Endocrinology & Diabetes Flashcards
Effects of increased cortisol in the body
Increased BP
Increased gluconeogenesis, lipolysis, proteolysis
Anti-inflammatory
Reduced bone function, immunity
Which areas of the adrenal gland produce which hormone?
Medulla: Adrenaline, noradrenaline
Cortex: (out to in)
- Glomerulus - Mineralocorticoids (aldosterone)
- Fasiculata - Glucocorticoids (cortisol)
- Reticular - Sex (androgens)
Go Find Rex, Make Good Sex
What controls calcium homeostasis in the body?
- Low calcium
- Parathyroid releases more PTH
- Acts in 3 places:
-Bones - osteoclasts break down bone
- Kidneys - retain Ca2+ and Vit D
- Intestines - absorb more Ca2+
Mg2+ also regulates PTH release
What controls the release of sex hormones?
- Hypothalamus releases GnRH
- Ant. Pituitary releases LH / FSH
- In males –> LH –> Testes release Testosterone and FSH stim. sperm maturation
- In females –> LH and FSH –> ovaries release estradiol and progesterone
What biochemical changes would you see in different types of Hypothyroidism?
- Primary = High TSH, low T3/T4
- Secondary = Low TSH, T3/4
- Treated / subclinical= High TSH, normal T3/4
Rising TSH indicates poor compliance
What biochemical changes would you see in different types of Hyperthyroidism?
- Primary= Low TSH, high T3/4
- Secondary = High TSH, T3/4
- Treated / subclinical = low TSH, normal T3/4
Presentation of congenital hypothyroidism
D5 Guthrie. Sx 6-12w
Protruding tongue
Hoarse cry
Delayed growth and development
Pale
Prolonged jaundice
Umbilical hernia
Congenital hypothyroidism cauases
Maternal iodine def.
Thyroid agenesis
Inborn error thyroid hormone synthesis
Pituitary dysfunction
Presentation of acquired hypothyroidism
Weigh gain / short
Thin skin / hair
Cold intolerance
Poor conc. / LD
Bradycardia
Goitre eg AI/ Hashimoto’s
Constipation
Low iodine
Presentation acquired hyperthyroidism
Weight loss, tall
Tachycardia
Diarrhoea
Reduced Conc.
Goitre
Eyes - Exophthalmos, opthalmoplegia, lid retraction, lid lag
Pre-tibial myxoedema
Causes of acquired hyperthyroidism
Mainly primary. More girls.
Graves’ - AI thyroiditis. TRAB Ab
Thyroiditis
Thyroid nodules
De Quervain’s thyroiditis - post-viral. Painful. Self-limiting.
Treatment for acquired hyperthyroidism
- Carbimazole - block thyroxine synthesis (SE neutropenia)
- ?2nd course
- Radical - thyroidectomy, radioactive iodine
Symptoms of hypocalcaemia
Tetany
Cramps
Paraesthesia
Stridor
Diarrhoea
Seizures
Biochemistry in hypoparathyroidism
Low PTH
Low Calcium
High Phosphate
Normal Alk Phos
Causes of hypoparathyroidism
DiGeorge
Magnesium deficiency
Genetic mutation of calcium sensing gene
AI
Presentation and biochemistry of pseudohypoparathyroidism
- Presentation: Short, obese, LD, SC nodules, short 4th metacarpal
- Biochemistry: Increased PTH and Phosphate, low Calcium, normal Alk Phos
= end organ resistance to PTH (defect in G protein signalling)
Symptoms of hypercalcaemia
Constipation
Lethargy
Polyuria
Anorexia
Polydipsia
Causes of hyperparathyroidism in children?
Rare
William’s
Later - adenoma, MEN
What hormones are affected in adrenal insufficiency?
LOW CORTISOL
LOW ALDOSTERONE
Causes adrenal insufficiency
AI - Addison’s
CAH
Haemorrhage / infarct
Infective - TB
X-linked adrenoleukodystrophy
Removal of long term steroids (Low ACTH / CRH)
Presentation of adrenal insufficiency
LOW SODIUM, HIGH POTASSIUM
Weight loss
Abdo pain / vomiting/ dehydration
Lethargy
Pigmentation
Infant - salt losing crisis
Crisis - Low BP, low GCS, N+V
What tests for adrenal insufficiency?
Short Synacthen test
ACTH stimulation
Treatment for adrenal insufficiency
Acute - IVT, glucose, hydrocortisone
Chronic - Hydrocortisone / fludrocortisone
Double steroids if unwell
Presentation of congenital adrenal hyperplasia
Virilisation of genitalia esp girls
Salt losing crisis
Hypoglycaemia
High 17-OHP at 72 hours
Genetics of CAH
Autosomal recessive
HLA on Ch 6 –> defect in enzyme for steroidogenesis
Presentation of adrenal excess
Short and fat + striae
Prox muscle weakness/ wasting
Bruising
Thin skin
OP
Red cheeks
Hirutism
Causes of adrenal excess (high cortisol)
- Low ACTH = Adrenal adenoma, arenal nodular hyperplasia, steroids
- High ACTH = Cushing’s disease, pituitary adenoma, ectopic ACTH (paraneoplastic)
What test would you do for adrenal excess
- Low dose Dex suppression test –> Cushing’s = no suppression
- High dose suppression test –> Cushing’s disease suppressed at 8mg, ectopic ACTH / adrenal adenoma not suppressed
Undetectable ACTH = adrenal tumour
Presentation of phaeochromocytoma
Episodic:
Headache
HTN
Tachycardia
Flushing/ sweating
Causes of Phaeochromocytoma
Adrenal medullary tumour
Raised adrenaline / noradrenaline
Increased risk in NF1
Ix Phaeochromocytoma
Urine catecholamines / metanephrines
Blood metanephrines
CT Abdo
Which hormones are secreted from the anterior pituitary gland?
TSH
ACTH
GH
Prolactin
LH
FSH
Which hormones are released from the Posterior pituitary gland?
ADH
Oxytocin
Presentation of growth hormone deficiency
Faltering growth after 6 months of age
Maxillary hypoplasia
Forehead prominence
Test for GH deficiency
GH provocation test
Random GH not useful
How does growth hormone cause growth?
Acts on IGF-1 at growth plate –> proliferation of chondrocytes
Causes of Diabetes Insipidus
- Neurogenic = Inadequate release ADH. Idiopathic, AI, pituitary disease
- Nephrogenic = Inadequate renal response ADH (defect vasopressin-2 reception or aquaporin-2). Drugs (lithium), CRF, post-obstructive uropathy, High glucose / Na+ / Ca2+
Diabetes Insipidus investigations
-Low urine osmolality, High serum Osmolality
- Hypernatraemia
- Water deprivation test - urine conc. <600 –> give desmopressin –> concentrates only in neurogenic. SE desmopressin = water retention –> hold when unwell.
- MRI head
Causes of SIADH
- CNS - meningitis, encephalitis, trauma, hypoxia
- Haemorrhage
- Guillain-Barre
- Resp - LRTI, TB
- Tumours - Thymoma, lymphoma, Ewing’s
- Drugs
What is Kallmann syndrome?
Defective GnRH release from hypothalamus
- Anosmia
- Colour blindness
- Delayed puberty
Presentation of pituitary apoplexy
Headache
Meningism
Low GCS
Visual field defect
Ophthalmoplegia
Physiological response to hypoglycaemia
Increased glucagon
Increased adrenaline –> Palp, tremor, sweating, pallor
How is mid-parental height calculated?
(Mum+Dad)/2 –> +7 in boys
- 7 in girls
Define Short stature
Height <2nd centile
2 SD away from mean
Causes of Short stature
- Familial
- Constitutional delay
- Iatrogenic eg steroids
- Nutritional
- Chronic disease (low IGF-1)
- Foetal alcohol syndrome
- Genetics - Russell- Silver, Turner’s, Noonan’s, Skeletal dysplasia, Prader-Willi, Trisomies, SHOX gene
- Endocrine - thyroid, GH, cortisol
Causes of Tall Stature
- Nutritional - same final height
- Genetic- Klinefelter’s, Marfan’s, Beckwith-Wiedemann, Sotos, NF
- Metabolic - Homocystinuria
- Endocrine - Hyperthyroid, precocious puberty, CAH, excess growth hormone
What is defined as precocious puberty?
Onset of puberty before
- 8 years in girls
- 9 years in boys
Causes of precocious puberty
- Gonadotrophin dependent (High LH and FSH) = Pituitary mass (bitemoporal hemianopia), brain injury. More common in girls.
- Gonadotrophin independent (Low FSH and LH) - adrenal tumours, CAH
Investigations precocious puberty
- LHRH stiulation test
- LH, FSH, testosterone / oestradiol
- L wrist xray
- Pelvic USS
- MRI brain
What can be used to delay precocious puberty?
Ig Gonadotrophin dependent, can use GnRH analogues eg Leuprorelin –> decreases LH / FSH
Causes of delayed puberty (>13y in girls, >14y in boys)
- General - illness, malnutrition, steroids
- Constitutional delay (more in boys)
- Systemic causes low gonadotrophin = CF, asthma, Crohn’s
- HPA disorder causing low gonadotrophin eg pituitary tumour, Kallmann, hypothyroid
- High FSH / LH and low androgens: Turner’s, Klinefelter’s, gonadal damage eg surgery, radio
Treatment of delayed puberty
- Girls = Oestradiol
- Boys = IM testosterone
Genetic association of Type 1 DM
HLA D3/4
Which auto-antibodies are associated with T1DM?
GAD
ZnT8
IA-2
T cell mediated damage to beta cells
Glargine mechanism of action
Molecular changes –> shifts isoelectric point –> slow release of bioactive molecules
Definition of severe DKA
pH <7.1
HCO3- <5
When is insulin started in DKA and at what dose?
1 hour after rehydration
0.05 - 0.1 units/kg/hr
Complication of rapid fluid correction in DKA
Cerebral oedema
Headache, agitation, irritability
Tx: Mannitol / hypertonic saline
Pathophysiology PCOS + Tx
-Excess LH –> stim ovarian androgen production and hyperinsulinaemia upregulates 17-alpha-hydroxylase + synthesises androgen precursors.
-High level of uninhibited oestrogen –> endometrial hyperplasia.
-Tx: OCP corrects hormonal imbalances –> suppress ovarian stimulation by suppressing release of LH / FSH.
What does low c-peptide levels mean?
Low endogenous production of insulin
Diabetic retinopathy - signs on fundoscopy
Microaneurysms
‘Dot-and-blot’ haemorrhages
Venous bleeding ‘Cotton wool’ spots.
Management of CF related DM
-Continue high calorie diet + exercise
-Start insulin and monitor blood glucose levels.
