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Symptoms and Signs – Differential Diagnosis of Hypoalbuminaemia
Reduced Synthesis
Malnutrition
Liver disease
Acute phase reaction
Increased Loss
Sample from IV infusion arm, pregnancy
Protein-losing enteropathy (coeliac disease, IBD, sprue, Whipple's disease, intestinal lymphoma, intestinal lymphangiectasia)
Nephrotic syndrome
Haemodilution
Burns
Bullous skin lesions
Rare
Familial idiopathic dysproteinaemia
Reduced Synthesis
Malnutrition
Liver disease
Acute phase reaction
Increased Loss
Sample from IV infusion arm, pregnancy
Protein-losing enteropathy (coeliac disease, IBD, sprue, Whipple's disease, intestinal lymphoma, intestinal lymphangiectasia)
Nephrotic syndrome
Haemodilution
Burns
Bullous skin lesions
Rare
Familial idiopathic dysproteinaemia
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Symptoms and Signs – Differential Diagnosis of Hypocalcaemia
Vitamin D resistance
Vitamin D deficiency
Surgical (after thyroidectomy or parathyroidectomy)
Respiratory alkalosis
Renal failure
reduced Mg2+, Fe2+ overload, increase Cu2+ (Wilson's disease)
Reduced Dietary intake/malabsorption
Pseudohypoparathyroidism (resistance to PTH)
Pancreatitis (acute)
Others
Liver disease
Lack of sunlight
Increase Phosphate: chronic renal failure, phosphate therapy
Iatrogenic: bisphosphonates, calcitonin, citrated blood (massive transfusion)
Hypoparathyroidism
Hypoalbuminaemia
Congenital (DiGeorge's syndrome)
Autoimmune
Artifact (collecting blood into an EDTA tube)
Anticonvulsants (e.g. phenytoin)
Vitamin D resistance
Vitamin D deficiency
Surgical (after thyroidectomy or parathyroidectomy)
Respiratory alkalosis
Renal failure
reduced Mg2+, Fe2+ overload, increase Cu2+ (Wilson's disease)
Reduced Dietary intake/malabsorption
Pseudohypoparathyroidism (resistance to PTH)
Pancreatitis (acute)
Others
Liver disease
Lack of sunlight
Increase Phosphate: chronic renal failure, phosphate therapy
Iatrogenic: bisphosphonates, calcitonin, citrated blood (massive transfusion)
Hypoparathyroidism
Hypoalbuminaemia
Congenital (DiGeorge's syndrome)
Autoimmune
Artifact (collecting blood into an EDTA tube)
Anticonvulsants (e.g. phenytoin)
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Symptoms and Signs – Differential Diagnosis of Hypochromia
Iron deficiency anaemia
Sideroblastic anaemia
Thalassaemia
Iron deficiency anaemia
Sideroblastic anaemia
Thalassaemia
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Symptoms and Signs – Differential Diagnosis of Hypogammaglobulinaemia
Congenital
X-linked, or as part of a combined immunodeficiency state
Acquired
Leukaemia (CLL)
Lymphoma
Marrow hypoplasia, myeloclerosis
Myeloma
Nephrotic syndrome, malnutrition, malabsorption, protein-losing enteropathy
Uraemia, steroids, severe infections
Congenital
X-linked, or as part of a combined immunodeficiency state
Acquired
Leukaemia (CLL)
Lymphoma
Marrow hypoplasia, myeloclerosis
Myeloma
Nephrotic syndrome, malnutrition, malabsorption, protein-losing enteropathy
Uraemia, steroids, severe infections
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Symptoms and Signs – Differential Diagnosis of Hypoglycaemia
Addison's disease
Alcohol
Excess insulin (or diabetics not having a snack after insulin injection), sulphonylureas, salicylate, pentamidine, quinine
Liver failure
lnsulinomas, hepatomas, sarcomas
Malaria
Post-gastrectomy
Renal failure
Addison's disease
Alcohol
Excess insulin (or diabetics not having a snack after insulin injection), sulphonylureas, salicylate, pentamidine, quinine
Liver failure
lnsulinomas, hepatomas, sarcomas
Malaria
Post-gastrectomy
Renal failure
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Symptoms and Signs – Differential Diagnosis of Hypogonadism
Female
1° hypogonadism (hypergonadotrophic)
Gonadal dysgensis
The genotype may be XO (Turner's syndrome), XX, XY (with disruption of the SRY
gene on Y chromosome or the downstream pathway), XO/XY or XO/XX
(mosaicism)
Gonadal damage
Infection (e.g. mumps)
Autoimmune
Surgery (pelvic)
Radiation
Chemotherapy, e.g. cyclophosphamide
Genetic mutations
LH/FSH beta subunit, LH receptor, FSH receptor, enzymes involved in oestrogen
synthesis (e.g. 17-hydroxylase deficiency), galactosaemia
2° hypogonadism (hypogonadotrophic)
Hypopituitarism
Pituitary tumour/surgery/radiation, infiltrations (e.g. lymphoma, sarcoidosis,
Langerhans cell histiocytosis, lymphocytic hypophysitis)
Functional/hypothalamic, e.g. strenuous exercise, weight loss
Congenital GnRH deficiency (when associated with anosmia: Kallmann's
syndrome), other genetic mutations, e.g. DAX1 (associated with congenital
adrenal hypoplasia), HESX1 (associated with septo-optic dysplasia), isolated LH
or FSH deficiency
Other causes of hypopituitarism: vascular/infection, etc. (See Hypopituitarism)
Hyperprolactinaemia
Systemic diseases
Cystic fibrosis
Crohn's disease/ulcerative colitis, malnutrition of any cause
Cirrhosis
Chronic renal failure
Thalassaemia: repeated blood transfusions leads to haemosiderosis and
hypothalamic dysfunction
Rare causes
Laurence-Moon-Beidl syndrome
Prader-Willi syndrome
Male
1° hypogonadism (hypergonadotrophic):
Gonadal dysgensis
Klinefelter's syndrome (XXY): testes are small and firm with dysgenetic
seminiferous tubules
Cryptorchism: undescended testes
Anorchia: Vanishing testis syndrome: testicular tissue present in fetal life but
absent in the adult
Gonadal damage
Infection (e.g. mumps, echovirus, group B arbovirus, lymphocytic
choriomeningitis),
Trauma, torsion
Autoimmune
Surgery (orchidectomy)
Radiation
Drugs/toxins: cyclophosphamide
Alcohol, marijuana, heroin: l testosterone levels
Genetic mutations
LH/FSH b subunits, LH receptor, FSH receptor, defects in enzymes involved in
testosterone synthesis, myotonic dystrophy
2° hypogonadism (hypogonadotrophic):
Hypopituitarism
Pituitary tumour/surgery/radiation/infiltrations; See Hypopituitarism
Congenital GnRH deficiency (idiopathic hypogonadotrophic hypogonadism)
(Kallmann's syndrome: GnRH deficiency+ one or more non-gonadal
congenital abnormalities e.g. anosmia), other genetic mutations, e.g. DAX1,
HESX1, Prop-1
Female
1° hypogonadism (hypergonadotrophic)
Gonadal dysgensis
The genotype may be XO (Turner's syndrome), XX, XY (with disruption of the SRY
gene on Y chromosome or the downstream pathway), XO/XY or XO/XX
(mosaicism)
Gonadal damage
Infection (e.g. mumps)
Autoimmune
Surgery (pelvic)
Radiation
Chemotherapy, e.g. cyclophosphamide
Genetic mutations
LH/FSH beta subunit, LH receptor, FSH receptor, enzymes involved in oestrogen
synthesis (e.g. 17-hydroxylase deficiency), galactosaemia
2° hypogonadism (hypogonadotrophic)
Hypopituitarism
Pituitary tumour/surgery/radiation, infiltrations (e.g. lymphoma, sarcoidosis,
Langerhans cell histiocytosis, lymphocytic hypophysitis)
Functional/hypothalamic, e.g. strenuous exercise, weight loss
Congenital GnRH deficiency (when associated with anosmia: Kallmann's
syndrome), other genetic mutations, e.g. DAX1 (associated with congenital
adrenal hypoplasia), HESX1 (associated with septo-optic dysplasia), isolated LH
or FSH deficiency
Other causes of hypopituitarism: vascular/infection, etc. (See Hypopituitarism)
Hyperprolactinaemia
Systemic diseases
Cystic fibrosis
Crohn's disease/ulcerative colitis, malnutrition of any cause
Cirrhosis
Chronic renal failure
Thalassaemia: repeated blood transfusions leads to haemosiderosis and
hypothalamic dysfunction
Rare causes
Laurence-Moon-Beidl syndrome
Prader-Willi syndrome
Male
1° hypogonadism (hypergonadotrophic):
Gonadal dysgensis
Klinefelter's syndrome (XXY): testes are small and firm with dysgenetic
seminiferous tubules
Cryptorchism: undescended testes
Anorchia: Vanishing testis syndrome: testicular tissue present in fetal life but
absent in the adult
Gonadal damage
Infection (e.g. mumps, echovirus, group B arbovirus, lymphocytic
choriomeningitis),
Trauma, torsion
Autoimmune
Surgery (orchidectomy)
Radiation
Drugs/toxins: cyclophosphamide
Alcohol, marijuana, heroin: l testosterone levels
Genetic mutations
LH/FSH b subunits, LH receptor, FSH receptor, defects in enzymes involved in
testosterone synthesis, myotonic dystrophy
2° hypogonadism (hypogonadotrophic):
Hypopituitarism
Pituitary tumour/surgery/radiation/infiltrations; See Hypopituitarism
Congenital GnRH deficiency (idiopathic hypogonadotrophic hypogonadism)
(Kallmann's syndrome: GnRH deficiency+ one or more non-gonadal
congenital abnormalities e.g. anosmia), other genetic mutations, e.g. DAX1,
HESX1, Prop-1
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Symptoms and Signs – Differential Diagnosis of Hypokalaemia
Gastrointestinal loss
Vomiting, diarrhoea, villous adenoma, VIPoma, fistulae, ileostomies
Renal loss
Excess mineralocortcoids (--potassium excretion)
Hyperaldosteronism
Increased Glucocorticoids: Cushing's syndrome, liquorice (inhibits 11 [3-hydroxysteroid
dehydrogenase and l glucocorticoid metabolism), 11 [3-hydroxysteroid
dehydrogenase deficiency
Congenital adrenal hyperplasia (11 [3-hydroxylase and 17 cr-hydroxylase
deficiency)
Increased Na+ delivery to distal nephron (-> i Na+ absorption and K' secretion)
Osmotic diuresis (e.g. in glycosuria)
Diuretics: thiazides and loop diuretics (also T aldosterone secretion)
Bartter's syndrome, Gitelman's syndrome
Others
Hypomagnesaemia
Renal tubular acidosis (type I & II)
Renal tubular damage
Liddle's syndrome (autosomal dominant condition, primary T in collecting tubule
sodium reabsorption and often potassium secretion)
Redistribution into the cells
Insulin, beta-agonists, alkalosis
Gastrointestinal loss
Vomiting, diarrhoea, villous adenoma, VIPoma, fistulae, ileostomies
Renal loss
Excess mineralocortcoids (--potassium excretion)
Hyperaldosteronism
Increased Glucocorticoids: Cushing's syndrome, liquorice (inhibits 11 [3-hydroxysteroid
dehydrogenase and l glucocorticoid metabolism), 11 [3-hydroxysteroid
dehydrogenase deficiency
Congenital adrenal hyperplasia (11 [3-hydroxylase and 17 cr-hydroxylase
deficiency)
Increased Na+ delivery to distal nephron (-> i Na+ absorption and K' secretion)
Osmotic diuresis (e.g. in glycosuria)
Diuretics: thiazides and loop diuretics (also T aldosterone secretion)
Bartter's syndrome, Gitelman's syndrome
Others
Hypomagnesaemia
Renal tubular acidosis (type I & II)
Renal tubular damage
Liddle's syndrome (autosomal dominant condition, primary T in collecting tubule
sodium reabsorption and often potassium secretion)
Redistribution into the cells
Insulin, beta-agonists, alkalosis
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Symptoms and Signs – Differential Diagnosis of Hypokalaemia
Gastrointestinal loss
Vomiting, diarrhoea, villous adenoma, VIPoma, fistulae, ileostomies
Renal loss
Excess mineralocortcoids (--potassium excretion)
Hyperaldosteronism
Increased Glucocorticoids: Cushing's syndrome, liquorice (inhibits 11 [3-hydroxysteroid
dehydrogenase and l glucocorticoid metabolism), 11 [3-hydroxysteroid
dehydrogenase deficiency
Congenital adrenal hyperplasia (11 [3-hydroxylase and 17 cr-hydroxylase
deficiency)
Increased Na+ delivery to distal nephron (-> i Na+ absorption and K' secretion)
Osmotic diuresis (e.g. in glycosuria)
Diuretics: thiazides and loop diuretics (also T aldosterone secretion)
Bartter's syndrome, Gitelman's syndrome
Others
Hypomagnesaemia
Renal tubular acidosis (type I & II)
Renal tubular damage
Liddle's syndrome (autosomal dominant condition, primary T in collecting tubule
sodium reabsorption and often potassium secretion)
Redistribution into the cells
Insulin, beta-agonists, alkalosis
Gastrointestinal loss
Vomiting, diarrhoea, villous adenoma, VIPoma, fistulae, ileostomies
Renal loss
Excess mineralocortcoids (--potassium excretion)
Hyperaldosteronism
Increased Glucocorticoids: Cushing's syndrome, liquorice (inhibits 11 [3-hydroxysteroid
dehydrogenase and l glucocorticoid metabolism), 11 [3-hydroxysteroid
dehydrogenase deficiency
Congenital adrenal hyperplasia (11 [3-hydroxylase and 17 cr-hydroxylase
deficiency)
Increased Na+ delivery to distal nephron (-> i Na+ absorption and K' secretion)
Osmotic diuresis (e.g. in glycosuria)
Diuretics: thiazides and loop diuretics (also T aldosterone secretion)
Bartter's syndrome, Gitelman's syndrome
Others
Hypomagnesaemia
Renal tubular acidosis (type I & II)
Renal tubular damage
Liddle's syndrome (autosomal dominant condition, primary T in collecting tubule
sodium reabsorption and often potassium secretion)
Redistribution into the cells
Insulin, beta-agonists, alkalosis
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Symptoms and Signs – Differential Diagnosis of Hypomagnesaemia
Renal losses: Diuretics (loop and thiazides)
Reduced Intake or GI losses: malnutrition, alcoholism, diarrhoea, malabsorption,
Other: Post-operative, post-parathyroidectomy, pancreatitis (acute), foscarnet
intestinal resection, intestinal fistulae
Drugs: nephrotoxins, e.g. aminoglycosides, amphotericin B, cyclosporine, cisplatin
Diabetes mellitus, hypercalcaemia, hyperthyroidism, hyperaldosteronism, tubular dysfunction (post-acute tubular necrosis, postobstructive diuresis, Bartter's or Gitelman's syndrome)
Alcohol abuse
Renal losses: Diuretics (loop and thiazides)
Reduced Intake or GI losses: malnutrition, alcoholism, diarrhoea, malabsorption,
Other: Post-operative, post-parathyroidectomy, pancreatitis (acute), foscarnet
intestinal resection, intestinal fistulae
Drugs: nephrotoxins, e.g. aminoglycosides, amphotericin B, cyclosporine, cisplatin
Diabetes mellitus, hypercalcaemia, hyperthyroidism, hyperaldosteronism, tubular dysfunction (post-acute tubular necrosis, postobstructive diuresis, Bartter's or Gitelman's syndrome)
Alcohol abuse
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Symptoms and Signs – Differential Diagnosis of Hyponatraemia
Pseudohyponatraemia:
Hyperproteinaemia (e.g. multiple myeloma), hypertriglyceridaemia Hyperglycaemia
Artifactual: taking blood from the arm into which low sodium solution is infused
Hypervolaemic (oedematous) patients:
Cirrohsis, CCF, nephrotic syndrome, renal failure (urine Na+>20)
Hypovolaemic (dehydrated) patients:
Renal loss (urine Na+>20): Diuretics (thiazides), renal tubular acidosis, saltlosing
nephropathy, adrenal insufficiency
Extra-renal loss (urine Na+ <20): diarrhoea, vomiting, burns, pancreatitis< />pan>
Euvolaemic patients:
Hypothyroidism, adrenal insufficiency, SIADH
