Endocrine Flashcards
Normal migration of thyroid gland?
Thyroid gland is out pouching or pharyngeal epithelium that descends into the neck. Connected to tongue by thyroglossal duct. The foramen cecum is the dorsal surface of tongue and is a remnant.
Presentation of thyroglossal duct cyst?
Anterior midline neck mass that moves with swallowing o r tongue movt
Lingual thyroid
If only thyroid tissue present, removal could lead to hypothyroidism (in children lethargy, jaundice, feeding problems, constipation)
Congenital adrenal hyperplasia etios
21-hydroxylase deficiency - most common; dec. glucocorticoids and mineralocorticoids with increased adrenal androgens; 11B-hydroxylase - decreased glucocorticoids and inc. adrenal androgens; 17a-hydroxylase - nl mineralo, dec. androgens, estrogens, cortisols; 5a-reductase - defective conversion of testosterone to dihydrotestosterone (responsible for fusion); Side chain cleavage - conversion of chop to pregnenolone; impaired synthesis of all steroid hormones; Tx = low-dose corticosteriods to suppress ACTH secretion
MEN I
3 P’s - (hyper)Parathyroidism, Pancreas (gastrinoma -> peptic ulcer), Pituitary adenoma. Commonly presents with kidney stones + stomach ulcers.
Treatment for male pattern baldness?
5-alpha-reductase inhibitors (e.g. finasteride) b/c it is thought that enzyme in scalp doesn’t work that well
Salt-wasting v. non-salt-wasting 21-hydroxylase deficiency presentations
Girls - same; birth with ambiguous genitalia
Boys - Salt-wasting will present at 1-2 weeks with FTT, dehydration, hyperkalemia, and hyponatremia. Non-salt-wasting will present at 2-4 yrs with early virilization.
What enzyme converts Vitamin D into active form?
1-alpha hydroxylase. Resides in kidneys.
Adrenal gland subdivisions?
Cortex - zona glomerulosa (mineralocorticoids,aldo), zona fasciculata (glucorticoids, cortisol), zona reticularis (androgens); GFR = ACA
Medulla
Be wary of what side effects by which thyroid drugs?
Agranulocytosis by methimazole or PTU. WBC w/ diff for fever
Thyroid peroxidase?
Oxidation of iodide to iodine, iodination of thyroiglobuline tyrosine, and iodotyrosine coupling that forms T3, T4. TPO ab’s for Hashimoto’s.
Papillary carcinoma of thyroid FNA
Finely dispersed chromatic, ground-glass (Orphan Annie Eye), w/ intranuclear inclusions and grooves, and psammoma bodies.
Mech of hypoglycemia symptoms?
Inc. secretion of epinephrine and NE lead to sweating, tremor, palpitations, hunger, nervousness. CNS symptoms later b/c higher brain center activity decreases to conserve glucose -> behavior, confusion, stupor, seizures. Selective Beta-blockers preferable in diabetics b/c Beta-2 blockade leads to inhibition of gluconeogenesis, glycogenolysis, and lypolysis
Congenital Hypothyroidism
Lethargy, poor feeding, prolonged jaundice, constipation, hypotonia, hoarse cry. Pale, dry skin w/ myxedema, MACROglossia. Umbilical hernia. Higher incidence of ASD/VSD.
Neurophysin
Carrier proteins for oxytocin (paraventricular nuclei) and ADH (supraoptic nuclei) produced in hypothalamic nuclei. Help shuttle them to posterior pituitary. Mutation in neurophysin II for vasopressin thought to be cause of AD diabetes insipidus.
Path of Hashimoto’s?
Mononuclear, parenchymal infiltration w/ well-developed germinal centers
Pheochromocytoma rule of 10’s
10% occur as part of hereditary (MEN2, VHL), 10% b/l, 10% are extra-adrenal, 10% malignant. Tumor of chromatin tissue of adrenal medulla that increases production of NE and EPI.
Endogenous opioids?
Beta-endorphin is one derived from proopiomelanocortin (also precursor to ACTH). Stress axis ~ opioid.
Path findings in pancreas for DMT2?
Deposits of amylin (an amyloid) found in pancreatic islets. Theory: lead to beta cell apoptosis and defective insulin secretion
How to distinguish between where alkaline phosphatase is coming from?
Bone-specific Aphos is denatured by heat. Liver APhos does not.
Achondroplasia
AD. FGFR-3 point mutation leading to increased INHIBITION of cartilage proliferation. Normal trunk, shortened proximal extremities, enlarged head and frontal bossing.
Glucagonoma
Alpha-cells of pancreatic islets. Necrolytic migratory erythema, Hyperglycemia.
VIPoma
Intractable diarrhea, metabolic acidosis, hypokalemia
Somatostatinoma
Tumor of pancreatic delta-cells. Abdominal pain, gallbladder stones, constipation, steatorrhea. 2/2 to somatostatin’s inhibitory effects of insulin, glucagon, gastrin, cholecystokinin, and secretin secretion.
Gastrinoma
Neuroendocrine tumor. JEJUNAL ulcer.
Metyrapone test
11-Beta-hydroxylase inhibitor. Test for integrity of HPA axis. B/c 11-deoxycortisol builds up and doesn’t inhibit ACTH, ACTH will be released leading to a build-up of 17-hydroxycorticosteroids, which are detected as normal HPA axis.
Cells of the adrenal medulla?
Chromaffin cells
Adrenal vein venous drainage?
Same as gondal veins. Right adrenal vein goes straight into IVC whereas L adrenal vein goes to L renal vein then IVC.
Anterior pituitary secretes what hormones?
FSH, LH, ACTH, TSH, prolactin, GH, melanotropin
Three types of pancreatic cells and where are they located?
alpha = glucagon (peripheral). Beta = insulin (central). Delta = somatostatin (interspersed)
Structure of insulin proper?
alpha and beta chain. 2 Disulfide bridges between chains. 1 disulfide bridge within alpha chain.
High insulin but NOT high C-peptide?
Suggests EXOGENOUS insulin
Regulation of insulin release overview?
GLUT-2 transports glucose into Beta cells -> glycolysis -> Inc ATP/ADP ration -> stoppage pf ATP-sensitive K+ efflux -> depolarization -> opening of voltage gated Ca2+ influx -> exocytosis of insulin granules
GLUT-1?
Found in RBC’s, brain, and cornea. Insulin-independent
GLUT-2?
Found in Beta-cells, liver, kidney, and small intestine. Bi-directional and insulin-independent.
GLUT-4
Insulin-DEPENDENT glucose transporter in adipose tissue and skeletal muscle.
GLUT-5
Fructose transporter in spermatocytes and GI tract. NOT insulin dependent.
Insulin’s effect on kidney?
Increased Na+ retention
CRH f(x)?
Released by hypothalamus and tells anterior pituitary to secrete ACTH, MSH, beta-endorphin.
Dopamine f(x) in endocrine system?
Released by hypothalamus to tell anterior pituitary to make LESS prolactin. (Therefore, dopamine antagonists -> increased prolactin; and DA agonists can treat prolactinomas)
GnRH f(x)?
Released by hypothalamus to increase FSH and LH. Pulsatile for puberty and fertility. Continuous suppresses axis. It is INHIBITED by prolactin.
The function of hypothalamic somatostatin?
Inhibits the release of GH and TSH from the anterior pituitary.
TRH f(x)?
Increases TSH AND prolactin.
Effects of growth hormone?
Linear growth and muscle mass via IGF-somatmedin produced in the liver. Direct effects of GH include insulin resistance, increased fat utilization, and protein synthesis.
How is GH regulated to cause growth?
In response to GHRH, GH released in pulses during sleep and exercise. Inhibited by glucose and somatostatin.
What synthesizes ADH?
Supraoptic nuclei of the hypothalamus.
V1 vs V2 receptors?
V1 receptors lead to increased vascular smooth muscle contraction. V2 leads to increased water permeability and reabsorption in collecting tubules via increased aquaporn transcription in principal cells.
What enzyme does ACTH activate?
Cholesterol desmolase (cholesterol -> pregnenolone). Inhibited by ketoconazole.
Hypertension, hypokalemia, low DHT enzyme deficiency? Presentation? Other labs?
17-alpha-hydroxylase deficiency. Failure to make 17-hydroxyprog/preg -> dec. cortisol and sex hormones. In males, ambiguous genitalia. In females, lack secondary sexual development.
Hypotension, hyperkalemia enzyme deficiency? Presentation? Other labs?
21-alpha-hydroxylase deficiency. Failure to make mineralocorticoids and cortisol. Presentation is salt-wasting infant or precocious puberty in males and virilization in females. Labs include INC renin, inc 17-hydroxyprogesterone.
11-Beta-hydroxylase deficiency?
HTN 2/2 increased 11-deoxycorticosterone (even though aldo is low). Shunting to sex hormones leads to virilization in females.
How does cortisol affect the immune response?
Inhibits leukotriene and prostaglandin production. Inhibits leukocyte adhesion. Blocks histamine release from mast cells. Reduces eosinophils. Blocks IL-2.
How does cortisol affect blood pressure?
It up regulates alpha-1 receptors in arterioles -> increased sensitivity to catecholamines -> HTN
Calcitonin function and regulation?
Decreases bone resorption (decreases [Ca2+]). Increased serum Ca2+ will cause calcitonin secretion. No effect on osteoblasts.
How does PTH affect the kidneys?
Increases Ca2+ reabsorption at DCT (via upregulation of basolateral Ca/Na exchanger). Decreases reabsorption of phosphate reabsorption by inhibiting Na-P anti porter. Stimulates kidney 1-alpha-hydroxylase -> increased 1,25 D3 production.
How does PTH affect the bones?
Increases calcium and phosphate resorption. Binds PTH receptor on osteoblasts, which make RANK-L -> bind to RANK receptor on osteoclast precursors to mature into osteoclasts = breakdown bone.
How is PTH regulated?
Decreased serum Ca will INCREASE PTH. Decreased Mg will also increase PTH unless REALLY low magnesium –> decreased PTH secretion (e.g. alcoholism)
Effects of vitamin D?
Increases intestinal absorption of both calcium and phosphate. Also increases bone resorption leading to increased serum calcium and phosphate.
Different forms of vitamin D?
D2 from plants. D3 from sunlight. Both are converted by 1-alpha-hydroxylase into 1,25-(OH)2
How is vitamin D regulated?
Increased production by inc. PTH, dec. [Ca2+], dec. Phosphate. Inhibits own production.
cAMP pathway endocrine hormones?
FLAT ChAMP = FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2), MSH, PTH. Calcitonin, GHRH, glucagon.
cGMP pathway endocrine hormones?
NO, ANP.
IP3 pathway endocrine hormones?
GOAT HAG = GnRH, Oxytocin, ADH (v1), TRH, HIstamine (H1), A-II, Gastrin
Steroid receptor pathway endocrine hormones?
VETT CAP = Vitamin D, Estrogen, Testosterone, T3/T4, Cortisol, Aldo, Progesterone
Intrinsic tyrosine kinase vs. receptor-associated tyrosine kinase using endocrine hormones?
Intrinsic = insulin, IGF, FGF, PDGF, EGF. Receptor-associated = Prolactin, immunomodulators, growth hormone.
How is T4 activated?
Via 5’-iodinase in the target tissue to make T3 (active). Some portion of T4 is also inverted into biologically inactive rT3.
How does TBG affect thyroid hormone levels?
TBG is synthesized by the liver and binds to T4/3 in the blood, serving as a reservoir for thyroid hormone. Pregnancy increases estrogen and inhibits hepatic breakdown of TBG -> increased total T4 and T3 but NORMAL free T4 and T3 (clinically euthyroid). Hepatic failure -> increased free thyroid (inhibiting synthesis of thyroid hormone)
Wolff-Chaikoff effect
Inhibition of organification and synthesis of thyroid hormones by high levels of iodide. (I-)
Thyroid peroxidase function?
Oxidizes pumped I- to I2 (as it traverses apical membrane). Organification of I2 into MIT or DIT (in lumen). Coupling reaction to make T4 and T3 on thyroglobulin. Inhibited by PTU and methimazole.
How does iodide even get into the thyroid?
Na-I co-transporter, which is unregulated by low levels of iodide. Blocked by anions (perchlorate, thiocyanate, pertechnetate)
What enzyme recycles left-over MIT and DIT?
Deiodinase.
Effects of thyroid hormone?
4 B’s = Brain maturation, Bone growth, Beta-adrenergic (B1), Basal metabolic rate increase
How does thyroid hormone increase the basal metabolic rate?
Increases Na/K ATPase activity -> increased O2 consumption, RR, and body temp.
Why is more T4 made then T3?
Because the coupling reaction is faster (DIT + DIT).
1st step in distinguishing between etios of Cushing syndrome?
Measure ACTH. If it is suppressed, the etiology is ACTH-independent (makes cortisol on its own) - e.g. adrenal tumor. If ACTH is high, then you know that this is an ACTH-dependent tumor.
How do you diagnose Cushing’s disease?
If ACTH high. (1) Dexamethasone suppression test will show suppression of cortisol, meaning that the source of the increased ACTH is pituitary = pituitary adenoma. OR (2) CRH stimulation test. If ACTH and cortisol rise in response to CRH, then pituitary adenoma is etio.
How do you diagnose Cushing’s disease?
If ACTH high. (1) Dexamethasone suppression test will show suppression of cortisol, meaning that the source of the increased ACTH is pituitary = pituitary adenoma. OR (2) CRH stimulation test. If ACTH and cortisol rise in response to CRH, then pituitary adenoma is etio.
Lab findings in hyperaldosteronism?
HTN, hypokalemia, metabolic alkalosis, normal Na+ 2/2 aldosterone escape (i.e. pressure natriuresis). Renin is high for secondary but low in primary.
Treatment for hyperaldosteronism?
Tx = spironolaction +/- surgery (if primary)
Addison disease lab and exam findings?
Hypotension, hyperkalemia, acidosis, skin and mucosal hyper pigmentation 2/2 to high MSH made as by-production of ACTH production.
Etios of addison disease?
Adrenal atrophy or destruction (autoimmune, TB, metastatic cancer).
Waterhouse-Friderichsen is associated with what organism?
Neisseria MENINGITIDIS
Neuroblastoma
Neural crest tumor of children commonly presengint as firm, IRREGULAR mass of abdomen. Homovanillic acid HIGH inuring. Bombesin positive. N-myc oncogene overproduction.
What are the symptoms of pheochromocytoma?
Come in “spells.” HA, HTN, perspiration, palpitations, pallor.
Labs in pheochromocytoma?
Increased urinary VMA. Increased plasma catecholamines.
Tx for pheochromocytoma?
Phenoxybenzamine (irreversible alpha blockade), THEN beta-blocker (reverse -> HTN crisis), THEN tumor resection.
Effects of hyper/hypthyroidism on serum cholesterol levels?
Increased LDL receptor expression in hyperthyroidism leads to hypocholesterolemia. Hypercholesterolemia is present, therefore, in hypothyroidism.
Very tender thyroid and hypothyroid?
Subacute thyroiditis = de Quervain. Self-limited often following flu-like illness.
Nontender moderatly enlarged hypothyroid?
Likely Hashimoto’s. Anti-TPO and Anti-thyroglobulin antibodies. HLA-DR5.
Histo and lab differences between Hashimoto’s and de Quervain’s?
Hashimoto’s has Hurthle cells, lymphoid aggregates with germinal centers. Subacute thyroiditis has granulomatous inflammation with high ESR.
Fixed, hard (rock-like) and painless goiter?
Riedel thyroiditis. Fibrosis of tissue.
Etios of congenital hypothyroidism?
Maternal hypothyroidism, thyroid agenesis, thyroid dygenesis, iodine deficiency, dyshormonogenic goiter.
Jod-Basedow phenomenon?
If patient with and iodine-deficiency goiter is given Iodine –> thyrotoxicosis can result
Mech of toxic multi nodular goiter?
Mutation of TSH receptor means patches of cells are making thyroid hormone regardless of regulation.
Mechanism of Graves disease findings?
Autoantibodies (IgG) stimulate TSH receptor, retro-orbital fibroblasts (increased glycosaminoglycan synthesis) and dermal fibroblasts (leading to pretibial myxedema)
Presentation of thyroid storm? And treatment?
Agitation, delirium, fever, diarrhea, coma, tachyarrhythmias -> death. Propanolol, Propylthiouracil, corticosteroids.
Medullary thyroid carcinoma?
Medullary are C-cells producing calcitonin. MEN 2a/b (RET). Histo shows AMYLOID stroma.
Follicular thyroid carcinoma?
Invades thyroid capsule. Histo shows uniform follicles.
Best prognosis thyroid cancer?
Papillary carcinoma.
Common side-effects of thyroidectomy?
Hoarseness (recurrent laryngeal), hypocalcemia (2/2 loss of parathyroid glands), transected INF. thyroid artery
Primary vs. secondary vs. tertiary hyperparathyroidism?
Primary is adenoma (hypercalcemic). Secondary is due to low Ca2+ levels/hyperphosphatemia seen often in renal disease leading to high PTH in response. Tertiary is a progression from secondary where the hyperparathyroid glands over-react and become autonomous = hyperCa and high PTH.
S/S of primary hyperparathyroidism?
HyperCa, hypercalciuria, hyPOphophatemia (PTH causes less reabsorption), increased alk-phos, increased cAMP in urine. Weakness, constipation, acute pancreatitis, depression.
S/s specific to secondary hyperparathyroidism?
B/c parathyroid hyperplasia is 2/2 to chronic renal disease -> renal osteodystrophy, hypocalcemia, hyperphosphatemia
Etios of hypoparathyroidism?
Surgical excision (accidental), autoimmune destruction, diGeorge syndrome.
Albright hereditary osteodystrophy
A pseudohypoparathyroidism 2/2 decreased organ sensitivity to PTH (and TSH, FSH, LH). Hypocalcemia, hyperphosphatemia, elevated PTH. Shortened 4/5th digit and short stature. AD.
Signs and symptoms of hypoparathyroidism?
Hypoca (and low-normal PTH). Chvostek sign (tap check -= contract). Trousseau sign (occlusion of brachial a. with cuff -> carpal spasm)
Prolactinoma treatment?
DA agonists (b/c they inhibit prolactin secretion). e.g. Bromocriptine and cabergoline.
Acromegaly cause and diagnosis?
Usu. caused by a pituitary adenoma releasing excess growth hormone. Dx = increased serum IGF-1, or a failure to suppress serum GH with glucose.
Tx for acromegaly if adenoma cannot be resected?
Octreotide (somatostatin analog) or pegvisomant (Growth hormone receptor antagonist)
Diagnosis of central vs. nephrogenic DI?
Water restriction test. In nephrogenic DI, no change in urine osmolarity. But, in central DI, >50% increase in urine osmolarity.
Treatment of central vs. nephrogenic DI?
Central treat with DDAVP and hydration. For nephrogenic DI, treat with indomethacin [constricts afferent], amiloride, HCTZ, hydration.
Diagnosis of central vs. nephrogenic DI?
Water restriction test. In nephrogenic DI, no change in urine osmolarity. But, in central DI, >50% increase in urine osmolarity. Etio of central from trauma usu. in hypothalamus NOT post. pituitary.
Treatment of central vs. nephrogenic DI?
Central treat with DDAVP (has little V1 effect!!!) and hydration. For nephrogenic DI, treat with indomethacin [constricts afferent], amiloride, HCTZ, hydration.
Treatment of SIADH?
Fluid restriction, IV hypertonic saline, conivaptan, tolvaptan [these guys are vasopressin receptor antagonists], demeclocycline [reduces collecting tubule’s response to ADH]
S/S of SIADH?
Water retention, hyponatremia, urine osmolarity > serum osmolarity. Usu. no LEE, bibasilar crackles, elevated JVP
In DKA, what is going on with proteins?
Insulin deficiency leads to a protein CATABOLISM -> increased llama AA’s and nitrogen loss -> contributes to osmotic diuresis.
Histology differences between type 1 and 2 diabetes?
In type II, will see islet amyloid deposits [IAPP]. In type I, will see leukocyte infiltrates.
Complications of DKA?
Life-threatening mucormycosis (e.g. Rhizopus), cerebral edema, cardiac arrhythmias, HF
Insulinoma S/S?
Whipple triad = episodic lethargy, syncope, diplopia. HIGH C-peptide (as opposed to normal in exogenous insulin usage)
Carcinoid syndrome S/s?
Recurrent diarrhea, cutaneous flushing, wheezing, right-sided valvular disease (b/c the 5-Ht damages right-side but is inactivated in the lung)
Dx carcinoid?
Increased 5-HIAA (hydroxyindoleacetic acid) in urine.
Treatment of carcinoid syndrome?
Resection. Ocretodie (somatostatin analog)
MEN 2A/B
Medical Physicians are Paranoid and Neurotic. Medullary carcinoma of thyroid, pheochromocytoma, parathyroid hyperplasia/mucosal neuromas. Ret.
MEN syndromes genetics?
AD
Mechanism of glucocorticoids?
Interaction with steroid response elements, inhibition of NF-kappaBeta.
Demeclocyline mech, usage, SE?
An ADH antagonist (a tetracycle) used for SIADH. Tox = nephrogenic DI, photosensitivity, bone/teeth problems
The many uses of ocreototide?
Acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, esophageal varices.
Mechanism of PTU/methimazole? Pregnancy?
Block TPO. PTU also blocks 5’-deiodinase, which decreases the peripheral conversion of T4 to T3. PTU is also used in pregnancy b/c methimazole may cause aplasia cutis.
Mechanism of sulfonylureas?
Block K+ channel of Beta-cell -> depolarization -> ca2+ increase -> insulin release
Mechanism of thiazolidinediones?
Binds to PPAR-gamma nuclear receptor to increase insulin sensitivity. (Increases adiponectin)
Effects of metformin?
Increases insulin sensitivity, increases glycolysis, decreases gluconeogenesis. Most serious side effect = lactic acidosis
Side effects of glitazones?
Wt gain, edema, hepatotoxicity, and HF.
Acarbose?
An alpha-glucosidase inhibitor, delaying sugar hydrolysis and glucose absorption in intestine = decreased post-prandial hyperglycemia.
Tolbutamide?
1st gen sulfonylurea. 1st gens have SE of disulfiram like reaction
Pramlintide?
Amylin analog - decreases gastric emptying and decreases glucagon.
Miglitol?
Another alpha-glucosidase
Exenatide?
A GLP-1 analog that increases insulin and decreases glucagon release. Via Gs system. SE of n/v, pancreatitis!
DPP-4 inhibitors?
Linagiptin, saxagliptin, sitagliptin. Increase insulin and decrease glucagon release. SE of mile urinary or respiratory infections.
Effect of free FA’s on insulin resistance?
Increases it w/ unclear mechanism.
