activity = bone releases Ca
**NO hypothalamic or pituitary gland control of parathyroid
Describe Primary Hyperparathyroidism
Increased secretion of PTH from parathyroid glands
**Causes increased blood calcium levels and decreased blood phosphate levels
What is the pathogenesis of Primary Hyperparathyroidism? Histology? Oral/Clinical signs?
Pathogenesis:
-Adenoma - secretes PTH
-Primary hyperplasia - increased PTH
Histology: benign tumor/hyperplasia of parathyroids
Oral/Clinical: “bones-stones-groans-moans”
-painful bones
-kidney stones
-GI pain/peptic ulcers/pancreatitis
-psychic moans/fatigue-depression
-adults- over 50yrs
**loss of lamina dura
**radiolucencies in jaws
Describe Parathyroid Adenoma
-Solitary, benign
-Single parathyroid gland
-Histology: proliferation of chief cells and decreased adipose tissue
Describe Parathyroid Primary Hyperplasia
-Enlargement of multiple parathyroid glands
-Histology: chief cell hyperplasia and decreased adipose tissue
What is the pathogenesis of Secondary Hyperparathyroidism? Histology? Oral/Clinical signs?
Pathogenesis: Renal failure causes phosphate retention = decreased blood calcium = increased PTH production/secretion
Histology: Chief cell hyperplasia and decreased adipose tissue
Oral/Clinical:
-bones-stones-groans-moans
**loss of lamina dura
**radiolucencies in jaws
*Hyperphosphatemia leads to metastatic calcification of blood vessels = ischemic necrosis of skin and other organs (calciphylaxis)
Describe Hypoparathyroidism?
Decreased production and secretion of PTH –> usually develops secondary to hypocalcemia
Decreased blood calcium leads to:
1) neuromuscular excitability
2) cardiac arrhythmias –> life threatening
What is the pathogenesis of hypoparathyroidism? The clinical/oral signs?
Pathogenesis:
1) surgery
2) aplasia
3) autoimmune disease
Oral/Clinical:
-hypoplasia in developing teeth
-perioral paresthesia; seuizures
-Trousseau sign (wrist/hand)
-Chvostek sign (facial nerve)
Describe Hypocalcemia
Decreased blood calcium levels –> usually the underlying cause of hypoparathyroidism
Hypocalcemia presents as:
1) Paresthesia
2) Neuromuscular excitability
*Chvostic sign
*Trousseau sign
3) Dental defects
4) Cardiac arrhythmias
Describe Hypercalcemia
Increased blood calcium levels –> leads to precipitation of calcium in organs (metastatic calcification)
What are the causes of Hypercalcemia that increase PTH
1) Parathyroid adenoma
2) Renal disease = secondary hyperparathyroidism
What are the causes of Hypercalcemia that decrease PTH
1) Bone malignancies
2) Malignancies producing increased calcium
3) Granulomatous disease
4) Vitamin D toxicity
Describe adrenal gland development
-Above and slightly medial to the kidneys
-Develops from 2 distinct embryologic tissues:
1) mesoderm –> forms the adrenal cortex
2) neuroectoderm –> forms the adrenal medulla
What controls the adrenal glands?
Hypothalamus and Anterior Pituitary gland, renal pathway, stress/fear
Describe the histology of the adrenal gland cortex
3 layers:
1) Zona glomerulosa –> produces aldosterone
2) Zona fasciculta –> produces cortisol
3) Zona reticularis –> produces steroid sex hormones
Describe the histology of the adrenal gland medulla
Composed of chromaffin cells (pheochromocytes) –> produce catecholamines
List and describe and adrenal cortex hormones
1) Aldosterone –> kidney
2) Cortisol –> body organs/tissues
-controlled by ACTH/CRH
3) Androgens/Estrogens –> ovaries/testes
-controlled by ACTH/CRH
List and describe adrenal medulla hormones
Epinephrine/Norepi –> body organs/tissues
Describe Cushing Syndrome
Excess cortisol levels
What is the pathogenesis of Cushing Syndrome? The histology?
Pathogenesis:
*Exogenous –> glucocorticoids administered (most common)
*Endogenous:
-hypersecretion of ACTH
-ectopic secretion of ACTH
-ACTH-producing malignant tumor
Histology:
*Exogenous –> bilateral cortical atrophy
*Endogenous –> bilateral hyperplasia or neoplasia
What is an adrenal crisis?
Adrenal gland is unresponsive to ACTH
*Pt’s on exogenous steroids develop adrenal atrophy –> if discontinued suddenly –> possible adrenal crisis
*Most pt’s regain adequate Cortisol response to stress w/in 2 weeks after cessation of steroid therapy
**Long term steroids taken every other day = not at risk for adrenal crisis
What do the sign/symptoms of cushing syndrome reflect?
increased glucose and decreased protein
What are the oral/clinical signs of cushing syndrome?
-HTN, weight gain
-Truncal obesity; ‘moon facies’, ‘buffalo hump’
-Thin skin, bruising, cutaneous striae
-Decreased muscle mass
-Hypergycemia - secondary diabetes
-Gastric ulcers; GI bleeds
-Poor wound healing; increased infections
-Osteoporosis/compression fractures
-Mood swings/psychosis
Describe Conn Syndrome
Chronic increased aldosterone levels with decreased renin
What is the pathogenesis of Conn syndrome? The histology? The oral/clinical signs?
Pathogenesis:
1) Bilateral hyperplasia of adrenal cortex
2) Aldosterone-producing adenoma
Histology:
1) Diffuse hyperplasia
2) Adenoma –> spironolactone bodies
Oral/Clinical:
-HTN
-Hypokalemia –> weakness, paresthesia
-Children/young adults
Describe Secondary Hyperaldosteronism
Increased aldosterone and increased renin
Describe 21-Hydroxylase Deficiency
Chronic increased androgen levels
What is the pathogenesis of 21-Hydroxylase Deficiency? The histology?
Pathogenesis: Congenital adrenal hyperplasia
Histology: Bilateral hyperplasia of the adrenal cortex
**21-hydroxylase is needed to make mineralocorticoids and glucocorticoids. Deficiency = decreased cortisol and decreased aldosterone production = cortisol/aldosterone deficiency. Substances for cortisol/aldosterone will build up –> forms excessive androgen
What are the oral/clinical signs of 21-Hydroxylase Deficiency?
-Masculinization in females (clitoral hypertrophy/hirsutism)
-Pseudo-hermaphroditism in female infants
-Enlargement of external genitalia in young men
-Oligospermia in men - but they are fertile
-Cortisol deficiency and aldosterone deficiency
Describe Bilateral Hemorrhagic Necrosis
Acute adrenocortical insufficiency = acute adrenal crisis
*No glucocorticoids/no mineralocorticoids/no catecholamines
What is the pathogenesis of Bilateral Hemorrhagic Necrosis? The histology? The oral/clinical signs?
Pathogenesis:
1) Septicemia
2) Anticoagulant therapy
3) Complication of pregnancy
4) DIC
Histology:
-Extensive necrosis of all 3 cortical layer cells
-Extensive necrosis of medullary cells
Oral/Clinical: Initially non-specific symptoms
-abdominal/thoracic pain; fatigue; anorexia; nausea
-leads to acute adrenal crisis
Describe the signs and symptoms of Acute Adrenal Crisis
-Significant decreased BP
-Hypoglycemia
-Coma
-Death w/o immediate steroid replacement
Describe Waterhouse-Friderichsen Syndrome
Massive bilateral adrenal hemorrhage specifically associated with overwhelming sepsis causing acute adrenal crisis
What is the pathogenesis of Waterhouse-Friderichsen Syndrome? The histology? The oral/clinical signs?
Pathogenesis: Neisseria meningitidis bacterial sepsis
Histology: Extensive necrosis
Oral/Clinical:
-children (mimics child abuse)
-acute hypotension
-skin purpura
-coma and death with 48 hours
*60% mortality
Describe Addison Disease
Primary Chronic Adrenal Insufficiency
-Chronic loss of all cortical hormones and increased ACTH
-Causes decreased BP; increased K; decreased Na; dehydration
What is the pathogenesis of Addison Disease? Histology? Oral/Clinical signs?
Pathogenesis: Autoimmune adrenalitis
Histology: Atrophy of adrenal cortex
Oral/Clinical:
-oral/skin hyperpigmentation
-hypotension
-salt craving
-anorexia; fatigue; weakness; diarrhea
**Treatment is hormone replacement; high risk for acute adrenal crisis
Describe Secondary Chronic Adrenal Insufficiency
Chronic decreased ACTH secretion = leads to decreased cortisol and decreased androgens
**NO deficiency of aldosterone / NO hyperpigmentation
What is the pathogenesis of Secondary Chronic Adrenal Insufficiency? The histology? The oral/clinical signs?
Pathogenesis:
-Metastasis to hypothalamus/pituitary gland
-Infection
-Radiation
Histology: Atrophy of adrenal cortex
Oral/Clinical:
-Anorexia
-Fatigue; weaknes
-Diarrhea
*Tx = hormone replacement; high risk for acute adrenal crisis
Describe Pheochromocytoma
Functioning tumor of adrenal medulla = increased catecholamines
-Can be benign or malignant; unilateral or bilateral
-25% of pheochromocytomas are associated with syndromes
What is the pathogenesis of Pheochromocytoma? The histology? The oral/clinical signs?
Pathogenesis: Neoplasia
Histology: Chromaffin cells
Oral/Clinical:
-HTN - 90%
-Episodes of “fight-or-flight” symptoms
*Contraindication for local anesthetic with vasoconstrictor
Describe Neuroblastoma
Malignant tumor developing from immature nerve cells
-Most often arises in medulla of adrenal glands
-Second most common childhood cancer
What is the pathogenesis of a Neuroblastoma? The histology? The oral/clinical signs?
Pathogenesis: Malignant neoplasia
Histology: Poorly differentiated neuroblasts
Oral/Clinical:
-Children under 5yrs
-Large abdominal mass
-Fever; weight loss
Describe Multiple Endocrine Neoplasia Syndromes
Group of autosomal-dominant inherited diseases caused by proliferative lesions of multiple endocrine organs
Describe MEN 2B - Multiple Mucosal Neuroma Syndrome
Autosomal dominant; single amino acid change in RET gene
What are the clinical signs of MEN 2B? Oral?
Clinical:
1) Mucosal neuromas
2) Pheochromocytomas
3) Medullary carcinoma of thyroid - 100%
Oral:
-Multiple oral neuromas = 1st manifestation of sx
-Lips/tongue most common sites
-Large thick lips
**Refer to physician
