Diabetes and Endocrine Flashcards
Classification of diabetes
Type 1: autoimmune beta cell destruction
Type 2: insulin resistance followed by beta cell failure
Maturity onset diabetes of the young
Medications .e.g. corticosteroids
Pancreatic insufficiency .e.g. cystic fibrosis, thalassaemia
Endocrine disorder .e.g. Cushing
Genetic/chromosomal syndromes .e.g. Downs, Turners
Neonatal: transient and permanent
Gestational diabetes
Presentation diabetes
Excessive drinking (polydipsia) Polyuria Weight loss Enuresis Skin sepsis Candida and other infections
Presentation DKA
Smell of acetone on breath Vomiting Dehydration Abdominal pain Hyperventilation (Kussmaul breathing) Hypovolaemic shock Drowsiness Coma and death
Aetiology T1DM
Molecular mimicary between environmental trigger and antigen on beta-cell surface of pancreas
Possible triggers: enteroviral infections, cow’s milk protein, overnutrition
Autoimmune destruction of the pnacreatic B cells causing insulin deficiency
T1DM associated diseases
Hypothyroidism
Addisons disease
Coeliac disease
Rheumatoid arthritis
Markers of beta-cell destruction
Antibodies to glutamic acid decaroxylase, islet cells, insulin
Diagnosis T1DM
Raised random blood glucose >11.1mmol/L Glycosuria Ketosis Fasting blood glucose >7mmol/L Raised HbA1c
Features T2DM
Severely obese children Family history PCOS in females Acanthosis nigrican: velvety dark skin in armpits or neck Skin tags
Patient education T1DM
Basic pathophysiology Insulin injection tech and sites blood glucose monitoring to allow insulin adjustment Blood ketones when unwell healthy diet: carb counting Regular exercise Insulin sick day and exercise adjustment Recognition of hypoglycaemia How to get advice 24/7 psychological impact of life long condition
Insulin
All insulin used in children is human
Concentration 100units/ml (U-100)
Types:
-rapid acting insulin analogues .e.g. insulin lispro
-long acting insulin analogues .e.g. levemir, lantus
-short acting soluble human regular insulin
-Intermediate acting
- predermined mixed preparations with 25-30% short acting component
Short acting insulin properties
Effect within 30-60m Peak effect 2-4h Duration 8h Given 15-30m before food E.g. Actrapid, Humulin S
Intermediate acting insulin properties
Onset 1-2h
Peak 4-12h
Isophane insulin: insulin and protamine .e.g. insulatard, Humulin I
Insulin injection technique
Subcutaneous injection
Anterior and lateral aspect of the thigh, buttocks and abdomen
Rotation of sites
Cx of repeated site use: lipohypertropy, lipoatrophy
Skin gentley pinched and insulin injected at 45’
Long needles/high angle causes painful bruised IM injection
Shallow dermal injections cause scarring
Factors increase blood glucose
Insufficient insulin Food especially carbohydrates Illness Menstruation (shortly before onset) Growth hormone Corticosteroids Sex hormones at puberty Stress
Factors decreasing blood glucose
Insulin Exercise Alcohol Some medications Marked anxiety/excitement Hot weather
Diet with T1DM
Match insulin dose to carbohydrate intake
High complex carbohydrate
Modest fat content <30% calories
High in fibre: sustained release of glucose
Monitoring blood glucose
Pre-meal 4-7mmol/L target
Diary of insulin doses and blood glucose
Typically BM taken before breakfast, lunch, dinner, bed
During illness, change in routine >5 tests per day
Blood ketone testing during illness or with poor control
HbA1c shows control over previous 6-12w
-misguiding in reduced rbc lifespan e.g. sickle cell, thalassaemia
Presentation hypoglycaemia
Hunger Tummy ache Pallor Irritability/ Unreasonable behaviour Sweatiness Feeling faint/dizzy/wobbly Seizure/coma
Mx Hypoglycaemia
Administration of easily absorbed gluycose .e.g. glucose tablets, sugary drink
Oral glucose gels on buccal mucosa
Glucagon injection kit for severe hypo with reduced GCS- IM glucagon
Ix DKA
Blood glucose <11.1mmol/L
Blood ketones >3mmol/L
Urea, electrolytes, creatinine (dehydration)
Blood gas analysis (severe metabolic acidosis)
Blood and urine cultures (indicated if infection underlying cause)
Cardiac monitoring: T wave changes in hypokalaemia
Weight (assessing dehydration)
DKA can cause a neutrophilia
Mx DKA
Fluids 0.9% saline 10ml/Kg in shock Gradual correction of dehydration over 24hrs Insulin infusion Potassium Identify underlying cause
Long term Cx T1DM
hypertension coronary heart disease cerebrovascular disease retinopathy nephropathy neuropathy
Problems with diabetes control
Eating too many sugary foods Infrequent or unreliable blood glucose testing Illness Exercise Eating disorders Family disruption Inadequate family motivation
Annual assessment diabetes
Normal growth and pubertal development Blood pressure check for hypertension Renal disease: screening for microalbuminuria Circulation: pulse and sensation Eyes: retinopathy and cataracts Feet: good foot care Screening for caeliac (only on presentation), thyroid Annual flu vaccination
Diabetic changes in puberty
Growth hormone, oestrogen and testosterone antagonise insulin action
Increase in insulin requirement during puberty to 2U/Kg/day
Increase marked during morning due to peak growth hormone secretion overnight
Ix Hypoglycaemia
Lab blood glucose
Growth hormone, IGF-1, cortisol, insulin, C-peptide, fatty acids, ketones, glycerol, branched-chain amino acids, acylcarnitine profile, lactate, pyruvate
Urine organic acids
Clinical features hypoglycaemia
Sweating
Pallor
CNS signs of irritability, headache, seizure, coma
Causes hypoglycaemia
Excess exogenous insulin beta cell tumours/disorders Drug induced .e.g. suphonylurea Autoimmune Beckwith syndreom Galactosaemia Liver disease Ketotic hypoglycaemia of childhood Inborn errors of metabolism Hormonal deficiency Leucine sensitivity Fructose intolerance Maternal diabetes Hormonal deficiency Aspirin/alcohol poisoning
Features ketotic hypoglycaemia
Young children readily become hypoglycaemic following short periods of starvation Often thin Low insulin levels resolves spontaneously in later life Prevented by regular glucose intake
Features transient neonatal hypoglycaemia
Exposure high levels of insulin in utero
Features hypoglycaemic hyperinsulinism of infancy
Recurrent severe neonatal hypoglycaemia Rare disorder of infancy dysregulation of insulin release by islet cells Profound nonketotic hypoglycaemia Localised lesions in the pancreas
Mx hypoglycaemic hyperinsulinism
High concentration glucose solutions
Diazoxide maintains safe blood glucose
Partial resection/total pancreatectotmy
Mx Hypoglycaemia
IV infusion of glucose (Max 5ml/Kg 10% glucose bolus)
-Excess volume can cause cerebral oedema
Oral glucose
IM glucagon
Corticosteroids in pituitary or adrenal dysfunction
Thyroid Physiology Neonatal Period
Small amount of thyroxine transfered from mother
Fetal thyroid produces reverse T3 (inactive T3 derivative)
After burth: surge in TSH, T3 and T4
TSH decline to normal adult levels within weeks
Preterm infants have low T4 for first few weeks, with normal TSH
Causes of congenital hypothyroidism
Maldescent of thyroid and athyrosis: remains as lingual mass or uniglobular small gland
Dyshormonogenesis: poor synthesis
Iodine deficiency
TSH deficiency: RARE, associated with pituitary dysfunction
Clinical features congenital hypothyroidism
Usually asymptomatic and identified on screening Falterning growth Feeding problems Prolonged Jaundice Constipation Pale, cold, mottled, dry skin Coarse facies Large tongue Hoarse cry Goitre Umbilical hernia Delayed development
Clinical features acquired hypothyroid
Females Short stature/poor growth Cold intolerance Dry skin Cool peripheries Bradycardia Thin, dry hair Pale, puffy eyes with loss of eyebrows Goitre Slow releasing reflexes Constipation Delayed puberty/amenorrhea Obesity SUFE Poor concentration Deterioration in school work/ learning difficulty
Mx congenital hypothyroid
Thyroxine started before 2-3w
Lifelong oral replacement of thyroxine
Titration to maintain normal growth
Features Autoimmune thyroiditis
Associated with Downs and Turners, Addisons, autoimmune diseases (vitiligo, rhuematoid arthritis, diabetes mellitus)
Common in females
Delayed bone age
Goitre present (may be physiological in pubertal girls)
Clinical features hyperthyroid
Anxiety, restlessness Increased appetite Sweating Diarrhoea Weight loss Rapid growth in height Advanced bone maturity Tremor Tachycardia, wide pulse pressure Warm, vasodilated peripheries Goitre (bruit) Learning difficulty and behavioural problems Eyes: exopthalmos, oipthalmoplegia, lid retraction, lid lag
Mx hyperthyroid
Carbimazole/propythiouracil: interefer with thyroid hormone synthesis
-risk neutropenia
Beta blockers: symptomatic for anxiety, tremor and tachycardia
Medicine continues for 2y to control thyrotioxicosis
-40-75% relapse
Permanent remission: radioiodine treatment or subtotal thyroidectomy
Causes of congenital pituitary disorders
Structural .e.g. midline defects
Pituitary hypoplasia or aplasia
Causes of acquired pituitary disorders
Brain tumour affecting hypothalamus or pituitary Cranial irradiation Trauma Infection Infiltration .e.g. histiocytosis Structural
Associated disorders hypoparathyroid
DiGeorge
Autoimmune disorders
Addisons Disease
Features of DiGeorge
Thymic aplasia
Defective immunity
Cardiac defects
Facial abnormality
Features pseudohypoparathyroidism
End-organ resistance to parathyroid hormone
PTH normal, serum Ca and PO4 abnormal
Associated abnormality pseudohypoparathyroidism
Short stature Obesity Subcutaneous nodules short 4th metacarpals learning difficulty teeth enamel hypoplasia calcification of basal ganglia
Features pseudopseudohypoparathyroidism
Abnormality associated with pseudohypoparathyroidism
Normal calcium, phosphate and PTH
Mx hypocalcaemia
IV calcium gluconate 10% diluted
Oral calcium and vitamin D anaolgues
Monitoring urine calcium excretion
Hyperparathyroidism features
High calcium Constipation Anorexia Lethargy Behavioural effects Polyuria Polydipsia Bony erosions of phalanges
Associated conditions hyperparathyroidism
Williams syndrome
Adenomas
Multiple endocrine neoplasia syndrome
Mx hypercalcaemia
Rehydration
Diuretics
Bisphosphonates
Features congenital adrenal hyperplasia
Virilisation of external genitalia in females -clitoral hypertrophy -fusion of labia In males: -penis enlargment -pigmentation of scrotum Salt losing adrenal crisis Tall stature and precocious puberty
Features salt-losing adrenal crisis
80% of males 1-3w old Vomiting Weight loss Hypotonia Circulatory collapse
Pathology congenital adrenal hyperplasia
Insufficient cortisol and mineralcorticoid secretion
21-hydroxylase deficiency
All products make excessive quantities of testosterone in absence of other pathways
Psotive feedback increases cholesterol synthesis
Dx congenital adrenal hyperplasia
Raised levels of metabolic precursor 17a-hydroxy-progesterone in blood In salt losers: -Low plasma sodium -High plasma potassium -Metabolic acidosis -Hypoglycaemia
Mx congenital adrenal hyperplasia
Corrective surgery to external genitalia within 1y
-possibly delay until after puberty for cliteral hypertrophy
Salt losing crisis: NaCl, glucose, hydrocortisone IV
Lifelong glucocorticoids to suppress ACTH
Monitoring of growth, skeletal maturity, plasma androgens
Mineralcorticoids in salt loss with slow weaning
Additional hormone replacement in illness or surgery
Cx hormone replacement congenital adrenal hyperplasia
insufficient: rapid initial growth, skeletal maturation, detrimental to final height
Excessive: skeletal delay, slow growth
Causes Addisons
Autoimmune process Haemorrhage/infection X linked adrenoleucodystrophy (rare) TB secondry to pituitary dysfunction/corticosteroid therapy
Features of adrenal insufficiency
Hyponatraemia Hyperkalaemia Hypoglycaemia Dehydration Hypotension Growth failure Circulatory collapse Vomiting Lethargy Brown pigmentation: gums, scars, skin creases
Dx Adrenal insufficiency
Hyponatreamia with hyperkalaemia with metabolic acidosis and hypoglycaemia
Low plasma cortisol and high ACTH
Synacthen test: cortisol remains low
Mx Adrenal insuffiency
Adrenal crisis: IV saline, glucose, hydrocortisone
Glucocorticoid and mineralcorticoid replacement
Increase (x3) dose of glucocorticoid during illness/surgery
Parental education IM hydrocortison injection
Features Cushing Syndrome
Growth failure/short stature Face and trunk obesity Red cheeks Hirsutism Striae Hypertension Bruising Carbohydrate intolerance Muscle wasting and weakness Osteopenia Psychological problems
Causes of cushings
Usually S/E long term glucocorticoids
-reduced by morning meds on alternate days
Pituitary adenoma
Ectopic ACTH producing tumours
Adrenocorticoid tumours (occurs with virilisation)
Ix Cushing Syndrome
Loss of normal cortisol diurnal variation
High midnight conc
High 24hr urine free cortisol
Failure to suppress 9am cortisol after night time dexamethaone
MRI brain and abdomen (tumour)
Causes Disorders of sex development
Congenital adrenal hyperplasia: excessive androgens causing virilisation of female
Androgen insensitivity syndrome
5a-reducatase deficieny: poor conversion to testosterone
Prada-will: gonadotrophin insufficiency
Ovotesticular DSD: XX ad XY cells present allows development of both tissues
