Endocrinology Flashcards
What are the major endocrine glands of the body?
Thyroid, adrenal, pituitary (+ hypothalamus), calcium/ parathyroid
What are different types of hormones?
Proteins and peptides, steroids, tyrosine and tryptophan derivatives
What are different types of hormone receptors?
G-protein coupled receptors, receptor tyrosine kinase families, receptors associated with tyrosine kinase activity, steroid hormone receptors
What is the structure of G-protein coupled receptors?
7 transmembrane domain and associated G-protein complex
What is the function of G-protein coupled receptors?
Main sensors of internal environment and activation of a limited number of regulatory signalling cascades
What are many endocrine disorders associated with?
Defects in G-protein coupled receptors
What is the insulin receptor?
Receptor tyrosine kinase
What receptors are linked to tyrosine kinase activity?
Cytokine receptors
Where are steroid hormones typically located?
Intracellularly = either in cytoplasm or nucleus
How do steroid hormone receptors act?
Steroid/receptor complex binds DNA response elements = results in changes in gene transcription
What are some factors that influence the ability to accurately measure hormone levels?
Pattern of secretion, presence of carrier proteins, interfering agents, stability of hormone, absolute concentrations
What is the major determinant of hormone concentration?
Rate of secretion = typically determined by highly refined feedback loops
What are some commonly measured hormones?
Thyroid hormones, steroid hormone production, growth hormone evaluation, reproductive and sex hormones, prolactin, calcium and parathyroid hormone
What are more specialist hormone tests?
Renin/aldosterone, catecholamines, gut hormones
How is thyroid hormone measured?
Using highly sensitive TSH assay = relies on highly regulated feedback control
What do variations in thyroid hormone levels mean?
Raised TSH = hypothyroid
Lowered TSH = hyperthyroid
When is TSH an unreliable marker of thyroid hormone?
During pituitary dysfunction
What is sick euthyroid syndrome?
Non-thyroidal illness = characterised by low free hormone levels and inappropriately low/normal TSH
When is thyroid function measured in sick euthyroid syndrome?
When considered central to the clinical picture = of limited use in acutely unwell patient
What does measuring 9am cortisol give an indication of?
HPA axis function (pituitary function)
What are some markers used to measure pituitary function?
FT4, FT3, TSH, IGF1, LH, FSH, E2/testosterone, U & Es, plasma/urine osmolarity
What are some tests that can be done to investigate pituitary function?
Dynamic tests = formal assessment of HPA axis
Imaging = MRI
How is the growth hormone axis assessed?
Formal assessment requires dynamic assessment
IGF1 measurement may indicate GH hypertension
What does the evaluation of female sex hormones depend on?
The timing in the menstrual cycle
What secrets prolactin (PRL)?
Lactotroph cells of the anterior pituitary
What controls prolactin release?
Under tonic inhibition by hypothalamic dopamine
Secretion regulated by a short loop negative feedback
What mediates the effects of prolactin?
Prolactin receptor (PRLR)
Why is it important to understand the principles of steroid hormone synthesis?
Helps to understand adrenal physiology and hormone production
What can defects in steroid hormone synthesis cause?
Specific endocrine disorders
Does biochemical testing occur before imaging is done?
Yes
What is dynamic testing done for?
Hormone excess/deficiency = hormone excess gets suppression test, hormone deficiency gets stimulation tests
What is imaging used for?
To localise or characterise disease
When is combined imaging/biochemical testing used?
Adrenal vein sampling, petrosal sinus sampling
What occurs due to cortisol deficiency?
Adrenal insufficiency = May be due to primary adrenal failure (eg Addison’s) or pituitary disease
What may be a cause of cortisol excess?
Cushing’s syndrome
What are some examples of dynamic tests?
Stimulation test = Synacthen test
Suppression test = dexamethasone suppression test
What are some features of Cushing’s syndrome?
Cushingoid facies, acne, hirsutism, abdominal striae, centripedal obesity, intracapsular and supraclavicular fat pads, proximal myopathy, osteoporosis, hypertension, impaired glucose tolerance
What are the different forms of Cushing’s syndrome?
Cushing’s disease, ACTH independent Cushing’s, ectopic ACTH, exogenous steroids
What are some features of Cushing’s syndrome?
Pituitary origin, rumour arising from corticotroph cells of anterior pituitary, most common form, more common in females, most are microadenomas
What occurs in ACTH independent Cushing’s?
Bilateral macronodular adrenal hyperplasia = causes by adrenal adenoma/carcinoma
What is the main cause of ectopic ACTH?
Malignancy
What screening tests are done for Cushing’s syndrome?
1mg overnight dexamethasone suppression test, 24hr urinary free cortisol, midnight cortisol
What is the formal diagnostic test done for Cushing’s syndrome?
Low dose dexamethasone suppression test = lack of suppression means positive for Cushing’s
How does measuring ACTH help diagnose Cushing’s syndrome?
ACTH low = adrenal origin likely
ACTH raised = need more investigations to determine between Cushing’s syndrome and ectopic ACTH
What does a rise in cortisol and ACTH on CRH tests indicate?
Pituitary source of Cushing’s syndrome
Why is an MRI of the pituitary done in suspected Cushing’s syndrome?
To evaluate the pituitary gland
Imaging also done for possible ectopic ACTH
When is inferior petrosal sinus sampling done in Cushing’s syndrome?
Used to lateralise tumour prior to surgery
