Endocrine Flashcards
Thyroid development
Thyroid diverticulum arises from floor of primitive pharynx and descends into neck.
Connected to tongue via thyroglossal duct
Thyroglossal duct disappears –> foramen cecum
Thyroid follicular cells derived from endoderm
Most common ectopic thyroid tissue site
tongue –> hypothyroidism
Thyroglossal cyst
anterior midline nech mass
moves with swallowing or protrusion of tongue
Remnant thyroglossal duct
Anterior pituitary
Secretes FSH, LH, ACTH, TSH, prolactin, GH, B endorphin
Derived from oral ectoderm
Posterior Pituitary
store and release vasopressin and oxytocin (made in hypothalamus and transported to posterior pituitary via neurophysins)
Derived from neuroectoderm
Adrenal Cortex
Mesoderm
Glomerulosa- Ang II regulates, release aldosterone
Fasciculata- regulated by ACTH and CRH, release cortisol
Reticularis- regulated by ACTH, and CRH, releases DHEA
Adrenal Medulla
Neural crest
Chromaffin cells
regulated by preganglionic sympathetic fibers
release epinephrine and norepinephrine
ADH level in DI
decreased in central DI
increased/normal in nephrogenic DI
CRH
Hypothalamus
increase ACTH, MSH, B endorphin
Dopamine
Hypothalamus
decrease prolactin, TSH
GHRH
Hypothalamus
increase GH
GnRH
Hypothalamus release FSH and LH Suppressed by hyperprolactinemia tonic GnRH --> suppress axis pulsatile GnRH --> puberty and fertility
MSH
Hypothalamus
increase melanogenesis by melanocytes
Oxytocin
Hypothalamus
Cause uterine contractions during labor. Milk letdown reflex in response to suckling
Prolactin
Anterior PItuitary Decrease GnRH stimulate lactogenesis, inhibit ovulation and spermatogenesis Excess --> decreased libido Inhibited by dopamine
Pituitary prolactinoma
amenorrhea, osteoporosis, hypogonadism, galactorrhea
Somatostatin
Hypothalamus
Decrease GH and TSH
TRH
Hypothalamus
increase TSH and prolactin
Growth Hormone
Anterior Pituitary
Linear growth and muscle mass somatomedin C secretion (liver). Increases insulin resistance
Secretion increase during exercise, deep sleep, puberty, hypoglycemia, CKD
Secretion decrease by glucose, somatostatin, somatomedin
Acromegaly/ gigantism
Acromegaly (adults) Gigantism (children)
Excess GH secretion
T(x) somatostatin analog, surgery
ADH
Synthesized in hypothalamus and stored in posterior pituitary
regulates blood pressure and serum osmolality via regulation of aquaporin channel insertion in principal cells of renal collecting duct.
Thyroid Hormone
produces T3 (active) and T4 (inactive) – thyroid follicles
Inhibited by glucocorticoids, B-blockers and PTU
Brain maturation, bone growth, B adrenergic effects, increase BMR, increase glycogenolysis and lipolysis, stimulate surfactant synthesis in babies
Wolff-Cahikoff effect
excess iodine turns off thyroid peroxidase –> decreased T3/T4 production
Increased TBG
in pregnancy, OCP use –> increase total T3/T4
Decreased TBG
in steroid use and nephrotic syndrome
Parathyroid Hormone
Chief cells of parathyroid
Increase free calcium in blood and GI via bone resorption and reabsorption in DCT. Increase calcitriol production by activating 1a hydroxylase in PCT
Stimulated by RANKL-RANK interaction
Secreted when low serum calcium and magnesium
Inhibited when high serum phosphate
Calcium Homeostasis
High pH –> albumin binds for Ca2+ –> decreased ionized Ca2+ –>cramps, pain, paresthesias –> increase PTH
Low pH –> albumin binds less Ca2+ –> increase ionized Ca2+ –> low PTH
Calcitonin
Parafollicular cells of thyroid
Decrease bone resorption
regulated by increase serum Ca2+ –> increase calcitonin secretion
Glucagon
a cells of pancreas
promotes glycogenolysis, gluconeogenesis, lipolysis, ketogenesis. Elevates blood sugar levels to maintain glucose
Secreted when hypoglycemic
Inhibited by insulin, hyperglycemia and somatostatin
Insulin synthesis
Preproinsulin (RER of pancreatic B cells) –> proinsulin (stored in secretory granules) –> insulin and C peptide
Insulin Functions
bind insulin receptors (TK) –> glucose uptake
increase glucose transport to skeletal muscle and adipose tissue, increase glycogen/ TAG synthesis
DOES NOT CROSS PLACENTA
Insulin dependent glucose transporters
GLUT4- adipose tissue, striated muscle, exercise
Insulin independent glucose transporters
GLUT1- RBC, brain, cornea, placenta GLUT2- B islet cells, liver, kidney, GI GLUT3- brain and placenta GLUT5- spermatocytes, GI SGLT1/2- kidney, small intestine
Insulin Regulation
Glucose enter B cells –> increase ATP from metabolism –> close K+ channels and depolarize B cell membrane –> VGCC open –> Ca2+ influx –> insulin exocytosis
increase insulin response with oral glucose via GLP1 or GIP, B2
decrease with a2
17a hydroxylase deficiency
increase mineralcorticoids Decrease K+ Increase BP Decrease Cortisol Decrease sex hormones decrease androstenedione XY ( ambiguous genitalia, undescended testes) XX (lack secondary sexual development)
21 hydroxylase deficiency
decrease mineralcorticoids increase K+ decrease BP Decrease Cortisol increase sex hormones increased renin activity, increased 17 hydroxyprogesterone Salt wasting in infancy XX (virulization)
11B hydroxylase
decrease aldosterone Decrease K+ Increase BP Decrease Cortisol increase sex hormones decrease renin activity HTN, precocious puberty in infancy XX (virilization)
Cortisol
Adrenal zona fasciculata
increase appetite, BP, insulin resistance, gluconeogenesis
Decrease fibroblast activity, inflammatory and immune response, bone formation
regulated by CRH (hypothalamus) –> ACTH (anterior pituitary) –> adrenal cortex
Ghrelin
stimulate hunger and GH release.
Produced by stomach –> lateral area of hypothalamus
Sleep deprivation, fasting and Prader Willi syndrome –> increase ghrelin production
Leptin
Satiety hormone
Produced by adipose tissue –> ventromedial area of hypothalamus
Mutation –> central obesity
sleep deprivation or starvation –> decrease leptin production
Endocannabinoids
Act on cannabinoid receptor in hypothalamus and nucleus accumbens –> increase appetite
Signaling pathway of steroid hormones
Circulate bound to specific binding globulins to increase solubility
Men: increase SHBG lowers free testosterone –> gynecomastia
Women: decrease SHBG raises free testosterone –> hirsutism
Increased estrogen –> SHBG
SIADH
Excessive free water retention
Euvolemic hyponatremic
cerebral edema, seizures
Urine osmolality > serum osmolality
Caused by ectopic ADH, head trauma, pulmonary disease, drugs
T(x): fluid restriction, salt tablets, ADH antagonists
Central DI
via pituitary tumor, autoimmune, trauma, surgery
decreased ADH
>50% increase in urine osmolality after administration of ADH analog
T(x) Desmopressin, Hyration
Nephrogenic DI
Hereditary
Normal/increased ADH levels
no change in urine osmolality with ADH administration
T(x): HCTZ, indomethacin, amiloride, hydration, salt restriction
Sheehan’s syndrome
Hypopituitary
ischemic infarct of pituitary after postpartum bleeding
Presents as failure to lactate, no period, cold intolerance
Empty sella syndrom
Hypopituitary
atrophy or compression of pituitary
common in obese women
associated with idiopathic intracranial HTN
Pituitary apoplexy
Hypopituitary
sudden hemorrhage of pituitary gland in presence of pituitary adenoma
presents with sudden onset of severe HA, visual impairment, bitemporal hemianopia, diplopia (CN III)
Acromegaly
Excess GH in adults
via pituitary adenoma
Large tongue with deep furrows, deep voice, large hands and feet, coarsening facial features with age, frontal bossing
Increased risk of colorectal polyps and cancer
D(x): increased serum IGF1, failure to suppress GH following oral glucose tolerance
T(x): resect, octreotide, DA agonist
Hypothyroidism
cold intolerance, decrease sweating, weight gain, hyponatremia
coarse brittle hair, diffuse alopecia, nonpitting edema, periorbital edema, constipation, decreased appetite, proximal muscle weakness, decreased libido and infertility, lethargic, brady
Increase TSH, decreases T3 and T4, hypercholesteremia
Hyperthyroidism
Heat intolerance, increased sweating, weight loss, pretibial myxedema, exophthalmos, diarrhea, osteoporosis and increase fracture, decreased libido and infertility, hyperactive, tachy
decreased TSH, increased T3 T4, decreased LDL, HDL and cholesterol
Hashimoto Thyroiditis
Hypothyroidism
Autoimmune with antithyroid peroxidase and antithyroglobulin Ab.
Associated with HLA DR3, DR5
incrased risk of NHL
Hurthle cells, lymphoid aggregates with germinal centers
Moderately enlarged, nontender thyroid
Postpartum thyroiditis
Hypothyroidism self limited up to 1 year after delivery Women are euthyroid following resolution Thyroid is painless and normal size Lymphocyteic infiltrate with occasional germinal center formation
Congenital hypothyroidism
Hypothyroid
Ab mediated maternal hypothyroidism, thyroid dysgenesis, iodine deficiency
Pot bellied, pale, puffy faced, protruding umbilicus, protuberant tongue, poor brain development
Subacute granulomatous thyroiditis
Hypothyroidism
self limited following flu like illness
granulomatous inflammation
increase ESR, jaw pain, tender thyroid
Riedel thyroiditis
Hypothyroidism
Thyroid replaced by fibrous tissue and inflammatory infiltrate.
IgG4 related systemic disease
fixed, hard, painless goiter
Graves Disease
Hyperthyroidism
IgG –> TSH receptors on thyroid (goiter), dermal fibroblasts (pretibial myxedema) and orbital fibroblasts (exophthalmos)
Activate T cells –> release inflammatory cytokines
Presents during stress
Associated with HLA DR3 and B8
tall, crowded follicular epithelial cells, scalloped colloid
Toxic Mandibular goiter
Hyperthyroidism focal patches of hyperfunctioning follicular cells distended with colloid working independently of TSH Increase release of T3 and T4 Hot nodules Not malignant
Thyroid Storm
Hyperthyroidism
worsen in acute stress
agitation, delirium, fever, diarrhea, coma, tachy
T(x): B blockers, propylthiouracil corticosteroids, potassium iodide
Jod Basedow phenomenon
Hyperthyroidism
Iodine induced
Iodine deficiency and autonomous thyroid tissue is made iodine replete (after iodine IV contrast or amiodarone use)
Causes of goiter
Smooth/diffuse –> graves, Hashimoto, iodine deficiency, TSH secreting pituitary ademona
Nodular –> toxic multinodular goiter, thyroid adenoma, cancer, cyst
Thyroid adenoma
Benign solitary growth
nonfunctional (does not cause hyperthyroidism)
absence of capsular or vascular invasion
Thyroid Cancer
D(x) fine needle aspiration
T(x) thyroidectomy
complications of surgery –> hypocalcemia, transection of recurrent laryngeal N, injury to the external branch of the superior laryngeal N
Papillary Carcinoma
Excellent prognosis
empty appearing nuclei with central clearing, psammoma bodies, nuclear grooves. increased risk with RET/PTC rearrangements and BRAF mutations, childhood irradiation
Palpable LN
follicular Carcinoma
Good prognosis
invade thyroid capsule and vasculature
uniform follicles, hematongenous spread
Associated with RAS mutations and PAX8-PPARy translocations
Medullary Carcinoma
From parafollicular C cells
produce calcitonin, sheets of polygonal cells in an amyloid stroma
Associated with MEN2A ad 2B
Undifferentiated/ Anaplastic Carcinoma
older patients rapidly enlarging neck mass compressive symptoms Poor prognosis Associated with TP53 mutation
Hypoparathyroidism
tetany, hypocalcemia, hyperphosphatemia
Chovstek sign- tap facial N –> facial muscles contract
Trousseau sign- occlusion of brachial A with BP cuff –> carpal spasms
Pseudohypoparathyroidism Type 1A
AD
maternally transmitted mutations (GNAS1 inactivating mutation via imprinting) - encode Gs protein a subunit–> inactivate adenylate cyclase when PTH binds to its receptor –> end organ resistance to PTH
Albright hereditary osteodystrophy (short stature, round face, subQ calcifications)
Increase PTH, low Ca2+, high phosphate
Pseudopseudohypoparathyroidism
AD
paternally transmitted mutations (imprinted GNAS gene) but no end organ resistance to PTH
Albright hereditary osteodystrophy
normal PTH, Ca2+, phosphate
Vitamin D Deficiency
decrease Ca2+
decrease phosphate
increase PTH
Hypoparathyroidism
decrease Ca2+
increase phosphate
decrease PTH
Secondary Hyperparathyroidism (CKD)
decrease Ca2+
increase phosphate
increase PTH
Pseudohypoparathyroidism
decrease Ca2+
increase phosphate
increase PTH
Hyperphosphatemia
decrease Ca2+
increase phosphate
increase PTH
Primary hyperparathyroidism
via parathyroid adenoma or hyperplasia
Hypercalcemia, hypercalciuria, polyuria, hypophosphatemia, increase PTH, ALP and urinary cAMP
bone pain, weakness, constipation, ab/flank pain, neuropsychiatric disturbances
Osteitis fibrosa cystica
cystic bone spaces filled with brown fibrous tissue
Due to high PTH
Primary Hyperparathyroidism
Secondary Hyperparathyroidism
secondary hyperplasia due to decrease Ca2+ absorption or increased phosphate
CKD
hypocalcemia, hyperphosphatemia, high ALP and PTH
Renal osteodystrophy –> bone lesions
Tertiary Hyperparathyroidism
Refractory hyperparathyroidism resulting from CKD
HIGH PTH and calcium
Familial hypocalciuric hypercalcemia
Defective G coupled Ca2+ sensing receptors in multiple tissues
High Ca2+ –> suppress PTH
Excess renal calcium reabsorption –> mild hypercalcemia and hypocalciuria with normal/high PTH
Diabetes Mellitus
polydipsia, polyuria, polyphagia, weight loss, DKA (type 1), hyperosmolar hyperglycemia (Type 2)
complications: diffuse thickening of BM in small vessels –> retinopathy, microaneurysms, glaucoma, nephropathy, CKD. Large vessel atherosclerosis, CAD, peripheral vascular occlusive disease, gangrene. Osmotic damage –> cataracts and neuropathy
D(x): HbA1c >6.5%, fasting blood glucose >126, 2 hour oral glucose tolerance >200
Type 1 DM
autoimmune T cell mediated destruction of B cells. Insulin always needed in T(x) <30 years Weak genetic predisposition Associated with HLA DR4, DR3 Severe glucose intolerance and high insulin sensitivity common DKA Islet leukocytic infiltrate
Type 2 DM
increase resistance to insulin Sometimes need insulin >40 years Associated with obesity and genetic predisposition Rare DKA IAPP deposits
DKA
Insulin absent ketones present (B hydroxybutyrate > acetoacetate)
Deadly
deliriumm Kussmael respirations, abdominal pain, dehydration, fruity breath
Hyperglycemia, increase H+, low bicarb, increase urine and blood ketones, leukocytosis, Normal/high K+, decrease insulin and acidosis
complications: mucormycosis, cerebral edema, cardiac arrhythmias, HF
T(x): IV fluids, insulin, K+
Hyperosmolar hyperglycemic state
insulin present, ketones absent
profound hyperglycemia –> excessive osmotic diuresis –> dehydration and increased serum osmolality
elderly Type 2 DM that can’t drink
Thirst, polyuria, lethargy, focal neuro deficits, seizures
Hyperglycemia, increased serum osmolality, normal pH, no ketones, Normal/ high serum K+
Complications: death, coma
T(x): IV fluid, insulin and K+
Cushing
increased cortisol
Exogenous –> low ACTH –> bilateral adrenal atrophy
Primary adrenal adenoma, hyperplasia –> low ACTH –> atrophy of adrenal gland NOT involved
ACTH secreting pituitary adenoma, paraneoplastic ACTH secretion –> bilateral adrenal hyperplasia
high cholesterol, urinary free cortisol, skin changes (striae, thinning), HTN, immunosuppression, neoplasm, growth retardation, hyperglycemia, amenorrhea, moon facies, buffalo hump, osteoporosis
Tests: high free cortisol on 24 hour urinalysis, increase late night salivary cortisol, no suppression with dexamethasone test
Nelson Syndrome
enlargement of pre-existing ACTH secreting pituitary adenoma after bilateral adrenalectomy for refractory Cushing disease –> high ACTH, mass effect
T(x): transsphenoidal resection, post op pituitary irradiation for residual tumor
Adrenal insufficiency
inability of the adrenal gland to generate enough glucocorticoids and/or mineralcorticoids for the body
weakness, fatigue, orthostatic hypotension, muscle aches, weight loss, GI disturbances
T(x): glucocorticoids/mineralcorticoids
Primary adrenal insufficiency
decreased gland function –> low cortisol, low aldosterone –> hypotension, hyperkalemia, met acid, hyperpigment
Acute: sudden onset, shock
Chronic: Addison disease (adrenal atrophy via autoimmune)
Waterhouse Friderichson syndrom: acute due to adrenal hemorrhage via N. meningitidis, DIC, shock
Secondary Adrenal insufficiency
Seen with low pituitary ACTH production.
NO skin hyperpigmentation or hyperkalemia
Tertiary Adrenal Insufficiency
Seen in patients with chronic exogenous steroid use, precipitated by abrupt withdrawal
aldosterone synthesis unaffected
Hyperaldosteronism
HTN, low/normal K+, met alk, secondary causes edema
Primary Hyperaldosteronism
Adrenal adenoma or bilateral adrenal hyperplasia
high aldosterone, low renin
Treatment resistant HTN
Secondary Hyperaldosteronism
Renovascular HTN, JG cell tumors and edema
Neuroendocrine Tumors
GI, pancreas, and lungs. Thyroid and adrenals
T(x): resection, somatostatin analogs
Neuroblastoma
Tumor of adrenal gland in children (<4years)
Originated from NCC on the sympathetic chain
abdominal distention and firm irregular mass that can cross midline
Hgih HVA and VMA in urine. Homer Wright rosettes
Associated with N myc
Pheohromochytoma
Tumor of adrenal gland in adults
Derived from chromaffin cells
Associated with germline mutations NF1, VHL, RET
Secrete epinephrine, NE and DA –> episodic HTN
EPO –> polycythemia
high catecholamines and metanephrines
T(x) irreversible a antagonists then B blockers
MEN 1
Pituitary tumors
Pancreatic endocrine tumors
Parathyroid adenomas
Associated mutation in MEN1, angiofibromas, collagenomas, meningiomas
MEN 2A
Parathyroid hyperplasia
Medullary thyroid carcinoma
Pheochromocytoma
Associated with RET mutation
MEN 2B
Medullary thyroid carcinoma
Pheochromocytoma
mucosal neuromas
Associated with marfanoid habitus and RET gene mutation
Insulinoma
Tumor of pancreatic B cell –> high insulin –> hypoglycemia
Whipple triad: low blood glucose with resolution of symptoms after normalization of glucose levels
high C peptide
Associated with MEN 1
T(x): surgery
Glucagonoma
Tumor of pancreatic a cells –> high glucagon
Dermatitis, Diabetes, DVT, declining weight, Depression, Diarrhea
T(x): octretide, surgery
Somatostatinoma
Tumor of pancreatic delta cells –> high somatostatin –> low secretion of secretin, cholecystokinin, glucagon, insulin, GIP
Present with diabetes, steatorrhea, gallstones, achlorydia
T(x): surgery, somatostatin analogs for symptom control
Carcinoid syndrome
Arise from neuroendocrine cells (intestine and lung)
Prominent rosettes, chromogranin A + and synaptophysin +
secrete 5HT –> recurrent diarrhea, wheezing, right sided heart valvular disease
T(x): surgery, somatostatin analog for symptom control
Zollinger Ellison Syndrome
gastrin secreting tumor of pancreas or duodenum
Acid hypersecretion–> recurrent ulcers in duodenum and jejunum
Ab pain, diarrhea
+ secretin stimulation test (gastrin remain elevated)
Associated with MEN 1`
Insulin prep
Bind insulin receptor
Adverse hypoglycemia, lipodystrophy, hypersensitivity, weight gain
Biguanides
Increase insulin sensitivity
inhibit mGPD –> inhibit hepatic gluconeogenesis and glucagon
Increase glycolysis
Adverse: GI upset, lactic acidosis, vit B12 deficiency, weight loss
Glitazones/ thiozolidinediones
Increase insulin sensitivity
Activate PPARy –> increase insulin sensitivity and adiponectin –> regulate glucose metabolism and FA storage
Adverse: weight gain, edema, HF, fractures
Delated onset
Sulfonylurea
chlorpropamide, tolbutamide
Close K+ channels in pancreatic B cell membrane –> cell depolarize –> insulin release via calcium influx
Adverse: disulfiram like reaction, hypoglycemia
Meglitinides
Nateglinide, repalglinide
Close K+ channels in pancreatic B cell membrane –> cell depolarize –> insulin release via calcium influx
Adverse: hypoglycemia
GLP1 analog
Exenatide, liraglutide
decrease glucagon, decrease gastric emptying, increase insulin
Adverse nausea, vomiting, pancreatitis, weight loss, increased satiety
DPP4 inhibitors
-liptin
inhibit DPP4 –> no GLP1 deactivation –> decrease glucagon, decrease gastric emptying, increase insulin
Adverse: respiratory and urinary infections, weight neutral, increased satiety
Na-glucose co transporter 2 inhibitor
-fozin
block reabsorption of glucose in PCT
Adverse: glucosuria, hyperkalemia, weight loss
a glucosidase inhibitor
acarbose, miglitol
inhibit intestinal brush border a glucoidases –> delated carb hydrolysis and glucose absorption –> low postprandial hyperglycemia
Adverse: GI upset, bloating
Amylin analongs
Pramlintide
low glucagon release, low gastric emptying
Adverse: Hypoglycemia, nausea, high satiety
Thionamides
propylthiouracil, methimazole
block thyroid peroxidase, inhibit oxidation of iodide –> inhibit thyroid hormone synthesis
Used in Hyperthyroidism. PTU in first trimester
Adverse: skin rash, agranulocytosis, aplastic anemia, hepatotoxicity.
Levothyroxine, liothyonine
Hormone replacement for T4 and T3
used in Hypothyroidism, myxedema. abused for weight loss
Adverse: tachy, heat intolerance, tremors, arrhythmias
Conivaptan, tolvaptan
ADH antagonists for SIADH
Demeclocycline
ADH antagonist and tetracycline
for SIADH
Desmopressin
Used in central DI, willebrand disease, sleep enuresis, hemophilia A
GH
used in GH deficiency, turner
oxytocin med
used to induce labor, control uterine hemorrhage
Somatostatin
used in acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, esophageal varices
Flurocortisone
synthetic analog of aldosterine
used in mineralcorticoid replacement in primary adrenal insufficiency
cinacalcet
sensitizes CaSR in parathyroid gland –> decrease PTH
used for secondary hyperparathyroidism in CKD, hypercalcemia in primary hyperparathyroidism or in parathyroid carcinoma
Adverse: hypocalcemia
Sevelamer
nonabsorbable phosphate binder that prevents phosphate absorption from the GI tract
used in hyperphosphatemia in CKD
Adverse: Hypophosphatemia, GI upset
