23. Lab Investigations of Endocrine Disorders Flashcards
Describe the 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
Describe thyroid hormones.
- Essential for normal growth and development
- Increase basal metabolic rate (BMR) and affect many metabolic processes
- Synthesized in thyroid via series of enzyme catalysed reactions, beginning with uptake of iodine into gland
- Synthesis and release controlled by TSH
- T4 main hormone secreted by thyroid, T3 is more biologically active – mostly formed by peripheral conversion from T4
- Effects are mediated via activation of nuclear receptor
What are the two types of disorders of thyroid function?
- Primary hyper/hypothyroidism: dysfunction is in thyroid gland
- Secondary: problem is with pituitary or hypothalamus (tertiary)
What is hyperthyroidism?
- Excessive production of thyroid hormones (thyrotoxicosis)
- Clinical features
- Weight loss
- heat intolerance
- palpitations
- goitre
- eye changes (Graves)
•In extreme: thyroid storm
List some causes of hyperthyroidism
- Graves disease (most common) - Due to stimulatory TSH-R antibodies
- Toxic multinodular goiter
- Toxic adenoma
•Secondary: excess TSH production (rare)
What is hypothyroidism, and how would you investigate it?
•Deficient production of thyroid hormones
•Clinical features:
- weight gain
- cold intolerance
- lack of energy
- goitre
- congenital - developmental abnormalities
•Investigations
- Raised TSH, reduced fT4
- Reduction in TSH and T4 suggests secondary (hypopituitarism)
List some causes of hypothyroidism
- Autoimmune thyroiditis (Hashimoto’s)
- Thyroid peroxidase antibodies (anti-TPO)
- Iodine defficiency
- Toxic adenoma
•Secondary – lack of TSH
What are the steroids of adrenal cortex?
- Zona glomerulosa = aldosterone
- Zona fasiculata = cortisol
- Zona reticularis = androstenedione/DHEA
What are the actions of adrenal steroids?
- Mineralocorticoids: salt and water balance in order to maintain plasma volume: maintenance of blood pressure over the long term
- Glucocorticoids: metabolism and immune function
Stress increases release, but minimal levels essential for normal function - Androgens: so called ‘weak androgens’
What are organs on which coritsol acts?
- brain
- bone
- CVS
- immune system
- kidney
- skin/connective tissue
- foetus
How is the secretion of the hormones of the adrenal cortex controlled?
Cortisol: synthesis and release regulated by hypothalamic-pituitary-adrenal axis (CRH, ACTH)
Aldosterone: controlled by RAAS
Adrenal androgens: ACTH (not gonadotropins)
What is the disease called with excess aldosterone?
Conn’s syndrome
What is the disease called with excess cortisol?
Cushing’s syndrome
Describe the dexamethasone suppression test.
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)
What are two ways in which you can get adrenocortical insufficiency?
Primary adrenocortical failure – Addison’s disease (typically autoimmune)
Secondary – impaired ACTH release
- Head trauma, tumour, surgery
- Abrupt steroid withdrawal
