Endocrine Topic 1 - General Flashcards
How is acromegaly treated/managed?
Surgery (often not curative)
Medical - somatostatin to inhibit GH
Radiotherapy - risk of hypopituitarism
What is the difference between gigantism and acromegaly?
Gigantism - overproduction of growth hormone in childhood
Acromegaly - overproduction of growth hormone/IGF-1 in adulthood (after epiphyseal fusion)
List the functional cell types in the anterior pituitary and the hormones they produce
- Somatotrophs (acidophils) - growth hormone, predominant cells type
- Lactotrophs (acidophils) - prolactin
- Corticotrophs (basophils) - adrenocorticotrophic hormone (ACTH), beta-lipotropin, alpha-melanocyte stimulating hormone, beta-endorphin
- Thyrotrophs (basophils) - thyroid stimulating hormone (TSH)
- Gonadotrophs (basophils) - FSH/LH
What is the action of ADH?
Binds to V2 receptor (G-protein coupled) on collecting tubules of the kidney, causes an increase in cAMP/PKA and therefore aquaporin 2 recruitment - increases water reabsorption
Also causes vasoconstriction to increase BP
From what are amine hormones derived?
Derived from amino acids
Define hyponatraemia
Serum Na+ below 135mmol/L
Define hypercalcaemia
High free calcium (45% of total)
What is the effect of a non-functioning pituitary adenoma?
Compresses surrounding structures e.g. optic chiasm, causing peripheral vision loss
List the causes of hyponatraemia
- Water excess
- Sodium and water excess
- Excess ADH
What is the clinical consequence of hyponatraemia?
Brain oedema (water moves into cells)
How is the cause of hypercalcaemia diagnosed?
- Measure PTH
- If low malignancy likely
- If normal/high - primary hyperparathyroidism
How is growth hormone release regulated?
Negative feedback - GH, IGF-1 or somatostatin
How is diabetes insipidus diagnosed?
- 8 hour water deprivation, give synthetic ADH, measure osmolality of urine
- Normal - 8hrs = >600, give ADH = >600
- Cranial DI - 8hrs = <300, give ADH = >600
- Nephrogenic DI - 8hrs = <300, give ADH = <300
What causes diabetes insipidus?
- Cranial or nephrogenic causes
- Cranial = ADH deficiency - idiopathic, genetic, trauma, tumours, infection
- Nephrogenic = resistance to ADH - genetic (AVPR2 mutation), secondary to drugs (e.g. lithium), metabolic upset, renal disease
How is hypopituitarism treated?
Multiple hormone replacement (cortisol first if all affected)
Describe the structure of the parathyroid glands
- Usually 4
- 2 secretory cell types
- Chief cells - most abundant, basophilic (stain purple)
- Oxyphil cells - acidophilic (stain pink)
- Often within thyroid capsule, if separate may have fine fibrous capsule surrounding
What causes water excess leading to hyponatraemia?
- Glucocorticoid deficiency
- Hypothyroid
- Psychiatric
- Drugs
- Inappropriate ADH secretion
What causes hypopituitarism?
- Tumours
- Radiotherapy
- Infarction - post-partum = Sheehan’s syndrome
- Infiltrations - sarcoid
- Trauma
- Congenital
Describe the action of steroid hormones
Lipophilic - pass through plasma membrane, act on intracellular receptor
What causes hypernatraemia?
Mostly due to dehydration - insensible/sweat loss, GI loss, diabetes insipidus, osmotic diuresis due to hypoglycaemia
What are the consequences of hypopituitarism?
- Can affect single axis (gonadotrophic most common) or all (panhypopituitarism)
- Leads to secondary gonadal/thyroid/adrenal failure
How is hypernatraemia corrected?
- Treat cause
- Estimate total body water deficit
- Avoid rapid correction (cerebral oedema)
- Use IV 5% dextrose
How is hyponatraemia treated?
- Severe/acute (unconscious/seizures) = hypertonic (8%) saline
- Less severe/chronic = treat cause, usually need fluid restriction, increase slowly
How is hyponatraemia due to excess ADH diagnosed?
- Osmolality of urine > plasma
- Urine sodium >30mmol/L
- Absence of adrenal/thyroid/pituitary/renal insufficiency
- No recent diuretic use
From what are steroid hormones derived?
Cholesterol
What is the effect of growth hormone?
Multiple effects - direct or through IGF-1 production
What are the complications of acute hypocalcaemia?
- Tetany
- Peri-oral numbness, muscle cramps, tingling of hands/feet
- Carpopedal spasm, laryngospasm, seizures
- Cardiac complications
- Dysrrhythmia, hypotension
Describe the embryonic origin of the pituitary gland
- Anterior and posterior lobes
- Anterior
- Directly regulated by hypothalamus
- From embryonic pharynx - oral ectoderm
- Posterior
- Down growth from diencephalon
- Neuroectoderm
- Fibroelastic capsule from primitive pia mater
How is acromegaly diagnosed?
Oral glucose tolerance test (no suppression of GH by high blood glucose concentration in acromegaly)
IGF-1 level (high in acromegaly) - longer half-life than GH
Pituitary MRI
How is the lactotrope axis regulated?
- Negative hypothalamic control - dopamine inhibits prolactin release from the pituitary
- Oestrogen has positive effect, stimulates prolactin release
- Stress stimulates
- Only action is in pregnancy - lactation (none in males)
Describe the clinical features of hypercalcaemia
- Stones - nephrolithiasis, nephrocalcinosis, diabetes inspidis
- Bones - bone pain, oesteoporosis, muscle weakness
- Thrones - polyuria
- Psychiatric overtones - depression, anxiety
- ECG - shortened QTc, bradycardia
What are the symptoms of diabetes insipidus?
- Extreme thirst
- Polyuria
- Nocturia
- No hyperglycaemia/hypercalcaemia
List the hormones secreted by the posterior pituitary
- Anti-diuretic hormone
- Oxytocin
How is hypocalcaemia treated?
- IV Ca2+ replacement - if tetany or cardiac manifestations, +/- IV magnesium
- Chronic management - Vitamin D supplement, oral calcium salts
- Underlying cause
How are the blood vessels of the pituitary functionally specialised?
Fenestrated
Describe the anatomical location of the pituitary
- Suspended from underside of brain by pituitary stalk (attached to hypothalamus)
- In front of pons, behind nose and hypothalamus
- Optic chiasm above
- Sits in in sella turcica (Turkish saddle) of the sphenoid bone - in hypophyseal fossa
List clinical disorders of the pituitary
- Posterior pituitary - diabetes insipidus (low ADH)
- Non-functioning pituitary tumours
- Functioning pituitary tumours - high prolactin, GH, ACTH or TSH
- Hypopituitarism
List the types of hormones and give examples of each
- Amine e.g. catecholamines - adrenaline, noradrenaline, dopamine
- Peptide e.g. pituitary hormones, insulin, leptin, ghrelin
- Steroid e.g. glucocorticoids - cortisol, mineralocorticoids - aldosterone, androgens, progesterone
What causes Na+ and water excess leading to hyponatraemia?
- Nephrotic syndrome
- Cardiac failure
- Cirrhosis
- Acute/chronic kidney disease
What stimuli trigger growth hormone releasing hormone secretion?
Stress, exercise, sleep, hypoglycaemia
From what are peptide hormones derived?
Amino acids
What is the effect of parathyroid hormone?
- Released in response to low serum calcium
- Increases bone resorption
- Increases kidney phosphate excretion and calcium reabsorption
- Increases calcitriol formation (therefore increased GI absorption of calcium)
- Net effect - increases serum calcium, phosphate same
What is the effect of calcitriol?
- Increased GI absorption
- Increased bone resorption
- Increased renal reabsorption
What are the signs/symptoms of acromegaly?
- Sweating
- Headaches
- Tiredness
- Joint pain
- Coarse facial features
- Increased tongue/hand/foot size
- Visual field loss
- Hypertension
- Impaired glucose tolerance
- Increased bowel cancer risk
- Heart failure
How are prolactinomas managed?
Dopamine agonist (cabergoline), surgery
What is the difference between an exocrine and endocrine gland?
- Endocrine - secretes hormones directly into bloodsteam
- Adrenal, thyroid, endocrine pancreas
- Exocrine - secretes into a duct
- Salivary, exocrine pancreas
Describe the classification of hypercalcaemia
- Mild < 3 mmol/L
- Moderate 3-3.5mmol/L
- Severe > 3.5 mmol/L
What are the effects of functioning pituitary adenomas?
- Corticotroph adenoma (ACTH secreting) - Cushing’s syndrome
- Somatotroph adenoma (GH secreting) - acromegaly
- Thyrotroph adenoma (TSH secreting) - hyperthyroidism
What causes inappropriate ADH secretion leading to hyponatraemia?
- Cancer - lung, lymphoma, leukaemia
- Pneumonia
- CNS infection/injury
- Drugs - opiates, thiazides, proton pump inhibitors, anti-convulsants, anti-depressants
What kind of receptors do amine hormones act on?
Mostly act on G-protein coupled receptors (or tyrosine kinase receptors)
Describe the cell types which can be distuingished histologicall in the anterior pituitary
- Chromophobes
- Palely stained
- Exhausted secretory cells
- Chromophils
- Strongly stained
- Active secretory cells
- Acidophils and basophils
- Acidophils - pink, stained by eosin
- Basophils - purple, stained by haematoxylin
How is the hypothalamic-pituitary-thyroid axis regulated?
T3/4 has negative feedback effect on pituitary/hypothalamus
Generally, what is the cause of hyponatraemia?
Usually due to a disorder of water balance e.g. renal impairment, diuretics (especially thiazide)
What causes hypercalcaemia?
- Primary hyperthyroidism (usually parathyroid adenoma)
- Malignancy - breast, lung, myeloma, bone (direct osteolysis)
What are the signs/symptoms of a prolactinoma?
- Galactorrhoea - production of milk
- Menstrual disturbance/subfertility in women
- Low libido/erectile dysfunction in men
- Low gonadotrophs
How is the hypothalamic-pituitary-gonadal axis regulated?
- Women - positive and negative feedback depending on time in cycle
- Inhibin produced by granulosa cells of ovaries inhibit FSH secretion
- Men - negative feedback through inhibin produced by Sertoli cells and androgens produced by Leydig cells
What are the clinical features of hyponatraemia?
- Asymptomatic
- Confusion
- Gait instability
- Drowsiness
- Seizures
List the hormones released by the hypothalamus and the effect they have
- Growth hormone releasing hormone - acts on the anterior pituitary to release growth hormone, leads to increased insulin-like growth factor 1 (IGF-1)
- Gonadotrophin releasing hormone (GnRH) - acts on anterior pituitary to released FSH/LH
- Corticotrophic releasing hormone - acts on anterior pituitary to release ACTH
- Thyroid releasing hormone - acts on anterior pituitary to release TSH
- Dopamine - acts on anterior pituitary to inhibit prolactin release
What is the most common functioning pituitary adenoma?
Prolactinoma
What is the action of oxytocin?
Needed for labour and breast feeding
How is hypercalcaemia treated?
- Dependent on severity, treat underlying cause
- Rehydrate - isotone 0.9% saline
- Bisphosphonate - osteoporosis, malignancy (Zoledronic acid)
- Calcitonin
- Glucocorticoids - inhibit Vitamin D production
- Parathyroidectomy
What causes hypocalcaemia?
- Low PTH - surgery, autoimmune, hypoparathyroidism
- Normal PTH - Vitamin D deficiency, chronic renal failure, calcium loss, drugs, hypomagnesaemia (PTH resistance)
Which drugs affect prolactin secretion?
- Any drug interacting with dopamine action can cause hyperprolactinaemia
- Antipsychotics - typical and atypical
- Antiemetics - metoclopramide, domperidone
- Antidepressants - SSRIs, MOAI, TCA
- Opiates
- H2 receptor antagonists
How is a prolactinoma diagnosed?
- Confirmed on MRI screening
- Microprolactinoma <1cm
- Macroprolactinoma >1cm
How are prolactinomas treated?
- Medical treatment is first line
- Dopamine (D2) agonists
- Cabergoline - long half-life, once/twice weekly
- Quinagolide
- Bromocriptine - short half-life
- Dopamine (D2) agonists
Describe the mechanism of action of ADH
- ADH (peptide hormone) secreted from posterior pituitary
- V1 receptors in vascular smooth muscle - vasoconstriction
- V2 receptors in distal tubule - aquaporin channel recruitment, reabsorption of water
What causes ADH secretion?
Low plasma volume/increased serum osmolality
Describe preparations of vasopressin (ADH)
- Desmopressin (DDAVP) - synthetic analogue of vasopressin with no vasoconstrictor effects and longer half-life
How is desmopressin administered in diabetes insipidus?
- Maintenance therapy for cranial diabetes insipidus
- Oral (bioavailability low)
- Sublingual
- Intranasal
- Acute therapy
- Subcutaneous
- Intramuscular
- Intravenous (variceal bleeding/shock)
Describe the negative feedback loop involved in thyroid hormone production
- Hypothalamus secretes thyrotropin releasing hormone (TRH)
- TRH stimulates secretion of thyroid stimulating hormone (TSH) by the anterior pituitary
- TSH stimulates the thyroid to secrete thyroxine (T4) and triiodothyronine (T3)
- High T4 has negative feedback effect on the hypothalamus and pituitary
Describe the absorption of levothyroxine
Incomplete gastric absorption, can be affected by other medication
Long half-life of 1 week in healthy patients, longer in myxoedema
