Endo Flashcards
Thyroid development
Where does it arise from?
Where does it descend to?
Connected to what by what?
Thyroid diverticulum arises from floor of primitive pharynx. Descends into neck. Connected to tongue by thyroglossal duct, which normally disappears but may persist as pyramidal lobe of thyroid
Foramen Cecum
Normal remnant of thyroglossal duct in tongue
Most common ectopic thyroid tissue site
Tongue
Presentation of thyroglossal duct cyst
Anterior midline neck mass that moves with swallowing
Presentation of persistent cervical sinus leading to branchial cleft cyst in lateral neck
Small mobile mass on side of neck that does not move with swallowing
What does the Fetal Adrenal Gland consist of?
Outer adult zone and inner active fetal zone
Adult zone of fetal adrenal gland
Activity?
Control of activity?
Dormant during early fetal life but begins to secrete cortisol late in gestation
Fetal pituitary and placenta make ACTH and CRH
What is fetal cortisol responsible for?
Fetal lung maturation and surfactant production
Embryological origin of adrenal cortex?
Mesoderm
Embryological origin of adrenal medulla?
Neural Crest Cells
Layers of Adrenal Gland w/ Secretory Products
“GFR –> Salt, Sugar, Sex
Deeper you go, the sweeter it gets”
Capsule
Zona Glomerulosa –> Aldosterone
Zona Fasciculata –> Cortisol, Sex Hormones
Zona Reticularis –> Sex Hormones (androgens)
Medulla –> Catecholamines (NE, Epi)
Zona Glomerulosa
Responsive to
Secretory Product
Renin-Angiotensin –> Aldosterone
Zona Fasciculata
Responsive to
Secretory Product
ACTH, Hypothalamic CRH –> Cortisol, Sex Hormones
Zona Reticularis
Responsive to
Secretory Product
ACTH, Hypothalamic CRH –> Sex Hormones (androgens)
Adrenal Medulla
Responsive to
Secretory Product
Preganglionic sympathetic fibers –> ACh –> Catecholamines (NE, Epi)
Most common tumor of adrenal medulla in adults?
Pheochromocytoma
Most common tumor of adrenal medulla in children?
Neuroblastoma
Pheochromocytoma vs Neuroblastoma in terms of clinical presentation
P –> episodic HTN
Adrenal gland venous drainage
L Adrenal –> L Adrenal Vein –> L Renal Vein –> IVC
R Adrenal –> R Adrenal Vein –> IVC
Posterior Pituitary Gland AKA Products Source of products? How are they transported? Embryological origin
Neurohypophysis
Secretes ADH and Oxytocin made in hypothalamus and shipped to PP via neurophysins (carrier proteins)
Derived from neuroectoderm
Anterior Pituitary Gland
AKA
Secretory Products
Embryological origin
Adenohypophysis
“My FLAT PiG”
Melanotropin (MSH), FSH, LH, ACTH, TSH, Prolactin, GH
Derived from oral ectoderm (Rathke’s Pouch)
Acidophils in the Anterior Pituitary gland secrete
GH and Prolactin
Basophils in the Anterior Pituitary gland secrete
“B FLAT”
Basophils –> FSH, LH, ACTH, TSH
Which hormones share the same α subunit?
FSH, LH, TSH, and hCG
Endocrine Pancreas
Name
Cell types: Products and Location
Embryological origin?
Islets of Langerhans "INsulin is on the INside" α: Glucagon, Peripheral β: Insulin, Central δ: Somatostatin, Interspersed Pancreatic Buds
Mechanism of Insulin Release
↑ Glucose metabolism –> ↑ ATP –> closing of K channels –> depolarization –> V gated Ca channels open –> insulin secretion
Does insulin cross the placenta?
No
What organs take up glucose independently of insulin?
“BRICK L”
Brain, RBCs, Intestines, Cornea, Kidney, Liver
GLUT1
Insulin independent in Brain and RBCs
GLUT2
Bidirectional in β cells, liver, kidney, and small intestine
GLUT4
Insulin dependent in adipose tissue and skeletal muscle
Effects of Insulin
Anabolic ↑ G transport into skeletal muscles and adipose tissue ↑ Glycogen synthesis and storage ↑ Triglyceride synthesis and storage ↑ Na retention by kidneys ↑ Protein synthesis in muscles ↑ K uptake by cells ↑ AA uptake by cells ↓ Glucagon release
What triggers an ↑ in insulin release
Hyperglycemia
GH (via insulin resistance)
β2 agonists
What triggers a ↓ in insulin release
Hypoglycemia, Somatostatin, α2 agonists
Insulin Receptor Cellular Pathway
Insulin –> Tyrosine Phosphorylation –> IP3 and RAS/MAP
IP3 –> Glycogen, Lipid, + Protein synthesis and GLUT4 vesicle mobilization
MAP/RAS –> Cell Growth and DNA synthesis
What does the brain use for energy during starvation?
Ketone bodies
What do RBCs use for energy during starvation
RBCs can only use glucose b/c they cannot preform aerobic respiration
Functions of Glucagon
Catabolic
↑ Gluconeogenesis, Glycogenolysis, Lipolysis, Ketone production
What is glucagon secreted in response to?
Hypoglycemia
What inhibits glucagon production?
Insulin, Hyperglycemia, Somatostatin
What does TRH do?
TRH –> TSH and Prolactin
What does DA do in the Pituitary gland?
DA –/ prolactin
What does CRH do?
CRH –> ACTH, Melanocyte Stimulating Hormone (MSH), β-endorphin
What does GHRH do?
GHRH –> GH
What does somatostatin do in the Pituitary?
Somatostatin –/ GH and TSH
What does GnRH do?
GnRH –> FSH and LH
What does Prolactin do in the pituitary?
Prolactin –/ GnRH
Prolactin
Source
Function in Breast
Function in Pituitary
Anterior Pituitary Gland
Stimulates milk production in breasts
Prolactin –/ GnRH synthesis and release which leads to an inhibition of ovulation and spermatogenesis
Regulation of Prolactin Secretion
DA from Hypothalamus –/ Prolactin secretion from Anterior Pituitary
Prolactin in turn increases DA synthesis and secretion in the Hypothalamus thereby inhibiting its own secretion
TRH –> Prolactin secretion
Affects of DA agonists on prolactin?
DA agonists (bromocriptine) inhibit prolactin and can be used to treat prolactinoma
What stimulates prolactin secretion?
TRH, DA antagonists (antipsychotics) and Estrogens (OCP, pregnancy)
Growth Hormone Name Source Function and MoA Pattern of release Regulation
Somatotropin
Anterior Pituitary Gland
Stimulates linear growth and muscle mass through IGF1/somatomedin secretion
↑ Insulin Resistance (Diabetogenic)
Pulsatile release in response to GHRH
Secretion ↑ during exercise and sleep
Secretion inhibited by glucose and somatostatin
Excess GH in adults vs children
Acromegaly in adults
Gigantism in children
Desmolase
Regulation
Action
ACTH –> Desmolase
Ketoconazole –/ Desmolase
D turns Cholesterol into Pregnenolone
Path of Aldosterone Synthesis
Pregnenolone –> [3β Hydroxysteroid dehydrogenase] –> Progesterone –> [21 hydroxylase] –> 11 deoxycorticosterone –> [11β hydroxylase] –> corticosterone –> [aldosterone synthase] –> Aldosterone
Path of Cortisol Synthesis
Pregnenolone –> [17α hydroxylase] –> 17 hydroxypregnenolone –> [3β Hydroxysteroid dehydrogenase] –> 17 hydroxyprogesterone –> [21 hydroxylase] –> 11 deoxycortisol –> [11β hydroxylase] –> Cortisol
or…
Pregnenolone –> [3β Hydroxysteroid dehydrogenase] –> Progesterone –> [17α hydroxylase] –> 17 hydroxyprogesterone –>
Path of Testosterone and DHT production
Pregnenolone –> [17α hydroxylase] –> 17 hydroxypregnenolone –> Dehydroepiandrosterone (DHEA) –> [3β Hydroxysteroid dehydrogenase] –> Androstenedione –> Testosterone –> [5α reductase] –> DHT
or…
17 hydroxyprogesterone –> Androstenedione
Synthesis of Peripheral Estrogens
Aromatase turns Androstenedione into Estrone
Aromatase turns Testosterone into Estradiol
Estrone can convert to Estradiol
Deficiencies in Bilateral Adrenal Hyperplasias
17α hydroxylase, 21 hydroxylase, 11β hydroxylase
Why do adrenal enzyme deficiencies lead to hyperplasia
↑ ACTH stimulation because of ↓ cortisol
17α hydroxylase deficiency Mineralcorticoids Cortisol Sex Hormones Presentation Male vs Female
Mineralcorticoids ↑
Cortisol ↓
Sex Hormones ↓
HTN, HypoK
Male: ↓ DHT –> pseudohermaphroditism (variable, ambiguous genitalia with undescended testes)
Female: Externally phenotypic female with normal internal sex organs but lack secondary sex characteristics
21 hydroxylase deficiency Mineralcorticoids Cortisol Sex Hormones Presentation
Mineralcorticoids ↓
Cortisol ↓
Sex Hormones ↑
Hypotension, HyperK, ↑ Renin activity, Volume depletion
Masculinization leading to pseudohermaphroditism in females
11β hydroxylase deficiency Mineralcorticoids Cortisol Sex Hormones Presentation
Mineralcorticoids: ↓ Aldosterone, ↑ 11-deoxycorticosterone Cortisol ↓ Sex Hormones ↑ HTN, Masculinization
Cortisol
Source
Function
Regulation
Adrenal Zona Fasciculata "BBIIG" Maintains BP ↓ Bone formation ↑ Insulin Resistance AntiInflammatory/Immunosuppressive ↑ Gluconeogenesis, lipolysis, proteolysis Inhibits Fibroblasts --> striae CRH (hypothalamus) --> Anterior Pituitary --> ACTH --> Cortisol production in Zona Fasciculata
How is cortisol transported in the blood?
Corticosteroid binding globulin (CBG)
How does cortisol maintain BP?
Upregulates α1 receptors on arterioles –> ↑ sensitivity to NE and Epi
How is cortisol an anti-inflammatory/immunosuppressive?
–/ production of leukotrienes and prostaglandins
–/ leukocyte adhesion
–/ histamine release
Reduces eosinophils
–/ IL2 production
How does excess cortisol alter CRH, ACTH and Cortisol secretion
Decreases all of them
How does chronic stress affect cortisol secretion?
Stress induces prolonged secretion
PTH
Source
Function
Chief Cells of Parathyroid ↑ Bone resorption of Ca and PO4 ↑ Kidney reabsorption of Ca in DCT ↑ Calcitriol production by stimulating kidney 1α Hydroxylase ↓ Reabsorption of PO4 in PCT
Regulation of PTH
↓ Serum Ca –> ↑ PTH
↓ Serum Mg –> ↑ PTH
↓↓ Serum Mg –> ↓ PTH
↑ Vit D –> ↓ PTH
Common causes of ↓ Mg
Diarrhea, Aminoglycosides, Diuretics, EtOH abuse
Number of Parathyroid glands
4 glands
How does PTH affect bone
Stimulate Ca release from bone mineral compartment
Stimulates osteoblastic cells
Stimulates bone resorption via indirect effect of osteoclasts
Enhances bone matrix degradation
Actions of Vit D
↑ Intestinal absorption of Ca and PO4
↑ Release of PO4 from bone matrix
↑ Bone resorption of Ca and PO4
Clinical manifestation of high PTH
↑ serum Ca, ↓ serum PO4, ↑ urine PO4
How does PTH affect osteoblasts and osteoclasts
PTH –> ↑ production of M-CSF and RANK-L in osteoblasts which stimulates osteoclasts
Source of Vit D
D3 from sun exposure in skin
D2 ingested from plants
Both converted to 25-OH in liver and 1,25-(OH)2 in the kidney
Regulation of Vit D
↑ PTH, ↓ [Ca], ↓ PO4 –> ↑ VitD
↑ Vit D inhibits its own production
24,25-(OH)2 D3
Inactive form of VitD
VitD deficiency in adults vs children
Children –> rickets
Adults –> osteomalacia
Calcitonin
Source
Function
Regulation
Parafollicular cells (C cells) of thyroid
↓ bone resorption of Ca
↑ serum Ca –> calcitonin secretion
Normal role of Calcitonin
“CalciTONin TONes down Ca levels”
Not important in normal Ca homeostasis but when active, opposes PTH
Which hormones use cAMP
“Go Go FLAT ChAMP”
GHRH, Glucagon, FSH, LH, ACTH, TSH, CRH, Calcitonin, ADH (V2 receptor), MSH, PTH
Which hormones use cGMP
“Vasodilators”
ANP, NO, EDRF (Endothelial Derived Relaxing Factor)
Which hormones use IP3
“HAG GGOAT”
Histamine (H1), Angiotensin II, Gastrin, GnRH, Oxytocin, ADH (V1 receptor), TRH
Hormones that use steroid receptors
“VETTT CAP”
VitD, Estrogen, Testosterone, T3/T4, Cortisol, Aldosterone, Progesterone
Hormones that use Intrinsic Tyrosine Kinases
“MAP kinase pathway - Think growth factors”
Insulin, IGF1, FGF, PDGF, EGF
Hormones that use Receptor-Associated (Non-Receptor) Tyrosine Kinase
JAK/STAT pathway
Think Acidophiles and cytokines - “PIG”
Prolactin, Immunomodulators (cytokines IL2, IL6, IL8, IFN), GH
In men, what are the effects of ↑ sex hormone binding globulin
Lowers free testosterone –> gynecomastia
In women, what are the effects of ↓ sex hormone binding globulin
Raises free testosterone –> hirsutism
In a women, what happens to SHBG during pregnancy?
↑ SHBG
Thyroid Hormone
Formulations
Source
T3 and T4
Follicles of thyroid. Most T3 is formed in target tissues
Function of Thyroid Hormone
T3 –> 4 Bs
Brain maturation
Bone Growth (synergism with GH)
β adrenergic effects: ↑ β1 receptors in heart –> ↑ CO, HR, SV, and contractility
↑ Basal metabolic rate: ↑ Na/K ATPase activity –> ↑ O2 consumption, RR, body Temp
↑ glycogenolysis, gluconeogenesis, lipolysis
How is TH transported in the blood
When is it active?
Thyroxine binding globulin binds most T3/T4 in blood
Only free hormone is active
When does TBG levels change?
↓ TBG in hepatic failure
↑ TBG in pregnancy or OCP (estrogen ↑ TBG)
What is the major thyroid product?
What is it converted into?
Where is it converted?
What converts it?
T4
Converted to T3 in peripheral tissues by 5’-deiodinase
Which thyroid product binds with greater affinity?
T3
Peroxidase in Thyroid
Oxidation and organification of Iodide as well as coupling of MIT and DIT
Propylthiourcil
MoA
Use
Tox
Inhibits Peroxidase and 5’-deiodinase
Hyperthyroidism
Tox: skin rash, agranulocytosis, aplastic anemia, hepatotoxicity
Methimazole
MoA
Use
Tox
Inhibits Peroxidase
Hyperthyroidism
Tox: skin rash, agranulocytosis, aplastic anemia, teratogen
Thyroid Hormone Regulation
Hypothalamus –> TRH –> Pituitary –> TSH –> Follicular cells of thyroid gland –> TH
Negative feedback by T3 to anterior pituitary ↓ sensitivity to TRH
Wolff-Chaikoff Effect
Excess I temporarily inhibits thyroid peroxidase –> ↓ iodine organification –> ↓ T3/T4 production
Function of Follicular Cells in Thyroid Gland
Take up I- and oxidize it to I2 for excretion into lumen. In lumen TG and I2 form MIT and DIT.
Take up TG and proteolysis occurs to release T3/T4
Cushing’s Syndrome
Primary Pathophysiology
Different kinds of causes
↑ cortisol
Exogenous vs Endogenous causes
1 cause of Cushing’s syndrome?
Exogenous steroids –> ↓ ACTH
Endogenous causes of Cushing’s Syndrome
Cushing’s Disease (70%): ACTH secretion from pituitary adenoma
Ectopic ACTH (15%): Non pituitary tissue makes ACTH (usually small cell lung cancer, bronchial carcinoids)
Adrenal (15%): adenoma, carcinoma, nodular adrenal hyperplasia. Low ACTH
Presentation of Cushing’s Syndrome
HTN, Wt Gain, Moon facies, Truncal obesity, Buffalo hump, Hyperglycemia (insulin resistance), Skin changes (thinning, striae),peptic ulcers, osteoporosis, amenorrhea, immune suppression
Dexamethasone Suppression Test on Cortisol Normal ACTH pituitary tumor Ectopic ACTH producing tumor Cortisol producing tumor
Low dose High Dose Suppressed Suppressed Remains ↑ Suppressed Remains ↑ Remains ↑ Remains ↑ Remains ↑
Primary Hyperaldosteronism Causes Presentation Distribution Treatment
Adrenal hyperplasia or aldosterone secreting adrenal adenoma (Conn’s Syndrome)
HTN, HypoK, Metabolic alkalosis, low Renin
Maybe bilateral or unilateral
Surgery to remove tumor and/or spironolactone
Secondary Hyperaldosteronism Pathophysiology Underlying Causes Associated with... Treatment
Renal perception of low intravascular volume –> overactive Rennin-Angiotensin system
Due to Renal Artery Stenosis, Chronic Renal Failure, CHF, Cirrhosis, Nephrotic Syndrome
Associated with high Renin levels
Treat with Spironolactone
Addison's Disease What is it? Pathophysiology Presentation Diseases that can lead to it
“Adrenal Atrophy and Absence of hormones from All 3 cortical layers”
Chronic primary adrenal insufficiency due to adrenal atrophy or destruction.
Deficiency in aldosterone and cortisol leads to hypotension (hyponatremic volume contraction), hyperK, acidosis, skin hyper-pigmentation
Autoimmune, TB, Metastatic Cancer
Why is skin hyper-pigmented in Addison’s disease?
MSH, a byproduct of ACTH production from POMC, is elevated
How is Primary adrenal insufficiency different from Secondary adrenal insufficiency
Secondary is from ↓ pituitary ACTH. No skin hyper-pigmentation and no hyperK
Waterhouse-Friderichsen Syndrome
What is it?
What is it due to?
What conditions is it associated with?
Acute Primary adrenal insufficiency
Due to adrenal hemorrhage
Associated with Neisseria meningitidis septicemia, DIC, and endotoxic shock
Pheochromocytoma Arise from Most tumors secrete Findings Associated with what other diseases?
Arise from chromaffin cells (neural crest cells)
Most secrete Epi, NE, and DA
Episodic HTN, Urinary vanillyl mandelic acid (VMA), ↑ plasma catecholamines
Associated with neurofibromatosis type 1, MEN Type 2A and 2B
Treatment of Pheochromocytoma
Tumor surgically removed only after effective α and β blockade is achieved
Irreversible α antagonists (phenoxybenzamine) must be given first to avoid hypertensive crisis. β blockers are then given to slow heart rate
Symptoms of episodic HTN
Pressure (elevated BP) Pain (headache) Perspiration Palpitations (tachycardia) Pallor
Rule of 10 with Pheochromocytoma
10% malignant 10% bilateral 10% extra-adrenal 10% calcify 10% kids
Path of DA, NE and Epi synthesis
Phenylalanine –> Tyrosine –> L DOPA –> DA –> NE –> Epi
Product of DA metabolism
HVA
Product of NE and Epi metabolism
VMA
Neuroblastoma Frequency Location Findings Presentation Genetics
Most common tumor of adrenal medulla in children
Can occur anywhere along the sympathetic chain
HVA elevated in urine
HTN less likely to develop
Overexpression of N-myc oncogene associated with rapid tumor progression
Hypothyroidism Temp Wt Activity GI Reflexes Myxedema Skin Hair Heart TSH TH
Cold intolerance Wt Gain with ↓ appetite Hypoactivity, lethargy, fatigue, weakness Constipation ↓ reflexes facial/periorbital myxedema Dry cool skin Coarse brittle hair Bradycardia, SOBE ↑ TSH ↓ free T4
Hyperthyroidism Temp Wt Activity GI Reflexes Myxedema Skin Hair Heart TSH TH
Heat intolerance Wt loss with ↑ appetite Hyperactivity Diarrhea ↑ reflexes Pretibial myxedema Warm moist skin Fine hair Chest pain, palpitations, arrhythmias, ↑ β adrenergic receptors ↓ TSH (if primary) ↑ Free or total T3 and T4
Hashimoto's Thyroiditis Kind of thyroidism Frequency Pathophysiology Genetics Risk Histology Physical exam Course of disease
Hypothyroidism
Most common cause of hypothyroidism
Autoimmune disorder (thyroid peroxidase and anti thyroglobulin Abs)
Associated with HLA DR5
Increased risk of non-Hodgkin’s lymphomas
Hurthle cells, lymphocytic infiltrate with germinal centers
Moderately enlarged nontender thyroid
May be hyperthyroid early in course (thyrotoxicosis during follicular rupture)
Cretinism
Kind of thyroidism
Pathophysiology with circumstances
Findings
Fetal Hypothyroidism
Endemic: Lack of dietary iodine
Sporadic: Defect in T4 formation or developmental failure in thyroid formation
Pot bellied, Pale, Puffy face, Protruding umbilicus and Protuberant tongue
Subacute Thyroiditis Name Kind of thyroidism Description Usually follows Histology Findings Course
de Quervain's Hypothyroidism Self limited Often following flu like illness Granulomatous inflammation ↑ ESR, Jaw pain, early inflammation, tender thyroid May be hyperthyroidism early in course
Reidel’s Thyroiditis
Kind of thyroidism
Pathophysiology
Findings
Hypothyroidism
Thyroid replaced by fibrous tissue (considered a manifestation of IgG4 related systemic disease)
Fixed, hard, painless goiter
Toxic multinodular goiter
Kind of thyroidism
PathoPhys
Malignant?
Hyperthyroidism
Focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation of TSH receptor
Rarely malignant
Jod-Basedow Phenomenon
Thyrotoxicosis if a pt with iodine deficiency goiter is made iodine replete
Graves' Disease Kind of thyroidism PathoPhys Presentation Often presents during
Hyperthyroidism
Autimmune with thyroid stimulating immunoglobulins
Ophthalmopathy (proptosis, EOM swelling), pretibial myxedema, ↑ connective tissue deposition, diffuse goiter
Often presents during stress (childbirth)
Thyroid Storm Kind of thyroidism What is it? What does it cause? What causes it? Findings
Hyperthyroidism
Stress-induced catecholamine surge leading to death by arrhythmia
Seen as a complication of Graves’ and other hyperthyroid disorders
↑ ALP due to increased bone turnover
Papillary Thyroid Carcinoma Frequency Prognosis Histology Predisposing factors
Most common thyroid cancer
Excellent prognosis
empty-appearing nuclei (Orphan Annie’s Eyes), Psammoma bodies, Nuclear grooves,
↑ risk with childhood radiation
Follicular Thyroid Carcinoma
Prognosis
Histology
Good prognosis
Uniform follicles
Medullary Thyroid Carcinoma Source What molecules does it produce? Histology Associated with what other diseases
Parafollicular C cells
Produces calcitonin
Sheets of cells in amyloid stroma
Associated with MEN types 2A and 2B
Undifferentiated/anaplastic thyroid cancer
Kind of pt?
Prognosis
Older pt with very poor prognosis
What is thyroid lymphoma associated with?
Hashimoto’s Thyroiditis
Primary Hyperparathyroidism
Usually caused by…
Findings
Symptoms
Usually an adenoma
HyperCa, Hypercalciuria (renal stones), ↑PTH, ↑ALP, ↑cAMP in urine
Often asymptomatic but can present with weakness and constipation
Osteitis Fibrosa Cystica
↑ PTH –> Cystic bone spaces filled with brown fibrous tissue –> bone pain
Secondary Hyperparathyroidism
What causes it?
Most often seen in what disease?
Findings
↓ Gut Ca absorption and ↑ Phosphate
Most often in chronic renal disease (low VitD)
HypoCa, HyperPO4 (in chronic renal disease), HypoPO4 (with other causes), ↑ALP, ↑PTH
Renal Osteodystrophy
Bone lesion due to secondary or tertiary hyperparathyroidism due to renal disease
Tertiary Hyperparathyroidism
What causes it?
Findings
Refractory (autonomous) hyperparathyroidism resulting from chronic renal disease. ↑↑PTH and ↑ Ca
Hypoparathyroidism
Causes
Findings
Surgical excision, autoimmune, DiGeorge Syndrome
HypoCa, Tetany, Chvostek’s Sign, Trousseau’s Sign.
Chvostek’s Sign
Tapping of facial nerve –> contraction of facial muscles
Trousseau’s Sign in Hypoparathyroidism
Occlusion of brachial artery w/ BP cuff –> carpal spasm
PseudoHypoparathyroidism Name Genetics PathoPhys Findings
Albright’s Hereditary Osteodystrophy
Autosomal dominant
Kidney unresponsive to PTH
HypoCa, Shortened 4th/5th digit, short stature
Low Ca, High PTH
Secondary Hyperparathyroidism
Low Ca, Low PTH
Hypoparathyroidism
High Ca, High PTH
Primary Hyperparathyroidism
High Ca, Low PTH
PTH independent HyperCalcemia
Most common pituitary adenoma
Prolactinoma
Prolactinoma
Findings
Treatment
Amenorrhea, Galactorrhea, Low Libido, Infertility DA agonist (bromocriptine or cabergoline)
Common presentation of pituitary adenoma
Bitemporal hemianopia from impingement on optic chiasm
Acromegaly
What is it?
What causes it?
Findings
Excess GH in adults
Typically caused by pituitary adenoma
Large tongue with deep furrows, Course facial hair, Insulin resistance
Acromegaly
Diagnosis
Treatment
↑ serum IGF1; Failure to suppress serum GH following oral glucose tolerance test; Pituitary mass on MRI
Resection followed by somatostatin analog (Octreotide)
Diabetes Insipidus
PathoPhys
Presentation
Central: Lack of ADH (pituitary tumor, trauma, surgery, histiocytosis x)
Nephrogenic: Lack of renal response to ADH (hereditary, hyperCa, Li, demeclocycline)
Thirst and Polyuria
Diabetes Insipidus
Findings
Diagnosis
Treatment
Urine specific gravity < 1.006; Serum osmolality > 290
Water deprivation test (urine osmolality doesn’t ↑)
Response to desmopressin distinguishes central vs nephrogenic
Fluid intake. For central: intranasal desmopressin. For Nephrogenic: hydrochlorothiazide, indomethacin, or amiloride
SIADH Characteristics Normal body response Dangerous complication Possible causes Treatment
Excess water retention, Low Na, Urine osmolarity > serum osmolarity
Body responds with ↓ aldosterone
Low Na can lead to seizures
Ectopic ADH (small cell lung cancer), CNS disorder, Head trauma, Pulmonary disease, Drugs (cyclophosphamide)
Fluid restriction, IV saline, Conivaptan, Tolvaptan, Demeclocycline
Hypopituitarism
What causes it?
Treatment
Nonsecreting pituitary adenoma, craniopharyngioma Sheehan's Syndrome Empty Sella Syndrome Brain injury, hemorrhage Radiation Treat with substitution therapy
Sheehan’s Syndrome
Postpartum ischemic infarct of pituitary. Usually presents with failure to lactate
Empty Sella Syndrome
Atrophy or compression of the pituitary. Often idiopathic. Common in obese women
Acute manifestations of Diabetes Mellitus
Polydipsia, Polyuria, Polyphagia, Wt loss, DKA (type1), HHS (type2), Unopposed secretion of GH and Epi (exacerbate hyperglycemia)
Reason for coma and death in DM?
Dehydration and Acidosis
Chronic manifestations of DM?
Nonenzymatic glycosylation and Osmotic damage
Nonenzymatic Glycosylation in DM
Small Vessels: diffuse thickening of basement membrane –> retinopathy (hemorrhage, exudates, microaneurysm, vessel proliferation), glaucoma, nephropathy (nodular sclerosis, progressive proteinuria, chronic renal failure, arteriosclerosis leading to HTN, Kimmelstiel Wilson nodules)
Large Vessels: Atherosclerosis, CAD, Peripheral vascular occlusive disease, gangrene –> limb loss cerebrovascular disease
Osmotic Damage in DM
Sorbitol accumulation in organs with aldose reductase
Neuropathy (motor, sensory, autonomic)
Cataracts
Tests for DM
Fasting serum glucose
Oral GTT
HbA1C (3 months)
DM1 Defect Insulin in treatment Age Obesity Genetics HLA Glucose intolerance Insulin sensitivity Ketoacidosis β cell # Serum insulin level Classic symptoms Histology
Autoimmune destruction of β cells Insulin always used Pt <30 Not obese Weak genetic connection HLA DR3 and DR4 Severe glucose intolerance High insulin sensitivity Ketoacidosis common β cell # ↓ Serum insulin ↓ Classic symptoms common Islet leukocytic infiltration
DM2 Defect Insulin in treatment Age Obesity Genetics HLA Glucose intolerance Insulin sensitivity Ketoacidosis β cell # Serum insulin level Classic symptoms Histology
Insulin resistance with progressive β cell failure Insulin sometimes used Pt >40 Obese Strong genetic connections No HLA Mild to moderate glucose intolerance Low insulin sensitivity Rare ketoacidosis β cell # variable w/ amyloid deposits Variable insulin levels Classic symptoms occur sometimes Islet amyloid deposits
Diabetic Ketoacidosis
Which DM
What precipitates it?
PathoPhys
DM1
Usually due to ↑insulin requirement from ↑ stress (infection)
Excess fat breakdown and ↑ ketogenesis from ↑ free fatty acids which are then made into ketone bodies (β hydroxybutyrate > acetoacetate)
DKA
Signs and Symptoms
Labs
Kussmaul Respirations, nausea, vomiting, abdominal pain psychosis/delirium, dehydration, fruity breath odor (acetone)
Hyperglycemia, ↑H+, ↓Bicarb (aniongap metabolic acidosis), ↑ blood ketone levels, leukocytosis, HyperK (but depleted intracellular K)
DKA
Complications
Treatment
Mucormycosis, Rhizopus infection, cerebral edema, cardiac arrhythmias, heart failure
IV fluids, IV insulin, K, Glucose
Carcinoid Syndrome
Most common tumor of which organ?
Rule of 1/3
Lab findings
Appendix
1/3 metastasize, 1/3 malignant, 1/3 multiple
5-HIAA in urine and niacin deficiency
MEN1
Name
Location of tumors
Common presentation
Wermer’s Syndrome
“Diamond”
Pituitary (Prolactin, GH)
Parathyroid
Pancreas (Zollinger Ellison, Insulinomas, VIPomas, Glucagonomas)
Commonly presents with kidney stones and stomach ulcers
MEN2A
Name
Location of tumors
Sipple’s Syndrome
“Square”
Parathyroid and Pheochromocytomas
Medullary thyroid carcinomas (calcitonin)
MEN2B
“Triangle”
Oral/intestinal ganglioneuromatosis (associated with marfanoid habitus)
Pheochromocytoma
Medullary thyroid carcinomas (calcitonin)
Genetics of MEN syndromes
Autosomal dominant
2A and 2B associated with ret gene mutation
Treatment for DM1
Low sugar diet + insulin replacement
Treatment for DM2
dietary modification, exercise for wt loss, oral hypoglycemics, insulin replacement
Insulin Replacement Drugs
Lispro (rapid) Aspart (rapid) Glulisine (rapid) Regular (short) NPH (intermediate) Glargine (long) Detemir (long)
Uses of insulin replacement drugs
DM1 and DM2, gestational diabetes, hyperK, stress-induced hyperglycemia
Toxicity of insulin replacement drugs?
Hypoglycemia, Hypersensitivity rxn
Biguanides Names MoA Uses Tox Contraindications
Metformin
↓ gluconeogensis, ↑ glycolysis, ↑ peripheral glucose uptake (insulin sensitivity)
First line DM2. Can be used in pts without islet function
GI upset, lactic acidosis
Contraindicated in renal failure
First generation sulfonylureas
Tolbutamide, Chlorpropamide
Second generation sulfonylureas
Glyburide, Glimepiride, Glipizide
Sulfonylureas
MoA
Use
Tox
Close K channels in β cells –> insulin release
DM2. Requires some islet function (useless in DM1)
1st gen: disulfiram-like effects
2nd gen: hypoglycemia
Glitazones/Thiazolidinediones Names MoA Use Tox
Pioglitazone, Rosiglitazone
↑ insulin sensitivity in peripheral tissue. Binds PPARγ nuclear receptor
DM2
Wt gain, edema, Hepatotoxic, heart failure
α glucosidase inhibitors Names MoA Use Tox
Acarbose, Miglitol
Inhibits intestinal brush border α glucosidase
Delayed sugar hydrolysis and glucose absorption
DM2
GI disturbances
Amylin analogs Names MoA Use Tox
Pramlintide
↓ glucagon
DM 1 and 2
Hypoglycemia, nausea, diarrhea
GLP1 analog Names MoA Use Tox
Exenatide, Liraglutide
↑ insulin, ↓ glucagon
DM2
Nausea, vomiting, diarrhea
DPP4 inhibitors Names MoA Use Tox
Linagliptin, Saxagliptin, Sitagliptin
↑ insulin, ↓ glucagon
DM2
Mild urinary and respiratory infections
Levothyroxine, Triiodothyronine
MoA
Use
Tox
Thyroxine replacement
Hypothyroidism, myxedema
Tachycardia, heat intolerance, tremors, arrhythmias
Use of GH as a medicine
GH deficiency and Turners Syndrome
Uses of octreotide
Acromegaly, Carcinoid, Gastrinoma, Glucagonoma, Esophageal varices
Uses of Oxytocin
Stimulates labor, uterine contraction, milk let-down. Controls uterine hemorrhage
Uses of Desmopressin
Central DI
Demeclocycline Class of drugs MoA Use Tox
Tetracycline
ADH antagonist
SIADH
Nephrogenic DI, Photosensitivity, abnormalities or bone and teeth
Glucocorticoids Names MoA Use Tox
Hydrocortisone, Prednisone, Triamcinolone, Dexamethasone, Beclomethasone
↓ production of leukotrienes and prostaglandins by inhibiting PLA2 and expression of COX2
Addison’s disease, Inflammation, Immune suppression, Asthma
Cushing’s syndrome, Peptic ulcers, Adrenocortical atrophy.
Adrenal insufficiency if stopped abruptly
