Endocrinology Flashcards
Prevalence of diabetes in children
1/500 children have diabetes. 96% type 1, 2% type 2.
Long term effects of DM
- leading cause of renal failure & blindness in people <60yrs & 2nd commonest cause of limb amputation
- increased risk miscarriages, still births (5 x increase) & congenital malformations in mums with DM
- estimated that 50% men with long standing diabetes are impotent
- Life expectancy -10 years
1st presentation of diabetes
- Polyuria (previously dry, now wetting bed)
- Polydipsia
- Weight loss
- Tiredness
- Blurred vision
- Abdominal pain
- Constipation
Diagnosis of diabetes
- Screening – Urine with glucose
- Blood sugar – Fasting >7.0mmol/L – Random >11.1mmol/
- High blood sugar could be due to stress response or infection
Symptoms of DKA
- Polyuria (previously dry at night, now wetting?)
- Polydipsia (excessive thirst)
- Breathless
- Tiredness, drowsy
- Weight loss
- Nausea & Vomiting
- Headache
- Abdominal pain
- Constipation
- Ketotic breath
- Dehydration
- Shock
Immediate management of DKA
Put in recovery position, call ambulance
Manage with ABC, fluids (with KCL added)
Insulin and glucose IV after 1 hr
Monitor (K+, Na+, Gluc, ECG, renal bloods). Aim to bring down blood glucose level by max 5mmol/hr
5 causes of hyperglycaemic crisis in T1DM patients
5 I's Infection Infarction Infant (pregnancy) Indiscretion (including cocaine use) Insulin lack (non adherence or inappropriate dosing).
What is the main risk of treatment in DKA
Cerebral oedema
Cerebral oedema symptoms
- Headache
- Drowsiness
- Incontinence
- Vomiting recurrence
- Decreased level of consciousness
- Bradycardia
- Rising BP
- Decreasing O2 sats
- Neurological signs
- Abnormal pupil responses
- Abnormal posturing
What do you do if you suspect DKA cerebral oedema?
⇒ Get help!
⇒ Reduce fluids by 1/3
⇒ IV Mannitol 0.25-1g / kg given over 20 min
⇒ Repeat again after 2 hours
How do you differentiate between the 1st presentation of T1 and T2 DM?
⇒ Islet cell antibodies will be found in the blood of a T1DM patient
What is part of the yearly screening for T1DM patients? When does this commence?
From age 12: • Coeliac • Thyroid function • Urine (microalbuminuria) • Cholesterol and lipid levels (fasting test) • HbA1c (35-45 is aim) • Fundoscopy • Feet filament test • Height and weight
Name 2 useful apps for management of DM
- Carbs & Cals
* MyFitnessPal
Describe how T1DM affects pregnancy
- High glucose acts as a teratogen
- Badly controlled diabetes can lead to deformities in the fetus
- Macrosomic babies-> shoulder dystocia
- Hypoglycaemia after birth is common (baby is used to a sugary environment so has high production of insulin as base level)
What is Maturity Onset Diabetes of the Young?
- 1-2% of diabetes cases
- Autosomal dominant mutation, strong family history of diabetes
- Not type 1 or type 2
- Insulin independence, absence of pancreatic autoantibodies (not type 1DM)
- Detectable endogenous insulin production (C-peptide measurable in hyperglycaemia) (not type 1DM)
- Lack of obesity, normal TG levels, high HDL levels (not type 2DM)
- Diabetes develops before the age of 25
What mutations might cause maturity onset diabetes of the young
HNF1A, Glucokinase, HNF1B (including Renal Cysts and Diabetes (RCAD)), HNF4A, IPF1, NEUROD1
Treatment of maturity onset diabetes of the young?
Usually insulin not used, instead sulphonylureas are used (eg gliclazide)
How can you kill a diabetic?
• Not recognising DKA
Hypoglycaemia
• Hypokalamia (when treating DKA)
• Cerebral oedema (when treating DKA)
How is the hypothalamus involved in thyroid hormone?
Hypothalamus production of TRH is influenced by negative feedback from circulating levels of TSH and T3 & T4
TRH (thyroid releasing hormone) from hypothalamus causes anterior pituitary gland (thyrotrophs) to produce TSH.
Where is TSH made?
Anterior pituitary gland, from thyrotrophs
What is the active form of thyroid hormone?
T3
Action of T3 & T4?
T3 +T4 ↑ basal metabolic rate, ↑O2 consumption
↑ cardiac output ↑ventilation ↑thermogenesis
↑number of ß-receptors in tissues-> ↑sympathetic function
Describe thyroid hormone physiology in fetus
In fetus it is responsible for brain, bone and lung maturation
The fetal hypothalamic-pituitary-thyroid system develops independently of the mother’s pituitary-thyroid axis.
How is the thyroid gland formed?
When does it begin to function?
During embryogenesis, primordial thyroid cells arise from epithelial cells on the pharyngeal floor; they then migrate caudally to fuse with the ventral aspect of the fourth pharyngeal pouch by 4 weeks gestation. The thyroid continues to develop anteriorly to the third tracheal cartilage.
Thyroglobulin is produced by 8 weeks gestation.
Trapping of iodine occurs by 10-12 weeks’ gestation, followed by the synthesis of iodothyronines.
Colloid formation and pituitary secretion of TSH occur by 12 weeks gestation.
What is congenital hypothyroidism?
What’s seen on blood tests?
Usually due to agenesis, dysplasia, or ectopy of the thyroid (75%).
Also caused by autosomal recessive defects in the organification of iodine (thyroid hormone synthesis) and defects in other enzymatic steps in T4 synthesis and release
Less/no T3&T4 produced by newborn.
Decreased negative feedback on TSH so really high TSH but low T3/T4.
Signs of congenital hypothyroidism
- Prolonged gestation
- Elevated birth weight
- Delayed stooling after birth, constipation
- Prolonged indirect jaundice
- Poor feeding, poor management of secretions, noisy respirations
- Large fontanels
- Myxoedema of the eyelids, hands, and/or scrotum
- Large protruding tongue (secondary to accumulation of myxoedema in the tongue)
- Goitre
- Hypothermia
- Decreased activity level
- Hoarse cry
- Umbilical hernia
When is congenital hypothyroidism usually diagnosed?
From the Guthrie heel-prick test day 5-8
Management of congenital hypothyroidism
- Levothyroxine 10 to 15 μg/kg/day within 2 weeks of life
- If untreated and severe-> cretinism and mental retardation
- Once treatment is initiated for congenital hypothyroidism, serum total T4 and TSH concentrations should be assessed monthly until the total or free T4 levels normalise, then every 3 months until the patient is aged 3 years. Thereafter, total T4 and TSH should be measured every 6 months.
What is the most common cause of acquired hypothyroidism in children?
Autoimmune Hashimoto’s thyroiditis
Signs and symptoms of acquired hyopthyroidism (10)
- Asymptomatic goitre
- Slow growth, delayed puberty
- Delayed osseous maturation
- Increased weight (obesity) despite decreased appetite
- Lethargy
- Dry skin, and puffiness
- Sleep disturbance, typically obstructive sleep apnea
- Cold intolerance, constipation
- Pseudoprecocious puberty (testicular enlargement in boys or early breast development or onset of vaginal bleeding in girls) & galactorrhoea
Differential diagnoses to hypothyroidism
- Constipation
- Short Stature
- Constitutional Growth Delay
- Hyposomatotropism
- Malnutrition
- Paediatric Depression
- Paediatric Growth Hormone Deficiency
- Paediatric Malabsorption Syndromes
What is hyperthyroidism? Usual cause in children
Overactive thyroid gland leading to ↑basal metabolic rate
Rare in children, usually caused by Grave’s disease.
Causes of hyperthyroidism
Graves disease Toxic adenoma, toxic nodular goitre Pituitary causes of thyrotoxicosis in childhood: Pituitary adenoma Pituitary resistance to T4
What is Grave’s disease? Signs? What is seen on blood tests?
- Antibody to infection mimics TSH & stimulates thyroid hormone production & antibodies against IGFs
- Large smooth thyroid
- Pretibial myxoedema (rare in children)
- Exophthalmus (eye popping)
- Ophthalmopathy (hyaluronan, GAGs, collagen and T&B cell infiltrates in periorbital space-> proptosis, chemosis, lid retraction, oedema)
- Low TRH and TSH, really high T3 & T4
Explain how toxic nodules work in hyperthyroidism
- Rare in children and masses are usually non functional
- Growth of nodules of thyroid tissue constantly producing T3 & T4 without TSH input
- T3 & T4 constantly produced at higher than normal levels
- Normal thyroid tissue no longer stimulated by TSH as it is above the set point
- Bumpy nodular thyroid
- Hot points on radioactive scan
Treatment of hyperthyroidism
- Surgery + replacement thyroxine
- Radioactive iodine + replacement thyroxine
- CARBIMAZOLE (anti-thyroid)
- PROPRANOLOL (treats symptoms)
- WARFARIN (in case of AF)
- PREDNISOLONE (for exophthalmos)
Function of aldosterone
- Sodium down, potassium up or hypotension-> juxtaglomerular cells -> RAAS
- Aldosterone works at distal convoluted tubule, sodium and water reabsorption (in exchange for either K+ or H+)
What is Conn’s syndrome?
Overproduction of aldosterone due to hyperactivity of the zona glomerulosa cells of the adrenal glands
Physiology of Conn’s syndrome?
Hyperactivity of the zona glomerulosa cells of the adrenal glands
• Retention of sodium
• Loss of potassium (hypokalaemia, weakness, lethargy)
• Alkalosis
• Hypertension
What mimics Conn’s?
Secondary hyperaldosteronism
Due to excessive RAAS activation
Renal artery stenosis, chronic heart failure and nephrotic syndrome can affect juxtaglomerular cell function and cause increased renin and increased aldosterone
How can you differentiate between Conn’s and 2º hyperaldosteronism?
• Aldosterone:renin blood test ↑aldosterone: ↡renin shows Conn’s
↑renin ↑aldosterone shows 2º hyperaldosteronism
• Saline suppression test
Expanded volume ↡aldosterone and renin levels in 2º hyperaldosteronism
In Conn’s, aldosterone not suppressed
Treatment of Conn’s
- Spironolactone (K+ sparing diuretic, anti-aldosterone)
* Adrenalectomy if unilateral
Name the layers of the adrenal gland
GFR Capsule (outside) Zona Glomerulosa (aldosterone) Zona fasciculata (cortisol) Zona Reticularis (androgens) Medulla (adrenaline)
What is hypoadrenalism?
= Deficiency of adrenal cortical hormones (cortisol + aldosterone)
Causes of hypoadrenalism?
- TB, HIV
- Metastatic tumour/lymphoma
- Addison’s disease
- Haemorrhage of adrenals (meningococcal septicaemia) or infarction
Signs and symptoms of hypoadrenalism
- Tiredness and weakness
- GI disturbance (abdo pain)
- Weight loss
- Postural hypotension + dizziness (due to low aldosterone) + fainting
- Hypoglycaemia (low cortisol) -> confusion-> convulsions -> death
- Hyperkalaemia (low aldosterone)
- Pigmentation (loss of negative feedback for melanocyte stimulating hormone)
- Other autoimmune disorders?
- Calcification of pinna of the ear (rare)
How is hypoadrenalism diagnosed?
- Hypercalcaemia, eosinophilia, hypoglycaemia, hyperkalaemia, hyponatraemia, metabolic acidosis
- Antibodies (adrenal cortex Ab, 21-hydroxylase antibodies)
- ACTH stimulation test (serum cortisol should risk, no rise = addison’s)
- Will rise in 2º adrenal failure (as bypasses the failing pituitary)
Treatment of hypoadrenalism
- Cortisol replacement (HYDROCORTISONE) 3xdaily
- Aldosterone replacement (FLUDROCORTISONE) 1xdaily
- DHEA replacement?
Signs and symptoms of Cushing’s
Moon face Buffalo hump Thin skin Easy bruising Central obesity Muscle weakenss Osteoporosis Ulcers Purple striae Enlarged heart Hypertension
What does cortisol do? (4)
- ↑lipolysis + mobilisation of fatty acids
- ↑Protein breakdown + mobilisation of amino acids
- ↑gluconeogenesis, glycogenesis and glycogen storage (prepare for starvation)
- Immunosuppression and anti-inflammatory actions
What is the difference between Cushing’s syndrome and Cushing’s disease?
Cushing’s syndrome
=Excessive cortisol release
Cushing’s disease = pituitary tumour that raises ACTH levels
What are the 5 causes of Cushing’s syndrome?
1) Tumour of adrenal gland
2) Pituitary tumour (↑ACTH) = Cushing’s disease
3) Hypersecretion of CRH from hypothalamus
4) Overadministration of glucocorticoid drugs (asthma, Crohn’s, organ transplantation)
5) Cancer-> ectopic ACTH production (eg small cell lung cancer)
How do you diagnose the cause of Cushing’s syndrome?
3 tests:
Dexamethasone suppression test (adrenal tumour/pituitary tumour/ectopic ACTH or not)
Baseline cortisol (cushing’s syndrome or not)
Petrosal sinus sampling (pituitary/ectopic ACTH)
Explain different results of Dexamethasone suppression test
- Give cortisol analogue at midnight, next day lots of steroid around but no ACTH and no cortisol (-ve feedback)
- If cortisol <40 normal
- If cortisol >40 and ACTH low = abnormal as cortisol has been produced without ACTH stimulation due to adrenal tumour
- In pituitary tumours the dexamethasone doesn’t reach the higher set point of the abnormal pituitary cells so ACTH and cortisol still produced. Would respond to higher dexamethasone levels
- In ectopic ACTH production, ACTH is really high + doesn’t suppress even with higher dexamethasone
Explain the different results from baseline cortisol tests
- From 24hr urine sample (high-> cushing’s)
* Salivary cortisol. Loss of diurnal variation-> cushing’s
Explain the different results from pertrosal sinus sampling
- ACTH concentration in arm and sinus = same = ectopic ACTH cancer
- ACTH concentration very high in sinus and low in arm = pituitary tumour
Treatment of Cushing’s
- Block cortisol production (METYRAPONE, KETOCONAZOLE, MITOTANE)
- Pituitary tumour excision (trans-sphenoidal hypophysectomy) +/- radiotherapy
- Ectopic ACTH usually palliative (surgery, chemo)
- Adrenal tumour excision
What is a phaeochromocytoma?
- Adrenaline and noradrenaline (NA) secreting tumour of the chromaffin cells of the adrenal medulla
- Produces massive spikes of adrenaline with non-physiological causes & no external stimuli
What is a tumour of the chromaffin cells called?
Phaechromocytoma
Signs and symptoms of phaemochromocytoma
- Overwhelming sense of doom
- Startled, anxiety
- Turns and headaches
- Sweating
- Tachyarrhythmias
- Hypertension (due to α receptors)
- Tremor
- Weakness
- Epigastric pain
- Constipation (Ileus)
- Cardiomyopathy
- Neurofibromatosis?
Diagnosis of phaeochromocytoma
CLONIDINE suppression test (α-2 agonist)
Treatment of phaeochromocytoma
- α blockade (PHENOXYBENZAMINE)
- Then ß-blockers for relaxation of smooth muscle and decrease HR (PROPRANOLOL)
- Surgical excision of tumour
Prognosis of phaeochromocytoma
Death due to coronary artery dissection due to spiked BP is common
What is CAH?
Congenital adrenal hyperplasia
What causes CAH? What does it cause?
= Deficiency in adrenal enzyme 21hydroxylase
↡ mineralocorticoids, ↡glucocorticoids
Excess androgens (don’t need 21-hydroxylase for androgens)
Ambiguous genitalia at birth, virilisation
What enzyme is involved in CAH?
21-hydroxylase
When mother is an insulin dependent diabetic, what is the baby more at risk of?
Macrosomia (shoulder dystocia) Hypoglycaemia RDS Polycythaemia Congenital malformations Hypertrophic cardiomyopathy
3 pathological causes of obesity
Prader-Willi syndrome
Cushing’s
Hypothyroidism
Signs of CAH
Hyponatraemia
Hyperkalaemia
Hypoglycaemia
