Laboratory Investigation of Endocrine Disorders Flashcards
Briefly describe hypothalamic-pituitary-thyroid axis
Circulating TH levels under negative feedback control at hypothalamic and pituitary levels
Synthesis and release of TH controlled by TSH
T4 main hormone secreted by thyroid, T3 is more biologically active – mostly formed by peripheral conversion from T4
Thyroid hormones - use
Essential for normal growth and development
Thyroid hormones - effect
Increase basal metabolic rate (BMR) and affect many metabolic processes
Effects are mediated via activation of nuclear receptor
Thyroid hormones - synthesis
Synthesized in thyroid via series of enzyme catalysed reactions, beginning with uptake of iodine into gland
Synthesis and release controlled by TSH
Thyroid hormones - T3 vs T4
T4 main hormone secreted by thyroid, T3 is more biologically active – mostly formed by peripheral conversion from T4
Disorders of thyroid function - describe the names
Terminology: euthyroid (normal range), hypothyroid (below), hyperthyroid (above)
Primary hyper/hypothyroidism: dysfunction is in thyroid gland
Secondary: problem is with pituitary or hypothalamus (tertiary)
Hyperthyroidism - define
Excessive production of thyroid hormones (thyrotoxicosis)
Hyperthyroidism - clinical features
Weight loss, heat intolerance, palpitations, goitre, eye changes (Graves)
In extreme: thyroid storm
Causes of hyperthyroidism
Graves disease (most common) - due to stimulatory TSH-R antibodies Toxic multinodular goiter Toxic adenoma Secondary: excess TSH production (rare)
Hypothyroidism - define
Deficient production of thyroid hormones
Hypothyroidism - clinical features
Clinical features
weight gain, cold intolerance, lack of energy, goitre
congenital - developmental abnormalities
Hypothyroidism - investigations
Raised TSH, reduced fT4
Reduction in TSH and T4 suggests secondary (hypopituitarism)
Causes of hypothyroidism
Autoimmune thyroiditis (Hashimoto’s) - thyroid peroxidase antibodies (anti-TPO) Iodine defficiency Toxic adenoma Secondary – lack of TSH
Describe functional zonation of cortex
Blood flows from outer cortex to inner medulla
Layer-specific enzymes; steroid synthesis in one layer can inhibit different enzymes in subsequent layers
Results in functional zonation of cortex with different hormones made in each layer
CYP21A - function and deficiency
CYP21A is the gene for 21-hydroxylase. It’s deficiency is the major cause of congenital adrenal hyperplasia.
Mineralocorticoids: action
Mineralocorticoids: salt and water balance in order to maintain plasma volume: maintenance of blood pressure over the long term
Glucocorticoids: action
Glucocorticoids: metabolism and immune function
Stress increases release, but minimal levels essential for normal function
Control of adrenal steroid secretion - list
Cortisol: synthesis and release regulated by hypothalamic-pituitary-adrenal axis (CRH, ACTH)
Aldosterone: controlled by RAAS
Adrenal androgens: ACTH (not gonadotropins)
Explain effect on cortisol reading due to its rhythm
Cortisol secretion fluctuates in a circadian rhythm, which means a random plasma cortisol reading cannot exclude abnormality, unless way outside of normal range.
Hyper-function of the adrenal cortex
Aldosterone excess:
Conn’s syndrome
Cortisol excess:
Cushing’s syndrome
What could cause hyperaldosteronism
Possibilities: renal artery stenosis, renin-producing tumour (reninoma – rare, but well-described), anything that stimulates RAAS.
Dexamethasone suppresion test - high vs low dose comparison
Dexamethasone: exogenous steroid
Low doses will normally supress ACTH secretion via negative feedback
Low dose fails to supress ACTH secretion with pituitary disease (Cushing’s)
Higher dose will supress ACTH secretion in Cushing’s
No supresssion with low or high dose: suggests ectopic source of ACTH (e.g., tumour elsewhere
Cushing’s disease - dexamethasone suppression test + plasma ACTH result
DST:
Low dose = no suppression
High dose = suppression
Plasma ACTH = high
Adrenal tumour disease - dexamethasone suppression test + plasma ACTH result
DST:
Low dose = no suppression
High dose = no suppression
Plasma ACTH = low
Ectopic ACTH - dexamethasone suppression test + plasma ACTH result
DST:
Low dose = no suppression
High dose = no suppression
Plasma ACTH = very high
Adrenocortical insufficiency - primary vs secondary
Primary adrenocortical failure – Addison’s disease (typically autoimmune)
Secondary – impaired ACTH release
Head trauma, tumour, surgery
Abrupt steroid withdrawal
Addison’s disease effects
Loss of:
Cortisol
Androgens
Aldosterone
High ACTH
Addison’s disease - action
Loss of –ve fb from cortisol will compromise the VP system
Addison’s disease - cause
Usually autoimmune
Dynamic tests of adrenal function - purpose
Assess ability of adrenal to produce cortisol in response to ACTH
Describe short synacthen test
Measure baseline cortisol (9am) and 30 min after 250 µg synacthen (synthetic ACTH) i.m.
Adrenal insufficiency is excluded by an increase in cortisol of >200 nmol/L and/or a 30 min value >550
Describe longs ynacthen test
Adrenal cortex ‘shuts down’ in absence of stimulation by ACTH – time needed to regain responsiveness
3-day stimulation with i.m. synacthen
In secondary (but not primary) adrenal insufficiency cortisol increases by >200 nmol/L over baseline
Long test not often necessary since ACTH assay can distinguish
