Endocrinology Flashcards

Question

Prolactin

Answer 1

Peptide hormone from anterior pituitary 199 amino acids, similar structure to GH and placental lactogen Gene on chrom6 Diurnal and ovulatory cycle Functions - lactogenesis, promotes breast development and decreases serum levels of oestrogen and testosterone Also produced in decidua, breast, brain, immune system

Answer 2

PHYSIOLOGICAL - pregnancy, lactation, exercise, stress, sleep, hypoglycaemia PHARMACOLOGICAL - TRH, oestrogen, dopamine antagonists, MAOI, cimetidine, verpamil PATHOLOGICAL - pituitary tumour, chest wall lesions, spinal cord lesions, hypothyroidism, chronic renal failure, liver failure

Answer 3

PHARMACOLOGICAL - dopamine agonists (pramipexole, ropinirole for Parkinson's) PATHOLOGICAL - Sheehan's syndrome, hypopituitarism, bulimia

Answer 4

From anterior pituitary Gene on chrom17 191 amino acids Most GH effects mediated by IGF Function mainly anabolic - increased protein synthesis - decreased protein catabolism - lipolysis - anti-insulin

Answer 5

PHYSIOLOGICAL - sleep, stress, exercise, hyperglycaemia PHARMACOLOGICAL - GHRH, oestrogen, adrenergic agonist, dopamine agonist PATHOLOGICAL - chronic renal failure, anorexia

Answer 6

PHYSIOLOGICAL - hyperglycaemia, elevated free fatty acids PHARMACOLOGICAL - somatostatin, progesterone, glucocorticoids PATHOLOGICAL - obesity

Answer 7

Released from anterior pituitary in response to CRH from hypothalamus Can be produced by immune cells (T-cells, B-cells, macrophages) Stimulates production of steroids from adrenals Released in circadian rhythm - highest in am Derived from pro-opiomelanocortin (POMC) By-products of MSH and endorphins

Answer 8

Produced in supra-optic and paraventricular nucleus of hypothalamus, stored in POSTERIOR pituitary Nanopeptide of 9 amino acids For smooth muscle contraction - uterine muscle, myoepithelial cells surrounding breast alveoli (letdown reflex) Oxytocin receptors are G-protein-coupled receptors, require Mg and cholesterol, also found in brain and spinal cord

Answer 9

Nanopeptide aka vasopressin From pre-pro-hormone prescursors synthesized in hypothalamus, then stored in posterior pituitary Released when body fluid volume decreases Function - vasoconstrictor, increased urine osmolarity, increased resorption of H2O at DCT and collecting duct, Na resorption in ascending loop of Henle, some implication in memory formation

Answer 10

↑ activity of Na-K ATPase so ↑ O2 consumption, heat production ↓ superoxide dismutase levels ↑β adrenergic receptors in myocardium (+ve ionotopic and chronotropic), skeletel muscle, adipose tissue, lymphocytes Blood ↑EPO ↑erythropoeisis ↑DPG content of erythrocyte Bone ↑turnover ↑resorption, osteopenia Metabolism ↑hepatic gluconeogenesis, ↑glycogenolysis, ↑lipolysis

Answer 11

Iodine absorbed from bloodstream via iodide trapping Thyroglobulin synthesis Iodination - iodine (I2) binds to tyrosine contained in thyroglobulin, so I2+tyrosine=moniodo (MIT), I2+MIT=DIT Then coupling of iodinated residues: MIT + DIT = T3, DIT + DIT = T4 Stored in colloid of follicular cells

Answer 12

↑TBG ↑T3/T4 (total, but free decreases) ↓TSH ↑renal clearance ↑deiodination of T3/T4 by placenta

Answer 13

Mediates stress response via mineralocorticoids and glucocorticoids Zona glomerulosa - mineralocorticoids Zona fasciculata - glucocorticoids Zona reticularis - weak androgens All synthesized from cholesterol

Answer 14

Cortisol and cholesterol, from zona fasciculata of adrenal cortex - protein catabolism - inhbit DNA synthesis, inhibit RNA and protein synthesis - formation of ATP - metabolism - increased gluconeogenesis, inhibits peripheral glucose usage, increases lipolysis - connective tissue and bone - inhibits fibroblasts, loss of collagen, increases bone resorption - renal - increases excretion of Na and water, increased GFR - increased secretion of stomach acid - blood - increase neuts, decrease lymphocytes

Answer 15

Mineralocorticoid (from zona glomerulosa of adrenal cortex) 21C atoms Part of renin-angiotensin system - resorption of Na from DCT and collecting ducts - excretion of H and K via kidneys - acts on posterior pituitary to release ADH Secretion regulated by renin-angiotensin system, sympathetic nerves, juxtaglomerular apparatus, carotid artery baroreceptors, plasma K and Na

Answer 16

Adrenal androgen production - age 7-9 in males age 6-7 in females Adrenal cortex secrete weak androgens - DHEA, DHEAS, androstenedione

Answer 17

Mainly chromaffin cells Modified neural crest cells that did not complete their development to postganglionic neurones, but retain same function Synthesize: Adrenaline Noradrenaline Dopamine

Answer 18

Tyrosine -> L-DOPA -> dopamine -> noradrenaline -> adrenaline Actions - lipolysis, glycogenolysis, salt and water balance, vasoconstriction, GI tract relaxation of smooth muscle, increased plasma levels of insulin and RAAS Acts on alpha and beta receptors (noradrenaline only on alpha) Dominant fetal catecholamine is L-DOPA Metabolised by MAO and COMT

Answer 19

JGA in kidney - juxtaglomerular cells of afferent arterioles, and macula densa (on ascending loop of Henle) Renin Angiotensinogen Angiotensin ACE

Answer 20

Secreted by JG cells in response to decreased bp and decreased Na Renin cleaves angiotensinogen to form angiotensin 1 (renin inhibitors treat HTN) Synthesized from preprorenin to prorenin to renin

Answer 21

Secreted by liver in reposnse to renin from kidney (in response to low BP) Production increased by oestrogen, and glucocorticoids

Answer 22

Synthesized from angiotensinogen (from liver) -> angiotensin 1 (with renin catalyst from kidney) angiotensin 1 -> angiotensin 2 (with ACE catalyst from lung) Vasoconstriction, and stimulates aldosterone secretion

Answer 23

In endothelial cells of pulmonary capillaries, brain and glomeruli Catalyses angiotensin1 -> angiotensin2 Also catalyses bradykinin breakdown, enkephalin breakdown, substance P breakdown

Answer 24

Anabolic - glycogen synthesis, TAG synthesis INHIBITS catabolism - inhibits glycogenolysis, inhibits ketogenesis, inhbits gluconeogenesis Stimulates glucose uptake into muscle, adipose tissue

Answer 25

Glucagon Cortisol Growth hormone Adrenaline Oestrogen Thyroid hormone Prolactin Human placental lactogen responsible for insuline resistance of pregnancy

Answer 26

Main target tissue is liver - glycogenolysis - inhibits glycogen synthesis - gluconeogenesis - lipolysis - ionotropic - causes release of insulin and catecholamines

Answer 27

Features - hyponatraemia, hypo-osmolality (<280), excessive renal excretion of Na, hypervolaemia, absence of oedema, normal renal and adrenal function Causes - tumours, CNS disease, resp disease, myxoedema, porphyria, drugs (vinblastine, SSRI, thiazides, carbamazepine), trauma, infection Treatment - fluid restrict 1L/day, diuretic, demclocycline (induces nephrogenic diabeteic insipidus), conivaptan (ADH inhibitor), can correct with hypertonic saline in emergency

Answer 28

Deficient ADH production Treat with desmopressin Assoc with PET, HELLP, acute fatty liver of pregnancy Neurogenic - idiopathic, familial, syphilis, TB, tumour, autoimmune Nephrogenic - chronic renal disease, hypokalaemia, hypercalcaemia, sickle cell disease, Sjogren's, lithium Gestational - vasopressinate produced in placenta breaks down ADH

Answer 29

Primary - Hashimoto's, iatrogenic, iodide deficiency Secondary - hypopituitarism Tertiary - hypothalamic dysfunction Can -> congenital hypothyroidism in fetus (cretinism) Assoc with pernicious anaemia, Sjogren's, RA, SLE, diabetes Tested for by Guthrie's

Answer 30

Cardiomegaly Decreased intestinal peristalsis Renal - reduced GFR, myoedematous facies Anaemia Amenorrhoea/menorrhagia Overweight Hands - dry, cool, rough, inelastic, non-pitting oedema, carpal tunnel Face - thin/dry hair, loss of outer 1/3 eyebrow, yellowish complexion Slow relaxing reflex

Answer 31

Treat with carbimazole and propylthiouracil, surgery, or radioactive iodine Causes - Graves' disease, toxic multinodular goitre, solitary adenoma (or rarer, pituitary adenoma, hydatidiform mole, teratoma, iatrogenic) Hands - AF pulse, sweating, tremor Weight loss Muscle weakness Heat intolerance Insomnia Eyelid retraction, lid-lag, exophthalmos

Answer 32

Primary adrenocortical insufficiency Hypotension, hypoNa, hypoglycaemia, hyperK, hyperpigmentation Causes - CAH, infection (TB, CMV), autoimmune, adrenal haemorrhage, infiltrative disorder (amyloidosis, haemochromotosis), drugs (ketoconazole, etomidate)

Answer 33

Chronic glucocorticoid excess ACTH dependent - pituitary adenoma (C disease), ectopic ACTH (small cell ca of lung, pancreatic, carcinoid, medullary ca of thyroid, phaeochromocytoma) ACTH independent - iatrogenic, adrenal neoplasm Hypertension, hyperglycaemia, hyperlipidaemia, hypokalaemia, amenorrhoea, osteoporosis, obesity

Answer 34

Primary hyperaldosteronism Caused by adrenal adenoma Low renin:aldosterone ratio Treat with spironolactone (K sparing) Hypokalaemia, hypernatraemia, hypertension

Answer 35

Tumours from chromaffin cells Secretes adrenaline, noradrenaline, dopamine Assoc with MEN2, neurofibromatosis Can be due to RET pro-oncogene mutations Hypertension, hyperglycaemia, sweating, headache Diagnose by urinary levels of VMA (vanillylmandelic acid) and metanephrines If untreated -> inhibition of renin-angiotensin system Treat - surgery, preop salt loading, avoid pure B blockers and give intra-op a blockers

Answer 36

Benign pituitary tumour -> hyperprolactinaemia Macro (tumour >10mm) or micro (<10) Headache, bitemporal hemianopia, galactorrhoea, hypogonadism, erectile dysfunction Treat - dopamine agonist, trans-sphenoidal surgery, radiotherapy May result in osteoporosis due to reduced oestrogen and testosterone

Answer 37

In utero default phenotype is female Male phenotype - sex-determining region Y hormone, testosterone (Wolffian ducts), Mullerian inhibiting substance (by sertoli cells)

Answer 38

Testes -> scrotum -> penis -> pubic hair Seminiferous tubule solid until age 5 Breasts -> increased growth velocity -> pubic hair -> axillary hair -> menarche Breast development determined by ovarian oestrogen Pubic hair by adrenal and ovarian androgens Average age menarche 12.3-12.8

Answer 39

Under endocrine control, GH and IGF Oestrogen important for epiphyseal fusion 2 years later in males than females Bone mineralisation peak - 14-16 in girls, 17.5 in boys

Answer 40

GnRH - pulsatile every 90-120mins, increased frequency increases LH:FSH ratio (but continuous secretion suppresses gonadotrophins) - increased ratio in midcycle FETAL - increases until mid gestation (LH and FSH peak at mid gestation, then decline until term) AGE 2-9 - juvenile pause gonadotrophins low PERIPUBERTAL - circadian gonadotrophin release, GnRH secretions increase frequency and amplitude in early sleep EARLY PUBERTY - peak LH+FSH during day LATE PUBERTY - peak all the time, diurnal rhythm eliminated

Answer 41

CORPUS LUTEUM - progesterone ↑ to term, 17-hydroxyprogesterone peaks at 5w ADRENAL - cortisol ↑, aldosterone plateau at 34w, CBG ↑, renin ↑ THYROID - total T3 and T4 ↑, then plateau after T1, free T3/T4 unchanged PARATHYROID - PTH ↑, serum calcium ↓, ionized unchanged PITUITARY - GH unchanged, LH+FSH low, ACTH unchanged, prolactin ↑ to term PLACENTA - hCG peaks 10w, hPL↑ with placental weight, CRH ↑ 20days pre delivery PANCREAS - insulin ↑in 2ndT, insulin resistance Oestriol/oestradiol/oestrone ↑ to term, tesosterone ↑, DHEA ↓

Answer 42

9 produced during pregnancy: hCG hPL Oestrogen Progesterone Corticosteroid CRH Relaxin ACTH TSH

Answer 43

Peptide hormone (glycoprotein), heterodimeric with 2 subunits (α identical to TSH, FSH, LH, and β unique) 244 amino acids Secreted by syncitiotrophoblast Peaks at 9-12 weeks to 290,000 Functions - prevent degradation of corpus luteum, induce ovulation, stimulates Leydig cells to produce testosterone Also secreted by some types of tumour - choriocarcinoma, germ cell tumour, hyaditidiform mole

Answer 44

190 amino acids linked by disulfide bonds Anti-insulin (diabetogenic) Secreted by syncytiotrophoblast Functions - induce lipolysis (raise FFAs) and decrease maternal insulin sensitivity Gene on chrom17 Same family as GH, prolactin Peaks at 35w gestation 15min half life

Answer 45

In last 5 weeks of pregnancy Similar to inflammatory process: Prostaglandin E2 Cytokines (esp IL8) Recruitment of neutrophils Synthesis of metalloproteinases (collagenases and elastase) Increased cervical tissue water content Reduction in cervical tissue collagen concentration, rearrangement and realignment of collagen

Answer 46

Fetal pituitary releases corticotrophin, which acts on fetal adrenals Fetal adrenals release cortisol and DHEAS Cortisol -> causes increased oestrogen production and formation of oxytocin receptors DHEAS -> metabolised in placenta, so further increase oestrogen levels Oestrogen -> release of prostaglandin F2α from decidua, causing myometrial contractions Placental CRH ↑ so ↑oxytocin, and PGF2α

Answer 47

NO withdrawal Progesterone withdrawal (switch from T1 to T2 progesterone receptors) Increased placental release of CRH and oestrogen Upregulation of oxytocin receptors Increased prostaglandin synthesis in uterus and fetal membranes Increased IL-1 andIL-8 Fetal release of cortisol and platelet-activating factor Catecholamines (β receptor agonists inhibit, α receptor agonists cause uterine contractions) Fetal posterior pituitary (umbilical A oxytocin > umbilical V oxytocin) Increased myometrial gap junctions during labour

Answer 48

Neuronal reflex triggered by pressure to cervix and vagina Causes spurts of oxytocin release During active and expulsive labour phases

Answer 49

↑ in prolactin (Bfeeding) and oxytocin ↓ in oestrogen, progesterone, thyroid Most take 6 weeks to return to normal Menses return - 28 weeks post partum if breastfeeding, 9 weeks post partum if not If not breastfeeding, prolactin levels drop 2w PP, so cessation of lactation

Answer 50

Maternal breast changes from 7w gestation Influenced by oestrogen, hPL, prolactin, ↓progesterone, oxytocin, LH, FSH LA is 98% reliable form of contraception ONLY IF: - exclusively breastfed (intervals between feeding no longer than 5h) - amenorrhoea less than 5mo PP

Answer 51

Carbohydrate - lactose, oligosaccharides Fat - polyunsaturated FA, palmitic A, oleic A, vaccenic A, conjugated linoleic A Protein - casein, lactoferrin, immunoglobulin, lyosymes, albumin Vitamin - A, B1, B2, C Cells - macrophages, lymphocytes + 2-arachidonyl glycerol (endocannabinoid), growth factors (epidermal GF, IGF), digestive enzymes, hormones (feedback inhibitor of lactation, prolactin, insulin, ACTH) By 5days PP volumes around 500ml/day

Answer 52

Maternal - weight loss (500kcal/day), maternal bonding, helps uterus contract post delivery ↓risk PPH, ↓risk breast/ovarian/endometrial ca Neonatal - ↓SIDS risk, protects against DM, ↓risk obesity, ↓atopy, ↓risk NEC, passive immunity and ↓ risk infection, mild laxative

Answer 53

For first 3-5 days post delivery 100ml/day Rich in vitamin A, lactoferrin, IgA, sodium

Answer 54

THYROID - hormone synthesis from 12w, T4 mostly PARATHYROID - from 1stT, low levels but calcitonin high, so fetus hypercalcaemic ADRENAL - cortex seen from 4w, steroidogenesis at 7w, fetal zone involution complete 1mo PP GONAD - testes seen at 6w + testosterone production at 10w, ovaries seen at 7-8w and oestrogen production from 20w PITUITARY - oxytocin and vasopressin from 12w, ant pituitary hormones at significant levels by 20w Gonads + adrenals development in 1stT due to hCG

Answer 55

Cortisol Oestrogen Adrenaline Thyroid hormone

Answer 56

Addison's = 9am Cortisol & Synacthen test Conn's = Renin/aldosterone ratio, saline (salt) suppression or fludrocortisone suppression test Cushing's = Dexamethasone suppression test or 24-hour urinary cortisol

Answer 57

I - hypogonadotrophic, low oestrogen - eg functional weight loss, pituitary tumour (central lesion, gonadotrophin deficiency) II - hypogonadotrophic, normal oestrogen - eg PCOS (lesion at hypothalamic-pituitary site, disorder of gonadotrophin action) III - hypergonadotrophic, low oestrogen - eg genetic, autoimmune, chemotherapy (ovarian failure)

Answer 58

PRIMARY Excessive parathyroid hormone production by parathyroid adenoma. -> hypercalcaemia SECONDARY Secondary to hypocalcaemia PTH rises to try and correct calcium Causes - chronic renal failure, vitamin D Deficiency TEARTIARY After long periods of excessive PTH secretion (i.e. long periods of secondary hyperparathyroidism) the parathyroid gland secretes PTH autonomously even if the cause of secondary hyperparathyroidism is corrected

Answer 59

- chronic condition secondary to PPH - pituitary gland necrosis -> hormone deficiency - 1 – 30 years after haemorrhage - most common cause of hypopituitarism in developing countries BECAUSE Pituitary hyperplasia occurs in normal pregnancy, due to the growth of prolactin-secreting lactotrophs -> large pituitary gland compresses the superior hypophysial arteries, which supply the anterior pituitary with rapid, low-pressure flow Severe PPH and hypotension leads to pituitary ischaemia and necrosis See - atrophy of the breasts, fatigue, decline in pubic/axillary/facial hair, dryness or wrinkling of the skin, hypothyroidismy (cold intolerance), chronic anaemia, hypoglycaemia, altered level of consciousness, infertility, hyponatremia, hypocortisolemia, and hypotension Symptoms may present consistently, or only when the patient is under stress All anterior pituitary hormones may be affected: growth hormone is first to be affected, followed by prolactin, FSH, LH, ACTH and TSH. Oestradiol, IGF-1, free T4, and cortisol are also affected Diagnosis confirmed by MRI of pituitary gland