Hormone Physiology in Health and Disease

Acute illness (non-thyroidal illness syndrome / “sick euthyroid”)

Common in hospitalised patients with sepsis, trauma, surgery, or critical illness.
Hormonal profile:
 o ↑ Cortisol – due to stress-induced activation of the HPA axis.
 o ↓ T3 (low total and free T3) with normal or low-normal T4 and TSH → "sick euthyroid" pattern.
 o ↑ Growth hormone, but with hepatic GH resistance, leading to low IGF-1.
 o ↑ Catecholamines and glucagon.
 o Stress hyperglycaemia – due to ↑ cortisol, catecholamines, insulin resistance.
Thyroid hormone replacement is not indicated unless true hypothyroidism is suspected.

Obesity

Hormonal alterations reflect and contribute to insulin resistance and metabolic syndrome.
Endocrine profile:
 o ↑ Leptin – due to increased adipose mass, but with leptin resistance.
 o ↓ GH – obesity suppresses GH secretion; IGF-1 may be low/normal.
 o ↑ Insulin – compensatory hyperinsulinaemia due to peripheral resistance.
 o Altered sex hormones – ↑ oestrogens (aromatisation), ↓ SHBG, ↑ androgens in women.
↑ risk of developing T2DM, PCOS, NAFLD.

Pregnancy
Major changes occur due to placental hormone production and increased metabolic demands.
Hormonal changes:
 o ↑ Oestrogen and progesterone → from placenta.
 o ↑ Cortisol – due to oestrogen-induced ↑ corticosteroid-binding globulin (CBG) and placental ACTH.
 o ↑ Insulin resistance – mediated by hPL (human placental lactogen), cortisol, progesterone.
  → Predisposes to gestational diabetes.
 o ↑ Thyroid-binding globulin (TBG) → ↑ total T3/T4 but normal free T3/T4.
 o Slight ↓ TSH in 1st trimester due to hCG cross-reactivity with TSH receptor.

Ageing
Gradual decline in several endocrine axes with advancing age.
Key changes:
 o ↓ Sex steroids:
  – Men: ↓ testosterone → late-onset hypogonadism.
  – Women: ↓ oestrogen → menopause.
 o ↓ Growth hormone and IGF-1 → contributes to sarcopenia and increased fat mass.
 o ↓ DHEA (adrenopause) – reduced adrenal androgens.
 o Slight ↑ in fasting glucose and insulin resistance.
 o ↑ risk of subclinical hypothyroidism and impaired glucose tolerance.

Endocrine Investigations

Static hormone tests
Single blood measurements taken at rest. Useful for hormones with stable levels.
Examples:
 o TSH, free T4, prolactin, sex hormones (e.g. testosterone, oestradiol), calcium, PTH.
 o Must interpret with circadian and menstrual variations in mind.

Dynamic hormone tests
Assess endocrine gland responsiveness by stimulation or suppression.
Indicated when static levels are equivocal or physiology is complex.
Common examples:
 o Dexamethasone suppression test (Cushing’s syndrome):
  – Low-dose: tests cortisol suppression.
  – High-dose: distinguishes pituitary vs ectopic ACTH.
 o Short Synacthen test (primary adrenal insufficiency):
  – Synthetic ACTH given → assess cortisol response.
  – Impaired in Addison’s disease.
 o Insulin tolerance test (ITT) – gold standard for GH and ACTH reserve.
 o OGTT with GH measurement – for acromegaly (failure to suppress GH).
 o Water deprivation test – for diagnosis of diabetes insipidus.

Always interpret tests in the context of timing, clinical state, and medication history (e.g. oestrogen increases TBG; steroids suppress HPA axis).