ENDOCRINOLOGY Flashcards
What does PTH do?
Increases serum calcium
Increases osteoclast activity to increase bone turnover releasing calcium and phosphaye
Increasesvitamin D3 production
Increases uptake of calcium in the kidneys
What are the causes of Primary Hyperparathyroidism?
Cancer of the parathyroid gland
80% Solitary Adenoma
(multifocal disease, hyperplasia, multiple adenoma, parathyroid carcinoma)
What are the clinical features of Primary Hyperparathyroidism?
- Elderly females with unquenchable thirst with inappropriately normal or raised parathyroid hormone*
Signs of hypercalcaemia
HTN
Raised ALP
How is Primary Hyperparathyroidism managed?
Fluids prevents stones
Total parathyroidectomy (remove the parathyroid glands) if:
- High blood calcium: Serum Calcium >1mg/dL above noral
- High urine calcium: Hypercalciuria >400 mg/day
- Life threatiening hypercalcaemia
- Nephrolithiasis
- > 50 y/o
- Neuromuscualr symptoms
- Reduction in bone mineral density
Calcimimetic agents: cinacalcet if not suitable for surgery
What causes Secondary Hyperparathyroidism?
Parathyroid gland HYPERPLASIA due to LOW CALCIUM due to CKD
What are the clinical features of Secondary Hyperparathyroidism?
Few symptoms
Eventually bone disease
Soft tissue calcification
How is Secondary Hyperparathyroidism managed?
Manage medically, indications for parathyroidectomy:
- Bone pain
- Persistent pruritis
- Soft tissue calcification
What are the causes of Tertiary Hyperparathyroidism?
Ongoing hyperplasia of all 4 glands after CKD is corrected
What are the clinical features of Tertiary Hyperparathyroidism?
Metastatic calcification Bone pain and/or fractures Nephrolithiasis Pancreatitis Raised ALP
How is Tertiary Hyperthyroidism managed?
Only treat after 12 month persistance because it usually resolves
Remove culprit gland or all
What are the causes of Malignant Hyperparathyroidism?
PTH related-peptide produced by some Squamous cell Lung cancers, Breast cancers and renal cell carcinomas
What are the hormone levels in the hypeparathyroidisms?
1’ Raised: PTH Calcium
Low: Phosphate
2’ Raised: PTH Phosphate
Lowered: Calcium Vitamin D
3’ Raised: PTH Calcium
Lowered: Phosphate Vitmain D
Malignant: Raised: Calcium
Lowered: PTH (because PTHrp is raised)
What are the causes of primary hypoparathyroidism?
Gland failure
- AI
- Di geoge syndrome
- Thyroid surgery
What are the features of primary hypoparathyroidism?
Hypocalcaemia
High phosphate
How is primary hypoparathyroidism manged?
Calcium supplements
Calcitriol
Synthetic pTH
What are the causes of secondary hypoparathyroidism?
Radiaiton
Surgery
Hypomagensia
What is pseudo hypoparathyroidism?
Target cells are insensitive to PTH (due to a G protein abnormality) so PTH is actually high (calcium is low)
- Low IQ
- Short stature
- Short 4th abd 5th metacarpals
- Calcified basal ganglia
What is pseudopsuedo hypoparathyroidism?
Same features but normal biochemistry
What do the zones of the Adrenal Cortex produce?
Zona Glomerulosa- Mineralcorticoids
Zona Fasiculata- Glucocorticoids
Zona Reticularis- Sex steroids
What is Cushing’s syndrome?
CLINICAL STATE reduced by chronic EXCESS of GLUCOCORTICOIDS, loss of normal feedback mechanism and loss of CORTISOL secretion circadian rhythm
What are the causes of Cushing’s syndrome?
ACTH independent:
the adrenal gland is making too much cortisol and the ACTH is low. ADRENAL TUMOUR or bilateral adrenal hyperplasia
ACTH dependent:
- Cushing’s disease: Bilateral adrenal hyperplasia from PITUITARY ADENOMA secreting ACTH
- ECTOPIC ACTH production e.g. Small cell lung cancer
What are the symptoms of Cushing’s syndrome?
Acne
Mood changes (depressed, lethargic irritable, psychosis)
Hirsutism
Increased weight
Acanthiosis Nigricans (brown velvety skin discoloration e.g. in axilla)
Erectile dysfunction/Irregular menses
Recurrent achilles tendon rupture
What are the signs of Cushing’s syndrome?
Infections Moon face Buffalo hump Central obesity Purple striae Poor healing Skin and muscle hypertrophy Bruising Osteoporosis
What are the tests for Cushing’s syndrome?
1st line:
- overnight DEXAMETHASONE SUPRESSION TEST (should suppress to <50nmmol/L
or
- 24 hour urinary free cortisol
2nd line:
48 hour dexamethasone suppression
High-dose DMST differentiates between pituitary and non-pituitary causes
What is Primary Adrenal Insufficiency?
Autoimmune (Addison’s), Infective (TB, HIV, meningiococcal septicaemia), Metastases and Anti-phospholipid syndrome cause significant BILATERAL damage to the adrenal glands. This IMPAIRS ALL 3 LAYERS of the cortex and loss of negative fb causes the PITUITARY INCREASES ACTH PRODUCTION
What are the signs and symptoms of reduced function of the Zona Glomerulosa?
Reduced production of mineralcorticoids so reduced serum aldosterone.
Increased sodium lost -> HYPONATRAEMIA -> water lost -> HoTN (postural)-craving for salt
K+ retained -> HYPERKALAEMIA
H+ retained -> METABOLIC ACIDOSIS
What are the signs and symptoms of reduced function of the Zona Fasiculata?
Reduced production of glucocorticoids so reduced serum cortisol
Reduced ability to mobilise glucose into blood stream causes HYPOGLYCAEMIA
Increased Vasodilation (cortisol is a vasoconstrictor) HOTN (POSTURAL)
SIADH (cortisol usually inhibits) HYPONATRAEMIA
MALAISE FATIGUE ANOREXIA WEIGHT LOSS WEAKNESS ABDOMINAL PAIN JOINT AND MUSCLE PAIN N&V MOOD CHANGES: depression and psychosis
What are the signs and symptoms of reduced function of the Zona Fasiculata?
Reduced testosterone in women (because adrenals are only source)
Reduced axillary and pubic hair, reduced libido
How is Primary Adrenal Insufficiency tested for?
Raised ACTH from pituitary due to lack of negative feedback from cortisol.
Short SYNACTHEN test: measure cortisol 30 min before and after giving 250ug IM of synacthen
9am cortsol <500mmol/L
Serum aldosterone levels
Na+, K+, BM, pH
How is Primary Adrenal Insufficiency managed?
Give HYDROCORTISONE
20-30mg/day in 2-3 divided doses with the majority in the morning
Avoid late in the day-can cause insomnia
Don’t stop
Double the dose if infection or increased stress
What is Acromegaly?
Excess of growth hormone
What are the causes of Acromegaly?
95% due to PITUITARY ADENOMA
<5% due to ectopic GHRH or GH production by other tumours
What are the features of Acromegaly?
Enlarged features, organs and
- Headaches
- Supraorbital bulging
- Vision defects
- Enlarged lips, tongue and nose: coarse features
- Jaw and dental changes
- Thyroid hypertrophy
- Voice changes
- Skin tags
- Galactorrhoea due to prolactin increase
- Cardiomegaly
- Hepatospleonmegaly
- HTN
- Carpal tunnel and enlarged hand breadth and feet
- Bowel polyps
- Nephromegaly
- Enlarged colon
- Acanthinosis Nigricans
- Osteoarthritis
What are the complications of Acromegaly?
HTN
DMT2
Cardiomyopathy
Colorectal cancer
How is Acromegaly tested for?
GH is not diagnostic
- OGTT with serial GH measurements, hyperglycaemia usually suppresses
- 25% have impaired glucose tolerence
- IGF-1 will be high
- MRI will show a pituitary tumour
How is Acromegaly managed?
Trans sphenoidal surgery to remove pituitary tumour
Somatostatin analouge inhibits GH
External irradiotion
Dopamine agonists used for raised prolactin
What is Metabolic Syndrome?
3 or more of:
- High waist circumference
- BMI >30 (central obesity)
- Raised trigylcerides
- Low HDL
- HTN
- Raised fasting blood glucose
individuals have insulin resistance (in muscle, liver and adipose) resulting in high levels of circulating insulin and C-Peptide levels
What is a phaeochromocytoma?
Neuroendocrine tumour of cromaffin cells in medulla of the adrenal glands that secretes high amounts of CATECHOLAMINES (mostly Noradrenaline and some Adrenaline)
How do Phaeochromocytomas present?
Sympathetic nervous system hyperactivity
- Skin sensations
- Riased H.R and Palpitations
- Raised BP
- Anxiety
- Diaphoresis (sweating)
- Headaches
- Pallor
- Weight loss
How are Phaeochromocytomas managed?
Measure catecholamines and metanephrines in blood
or urine
Give alpha adrenoceptor blocker (e.g. phenoxybenzamine) or SAA Antagoinst to preduce risk of hypertension during surgery
Salt load due to volume depletion
NEVER USE NON-SELECTIVE B BLOCKERS
Syrgically resect
What is the inheritence pattern of Multiple Endocrine Neoplasias?
A.D
What is MEN-I?
3 Ps
Parathyroid: hyperplasia -> hyperparathyroid
Pituitary tumours e.g. Prolactinoma
Pancreatic tumours e.g insulinoma/glucagonoma
+ adrenal
+ thyroid
MEN-I gene
What is MEN-IIa?
2 Ps
Medullary THYROID CA
Paraythyroid
Pheochromocytoma
RET Oncogene
What is MEN-IIb?
1 P
Medullary THYROID CA
Pheochromocytoma
+ marfanoid
+neuromas-thickening of nerve tissue in parts of body
RET Oncogene
What is Diabetes Mellitus?
Chronic hyperglycaemia due to reduced endogenous insulin or reduced effectiveness of insulin
What is DMT1?
AI destruction of B cells in Islets of Langerhans resulting in absolute insulin deficiency
HLA-DR3/4
Presents with: Polyuria, Polydipsia and DKA
What is DMT2?
Excess adipose tissue results in a RELATIVE INSULIN DEFICIENCY (not enough to go round)
Often found incidentally but may present with polydipsia and plyuria
What is Pre-diabetes?
FBG: 6.1-6.8
HbA1c : 42-47 (6-6.4%)
Not yet diabetic but likely to go on to develop DMT2 without intervention
What is MODY?
Maturity Onset Diabetes of the Young
A.R inheritance, affects insulin production
Presents like DMT2 <25y
Sulfonylureas work very well
What is LADA?
Latent AI Diabetes in Adults
DMT1 that presents later in life
What are other causes of Diabetes?
- Acromegaly
- Chronic pancreatitis
- Hyperthyroidism
- Haemochromatosis
- Phaeochromocytoma
- Insulinoma
- Cushing’s (increased glucocorticoids)
What are the tests for Diabetes?
Finger-prick
One off BG: fasting or non-fasting
HbA1c: average blood sugars over 3 months
GTT: 75mg test blood sugars 2 hours later
What are the criteria for diagnosing Diabetes?
Symptomatic: Fasting > 7.0 mmol/L
Random (or GTT) >11.1 mmol/L
If Asymptomatic these need to be demonstrated on two separate occasions
HbA1c > 48 (6.5%)
When can HbA1c not be used?
- glucocorticoids
- children
- haemolytic anaemia
- untreated iron deficiency anaemia
- HIV
- CKD
What are the risk factors of Diabetes?
Microvascular:
- Retinopathy
- Neuropathy
- Nephropathy
Macrovascular:
- Stroke (x2)
- CVD (x4)
What blood pressure should be aimed for in Diabetes?
<140/80 unless end-organ failure then <135/80
What are the stages of Diabetic Retinopathy?
Background
Pre-proliferative
Proliferative
Maculopathy
What are the features of Background Diabetic Retinopathy?
- Microaneurysms (dots)
- Haemorrhages (blots)
- Hard exudates (lipid deposits)
Refer if any of these are near the macula
What are the features of Pre-proliferative Diabetic Retinopathy?
- Haemorrhage
- Venous beading
- Cotton-wool spots (infarcts)
Refer
What are the features of Proliferative Diabetic Retinopathy?
New vessels have formed
Refer as an emergency
What are the features of Maculopathy Diabetic Retinopathy?
Reduced acuity
Due to high retinal blood flow Cotton wool spots Blot haemorrhages New vessels Ischaemic areas proliferate, bleed, fibrose and detach from the retina
Give prompt steroids
What are the types of cataracts?
Snowflake-juvenile
Senile- earlier onset in diabetics
What are the two types of Diabetic Foot?
Ischaemic (micro and macrovascular)
Neuropathic
What are the features of Ischaemic Diabetic Foot?
Critical toes Absent dorsalis pedis -> do doppler Ulceration - Punched out - Painless - Areas of thick caluss
Check feet, chriopody
What are the features of Neuropathic Diabetic Foot?
Injury/infection over pressure points e.g. metatarsal heads
Reduced sensation: ‘stocking’ distribution
Test with Monofilament-patchy loss
Absent ankle jerk
Deformities:
- Pes Cavus: high arch
- Claw toes
- Loss of transverse arch
- Rocker bottom foot
- Charcot’s foot: repeated joint injury, weakining of the bones
How are Diabetic foot problems assessed?
- Neuropathy: Monofilament
- Ischaemia: doppler
- Boney deformities: do x-ray
- Infection
What are the types of Diabetic neuropathy?
Symmetrical sensory Polyneuropathy: peripheries ‘glove and stocking’, worse at night
Amyotrophy: painful wastage of Quadriceps of Femoral muscles
Mononeuritis Multiples: damage to >2 nerve arease.g. CN III and VI
Autonomic neuropathy:
- Postural fall in BP
- Vagal neuropathy
- Gastroparesis
- Gustatory sweating
- Urine retention
- Erectile dysfunction
- Diarrhoea
What is Hypoglycaemia?
Plasma glucose <3 mmol/L
How does Hypoglycaemia present?
Autonomic:
- Dizziness
- Anxiety
- Palpitations
- Tremor
- Sweating
- Abdominal pain
Neuroglycopenic:
- Confusion
- Coma
- Seizures
- Personality changes
- Mutism
- Vision issues
What are the two types of Hypoglycaemia?
Fasting: often in pre-existing diabetes due to INSULIN or SULPHONYLUREAS w/ increased activity, missed meal or overdose
OR
EXPLAIN
EXogenous drugs e.g. access to someone else's diabetic meds Pituitary insifficiency Liver issues Addison's Insulinoma/Immune Non-pancreatic cancer
Post-prandial: e.g. in gastric/bariatric surgery
How is Hypoglycaemia managed?
ORAL SUGAR + LONG ACTING STARCH
OR
IV 50% Glucose 25-50ml with 0.9% saline
OR
IM Glucagon Img, repeat in 20 min + ORAL CARB
What are the causes of Hypothyroidism?
Primary: problem with the gland e.g. AI
- Hashimoto’s
- Priamry Atrophic Hypothyroidism
- Subacute Thyroiditis (De Quervain’s)
- Riedel Thyroiditis
- Drugs
- Iodine deficiency (lacking in diet, MCC in developing world)
- Thyroidectomy or Radioiodine treatment
- Post-partum
Secondary: pituitary gland disorder e.g. Pituitary Apoplexy
Congenital: Thyroid dysgenesis or dyshomogenesis
What are the Congenital Hypothyroidisms?
Thyroid Dysgenesis
Thyroid Dyshomogenesis
- Turner’s
- Down’s
- coeliacs
1/4000- Screen at birth with heel-prick and treat within 4 weeks to avoid irreversible cognitive impairment (Cretinism)
Features:
- Prolonged neonatal jaundice
- Delayed mental and physical development (short stature)
- Puffy face
- Macroglossia
- Hypotonia
What is Hashimoto’s Thyroiditis?
- AI associated with DMT1, Addison’s and Pernicious Anaemia
- Antithyroglobulin antibodies
- Antithyroid peroxidase
Can cause transient Thyrotoxicosis in acute phase (Hashitoxicosis)
Firm and Non-tender GOITRE due to LYMPHOCYTIC and PLASMA CELL INFLITRATION
More commen in women, 60-70
What is Primary Atrophic Hypothyroidism?
Diffuse LYMPHOCYTIC INFILTRATION causing ATROPHY so no goitre
What is Subacute Thyroiditis (De Quervain’s) when Hypothyroid?
Hypothyroidism 3 weeks after initial onset (prior to this hyper/euthyroid) ultimately caused by viral infection
Painful goitre
Reduced Iodine scan uptake
Increased ESR
What is Riedel’s Thyroiditis?
Rare
Associated with Retroperitoneal fibrosis
Fibrous tissue replaces the parenchyma causing a HARD and FIXED PAINLESS GOITRE
What drugs can cause Hypothyroidism?
Lithium
Amiodarone
(Carbimazole)
What are the features of Hypothyroidism?
- Dry scalo
- TATT
- Dementia
- Non-pitting oedema
- Cold intolerence
- Hoarse voice
- Bradycardia
- Weight gain
- Dry, yellow skin
- Constipation
- Carpal tunnel
- Menorrhagia
- Myalgia, cramps and weakness
- Reduced tendon reflexes
- MACROCYTIC NORMOBLASTIC ANAEMIA
- Acanthinosis nigricans
How is Hypothyroidism managed?
Give LEVOTHYROXINE 50-100mg OD
(Start lower in elderly and IHD)
Check levels 8-12 weeks after dose change
INCREASE by 25-50mg in PREGNANCY
What are the ARDs of Levothyroxine?
- HYPERTHYROIDISM
- Reduced BONE MINERAL DENSITY
- Worsen ANGINA
- AF
- Interacts with IRON ABSORPTION so take 2 HOURS apart
What are the causes of Thyrotoxicosis?
Vast majority is Primary
- Grave’s disease
- Toxic Multinodular goitre
- Drugs
- Subacute thyroiditis
- Post-partum thyroiditis in the acute phase
- Acute phase of Hashimoto’s
Never congenital and only 1% are secondary
What is Grave’s disease?
50% of Thyrotoxicosis
TSH receptor stimulating antibodies in 90%
Anti-thyroid peroxidase in 75%
Specific signs to Grave's disease: - EYE involvement - Pretibial MYXODEMA - Thyroid ACROPACHY: soft tissue swelling of hands and clubbing Periositis in metacarpals
Females 30-50
What is a Toxic Multinodular Goitre?
AUTONOMOUSLY FUNCTIONING thyroid NODULES that secrete excess thyroid hormones
NUCLEAR SCINTIGRAPHY-patchy uptake of iodine
What are the drug causes of Thyroiditis?
Amiodarone
Levothyroxine
What is Subacute Thyroiditis (De Quervain’s)?
Following VIRAL Infection
4 PHASES:
1-Acute phase-3-6weeks-HYPERTHYROID
- Painful goitre
- Give NSAIDs and steroids
2-1-3weeks-EUTHYROID
3-weeks-months-HYPOTHYROID
4-Structure and function back to normal
Global reduction in thyroid uptake on iodine-131 scan
What are the features of Thyrotoxicosis?
- Restless
- Anxiety (labile emotions)
- Heat Intolerence
- Sweating
- Goitre with nodules and bruit
- Palpitations, arrhythmias (AF)
- Palmar Erythema
- Tremor
- Diarrhoea
- Acropachy
- Oligomenorrhoea
- Weight loss (although weight gain in 10% of cases)
- Pretibial Nyoxdena-oedematous swelling above lateral malleoli
- RAISED ESR, LFT and CA2+
How is Thyrotoxicosis managed?
- Thyroidectomy
- Propanolol
- Carbimazole 40mg (blocks thyroid peroxidase from coupling and iodinating tyrosine residues on thyrogloblin reducing Thyroid hormone reduced T3 and T4)
Give in high doses for 6 weeks until Euthyroid - Radioiodine
What are the ADRs of Carbimazole?
Agranulocytosis
Crosses placenta
What are the hormone levels in Thyrotoxicosis?
TSH down
T4 up
What are the hormone levels in Primary Hypothyroidism?
TSH up
T4 down
What are the hormone levels in Secondary Hypothyroidism?
TSH down
T4 down
What are the hormone levels in Sick Euthyroidism?
TSH down (or normal)
T4 down
T3 down
Caused by a non-thyroidal SYSTEMIC ILLNESS, reversible
TENDER GOITRE
What are the hormone levels in Subclinical Hypothyroidism?
TSH up
T4 normal
Pre-hypo, T4 still normal
2-5% progression risk/year which is higher if autoantibodies are present
What are the hormone levels in Poor Thyroxine Compliance?
TSH up
T4 Normal
Patients taking Levothyroxine just before their blood test
What are the hormone levels in Steroid use?
TSH down
T4 normal
TSH lags
How should Sub-Clinical Hypothyroidism be managed?
TSH 4-10mU/L + normal T4
IF <65year + symptoms Trial Levothyroxine (stop if no improvement to symptoms)
IF >80years/asymptomatic
Observe and repeat thyroid function in 6months
TSH >10mU/L
<70years TREAT
>80 Observe and repeat thyroid function in 6months
What are the Thyroid Eye Features?
Retro-orbital inflammation
No signs, no symptoms Only signs, no symptoms Soft-tissue involvement Ptosis Exopthalmos Conjunctival ulceration Sight-loss
What are the types of Thyroid Cancer?
Rarely secrete hormones so don’t present with hypo/hyperthyroidisms
PAPILLARY CARCINOMA 70% FOLLICULAR 20% MEDULLARY CARCINOMA 5% ANAPLASTIC CARCINOMA 1% LYMPHOMA
What are the features of Papillary Thyroid Carcinoma?
Young females
Very good prognosis
Mix of PAPILLARY and COLLOIDAL filled follicles
Tumour papillary projections + pale empty nuclei
Seldom encapsulated
Lymph node metastasis predominately to cervical lymph nodes
Thyroglobulin tumour marker
What are the features of Follicular Thyroid Cancer?
ADENOMA: Solitary thyroid nodule (usually) can be toxic and produce T3 + T4
CARCINOMA: females >50
- Macroscopically encapsulated, microscopically capsular invasion can be seen
- Vascular invasion predominates
- Multifocal disease is rare
Can only tell the diff in hemithyroidectomy
Thyroglobulin tumour marker
How are Papillary and Follicular Thyroid cancers?
- Total thyroidectomy
- Radiodine 131 to kill residual cells
- Repeat thyroglobulin levels to detect recurrence early
What are the features of Medullary Carcinoma?
Cancer of parafollicula cells
MEN-2 or sporadic
Secrete Calcitonin so use as tumour marker
Lymphocytic and haemategenous metastasis
Nodal disease = poor prognosis
May have amyloid deposits
What are the features of Anaplastic Thyroid Carcinoma?
v rARE
Elderly females
Local invasion common
Resect if poss
What are the features of Thyroid Lymphoma?
Associated with Hashimoto’s
Present with dysphagia or stridor
What are the complications of Thyroid surgery?
- Damage to recurrent laryngeal n.
- Bleeding into a confined space causing respiratory compromise and laryngeal oedema
- damage to the thyroid gland causing hypothyroidism
What is Diabetes Insipidus?
polyuria and polydipsia due to lack of ADH or ADH resistance
What are the causes of Diabetes Insipidus?
Central: LACK of ADH due to damage to the HYPOTHALAMUS and PITUITARY
Nephrogenic: genetic RESISTANCE of kidneys to ADH
Dipsogenic: abnormal thirst mechanism in the hypothalamus
Gestational
What are the osmolalities in Diabetes Insipidus?
High plasma osmolality
Low urine osmolality <700mOsm/kg
Opposite of SIADH
What are the causes of Hyperaldosteronism?
Primary: CONN’S
Uni/Bilateral tumour in the adrenal glands
Secondary:
- Renal artery stenosis
- Congestive heart failure
- Cirrhosis
- Nephrotic syndrome
What are the features of Conn’s Syndrome (primary hyperaldosteronism)?
High aldosterone:
Hypernatraemia: HTN
Hyperkalaemia:
- Cramps
- Paraesthesia
- Polyuria
- Polydipsia
and low H+:
Metabolic Alklalosis
What is the pathophysiology of Secondary Hyperaldosteronism?
Cirrhosis/Npehrotic syndrome - low albumin - low colloid OSMOTIC PRESSURE - HoTN
OR
Renal artery stenosis/HF
all lead to…
Not enough blood to kidney
Increase Renin
Increase aldosterone
detect in venous sampling
How are Primary Hyperaldosteronism and Secondary Hyperaldosteronism differentiated?
RENIN:ALDOSTERONE RATIO
How is Hyperaldosteronism managed?
primary: laproscopic removal of adrenal tumours
Sprionolactone: aldoseterone antagonist
