1
Q
describe the posterior pituitary gland production of hormones
A
- hypothalamus
- posterior pituitary gland
- produce oxytocin -> causes uterus contraction and expresses milk
- produces ADH which acts at V2 receptors in collecting ducts to increase water reabsorption and V1 receptors on blood vessels
2
Q
which hormones does the anterior pituitary gland produce
A
- GnRh -> LH and FSH
- TRH -> TSH
- PRH -> prolactin
- GHRH -> growth hormone
- CRH -> ACTH
3
Q
describe the action of ACTH
A
- hypothalamus stimulated
- corticotropin relasing hormone release
- acts at anterior pituitary gland to release ACTH
- acts at adrenal cortex by binding to melanocortin 2 receptors and stimulates zona fasciculata to produce cortisol and zone reticularis to produce androgens
4
Q
regions of adrenal cortex and actions
A
- zona fasciculata -> produce cortisol and glucocorticoids
- zona reticularis -> produce androgens
- zona glomerulosa -> produce mineralocorticoids (aldosterone) - controlled by renin angiotensin system
5
Q
describe growth hormone release
A
- hypothalamus stimulated and release growth hormone releasing hormone
- acts at anterior pituitray gland and produces growth hormone
- growth hormone acts at liver and stimulates insulin growth factor 1
- causes lipolysis, glycogenolysis , protein synthesis, muscle strength, skeletal growth
6
Q
action of LH
A
TESTES -> stimulates leydig cells and produces testosterone
OVARIES -> binds to theca cells + follicular cells to cause steroidgenesis + produce oestrogen
7
Q
action of FSH
A
TESTES -> drives sperm production in sertoli cells and synthesis of androgen binding proteins
OVARY -> binds to granulosa cells to stimulate follicle growth, convert androgens to oestrogen and progesterone production
8
Q
risk factors for type 1 diabetes
A
- family history - twins 30-50% risk of other twin developing diabetes
- genetics - DR3, DR4, DQA, DQB
- viral trigger
- autoimmune conditions
- cystic fibrosis
- down syndrome
9
Q
embryology of pancreas
A
develops week 5
2 outpouchings develops from ENDODERM lining of duodenum :
1. ventral bud -> lower part of head
2. dorsal bud - upper part of head, neck and tail
from week 7, secretion of hromones
week 10, alpha cells diefferentiate first, then delta and beta
week 15, glucagon detected
10
Q
cells of islets of langerhans in pancreas
A
alpha cells - produce glucagon (promotes gluconegogenesis in liver)
beta cells - produces insulin
delta cells - produce somatostatin
11
Q
action of insulin
A
increase glucose uptake into adipose tissue and muscle (via gLUT4 receptor) + suppresses hepatic glucose release and stimulates glycogen synthesis
insulin release from beta cells when blood sugar high and detected by ATP sensitive k channel
12
Q
pathophysiology of type 1 diabetes
A
- immune mediated destruction of beta cells via CD4 T lymphocytes (glutamic acid decarboxylase antibdoies, insulin antibodies, islet autoantigen 2)
- once 80-90% beta cells destroyed, symptoms develop and deficiency of insulin
- increase in counter regulatory hormones (cortisol, adrenaline, growth hormone) and promotes gluconeogenesis, glycogenolysis and ketogenesis in liver
13
Q
presentation of type 1 diabetes
A
DKA !!
polyuria - caused by overloading of SGLT2 receptors in PCT
polydipsia
weight loss
tiredness
increased skin infections
14
Q
diagnosis of type 1 diabetes
A
random glucose >11.1mmol
fasting blood sugar > 7.0 mmol/l
15
Q
investigations to do in type 1 diabetes
A
- coeliac and TFT markers
- HbA1c - average blood sugar over 8 weeks
- antibody markers e.g. GAD, islet cells, insulin
- U&E
- c peptide - indicates T2DM
- triglycerides - low HDL, elevated triglycerides
16
Q
target blood sugars
A
waking and before meals: 4-7
after meals: 5-9
for hypoglycaemia - give 10 g oral sugar
17
Q
types of insulin therapy
A
- basal bolus regime
- long acting insulin (40% daily dose)
- short acting insulin with carb counting (60% daily dose - 20% each meal) - continuous insulin pump
regular amount of rapid acting insulin, resisted every 2-3 days
18
Q
annual screening in diabetes
A
blood pressure
urine dipstick - early morning urine albumin : creatinine ratio
eye screen
autoimmune disease screen
19
Q
what is the somogyi effect
A
well controlled with night time hypoglycaemia and early morning glycosuria
common with fast acting insulins and managed by reducing insulin dose
20
Q
indicators of type 2 diabetes
A
obesity **
strong family histroy
acanthosis nigricans (dry, dark patches of skin in axilla or groin)
PCOS
strong FH
21
Q
pathology of T2DM
A
insulin resistance + reduced insulin secretion
22
Q
management of t2DM
A
weight loss and exercise
metformin (suppresses hepatic glucenognesissi)
+/- sulfonylureas
23
Q
cause of maturity onset related diabetes mellitus
A
genetic defect in HNF gene (glucokinase receptor = glucokinase deficiency) in beta cells
autosomal dominant
causes asymptomatic, non obese with mildly raised chronic blood sugars
24
Q
screening for MODY
A
urine c peptide creatinine ratio
and genetic testing
25
causes of hypoglycaemia
ENDOCRINE
hyperinsulinism, growth hormone deficiency, hypothyroidism
METABOLIC
fatty acid oxidation disorders, glycogen storage disorders
NEONATAL
hypothermia, maternal meds / GDM, prematurity, polycythaemia, beckwith wiedeman
OTHER
sepsis, malabsorption, diabetes, liver failure
26
define gluconeogenesis
generation of glucose from non carbohydrate substrates e.g. pyruvate, lactate, glycerol in the liver
occurs during time of fasting/ starvation/ exercise
27
define glycogenolysis
breakdown of glycogen in the hepatocytes to produce glucose for cell utilisation
28
presentation of hypoglycaemia
autonomic - tremor, pallor, tachycardia, sweating
behavioural - irritable, hungry, tantrums
neurological - headache fatigue, lethargy, comas, seizures
29
hypoglycaemia screen
1. blood glucose
2. blood ketones - if low/normal = fatty acid oxidation probelm or ketogenesis problem
3. insulin and c peptide levels - should be suppressed, high = hyperinsulinaemia
4. lactate - increased in glycogen storage disorder
5. free fatty acids
6. ammonia - elevated in inborn errors of metabolism
7. acylcarnitines - abnormal in fatty acid defects
8. urinary organic acids
30
pathophysiology of DKA
1. deficiency of insulin
2. increase in counter regulatory hormones
3. increase production of glucose from liver thoygh glycogenolysis and gluconeogenesis
4. free fatty acids converted to ketones by glucagon (acetoacetic acid and beta hydroxybutyric acid)
31
presentation of DKA
vomiting, abdo pain
dehydration
fever
kussmauls bretahing
shcok
drowsiness
32
severity of DKA
mild: ph 7.2-7.29 (5% dehydration)
moderate: ph 7.1 - 7.19 (7% dehydration)
severe: ph < 7.1 +/- bicarb <5 (10% dehydration)
33
management of DKA
1. ABCDE
2. IV fluids: 10ml/kg iV fluid bolus of 0.9% saline over 60 minutes (20ml/kg if shocked)
2. iV fluids: deficit (over 48 hours) + maintenance (24hrs)
3. insulin therapy 0.1units/kg/hr continuous pump (start 1-2 hours after fluid)
4. blood glucose and ketones checked 1-2 hourly + gas and U&E every 4 hours
34
complication of DKA and management
CEREBRAL OEDEMA - within 12 hours
treat with 20% mannitol 1g/kg over 10-15 minutes or 3% hypertonic saline
35
risk factors for developing cerebral oedema in DKA
younger age
low pCO2
>40ml/kg fluid bolus
36
circulation of thyroid hormones
70% of T4 and 50% of T3 bound to thyroxine bidning globulin in circulation
0.03% T4 nad 0.3% T3 unbound in circulation
37
causes of congenital hypothryoidism
1. ectopic gland - most common cause in developed countries
2. iodine deficiency - most common cause worldwide
3. dyshormongenesis - consanguinous marriages
4. thyroid dysgenesis - fails to develop
5. Hashimotos
38
describe hashimotos disease
painelss goitre and hypothyroidism
high anti thyroglobulin antibodies + high anti thyroid microsomal antibodies + high TPO antibodies ****
39
detection of congenital hypothyroid
NEWBORN SCREENING - TSH measured day 5 of life
if >10 -> USS and isotrope scanning
40
presentation of neonatal hypothyroid
symptoms around 6 weeks old
poor feeding
prolonged jaundice
hypotonia
constipation
myxoedema - macroglossia, coarse facie, swollen eyelids
cold mottled skin
41
causes of acquired hypothyroidism
Hashimotos
autoimmune thyroiditis
post thyroid surgery
radiation
iodine deficiency
42
describe thyroglossal cyst
midline neck cyst
moves on tongue protrusion
USS and surgical excision
43
blood results for hypothyroidism
low T4, raised TSH
44
blood results for poor compliance with hypothyroidism
normal T4, high TSH
45
embryology of parathryoid gland
originates from 3rd and 4th branchial arches
46
blood test of hypoparathyroid
low PTH
low Calcium
raised phosphate
47
causes of hypoparathyroidism
1. Di george syndrome
2. removal of thyroid gland affecting parathyroid
3. Mg deficiency
4. autoimmune disease
5. pseudohypoparathyroidism
48
blood tests for pseudohypoparathyroidism
high PTH
low Ca
high phosphate
49
signs of hypercalcaemia
paraesthesia
cramps
tetany - Chvoseks sign
diarrhoea
carpal spasm - Trousseus sign
ECG - short QT, VF, Osborn waves
50
causes of hypercalcaemia
1. TB
2. sarcoidosis
3. FH of MEN1
4. vit D therapy
5. williams syndrome
6. bone mets, myeloma
7. paraneoplastic syndrome
51
cause of hyperthyroidism
Graves disease ***
thyroid carcinoma
52
blood tests in Graves disease
raised T3 and raised T4
low TSH
thryoid stimulating hormone receptor antibody
53
management of graves disease
1. carbimazole
2. propranolol and iodine solution if severely throtoxicsosi
4. radioiodine and surgery
54
inheritance of CAH
autosomal recessive
55
most common cause of CAH
21 hydroxylase deficiency in 90% of cases on chromosome 6
causes :
1. accumulation of 17-alpha- hydroxyporgesterone which can be converted to androgens
2. reduced aldosterone production
56
how do girls with CAH present at newborn
virilisation and ambiguous genitalia
57
how do boys with CAH present
in first week of life with 'adrenal crisis' / 'salt losing crisis'
hypotension
vomiting
dehydration
poor feeding
virilisation in boys
58
blood results of 'salt losing crisis' in CAH
hyperkalaemia
hyponatraemia
hypoglycaemia
metabolic acidosis
59
how to test for CAH
1. karyotype*
2. 17 hydroxyprogesterone raised* - need to be at least 72 hours old
3. pelvic USS
4. 11-doxycortisol reduced
60
management of CAH
1. hydrocortisone
2. fludrocortisone
3. sodium replacement in 1st year of life
IN SALT LOSING CRISIS:
1. IV 10% dextrose 3ml/kg
2. iV hydrocortisone 60mg/m2
3. IVF with O.9% saline
61
cause of cushings syndrome
1. iatrogenic steroids
2. pituitary tumour secreting excess ACTH
3. adrenal adenomas or carcinomas
4. MEN1
5. mccune albright syndrome
62
presentation of cushings syndrome
1. central weight gain, risk of diabetes, moon face (due to insulin resistance and increased blood sugar)
2. increased infections (immunosupressed)
3. muscle weakness
4. easy bruising, striae (impacts collagen synthesis)
5. hypertension, risk fo CV disease
6. depressed, irritable, mood variable
63
investigations for cushings syndrome
1. 24 hour urinary free cortisol levels high ** - loss of diurnal variation of cortisol
2. serum ACTH levels
3. IPSS *
4. dexamethasone suppression test
5. MRI head !
64
management of cushings
surgical intervention for tumours
metyrapone - lowers cortisol level
65
blood results of long term steroid use
1. low cortisol
2. low ACTH
3. low CRH
causes suppression of the HPA and reduced synthesis of CRH and ACTH and downregulation of natural glucocorticoid
need to manage infectiosn with double dose steroids
66
describe GH deficiency
inadequate production or secretion of growth hormone by anterior pituitary gland
can be idiopathic, genetic, acquired through trauma/ radiation
67
presentation of GH deficiency
short stature - present early or mid childhood
delayed skeletal maturation - bone age younger than chronological age
reduced muscle bul and increased s/c fat
isolated
68
describe diabetes insipidus
insufficient ADH causing high volumes of dilute urine and hypernatraemia dehydration
69
central/ cranial causes of diabetes insipidus
= DEFICIENCY OF ADH DUE TO REDUCECD SECRETION BY HYPOTHALAMUS
trauma
post radiotherapy
infections
craniopharyngioma - following neurosurgery
hypothalamic glioma
familial AD neurohypophydeal DI
70
nephrogenic causes of diabetes insipidus
= RESISTANT TO ADP IN KIDNEYS
renal damage e.g. CD
nephrotoxic medications e.g. lithium
hypokalaemia, hypercalcaemia
hyperglycaemia induced osmotic diuresis
71
Presentation of diabetes insipidus
polyuria
dehydration
polydipsia
72
diagnostic tests for diabetes insipidus
1. paired urine and serum osmolalities
dilute urine (osmolality <750) + hyperosmolar state (>295)
2. MRI brain
3. water deprivation test - once given desmopressin dose, if get a rise in urine = cranial DI / if no rise in urine osmolality = nephrogenic DI
73
management of central diabetes insipidus
desmopressin
74
management of nephrogenic diabetes insipidus
thiazide diuretics (inhibit NaCl cotransporter in the DCT and increase proximal tubular Na and water reabsorption)
75
describe SIADH
excessive secretion of ADH causing water retention and leading to dilutional hyponatraemia
76
causes of SIADH
1. tumours - small cell lung cancer, brain tumours, thyoma, Ewings sacroma
2. CNS - trauma, infection, haemorrhage
3. medications - thiazide diuretics, SSRI, anti epileptics
4. TB
77
presentation of SIADH
headache
confusion
lethargy
N&V
hyponatraemia - muscle cramps
78
diagnostic tests for SIADH
1. serum osmolality - low
2. urine osmolality - high (concentrated urine)
3. hyponatraemia
79
management of SIADH
1. fluid restriction
2. monitoring electrolytes
3. vasopressin receptor antagonists e.g. tolvaptan
80
describe phaeochromocytomas
neuroendocrine chromaffin cell tumour which commonly occurs in the adrenal medulla
associated with NF1
81
Presentation of phaeochromocytomas
headache
sweating
palpitations
diarrhoea
severe hypertension
82
diagnostic test for phaeochromocytomas
urine catecholaemines metabolites
83
management of phaeochromocytomas
1. alpha adrenoreceptor blockade
2. surgical excision
84
inheritance of MEN type 2b
autosomal dominant - mutation in RET proto oncogene
85
presentation of MEN type 2b
1. mucosal neuroma
2. medullary thryoid cancer
3. pituitary tumour
4. parathyroid hyperplasia -> hyperparaparathyroidism
86
inheritance of kallmann syndrome
X linked recessive
isolated deficiency of GnRH -> causes hypogonadism, infertility and incomplete/ absent puberty
87
presentation of kallman syndrome
hypogonadotropic hypogonadim
obesity
anosmia
colour blind
88
normal puberty ages
8-14 y/o in girls
9 - 14 y/o in boys
89
normal puberty patten in girls
1st sign = breast development (breast buds appear at age 11 in 50%)
2. pubic and axillary hair growth
3. menarche 2-3 years after breast bud development
4. peak height velocity
90
normal puberty pattern in boys
1st sign= testicular enlargement to > 4mls (usually 12- 13 y/o)
2. pubic hair growth 1-2 years after
3. penile and scrotal enlargement one year after testicular enlargement
4. later signs = growth spurt (once testicular growth >10mls) deep voice, acne, facial hair
91
define precocious puberty
secondary sexual characteristics (breast bud enlargement and testicular enlargement) develop before age of 8 in GIRLS and before of 9 in BOYS
92
2 type of precocious puberty
1. true central precocious puberty (80%)
= gonadotropin dependent = premature stimulation of HPA axis, causes same physiological pattern of puberty
2. androgen mediated precocious puberty (20%)
= gonadotropin independent= early excess andogen secretions, causes virilisation
93
causes of true central precocious puberty
1. idiopathic - girls (80%), premature physiological puberty
2. CNS abnormalities - NF1, septo optic dysplasia ,tumours, hydrocephalus
3. leydig cell tumours (secrete testosterone)
94
causes of androgen mediated precocious puberty
1. adrenal disorders - CAH, severe hypothyrodisim, adrenal tumours
2. russel silver syndrome
3. mccune albright syndrome
causes secondary sexual characteristics with pre pubertal testes
95
features of mccune albright syndrome
fibrous dysplasia
cafe au lait macules
endocrine hyperfunction - thyrotoxicosis, cushings
early puberty
mutation in gNAS-1
96
investigations for precocious puberty
1. gonadotropin levels - differentiates between central and androgen related causes
central = high FSH and high LH and high sex steroids
androgen = low FSH and low LH
2. androgen levels (testosterone and oestrogen)
3. pelvic USS
4. hand and wrist X R to assess bone age
97
management of precocious puberty
central = gonadotropin releasing hormone anologues to suppress gonadoptropins
androgen = GnRH anologues
98
describe delayed puberty
onset of sexual development later than 13 y/o in girls and 14 y/o in boys
99
causes of delayed puberty
1. constitutional delay ***
2. chronic illness e.g. anorexia, CD, post chemo, coeliac, hypothyroid
3. malnutrition
4. genetic - klinefelters, Kallmann syndrome, turners, prader willi syndrome
5. chronic steroid use
6. hypogonadotropic hypogonadism - low FSH, LOW FH and low testosterone. reduced GnRH
100
investigations for delayed puberty
1. LH and FHS
2. Testosterone and oestradiol
3. prolactin + TFT
4. karyotype
5. bone age
101
how to calculate mid parental height
(dads height + mums height)/2
+7cm for boys
-7cm for girls
plot on growth chart for 18 y/o
shoudl be within 2 centile spaces
102
causes for tall stature
1. constituitional tall stature - tall parents, normal growth velocity, have advanced bone age
2. genetics - marfans, klinefelters, sotos (lareg head and obesity), beckwith wiedeman
3. endocrine - hyperthryroid, growth hormone excess, CAH, precocious puberty
4. homocystinuria
103
causes of short stature
1. constitutional delay of growth - had deceleration of height in 1st 3 years, normal in child and accelerated in adolescent
2. familial short stature
3. primary growth disorder e.g. downs, prader willi, turner, noonan, achrondoplasia
4. endocrine - hypothyroid, hypopituitarism, Cushings, glycogen storage disorders, growth hormone deficiency
5. malnutrition, neglect, psychosocial deprivation
6. chronic disease e.g. CKD, CHD, coeliac
104
investigations for short stature
1. mid parental height
2. bone age *
3. karyotype
4. TFT, coeliac, FBC
5. serum IGF1 and IGFBP3 - better levels than GH (variation in day)
weight: if high -> GH deficiency, hypothyroid
proportionate height and weight -> genetic testing
105
side effects of carbimazole
cholestatic liver injury -> itching
nausea, vomiting, diarrhoea
thinning of hair
agranulocytosis
106
which hormone stops growth
oestrogen -terminates growth by causing fusion of epiphysis at long bones
106
mechanism of action of sulfonylureas
act at ATP sensitive K channel in beta cells and increases release of insulin
SE = hypoglycaemia, weight gain
106
ECG in hyperkalaemia
tall tented T waves
PR prolonged
106
bloods for central hypothyroidism
reduced TSH
reduced T3/T4
106
Define congenital hypopituitarism
deficiency of GH + at least one other anterior pituitary hormone
microgenitalia, jaundice, hypoglycaemia, jittery
107
role of leptin
reduces food intake and appetite - produced in adipose cells and acts on hypothalamus
108
features of sotos syndrome
large since birth
tall
macrocephaly
long narrow face and pointed chin
down slanting palpebral fissures
developmental delay and LD
protrduing forehead
FOP/TAS
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