Basic Principles of Endocrinology Flashcards
Hormone sub-types and examples of each class?
- Protein and peptides - amino acid chains of variable length, e.g: insulin, GH, prolactin
- Steroids - derived from cholesterol, e.g: cortisol, testosterone
- Tyrosine and tryptophan derivatives, e.g: adrenaline, thyroid hormones, melatonin
Action time of the hormone sub-types?
Proteins and peptide hormones and tyrosine/typtophan derivatives act quickly
Steroid hormones exert their effect over a long period of time
Types of hormone receptors?
GPCRs (largest group and the main sensors of the internal environment)
Recetpor tyrosine kinase (RTK) families, e.g: insulin receptor is the prototype RTK
Receptors assoc. with tyrosine kinase activity, e.g: cytokine receptors like prolactin receptor and GH receptor
Steroid hormone receptors
Structure of GPCRs?
7 transmembrane domain assoc. with a G-protein complex (consists of α, β and γ); end result is activation of a limited no. of regulatory signalling cascades, e.g: cAMP and IP3
Describe steroid hormone receptors
Part of the nuclear receptor family, inc. oestrogen and androgen receptors
Typically intracellular, either in the cytoplasm or nucleus and the steroid/receptor complex can bind to DNA receptor elements; this results in changes in gene transcription
Several factors that affect accurate measurement of hormone levels?
Pattern of secretion (e.g: peaks and troughs must be considered)
Presence of carrier proteins
Interfering agents (e.g: antibodies that interfere with the assay)
Stability of hormone (consider the 1/2-life)
Absolute concentrations
When might TSH not be a reliable marker of thyroid status?
Pituitary dysfunction (i.e: secondary hypothyroidism or TSHoma)
As long as the feedback loop remains intact, TSH will appear normal
Describe sick euthyroid syndrome
Thyroid function seems abnormal but it is due to non-thyroidal illness
Thyroid function in an acutely unwell patient is of limited value
Characterised by low free hormone levels and inappropriate low/normal TSH
Tests for pituitary function?
9am cortisol (there is a cortisol peak when the patient wakes up and it is almost undetectable by midnight)
FT4, FT3, TSH
Prolactin
IGF1 (checks the growth hormone axis, as GH levels are pulsatile and difficult to interpret accurately)
LH, FSH, E2/testosterone
U&Es, plasma/urine osmolarity
Dynamic tests may also be used, as can imaging
Describe the HPA axis
Hypothalamus secretes corticotrophin-releasing hormone (CRH)
Stimulates the anterior pituitary to secrete adrenocorticotrophic hormone (ACTH)
Stimulates the adrenal cortex to secrete cortisol, which has multiple physiological effects
This consists of -ve feedback loops
Describe circadian cortisol secretion
There is a cortisol peak when the patient wakes up and it is almost undetectable by midnight
This means that a random cortisol measurement is of little value but a 9am cortisol can give an indication of HPA axis function
How is the HPA axis formally assessed?
Requires dynamic testing
How to assess the GH axis?
Random GH measurement if of little value, as levels are pulsatile
Formal assessment requires dynamic testing but IGF-1 measurement may indicate GH hypersecretion
Describe the circadian rhythm of testosterone
Varies throughout the day and so it should be measured at 9am
Changes in female sex hormones?
Depends on timing in the menstrual cycle
Secretion of prolactin?
Secreted by lactotroph cells of the anterior pituitary; this is regulated by a short-loop -ve feedback
Under tonic inhibition by hypothalamic dopamine
Prolactin receptor?
Effects are mediated by prolactin receptor (PRLR) in the breast
Physiological causes of hyperprolactinaemia?
Pregnancy, lactation, nipple stimultion
Analytical causes of hyperprolactinaemia?
Macroprolactinaemia
Pathological causes of hyperprolactinaemia?
Prolactinomas and mixed-secreting adenomas
Hypothalamic and pituitary stalk disorders: • Compressive macroadenoma • Hypophysitis • Granulomatous disease • Rathke cleft cyst • Irradiation and/or trauma • Tumours
Medications:
• Dopamine antagonists (domperidone, metoclopramide, prochlorperazine)
• Anti-depressants, oestrogenes, opiates
Chronic renal failure
Ectopic prolactin secretion:
• Ovarian dermoids
• Hypernephroma
• Bronchogenic carcinoma
Idiopathic (unknown)
Regulation of thirst and water balance?
Vasopressin causes:
• Vasoconstriction to increase systemic vascular resistance
• Fluid reabsorption in the kidneys to increase blood volume
Both result in increased BP
Alterations in the steroid biosynthesis pathway can cause?
Congenital adrenal hyperplasia (CAH)
This is caused by deficiencies in CYP21A2, CYP17A1 and CYP11B1
Dynamic testing to detect hormone excess/deficiency?
Hormone excess - suppression test
Hormone deficiency - stimulation test
Causes of cortisol deficiency?
This is adrenal insufficiency, caused by:
• Primary adrenal failure, e.g: Addison’s disease (most common cause of adnreal insufficiency)
• Pituitary disease
Causes of cortisol excess?
This is Cushing’s syndrome, caused by:
• Pituitary origin (if not specified, Cushing’s syndrome is pituitary Cushing’s)
• Adrenal origin
• Ectopic ACTH
• Exogenous steroids - oral, inhaled, topical, injectable
Signs of Cushing’s syndrome?
- Cushingoid facies
- Acne
- Hirsutism
- Abdominal striae & centripetal obesity
- Interscapular & supraclavicular fat pads
- Proximal myopathy
- Osteoporosis
- Hypertension
- Impaired glucose tolerance
Describe Cushing’s syndrome (AKA pituitary Cushing’s)
Tumour arising from the corticotroph cells of the anterior pituitary (most are microadenomas) and this account for the majority of Cushing’s
More common in females
Describe ACTH-independent Cushing’s
Adrenal adenoma/carcinoma
Bilateral macronodular adrenal hyperplasia
Describe ectopic ACTH
Malignancy
Screening tests for Cushing’s?
There is too much cortisol so SUPPRESSION TESTS are required:
• 1mg overnight dexamethasone suppression test (switches off cortisol production so, normally, cortisol will be undetectably low)
• 24 hour urinary free cortisol
• Midnight cortisol (normally this should be very low)
Formal diagnostic test for Cushing’s?
Low dose dexamethasone suppression test
Failure to suppress means the patient has Cushing’s syndrome
Why is ACTH used to check for Cushing’s?
Determines further Ix:
• If low - adrenal origin is likely
• If raised, must distinguish Cushing’s disease and ectopic ACTH
Interpreting Ix results for Cushing’s?
Rise in cortisol and ACTH on CRH test indicates a pituitar source (rather than an ectopic one)
Other Ix for Cushing’s syndrome?
MRI pituitary
Inferior petrosal sinus sampling (drain pituitary blood supply)
Imaging for possible ectopic ACTH
