Endo Flashcards
HT eye changes
RB
Grade 1: Silver wiring (Increased arteriolar light reflex)
Grade 2: AV nipping (deflection of venule at AV crossing points)
Grade 3: Flame-shaped hemorrhage, cotton wool spot,
Grade 4: Papilledema
Look for LVH, HF
DM eye changes
RB
Non-proliferative
- Microaneurysm
- Dot-blot hemorrhage
- Hard exudates
Pre-proliferative
- Cotton wool spots
- Venous beading
- Hemorrhages, IRMA (intraretinal microvascular abnormalities)
Proliferative
- NVD/NVE (Neovascularization at disc / elsewhere)
- Photocoagulation scars
- Vitreous hemorrhage
MEN 1 (Multiple endocrine neoplasia)
Chromo 11 - MEN 1 gene
(aka Wermer syndrome)
- Pituitary adenoma (Prolactinoma)
- Pancreas endocrine tumor
- Parathyroid hyperplasia/adenoma
MEN 2A/2B
Multiple endocrine neoplasia
Chromo 10 - RET gene 2A - Parathyroid hyperplasia - Medullary CA thyroid - Pheochromocytoma
2B
- Mucosal neuroma
- Medullary CA thyroid
- Pheochromocytoma
Gliptins
Dipeptidyl peptidase-4 inhibitor (DPP4 inhibitor)
Whipple’s triad
- Hypoglycemic Sx
- Low plasma glucose (not by H’stix)
- Sx relief after increase back plasma glucose
Indicates insulinoma
Insulin types
- Ultra-short acting (Rapid)
- Short-acting (Human insulin)
- Intermediate-acting (usu start with this in Type 2)
- Long-acting (Basal; usu for type 1)
- Pre-mixed
SE of Insulin
- Hypoglycemia
- Weight gain
- Lipodystrophy / Lipohypertrophy
- Routine rotation of injection site recommended
Dose of Insulin for Type 1 DM
- 0.5 unit/kg/day
- Half as basal; half as bolus (further break into tds)
Types of oral DM drugs
x7
- Biguanide (Metformin)
- Sulphonylurea (Gli-)
- Meglitinide (-glinide)
- Alpha-glucosidase inhibitor (Acarbose)
- Thiazolidinediones (-glitazone)
- DPP4 inhibitors (-gliptins)
- SGLT2 inhibitors (-gliflozins)
Biguanide
Metformin
- Increase insulin sensitivity
- Decrease hepatic glucose production
Increased risk of DM
- DM in 1st degree relatives
- History of GDM
- Age >45
- Obesity, HT, dyslipidemia
Metabolic syndrome
Cluster of metabolic disorders linked by insulin resistance and asso w/ accelerated atherosclerosis
- Glucose intolerance or T2 DM
- HT
- HyperTG
- Decrease HDL
- Central obesity (90cm in M; 80cm in F)
Any 3 or more
Sx of Hypoglycemia
Adrenergic
- Palpitation
- Sweating
- Tremor
Neuroglycopenic
- Hunger sensation
- Restless, anxiety
- Finger, peri-oral numbness
- Altered consciousness, drowsiness, coma
Presentation of DKA
- Lethargy
- Dehydration / Hypotension (due to glycosuria)
- SOB / Kussmaul breathing (rapid, deep) due to metabolic acidosis
- Fruity odor (ketones)
- Altered consciousness (due to cerebral edema)
- N/V
- Abd pain
Presentation of Hyperosmolar non-ketotic coma
No N/V, abd pain, Kussmaul breathing
- Severe hyperglycemia and dehydration
- Depressed sensorium (lack of thirst response: when serum osmolarity >340)
Tx of DKA
- Replace salt and water deficit - IV NS + K supplement (guided by serum K and renal fx)
- Insulin - low dose (5-10 u/h) by continuous IV infusion. ↓Rate when BG <13 mmol/L
- Correct acidosis - pH rises with rehydration and insulin. HCO3 infusion if pH <7.1
- Identify and treat the cause of DKA
- Monitor clinical response, BP/P, urine output; CVP and ECG as indicated
- Emergency measures/care of the unconscious patient
H’stix
Haemoglucostix
Ix for DKA
- Plasma glucose
- Urine/Serum ketones
- Blood gas
- Electrolytes
- Look for precipitating infections (RS, GI, septicemia, meningitis)
DKA prevent advice
RB
Reinforcement of “sick-day” rules
- More freq monitoring of BG during illness
- Check urine or blood for ketones
Marked hyperglycemia require temp adjustment of insulin regimen, if also has ketosis, seek medical help
Causes of HyperPRL
RB
- Tumor (pressure effect / functional prolactinoma / GH+PRL tumor)
- Physiological: preg, breastfeeding
3 Stress, e.g. venipuncture - Drugs, e.g. methyldopa, chlorpromazine, OCP
- Hypothyroidism
Tx of Prolactinoma
RB
Medical as primary tx
- Dopamine agonists (Bromocriptine, Cabergoline)
Surgery if drug intolerance/resistance/compliance
Other pit tumors –> transphenodal surgery
Most common causes of HyperCa
RB
- Primary hyperPTH
- HyperCa of malignancy
Others
- Excessive Vit D / Ca intake
- Hyperthyroidism
- Sarcoidosis
- Active TB
- Familial hypocalciuric hyperCa
Ix for HyperCa
RB
- Serum albumin
- Serum phosphate
- ALP
- RFT
- PTH
- 24h urinary Ca excretion
Also,
- AXR, USG kidneys for stones
- Bone mineral density assessment
HyperPTH classification
RB
Primary
- 80% adenoma; 20% multiple adenoma / hyperplasia; 1% carcinoma
Secondary
- Due to hypoCa in CRF
Tertiary
- Autonomic secretion of PTH after prolonged duration of secondary (e.g. CRF in dialysis)
Ix to localize abnormal parathyroid gland
RB
USG, CT, MRI
Radioisotope (Thallium/Sestamibi) scan
Intra-op USG
**Sestamibi scan better than conventional
Indication for surgery for primary hyperPTH
RB
- Serum total Ca 1mg/dL (0.25mM) above ULN
- Hypercalciuria (24h >400mg)
- CrCl reduced by >=30%
- Renal stone
- Osteoporosis
- Age <50
Hyperthyroid + neck swelling causes
RB
- Graves’ disease
- Toxic multinodular goiter
- Toxic thyroid adenoma
- Subacute thyroiditis
Mechanism of anti-thyroid drugs
RB
Inhibit TH synthesis - block organification of iodide and coupling of iodotyrosines
PTU in high dose inhibit T4 to T3 conversion
Immunomodulatory effects to reduce thyroid autoAb levels
SE of Anti-thyroid drugs
(Thiouracil derivatives (Thionamides): Methimazole, Carbimazole, Propylthiouracil
Lithium - block NaI transporter)
RB
- Rash (5%)
- Agranulocytosis (0.1%)
- Cholestatic jaundice, hepatotoxicty (esp PTU), acute arthralgia, ANCA induced vasculitis
Graves ophthalmopathy NO SPECS classification
- No S/S
- Only signs (Lid lag, retraction, stares), no Sx
- S/S, Soft tissue (swelling, redness)
- Proptosis
- EOM
- Corneal
- Sight loss (optic n. atrophy)
Sx of Hyperthyroidism
- LOW
- Palpitation
- Nervousness
- Easy fatiguability
- Excessing sweating
- Heat intolerance
- Hand tremor
- Diarrhea
- Hair loss
- Eye problem
?Amenorrhea
Signs of Hyperthyroidism
- Goiter
- Thyrotoxic eye signs (lid lag, lid retraction, periorbital edema, exophthalmos, EOM, corneal involvement, sight loss)
- Pretibial myxedema (for Graves)
TRAb
TSH receptor Ab
Prognostic indicator of outcome of Graves after end of antithyroid drugs
Radioisotope thyroid scan in different types of hyperthyroidism
Graves –> Diffuse, increase
MNG –> Heterogenous
Toxic adenoma –> Increase focal, rest reduced
TSH-secreting pit adenoma –> Diffuse, increase
Thyroiditis / Iatrogenic / T4 overdose –> Decrease
Thyroid surgery Cx
- Vocal cord dysfunction
- Damage RLN, external branch of superior laryngeal n.
- Hypothyroidism
- Bleeding
- Tracheomalacia
- Thyroid storm
- Wound Cx: hypertrophic scar
Indication for RAI
- Thyrotoxic heart disease
- Relapse after surgery
- CI to surgery
- Adult >30y
Cx of RAI
- Hypothyroidism
- Fetal risk (avoid preg in 6-12m)
- No breastfeeding (excreted in milk)
- Thyroid eye disease
- Radiation thyroiditis –> thyroid storm
Tx of Graves’ ophthalmopathy
- Make euthyroid
- Immunosuppressants (for infiltrative ophthalmopathy)
- Steroid
- Cyclosporin A
- Plasmapheresis
- Ig
- Orbital irradiation
- Orbital decompression, eye muscle operation
Thyrotoxic periodic paralysis
- In Male
- HypoK (no net loss, due to IC shifting by insulin)
- Occur during hyperthyroid (not in euthyroid)
- Motor involvement (skeletal muscles, seldom RS)
- Cardiac arrhythmias
- Tx: Spontaneous recovery, faster if IV K infusion
- Prevent by low salt diet, appropriate carbohydrate intake, Spironolactone, Propranolol
Sx of Hypothyroidism
- Weight gain
- Cold intolerance
- Coldness
- Constipation
- Menstrual irregularities (menorrhagia?)
- Muscle cramps
- Chest pain
Children: Growth retardation, mental retardation
Signs of Hypothyroidism
- Dry skin
- Hoarseness of voice
- Slow reflex
- Bradycardia
- Pallor
Half life of TSH / T3 / T4
TSH: 1h
T3: 1 day
T4: 1 wk
Bone, Stone, Groan, Moan for HyperCa
Bone pain
Renal stone
GI: Constipation, abd pain
Psychiatric moans (psychosis, depression)
Steroid SE
Obesity
- Truncal in distribution, moon face, buffalo hump, supraclavicular fat pads
Skin changes
- Acne, thin skin, excessive bruising, purple striae, pigmentation (Ectopic ACTH or Pituitary Cushing’s)
Proximal myopathy
Psychiatric disturbances in severe cases
- Non-specific, depression, euphoria, frank psychosis
Hirsutism, oligo/amenorrhea in F; impotence in M
Osteoporosis in long term steroid administration
HT, DM
Cx of Cushing syndrome
RB
- CVS: HT, fluid retention
- Metabolic: Glucose intolerance, central obesity, HL, hypoK
- MSS and skin: thin skin, bruises, striae, proximal muscle weakness, osteoporosis
- Immune: Immunosuppression
- Psychiatric: Irritability, depression, psychosis
- Androgen excess (not in Exogenous): Acne, hirsuitism
- For Iatrogenic: AVN, glaucoma, posterior subcapsular cataract
Mx of Cushing syndrome
RB
- Mx concomitant problems: HT, DM, HypoK
- Surgery - for cure: Transphenoidal surgery for pit; adrenalectomy for adrenal
- Medical: control hypercortisolism before surgery / persist after surgery
- Metyrapone: Block cortisol synthesis at the final 11β-hydroxylase step; also use to Dx adrenal insufficiency
- Ketoconazole: Inhibit cortisol and androgen secretion; SE = Hepatotoxicity; actually an anti-fungal
Inferior petrosal sinus sampling (IPSS)
- For Dx of Cushing’s disease
- Pit gland drains to inferior petrosal sinus
- Increased ACTH compared to the periphery suggests Cushing’s disease
- Equivocal levels of ACTH indicate ectopic or paraneoplastic Cushing’s Syndrome
- The sample is usually taken after administration of CRH or DDAVP
Classical signs of Acromegaly
RB
- Prominent supraorbital ridges
- Large nose
- Prognathism
- Deep voice
- Oily skin
- Thick lips, mal-occlusion, increased interdental separation, macroglossia
- Bitemporal hemianopia, optic atrophy/papilledema
- Goiter
- Large feet, thick heel pads
- HT, DM, OA
Important Ix for Acromegaly
RB
- OGTT (measure glucose, GH): GH not suppressed
- IGF-1 increased
- MRI pituitary
- Other ant pit hormones
Cx of Acromegaly
RB
- Facial and skeletal disfigurement
- Jaw mal-occlusion and overbite
- Arthropathy
- Nerve entrapment, CTS
- HT, LVH
- OSA
- DM
- Colon polyps, CA
- Hypopit secondary to mass efect
- Visual defect due to optic chiasm compression
*May have goiter due to viseromegaly; may have hyperthyroidism
Mx of Acromegaly
RB
- Trans-sphenoidal surgery
- Medical:
- Dopamine agonist: Bromocriptine, Cabergoline
- Somatostatin agonist: Octreotide
- GH antagonist: Pegvisomant
- Primary or adj RT
Important Ix for Cushing syndrome
RB
- 24h free urinary cortisol
- Plasma Cortisol and ACTH at 9am and midnight:
- Loss of diurnal rhythm of cortisol secretion
- ACTH (low if adrenal cause; high if ACTH-dependent Cushing syndrome) - Screening: 1mg overnight dexamethasone suppression test
- Diagnostic of Cushing syndrome: 48h low dose dexamethasone suppression test
- High dose dexamethasone suppression test: suppressed = pit-dependent Cushing’s disease
- Corticotropin release factor stimulation test:
Rise in ACTH (>50%) and cortisol (>20%) = pit-dependent Cushing’s disease - MRI pituitary
MRI/CT adrenals
Search for underlying malig if ectopic ACTH - Inferior petrosal sinus sampling for ACTH:
confirm + localization of pit adenoma producing ACTH
Important Ix for Graves
RB
- TFT: serum TSH
- Thyroid autoAbs: TSH receptor Ab (TRAb)
- Radionuclide scan
- Diffuse in Graves
- Patchy inhomogenous for Toxic multinodular goiter
- Localized increase + other decreased = Toxic adenoma
- Decrease/no uptake in Subacute thyroiditis
- USG: Diffuse enlargement with homogenous echogenicity
Cause of secondary HT
RB
- Renal: Renal a. stenosis, CRF, IgAN
- Vascular: Coarctation of aorta
- Metabolic: Conn’s syndrome, Cushing’s syndrome, Pheo
- Drugs: MC, GC
How to form Vanillylmandelic acid (VMA)
- Catecholamines get methylated by COMT in liver and kidney
- Methylated catecholamines are then deaminated and finally oxidized to vanillylmandelic acid (VMA) which is excreted in urine
- COMT = Catecholamine-o-methyl transferase
Pheochromocytoma facts
- Arises from chromaffin cell of adrenal medulla
- 20% extra-adrenal; 24% familial (MEN2, neurofibromatosis)
- Up to 36% malignant
- Extra-adrenal tumors tend to produce NA whereas adrenal tumors usually produce both NA + A
Presentation of Pheochromocytoma
- Due to excess catecholamine secretion
- HT, headache, palpitation, pallor, anxiety, tremor, dizziness
- Hypermetabolism, sweating, LOW, glucose intolerance, angina - Due to Cx
- LVF, CVA, MI, encephalopathy
Dx of Pheochromocytoma
- Urinary VMA (Vanillylmandelic acid)
- Urinary catecholamines and their metabolites (Metanephrine and normetanephrine)
* *Beware of drug and dietary interference (e.g. BB, methyldopa) - Plasma catecholamines if available
- Localization by imaging
4a. CT/MRI
- Contrast ingestion may induce a pressor crisis and patients should be prepared with complete adrenoceptor blockade
4b. Meta-iodo-benzyl guanidine (MIBG) scan
- Taken up by chromaffin tissue
- Labelled with radioactive iodine (I-123) and results in adrenomedullary images 24-48h after injection
Tx of Pheochromocytoma
- Surgery
- Full α+β blockade before surgery or any procedures to prevent crisis
- Initially blockade with Phenoxybenzamine (Nonselective α-blocker) , then β-blockade with Propranolol
- Important to institute α-blockade first
- If β-blocker administered first, vasoconstriction due to unopposed α-adrenoceptor activity may occur and exacerbate HT
Distribution of fat measurement
Assessed clinically by Waist:Hip ratio or Waist circumference
- Upper body obesity: WHR >= 0.95 in M // >=0.8 in F
- Waist circumference (as a measure of central obesity): >=90cm in M // >=80cm in F
Secondary causes of obesity
- Hypothyroidism
- Cushing syndrome
- Hypogonadism in M
- PCOS in F
- GH deficiency
- Hypothalamic tumors
Mx of severe hyperCa
- Fluid replacement
- NS
- Excrete Ca by inhibition of Na reabsorption @ PT and Loop
- Monitor fluid and electrolyte balance - Frusemide
- To increase urinary Ca excretion
- Only give after adequate fluid hydration - Bisphosphonates
- ↓Bone resorption
- IV preparations potent and rapid onset
- Currently the most commonly used tx - Calcitonin
- ↓Bone resorption
- Fall in Ca is small
- Lack of severe SE
- Rapid onset of action - Corticosteroids
- ↓Bone turnover
- Useful in patients with myeloma, leukemia, lymphoma, sarcoidosis, vitamin D intoxication
Presentation of HypoCa
- Paresthesia, circumoral嘴邊的numbness
- Tetany (Trousseau’s sign, Chvostek’s sign)
- Hyperventilation
- Convulsion
- Laryngeal spasm
- ECG: prolonged QT interval
Tx of HypoCa
- Severe: IV Ca gluconate by infusion
- Mild: Oral replacement of Ca; 1,25 (OH)2D3
HbA1c FP, FN
FP:
- CKD (glycation↑)
- Iron deficiency (erythropoiesis↓)
- Assay issue (bilirubin)
FN:
- ↓life span (blood loss, hemolysis, hypersplenism)
- Blood transfusion
Somogyi and Dawn phenomenon
Somogyi
- Rebound hyperglycemia before meals or during night as hypoglycemia stimulates release of counter-acting hormones; sometimes overcompensation causing hyperglycemia
- Good HbA1c, high FG despite increase dose of morning basal insulin
Dawn
- Early morning hyperglycemia due to surge of counteracting hormones during sleep as insulin wanes during night, between 4 to 7am
- Physiological
Differentiate by Differentiation - 2am h’stix - Continuous glucose monitoring system - Hypoglycemia at 2am --> Somogyi phenomenon
Mx
Somogyi –> reduce bedtime coverage (adequate carbohydrate intake, snack before night)
Dawn –> increased bedtime coverage (NPH or long acting; later in evening or at bedtime)
Precipitating factors for DKA/HHS
- Infection, OT, trauma, severe emotional stress
- MI, Stroke (esp. in elderly)
- Drug e.g. steroid
Anti-TPO Abs
wiki
Anti-thyroid peroxidase Abs
In 90% of Hashimoto’s thyroiditis, 75% of Graves’ disease and 10-20% of nodular goitre or thyroid carcinoma
Other causes of Hyperprolactinemia
non-stressed PRL usu <3x normal
*Pain when sticking needle will increase PRL level; leave it for 30 mins to take blood to get the basal PRL level
Physiological (Pregnancy, Lactation)
Pathological
1. Lesions (e.g. tumors) involving hypothalamus or pituitary stalk
2. Estrogen containing medications (E can stimulate PRL producing cells)
3. Drug affecting central dopaminergic regulation (anti-psychotic drugs, anti-emetics, alpha methyldopa, H2 antagonists)
4. Idiopathic
Others
- Hypothyroidism: ↑TRH (Thyrotropin releasing hormone)
- Renal failure: Impaired dopamine action, reduced PRL clearance
- Chest injury
Dx of GH producing tumors
- ↑Serum IGF-1
2. Non-suppressible Serum GH during OGTT
Dx of Prolactinomas
- Prolactin; usually >10x normal
- Tumor shrinkage by >50% in 90% patients when treated with dopamine agonists
