Endocrinology Flashcards
Mifepristone
Synthetic steroid
Can be ised for tx of hyperglycemia in patients with cushings syndrome
Glucocorticoid receptor antagonist
Monitoring for nonfunctioning Pituitary adenomas
Macro:
-6 monthly MRI
Micro:
yearly MRI
Tx of pituitary adenomas producing prolactin
Dopamine Agonist
- Carbegoline
- Bromocriptine
Cut offs for prolactin level to suggest functioning vs non functioning macroadenoma
> 4000 = functoning macroadenoma
ADH
Increases permeability of cells in distal tubule and medullary collecting ducts
What is water deprivation test used for
Assessing for diabetes insipidus
Interpreting water deprivation:
-Nil significant increase in urine osmolality as tiem goes
Post desmopressin
-Significant increase in urine osmolality
Central DI
Interpreting water deprivation:
–Nil significant increase in urine osmolality as tiem goes
Post desmopression:
-No elevation in urine osmolality
Nephrogenic DI
Interpreting water deprivation:
-Incraseing urine osmolality >600 mosmol/kg
Post desmopression:
-No response
Primary polydipsia
Urine Osm suggestive of DI
<300 mosmol/L
Associated with High-normal Serum osm
MX of Central DI
Mild polyuria <3L/Day no Tx needed if thirst centre intact
OTherwise desmopressin 100 microg BD-TDS
Mx of SIADH
Fluid restriction
Salt tablets and frusemide in some cases
Severe: Hypertonic saline
Vasopressin receptor angatonists (Vaptans)
CAuses of decreased GH
DaytimeHyperglycemiaAgingObesity
Control of GH
- Ghrelin (gastric derived peptide) à stimulates GH release
* Somatostatin à inhibits GH secretion
IGF-1 (insulin-like factors) à negative feedback loop; inhibits release
Diagnosis of GH Deficiency
Most specific: IGF-1 measured in insulin tolerance test (low)
Ix for Acromegaly
Oral glucose tolerance test:
1. IGF -1 level High
NORMAL = GH <1ng/mL after 75g of oral glucose
Acromegaly = GH >2ng/mL
• Pituitary MRI
If NEGATIVE = Chest/abdo CT to identifies ectopic source
Tx of Acromegaly
- Stomatostatin analgoue (octreotide, pasireotide)
- Dopamine agonist (carbegoline, bromocriptine)
- GH receptor antagonist (pegvisomant)
APS 1
autoimmune polyglandular syndrome
hypoparathyroidism/chronic mucutaneous candidiasis (Th17) in mid 20s followed by adrenal insufficiency
APS 2
presents age 40; primary adrenal insufficiency (main feature), autoimmune thyroid disease and T1DM
Ix for Addison’s
Morning Cortisol <90 nmol/L
Short synacthen test
-Only useful in ruling out primary hypoadrenalism
○ Normal = rise >250 nmol/L with 30 minute value of >550 nmol/L
-Primary insufficiency = sub-normal increase
Gold standard Ix for hypoadrenalism
Insulin tolerance test
-CAuses hypoglycemia which is stressful and shuld produce ACTH
Adrenoleukodystrophy
XLR
Features: -Addison's ○ Dementia ○ Blindness -Quadriparesis ○ Spasticity -Polyneuropathy
Diagnosed on plasma very long chain fatty acids (VLCFA) and gene testing
Adrenal incidentaloma Mx
• Functioning – surgical removal
• Non-functioning:
• <4cm and non suspicious features on scanning à repeat scan in 6 to 12 months
• >4cm and suspicious features on scanning à remove surgically
-<2cm – no follow-up required as rule; unless concerning features on screening
Specific features of Cushings
• Facial plethora
• Proximal myopathy
Purple striae
Pseudocushings
Suppressed with low dose dexamethasone testing
Mild hypercortisolism
Tx of Cushings disease
- Transphenoidal resection of pit adeno
- RTx
- MEdical
- Ketoconazole SE androgen inhibition
- Pasireotide: Somatostatin receptor antagonist sE Hyperglycemia
- Mifepristone
- MEtyrapone - Bilateral adrenalectomy
CAH pathophys
Autosomal recessive disorder of 21-hydroxylase deficiency
CYP21 gene on chromosome 6
21-hydroxylase deficiency (93%) results in decreased aldosterone and cortisol synthesis, high ACTH levels and subsequent adrenal stimulation with diversion of the steroid precursors into androgenic pathways
CLASSIC 21-HYDROXYLASE DEFICIENCY (CONGENITAL ADRENAL HYPERPLASIA)
salt-wasting and adrenal sufficiency or with virilisation as neonates
• NON-CLASSIC 21-HYDROXYLASE DEFICIENCY
present in young adulthood with signs of androgen excess
Late childhood – premature pubarche, acne, accelerated bone age
Adolescent and adult females – acne, hirsutism, menstrual irregularity
Ix for CAH
○ High serum 17-hydroxyprogesterone
○ Exaggerated response to ACTH stimulation test (synacthen) with ↑ 17-hydroxyprogesterone levels
Tx CAH
○ Women – cyproterone acetate/OCP – for hirsutism, acne, oligomenorrhoea; dexamethasone for ovulation induction
○ Men – not necessary unless testicular masses or oligospermia, possibly dexamethasone
Ix for Conn’s
ARR >30 and Plasma aldosterone concentration >20ng/dl = 90% sensitivity/specific for hyperaldosteronism
Other tests:
- SAline infusion test: positive if no suppression of plasma aldosterone
- Salt suppresion test
- Fludrocortisone suppresion test
Mx of Conn’s
Adrenalectomy
Medical
- Spiro
- Amiloride
Carney Triad
gastric stromal tumour, pulmonary chondaromas, phaeo
Ix for Phaeo
Best test:
-24 hour urine catecholamines and metanephrines
Best screening:
Plasma fractionated metanephrines
Confirmation tests:
- Clonidine suppression test: if no suppression, then phaeo
- Chromogranin A elevated
- Neuropeptide Y elevated
Mx of Phaeo
Resect lesion
Medical: Alpha blockers
Phenoxybenzamine
prazosin
Hormones that increase appetite
Ghelin
Hormones that decrease appetite
CCK
GLP1
PYY
Leptin
MEN1
Hyperparathyroid
Pituitary macroadenoma
Pancreas - insulinoma, gastrinoma
MEN1/MENIN
MEN2A
TAP
Thyrioid - medullary cancer
Adrenal - Phaeo
Primary prarthyroid hyperplasia
RET
MEN2B
TAN
Thyroid - medullary cancer
Adrenal - pheao
Neuromas, marfanoid habitus, Hirschsprungs
RET
Carcinoid Syndrome
- Serotonin secretion
- Associated with metastatic midgut carcinoid tumor
- FEatures: flushing/diarrhea/TR/pellegra like skin lesions
Ix:
- 5-HIAA in urine
- Urine/plasma 5-HT
Mx:
- Ondansetron
- Octreotie
Zollinger Ellison Syndrome
• Non-beta islet cell gastrin-secreting tumour of the pancreas
○ Usually located in pancreas, duodenum or abdominal lymph nodes
Ix
○ Secretin infusion – increase in gastrin >200 pg within 15 minutes of secretin injection = >90% of sensitivity and specificity
○ Fasting gastrin levels
○ Gastric acid secretion – normal = 10mEq/hour; ZES > 15 mEq/hour
Mx – PPI/H1 receptor antagonists; octreotide
VIPoma
80% solitary pancreatic masses; usually >3cm at diagnosis
Features
-Large volume watery diarrhea, hypokalemia, hypochlorhydria, dehydration
Persistance of diarrhea on fastin means secretory
Kallman’s Syndrome
• Hypogonadtrophic hypogonadism and anosmia
Failure of migration of GnRH neurons
Features:
• Male – delayed puberty +/- micropenis
Female – delayed puberty and lacks of secondary sex characteristics
Assocaitions:
-Cleft palate, hearing loss, color blindness
DKA Criteria
Hyperglycemia >14
Ketosis
pH <7.3 (Bicarb <20 mmol)
HHS Criteria
Hyperglycemia >30
Minimal ketoisis
Serm OSm >320
When to start giving IV Dextrose in DKA to prevent cerebral dextrose
DKA serum BG <11.1 swap to IV Dextrose and halve insulin infusion rate (HHS serum BG<15)
Hospital target for BSLs
5-10
in and out of ICU
Which DDP4i does not need renal dose adjustment
linagliptin
Hba1c target in pregnancy
<6
T1DM in which family member increases the risk of most of someone getting T1DM
Sibling!
Then Father
HLA DR associated with T1DM
DR3 and DR4
T1DM Retinopathy screening
At diagnosis • Then every 1 to 2 years • Children -commence at puberty
PRimary pigmented nodular adrenal disease mutation
PRKAR1A mutation
Diagnostic criteria for PCOS
2 of 3:
- Oligo/anovulation
- Clinical and/or biochemical hypernadrogenism
- Polycystic ovaries
Diagnostic criteria for hypergonadotrophic hypogonadism
2 x FSH > 40 U/L at least 1 month apart or ↓ [oestradiol] & elevated FSH, in the context of amenorrhoea and menopausal symptoms
Female athlete triad
Amenorrhoea, low bone density and eating disorder among female athletes
Corr Sodium when hyperglycemic
Divide BSL by 3 and add to Na
MAx correction of NA per day in chronic hyponatremia
8 mmol/day
Severe and symptomatic hyponatremia management
100-150 ml 3% saline over 15 mins
-Rises Na by 2-3 mmol
Aim to increase by 4-6 mmol over 2-3 hours
Sick euthyroid
Diagnosis –
•
If TSH>10 –true hypothyroidism
•
If T3 raised and TSH undetectable -hyperthyroidism
•
If low T4 and T3 and TSH < 10 -exclude pituitary disease (Prolactin/LH/FSH/Cortisol)
Tx of MNG/Toxic adenoma
• Same option as for Graves’ disease • I131 particularly suited to TA • MNG -I131 or surgery if large goitre, obstructive symptoms or suspicion of malignancy • Thionamidetherapy less favoured as remission is unlikely
Type 1 Amiodarone Thyrotoxicosis
Increased thyroid hormonse synthesis due to iodine load
Vascularity normal or reduced
Tx: CMZ
Type 2 Amiodarone thyrotoxicosis
Thyrocye cytotoxicity
IL-6 and TG elevated
Reduced vascularity
PRednisolone
Subclinical hyperthyroidism
Subnormal TSH with normal T4 and T3
Tx:
-if TSH <0.01, MNG, existing OP/heart disease, older patients
Consequences of TSH <0.01 in subclinical hyperthyroidism
Progression to overt disease
OP
AF
HEart failure
Thyroid storm Mx
IV propanolol
PTU Q4H (lowers T3 faster than CMZ)
Lugol’s solution - only in prep for emergency thyroidectomy - use >4 days exacerbates thyrotoxicosis
Hydrocort - Blocks T4 to T3 conversion
Cholestyramine - to increase T4 clearance
PLEX
Hypothyroid Mx
• L thyroxine -dose adjusted to achieve TSH around 1mIU/L • No dose adjustment for 2 weeks • Start low (25 or 50ug) if IHD • T3 not needed • Increase by 50% in pregnancy • In pituitary disease beware unmasking HPA axis dysfunction
Subclinical Hypothyroid
Higher with higher iodine intakes and in Down syndrome and type 1 diabetes
Symptoms, lipids and cardiac function may improve if TSH > 10
•
TSH < 10 no evidence of benefit (symptoms do not improve in placebo controlled studies)
•
Treat if pregnant (TSH >4.0) or contemplating pregnancy
Myxoedema Coma Mx
Hydrocort in case of any adrenal insufficiency
T4 loading
Avoid water overload
Subacute Thyroiditis
Likely due to viral infection
Painful swollen thyroid Thyrotoxicosis Sx for 2-8 weeks No isotope uptake USS - enlarged hypoechoic gland with reduced vascularity
Thyrotoxicosis then hypothyroidism then recovery
Mx:
- NSAIDS
- Can trial PNL 40 mg then taper
- Can have thyroxin for hypothyroid phase
90% resolves completely
Lymphocytic and post partum thyroiditis
Painless enlarged thyroid
Low echogenisity on USS and zero isotope uptake
Thyrotoxicosis is limited, followed by hypothyroidism that persists in 20-30%
High risk of eventual hypothyroidism
Thyroid lesions fo rFNA
•
TSH –if suppressed (<0.01 mIU/l) lesion may be “hot” and isotope (Tc99m) uptake scan should be performed. If hot –no FNAC
•
Lesion > 2cm and not a cyst or spongioformlesion then FNA
•
Lesions 1-2 cm selected on the basis of high risk US features TI-RADS 3-5
•
Lesions < 1 cm repeat evaluation in 6-12 months
•
Lesions that increase by 30% volume or 10% in diamshould be biopsied
Papillary Thyroid carcinoma
Most common thyroid cancer
Overlapping nucleii, grooves, “orphan annie”
and Psammomabodies
USually indolent, but can be metastatic to bone and lung
Usually BRAF mutation
Follicular thyroid carcinoma
Loss of follicular structure and increased atypia in undifferentiated tumours
Distinguished from FA by capsular and vascular invasion post surgery
Poor prognosis due to usually presenting late
Teprotumumab
For thyroid eye disease
Bad features of thyroid nodules
-Solid
-Very hypoechoic
-Taller than wider
-Lobulated/irreguler
Extrathyroidal extension
-Microcalcifications
-Punctate echogenic foci
P1NP
Synthesised by osteoblasts
Procollagen type 1 has short N-and C-terminal extensions that we can measure when cleaved during conversion from procollagen to collagen
Vit D Deficiency classification
• Adequate ≥ 50 nmol/L • Mild deficiency 30–49 • Moderate deficiency 12.5–29 • Severe deficiency < 12.5
Alendronate
Increased spine BMD by 9% and hip BMD by 6% over 3 years
Incidence of new fractures reduced by ~50% compared with placebo
Risendronate
Increased spine BMD by 4–5% and hip BMD by 2–4% versus placebo over 3 years
risedronatereduced vertebral fractures by 40–50%
Zolendronic Acid
Most potent bisphosphonate
Vertebral fractures reduced by 70% • Hip fractures reduced by 41% • Non vertebral fractures reduced by 25%
Duration of bisphosphonates
•
In women at high risk (low hip T-score, hxfracture), continuation of treatment for up to10 years oral and 6 years IV should be considered with periodic evaluation
•
For women not at high risk after 3-5 years, a drug holiday of 2-3 years can be considered
Risk factors for ONJ
High-dose IV bisphosphonates, • Longer duration of treatment with bisphosphonates • Glucocorticoid use • Alcohol abuse and tobacco use • Cancer • Advanced age • Poor dental hygiene and those who undergo a dental procedure such as dental extraction
Teriparatide
PBS Criteria
PBS Criteria:
A bone mineral density (BMD) T-score of –3.0 or less AND
•
2 or more fractures due to minimal trauma AND
•
At least one new symptomatic fracture after at least 12 months of continuous treatment with antiresorptive therapy at adequate doses
Teriparatide SE and CI
Main SE dizziness, leg cramps, pain at injection site
Benefit in terms of BMD seems to wane after discontinuation unless followed by an antiresorptive
CI-Paget’s disease, skeletal irradiation, unexplained increases in ALP, pre-existing malignancy, renal stones, gout
Denosumab
Human monoclonal antibody to the receptor activator of nuclear factor kappaBligand (RANKL), an osteoclast differentiating factor
nhibits osteoclast formation, function and survival
•
Decreases bone resorption
9% gain BMD LS and 4% hip
Reduction in VF-68% • Reduction in non vertebral fracture-40% • Reduction in hip fracture-20%
When discontinuing denosumabtherapy, bisphosphonates should be considered to prevent or reduce the rebound increase in bone turnover
Denosumab + Teriparatide
Two years of concomitant teriparatide and denosumabtherapy increases BMD more than therapy with either medication alone and more than has been reported with any current therapy.
Insulinoma
Gold standard testing:
• 72hour fast with measurements of insulin, glucose and C-peptide
C peptide: <200 pmol = no insulinoma; >200 pmol = diagnostic of insulinoma
FEatures
• Hypoglycaemia = typically early in morning or just before meal
○ Diplopia, weakness
Rapid weight gain
Paget’s Disease
Ix • High ALP • High C and N-telopeptides ○ High in both serum and urine High osteocalcin
Indication for Tx
• Severe bone pain – not responding to analgesia
• Neurological Cx
• High output cardiac failure
• Hypercalcaemia
Preparation for elective orthopaedic surgery
Tx
- NSAIDS
- Bisphosphonates
Romosozumab
Sclerostin is an osteoblast inhibitor
mAB to sclerostin
Better than teriparatide/alendronate for vertebral fractures and reduction in clinical fractures
Rebound in BMD on cessation
Medullary thyroid cancer
Vandetanib improves progression free survival
Calcitonin levels correlate with tumor burden
Test for RET mutation
neuroendocrine tumour of para-follicular/C-cells of thyroids – secretes calcitonin
HNF1A mutation
MODY 3
-sensitive to sulphonurea
GCK mutation
MODY 2
-Ccan stop glucose lowering therapy once reached baseline
Anti-thyroid perioxidase (TPO)
90% of Hashimoto’s thyroiditis, 75% of Grave’s disease, 10% of multi-nodular goitre
Anti-thyrogloublin (TG)
70% of Hashimoto’s thyroiditis; 60% of idiopathic hypothyroiditis, 30% of Grave’s disease
TSH receptor antibodies
70 to 100% of Grave’s disease
Thyroxine malabsorption
- Malabsorption:
- Coeliac disease
- Small bowel surgery
- Oestrogen therapy
- Drugs that interfere with T4 absorption = ferrous sulfate, cholestyramine
• Increased clearance: • Lovastatin • Amiodarone • Carbmazepine Phenytoin
Post PArtum Thyroiditis
- Occurs within 1 years after childbirth
- Anti-TPO antibody = high in 60 – 85% of patients
- Risk factors:
- Anti-TPO positive prior to pregnancy
- T1DM
- Previous episode of post-partum thyroiditis
- Treatment:
- Propranolol can be safely used even if breast-feeding
Thyroid in Pregnancy
- Increased in thyroxine-binding globulin (TBG)
- Increase is due to decreased hepatic clearance and increases synthesis (triggered by oestrogen)
Beta HCG mimics TSH and increases production of T3/T4
Gestational Hyerthyroidism
• Non-autoimmune; no goitre
• Almost all patients resolved by 20 weeks
• LOW, maternal tachycardia may occur
• Only 12% will have elevated FT3
If persistent beyond 20 weeks à then treat; consider Grave’s disease
Anaplastic Thyroid cancer
; undifferentiated tumour of thyroid follicular epithelium
Generally in age 65
Extensive local invasion and compression Sx are prominent
Thyroid lymphoma
- Often arises in background of Hashimoto’s thyroiditis; diffuse large B cell lymphoma is the most common
- Highly sensitive to the external radiation
