Ch 25 - Endocrine & metabolic disorders

Question 1

Classification of Diabetes:

Type 1, 2, 3, 4

Answer 1

1. Autoimmune B cell destruction > insulin deficiency (miost childhood diabetes)
2. Insulin resistance which eventually leads to b cell failure; usually obesity related, +ve FH, Indians
3. Other specific types e.g. MODY (genetic defect in B-cell function due to glucokinase or TF mutations), genetic insulin defects, infections, drugs etc.
4. GDM

Question 2

DM features (3)

Answer 2

1. polyuria + polydipsia
2. weight loss
3. DKA

Question 3

DM Ix (4)

Answer 3

• Random blood sugar > 11.1
• Fasting blood sugar > 7
• Raised HbA1c
• Signs of IR e.g. acanthosis nigricans (dark velvety skin on neck and armpits)
  *

Question 4

DM: management (always education 1st): insulin types (2), admin (2), regimens (2)

Answer 4

Insulin:

• Short acting soluble human insulin e.g. actrapid, Humulin S, novorapid (before meals)
• Intermediate acting e.g. insulatard, humulin I
• Long acting e.g. Lantus

Admin:

• subcut > rotate sites to prevent lipoatrophy
• insulin pumps

Regimens:

• twice daily: mixed in morning & evening (short + intermediate)
• Thrice daily: long acting at night, mixed in morning, short in evening

Question 5

DKA: features (5), management (4)

Answer 5

Features:

• dehydration, vomiting
• sweet smelling breath
• abdo pain
• Kussmaul breathing - due to acidosis
• coma/ shock

Management:

Admit > IV 0.9% saline 10ml/kg (not 20 because of risk of cerebral oedema) + insulin infusion + potassium

Re-establish oral fluids + subcut insulin + treat underlying cause

Question 6

Hypoglycaemia: features (4), Rx (3)

Answer 6

<4 mmol/l:

• hunger, stomache ache, sweatiness, faintess, ‘wobbly legs’
• pallor, irritability, seizures

Rx:

• glucose tabs/ sugary drink if severe give IM glucagon
• Then give complex carb e.g. biscuit/ sandwich

Question 7

Causes of hypoglycaemia (4)

Answer 7

insulin excess:

• e.g. DM
• insulinoma

without hyperinsulinaemia:

• ketotic hypoglycaemia of childhood (due to short period of starvation)
• in born errors of metabolism e.g. glycogen storage disorder
• hormonal def e.g. low GH, low ACTH, CAH, Addison

Question 8

Ix of hypoglycaemia (4), management (2)

Answer 8

GH, IGF-1, cortisol, insulin, C-peptide, ketones, lactate, pyruvate

Rx:

• IV 10% dextrose slowly (prevent cerebral oedema)
• if fail to respond > IM glucagon

Question 9

Congenital hypothyroidism: causes (4), features (5), Ix (1), Rx (1)

Answer 9

Causes: agenesis/maldescent, dyshormonegenesis, idodine def, TSH def

Features: hoarse cry, goitre, coarse facies, cool peripheries, constipation, macroglossia, jaundice

Ix: Guthrie test (raised TSH)

Rx: T4

Question 10

Hyperthyroidism: cause (1), features, Ix (2), Rx (4)

Answer 10

Cause - graves

F - similar to adults; exopthalmus less common

Ix - raised T4/3, low TSH, anti-TPO/ TG abs

Rx:

• propyluracil/ carbimazole
• BB
• thyroidectomy
• radioidoine

Question 11

Hypoparathyroidism: main cause in infants (1), chilren (1)

Pseudohypoparathyroidism: serum Ca/PO4 & PTH (high/low or normal), features (4)

Pseduopseudohypoparathyroidism: serum Ca/PO4 & PTH (high/low or normal)

Answer 11

Usually due to DiGeorge in infants & Addisons in children (high Ca low PO4 > spasms fits, diarrhoea)

Pseudo - end organ resistance to PTH (mutation in signaling molecule) > serum Ca/ PO4 abnormal, PTH may be normal/high. Features include: short stature, obesity, subcut nodules, short 4th/5th metacarpals.

Pseudopseudo - clin features of pseudoHPT, but Ca/PO4/PTH all normal

Question 12

Rx of Hypocalcaemia (3)

Answer 12

• Iv 10% Ca gluconate
• oral Ca
• high dose vit D

Question 13

Hyperparathyroidism features (4), Rx (3)

Answer 13

F: constipation, lethargy, anorexia, polyuria, polydipsia, bony phalange erosions

Rx - bisphosphonates, rehydration, diuretics

Question 14

Adrenal cortical insufficiency: causes (3), features (5)

Answer 14

CAH, Addisons, hypopituitarism

Features

• salt losing crisis
• hypotension
• hypoglycaemia
• chronic ill health + pigmentation
• undescended testicle - CAH

Question 15

Adrenal cortical insufficency: Ix ( 5), Rx (4)

Answer 15

Hyponatremia, hyperkalaemia, acidosis, hypoglycaemia

Low plasma cortisol, high plasma ACTH (unless hypopituitarism), SynACTHen test - plasma cortisol remains low

Rx: crisis > IV saline + glucose + glucocorticoid + mineralocorticoid

Question 16

Cushing syndrome: Causes (3), features (5), Ix (3), Rx (3)

Answer 16

C:

1. long term glucocorticoids e.g. for asthma/ nephrotic syndrome
2. pituitary adenoma
3. ectopic tumours
4. adrenocortical tumour

F: short stature, obesity, striate, HTN, bruishing, mypoathy, osteopenia

Ix:

1. 24hr urinary free cortisol high
2. high dose Dex suppression failure
3. CT/ MRI

Rx:

1. unilateral adrenalectomy
2. radiotherapy
3. transphenoidal resection

Question 17

PKU: cause (1), features (4), Rx (1)

Answer 17

Cause: deficiency in phenylalanine hydroxylase

F: usually picked up in guithrie test; else present within 1st year with developmental delay, musty odour, usually blue-eyed fair haired, seizures, eczema

Rx - restriction of dietary phenylalanine (but enough to ensure neuro development)

Question 18

Homocystinuria: cause (1), features (5), Rx (2)

Answer 18

Cause - cystathionine synthetase def; which results in failure of methionine metabolism > homocysteine accumulation

F - developmental delay, ocular lens subluxation (ectopia lentis), LD, psych disorders, convulsions, marfanoid habitus, thromboembolic episodes, malar flush

Rx: pyridoxine (50% respond) if not > low methionine diet + supplement with cysteine + betanine

Question 19

Tyrosinaemia (type 1): cause, features (2), Rx (2)

Answer 19

Cause - autosomal recessive def in fumarylacetoacetase

F - accumulation of toxic metabolites > liver failure + renal damage > Fanconi syndrome

Rx - NTBC (a drug) which inhbitis enzyme that catabolizes tyrosine so must have a low tyrosine & phenylalanine diet

Question 20

Galactosaemia: definition, features (5), rx(1)

Answer 20

D - Gal-1-PUT deficiency - essential for galactose metabolism

F - so when lactose-containing milk feeds introduced affected infants feed poorly, vomit, develop jaundice, hepatosplenomegaly & liver failure. Cataracts if untreated. LDs even if treated early

M - lactose + galactose free diet for life

Question 21

Familial hypercholesterolaemia: definition, features (3), Ix (1), Rx (2)

Answer 21

D - autosomal dominant disorder due to LDL receptor defect

F - xanthomata on skin + tendon; CHD by 50-60, if homozygous CVD in 2nd decade

Ix - serum cholesterol > 3.3

Rx - statins if LDL high + FH of CVD; fibrates

Question 22

What is Glycogen storage disorder

Answer 22

Recessive disorder whih have specific enzyme defects that prevent mobilization of glucose from glycogen > resulting in abnormal accumulation of glycogen in liver and/or muslce.

Question 23

Glycogen storage disorders: type 1, 2, 3, 5

Answer 23

Type 1 (von Gierke): G6P deficiency > enlarged liver and kidneys (which causes truncal obesity), growth failure, hypoglycaemia, doll facies, hypotrophic muscles (good prognosis)

Type 2 (pompe): lysosomal alpha glucosidase def: hypotonia, cardiomegaly, death from HF. Can be management with enzyme replacement myzozyme

Type 3 (cori): amylo 1,6 glucosidase def: milder features of type 1. managed with high protein diet to prevent growth retardation

Type 5 (mcardle): presentas in childhood, temp weakness, muscle cramps post-exercise, myoglobulinuria