The thyroid diverticulum arises from…
the floor of the primitive pharynx and descends into the neck.
The thyroid diverticulum is connected to the…
tongue by the thyroglossal duct, which normally disappears but may persist as a pyramidal lobe of the thyroid.
The normal remnant of the thyroglossal duct is the…
foramen cecum.
The most common ectopic thyroid tissue site is the…
tongue.
A thyroglossal duct cyst presents as…
an anterior midline neck mass that moves with swallowing or protrusion of the tongue.
A persistent cervical sinus leads to a…
branchial cleft cyst in the lateral neck.
The zona glomerulosa of the adrenal is regulated by…
renin-angiotensin and secretes aldosterone.
The zona fasiculata is regulated by…
ACTH, CRH and secretes cortisol (and sex hormones).
The zona reticularis is regulated by…
ACTH and CRH and secretes sex hormones (androgens).
The chromaffin cells of the medulla are regulated by…
preganglionic sympathetic fibers (ACh) and secrete catecolemines (NE and epinephrine).
Pheochromocytoma is the…
most common tumor of the adrenal medulla in adults and presents with episodic HTN.
Neuroblastoma is the…
most common tumor the adrenal medulla in children. It rarely causes hypertension.
The left adrenal gland is drained by the…
left adrenal vein to the left renal vein to the IVC.
THe right adrneal gland is drained by the…
right adrenal vein to the IVC.
The posterior pituitary (neurohypophysis) secretes…
vasopressin (aka ADH) and oxytocin.
Vasopressin and oxytocin are made in the…
hypothalamus and are shipped to the posterior pituitary via neurophysins.
The posterior pituitary is derived from…
neuroectoderm.
The anterior pituitary (adenohypophyisis) secretes…
FSH, LH, ACTH, TSH prolactin, GH and melanotropin (MSH).
Anterior pituitary is derived from…
oral ectoderm (Rathke pouch).
Acidophils
GH and prolactin
Basophils
FSH, LH, ACTH, TSH
The Islets of Langerhans are collections of…
alpha, beta, and delta endocrine cells arising from pancreatic buds.
alpha cells secrete…
glucagon.
beta cells secrete…
insulin
delta cells secrete…
somatostatin
Preproinsulin is synthesized in the…
RER and cleavage of the “presignal” leads to proinsulin (stored in secretory granules).
Cleavage of proinsulin leads to…
exocytosis of insulin and C-peptide equally.
Insulin and C-peptide are both increased in…
insulinoma whereas exogenous insulin lacks C-peptide.
Function of Insulin
Binds insulin receptors (tyrosine kinase activity), inducing glucose uptake (carrier-mediated) in insulin-dependent tissues and gene transcription.
Anabolic effects of Insulin (7)
- increased glucose transport in skeletal muscle and adipose tissue 2. increased glycogen synthesis and storage 3. increased triglyceride synthesis 4. increased Na+ retention (kidneys) 5. increased protein synthesis 6. increased cellular uptake of K+ and amino acids 7. decreased glucagon release
Unlike glucose, insulin does not…
cross the placenta.
Insulin dependent glucose transporters:
GLUT-4 (adipose tissue and skeletal muscle) These have lower Km and increased affinity.
Insulin independent transproters
-GLUT-1 (RBCs, brain, cornea) -GLUT-5 (fructose - spermatocytes, GI tract) -GLUT-2 (bidirectional - beta islet cells, liver, kidney, SI)
The brain utilizes glucose for…
metabolism normally and ketone bodies during starvation.
RBCs always utilize glucose because they…
lack mitochondria for aerobic metabolism.
The major regulator of insulin release is…
glucose. GH and beta2 agonists also increase insulin.
When glucose enters beta cells, there is…
increased ATP generated from glucose metabolism which closes K+ channels and depolarizes the beta cell membrane. This causes opening of voltage gated Ca2+ channels leading to calcium influx and stimulation of insulin exocytosis.
Function of Glucagon:
Catabolic effects: -glycogenolysis, gluconeogenesis -lipolysis and ketone production
Glucagon is secreted in response to…
hypoglycemia.
Glucagon is inhibited by…
insulin, hyperglycemia and somatostatin.
CRH increases…
ACTH, MSH, beta-endorphin.
CRH decreases in…
chronic exogenous steroid use.
Dopamine decreases…
prolactin.
Dopamine antagonists can cause…
galactorrhea.
GnRH increases…
FSH and LH.
GnRH is regulated by…
prolactin.
Tonic GnRH acts to…
suppress the HPA axis.
Pulsatile GnRH leads to…
puberty and fertility.
Prolactin decreases…
GnRH.
A pituitary prolactinoma leads to…
amenorrhea and osteoporosis.
Somatostatin decreases…
GH and TSH.
Somatostatin analogs are used to treat…
acromegaly.
TRH increases…
TSH and prolactin.
Prolactin stimulates…
milk production in the breast; it inhibits ovulation in females and spermatogenesis in males by inhibiting GnRH syntehsis and release.
Excessive amounts of prolactin are associated with…
decreased libido.
Prolactin secretion from the anterior pitutiary is regulated…
by tonic inhibition from dopamine from the hypothalamus.
Prolactin in turn inhibits…
its own secretion by increased dopamine synthesis and secretion from the hypothalamus.
GH stimulates…
linear growth and muscle mass through IGF-1/somatomedin secretion. It causes increased insulin resistance.
GH is released in…
pulses in response to GHRH.
Secretion of GH is increasd during…
exercise and sleep.
Secretion of GH is inhibited by…
glucose and somatostatin.
ADH is synthesized in the…
supraoptic nuclei of the hypothalamus.
ADH regulates…
serum osmolarity (V2 receptors) and blood pressure (V1 receptors).
Primary function of ADH is…
serum osmolarity regulation (ADH decreases serum osmolarity and increases urine osmolarity) via regulation of aquaporin channels in the principal cells of the renal collecting duct.
ADH is decreased in…
central diabetes insipidus but normal or increased in nephrogenic DI and primary polydipsia.
Nephrogenic DI can be caused by…
a mutation in the V2 receptor.
Desmopressin is an…
ADH analog used as treatment for central DI.
Regulation of ADH is…
primaryily via osmoreceptors in the hypothalamus and secondary through hypovolemia.
17alpha-hydroxylase deficiency steroid/hormone levels
-increased mineralocorticoids -decreased cortisol -decreased sex hormones
17alpha-hydroxylsae deficiency labs
-hypertension -hypokalemia -decreased DHT
Presentation of 17alpha-hydroxylase
XY: pseudohermaphroditism (ambiguous genitalia, undescended testes) XX: lack secondary sex devleopment
21-hydroxylase deficiency steroid/hormone levels
-decreased mineralocorticoids -decreased cortisol -increased sex hormones
21-hydroxylase deficiency labs
-hypotension -hyperkalemia -increased renin -increased 17-hydroxyprogesterone
Presentation of 21-hydoxylase deficiency
in infancy with salt wasting or childhood with precocious puberty XX: virilization
11beta-hydroxylase deficiency steroid/hormone levels
-decreased aldosterone -increased 11-deoxycortisone -decreased cortisol -increased sex hormones
Labs of 11beta-hydroxylase deficiency
hypertension (low renin)
Presentation of 11beta-hydroxylase deficiency
XX: virilization
All congenital adrenal enzyme deficiencies are characterized by an…
enlargment of both adrenal glands due to increased ACTH stimulation (due to decreased cortisol).
Functions of cortisol (6)
- increased bp 2. increased insulin resistance 3. increased gluconeogenesis, lipolysis and proteolysis 4. decreased fibroblast activity (causes striae) 5. decreased inflammatory/immune responses 6. decreased bone formation (decreased osteoblast activity)
Cortisol increases bp by…
upregulating alpha1 receptors on arterioles leading to increased sensitivity to NE and epinephrine.
Cortisol causes decreased inflammatory and immune responses (5):
- inhibits production of leukotrienes and prostaglandins 2. inhibits leukocyte adhesion (leading to neutrophilia) 3. blocks histamine release from mast cells 4. reduces eosinophils 5. blocks IL-2 production
Cortisol is bound to…
corticosteroid binding globulin (CBG).
Exogenous cortisol can cause…
latent reactivation of TB and candidiasis (due to blocked IL-2).
PTH is secreted by…
the chief cells of the parathyroid.
Functions of PTH
- increased bone resorption of calcium and phosphate 2. increased kidney reabsorption of calcium in DCT 3. decreased reabsorption of phosphate in the PCT 4. increased 1,25-(OH)2D3 (calcitriol) production by stimulating kidney 1alpha-hydroxylase
Overall, PTH acts to..
increase serum calcium, decrease serum phosphate and increased urine phosphate.
PTH increases the production of…
macrophage colony-stimulating factor and RANK-L (receptor activator of NF-kappaB)
RANK-L binds…
RANK on osteoblasts leading to osteoblast stimulation and increasd calcium.
PTH-related peptide (PTHrP) functions like…
PTH and is commonly increased in malignancies (ex. paraneoplastic syndrome).
PTH secretion is increased by…
decreased serum calcium or magnesium.
PTH secretion is decreased by…
greatly decreased serum magnesium.
Common causes of decreased magnesium include..
diarrhea, aminoglycosides, diruetics and alcohol abuse.
Plasma calcium exists in 3 forms:
- ionized (45%) 2. bound to albumin (40%) 3. bound to anions (15%)
An increase in pH leads to an increased affinity of…
albumin (negative charge) for calcium leading to clinical manifestations of hypocalcemia (cramps, pain, paresthesias, carpopedal spasm).
Vitamin D3 comes from…
sun exposure.
Vitamin D2 is ingested from…
plants.
Both D2 and D3 are converted to…
25-OH in the liver and to 1,25-(OH)2 (active form) in the kidney.
Function of Vitamin D
- increase the absorption of dietary calcium and phosphate 2. increase bone resorption leading to increased serum calcium/phosphate
Production of the active form of vitamin D is stimulated by…
increased PTH, decreased calcium, and decreased phosphate.
Deficiency of Vitamin D causes…
rickets in kids and osteomalacia in adults.
Vitamin D deficiency is caused by…
malabsorption, decreased sunlight, poor diet and chronic kidney failure.
Calcitonin comes from the…
parafollicular (c cells) of the thyroid.
Function of calcitonin
decrease bone resorption of calcium
Calcitonin secretion is stimulated by…
increased serum calcium.
Calcitonin opposes the actions of…
PTH. It is not important in normal calcium homeostasis.
cAMP is the signaling pathway for the following endocrine hormones:
- FSH 2. LH 3. ACTH 4. TSH 5. CRH 6. hCG 7. ADH 8. MSH 9. PTH 10. calcitonin 11. GHRH 12. glucagon
cGMP is the signaling pathway for the following endocrine hormones:
- ANP 2. NO
IP3 is the signaling pathway for the following endocrine hormones:
- GnRH 2. oxytocin 3. ADH 4. TRH 5. Histamine 6. AngII 7. Gastrin
Steroid receptor is the signaling pathway for the following endocrine hormones:
- Vitamin D 2. Estrogen 3. Testosterone 4. T3/T4 5. Cortisol 6. Aldosterone 7. Progesterone
Intrinsic tyrosine kinase is the signaling pathway for the following endocrine hormones:
- insulin 2. IGF-1 3. FGF 4. PDGF 5. EGF
Receptor associated tyrosine kinase is the signaling pathway for the following endocrine hormones:
- Prolactin 2. immunomodulators 3. GH
Steroid hormones are lipophilic and therefore must…
circulate bound to specific binding globulins which increase their solubility.
In men, increased SHBG leads to…
lower free testosterone leading to gynecomastia.
In women, decreased SHBG leads to…
increased free testosterone leading to hirsutism.
SHBG is increased by…
OCPs and pregnancy. (free estrogen levels remain the same)
T3 and T4 are…
iodine-containing hormones that control the body’s metabolic rate
T3/T4 come from..
the follicles of the thyroid.
Functions of T3/T4
- bone growth 2. CNS maturation 3. increased beta1 receptors in the heart (increased CO, HR, SV, contractility) 4. increased metabolic rate via increased Na+/K+ ATPase activity (increased O2 consumption, RR and temp) 5. increased glycogenolysis, gluconeogenesis and lipolysis
TBG binds…
almost all T3/T4 in the blood. Only free hormone is active.
The major thyroid product is…
T4. It is converted into T3 in the peripheral tissue by 5’-deiodinase. T3 binds receptors with greater affinity.
Peroxidase is the enzyme responsible for…
oxidation and organification of iodide as well as coupliting of MIT and DIT.
Propylthiouracil inhibtis both…
peroxidase and 5’-deiodinase. Methimazole inhibits peroxidase only.
3 causes of Cushing Syndrome
- exogenous corticosteroids (#1 cause) 2. primary adrenal adenoma, hyperplasia or carcinoma 3. ACTH-secreting pituitary
Exogenous corticosteroids result in..
decreased ACTh and bilateral adrenal atrophy.
Primary adrenal adenoma, hyperplasia or carinoma results in…
decreased ACTH and atrophy of the uninvolved adrenal gland. This can also present as primary aldosteronism (Conn Syndrome).
ACTH-secreting pituitary adenoma is true…
Cushing disease.
An ACTH secreting pituitary adenoma or paraneoplastic ACTH secretion (SCLC or bronchial carcinoids) results in…
increased ACTH, bilateral adrneal hyperplasia.
Findings of Cushing Syndrome
-HTN -weight gain -moon facies -truncal obesity -buffalo hump -hyperglycemia (insulin resistance) -skin changes (thinning, striae) -osteoporosis -amenorrhea -immune suppression
Screening tests for Cushing’s include:
- increased free cortisol on 24 hr U/A 2. midnight salivary cortisol 3. overnight low-dose dexamethasone suppression test
Primary hyperaldosteronism is caused by…
adrenal hyperplasia or an aldosterone-secreting adrenal adenoma (Conn syndrome) resulting in HTN, hypokalmeia, metabolic alkalosis and low plasma renin.
In primary hyperaldosteronism, sodium is…
normal due to aldosterone escape.
Treatment for primary hyperaldosteronism
surgery to remove tumor and/or spironolactone
Secondary hyperaldosteronism is the…
renal perception of low intravascular volume resulting in an overactive RAAS. High plasma renin.
Secondary hyperaldosteronism is due to…
renal artery stenosis, CHF, cirrhosis or nephrotic syndrome.
Treatment for secondary hyperaldosteronism
spironolactone
Addison Disease is…
primary adrenal insufficiency due to adrenal atrophy or destruction.
In Addison disease, there is a deficiency of…
aldosterone and cortisol casuing hypotension, hyperkalemia, acidosis and skin/mucosal hyperpigmentation.
Secondary adrenal insufficiency (decreased pituitary ACTH production) has no…
skin hyperpigmentation and no hyperkalemia.
Waterhouse-Friderichsen Syndrome is…
acute primary adrenal insufficiency due to adrenal hemorrhage associated with Neisseria meningitidis septicemia, DIC and endotoxic shock.
Neuroblastoma results from…
neural crest cells and occurs anywhere along the sympathetic chain.
Neuroblastoma most commonly presents as…
abdominal distension and a firm, irregular mass that can cross the midline.
Lab results of neuroblatoma
-increased HVA in urine (breakdown product of dopamine) -bombesin + -overexpression of N-myc
Neuroblastoma histology
-rosettes and small, round, blue/purple nuclei
Pheochromocytoma is derived from…
adrenal chromaffin cells (from neural crest).
Pheochromocytoma rule of…
10s: 10% malignant 10% bilateral 10% extra-adrenal 10% calcify 10% kids
Most pheochromocytomas secrete…
epinephrine, norepinephrine, and dopamine which can cause episodic HTN.
Pheochromocytomas are associated with…
von Hippel-Lindau disease, MEN 2A and 2B.
Pheochromocytoma Findings
-urinarry VMA (breakdown product of NE and epinephrine) -increased serum catecholamines
Treatment of Pheochromocytoma
- irreversible alpha-antagonists (phenoxybenzamine) 2. then beta-blockers 3. then surgery (alpha then beta to aovid hypertensive crisis)
Hypothyroidism signs/symptoms (8)
- cold intolerance 2. weight gain, decreased appetite 3. hypoactivity, lethargy, fatigue 4. constipation 5. decreased reflexes 6. myxedema (facial/periorbital) 7. dry, cool skin; coarse, brittle hair 8. bradycardia, dyspnea on exertion
Hyperthyroidism signs/symptoms (8)
- heat intolerance 2. weight loss, increased appetite 3. hyperactivity 4. diarrhea 5. increased reflexes 6. pretibial myxedema 7. warm, moist skin; fine hair 8. chest pain, palpitations, arrhythmias
Lab findings of hypothyroidism
-increased TSH -decreased T3/T4 -hypercholesterolemia (due to decreased LDL receptor)
Lab findings of hyperthyroidism
-decreased TSH -increased free/total T3/T4 -hypocholesterolemia
Hashimoto thyroiditis is…
an autoimmune hypothyroidism due to antithyroid peroxidase and antithyroglobulin antibodies.
Hashimoto thyroiditis is associated with…
HLA-DR5 and increased risk of non-Hodgkin lymphoma.
Hashimoto may be hyperthyroid early in the course due to…
thyrotoxicosis durin gfollicular rupture.
Histologic findings of Hashimoto
-Hurthle cells -lymphoid aggregate with germinal centers
In hashimoto, the thyroid will be…
moderately enlarged, nontender.
Congenital hypothyroidism (cretinism)
severe fetal hypothyroidism due to maternal hypothyroidism, thyroid agenesis, thyroid dysgenesis, iodine deficiency or dyshormongenic goiter.
Findings of Congential Hypothyroidism
6 Ps 1. Pot-bellied 2. Pale 3. Puffy-faced child 4. Protruding umbilicus 5. Protuberant tongue 6. Poor brain development
Subacute thyroiditis de Quervain is…
self-limited hypothyroidism following a flu-like illness.
Histology of Subacute thyroiditis de Quervain
granulomatous inflammation
Riedel thyroiditis is…
thyroid replaced by fibrous tissue (hypothyroid). The fibrosis may extend to local structures miimicking anaplastic carcinoma.
Riedel thyroiditis is considered a manifestation of…
IgG4 related systemic disease.
Findings of Riedel thyroiditis
-fixed, hard painless goiter
Toxic multinodular goiter (hyperthyroidism)
focal patches of hyperfuncitoning follicular cells working independently of TSH due to mutation in TSH receptor; increases release of T3 and T4
Jod-Basedow phenomenon
thyrotoxicosis if a pt with idoine deficiency goiter is made iodine replete
Graves disease is a form of…
hyperthryoidism due to autoantibodies (IgG) that stimulate TSH receptors on the thyroid, retro-orbital fibroblasts (exophthalmos, proptosis) and dermal fibroblasts (pretibilal myxedema)
Graves disease often presents during…
stress (childbirth).
A thyroid storm is a…
stress-induced catecholamine surge seen as a serious complication of Graves and other hyperthyroid disease.
Thyroid storm presents with…
agitation, delirium, fever, diarrhea, coma and tachyarrhythmia. May be increased ALP.
Treat thyroid storm with…
the 3 Ps: 1. Propranolol (beta-blockers) 2. Propylthiouracil 3. Prednisolone (corticosteroids)
Multinodular goiter histology
follicles of various sizes distended with colloid and lined by flattened epithelium with areas of fibrosis and hemorrhage
Complications of thyroidectomy include:
- hoarseness (recurrent laryngeal nerve damage) 2. hypocalcemia (removal of parathyroids) 3. transection of inferior thyroid artery
Papillary thyroid carcinoma
-empty appearing nuclei (orphan annie eyes) -psammoma bodies -nuclear grooves
There is increased risk for papillary thyroid carcinoma with…
RET and BRAF mutations and childhood irradiation.
Follicular thyroid carcinoma
-invades thyroid capsule -uniform follicles
Medullary thyroid carcinoma
-from parafollicular C cells -produces calcitonin -sheets of cells in an amyloid stroma
Medullary thyroid carcinoma is associated with…
MEN 2A and 2B (RET mutations).
Undifferentiated/anaplastic thyroid carcinoma
-older patients -invades local structures
Lymphoma of the thyroid is associated with..
Hashimoto.
Primary hyperparathyroidism is usually due to an…
adenoma and causes: -hypercalcemia -hypercalciuria (stones) -hypophosphatemia -increased PTH -increased ALP -increased cAMP in urine
Primary hyperparathyroidism may present with…
weakness, constipation, flank/abdominal pain, and depression.
Osteitis fibrosa cystica is…
cystic bone spaces filled with brown fibrous tissue. Associated with primary hyperparathyroidism.
Secondary hyperparathyroidism is…
secondary hyperplasia due to decreaesd gut calcium absorption and increased phosphate. This most often occurs in chronic renal disease.
Findings of secondary hyperparathyroidism include…
hypocalcemia, hyperhophsatemia, increased ALP and increased PTH.
Tertiary hyperparathyroidism is…
refractory hyperparathryoidism from chronic renal disease. Has greatly increased PTH and increased calcium.
Renal osteodystrophy is…
bone lesions due to secondary or tertiary hyperparthyroidism.
Hypoparathyroidism is due to…
accidental surgical excision of parathyroid glands, autoimmune destruction or DiGeorge.
Findings of Hypoparathyroidism
-hypocalcemia -tetany -Chvostek sign -Troussea sign
The chvostek sign is…
tapping of the facial nerve causes contraction of facial muscles.
The trousseau sign is…
occlusion fo the brachial artery with a bp cuff leads to carpal spasm.
Pseudohypoparathyroidism (Albright hereditary osteodystrophy) is an…
autosomal dominant unresponsiveness of the kidney to PTH. Presents with hypocalcemia, shortened 4th/5th digit and short stature.
The most common pituitary adenoma is a…
prolactinoma.
Nonfunctional pituitary adenomas present with…
mass effect (bitemporal hemianopia, hypopituitarism and headache).
Functional pituitary adenoma presentationis dependent on…
the hormone produced: -prolactinoma: amenorrhea, galactorrhea, low libido, infertility -somatropic adenoma: acromegaly
Treatment of prolactinoma
dopamine agonists (bromocriptine or cabergoline)
Acromegaly is…
excess GH in adults typically caused by pituitary adenoma
Findings of acromegaly (5)
-large tongue with deep furrows -deep voice -large hands and feet -coarse facial features -imparied glucose tolerance
Diagnose acromegaly with…
increased serum IGF-1; failure to suppress serum GH following oral glucose tolerance test; pituitary mass seen on brain on MRI.
Treatment for acromegaly
-pituitary adenoma resection -treat with octreotide or pegvisomant
Increased GH in children leads to…
gigantism (increased linear bone growth); cardiac failure is the most common cause of death
Diabetes insipidus is characterized by…
intense thirst and polyuria with an inability to concentrate urine due to lack of ADH.
Central DI is due to…
pituitary tumor, autoimmune, trauma, surgery, encephalopathy
Findings of Central DI
-decreased ADH -urine specific gravity < 1.006 -serum osmolarity > 290 -hyperosomotic volume contraction
Diagnosis of Central DI
water restriction test: >50% increase in urine osmolarity
Treatment of Central DI
-intranasal DDAVP -hydration
Nephrogenic DI is due to…
hereditary ADH receptor mutation, secondary to hypercalcemia, lithium or demeclocycline.
Findings of Nephrogenic DI
-normal ADH levels -urine specific gravity < 1.006 -serum osmolarity > 290 -hyperosomtic volume contraction
Diagnosis of Nephrogenic DI
water restriction test: no change in urine osmolarity
Treatment of Nephrogenic DI
-HCTZ -indomethacin -amiloride -hydration
The water restriction test is…
no water intake for 2-3 hrs followed by hourly measurements of urine volume, osmolarity and plasma sodium and osmolarity.
SIADH features (3):
- excessive water retention 2. hyponatremia with continued urinary Na+ excretion 3. urine osmolarity > serum osmolarity
In SIADH, the body responds to water retention with…
decreased aldosterone (which causes hyponatremia) to maintain near normal volume status.
In SIADH, very low serum soidum levels can lead to…
cerebral edema and seizures.
SIADH should be corrected…
slowly to prevent cetnral pontine myelinosis.
Causes of SIADH (4):
- ectopic ADH (small cell lung carcinoma) 2. CNS disorders/head trauma 3. pulmonary disease 4. drugs
Treatment of SIADH:
- fluid restriction 2. IV hypertonic saline 3. Conivaptan 4. Tolvaptan 5. demeclocycline
Hypopituitarism is uncersecretion of the pituitary hormones due to:
-nonsecreting pituitary adenoma, craniopharyngioma -Sheehan syndrome -empty sella syndrome -brain injury, hemorrhage -radiation
Empty sella syndrome is…
atrophy or compression of the pituitary common in obese women.
Treatment for hypopituitarism
HRT (corticosteroids, thyroxine, sex steroids, GH)
Acute manifestations of diabetes mellitus
-polydipsia -polyuria -polyphagia -weight loss -DKA (type 1) -hyperosmolar coma (type 2)
Nonenzymatic glycosylation due to chronic DM leads to:
- small vessel disease (diffuse thickening of the basement membrane) 2. large vessel atherosclerosis, CAD, peripheral vascular occlusive disease and gangrene
Small vessel disease in DM leads to…
- retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation) 2. glaucoma 3. nephropahty (nodular sclerosis, progressive proteinuria, chronic renal failure, arteriolosclerosis, HTN, Kimmelstiel-Wilson nodules)
In DM, large vessel atherosclerosis, CAD, peripheral vascular occlusive disease and gangrene lead to…
limb loss, cerebrovascular disease.
Osmotic damage in chronic DM is due to…
sorbitol accumulation in organs with aldose reductase and decreased sorbitol dehyrogenase. It causes: -neuropathy -cataracts
Tests for Diabetes Mellitus
- fasting serum glucose (> 126) 2. oral glucose tolerance test 3. HbA1c (reflects average blood glucose over prior 3 months)
Primary defects of T1 and T2 DM
T1: autoimmune destruction of beta cells T2: increased resistance to insulin, progressive pancreatic beta-cell failure
Treatment with insulin in T1 and T2 DM
T1: always T2: sometimes
Age of T1 and T2 DM
T1: less than 30 T2: more than 40
Association of T1 and T2 DM with obesity
T1: no T2: yes
Genetic predisposition of T1 and T2 DM
T1: relatively weak (50% concordance in identical twins), polygenic T2: relatively strong (90% concordance in identical twins), polygenic
Association of T1 and T2 DM with HLA system
T1: HLA DR3 and 4 T2: none
Glucose intolerance of T1 and T2 DM
T1: severe T2: mild to moderate
Insulin sensitivity of T1 and T2 DM
T1: high T2: low
Ketoacidosis T1 and T2 DM
T1: common T2: rare
beta-cell numbers in the islets of T1 and T2 DM
T1: decreased T2: variable (with amyloid deposits)
Serum insulin level of T1 and T2 DM
T1: decreased T2: variable
Classic symptoms of polyuria, polydipsia, polyphagia and weight loss in T1 vs. T2 DM
T1: common T2: sometimes
Histology of T1 and T2 DM
T1: islet leukocyte infiltrate T2: islet amyloid polypeptide (IAPP) deposits
Diabetic ketoacidosis is usually due to…
increased insulin requirements from increased stress (infxn). It leads to excess fat breakdown and increased ketogenesis from increased free fatty acids, which are then made into ketone bodies.
Signs/symptoms of diabetic ketoacidosis (6)
-Kussmaul respirations (rapid/deep breathing) -nausea/vomiting -abdominal pain -psychosis/delirium -dehydration -fruity breath odor (due to exhaled acetone)
Diabetic Ketoacidosis Labs
-hyperglycemia -increased H+ -decreased HCO3- (anion gap metabolic acidosis) -increased ketone levels -leukocytosis -hyperkalemia (with depleted intracellular K+)
Complications of diabetic ketoacidosis
-life threatening mucormycosis (usually caused by Rhizopus infxn) -cerebral edema -cardiac arrhythmias -heart failure
Treatment for diabetic ketoacidosis
-IV fluids -IV insulin -K+ -glucose if necessary
Insulinoma is a…
tumor of the beta cells of the panreas taht leads to hypoglycemia.
Insulinoma presents with the…
whipple triad of episodic CNS symptoms (lethargy, syncope, and diplopia)
Symptomatic insulinoma pts have…
decreased blood glucose and increaesed C-peptide levels.
Carcinoid syndrome is caused by…
carcinoid tumors (neuroendocrine cells) esp. metastatic small bowel tumors which secrete high levels of serotonin.
In carcinoid syndrome, high serotonin is not seen if…
the tumor is limited to the GI tract bc 5-HT undergoes first-pass metabolism.
Carcinoid syndrome results in…
-diarrhea -flushing -asthmatic wheezing -right-sided valvular disease
Labs for Carcinoid syndrome
-increased 5-HIAA in urine -niacin deficiency
Treatment for Carcinoid syndrome
-resection -somatostatin analog
Zollinger-Ellison syndrome is…
a gastrin-secreting tumor of the pancreas or duodenum. May be associated with MEN 1.
In ZE syndrome, acid hypersecretion causes…
recurrent ulcers in the distal duodenum and jejunum.
ZE syndrome presents with…
abdominal pain and diarrhea.
MEN 1 Characteristics
- parathyroid tumors 2. pituitary tumors 3. pancreatic endocrine tumors (ZE, insulinomas, VIPomas, glucagonomas)
MEN1 commonly presents with…
kidney stones and stomach ulcers.
MEN 2A characteristics
- medullary thyroid carcinoma 2. pheochromocytoma 3. parathyroid hyperplasia
MEN 2B charcteristics
- medullary thryoid carcinoma 2. pheochromocytoma 3. oral/intestinal ganglioneuromatosis (associated with Marfanoid habitus)
MEN 2A and 2B are associated with…
ret gene mutations.
