Endocrinology Flashcards
Hormone
- substance produced and secreted by a gland or from cells/tissues
- into the bloodstream that circulates
- and acts at a target site remote from the source
Ovarian hormones
11!
Oestrogen - oestrone E1 (in menopause), oestradiol E2 (most active, primary in non-pregnant), Oestriol E3 (primary in pregnancy)
Progesterone
Angrogens (25% of total, other 25% from adrenal glands and 50% from peripheral conversion of androstenedione)
Inhibin
Relaxin
Activin
Oxytocin
Vasopressin
Pro-renin
Follistatin
Prostaglandins
Markers of corpus luteum function
17-hydroxyprogesterone (not from placenta)
Relaxin
Oestrogen
Oestrone E1 (in menopause)
Oestradiol E2 (most active, primary in non-pregnant)
Oestriol E3 (primary in pregnancy)
- produced by developing follicles in ovary, corpus luteum, placenta, liver, adrenal glands, breast, adipocytes
- in plasma binds to SHBG (sex hormone binding globulin) and albumin
- metabolized in liver to E1 and E3
- excreted in kidney as oestriol glucuronide
- 2 main receptor subtypes α and β
Oestrogen functions
Cardiovascular - vasodilator (↑ NOS so ↑ in NO), preventative against atherosclerosis
Bone - maintenance of density (decreases resorption by antagonizing PTH), fusion of epiphyseal plates
Increases clotting - ↑ levels of factors II, VII, IX, X and plasminogen, ↓ anti-thrombin 3, ↑ platelet adhesiveness
Gastrointestinal - ↓ bowel motility, ↑ bile
Metabolic - ↑ HDL levels, ↓ LDL levels, ↓cholesterol, ↑ TAG synthesis
Skin pigmentation by increased phaeomelanin - nipple, areola, genital
Progesterone
Source - corpus luteum, adrenal glands, placenta (+ a type of plant)
Store - adipose tissue
Bound in plasma - CBG (corticosteroid-binding globulin) and albumin
Metabolized - in liver to pregnanediol
Excreted - by kidney as pregnanediol glucuronide
Pre-ovulation <2ng/ml
Post-ovulation 5ng/ml
At term 100-200ng/ml
Progesterone functions
Uterus, cervix, vagina - converts proliferative to secretory endometrium, thickens endometrium, inhibits uterine contraction until term
Increases core temp following ovulation
Smooth muscle relaxant
Catabolic (increase appetite)
Increase aldosterone (Na and H2O retention)
Reduce pressor responsiveness to angiotensin2
Respiration - increased ventilator response to CO2, decreased arterial and alveolar pCO2
Inhibits lactation during pregnancy
Neuroprotective -?tx for MS
Inhibins
Peptide members of transforming growth factor (TGF)β family
Secreted by ovarian granulosa cells, produced in gonads, pituitary gland, placenta
Selectively inhibits FSH but NOT LH secretion
Inhibin A - part of quad screen test in 1stT ↑, with ↑βhCG, ↓AFP, ↓oestriol suggestive of Down’s syndrome
Inhibin B
Activins
Peptide members of TGFβ family
Derived from ovarian granulosa cells, pituitary gonadotropes
Function - ↑ FSH action in ovary, ↑FSH secretion in pituitary, inhibit prolactin, growth hormone and ACTH responses
Relaxin
Produced by corpus luteum, placenta, breast, prostate
Relaxes pelvic ligaments in pregnancy, some role in cervical dilatation, inhibits contractility of myometrium
Testes secretions
MAIN HORMONES
Testosterone
DHT (paracrine)
Oestradiol
MINOR HORMONES - DHEA, androstenedione, oestrone, pregnenolone, progesterone, 17α-hydroxypregnenolone, 17α -hydroxyprogesterone
Testosterone
Anabolic steroid
Secreted by testis (Leydig cells), ovary (theca cells), adrenals (zona reticularis), placenta (cyto or syncytiotrophoblastic cells)
In serum - 2% free, 60% bound to SHBG, 38% to albumin
Effects on tissues via activation of nuclear androgen receptors OR aromatization of testosterone to oestradiol (in bone/brain)
Converted to DHT by 5α-reductase
Excreted in urine as 17-ketosteroid
5α-reductase
Converts testosterone -> DHT
2 isoforms
Produced in skin, seminal vesicles, prostate, epididymis, brain
Deficiency = low DHT, increased testosterone, gynaecomastia, ambiguous genitalia at birth
Sex hormone binding globulin
Glycosylated dimer protein
Synthesized by liver
Gene on chromosome 17
Higher levels in females, rises in pregnancy
↑ by oestrogen, tamoxifen, phenytoin, thyroid hormone
↓ by exogenous androgens, progestin, glucocorticoids, growth hormone, hypothyroidism, obesity
Hypothalamic hormones
Paraventricular nucleus - adjacent to 3rd ventricle, within blood-brain barrier, has magnocellular (oxytocin, ADH) and parvocellular (CRH, ADH, TRH) neurones
Arcuate nucleus - dopamine, GHRH
Pre-optic nucleus - GRH
Peri-ventricular nucleus - somatostatin
Supraoptic and paraventricular nuclei - ADH, oxytocin
Dopamine
Prolactin-inhibitory hormone
Produced in arcuate nucleus of hypothalamus, and substantia nigra, medulla of adrenal glands
Functions - important role in behaviour, cognition, voluntary movements, inhibits prolactin, inotropic, chronotropic, induces vomiting via chemoreceptor trigger zone
Does not cross blood brain barrier
Metabolized by catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO)
GnRH
Pulsatile release - high frequency in follicular phase, slows in late luteal phase
Low activity in childhood
Half life 2-4mins
Gene located on chromosome 8
Insulin increases activity, prolactin decreases
Somatostatin
GHRH inhibitor
Secreted by stomach, intestine, pancreatic D-cells, thyroid parafollicular cells, periventricular nucleus of hypothalamus
INHIBITORY functions
↓ growth hormone
↓ TSH
↓ release of GI hormone (gastrin, CCK, secretin, vasoactive intestinal peptide, motilin, insulin, glucagon)
↓ gastric emptying, blood flow and intestinal contractions
↓ release pancreatic hormones
Thyrotrophin-releasing hormone
Stimulates release of prolactin and TSH
Secreted by paraventricular nuclei of hypothalamus
Melatonin
Synthesized from serotonin
Associated with biorhythms
Inhibits gonadotrophins
Produced in pineal gland, retina, lens of eye, GI tract, suprachiasmatic nucleus
Increased secretion in response to hypoglycaemia and darkness
Classification of anterior pituitary hormones
Corticotrophin-related peptides - ACTH, MSH
Somatomammotrophin peptides - growth hormone, prolactin
Glycoproteins (2 subunits α and β) - TSH, gonadotrophins LH and FSH
FSH
Glycoprotein from anterior pituitary
Released in response to GnRH
2 subunits - α gene on chrom6 and β gene on chrom11
Functions - stimulates maturation of germ cells, stimulates ovary to produce Graafian follicle OR induces Sertoli cells to synthesize and secrete inhibin
3-4hr half-life
Receptors ONLY in granulosa cells
High FSH due to - premature menopause, reduced ovarian reserve, gonadal dysgenesis, castration, CAH
LH
Heterodimeric glycoprotein from anterior pituitary
2 subunits - α gene on chrom6 (identical 92 amino acids to TSH, FSH, hCG) and β gene on chrom19
In females - triggers ovulation, prevents apoptosis of corpus luteum, stimulates oestrogen and progesterone production
In males - stimulates leydig cells to produce testosterone
Receptors in granulosa cells and theca cells
Low LH due to - Kallmann’s, hypothalamic suppression, hypopituitarism, hyperprolactinaemia
High LH due to - premature menopause, gonadal dysgenesis, castration, PCOS, CAH
LH surge
Biphasic
Ovulation 36hr after surge, 16-26 hr after peak LH
20min half life
Causes - prostaglandin production, progesterone secretion from corpus luteum, resumption of meiosis by oocyte
Prolactin
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
Hyperprolactinaemia causes
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
Hypoprolactinaemia causes
PHARMACOLOGICAL - dopamine agonists (pramipexole, ropinirole for Parkinson’s)
PATHOLOGICAL - Sheehan’s syndrome, hypopituitarism, bulimia
Growth hormone
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
Causes of raised serum GH
PHYSIOLOGICAL
- sleep, stress, exercise, hyperglycaemia
PHARMACOLOGICAL
- GHRH, oestrogen, adrenergic agonist, dopamine agonist
PATHOLOGICAL
- chronic renal failure, anorexia
Causes of decreased serum GH
PHYSIOLOGICAL
- hyperglycaemia, elevated free fatty acids
PHARMACOLOGICAL
- somatostatin, progesterone, glucocorticoids
PATHOLOGICAL
- obesity
ACTH
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
Oxytocin
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
ADH
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
Thyroid hormone action
↑ 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
Thyroid hormone production
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
Thyroid changes in pregnancy
↑TBG
↑T3/T4 (total, but free decreases)
↓TSH
↑renal clearance
↑deiodination of T3/T4 by placenta
Adrenal cortex
Mediates stress response via mineralocorticoids and glucocorticoids
Zona glomerulosa - mineralocorticoids
Zona fasciculata - glucocorticoids
Zona reticularis - weak androgens
All synthesized from cholesterol
Glucocorticoids
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
Aldosterone
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
Adrenarche
Adrenal androgen production
- age 7-9 in males
age 6-7 in females
Adrenal cortex secrete weak androgens - DHEA, DHEAS, androstenedione
Adrenal medulla
Mainly chromaffin cells
Modified neural crest cells that did not complete their development to postganglionic neurones, but retain same function
Synthesize:
Adrenaline
Noradrenaline
Dopamine
Adrenaline
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
Renin-angiotensin system
JGA in kidney - juxtaglomerular cells of afferent arterioles, and macula densa (on ascending loop of Henle)
Renin
Angiotensinogen
Angiotensin
ACE
Renin
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
Angiotensinogen
Secreted by liver in reposnse to renin from kidney (in response to low BP)
Production increased by oestrogen, and glucocorticoids
Angiotensin
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
ACE
In endothelial cells of pulmonary capillaries, brain and glomeruli
Catalyses angiotensin1 -> angiotensin2
Also catalyses bradykinin breakdown, enkephalin breakdown, substance P breakdown
Insulin effects
Anabolic - glycogen synthesis, TAG synthesis
INHIBITS catabolism - inhibits glycogenolysis, inhibits ketogenesis, inhbits gluconeogenesis
Stimulates glucose uptake into muscle, adipose tissue
Insulin antagonists
Glucagon
Cortisol
Growth hormone
Adrenaline
Oestrogen
Thyroid hormone
Prolactin
Human placental lactogen responsible for insuline resistance of pregnancy
Glucagon
Main target tissue is liver
- glycogenolysis
- inhibits glycogen synthesis
- gluconeogenesis
- lipolysis
- ionotropic
- causes release of insulin and catecholamines
SIADH
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
Diabetes insipidus
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
Hypothyroidism causes
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
Congenital hypothyroidism features
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
Hyperthyroidism
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
Addison’s disease
Primary adrenocortical insufficiency
Hypotension, hypoNa, hypoglycaemia, hyperK, hyperpigmentation
Causes - CAH, infection (TB, CMV), autoimmune, adrenal haemorrhage, infiltrative disorder (amyloidosis, haemochromotosis), drugs (ketoconazole, etomidate)
Cushing’s syndrome
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
Conn’s disease
Primary hyperaldosteronism
Caused by adrenal adenoma
Low renin:aldosterone ratio
Treat with spironolactone (K sparing)
Hypokalaemia, hypernatraemia, hypertension
Phaeochromocytoma
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
Prolactinoma
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
Sex determination
In utero default phenotype is female
Male phenotype - sex-determining region Y hormone, testosterone (Wolffian ducts), Mullerian inhibiting substance (by sertoli cells)
Puberty in males/females
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
Growth spurt in puberty
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
GnRH and gonadotrophin changes up to puberty
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
Endocrine changes in pregnancy
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 ↓
Placental hormones
9 produced during pregnancy:
hCG
hPL
Oestrogen
Progesterone
Corticosteroid
CRH
Relaxin
ACTH
TSH
hCG
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
hPL
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
Cervical ripening induced by
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
How does fetus trigger partuition (hormones)
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
Other factors triggering labour
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
Ferguson reflex
Neuronal reflex triggered by pressure to cervix and vagina
Causes spurts of oxytocin release
During active and expulsive labour phases
Hormones in puerperium
↑ 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
Lactation + lactational amenorrhoea
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
Composition of breast milk
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
Benefits of breastfeeding
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
Colostrum
For first 3-5 days post delivery
100ml/day
Rich in vitamin A, lactoferrin, IgA, sodium
Fetal endocrine development
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
Surfactant production controlled by which hormones
Cortisol
Oestrogen
Adrenaline
Thyroid hormone
Endocrine disorder testing
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
WHO type ovulation disorders
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)
Hyperparathyroidism
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
Sheehan’s syndrome
- 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
