Endocrine Flashcards
insulin receptor
tyrosine kinase receptor that induces glucose uptake into insulin-dependent tissues via GLUT-4 receptors and affects gene transcription.
Regulation of insulin release
Glucose enters beta cell and is metabolized, increasing ATP. ATP closes K+ channels leading to depolarization. VG Ca++ channels open leading to Ca++ influx and exocytosis of insulin.
Effects of somatostatin
Decreases growth hormone and TSH release from the pitutiary. Analogues can thus be used to treat acromegaly.
Effects of TRH
increases TSH and prolactin
Two functions of growth hormone
Stimulates growth through IGF-1
Increases insulin resistance (diabetogenic)
Regulation of growth hormone
Released in pulses in response to GHRG. Secretion higher during exercise and sleep. Secretion inhibited by glucose and somatostatin.
Ghrelin
Stimulates hunger and GH release. Produced by stomach
Leptin
Satiety hormone produced by adipose tissue
Regulation of ADH
Osmoreceptors in hypothalamus
Hypovolemia
17-alpha-hydroxylase deficiency
High mineralocorticoids; low cortisol and sex steroids. High BP, low K+, low androstenedione, non-virilizing. Males have ambiguous genitalia at birth, females lack secondary sex development.
21-hydroxylase deficiency
Most common cause of CAH. high sex hormones; low mineralocorticoids and cortisol. Low BP and high K+. High 17-OH-progesterone and high renin activity.
11beta-hydroxylase deficiency
Low aldosterone and cortisol but high 11-beta-deoxycorticosterone results in increased BP. High sex hormones. Virilization and salt wasting.
Cortisol functions
BIG FIB:
- increases BP
- increases insulin resistance
- increases gluconeogenesis
- decreases fibroblast activity which is what causes striae in cushings
- decreases inflammatory/immune response: inhibits leukotriene and PG production, inhibits WBC adhesion resulting in neutrophilia, blocks histamine release, reduces eosinophils, blocks IL-2 production
- decreases bone formation
functions of vitamin D
- increaes absorption of Ca++ and phosphorus in gut
- increases bone resorption, increasing Ca++ and phosphorus
regulation of vitamin D
Active levels increased by high PTH and low Ca++ and phosphorus
Functions of PTH
- increases bone resorption of Ca++ and phosphorus by increasing production of RANK-L which binds RANK receptor on osteoclasts to stimulate them
- increases kidney reabsorption of Ca++ in distal tubule
- decreases reabsorption of phosphorus in distal tubule
- increases active vitamin D production in kidney
Regulation of PTH
increased by low Ca++, high phos, low Mg++. Decreased by very low Mg++.
Hormones that signal through cAMP
FLAT ChAMP: FSH, LH, ACTH, TSH, CRH, hCG, ADH, MSH, PTH, calcitonin, GHRH
Pituitary hormones: FSH, LH, TSH, ADH (V2 receptor), ACTH, MSH (all but prolactin and oxytocin)
Hypothalamic hormones: CRH, GHRH
Others: hCG, PTH, calcitonin, glucagon
Hormones that signal through cGMP
ANP, BNP, NO
Hormones that signal through IP3
GOAT HAG: GnRH, oxytocin, ADH (V1 receptor), TRH, histamine (H1 receptor), angiotensin II, gastrin
Hormones that signal through intracellular receptor
Steroid hormones, thyroid hormone, vitamin D
Hormones that signal through intrinsic tyrosine kinase
Insulin, IGF-1, other growth factors
Hormones that signal through receptor-associated tyrosine kinase (JAK/STAT)
PIGG(L)ET: prolactin, immunomodulators, GH, G-CSF, EPO, thrombopoietin
Functions of T3
4Bs:
- brain maturation
- bone growth
- beta-adrenergic effects
- increased basal metabolic rate
Symptoms of adrenal insufficiency
Weakness, fatigue, orthostatic hypotension, muscle aches, weight loss, GI disturbance, sugar/salt cravings
Primary vs secondary vs tertiary adrenal insufficiency
Primary: Def of aldo and cortisol. Hypotension, hyperkalemia, and metabolic acidosis. ACTH high resulting in hyperpigmentation. Can be acute due to massive hemorrhage or chronic due to Addison disease
Secondary: Decreased ACTH production. No hyperpigmentation or hyperkalemia
Tertiary: Abrupt withdrawal of chronic exogenous steroid use
Neuroblastoma of adrenal medulla
Most common tumor of adrenal medulla in kids. Usually seen in those less than 4. Neural crest derivative with overexpression of N-myc. Pathology includes Homer-Wright rosettes.
Presents with abdominal distension and firm, irregular mass (vs smooth Wilms tumor). May see dancing eyes-dancing feet.
Labs: elevated HVA, VMA in urine due to breakdown or dopamine and NE. Bombesin and neuron-specific enolase pos.
Genetic syndromes associated with pheo
NF1, VHL, MEN2A, MEN2B
treatment of pheo
1) irreversible alpha antag (before beta blocker to prevent hypertensive crisis)
2) beta blocker
3) surgery
Reflexes in hypoand hyperthyroidism
decreased in hypo, increased in hyper
Autoantibodies and HLA type in hashimoto thyroiditis
anti-thyroid peroxidase, antimicrosomal, antithyroglobulin
HLA-DR5 associated
Tender vs non-tender thyroid in hypothyroidism
Nontender: hashimoto, Riedel thyroiditis
Tender: subacute thyroiditis
Congenital hypothyroidism presentation
pot-belly pale puffy face protruding umbilicus protuberant tongue poor brain development
subacute thyroiditis
self-limited
hyperthyroid progressing to hypothyroid
granulomatous inflammation
very tender thyroid
Riedel thyroiditis
thryoid replaced by fibrous tissue
IgG4-related systemic disease
fixed, hard, painless goiter
Presentation of Graves disease
hyperthyroidism, exophtalmos, pretibial myxedema
toxic multinodular goiter
focal patches of hyperfunctioning follicular cells due to TSH receptor mutation. Hot nodules rarely malignant
Thyroid storm
Stress induced catecholamine surge due to thyrotoxicosis. Agitation, delirium, fever, diarrhea, coma, tachyarrhythmia.
Treatment: beta blocker, propylthiouracil, corticosteroids
Thyroid cancers: papillary, follicular, medullary, anaplastic, lymphoma
Papillary carcinoma: Most common and excellent prognosis. Empty-appearing nuclei with central clearing. Psammoma bodies with nuclear grooves.
Follicular carcinoma: Good prognosis. Distinguished from follicular adenoma by invasion of the capsule.
Medullary carcinoma: C-cell drived. Produces calcitonin. Associated with MEN2A and 2B
Anaplastic carcinoma: seen in older patients. Very poor prognosis
Lymphoma: associated with hashimoto
Symptoms of hypoparathyroidism
Hypocalcemia and tetany.
Chvostek sign: tap facial nerve and see contraction of facial muscles
Trousseau sign: occlude brachial artery with BP cuff and see carpal spasm
Pseudohypoparathyroidism
AD condition in which kidney unresponsive to PTH. Causes hypocalcemia, shortened 4th/5th digits, short stature
Familial hypocalciuric hypercalcemia
Defective Ca++ receptor on parathyroid cells so PTH not suppressed. High calcium with normal to high PTH.
Presentation of acromegaly
Large tongue with deep furrows Deep voice Large hands and feet Coarse facial features Insulin resistance Risk of colorectal polyps and cancer
Sheehan syndrome
Ischemic infarct of pituitary following postpartum bleeding leading to hypopituitarism. Presents with failure to lactate, absent menstruation, cold intolerance.
Empty sella syndrome
Atrophy or compression of pituitary leading to hypopit. Common in obese women
Pituiary apoplexy
Sudden hemorrhage of pituitary leading to hypopit
Diabetic complications of osmotic damage
Sorbitol accumulates in organs with aldolase reductase is what causes the damage. Neuropathy and cataracts.
Diabetic complications due to small vessel disease
Diffuse thickening of BM. Retinopathy, glaucoma, neuropathy, nephropathy.
Type I diabetes: HLA association
HLA-DR3 and HLA-DR4
Zollinger-Ellison syndrome
Gastrin-secreting tumor in pancreas or duodenum. Acid hypersecreting reulting in ulcers.
presentation: abdominal pain and diarrhea
Diagnosis: Pos secretin stim tes (gastrin stays high after giving secretin which should suppress it
Associated with MEN 1
MEN1
Parathyroid tumors, pituitary tumors, pancreatic endocrine tumors (zollinger-ellison syndrome, insulinomas, VIPomas, glucagonomas)
MEN2A
Parathyroid hyperplasia, pheochromocytoma, medullary carcinoma, marfanoid habitus, RET mutation
MEN2B
Pheochromocytoma, Medullar thyroid carcinoma, oral/intestinal ganglioneuromatosis, marfanoid habitus, RET mutation
Names of insulins
Rapid acting: aspart, glulisine, lispro
Short acting: regular insulin
Intermediate acting: NPO
Long acting: glargine, detemir
Metformin
MOA: unkown, decreases gluconeogenesis, increases glycolysis, increases peripheral glucose uptake (insulin sensitizer)
Use: Oral for type 2 DM. Modest weight loss.
ADRs: lactic acidosis (contraindicated in renal insufficiency)
Sulfonylureas
Names: chlorpropramide and tolutamide (first gen); glimepiride, glipizide, glyburide (second gen)
MOA; Close K+ channel in beta cell membane resulting in depolarization and insulin release
Use: Type 2 DM only
ADRs: risk of hypoglycemia; disulfiram-like effects for first gen only
DDIs: non-specific beta blockers can mask symptoms of hypoglycemia
Thiazolidinediones
Names: pioglitazone, rosiglitazone
MOA: increase insulin sensitivity by binding PPAR-gamma
Use: Type 2 DM
ADRs: weight gain, hepatotoxicity, risk of fracture
GLP-1 agonists
Names: exenatide, liraglutide
MOA: increase insulin, decrease glucagon release
Use: Type 2 DM
ADRS: pancreatitis, N/V
DPP-4 inhibitors
Names: linagliptin, saxagliptin, sitagliptin
MOA: increase insulin, decrease glucagon release
Use: Type 2 DM
ADRs: urinary or resp infections
Amylin analogs (pramlintide)
MOA: decreases gastric emptying and decreases glucagon
Use: Type 1 and type 2 DM
ADRs: hypoglycemia
SGLT-2 inhibitors (canagliflozin)
MOA: blocks reabsorption of glucose in prox collecting tubule
Use: Type 2 DM
ADRs: UTIs and yeast infections due to glucosuria
alpha-glucosidase inhibitors
Names: acarbose, miglitol
MOA: inhibits intesinal brush border alpha glucosidases, delaying glucose absorption and decreasing postprandial hyperglycemia
Use: type 2 DM
Propylthiouracil and methimazole
MOA: block thyroid peroxidase, inhibiting oxidation and organification of iodine and thus inhibiting thryoid hormone synthesis. PTU also blocks peripheral conversion of T4 to T3
Use: Hyperthyroidism. PTU used in pregnancy because methimazole is possible teratogen
ADRs: agranulocytosis, aplasatic anemia
ADH antagonists
Names: Conivaptan, tolvaptan, demeclocycline
MOA: block ADH receptor
Use: SIADH
ADR: demeclocycline is of tetracycline family and so can cause bone and teeth abnormalities
Octreotide
MOA: somatostatin analogue
Use: acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, esophageal varices
Cinacalcet
MOA: sensitizes parathyroid gland to calcium, decreasing PTH
Use: primary or secondary hyperparathyroidism
Bromocriptine
MOA: dopamine agonist
Use: hyperprolactinemia
Central DI: damage to pituitary vs hypothalamus
Damage to pituitary or infundibulum causes only transient DI because hypothalamic axons regenerate and hypertrophy. Damage to hypothalamic neurons results in permanent DI
Acetyl coA carboxylase
Fatty acid metabolism enzyme: converts acetyl coA to malonyl coA
Glycerol kinase
Part of gluconeogenesis from triglycerides
Parathyroid Ca++ sensing receptors
Transmembrane G protein coupled receptors
Neurophysins
Carrier proteins for oxytocin and vasopressin
glucagon receptor activates
Acts through Gs coupled receptor. Binds to receptor, alpha subunit releases GDP and binds GTP so can dissociate. Gs activates adenylate cyclase, which converts ATP to cAMP. cAMP activates PKA which phosphorylates serine/threonine residues in enzymes to activate or deactivate the,
