Hypothalamic- pituitary- adrenal axis: clinical aspects Flashcards
Adrenal cortex hormone production
Glucocorticoid
- cortisol
Mineralocorticoid
- aldosterone
Sex steroids
- androgens
Binding proteins
90% cortisol bound to cortisol binding globulin
Receptors
Intracellular glucocorticoid and mineralocorticoid receptors
Enzymes
11- beta- hydroxysteroid dehydrogenase
Effects of glucocorticoids
Maintenance of homeostasis during stress (e.g. haemorrhage, infection, anxiety)
Anti-inflammatory
Energy balance/ metabolism
Formation of bone and cartilage
Regulation of blood pressure
Cognitive function, memory, conditioning
Circadian rhythm: cortisol levels
Rise during the early morning
Peak just prior to awakening
Fall during the day
Are low in the evening
Ultradian rhythm
Spontaneous pulses of varying amplitude
Amplitude decreases in the circadian trough
11-B-HSD enzymes
Tissue specificity:
- gating of GC access to nuclear receptors
- amplification of GC signal in target cells
Too much cortisol causes
Cushing’s syndrome
Features of Cushing’s syndrome
Weight gain
Central obesity
Hypertension
Insulin resistance
Neuropsychiatric problems
Osteoporosis
Pathogenesis of Cushing’s syndrome
Excess cortisol
- pituitary adenoma: ACTH secreting cells
- adrenal tumour: adenoma
- ectopic ACTH: carcinoid, paraneoplastic
- iatrogenic: steroid treatment
Clinical features of Cushing’s syndrome
Central obesity with thin arms and legs
Fat deposition over upper back
Rounded moon face
Thin skin with east bruising, pigmented striae
Hirsutism
Hypertension
Diabetes
Psychiatric manifestations
Osteoporosis
Too little cortisol
Addison’s disease
Pathogenesis of Addison’s disease
Primary adrenal insufficiency
- usually autoimmune in UK
- rare causes include metastases or TB
- decreased production of all adrenocortical hormones
Other causes of hypoadrenalism
- secondary to pituitary disease
- iatrogenic
Clinical features of Addison’s disease
Malaise, weakness, anorexia, weight loss
Increased skin pigmentation (knuckles, palmar creases, around/ inside the mouth, pressure areas, scars)
Hypotension/ postural hypotension
Hypoglycaemia
Type 1 autoimmune polyendocrine syndromes
Rare
Onset in infancy
Ar (AIRE gene)
Common phenotypes
- Addison’s disease
- hypoparathyroidism
- candidiasis
Type 2 autoimmune polyendocrine syndromes
Commoner
Infancy to adulthood
Polygenic
Common phenotype
- Addison’s disease
- T1 diabetes
- autoimmune thyroid disease
Autoimmune conditions that may occur together
Type 1 diabetes
Autoimmune thyroid disease
Coeliac disease
Addison’s disease
Pernicious anaemia
Alopecia
Vitiligo
Hepatitis
Premature ovarian failure
Myasthenia gravis
Clinical implications of autoimmune polyendocrine syndromes
High index of suspicion for additional autoimmune endocrine disorders
Consider screening in patients with T1 DM and or/ Addison’s disease
- coeliac screen
- thyroid function tests
Assessment of the HPAA
Basal
- blood: cortisol, ACTH
- urine: cortisol
- saliva: cortisol
Dynamic tests
- stimulated
- suppressed
Two golden rules
Never start investigations for an endocrine condition unless symptoms and signs suggest they have it
Never image any endocrine gland until you have established the diagnosis biochemically
Imaging
Once you have confirmed that a patient has Cushing’s syndrome, consider
- CXR
- MRI pituitary
- CT adrenals
Patients with Addison’s disease seldom need imaging unless you are concerned they may have TB/ metastatic cancer
Management of Cushing’s syndrome
Surgical (depending on the cause)
- transphenoidal adenectomy
- adrenalectomy
Pituitary radiotherapy
Management of Addison’s disease
Steroid hormone replacement therapy
Patients with primary adrenal insufficiency also need mineralocorticoid replacement therapy
Patients with secondary adrenal insufficiency will often be taking other hormone replacement therapy
