Metabolic Rate, Growth and Disease

glucocorticoids

• class of steroid hormones

• effect glucose metabolism

• cortisol→ human, cortisone→ pharmaceutical

• produced in zona fasiculata of adrenal gland

cortisol feedback loop

• hypothalamus releases CRH

• CRH stimulates pituitary gland to produce ACTH

• ACTH stimulates adrenal gland to secret cortisol

• cortisol acts as negative feedback→ stops release

diurnal rhythm

• highest cortisol levels 30 minutes after waking

• declines throughout the day

• regulated by suprachiasmatic nucleus of the hypothalamus

role of cortisol

• GC receptors present almost all cells

• affects all body systems

• increased production in times of stress

• essential for foetal development

• increases 2-4x during pregnancy

actions of cortisol in the immune system

• reduced inflammation

  • suppress B cell antibody production

  • apoptosis of T cells

  • reduced neutrophil migration

actions of cortisol on glucose

• increase glucose availability to brain

• acts on liver, pancreas muscle, adipose tissue

• increased gluconeogenesis and lipolysis

• reduced glycogen synthesis

• reduced insulin production, increased glucagon synthesis

actions of cortisol on cardiovascular system

• circadian rhythm affects BP and HR

• increased cardiovascular tone

actions of cortisol on the nervous system

• GC receptors found throughout CNS

• part of fight or flight response

Addison’s disease

• adrenal insufficiency

primary causes of addison’s disease

• autoimmune

• chronic granulomatous disease

• malignancy

• haemorrhage

• infective

• drug related

• prior irradiation

secondary causes of addison’s disease

• secondary causes

• insufficient ACTH production

  • pituitary disease

  • exogenous steroids

signs and symptoms of addison’s disease

• weakness and fatigue

• hypotension

• hypoglycaemia

• weight loss

• reduced body hair

• hyperpigmentation→ primary only

• hypokalaemia and hyponatraemia

addisonian crisis

• inability to produce cortisol in stressful situation

• infection, trauma, surgery, medication non-compliance

• low BP, low BM

• high potassium

• nausea, vomiting, confusion, pyrexia

investigations for addison’s disease

• random cortisol level

  • 9am cortisol <100- urgent admission

  • >420 excludes adrenal insufficiency

• U&Es- raised urea, creatinine, acidosis, hyponatraemia, hyperkalaemia

• normocytic normochromic anaemia

• SST, ECG

SST

• short synacthen test→ for adrenal insufficiency

• not for use in critically ill, stop HRT, OCP 6 weeks prior

1. basal cortisol level taken

2. synthetic ACTH injected

3. cortisol levels taken at 30 and 60 minutes

   • >420 is adequate after 30 mins

treatment for addison’s disease

• crisis→ IV steroids, IV fluids

• replacement dose→ hydrocortisone

• may require fludrocortisone→ mineralocorticoid

cushing’s syndrom

• prolonged exposure to excess steroid

• endogenous or exogenous

• peak incidence 25-40

cushing’s disease vs cushing’s syndrome

• cushing’s disease→ pituitary tumour, ACTH dependant

• Cushing’s syndrome→ excess cortisol from any other cause

signs and symptoms of Cushing’s disease

• weight gain

• proximal muscle weakness

• bruising

• striae

• hypertension

• osteoporosis

• diabetes

• impaired immune function

investigations for cushings

• ONDST→ overnight dexamethasone suppression test

• late night salivary cortisol

• 24 hour urinary cortisol

• ACTH

• HDDST→ high dose dexamethasone suppression test

• imaging

treatment for cushings

• surgery→ removal of causal tumour

• medication, radiotherapy

thyroid function

• controls basal metabolic rate

• produces 2 hormones:

  • T4→ thyroxine

  • T3→ triiodothyronine

thyroid hormone synthesis

• tyrosine and iodine essential for thyroxine production

• iodine taken from blood by thyroid epithelial cells

• tyrosine produced from thyroglobulin

  • thyroglobulin synthesised from thyroid epithelial cells and secreted into lumen of follicle

thyroid peroxidase

• enzyme on thyroid epithelial cells→ essential for

  • iodination of tyrosines on thyroglobulin

  • synthesis of T4 and T3

hypothyroidism

• usually primary→ failure of thyroid to produce thyroxine

• can be caused by

  • excess or deficient iodine

  • autoimmune

  • iatrogenic

  • thyroiditis

  • pituitary damage

symptoms of hypothyroidism

• thinning hair and hair loss

• puffy face

• enlarged thyroid

• dry and coarse skin

• slow heartbeat

• poor appetite

• constipation

• cool extremities

• carpal tunnel syndrome

• weight gain

• tiredness

treatment of hypothyroidism

• aim to correct metabolic derangement to improve symptoms

• daily dose of T4

primary vs secondary hyperthyroidism

• primary:

  • Graves disease

  • toxic goitre

  • solitary nodule

  • thyroiditis

• secondary:

  • pituitary tumour

  • iatrogenic

symptoms of hyperthyroidism

• excessive sweating

• heat intolerance

• increased bowel movements

• tremor

• nervousness, agitation

• rapid heart rate

• weight loss

• fatigue

• decreased concentration

• irregular and scrant menstrual flows

presentation of thyrotoxicosis

• younger patients→ more symptoms and sympathetic activation

• older patients→ CVS symptoms

• patients with Graves→ more symptomatic

grave’s disease

• autoimmune disease

• opthalmopathy:

  • diplopia

  • proptosis

  • peri-orbital oedema

• pre-tibial myxoedema dermopathy

treatment of thyrotoxicosis

• carbimazole, anti-thyroid agents

• beta blockers

• Lugol’s iodine

• glucocorticoids

• cholestyramine

• radioactive iodine

• surgery→ thyroidectomy

thyroid in foetal development

• increased thyroxine requirement during pregnancy

• developing foetus initialy reliant on maternal thyroxine

• foetal thyroid reaches maturity at 11 weeks, foetus thyroid hormones at 16 weeks

hypothyroidism in babies

• lack of maternal thyroxine

• 85% due to thyroid agenesis

• early treatment with thyroxine may be needed

growth hormone

• also known as somatotropin

• hormone of post natal growth and adult development

• maintains lean body mass and bone mass

• release follows circadian rhythm

growth hormone release

• stimulated by GHRH

• inhibited by somatostatin

effects of growth hormone

• protein metabolism→ anabolic effect

• promotes lipolysis

• antagonistic to insulin

• promotes linear growth and transforms cartilage into bones

• enhances milk production

gigantism

• hypersecretion in children before closure of epiphyseal long bones

• usually tall, large hands and feet, coarse facial features, loss of libido, impotence, hyperglycaemia, macrocephaly

agromegaly

• excess growth hormone in adults after fusion of epiphysis

• enlarged hands and feet, coarse facial features, prognathism, macroglossia

• hypertension, sleep apnoea, DM type 2

treatment of hypersecretion of growth hormone

• transsphenoidal surgery is primary treatment

• medical therapy→ somatostatin

• GH receptor antagonists

• radiation