Endocrine

Question 1

a-glucosidase inhibitors (Acarbose, Miglitol): 作用机制？适应于哪些疾病？副作用和禁忌症？

Answer 1

作用机制：inhibit intestinal brush border a-glucosidases, delay sugar hydrolysis and glucose absorption - ↓ postprandial hyperglycemia 适应于哪些疾病: mono therapy or combined for type II DM 副作用: GI disturbance

Question 2

addison disease: ；累及？症状？鉴别诊断？

Answer 2

chronic 1° adrenal insufficiency (acute = Waterhouse - Frederichsen syn) affect all 3 layers of adrenal cortex, ↑ ACTH, ↓ aldosterone, ↓ cortisol, ↑ MSH (by-product of ↑ ACTH from POMC: pro-opiomelanocortin 阿片-促黑素细胞皮质素原,阿黑皮素） 症状：hypotension, hyperkalemia, acidosis, skin/mucosal hyper pigmentation (due to ↑ MSH) 鉴别：与2° adrenal insufficiency 区分：后者↓ pituitary ACTH production, no skin/mucosal hyper pigmentation, no hyperkalemia

Question 3

ADH (vasopressin): function? 生成部位？作用于什么器官和细胞？调控什么，以及receptors? ADH由什么控制？ Associated with which diseases?

Answer 3

function: ↓ serum osmolarity, ↑ urine osmolarity 生成部位: supraoptic nuclei of hypothalamus 作用于什么器官和细胞: renal collecting duct (regulate aquaporin channel transcription) 调控什么,以及receptors: regulate serum osmolarity via V2-receptor, regulate BP via V1 receptor ADH由什么控制: 最重要的是osmoreceptors in hypothalamus, secondary is hypovolemia Associated with which diseases: ↓ in central diabetic insipid us (DI) [note: 与肾源性或者原发性尿崩症无关】 Desmopressin (ADH analog)用于治疗DI

Question 4

Anatomy of adrenal gland? 从外到内哪几层？分别产生什么激素？

Answer 4

cortex: GFR (the deeper you go, the sweeter it gets” - salt, sugar, sex! outer: G - zone glomerrulosa - aldosterone middle: F: zone fasiculate - cortisol, sex hormones inner: R: -zone reticularis - sex hormone medulla: ANS特化的交感节后神经元，- Epi, NE (pheochromocytoma in adults, neuroblastoma in children)

Question 5

calcitonin: 生成部位？function? 作用于什么器官和细胞？ 调控？

Answer 5

生成部位 - parafollicular cells (C cells) in thyroid function - oppose PTH, ↓ Ca2+ 作用于什么器官: bone ( ↓ bone resorption of Ca2+) 调控： ↑ serum Ca2+ causes calcitonin secretion

Question 5

Biguanides (metformin)最严重的副作用是？禁忌症？

Answer 5

lactic acidosis （could be fatal，二甲双胍很多年都无法在美国通过FDA approval, 就是因为乳酸中毒的副作用); 90% 以原型从肾脏排出，contradicated in renal failure

Question 6

carcinoid syn: definition? which hormone involved? Caused by? Cx? Rx?

Answer 6

Neuroendocrine tumor, especially metastatic small bowel tumors ↑ 5-HT Cx: recurrent diarrhea, cutaneous flushing, asthmatic wheezing, right-sided valvular disease Lab: ↑ 5-HIAA in urine Rx: resection + somatostatin analog (e.g., octreotide)

Question 7

Chvostek sign Trousseua sign

Answer 7

Chvostek sign: tap the cheek - (tap the facial N, cause contraction of facial muscles) Trousseua sign: cuff the triceps (occlusion of brachial artery with BP cuff), - carpal spasm sign for hypoparathyroidism

Question 7

cause of DKA (common in Type I DM)? Biochemistry? change of K+? treatment?

Answer 7

caused by ↑ of insulin requirement due to ↑ stress (e.g., infection) excess fat breakdown and ↑ ketogenesis from ↑ FAA, which are made into ketone bodies (beta-hydroxybutyrate > acetoacetate) 血K+ ↑, 但是！！ intracellular K+ depletion (transcellular shift from ↓ insulin. 治疗上要补钾 而且DKA中有可能需要补glucose if necessary to prevent hypoglycemia

Question 8

cortisol: 生成部位？function? 作用于什么器官和细胞？ cortisol由什么控制？

Answer 8

生成部位: adrenal gland zona fasciculate function, 作用于什么器官和细胞: BIG FIB B: ↑ BP (↑ a1-receptor on arterioles) I: ↑ insulin resistance (diabetogenic) - 糖皮质激素整体作用是升高血糖的 G: Gluconeogenesis, lipolysis, proteolysis - 升高血糖 F: ↑ fibroblast activity (这就是为什么Cushings导致皮肤出striae) I: ↓ inflammatory and immune responses B: ↓ bone formation cortisol由什么控制: 下丘脑CRH刺激ACTH release from pituitary; excess cortisol 通过负反馈↓ CRH, ACTH and cortical secretion chronic stress ↑ prolonged secretion

Question 9

Define: Zollinger-Ellison Syn which hormone involved? Cx? Associated with?

Answer 9

Gastrin-secreting tumor of pancreas or duodenum Cx: abdominal pain (peptic ulcer disease), diarrhea (malabsorption) May associated with MEN 1

Question 10

demeclocycline是什么药？毒副作用？

Answer 10

脱甲氧四环素。 ADH antagonist, used for SIADH (sym of inappropriate ADH secretion) toxicity: nephrogenic DI, photosensitivity, abnormalities of bone and teeth

Question 10

delayed puberty + anosmia (嗅觉缺失）- Dx? gene mutations associated with this disease?

Answer 10

Kallmann syn failure of GnRH-secreting neurons to migrate from olfactory placed to hypothalamus gene mutations associated with this disease: KAL-1 or FgfR-1 (required for this migration)

Question 11

developmental base for midgut pathology such as omphalocele, etc?

Answer 11

Midgut (from duodenum to proximal 2/3 of transverse colon) development: 6th week: herniate through umbilical ring 10th week: return to abdominal cavity + rotates around SMA （肠系膜上动脉） 如果这个过程受损，出现malroration of midgut, omphalocele (脐突出， 这个病和gastroschisis腹裂的鉴别要点在于脐突出表面有腹膜，腹裂没有）， intestinal atresia or stenosis, volvulus 肠扭传

Question 12

Dx: genotype 47 XXY, hypogondasim, eunuchoid （无睾丸），small firm testes, thin/tall， could be mentally retarded 47XXY的成因？ 病人廋高的原因？

Answer 12

Klinefelter Syn, ↓ serum T, ↓ sperm count, ↑ serum LH and FSH (虽然是男性外观和雄激素，也受LH, FSH调控！), due to loss of negative feedback from T and inhibit 47XXY的成因 - non-disjunction of the sex chromosomes during meiotic division in EITHER parent 病人廋高的原因？ hypogonadism causes epiphyseal 骺[软骨]板 fusion to be delayed

Question 13

Dx: 甲状腺切片见Orphan Annie eyes (empty appearing nuclei)? gene mutations?

Answer 13

Thyroid Papillary carcinoma ↑ risk with RET and BRAF mutations

Question 14

Dx: 甲状腺切片见solid sheets of cells with amyloid deposition? associated with which gene mutations?

Answer 14

medullary carcinoma, from C cells - produce calcitonin associated with MEN2A and 2B (RET mutation)

Question 15

endocine pancreas3种cell types? 各自产生什么激素？在胰岛里的排布？

Answer 15

外层：alpha cells (glucagon) 胰高血糖素 里层：beta cells (insulin） - Insulin Inside interspersed: delta cells (somatostatin) 生长抑素

Question 16

function of 5a-reductase? / aromatase?

Answer 16

5a-reductase: convert T to DHT (r = “rebecca”, who is working on T aromatase: convert T to E2

Question 17

GH (somatotrophin): 正负调控由什么控制？ 和insulin什么关系？ too much causes which diseases?

Answer 17

正调控：exercise, sleep 负调控：glucose, somatostatin (生长抑素由胰岛delta细胞分泌） GH本身会↑ insulin resistance too much GH: acromegaly in adults, gigantism in children

Question 18

Hashimoto thyroiditis: Ab against what? Associated with HLA-? ↑ risk for which disease? 特征性histological findings? 甲状腺触诊断发现？

Answer 18

autoimmune, Ab against peroxidase, anti-thyroglobulins Associated with HLA-DL5 ↑ risk for non-Hodgkin lymphoma 特征性histological findings: Hurthle cells (lymphoid aggregates with germinal centers) 甲状腺触诊断: moderately enlarged, contender thyroid

Question 18

Goiter: 疼痛时考虑？这个病的组织学特征？ 无痛时考虑？

Answer 18

疼痛时考虑 subacute thyroiditis (de Quervain = pian) , 自限性， follow flu-like illness 组织学特征: granulomatous inflammation 无痛时考虑： Riedel thyroidistis (fibrosis导致的甲减， fixed, hard rod-like goiter) iodine deficiency, Wolff-chaikoff effect (excess iodine suppress TSH), painless thyroiditis

Question 18

hyperparathyrodism: 鉴别primary, secondary, vs. tertiary各种的症状和病因？

Answer 18

primary： 甲状旁腺本身的adenoma引起， 1) hypercalcemia, hypercalciuria (renal stones), hypophosphatemia 2) ↑ PTH, ↑ ALP, ↑ cAMP in urine 3）常常无症状，如果有症状：weakness+constipation (groans), abdominal/flank pain (kidney stones, pancreatitis) 4) depression (psychiatric overtones) XR见到osteitis fibrosa cystica - cystic bone spaces filled with brown fibrous tissue - bone pain 总结为”stones, bones, groans, psychiatric overtones secondary: 由chronic renal diseases引起 - cause hypovitaminosis D - ↓ gut Ca2+ absorption from gut and ↑ PO4(3-) [注意这个钙和磷相反的关系: 血钙在这里是降低的！这一点和primary, tertiary都不同） tertiary：顽固性（autonomous) hyperparathyroidism, 也是由chronic renal disease引起，↑↑↑ PTH,

Question 18

hypoparathyrodism要和哪两个遗传病鉴别？

Answer 18

DiGeorge Syn Pseudohypoparathyroidism (Albright hereditary oestodystrophy): AD, kidney does not respond to PTH, 表现为低钙， 矮小，第4、5指节短

Question 19

Insulin: 4种剂型的代表药物？peak时间？duration? 用途？

Answer 19

1. fast acting: LAG (lispro, aspart, glulisine) 45-75 min peak，act up to 3 -4 hr, 刚好和餐后血糖上升配合，是控制餐后（postprandial)血糖的最佳选择。适用于DM1, DM2, GDM 2. regular insulin - short acting peak 2-4 hr, IV, 用于DKA降血钾（注意：这些病人常常要联用glucose去防止血糖被降得过低！！！） 3. intermediate acting: NPH (neutral protamine Hagedorn），+ protamine and Zn+的胰岛素混悬液，在皮下注射部位缓释。 peak 4-12 hr, 最长到18 hr 有效，一日2次 4. long acting: DG (Detemir, Glargine） sv, no peak time, act to 24 hrs, once a day to control basal glucose

Question 20

MEN I, 2A, 2B各累及什么内分泌腺？

Answer 20

MEN 1 (3P): pituitary (prolactin or GH), parathyroid, pancreas (表现形式多，可能为Zollinger-Ellison sym (gastrin), insulinoma, VIPoma, glucagonomas MEN 2A (2P): thyroid (medullary thyroid carcinoma, ↑ calcitonin), parathyroids, pheochromocytoma MEN 2B: (1P) pheochromocytoma, thyroid (medullary thyroid carcinoma, ↑ calcitonin), oral/intestinal ganglioneuromatosis (mucosal neuromas) associated with marfanoid habitus MEN 2A and 2B: associated with ret gene mutation (GDNF receptor tyr kinase)； 颈部组织学切片发现nests of polygonal cells with Congo-red positive deposits - medullary thyroid carcinoma All are AD (all MEN are dominant)

Question 22

Neuroblastoma: 好发人群？Cx? 尿里什么指标升高？和哪个癌基因associated?

Answer 22

children < 4 yrs Cx: abdominal distension, firm irregular mass that can cross the midline [鉴别： Wilms tumor （nephroblastoma）： smooth and unilateral] urine HVA (Dopamine代谢产物）↑ associated with N-myc

Question 24

pheochromocytoma: 5 rules of “10”s 5 Ps (症状） Associated with disease? Lab? treatment

Answer 24

5 rules of “10”s: bcemk 10% bilateral 10% calcify 10% extra-adrenal 10% malignant [note: 恶性细胞特点：dysmorphic nuclei] 10% kids 5 Ps (症状: Pressure ↑ Pain (headache) Pallor Perspiration 出汗 Palpitation (tachycardia) Associated with diseases: Von-Hippel-Lindau MEN 2A and 2B Lab: ↑ urinary VMA (NE, Epi代谢物）， plasma Cath ↑ treatment: 先用irreversible a-antoganists (phenoxybenzamine) 阻断alpha 受体，然后再上BB (以避免高血压危象）；最后tumor resection

Question 25

posterior pituitary gland: 神经垂体还是腺垂体？产生什么激素？ anterior?

Answer 25

posterior pituitary gland: neurohypophysis, derived from neuroectoderm; hypothylamus produces 2 hormones (vasopression = antidiruetic hormone ADH) + oxytocin, transport into 垂体后叶 by carrier protein neurophysins anterior pituitary gland: A = A (adenohypophysis) FLAT PiG: FSH, LH, ACTH, TSH; ProlactIn, GH

Question 27

primary hyperaldosteronism 里为什么血钠正常，也没有组织水肿？

Answer 27

aldosterone escape机制：一过性血钠升高和储留水之后，组织间隙渗透压 ↑， 导致水钠“back flow”,回流入肾小管tubule In patients with hyperaldosteronism, chronic exposure to excess aldosterone does not cause edema as might be expected. Aldosterone initially results in an increase in Na reabsorption in these patients through stimulation of ENac channels in principal cells of the renal collecting tubules. Increased ENac channels situated in the apical membranes of the principal cells allow for more Na reabsorption, which may cause a transient increase in fluid reabsorption as well. However, within a few days, Na reabsorption returns to normal as evidenced by normal urinary Na levels in these patients. When hydrostatic pressures are raised in the peritubular capillaries such as seen in hyperaldosteronism, Starling forces begin to favor “backflow” of Na and water from the interstitium into the tubules—thus, increasing Na excretion. This is the proposed mechanism of “mineralocorticoid escape” for how patients with increased levels of aldosterone are able to maintain Na balance and avoid an edematous state.

Question 29

prolactin: 正负调控由什么控制？自身反馈？

Answer 29

正调控：TRH 负调控：Dopamine (DA agonists such as bromocriptine 治疗prolactinoma； DA antagonists - antipsychotics会引起泌乳） Prolactin通过上调dopamine，负反馈抑制自身的分泌

Question 31

PTH: 生成部位？function? 作用于什么器官和细胞？ PTH由什么控制？ PTHrp ↑ indicates?

Answer 31

PTH: 生成部位: chief cells of parathyroid function? 作用于什么器官和细胞- 1） 作用于bone： ↑ reabsorption of Ca2+ and PO4(3-) [note: 在骨上是一个indirect作用：PTH ↑ production of M-CSF and RANK-L (receptor for NFkB), RANK-L binding to NFkB in osteoclasts, 激活破骨母细胞，降解bone matrix, 释放钙入血流 2) 作用于肾脏近端卷曲管： ↑ reabsorption of Ca2+ 3) 作用于肾脏远端卷曲管： ↓ reabsorption of PO4(3-) 4）肾脏：↑ 1a-hydroxylase, ↑ 1,25-(OH)2-D3 production net results: 1) ↑ serum [Ca2+】，↓ serum PO4(3-), ↑ urinary PO4(3-) PTH由什么控制？serum Ca2+, Mg2+ PTHrp ↑ indicates: malignancies (e.g., paraneoplastic syn)

Question 32

T3/T4: which one made in thyroid, which one in peripheral targets? which one has higher affinity to Rs? regulation of TBG? Es inhibited by methimazole (他巴唑）？by propylthiouracil (巯基尿嘧啶）？ regulation?

Answer 32

T4: major one made in thyroid follicles, low affinity T3: convert from T4 by 5’-deiodinase in target tissues, high affinity T3/T4 bound to TBG is not active; only free form is active TBG ↓ in hepatic failure, ↑ in pregnancy or OCP (by E2) methiamazole inhibits only peroxidase (负责把无极碘氧化为有机碘，以及coupling to MIT and DIT的酶） Propylthiouracil inhibits both peroxidase and 5’-deiodinase Regulation: 1) stimulated by TRH-TSH; 2) negative feedback by T3/T4 (work on pituitary to ↓ sensitivity to TSH) 3) stimulated by stimulating immunoglobulins (TSIs) - Grave’s 4). Wolff-Chaikoff effect: excess iodine temporarily inhibits peroxidase

Question 33

thyroid storm最常见的死因？ 治疗？

Answer 33

最常见的死因： tachycardia 治疗: 3P BB (propranolol) propylthiouracil (inhibitor for peroxidase and 5’-deiodinase, 抗甲亢药） corticosteroids (prednisolone)

Question 34

TZDs (Glitazones/thiazolidinediones: Pioglitazone, Rosiglitazone): 作用机制？适应于哪些疾病？副作用和禁忌症？

Answer 34

作用机制： bind to PPAR-Ɣ and ↑ adiponectin, Glut-4, etc; - decrease insulin resistance (不直接作用于血糖水平，所以不会引起低血糖） 适应于哪些疾病： type 2 DM, metabolic syn, NASH (nonalcoholic fatty liver disease), polycystic ovarian disease - 这些病特点都是 ↑ insulin resistance 副作用和禁忌症: 1) hepatotoxicity 2) water retention (weight gain, edema, congestive HF), TZDs使用↓必须检察肝功能（ALT): measured at baseline, then at 12 wks, then periodically NYHA class III and IV 心衰是TZD绝对禁忌症

Question 35

Waterhouse-Friderichsen Syn: cause?

Answer 35

acute 1° adrenal insufficiency due to adrenal hemorrhage MC: Neisseria meningitidis septicemia, DIC, endotoxic shock

Question 36

which endocrine hormones use cAMP as signaling pathway? cGMP?

Answer 36

cAMP: FLAT ChAMP 大部分下丘脑和垂体激素 F: FSH LH ATCH TSH CRH hCH ADH (note: V2 receptor only - regulate osmolarity; v1 receptor uses IP3 to regulate BP) MSH, PTH / calcitonin (这一组功能相反） GHRH glucagon cGMP: NO, ANP

Question 37

which endocrine hormones use IP3 as signaling pathway?

Answer 37

“GOAT HAG” GnRH Oxytoxin ADH (v1 receptor to control BP) TRH Histamine (H1 receptor) Angiotensin II Gastrin

Question 38

which endocrine hormones use receptor-associated tyrosine kinase as signaling pathway? which endocrine hormones use intrinsic receptor-tyrosine kinase as signaling pathway?

Answer 38

receptor-associated tyrosine kinase: PIG prolactin Immunomodulators (cytokines, ILs, IFN) GH intrinsic receptor-tyrosine kinase: Insulin, IGF-I, FGF, PDGF, EGF

Question 39

Which glucose transporter(s) are insulin-dependent/ independent? work on which organs?

Answer 39

insulin-dependent: GLUT4 (adipose tissue, skeleton muscle) insulin independent: GLUT1 (RBC, brain, cornea), 5 (GI, spermatocysts), 2 (2= bi-directional, b islet cells, liver, kidney, small intestine) BRICK L: = Insulin-independent glucose uptake Brain, RBCs, Intestines, Cornea, Kidney, Liver

Question 40

Why does ↑ pH have Cx of hypocalcemia?

Answer 40

Plasma calcium exists in 3 forms: ionized (45%) bound to albumin (40%) bound to anions (15%) ↑ pH - ↑ affinity to albumin (negatively charged) - Cx of hypo calcium [cramps, pain, paresthesias, carpopedal spasm 腕足痉挛)

Question 41

婴儿在切除sublingual mass后出现甲减症状，诊断？原因？ 其他哪种endocrinological disorder会share类似的发育学病因？

Answer 41

“lingual thyroid” - failure of MIGRATION of developing thyroid to the neck migration的缺陷还会引起 1) Kallmann’s syn: GnRH-secreting neurons fail to migrate from the olfactory placode (嗅基板）to the hypothalamus 2) cryptorchidism: testes fail to migrate from intra-abdominal location to scrotum

Question 43

孕妇triple test: AFP ↑的诊断？↓ 的诊断？

Answer 43

孕妇triple test: AFP, hCG, E3 between 16 - 18 wks AFP ↑的诊断: most likely, an error in dating the gestation! neural tube defects, anterior abdominal wall defects, multiple gestation ↓ 的诊断: Down’s syn

Question 44

鉴别primary vs. secondary hyperaldosteronism?

Answer 44

primary hyperaldosteronism: caused by adrenal hyperplasia or Conn sun （aldosterone-secreting adenoma), low plasma renin secondary hyperaldosteronism: caused by renal stenosis, CHF, cirrhosis, nephrotic syn; renal perception of low volume, → over activate RAS; high plasma renin