Endocrinology Flashcards
Anatomy of the thyroid gland
2 lobes joined by a central isthmus
Sits anteriorly to thyroid cartilage in the neck - distinguished from other neck features by its movement on swallowing
Vascular supply of the thyroid gland
Inferior and superior thyroid arteries
Constituents of thyroid tissue
Colloid - stores iodinated thyroglobulin
Follicular cells - synthesises thyroglobulin
Neuroendocrine cells (c-cells) - secrete calcitonin
Types of thyroid hormones
T4 (thyroxine) - main circulating hormone - converted peripherally to T3
T3 (triiodothyronine) - more potent and shorter acting
How are thyroid hormones transported?
Thyroxine binding blobulin (TBG)
Transthyretin
Albumin
Thyroid hormone receptors
Free hormone acts on intracellular thyroid receptors
TRα
TRβ
Actions of thyroid hormones
Increase basal metabolic rate and growth in children
Increase heart rate
Effect CNS and reproductive system
Interpretation of thyroid function tests
TRH stimulates pituitary TSH secretion
This drives T3 and T4 secretion
Features of primary hypothyroidism
Problem with thyroid gland itself - commonly autoimmune
Characterised by reduced circulating T4 and high TSH
Features of secondary hypothyroidism
Due to TSH deficiency - usually pituitary disease
Characterised by low T4 and non-elevated TSH
Features of hyperthyroidism
Characterised by increased T3/T4 with suppressed TSH
Things that can affect thyroid function tests
Acute illness
Medication - lithium and amiodarone
Pregnancy
Define thyrotoxicosis
Hyperthyroidism
Commonly affects young women
Causes of thyrotoxicosis
Autoimmune (Graves) - presence of TSH receptor stimulating antibodies
Nodular hyperthyroidism - autonomous secretion of T3/T4
Thyroiditis - inflammation of the thyroid gland causing release of thyroxine
Features of Graves disease
Hyperthyroidism
Commonly affects young women
Follows a relapsing-remitting course
Features of nodular hyperthyroidism
Typically presents at an older age
Either solitary toxic nodule or numerous nodules situated within a toxic multi-nodular goitre
Features of thyroiditis
Follows - viral infection - medication - amiodarone - childbirth Often followed by hypothyroid phase
Symptoms of hyperthyroidism
Increased sympathetic action
- weight loss with increased appetite
- insomnia
- irritability
- anxiety
- heat intolerance
- palpitations
- tremor
- pruritus
- increased bowel frequency and loose motions
- menstrual disturbance and reduced fertility
How may hyperthyroidism present in elderly patients?
Reduced energy levels - apathetic thyroidtoxicosis
Signs of hyperthyroidism
Resting tachycardia - sinus rhythm or atrial fibrillation
Warm peripheries
Resting tremor
Hyperflexia
Lid lag - increased sympathetic tone of upper eyelid`
Clinical features of Graves disease
Lid retraction
Exopthalmus
Thydroid eye disease
Skin changes - pre-tibial myxoedema and thyroid acropachy
Investigations for hyperthyroidism
Elevated free T4 and T3 with undectebtable TSH
Thyroid peroxidase antibodies are unspecific markers
TSH-receptor stimulating antibodies more specific
Imaging for hyperthyroidism
Nuclear imaging - determine functionality and cause
- Graves disease - uniform uptake
- Nodular disease - increased uptake in autonomous nodules
- Thyroiditis - absent uptake
USS - nodular thyroid disease but not activity
Treatment for hyperthyroidism
Medication - thionamides reduce synthesis of T3+4 - carbimazole and propylthiouracil - beta-blockers to control symptoms Surgery - thyroidectomy Radioactive iodine
Potential side-effects of thionamides
Agranulocyotisis - bone marrow suppression
- unexplained sore-throat or fever
- urgent full-blood count to exclude pancytopaenia
Generalised rash - disappears after cessation
What does radioactive iodine therapy involve?
Single dose of 131I
Cons of radioactive iodine
Pregnancy
May flare up eye disease in patients with pre-exisitng ophthalmopathy
Causes hypothyroidism - requires lifelong thyroxine replacement
Patients emit small amount of radiation after administration - avoid close contact to young children and pregnant women
Complications of thyroid surgery
Bleeding
Infection
Damage to recurrent laryngeal nerve
Temporary or permanent hypocalcaemia
Features of thyroid surgery
Effective definitive treatment for those who can’t comply with radiation restriction - mothers with young children
Thyroid function should be controlled pre-op to avoid anaesthetic problems
Beta-blockers used during anaesthetic if thyroid function not optimal - prevent peri-operative atrial fibrillation
Causes of primary hypothyroidism
Autoimmune disease - Hashimotos thyroiditis Pregnancy Iodine deficiency -> cretinism Drugs - amiodarone - lithium Iatrogenic - intentional treatment of hyperthyroidism - inadvertent damage from radiation to head/neck
Causes of secondary hypothyroidism
TSH deficiency
- due to hypothalamic-pituitary disease
Characterised by low free T4 with non-elevated TSH
Clinical features of hypothyroidism
Weight gain Cold intolerance Fatigue Constipation Bradycardia Myxoedema - thickening of skin and puffiness around eyes
Investigations for hypothyroidism
Low fT4 with elevated TSH
Thyroid antibodies - auto-immune hypothyroidism
Thyroid peroxidase - Hashimotos thyroiditis
Treatment for hypothryoidism
Thyroxine replacement - dose sufficient to improve symptoms and normalise thyroid function
- 50-100ug/day
- elderly pts and those with IHD started on 25ug/day
Issues with thyroxine replacement therapy
Persistently elevated TSH
- under-replacement
- poor compliance
- malabsorption - coeliac disease, concurrent medication (iron, calcium or PPIs)
Suppressed or undetectable TSH
- over-replacement
- increased risk of atrial fibrillation and osteoporosis
Define subclinical hypothyroidism
Normal fT4 with elevated TSH
If pts asymptomatic treatment may not be needed
Features of cortisol
Glucocorticoid
Synthesis regulated by ACTH
Highest at 08:00 and lowest at midnight
Most bound to cortisol binding globulin (CBG) and albumin
Cortisol feedback loop
Cortisol exerts negative feedback on:
- hypothalamus - reduce CRH and vasopressin
- anterior pituitary - reduce ACTH
Features of adrenal androgens
Mainly controlled by ACTH
DHEA, DHEA-S and androstenedione are converted to more potent testosterone and dihydrotestosterone in peripheral tissues
Exert effects on sebaceous glands, hair follicles, prostate gland and external genitalia
Features of mineralcorticoids
Aldosterone
Regulated by renin-angiotensin system
Features of RAAS system
Renin activated in response to low circulating blood volume, hyponatreamia or hyperkalaemia
Catalyses conversion of angiotensin to angiotensin I
Converted to angiotensin II by ACE
Stimulates aldosterone release upon binding to angiotensin receptor
Aldosterone acts on renal distal convoluted tubule on its receptor to cause sodium retention and potassium loss
Layers of the adrenal cortex
Zona glomerulosa - mineralcorticoids - aldosterone
Zona fasciculata - glucocorticoids - cortisol
Zona reticularis - androgens - DHEA
Features of the adrenal medulla
Sympathetic nervous system tissue Secretes - adrenaline - noradrenaline - dopamine
What is Addisons disease
Primary adrenal insufficiency
Destruction of adrenal gland or genetic defects in steriod synthesis
Effects all 3 zones
Symptoms of Addisons disease
Non-specific and gradual onset
Fatigue
Weakness
Anorexia
Weight-loss
Nausea
Abdo pain
Dizziness and postural hypotension - mineralocorticoid deficiency
Hypoglycaemia, increased pigmentation - glucocorticoid loss
Reduced libido and loss of axillary and pubic hair - androgen deficiency
Investigations for Addisons disease
Biochemical hallmarks - hyponatraemia - hyperkalaemia - raised urea - hypoglycaemia - mild anaemia Confirmatory tests - low 9am cortisol - raised ACTH concentration
Management of Addisons diseasee
Lifelong glucocorticoid and mineralcorticoid replacement therapy
- hydrocortionse 1st line - double at times of illness
- fludrocortisone
Provide steriod emergency card, encourage to wear medical alert jewellery and emergency contacts for endocrine team
Causes of secondary adrenal insufficiency
ACTH deficiency
- long term steriod use - sudden cessation -> adrenal crisis
Define a phaeochromocytoma
Catecholamine-secreting tumour which arises from the adrenal medulla
Define a paraganglioma
Catecholamine-secreting tumour which arises from the extra-adrenal chromaffin tissue
Clinical features of phaeochromocytoma
Headache Sweating Pallor Palpitations Anxiety/panic attacks Hypertension
Complications of untreated phaeochromocytoma
Hypertensive crisis Encephalopathy Hyperglycaemia Pulmonary oedema Cardiac arrhythmias Death
Investigations for phaeochromocytoma
Elevated catecholamines - 24hr urinary catecholamines - plasma metanephrines Radiological localisation of the tumour - CT or MIR abdo - 123I-MIBG - PET
Management of phaeochromocytoma
Surgical excision - laparo or open
Alpha+/-beta blockers at diagnosis
- phenoxybenzamine or doxazosin
Growth pituitary axis
GH is secreted in pulsatile manner - peak during REM sleep Acts on liver to produce IGF-1 Role in MSK growth in children Positive control - GHRH Negative control - somatostatin
Adrenal pituitary axis
ACTH has circadian rhythm - peak in early morning and lowest at midnight
ACTH stimulates cortisol release
Positive control - CRH
Negative control - cortisol
Gonadal pituitary axis
FSH leads to ovarian follicle development in women and sperm production in men
LH
- women - mid-cycle ovulation during LH surge and formation of corpus lutem
- men - testosterone secretion from the Leydig cells of testes
Positive control - GnRH
Negative control - testosterone, cortisol
Thyroid pituitary axis
TSH drives thyroxine release via stimulation of TSH receptors in the thyroid gland
Positive control - TRH
Negative control - thyroxine
Prolactin pituitary axis
Prolactin causes lactation
Direct inhibitory effect on LH and FSH
Negative control - dopamine
Clinical assessment of pituitary gland
Functional pituitary tumours = clinical syndromes - acromegaly - GH - Cushings disease - ACTH - prolactinoma - PRL - TSHoma - TSH Non-functioning - hypopituitarism - compression of local structures - bitemporal hemianopia
Biochemical assessment of pituitary gland
Prolactin and TSH do not fluctate at time of day
LH and FSH
- women - within 1st 5 days of menstrual cycle
- men - 0900 in fasting state
Basal cortisol checked at 0900
IGF-1 maker of GH - low levels suggest GH deficiency, high levels suggest GH excess
Dynamic tests of pituitary gland
Synacthen test - assess primary adrenal failure and pituitary ACTH reserve
- atrophy of adrenal cortex -> inadequate response to synacthen
- not acute
Insulin Tolerance Test - ACTH and GH reserve
- frank hypoglycaemia achieved with symptoms - ACTH and GH will rise
- not performed in pts with IHD or epilepsy due to risk of triggering coronary ischaemia and seizures
Pituitary gland imaging
MRI - injection of contrast - > 1cm = macro-adenomas - < 1cm = micro-adenomas CT if unable to have MRI PET to determine functionality
Differenentials for high prolactin levels
Pregnancy Medication - dopamine antagonists - anti-emetics, anti-psychotics Profound hypothyroidism PCOS
Features of a micro-prolactinoma
More frequently in women than men < 1cm Present with - menstrual disturbance - hypogaonadism in men - galactorrhoea - infertility
Distinguishing features of PCOS compared to prolactioma
Androgenic symptoms - hitsutism - acne Less elevated prolactin levels - <1000 miU/L Absence of pituitary lesion on MRI
Features of macro-prolactinomas
> 1cm
More common in men
Prolactin > 5000 miU/L
Treatment for prolactinomas
Dopamine agonists (D2)
- cabergoline - 1/2 weekly - better tolerance
- bromocriptine - daily
Side effects of D2 agonists
Nausea
Postural hypotension
Psychiatric disturbance
Complications of treatment of macro-prolactinomas
CSF leak due to rapid reduction of size of lesion
- risk of meningitits
Cardiac valve abnormalites in Parkinson’s disease
Causes of high prolactin
Pituitary - prolactinoma - non-functioning adenoma - infiltrative disease Hypothalmic - tumours - infiltrative disease Secondary - renal failure - primary hypothyroidism - adrenal insufficiency - PCOS Analytical - macroprolactin - heterophilic antibodies Medication - antipsychotics - antiemetics - antihypertensives - oestrogen Physiological - pregnancy - breast stimulation - stress
Causes of acromegaly
GH-secreting pituitary tumour
Complications of untreated acromegaly
Disfiguring features
Premature death from CVS disease
Increased risk of bowel cancer
Clinical features of acromegaly
Increased size of hands and feet
Facial features become coarser - frontal bossing of forehead, protrusion of chin and widely spread teeth
Soft tissue swelling - enlargement of tongue and soft palate, sleep apnoea, puffiness of hands, carpal tunnel syndrome
Sweating
Headaches
Hypertension
Diabetes mellitus
Investigations for acromegaly
Oral glucose tolerance test and IGT-1
- failure to suppress GH after OGTT and elevated IGF-1 levels
Pituitary MRI shows tumour
Management of GH-secreting pituitary tumours
Medical - somatostatin analogues improve symptoms and control GH and IGF-1 - GH receptor blockers control IGF-1 - dopamine agonists may control GH Radiotherapy - external beam - stereotactic - more targeted treatment at higher dose Surgery - treatment of choice
Monitoring of acromegaly
OGTT post-surgery to indicate if persistent disease
Long term follow up to monitor GH and IGF-1 levels and exclude recurrence
Periodic screening colonoscopy
Define non-functioning pituitary adenomas (NFPAs)
Biochemically inactive tumours
Clinical features of NFPAs
Visual field loss
Headache
Hypopituitarism
Indications for surgical treatment of NFPAs
Visual field defect of threat to vision
Trans-sphenoidal or trans-cranial
Causes of acquired hypopituitarism
Pituitary tumour
Inflammatory and infiltrative disorders
Traumatic brain injury
Radiotherapy
Clinical features of hypopituitarism
Lethary Weight gain Sexual dysfunction Short stature in children Acute hypo-adrenal crisis - hyponatraemia - hypotension
Investigation for hypopituitarism
Exclusion of adrenal insufficiency
Secondary hypothyroidism - low T4 and non-elevated TSH
Secondary hypogonadism - low sex hormones with non-elevated LH and FSH
GH deficiency - low IGF-1 levels
MRI - empty fossa or pituitary tumour
Treatment for hypopituitarism
ACTH deficiency - hydrocortisone replacement
TSH deficiency - thyroxine replacement
Gonadotropin deficiency
- men - testosterone
- women - oestrogen and progesterone
GH deficiency - GH as daily subcut injection
Features of Cushings Disease
Central obesity Dorso-cervical fat pad Increased roundness of face Red face - plethora Thick skin Easy bruising Proximal myopathy
Complications of Cushings Disease
Hypertension
Premature osteoporosis
Diabetes mellitus
Investigations for Cushing’s Disease
Screening
- alcoholism and severe depression may cause a cushingoid look
- 24hr urine free cortisol - elevated
- low dose dexamethasone suppression test - failure to suppress
- overnight dexamethasone suppression test - failure to suppress
Differentials for Cushing’s disease
Pituitary - pituitary MRI Adrenal - accelerated hirsutism - low ACTH Ectopic ACTH due to lung cancer or another malignancy - hypokalaemia - smoker - weight loss - whole body CT or PET scan
Management of Cushing’s disease
Adrenal tumour -> Laparoscopic adrenalectomy
Ectopic ACTH -> Treatment of underlying malignancy
Pituitary adenoma -> Trans-sphenoidal removal of the pituitary adenoma
Medical treatment
- Metyrapone
- Ketoconazole
- Radiotherapy
Symptoms of hyponatraemia
Early - headache - nausea - vomiting - general malaise Late - confusion - agitation - drowsiness Acute Severe - seizures - respiratory depression - coma - death
Investigations for hyponatraemia
Full history and examination Drug history - thiazide diuretics Hydration status Biochemical investigations - serum osmolality - urine osmolality - urine sodium - thyroid function - assessment of cortisol reserve - 09:00 cortisol or synacthen test
Treatment of hyponatraemia
Acute severe
- hypertonic saline - prevent cerebral oedema
Cause-specific treatment
Appropriate fluid replacement - normal saline
Characteristics of SIADH
Low plasma Na+
Low serum osmolality
High urine osmolality
High urine Na+
Causes of SIADH
Malignancy - lung small cell - pancreas - prostate - thymus - lymphoma CNS disorders - meningoencephalitis - abscess - stroke - subarachnoid/subdural haemorrhage - head injury/neurosurgery - vasculitis Chest diease - TB - pneumonia Drugs - opiates - psychotropics - SSRI - cytotoxics
Treatment of SIADH
Treat cause
Restrict fluid
Consider salt + loop diuretics if severe
Vasopressin receptor antagonists
Causes of hyponatremia
Urine osmolality < 100 mOsm/kg
- primary polydipsia
- inappropriate IV fluids
- low solute intake
Urine osmolatlity > 100 mOsm/kg
- urine Na+ < 30 mmol/L
- low effective arterial volume
- heart failure
- portal hypertension
- nephrotic syndrome
- hypoalbuminaemia
- GI loss
- urine Na+ > 30 mmol/L
- normal apparent circulating volume
- SIADH
- NSAIDs
- low effective arterial volume
- primary salt wasting
- vomiting
- hypoadrenalismDefine Diabetes Insipidus
Cranial - vasopressin deficiency
Nephrogenic - vasopressin resistance
Leads to passing of large volumes of dilute urine with profound unquenchable thirst
Biochemical hallmarks of DI
High serum osmolality
Low urine osmolality
High urine volume
Complications of DI
Hypernatraemia
Dehydration
Death
Cranial vs nephrogenic DI
Cranial usually seen in pituitary disease
Strong family history suggests genetic cause
Nephrogenic
- metabolic and electrolyte disturbance
- renal disease
- drugs affecting the kidney
Common causes of hypercalcaemia
Primary hyperparathyroidism - non-suppressed PTH
Malignancy - suppresed PTH levels
TB and sarcoidosis - suppressed PTH
Definition of hypercalcaemia
Serum calcium > 2.6 mmol/L
Malignant causes of hypercalcaemia
Squamous cell epithelial tumours - secretion of PTH-related peptide (PTH-rP)
Primary hyperparathyroidism causes
Single parathyroid adenoma
Parathyroid hyperplasia - genetic cause
Investigations of hypercalcaemia
High PTH - primary hyperparathyroidism Low PTH - malignancy Low phosphate - PTH causes excretion High ALP - increased bone turnover Bone density reduced - distal radius Nephrocalcinosis - renal USS
Clinical features of hypercalcaemia
Non-specific symptoms - tiredness - generalised aches and pains - abdo pain - constipation - kidney stones Primary hyperparathyroidism - asymptomatic Nephrogenic DI - polyuria and polydipisa
Define familial hypocalciuric hypercalcaemia (FHH)
Genetic defect in calcium sensing receptor
Low urine calcium/creatinine ratio
Family history of mild hypercalcaemia
Localisation of parathyroid adenoma
USS - 70-90%
SETAMIBI isotope scanning used alongside USS
Treatment of hyperparathyroidism
Surgery - serum calcium > 2.85 mmol/L or symptoms debilitating - young patients - parathyroidectomy Medical management - calcimimetic drugs Simple observation
Acute severe hypercalcaemia
Medical emergency
Presentation
- profound dehydration
- renal impairment
Define hypocalcaemia
Serum calcium < 1.9 mmol/L
Causes of hypocalcaemia
Post-surgical hypoparathyroidism Post-thyroidectomy - usually temporary - may be permanent due to damage or removal of parathyroid glands Severe vitamin D deficiency
Vitamin D deficiency presentation
Low phosphate - elevated PTH levels
Seizures and tetany in neonates - due to hypocalcaemia
Features of hypomagnesaemia
Causes functional hypoparathyroidism - normal or low PTH
Causes of hypomagnesaemia
GI loss
Alcohol
Drugs - PPIs
Clinical features of acute severe hypocalcaemia
Laryngospasm
Prolonged QT interval
Seizures
Clinical features of hypocalcaemia
Muscle cramps
Carpo-pedal spasm
Peri-oral and peripheral paraesthesia
Neuro-psychiatric symptoms
Positive Chvosteks sign - facial spasm when cheek gently tapped
Trousseasus sign - carpo-pedal spasm induced after inflation of sphygmomanometer
Treatment of hypocalcaemia
Calcium replacement
- acute - 10ml 10% calcium gluconate IV over 30 mins
- mild - 5mmol/6h PO calcium
Reverse cause
Treatment of vitamin D deficiency
Loading dose cholecalciferol
20,000 IU per week for 7 weeks
Maintenance dose of 1-2000 IU per week
Treatment of hypoparathyroidism
1-alfacalcidol 0.25mcg/day or calcitriol - dose titration according to clinical and biochemial response
Oral calcium supplements - Sandocal and Adcal D3
Aim to keep calcium levels at lower end of normal - reduce risk of nephro-calcinosis
Treatment of magnesium deficicency
Acute - precipitating drugs stopped - IV MgSo4 24mmol/24hrs Chronic - GI loss or alcohol ingestion - specialist input
Define psuedo-hypoparathyroidism
Mutation in G protein coupled to PTH receptor
Leads to PTH resistance
Characteristics of pseudo-hypoparathyroidism
Characterised by
- hypocalcaemia
- high phosphate
- high PTH
- normal vitamin D
Clinical features of pseudo-hypoparathyroidism
Short stature
Round face
Short 4th and 5th metacarpals
