Endocrine Pathology Flashcards
Hormones released from anterior lobe of pituitary gland
- Growth hormone (GH)
- Prolactin (PRL)
- Follicle Stimulating hormone (FSH)
- Luteinizing hormone (LH)
- Adrenocorticotropic hormone (ACTH)
- Thyroid Stimulating hormone (TSH)
- Melanocyte Stimulating hormone (MSH)
Hormones released from posterior lobe of pituitary gland
- Vasopressin (Antidiuretic Hormone, ADH)
- Oxytocin
Key point of hyperpituitarim
- Adenomas are responsible for excess hormone production
Significance of pituitary location
- Optometric considerations
Hyperpituitarism
- Growth hormone overproduction
- Somatotroph cell adenomas
- Mutations in the GNAS1 gene
Growth hormone overproduction depends on
- Patient’s Age
- Gigantism
- Acromegaly
Gigantism results from
- Excess GH in child
- Before epiphyseal closure
Gigantism
- Elongated arms and legs
- Generalized increase in body size
Acromegaly results from
- Excess GH in adults
- After epiphyseal closure
Acromegaly
- Bone density increase
- Enlargement of mandible, hands, feet
- Gonadal disturbances
- Diabetes
Most frequent type of hyperfunctioning pituitary adenoma
- Prolactinomas (Lactotroph Adenomas)
Role of prolactin
- Maintain lactation
Lactation suppression occurs via
- GnRH Hypothalamus / Pituitary Axis
- Reduction of FSH / LH
Increased serum levels of prolactin (>100ug/L)
- Adenoma
- Physiologic hyperprolactinemia of pregnancy
- Interference with normal dopamine inhibition
Physiological causes of hyperprolactinemia
- Sleep
- Stress
Drug induced causes of hyperprolactinemia
- Haloperidol
- Reserpine
- H2 antagonist
- Fluoxetine
Systemic causes of hyperpituitarism
- Hypothyroidism
- CRF
- Cirrhosis
Hormonal causes of hyperprolactinemia
- Estrogen
Prolactinoma symptoms
- Amenorrhea
- Galactorrhea
- Infertility
- Loss of libido
Diagnosis of prolactinoma
- Presenting symptoms
History of systemic Illness, drugs/medications - MRI
- Transsphenoidal resection
Hypopituitarsim
- Decreased secretion of pituitary hormones
- Diseases of the hypothalamus
- Disease of the pituitary
Pituitary diseases involved in hypopituitarism
- Nonsecretory pituitary adenomas
- Surgery or radiation
- Ischemic necrosis (Sheehan Syndrome)
Sheehan Syndrome
- Sudden infarction of the anterior lobe
- Hemorrhage or shock during delivery
- Ischemic necrosis
Sheehan Syndrome symptoms
- Lactation failure
- ACTH deficiency
- TSH deficiency
Thyroid hormones
- 3,5,3’,5’-Tetraiodothyronine (T4 thyroxine)
- 3,5,3’-Triiodothyronine (T3)
- 3,3;,5’Triiodothyronine (rT3)
Pathology of thyroid disease
- G Protein
- cAMP
- Target genes
- Expression
- Feedback inhibition
Effects of thyroid hormones
- Normal human maturation
- Normal brain development
- Normal growth
- Influence BM
- Increase heart rate, contractility and CO
- Stimulate lipolysis
- CHO absorption
Causes of hyperthyroidism
- Pituitary Adenoma
- Germ Cell Tumors
- Follicular Adenoma
- Toxic Multinodular Goiter
Grave’s Disease (hyperthyroidism)
- Thyrotoxicosis
- Infiltrative Ophthalmopathy
- Infiltrative Dermopathy
Grave’s Disease (hyperthyroidism) pathogenesis
- Autoimmune disorder
- Thyroid stimulating immunoglobulins (TSI)
- Thyroid growth stimulating immunoglobulins (TGI)
Thyroid follicular epithelium in Grave’s Disease
- Diffuse hypertrophy
- Diffuse hyperplasia
Clinical aspects of Grave’s Disease
Hypermetabolic state:
- Nervousness
- Palpitations
- Weakness
- Weight loss
- Heat intolerance
Clinical presentation of Grave’s Disease
- Exophthalmos
- Thyroid Storm
- Cardiovascular Insufficiency
Diagnosis of Grave’s Disease (hyperthyroidism)
- Increased sTSH
- Decreased T3 and T4
Etiology of hypothyroidism
- Thyroid tissue deficiency
- Iodine deficiency
- Hypothalamic lesion
- Hypopituitarism
- Peripheral resistance
Cretinism associated with hypothyroidism
- Associated with iodine deficiency
- Offspring of iodine deficient mothers
- Iodine is essential for thyroid hormone synthesis
Manifestation of cretinism
- Severe mental retardation
- Protruding tongue
Clinical presentation of myxedema in hypothyroidism
- Apathy
- Cold Intolerance
- Mucopolysaccharide - rich edema
- Coarsening of facial features
Diagnosis of hypothyroidism
- Increased TSH
- Decreased T4
Thyroid nodules (neoplasm of the thyroid gland)
- Solitary, Neoplastic
- Younger Patient, Neoplastic
- Hx of radiation, Thyroid CA
- Radioactive iodide uptake, Benign lesion
Papillary carcinoma
- Most common CA of thyroid
- Radiation exposure
Pathology of papillary carcinoma
- Branching papillae
- Fibrovascular cores
- Orphan Annie nuclei (cytoplasmic invaginations)
Clinical findings of papillary carcinoma
- Non-functional
- Painless
- Good prognosis
Action of Cortisol (Glucocorticoids)
- Stress Hormone
- Maintain plasma glucose (increase gluconeogenesis)
- Lipolysis
- Muscle activity
Muscle activity of cortisol (glucocorticoids)
- Decrease glucose uptake and metabolism
- Decrease protein synthesis
- Increase amino acid release (protein breakdown)
Hypercortisolism
- Cushing Disease
- Primary pituitary lesion secreting ACTH
Cushing Syndrome (hypercortisolism) may result from
- Adrenal Adenoma
- Adrenal CA
- Bilateral adrenal hyperplasia
Two types of Cushing Syndrome
- Latrogenic
- Paraneoplastic
Clinical manifestations of hypercortisolism)
- Striae
- Moon facies
- Buffalo hump
- Osteoporosis
Laboratory findings of hypercortisolism (hyperadrenalism)
- Hyperglycemia
- Hypokalemia
- Increased serum cortisol
- ACTH (depends)
Pathology of hyperadrenalism (hypercortisolism)
- Adrenal Adenoma
- Adrenal CA
- Bilateral hyperplasia
- Benefit from steroid treatment
Endocrine pancreas produces
- Beta insulin
- Delta cells
- Alpha glucagon
Actions of pancreatic hormones in adipose tissue
- Increase glucose uptake
- Increase lipogenesis
- Decrease lipolysis
Actions of pancreatic hormones in striated muscle
- Increase glucose uptake
- Increase glycogen synthesis
- Increase protein synthesis
Actions of pancreatic hormones in the liver
- Decrease gluconeogenesis
- Increase glycogen synthesis
- Increase lipogenesis
Beta cell response to increasing blood sugar
- Glucose enters cell via GLUT-2 channel
- Stimulation and release of insulin
- Membrane Depolarization
- Insulin release
Insulin binds to target tissues causing
- Protein synthesis (GLUT-4 channels)
- Glucose enters target tissues
- Blood concentration of glucose declines
Pathology of the endocrine pancreas significantly increases the risk of developing
- Cardiovascular disease and mortality
- Decreases life expectancy
- Decreases life expectancy in the absence CVD
Type I diabetes etiologies can be
- Genetic
- Autoimmunity
- Environmental
Diagnosis of Type II diabetes
- Random glucose > 200 mg/dL
- Fasting glucose > 126 mg/dL (on more than one occasion)
- Abnormal oral glucose tolerance test
Pathogenesis of Type II diabetes
- Derangement in Beta cell secretion of insulin
- Beta cell damage
- Beta cell exhaustion
- Amyloid Deposition
Type II diabetes effects
- Decreased response of peripheral tissues to respond to insulin
- Post receptor signaling is decrease in insulin receptors
Pathways qssociated with pathogenesis of long-term diabetic complications
- Formation of advanced glycation end products (AGEs)
- Activation of protein kinase C (PKC)
- Intracellular hyperglycemia with disturbances in polyol pathways
AGEs bind to a specific receptor
- RAGE receptor
Located in
- Inflammatory Cells
- Endothelium
- Vascular smooth muscle
Detrimental properties of AGEs in the vascular compartment
- Release cytokines from inflammatory cells
- Generate ROS in endothelial cells
- Increases procoagulant activity in endothelium
- Enhanced proliferation of vascular smooth muscle
- Increased synthesis of ECM
Release of cytokines from inflammatory cells as a result of AGEs
- TGF – β ; deposition of excess basement membrane material
- VEGF ; responsible for changes in diabetic retinopathy
Extracellular matrix (ECM) alterations by AGEs
- ECM - Proteins hold cells and tissues together
- AGE accumulation in ECM
AGE accumulation in the ECM
- Cross-linking of polypeptides of same protein (e.g., collagen type I and IV, Elastin)
Effects of cross-linking of polypeptides of same protein (e.g., collagen type I and IV, Elastin) when AGEs accumulate in the ECM
- Decreases vascular compliance (stiffens blood vessels)
- Causes leakage of vessels in systemic circulation and retinal blood vessels
ECM alterations as a result of AGE accumulation causes
- Trapping of nonglycated proteins (e.g., LDL, albumin, plasma proteins) which…
- Accelerates atherosclerosis
- Basement membrane thickens
Tissues that do not require insulin for glucose transport
- Nerves
- Lenses
- Kidneys
- Blood vessels
In the tissues that do not require insulin for glucose transport, glucose is metabolized to
- Sorbitol (oxidative stress)
Glucose metabolism to Sorbitol depletes
- NADPH
NADPH is needed for
- Gluthathione Regeneration
Depletion of NADPH due to metabolism of glucose to sorbitol causes
- Less NADPH availability
- Less glutathione regeneration
- Oxidative damage
Diabetic complications associated with
- Cataracts
- Oxidative injury to lens
- Gangrene secondary to atherosclerosis
- Diabetic neuropathy leading to ulcers
- Proliferative retinopathy
- Nephrosclerosis
Basic anatomy/histology of the parathyroid gland
- Chief cells with CaSR (calcium sensing receptor)
Parathyroid gland function
- Synthesis and secretion of parathyroid hormone
- Maintains Ca+2 in circulation
Hyperparathyroidism causes
- Vitamin D deficiency
- Bone homeostasis
Primary hyperparathyroidism may arise from
- Hyperplasia
- Adenoma
- Carcinoma
Secondary hyperparathyroidism may arise from
- Prolonged hypocalcemia
Prolonged hypocalcemia causes
- Increased PTH secretion
- Osteoclast stimulation
Osteoclast stimulation in secondary hyperparathyroidism can cause
- Chronic renal failure
- Impaired vitamin D synthesis
- Malabsorption syndromes
Chronic renal failure results in
- Hyperphosphatemia
Hyperphosphatemia (from chronic renal failure) results in
- Secondary hyperparathyroidism
- Hypocalcemia develops (damaged kidneys)
- PTH secretion increases at all levels of serum Ca2+
- Increases osteoclast activity
- Metabolic acidosis
Morphology of hyperparathyroidism
- Cancellous bone shows dissecting osteitis
Pathology of hyperparathyroidism
- Microfractures and secondary hemorrhages
- Brown Tumor
- Cystic degeneration
Brown tumor
- Vascularity, hemorrhage, and hemosiderin deposition
Cystic degeneration causes severe hyperparathyroidism, resulting in
- Increased bone cell activity
- Peritrabecular fibrosis
- Cystic Brown tumors
Morphology of severe hyperparathyroidism
- Generalized Osteiti Fibrosa Cystica -von Recklinghausen Disease of Bone
Pathological findings of hyperparathyroidism in bone
- Osteoporosis
- Osteitis fibrosa cystica
- Fractures
Pathological findings of hyperparathyroidism in the thyroid gland
- Parathyroid adenoma
Pathological findings of hyperparathyroidism in the kidney
- Nephrolithiasis
- Polyuria
- Nephrocalcinosis
Pathological findings of hyperparathyroidism in the brain
- Depression
- Seizures
Pathological findings of hyperparathyroidism in the GI/abdominal region
- Gallstones
- Peptic ulcers
- Acute pancreatitis
Metabolic Syndrome of the endocrine pancreas
- Central obesity
- Atherogenic dyslipidemia
- Insulin resistance or glucose intolerance
- Prothrombotic state
- Raised blood pressure
- Proinflammatory state
