Basic Principles of Endocrinology

Question 1

Hormone sub-types and examples of each class?

Answer 1

1. Protein and peptides - amino acid chains of variable length, e.g: insulin, GH, prolactin
2. Steroids - derived from cholesterol, e.g: cortisol, testosterone
3. Tyrosine and tryptophan derivatives, e.g: adrenaline, thyroid hormones, melatonin

Question 2

Action time of the hormone sub-types?

Answer 2

Proteins and peptide hormones and tyrosine/typtophan derivatives act quickly

Steroid hormones exert their effect over a long period of time

Question 3

Types of hormone receptors?

Answer 3

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

Question 4

Structure of GPCRs?

Answer 4

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

Question 5

Describe steroid hormone receptors

Answer 5

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

Question 6

Several factors that affect accurate measurement of hormone levels?

Answer 6

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

Question 7

When might TSH not be a reliable marker of thyroid status?

Answer 7

Pituitary dysfunction (i.e: secondary hypothyroidism or TSHoma)

As long as the feedback loop remains intact, TSH will appear normal

Question 8

Describe sick euthyroid syndrome

Answer 8

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

Question 9

Tests for pituitary function?

Answer 9

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

Question 10

Describe the HPA axis

Answer 10

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

Question 11

Describe circadian cortisol secretion

Answer 11

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

Question 12

How is the HPA axis formally assessed?

Answer 12

Requires dynamic testing

Question 13

How to assess the GH axis?

Answer 13

Random GH measurement if of little value, as levels are pulsatile

Formal assessment requires dynamic testing but IGF-1 measurement may indicate GH hypersecretion

Question 14

Describe the circadian rhythm of testosterone

Answer 14

Varies throughout the day and so it should be measured at 9am

Question 15

Changes in female sex hormones?

Answer 15

Depends on timing in the menstrual cycle

Question 16

Secretion of prolactin?

Answer 16

Secreted by lactotroph cells of the anterior pituitary; this is regulated by a short-loop -ve feedback

Under tonic inhibition by hypothalamic dopamine

Question 17

Prolactin receptor?

Answer 17

Effects are mediated by prolactin receptor (PRLR) in the breast

Question 18

Physiological causes of hyperprolactinaemia?

Answer 18

Pregnancy, lactation, nipple stimultion

Question 19

Analytical causes of hyperprolactinaemia?

Answer 19

Macroprolactinaemia

Question 20

Pathological causes of hyperprolactinaemia?

Answer 20

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)

Question 21

Regulation of thirst and water balance?

Answer 21

Vasopressin causes:
• Vasoconstriction to increase systemic vascular resistance
• Fluid reabsorption in the kidneys to increase blood volume

Both result in increased BP

Question 22

Alterations in the steroid biosynthesis pathway can cause?

Answer 22

Congenital adrenal hyperplasia (CAH)

This is caused by deficiencies in CYP21A2, CYP17A1 and CYP11B1

Question 23

Dynamic testing to detect hormone excess/deficiency?

Answer 23

Hormone excess - suppression test

Hormone deficiency - stimulation test

Question 24

Causes of cortisol deficiency?

Answer 24

This is adrenal insufficiency, caused by:
• Primary adrenal failure, e.g: Addison’s disease (most common cause of adnreal insufficiency)
• Pituitary disease

Question 25

Causes of cortisol excess?

Answer 25

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

Question 26

Signs of Cushing’s syndrome?

Answer 26

• Cushingoid facies
• Acne
• Hirsutism
• Abdominal striae & centripetal obesity
• Interscapular & supraclavicular fat pads
• Proximal myopathy
• Osteoporosis
• Hypertension
• Impaired glucose tolerance

Question 27

Describe Cushing’s syndrome (AKA pituitary Cushing’s)

Answer 27

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

Question 28

Describe ACTH-independent Cushing’s

Answer 28

Adrenal adenoma/carcinoma

Bilateral macronodular adrenal hyperplasia

Question 29

Describe ectopic ACTH

Answer 29

Malignancy

Question 30

Screening tests for Cushing’s?

Answer 30

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)

Question 31

Formal diagnostic test for Cushing’s?

Answer 31

Low dose dexamethasone suppression test

Failure to suppress means the patient has Cushing’s syndrome

Question 32

Why is ACTH used to check for Cushing’s?

Answer 32

Determines further Ix:
• If low - adrenal origin is likely
• If raised, must distinguish Cushing’s disease and ectopic ACTH

Question 33

Interpreting Ix results for Cushing’s?

Answer 33

Rise in cortisol and ACTH on CRH test indicates a pituitar source (rather than an ectopic one)

Question 34

Other Ix for Cushing’s syndrome?

Answer 34

MRI pituitary

Inferior petrosal sinus sampling (drain pituitary blood supply)

Imaging for possible ectopic ACTH