Endocrine Flashcards
What’s the most common adrenal incidentaloma?
- mostly non-functioning
- subclinical cushing
> GC secretory
Rotterdam criteria
2/3:
- Hypoandrogenism (clinical or biochemical)
- Menstrual irrgularities
- Polycystic overies on USS (>12 antral follicles in 1 ovary or >10cm3 in vol)
20% of women with PCO have PCOS
20% of patients with PCOS have absent PCO
20% of patients without PCOS have PCO
Insulin stress test
Indications:
To test anterior pituitary growth hormone and ACTH reserve in patients suspected or confirmed as having anterior pituitary failure.
CI:
- epilepsy
- cardiac rhythm disturbances, ischaemic heart disease
- previous cerebrovascular accidents, or any unexplained fits or collapses.
- Adrenal Insufficiency
Protocol:
Estrogen containing medications such as HRT or the pill must be stopped six weeks prior to this test. Patients should be fasting from midnight before the test, and are asked to bring their medications with them for documenting at the start of the test, and to be taken at the end of it.
ECG, 9am cortisol, free thyroxine must all be performed and checked by a doctor before proceeding with this test.
PCOS
Rotterdam criteria
- prevalence of gestational diabetes, impaired glucose tolerance and type 2 diabetesare significantly increased in PCOS, with risk independent of, yet exacerbated by, obesity
- 2-6 x increased risk of endometrial cancer
Complications:
Infertility, miscarriage
Metabolic sx
Sleep apnoea, NAFLD
Depression, Endometrial cancer
Biochemical:
- LH excess
- Hyperinsulinemia
- Reduced SHBG - due to insulin resistance
- Testosterone/FAI/bioavailable T
- Androstenediones or DHEAS are often elevated
DDx that needs to be excluded: thyroid, hyperPRL, cushing sx, non-classical CAH (17-OHP), androgen secreting tumour, ovarian failure (^FSH), hypthalamic amenorrhoea (low GnRH,LH/FSH)
In hereditary haemochromatosis, does venesection help with sexual dysfunction?
No
- you need to give testosterone
When do you treat subclinical hypothyroidism?
- TSH ≥10mIU/l on two separate occasions three months apart.
- <65-70: TSH 7-9.9
- > 65-70:
For women with subclinical hypothyroidism (TSH values above first trimester-specific normal reference range with normal free T4) who are trying to conceive and who have ovulatory dysfunction or infertility, initiating T4 replacement is suggested
Pregnancy and thyroid function
- release of estrogen encourages the production of thyroxine binding globulin
- Total T4 increases, free T4 remains stable
- bHCG stimulates the release of T4, thus** TSH level drops **
Hypokalaemic periodic paralysis
- Autosomal dominant inherited **(non-penetrance is common) **defect in calcium or sodium ion channel on muscle membrane
- Male > female (clinical)
- common precipitate:
> Exercise
>Carbohydrate load
>Stress
Need to rule out TPP and HyperKPP
Prevention:
- Acetazolamide
- K+ sparing diuretics
Associated features Later-onset myopathy
Typical lipid profile in T2DM
- high concentration of TG and small dense LDL low - concentration of HDL cholesterol.
- LDL normal
- Insulin resistance is believed to contribute to this atherogenic dyslipidemia by increasing the hepatic secretion of VLDL and other apolipoprotein (apo)B-containing lipoprotein particles, as a result of increased free fatty acid flux to the liver.
How does thyrotoxicosis result in osteoporosis?
- reduced estrogenisation –> osteoporosis
MODY
Managment of nephrogenic DI
- low salt and low protein
- thiazide diuretic (2nd line)
How do you develop gynacomastia in cirrhosis?
In cirrhosis (as well as alcohol dependency) there is increased activity of peripheral aromatase which converts testosterone to estrogen. This buildup of estrogen causes the development of female secondary sexual characteristics such as breast development
Amiodarone induce thyroid disease
The presentation here, with a very high T4 and suppressed T3, and a background of previous CVD suggests the patient likely has an amiodarone induced thyrotoxicosis. There are two main types of this disease: 1. is due to increased thyroid hormone synthesis due to an increased iodine load. 2 is more like a thyroiditis with thyrocyte toxicity. The distinction between the two types is difficult but is most reliably done by vascular USS - the presence of normal or increased uptake suggests type I, whereas Type II is suggested by decreased uptake
Fenofibrate
- peroxisome proliferator receptor alpha activator used to lower LDL-C, total-C, triglycerides, and Apo B, while increasing HDL-C in hypercholesterolemia, dyslipidemia, and hypertriglyceridemia
- prevent diabetic retinopathy.
Which nerve on the eye is commonly affected in diabetes?
sixth nerve
what’s mechanism of steroids induced osteoporosis?
inhibition of bone formation which is done by an increase in death of osteoblasts.
ventromedial nucleus of the hypothalamus
distinct morphological nucleus involved in terminating hunger, fear, thermoregulation, and sexual activity.” This nuclear region is involved with the recognition of the feeling of fullness.
TPO Ab and pregnancy
- An increased risk of adverse pregnancy outcomes has been reported in euthyroid women with elevated thyroid peroxidase (TPO) antibody concentrations.
- Increased risk of fetal loss, preterm delivery, perinatal mortality, and** large for gestational age** infants has been reported in euthyroid women with high serum TPO antibody concentrations
- high risk for developing subclinical hypothyroidism in the first trimester and thyroiditis in the postpartum period
pseudohypoparathyroidism
PTH resistance due to g-protein deficiency
elevated PTH
hypocalcaemia
N or E phosphate
Graves’ orbitopathy
an autoimmune disease of the retroocular tissues
Risk factors for the development of Graves’ orbitopathy include:
- genetics, female sex, smoking, and prior radioiodine therapy.
TSHR antibody and activated T cells play an important role in pathogenesis of Graves’ orbitopathy by activating retroocular fibroblasts and adipocytes.
The volume of both the extraocular muscles and retroocular connective and adipose tissue is increased, due to i**nflammation and the accumulation of **hydrophilic glycosaminoglycans (GAG), principally hyaluronic acid, in these tissues
GAG secretion by fibroblasts is increased by activated T cell cytokines and by the activation of the receptors for TSH and insulin-like growth factor-1 (IGF-1).
RAI can worsen symptoms
Mod-sev disease - tx with steroids
Non classical CAH
21 alpha hydroxylase
The synacthen test is used to distinguish PCOS from non classical CAH. Synacthen is administered and concurrent **17hydroxy progesterone **levels are measured.
AR
Not present at birth
Fanconi syndrome
- type 2 renal tubular acidosis, accompanied by hypophosphataemia, glycosuria, and aminoaciduria
Presenting features include polyuria, polydipsia, osteomalacia (rickets and growth failure in children) and symptoms secondary to the electrolyte abnormalities associated with the disorder.
Causes:
Rifampicin
cystinosis (most common cause in children)
Sjogren’s syndrome
multiple myeloma
nephrotic syndrome
Wilson’s disease
What are the medical therapy options for hyprecortisolism?
- ketoconazole, mitotane -reduce cortisol synthesis
- pasireotide, or cabergoline:
HLA subtypes is associated with subacute thyroiditis
HLA B35
Pre-eclampsia
- Roughly 30% of pre-eclampsia occurs in the post partum period.
- recurrence of Pre-eclampsia is roughly 8%
- risk of recurrence is higher in patients who initially had pre-eclampsia early
- Low-dose aspirin therapy during pregnancy modestly reduces the risk of preeclampsia in women at high risk for developing the disease.
*
nelson syndrome
Osteoporosis:
- SERMs have only been shown to reduce the risk of vertebral fractures in osteoporosis
When is PTU preferred over carbimazole?
- first trimester of pregnancy
- acute thyroid storms
- this is because PTU not only acts on inhibiting the action of TPO, it also works by **blocking the conversion of T4 to T3 **- which is essential in the acute crisis state.
which cancers associated with acromegaly?
colon, breast and prostate cancer
colonoscopies for all acromegaly patients over the age of 50
Craniopharyngiomas
- benign nonglial epithelial CNS tumor, constituting 1% to 3% of intracranial tumors in adults, most often located near the optic chiasm
- bimodal incidence: 5-14, 50-70
- sudden vision loss and intracranial HTN are the most common presentation
normal pubertal development
The first sign of puberty is thelarche, or budding of the breasts. This occurs after the age of 8 and mainly estrogen driven.
Pubarche is mostly androgen driven
menarche is driven by a combination of the hypothalamic pituatary progesterone axis.
The timing of puberty is predominantly driven by genetics
What TB meds impairs the absorption of thyroxine?
rifampicin
Diabetic retinopathy
- Retinal edema and hard exudates are caused by the breakdown of the blood-retina barrier, allowing leakage of serum proteins, lipids, and protein from the vessels
- Soft exudates are caused by nerve fiber layer infarct.
- Visual loss in non proliferative retinopathy is predominantly driven by macular edema
Thyroid basic
Half life:
- T4: 7 days
- T3 >1 day
- T3 and T4 are poorly soluble in water and therefore highly protein bound to thyroid hormone binding proteins
Hunger
inhibition: Leptin, Amylin, Insulin, CCK, GLP-1
Stimulation:
- Ghrelin, NP-y, CART
*Arcuate nucleus of brain - hunger stimulation
Congenital deficiency of melanocortin-4 receptor (MC4R)
- early onset obesity and taller than average height
- AD inheritance
Absence of what hormone or gene promotes obesity?
- Leptin
- SNRPN in prader-willi sx
calcium and vitamin D replacement
- only beneficial for primary prevention
- primary prevention of fractures is most evident in **institutionalized elderly patients **rather than community dwelling patients.
A recent meta analyses in China looking at the overall effect of vitamin D replacement in the general population was not particularly effective.
Pregnancy and acromegaly
- Most women with untreated acromegaly have menstrual dysfunction and infertility: due to reduced LH anf FSH, hyperprolectinemia
Preconception:
- tight control of GH and IGF-1
- SS analogs STOP 2 months prior and pregvisomant STOP 1 month prior
*can use short acting octreotide for signs/sx until conception
During pregnancy:
- During pregnancy, medical therapy should be withheld. Short-acting octreotide can be used, but only for **control of headache and adenoma size **
- for macroadenoma: monitor visual field, if defect then MRI –> +/- surgery
-
glucagonoma
- Necrolytic migratory erythema (NME) is the presenting feature of glucagonoma syndrome in approximately 70 percent of patients.
*NME is not specific to glucagonoma. It likely dur to hyponutrition and AA deficiency
The diagnosis of NME is made with skin biopsies obtained from the edge of the lesions, which reveal superficial necrolysis with separation of the outer layers of the epidermis and perivascular infiltration with lymphocytes and histiocytes
Familial hypercholesterolemia
- Mutations in the LDLR, APOB, and PCSK9 genes may be present,
- AD inheritance
RAI and pregnancy
AVOID for atlease 4-6 months
Avoid pregnant women and children for 5 days and 23 nights
What is the most common and most specific eye sign with grave’s dx?
Specific: Exopthalmos
Most common: lid retraction
Prenancy and cortisol
Normal pregnancy is associated with changes in the maternal hypothalamic-pituitary-adrenal (HPA) axis, including increased production of cortisol-binding globulin (CBG); increased concentrations of serum, salivary, and urinary free cortisol (UFC); and lack of suppression of serum cortisol after dexamethasone. In addition, the placenta produces corticotropin (ACTH) and corticotropin-releasing hormone (CRH). Thus, the biochemical diagnosis of CS during pregnancy is more challenging than in the nonpregnant state.
suprachiasmatic nucleus
is responsible for controlling circadian rhythms
Mifepristone
Metyrapone
Pasireotide
Ketaconazole
Treatment for hypercortisolism:
1. Synthetic stroid - blocks the effect of cortisol
2. inhibits 11 betahydroxylase –> reduced conversion of 11-deoxycortisol to cortisol
3. SS analongue –> reduce ACTH production
4. inhibits androgen synthesis
Acromegaly
Clinical features
hand and foot enlargemnt, facial bone enlargement, acral/soft issue changes
Associated with cardiovascular, respiratory and cerebrovascular impairment
Also malignancy: ?colon
Acromegaly
Diagnosis
IF there is clinical features and high IGF-1, you do not need to do Gluc suppression test. Can go straight to MRI
What cells produce growth hormone?
somatotroph cells in the pituitary
secreted in pulsatile fashion
liver produces IGF-1
Treatment for acromegaly
Surgery is the treatment of choice; most commonly transphenoidal
- Microadenoma: >85% cure
- Macroadenoma- only if there is local mass effect. The cure is only 40-50%
Octreotide in acromegaly
SS analogue
actingon receptor subtype 2 and 4 –> inhibit GH secretion
Other tx options for acromegaly
- cabergoline: dopamine agoinist
- pegvisomant: GH-R antagonist
ADrenal crisis
sx: N/V, hypotension, severe lethargy, weakness, altered mental state, hyponatraemia, hyperkalaemia, hypercalcaemia, hypoglycaemia, neutropenia, lymphocytosis, eosinophilia, and mild normocytic anaemia
*oral fludrocortisone is required in a crisis, if IV hydrocort is >50mg/24h in a pt with primary adrenal insufficiency
Adrenal incidentaloma
Majority are benign:
- Adenoma is most common (80%)
- non functioning -75%
- Cortisol secreting 12%
- Pheao:7%
- Adrenocorticol carcinoma 8%
> 1cm mass in the adrenals
- >4cm is suspicious for malignancy
- adrenal mets are typically bilateral: common cancers- lung, kidney, colon, breast, pancreas, stomach
- rule out pheao prior to FNA - risk of hypertensive crisis
Hounsfield:
<10: most likely adenoma
>10 (more dense). - usually >25: carcinoma, pheo, mets
Texture:
- homogenous: adenoma
- Hetero with cystic area: pheo
- Hetero with mixed: carcinoma or mets
Inx:
NCCT
Ald:renin ratio
DST: >138nmol/L: autonomous
fasting plasma metanephrine
<4cm: no further inx
Biopsy is not done due to risk of seeding and pheo
If bilateral adrenal tumours - screen for CAH - serum 17 hydroxyprogesterone concentration (mane)
Malignant risk:
- unilateral >6cm - surgical removal
Type 1 APS
- starts in childhood
- rare
- starts with candida
- then hypoparathyroidism
- then adrenal failure
Mutation in AIRE gene
Type 2 APS and Schmidt’s syndrome
More common
in Women
peak incidence 30s
Chr6 plays a predominant role
Presense of one AI, increases the chance of another
Schmidt’s: Adrenal insufficiency with either T1DM, or hypothyroidism
Polygenic
T1DM, coeliac, AI gastritis, PA, vitiligo, POI, alopecia areata
IPEX
immune dysfunction
polyendocrinopathy
enteropathy
X-linked
associated with** FOXP3 gene**
required for **T reg cell **function
early onset T1DM, AI enteropathy, dermatitis, eosinophilia, elevatef IgE
What do you monitor in:
1: PTC
2. MTC
- Anti-TG
- Calcitonin
Adiponectin
Low = high body fat
Solely produced in adipose tissue
causes fat catabolism
mutation can cause insulin resistance
anti inflammatory
What causes raised TBG?
Estrogen
Tamoxifeb
Raloxifen
Methadone
What causes low TBG?
Nictonic acid
GC
Danzol
Androgens
What causes low TBG?
Nictonic acid
GC
Danzol
Androgens
What Ig is Anti-TSHR
IgG
Turner’s Syndrome
XO
- Recombinant hGH should be given when girls fall below 5th percentile for age
- short, elbow deformity, wide spaced nipple, brown spots nevi
Cardiac: coarctation, bicuspid aortic valve, MVP
HTN, IHD, dissection
ECHO 3-5 y
Renal: Horseshoe kidney
Autoimmune hypothyroidism
Hearing loss
Metabolic sx
Osteoporosis
Coeliac sx
Ab LFT
What do you use synacthen test for?
to confirm adrenal insufficiency
Calcium binding and pH
Acidosis –> elevated free Ca
Alkalosis –> decrease free Ca
What cells produce calcitonin?
C-cell
Thyorid parafollicular cells
CaSR action on the renal tubules
PCT: inhibits phosphaturic action of PTH
LOH: inhibits salt reabsorption
DCT: inhibits PTH mediated calcium reabsorption
CD: inhibits ADH action
Autosomal dominant hypocalcaemia
Gain of function mutation of CaSR
Shift Ca-PTH curve to the left - thus sets a lower ca target
results hypercalcuria –> stone
loss of Mg –> hypomagnesemia
Mostly asymp and don’t need tx
Cerebral calcification is also noted - spec. BG
benefits of surgery in primary hyperPTH
- sustained improvement in bone density
- reduction in fractures
- reduced renal stones
- improvement in neurocognitive elements
Types of adipocytes:
White: main cell type
- energy yielding TG and cholesterol ester
- Secrete leptin and adiponectin
- central white adipocyte –>high risk of metabolic sx
Brown:
- has sympathetic innervation: can be stimulated to burn calorie with cold exposure
- observed in paravertebral, supraclavicular and mediastinal area
- newborns have more
Thermogenic beige:
- brown-white: can be found within white adipocyte
- browning of white fat can be induced with cold exposure and exercise
Brown is associated with marked improvement metabolic parameters
complications of cushing sx
HTN
DM
CVD
infection
osteoporosis
Diabetic nephropathy
Intensive glycaemic control can reduce progression of DN in T1DM; and the benefit persist even if they return to suboptimal glycaemic control (Legacy)
REnoprotective of ACEI and ARB are dose related
When would you consider bicarb in DKA?
when pH drops below 7.0
Sexual dysfunction in men
- Premature ejaculation
- ED - inability to achieve or maintain an erection adequate for satisfactory sexual activity
ED:
- prevalence increases with age
- diabetes is a common cause: 4x more likely and earlier onset (15y)
- Drugs: beta blocker, HCT, SSRIs
- Measure early morning T
<5.5 is the minimum you need to maintain an erection
>12: not deficient
<12: repeat 1 week later with LH, + prolactin
- PRecusor for CVD
Tx options:
1. Lifestyle
2. PDE5 inhibitor - successful on 60% (including those with spinal cord injury)
3. TRT
4. Intracavenous injection
5. VCD
6. Intraurethral PG
7. Surgical prostheses
ACC
Rare
Poor prognosis
USually present with hormone secretion: cortisol>Androgen>estrogen
2 hormones suggests ACC
it could also be non hormonal mass
Mitotane:
- causes adrenal necrosis
- longer recurrence free survial/PFS
Chemo:
- etoposide, doxarubicin and cisplatin
- survival still remains low
Adrenal insufficiency:
Low plasma cortisol, confirmed by synacthen test
Secondary adrenal insufficiency is more common than primary * with secondary mineralocorticoids will not be affect
Hyperpigmentation and hyperkalaemia in primary AI
Hyponatraemia occurs in both
Primary AI: highest risk of adrenal crisis
Autoimmune addison’s disease
21 hydroxylase antibody check in Primary AI in someone >6mo
in order:
- - increase renin
- Increase K+, lower Na
- Increase ACTH
- Lower cortisol
Causes of primary AI
Autoimmune adrenal failure (80%)
TB (10-20%)
Mets/lymphoma
Granulmoa (Histoplasmosis)
Adrenal haemorrhage
Congenital:
- Adrenoleukodystrophy (Male, VLCFA)
>X-linked condition that affects the nervous system (myelin) and adrenals
- CAH
- Congenital adrenal hypoplasia
- ACTH resistance
Causes of secondary adreanl insufficiency
Pituitary tumour is the most common
Radiation
Sheehan’s post delivery
Treatment for AI
- GC:
> weight based
Hydrocortisone (plasma half life 90mins, thus need BD or TDS dosing)
Cortisone acetate - less potent
Alternative: prednisolone
*Dex does not have mineralocorticoid acitivity, where as others do at high doses
*Dex not recommended in pregnany as it’s not inactivated by the placenta
- MC:
- Fludrocortisone (100mcg/d, uptitrate to 300microgram)
- HTN: reduce the dose, do not STOP, as it can cause salt hunger
CAH
Cortisol and aldosterone deficiency and androgen excess (due to shutning) due to defect in **21-hydroxylase **
1 in 10, 000 prevalence
Tx:
- replace MC and GC
Too little GC:
- hyperandrogenism
- ACTH excess - hyperpigmentation and TARTs
Too much GC:
- cushing syndrome
- Short stature
Primary aldosteronism
How to scree: Aldosterone:renin ratio
Dx:
Saline suppression test - renin suppressed by renin, not aldosterone –> PA
–>
Adrenal venous sampling
Tx:
- medical: Spironolactone, eplerenone, amiloride
- surgical if unilateral
- GC remediable aldosteronism
MAny channelopathies can cause it
the main mutation is KCNJ5 - leave the K+ channel open
Cushing
- striae >1cm, purple
- hirsutism
- moon face
- buffalo hump
- bruising
Early: central weight gain, HTN, hyperglycaemia, hyperTG
- female: oligomenorrhoea, hirsutism
- brain: cognitive mood changes, reduced concentration and attention
LAte: skin thinning - bruising, muscle thinning –> weakness, bone thinning –> osteoporosis
Terminal: proneness to infections
50% mortality in 5 years
Pituitart tumour: 70%
Ectopic ACTH
Adrenal (3 to 10 per mil)
Cortisol increases in Stress, starvation, pregnancy, anorexia nervosa, dementia
Cushings investigation
- 24h UFC (>2 tests)
- Overnight 1mg DST
- Late night salivary cortisol (>2 tests)
above specificity and sensitivty ~80%)
Plasma ACTH:
<5: ACTH independent –> adrenal CT
- Adrenal lesion: adenoma, carcinoma, BMAH
- no lesion: exogenous GC, PPNAD
> 20: ACTH dependent
- Pituitart MRI: adenoma >6mm
- Positive CRH response (most sensitive)
- Suppression with 8mg dex
if all positive: CUSHING’s disease
Inconclusive –> IPSS
- positive gradient: CD
- no gradient: CT CAP ?ectopic
~40% with CD will have a normal MRI
~10% incidentaloma
Cushings investigation
- 24h UFC (>2 tests)
- Overnight 1mg DST
- Late night salivary cortisol (>2 tests)
above specificity and sensitivty ~80%)
Plasma ACTH:
<5: ACTH independent –> adrenal CT
- Adrenal lesion: adenoma, carcinoma, BMAH
- no lesion: exogenous GC, PPNAD
> 20: ACTH dependent
- Pituitart MRI: adenoma >6mm
- Positive CRH response (most sensitive)
- Suppression with 8mg dex
if all positive: CUSHING’s disease
Inconclusive –> IPSS
- positive gradient: CD
- no gradient: CT CAP ?ectopic
~40% with CD will have a normal MRI
~10% incidentaloma
Cushing’s
treatment
Pituitart cushing: tx is surgery - ~80% success rate
recurrence: repeat surgery or RT (is slow)
Medical:
- Pasireotide: SSRA 5
- Cabergoline: D2RA * not as effective
Adrenal:
- Nelson’s syndrome: post bilateral adrenalectomy as no negative feedback
- Mitotane
Reversible:
-Ketokonazole:
reduce cortisol synthesis, and also has some affect on ACTH production. ADR: liver toxicity
- Metyrapone: inhibits 11 betahydroxylase –> reduced conversion of 11-deoxycortisol to cortisol
- Etomidate IV: sedative
>
Etomidate inhibits the mitochondrial cyto- chrome p450-dependent adrenal enzyme 11b- hydroxylase that catalyses the production of cortisol from deoxycortisol
> emergency situation: i.e. psychosis
GR blockade:
- Mifepristone
What kind of chemo has the highest riks of premature ovarian failure?
- Alkalating agents:
i.e. cyclophosphamide, bulsulfan, ntrosureas
also platinum based chemo that has some alkylating properties
Apparent mineralocorticoid excess
AME 1: defect in 11beta-hydroxysteroid
*Licorice inhibits this
AME2: overwhelming cortisol excess
What’s scoring sx for hirsutism?
Frriman Galway
>4-6 indicates hirsutism
Causes of hirsutism in females?
Common:
Idiopathic, PCOS
Uncommon:
Drugs: Danazol, OCP
CAH
Hyperthecosis
OVarian/adrenal tumours
Severe insulin resistance
HyperPRL
Cushing sx
PCOS
Managment
- weight loss is more effective than drugs
- 5-10% reduction is enough to restore ovulation and increase insulin sensitivity
- wt loss also increases SHBG –> reduce T and androgen stimulation of skin, improves menstraul function, conception, and reduced miscarriage rates
-Caloric restriction is more important than macronutrient composition <5000KJ/day
OTher:
- exercise
- smoking cessation
Hirsutism:
- COCP: most effective in suppressing ovarian androgen production. Increases SHBG and reduces androgen by 50%. It takes a long time i.e. 6-12 mo
- Androgen blockade with COCP
>Spironolactone, cyproterone acetate
- Insulin sensitiser: METFORMIN if high metobolic risk
- Eflornithine - topical
Menstrual dysfunction:
- COCP: use lowest effective estrogen dose - regulates mentrual cycle and contraception
- Progestin only incl. mirena: endometrial protection and contraception
- Cyclical progestin: medroxyprogestrone
>aim 4 bleed/year for endometrial protection
Infertility:
Ovulation induction:
- weight loss
- Letrozole - first line
- Clomiphene: ~80% ovulate, 50% conceive
- Metformin
- Gonadotrophin therapy
- IVF
Primary Amennorrhoea
- absence of menses by age 16 years
- absense of breast development or menses by age 13
Secondary:
- absent for >6 month, with past menses
hormones required for puberty
Thelarche: estrogen
Pubarche/Adrenache: androgens
Menarche: GnRH, FSH/LH, E2, progestrone
Anosmia and ammenorrhoea - what are you thinking?
Kallman’s syndrome
Causes of amenorrhoea
Hypothalamus:
- Dysfucntional: exercsie, wt/nutrition
- Neoplasm
- Isolated gonadotrophin deficiency: Kallmann syndrome, idiopathic
Pituitary:
- neoplasm
- hypopituitarism: post-treatment, Sheehan’s
Endocrine:
- hypothyroid
- HyperPRL
Ovarian:
- Gonadal dysgenesis (high FSH, no breast): Turner’s
- Ovarian failure
- PCOS
Outflow:
- Mullerian agenesis
- Vaginal atresia
- Imperforate hymen
- Asherman syndrome
Kallmann’s sx
X-linked recessive trait
failure of GnRH-secreting neurons to migrate to the hypothalamus.
lack of smell (anosmia) in a boy!!!
Management:
testosterone supplementation
gonadotrophin supplementation may result in sperm production if fertility is desired later in life
Primary ovarian failure:
Hypergonadotrophic hypogonadism <40
Causes: Iatrogenic, AI, Genetic, idiopathic
FSH >40 (2 samples 1 month apart)
in the context of amennorrhea/menopausal sx
Genetic:
-karyotype
FMR1 premutation if FHx, mental retardation or temor/ataxia - Fragile X: X-linked dominant
other mutations:
- AIRE, FOXL2, GALT, FSHR
AI causes:
- Thyroiditis, T1DM, MG, hypoPTH
- Addison’s
Management
- Cyclical HRT (E and P): maintain BMD, sexual health, QoL
Hypthalamic amenorrhoea (functional)
proposed mechanism:
- leptin (low levels)
- cortisol (stress related CRH inteferes and inhibits GnRH
- Exercise
ED
TRT does improve ED but not to the same extend as PDE5i
Which cells produce T?
Leydig
It’s under the stimulation of LH
Effect of FSH on the male gonads?
FSH stimulates sertoli cells and seminiferous tubules to stimulate spermatogenesis
T –> DHT
by 5alpha reductase
DHT is involved in external genitalia
Sebum production
Prostate development and growth
Skin
Hair follicles
T –> E
Aromatase
Eostradiol:
Epiphyseal fusion
Accrual of bone mass
Sexual behaviours
Verbal memory
Plasma lipids
Male hypogonadism
Signs and symptoms
Pre-pubertal:
Very small testes
Micropenis
Cryptochidism
Anosmia (kallman’s)
Gynaecomastia
Eunuchoidal proportion
Decreased body hair
High pitched voice
Decreased libido, bone mass, and muscle mass
Post-puberty:
- Lethargy, fatigue
- Decreased energy or endurance
- Low mood, irritability, poor concentration, impaired short term memory
- Deteriorating work performance
- hot flushes
Bone
Muscle
Increased fat
Gynaecomastia
Decreased libido, ED *uncommon to present with this as it needs to be less than 5
Male hypogonadism
Investigations
- Sx +signs
- Low T in the morning on 2 occasions
*in the absence of acute illness, drug misuse, eating dx, XS exercise
Check not on: opioids, GC, ketaconazole
T is 55% loosely bound to albumin
40% tightly bound to SHBG
Mass spec is the preferred method
Conditions that alter SHBG
Increase:
-ageing
- liver disease
- HIV
- oestrogen
- phenytoin
- Tamoxifen
- Hyperthyroidism
- PRegnancy
- Anorexia
Decrease:
- Obesity
- insulin R
- t2DM
- hypothyroid
- GC
- GH excess
- Androgen, progestin
- nephrotic sx
Primary hypogonadism (male)
- low T, high FSH/LH
Causes:
- Klinefelter’s XXY (most common)
> firm small testes, Mosiax 46XY or 47 XXY
> infertile due to tubular damage
- Y-chr microdeletion
- mutation in LH/FSH R
-** myotonic dystrophy**
- cryptorchidism
- testicular trauma or torsion
- Testicular radiation
- Mumps orchitis
- Orchidectomy
- Chemo (alkylating - i.e. CYC)
- AI testicular failure
- **haemochromatosis **
- Variocele
- Alcohol excess
SEcondary hypogonadism
- Low T, low gonadotrophins
*natural fertility can be restored with gonadotrophin therapy
Causes:
Kallman’s
PRader willi
Mutation in beta subunit of LH/FSH
Multiple pituary hormone def
Acquired:
- pituitary tumour/apoplexy
- Infiltrative: haemochromatosis, sarcoidosis, histiocytosis
- idiopathic
Functional:
- hyperprolactinemia
- med: opioid, GC, ketaconazole, anabolic steroids
- Alcohol/cannabis
- Nutrients def or excessive exercise
- Morbid obesity
- Eating disorder
- systemic illness
TRT
Testosterone replacement therapy
Goal: maintain seconary sexual characteristics, sexual function, body composition and QoL
Contraindicated:
- Prostate and breast ca
Precaution:
- prostatomegaly
- eleavted PSA
- LUTS
- untreated polycythaemia
- untreated OSA (can transiently get worse)
- untreated CHF
- acute MI in the last 6 months
ADR:
- erythrocytosis (EPO production and BM stimulation)
- postatic SE
- ACne
- Breast tenderness/gynaecomastia
- Reduced sperm production and infertility
- Leg oedema - worsening HF
- transient worsening of OSA
- growth of breast ca
Hungery bone syndrome
- severe hypocalcaemia lasting >4 days within 1 month post-parathyroidectomy
- giving preop calcitriol reduced incidence
Complications of hypocalcaemia:
parathesia, tetany, laryngeal spasm, seizures, cardiac arrhythmias, HF (Chvostek, Trousseurs)
other electrolyte:
- hypomg - correcting help correct hypocalcium
- hypophosphate (you don’t replace as it can worsen hypocalcaemia, unless very severe)
-** hyperkalaemia **
Citrate is important in the energy production and Mo/Dendritic cell function
- itraconate:antibacterial effect
MEN
Autosomal dominant
MEN1: PPP (pit, para, pan), MEN1 gene mutation –> Mentin protein affected
MEN2A: RET mutaton –> TK receptor
- MTC + pheo + parathyroid
MEN2B: RET mutation –> TK receptor
- MTC + pheo
- associated: marfanoid, mucosal neuromas, medullated corneal fibrese and intestinal autonomic ganglion dysfunction –> megacolon
MEN4: CDNK1 mutation –> CD kinase inhibitor
- Parathyroid + pit with association wiht tumour of the adrenals, kidneys and repro organs
RET:
- chr 10
- contains 21 exons
-** proto-ocogene **
- Gain of function: MEN2A/2B
- Loss of function: Hirschsprung disease
Which cancers are associated with VHL gene mutation?
RCC, phaeo, retinal angioma, haemangioblastoma
MODY
Maturity onset diabetes of the young
inherited autusomal dominant
single gene mutation
diabetes <35 with atypical features for t1dm or t2dm
MODY
atypical features of T1DM
absence of pancreatic islet cell autoantibodies
evidences of endogenous insulin production
measureable c-peptide in the presence of high BSL
low insulin requirement (<0.5U/kg/day)
lack of ketoacidosis wth no insulin tx
MODY
Atypical features of T2DM
onset <45
lack of obesity
normal TG and HDL-C
extreme sensitivity to sulphonylureas
MODY
Genes
MODY 3: HNF1a (Chr 12q) - most common, sensitive to sulphonylureas
MODY2: Glucokinase, present from birth
Microvascular complications are unlikely/rare
Does not neccessarity need medical therapy
MODY 5
* rare
* due to a defect in the HNF-1 beta gene
liver and renal cysts
Pagets
uncontrolled bone turnover
Normal ca/po4 but raised ALP
-primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity.
- The skull, spine/pelvis, and long bones of the lower extremities are most commonly affected.
predisposing factors:
- male
- northern latitude
- FHx
> SQSTM1 mutation –> defect in p62 –>RANKL induced NF-kB –> osteoclastic activity
- age
Sx:
bone pain
bowing of tibia, bossing of skull
abnormal remodelling, enlarged bones, marrow fibrosis, increased vascularity
complications associated with area
HIGH OUTPUT HF
deafness (cranial nerve entrapment)
bone sarcoma (1% if affected for > 10 years)
fractures
skull thickening
high-output cardiac failure
Inx:
ALP + LFTs
other markers of bone turnover:
-P1NP
C-telopeptide
N-telepeptide in urine
hydroxyproline in urine
CXR:
- osteolysis (early) –> osteoscloresis (late)
- skull x-ray: thickened vault, osteoporosis circumscripta
bone scintigraphy:
-increased uptake is seen focally at the sites of active bone lesions
Management:
- indications for treatment include
bone pain
skull or long bone deformity
fracture
periarticular Paget’s
Tx:
bisphosphonate (either oral risedronate or IV zoledronate)
Painful neuropathy in diabetes
most common type:
distal symmetric, length dependent polyneuropathy
Prevalence in T2DM is twice that of T1DM
In Type 1 you can slow progression with tight glycaemic control, it’s not the same in T2DM
- this could be possibly due to earlier onset of neuropathy in T2DM
Gastroparesis
delayed in gastric emptying in the absence of mechanical obstruction
Sx: post-prandial fullness, early satiety, bloating, N/V
Typically develops >10yr after dx of DM
Vagal neuropathy: reduced pyloric relaxation, impairment of antral contraction, disturbed antropyloric co-ordination, reduced gastric secretions
Enteric neuropathy: impairment of myenteric plexuses (between longitudinal and circular muscles)
Loss of ICC:(most common enteric neuropathology) in diabetes and idiopathic gastroparesis.
ICC damage due to lack of insulin, IGF-1 and increased oxidative stress (diabetes is a high oxidative state)
GLP-1 treatement:
PCOS
Phenotypes
A and B (no PCO) are the most common; higher risk of insulin resistance (thus hyperandrogenism contributes to this)
ABC (no oligomenorrhoea) associated with metobolic syndrome
PCOS has no association to breast ca
Why do you use metanephrine to dx phaeo?
the catecholamines secreted by the tumour is metabolised by the chromaffin cells
Plasma fractionated metanephrines have a 96% sensitivity, but 75-85% specific (complicated by age, drugs, HTN)
Thus 24h urinary fractionated catacholamines and metanephrines should be performed
- high specificity: epinephrine (99.9%), then metanehrine (99.7%) norepineprines 99.5%, dopamine 99.3%
Clonidine suppression test can be used as a confirmatory test
*urinary VMA and plasma catecholamine are not used due to low accuracy
T2 MRI can distinguish pheao from other adrenal tumours:
- hyperintense cf liver, where others will be isointense
MIBG scan can detect tumours that are not detected by CT or MRI
HbA1c
Falsely decreased:
- decreased average age of Hb: blood loss, haemolytic anaemia, CKD
- increased turnover: pregnancy, EPO therapy, Chronic liver disease (splenomegaly)
- decreased protein glycation: high dose Vit C, E, alcohol, antiviral (ribavirin), TMP
Falsely elevated:
Increase age: asplenia
reduced turnover: iron def. anaemia, Vit B12, folate def
increased protein glycation: IDA
Amio. IT: how to differentiate between 1 and 2
- assciated with underlying thyroid disease
- increased vascularity
- large goitre
- high uptake of RAI
- no response to steroid
2: low uptake of RAI
- decreased blood flow
- Raised IL-6, and thyroglobulin levels
- TPO ab negative
- T4»»T3
- responds to steroids
PET incidentaloma: benign or malignant
malignant
USS features of thyroid nodules, suggestive of malignant nodule
- SOLID
- marked HYPOechogenecity
- intranodular vascularity
- absence of halo
- Irregular margin
-** Central microcalcification**
cervical LN
>4cm - remove despite benign cytology (high false negative rate)
single cold nodule on radionuclide scan
What size of primary thyroid tumour do you remove the thyroid
??
> 1cm
Which B vitamin interferes with TFT?
Biotin
B7
Affects both TSH and T4 reporting
so STOP, an re assess in 3-4 weeks
Drugs that causes spurious TFT results?
Amiodarone
Biotin
Carbamazepine (central hypo)
Enoxaparin (high T4/T3)
Heparin (H T4/T3)
Phenytoin (LT4/T3)
Amiodarone and thyroid
- high iodine content
- long half life (100 days)
- it can cause a spectrum of thyroid dysfucntion:
> hypothyroidism
> AIT type 1: increased de novo synthesis
> AIT type 2: destructive thyroiditis
> mixed
Drug effect:
1. direct toxicity to follicular cells (AIT2)
2. beta blockade effect - mask thyrotoxicosis
3. inhibit 5’-monodeiodination of T4-T3
Iodine effect:
- Wolff Chaikoff effect (autoregulation)
> fail to escape
- Jod Basedow effect - areas of autonomous secretion –> excess thyroid hormone synthesis
- poor correlation between biochemical level and clinical manifestation
- ## Extreme wt loss and myopathy = life threatening
AIT 1 vs AIT 2
- AIT 1: more common in early phase
> TRAb may be positive
> Normal or increased vascularity on USS - AIT 2 common in late or post discontinuation (AIT2 is more common than AIT1)
> reduced vascularity on USS
> rapid response to steroids
Immunotherapy and thyroid
CTLA4 inhibitors: more central hypo
PD1 : primary hypo or hyper
Hypo is 2-3 x more than hyper
Do not necessarily need to stop
Lithium and endocrinopathy
Hypothyroidism with goitre
Parathyroid hyperplasia - hyper calccium
Nephrogenic DI
RF:
FEMALE
>40
>presense of TPO
>duration of use
Drugs that prevent T4–> T3 conversion peripherally
Amiodarone
GC
Propanolol
PTU
How does cholestyramine affect T4
reduces absorption
Pathognomonic signs for graves
- diffuse goitre
- Thyroid eye:
- bilatreal proptosis
- periorbital oedema
- scleral injection
- lid retraction - Peritibial myxoedema
- Acropachy (clubbing)
Graves
TRAb
–> thyroid hyperplasia
Female >male (8x)
40-60y
Uniform normal or diffuse high uptake
+/- TPO Ab +ve
Toxic multinodular goitre
nodule autonomy
female>male
50+ y
Uptake:
- normal or elevated multifocal uptake with surrounding suppression
TSHRab negative
TPO ab neg or low
Toxic adenoma
30-50 y
slow growing often >3cm
(otherwise similar to TMG)
Which tx modality for grave’s disease can exac thyroid eye disease?
RAI
Common and severe SE of antithyroid medications
Common:
GI
fever, athralgia, rash, transient mild neutropenia
Severe - uncommon
- agranulocytosis
- PTU- hepatocellular injury
- Cholestatic with CBZ
- Aplasia cutis and choanal or oesophageal atresia
- Polyarthritis
- ANCA +ve vasculitis (PTU>CBZ)
Subclinical HYPERthyroidism
- associated with AF, CCF, CAD, bone loss, #, dementia
- esp in >65 and post-menopausal women
Recommend TREATMENT if ** TSH <0.1 **
thyroid basic
- nuclear receptors; modify gene transcription
- increase metabolic rate but increasing NA/K+ ATPase activity, increased O2 consumption, increasesd respiration, heat generation, and increased cardiovascular activity
- potentiate the effect of GH, catecholamines (* upregulate the receptors*) glucago, cortisol
- –> gluconeogenesis, ketogenesis, proteolysis –> mimick starvation
increase T3 to T4 ratio in iodine deficiency
–> due to increased activity of 5’ deiodinase
- plasma thyroglobulin is used to monitor for rsidual thyroid tissue post surgery (tumour marker for thyroid cancer recurrence)
calcitonin: if suspicious of MTC
In a radioisotope Tech-99 scan is hot or cold nodule that suggest malignancy?
cold
RAIU scan
test of function: order if patient is thyrotoxic
■ RAIU measures the turnover of iodine by thyroid gland in vivo
■ if ↑ uptake (e.g. incorporated), gland is overproducing thyroid hormone (hyperthyroid)
■ if ↓ uptake (e.g. not incorporated), gland is leaking thyroid hormone (e.g. thyroiditis), exogenous thyroid hormone use, or excess iodine intake (e.g. amiodarone or contrast dye, which has high iodine content)
What reduces the accuracy of FNA in thyroid biopsy?
more than 50% cystic or posterior location
Hashimoto’s thyroiditis
- chronic autoimmune thyroiditis characterized by both cellular and humoral factors in the destruction of thyroid tissue
Etiology and Pathophysiology
* defect in a T-suppressor clone leads to cell-mediated destruction of thyroid follicles
* B lymphocytes produce antibodies against thyroid components including thyroglobulin, thyroid peroxidase, TSH receptor, Na + /I – symporter
Risk Factors
* F:M=7:1
* genetic susceptibility: increased frequency in patients with Down’s syndrome, Turner’s syndrome, certain HLA alleles, cytotoxic T-lymphocyte-associated protein 4** (CTLA-4)**
* family Hx or personal Hx of other autoimmune diseases
* cigarette smoking
* high iodine intake
Myxedema coma
- medical emergency – **severe hypothyroidism **complicated by trauma, sepsis, cold exposure, MI, inadvertent administration of hypnotics or narcotics, and other stressful events
- rare; high level of mortality (up to 40%, despite therapy)
Clinical Features
* decreased mental status and hypothermia are hallmark symptoms
* hyponatremia, hypotension, hypoglycemia, bradycardia, hypoventilation, and generalized nonpitting edema often present
check ACTH and cortisol for evidence of adrenal insufficiency
Treatment
* aggressive and immediate treatment required
* ABCs: ICU admission
* **corticosteroids **(for risk of concomitant adrenal insufficiency): hydrocortisone 100 mg q8 h
* L-thyroxine 0.2-0.5 mg IV loading dose, then 0.1 mg IV once daily until oral therapy tolerated; also consider T3 therapy
* supportive measures: mechanical ventilation, vasopressors, passive rewarming, IV dextrose, fluids if necessary (risk of overload)
* monitor for arrhythmia
Thyroid cancers
If a pituitary tumour is large but prolactin is only elevated slightly
it’s unlikely a prolactinoma, as the prolactin level should correlate with tumour size – thus surgery
but if a small tumour and very high prolactin, then cabergoline is the first line
Pituitary adenoma
- micro <10mm, macro >10mm
- ## Prolactinomas are the most common
Clinical feattures of prolactinoma:
Female:
galactorrhea
Amenorrhoea
infertility
Male:
Hypogonadism
reduced libido
ED
gynaecomastia
infertility
Both:
HA - due to stretching the dura
visual field deficit
Osteoporosis
If you suspect prolactinoma:
- prolactin level and macroprolactin level
- pregnancy test
- serum TSH (as TRH can stimulate prolactin)
- serum T
- cortisol and synacthen
- renal function
MRI/CT
- if no lesion:
- -> consider medications that may elevate it:
> antipsychotic, metoclopramide and domperidone, methyldopa
Which is better, cabergoline or bromocriptine?
Cabergoline (ergot derivative)
- more efficacious
Trans-sphenoidal adenonectomy is the preferred choice for macroprolactinoma and failed microprolactinoma
Continuous glucose monitoring
rtCGM: less accurate in the lower glucose range
- beneficial for both type 1 and 2 DM; regardless of which insulin delivery method they use
- - reduces HbA1c, time spent in hypoglycaemia (T1DM only), and hyperglycaemic range
- reduction in mod-sev hypos in both DM cf. self monitoring
- benefit are seen in those with good glycaemic control as well
PTC
most common thyroid cancer
- associated with exposure to radiation
Route of spread: lymph
Histology: psamomma bodies, papillary architecture, orphan annie nuclei
Palpable LN
Positive I131 uptake
Positive prognosis (98% at 10y)
Tx:
- surgery
- RAI ablation and thyroxine
Monitor thyroglobulin for recurrence, most recurrence occur within the first 5 years
basal serum TG <0.1ng/ml and normal USS: free of disease NPV 100%
but if it’s between 0.1-1.0, then you need the rhTSH stimulated TG level
TG is marker of residual or reccurence of papillary and follicular thyroid cancer
Follicular thyroid cancer
4-6%
haem spread, thus far away mets
FEMALE 3:1
Can’t identify on FNA
Favourable prognosis
Thyroid lymphoma
mostly DLBCL
hx of hashimoto’s increases risk by 60x
FEMALE 4:1
dysphagia, dyspnea, stridor, hoarseness, neck pain, facial edema, accompanied by “B” symptoms*
5 yr survival Stage IE: 55%-80% Stage IIE: 20%-50% Stage IIE/IV: 15%-35%
**Non-surgical **
Combined radiation Chemotherapy (CHOP)
MTC
Medullary cancer
MEN2a/b
aMyloid
Median node dissection
May secrete calcitonin, PG, ACTH, serotonin, kallikrein or bradykinin
role of nuclear scan in thyroid nodule
minimal value
Anaplastic thyroid cancer
<1%
Giant cells and spindles
More common in elderly
70% in women
20-30% would have a hx of thyroid ca (mostly PTC) or nodular goitre
Rapidly enlarging mass
R/o lymphoma
Thyroid cancers and driver mutations
Vast majority of the driver mutations come from teh MAPK pathway, which dominates the oncogenesis of papillary/follicular cancers (85% of thyroid cancers)
BRAF V600E accounts for majority
Others:
RAS
NTRK
ALK
RET -MTC
Anaplastic: mutational variation in multiple pathways
risk of malignancy in a hyperfunctioning nodule
low
Indications for FNA of a thyroid nodule
nodule >1cm + high suspicion
>1.5cm + modest
>2.5cm + mild
if cytology is non-diagnostic: repeat FNA in 3 months
if FNA is positive for BRAF mutation: chance of cancer is 100%, RAS mutation chance is 80-90%
Hormonal therapy for gender reassignment
Masculinising: TD/IM T
Feminising: TD/PO estradiol
+ antiadrogen therapy (required to lower endogenous T and inhibit it’s effects - options: Spironolactone and Cyproterone acetate
GnRH anologues are only used in adolescents
*progestin can increase risk of CAD, thrombosis, weight gain. No evidence for breast growth
Monogenetic cause of human obesity
mc4-r mutation
how does leptin reduce food intake
byt reducing the expression of NP-y and agouti-related peptide
How do steroids induce osteoporosis?
- direct inhibition of osteoblast function
- direct enhancement of bone resorption
- inhibition of GI calcium absorption
- increased urine calcium loss
- inhibition of sex steroids
Familial hypocalciuric hypercalcaemia
AD
defect in CaSR
inappropriate PTH secretion and Ca reabsorption
what do you test to predict risk neonatal grave’s thyrotoxicosis?
TSH-R Ab in the 3rd trimester
which anti TB reduces the AUC of prednisone?
Rifampicin
Poor prognostic factors post tx for graves
MAle
Large goitre
Persistently elevated TSH-R ab
Severe biochem dx
medication used in obesity
orlistat reversible inhibitor of gastrointestinal lipases indicated for weight loss and weight maintenance.
Phentermine *sympathomimetic anorectic agent used as a short-term adjunct therapy that is included in a regimen of weight reduction in cases of exogenous obesity.
topiramate
Naltrexone
medication used in obesity
orlistat reversible inhibitor of gastrointestinal lipases indicated for weight loss and weight maintenance.
Phentermine *sympathomimetic anorectic agent used as a short-term adjunct therapy that is included in a regimen of weight reduction in cases of exogenous obesity.
topiramate
Naltrexone
Liraglutide
benefits of bariatric surgery
sustained weight loss, reduction of obesity related comorbidities, mortality
improvement in QoL
**Wet beriberi, **
characterized by high cardiac output with predominantly right-sided heart failure and lactic acidosis
due to thiamine deficiency
thiamine is absorbed in the jejunum
Zinc
maintain immune system
assocaited with cell division, growth, wound healing and CHO metabolism
sx: hair loss, metallic taste
Lithium and DI
causes nephrogenic DI
there is a correlation with duration of treatment and total lithium dose
it’s reversible
Lithium and DI
causes nephrogenic DI
there is a correlation with duration of treatment and total lithium dose
it’s reversible
Risk of developing T1DM and family
Patients with the highest risk of risk of developing type 1 diabetes include patients with an identical twin who have type 1 diabetes, patients who have high risk HLA subtypes (HLA DR4-DQ8 and/or DR3-DQ2) as well as having a sibling with type 1 diabetes, and patients with multiple first degree relatives with T1DM. Interestingly having a father with T1DM increases the risk of developing diabetes in the index more-so than having a mother with T1DM.
Aspirin-exacerbated respiratory disease occurs more commonly in females. Other causes of nasal polyps include idiopathic nasal polyps (which typically affect males in their 60s), cystic fibrosis (in patients 16 years and younger) and Eosinophillic granulomatosis with polyangiitis (which is associated with elevated eosinophil levels)
Patients may have normal antibody levels, but these antibodies are not functional. Therefore often functional testing is required, such as measuring the antibody response following vaccine administration (usually a polysaccharide antigen from pneumonia vaccine)
90% of hives is not allergy mediated - ie not IgE mediated degranulation of mast cells. Common causes include physical urticaria (eg temperature driven, pressure driven). 50% of cases of hives without an obvious cause may be driven by IgG antibodies against mast cells
Generally speaking, urticaria tends not to progress to anaphylaxis with the exception of cold urticaria, where the occurrence of severe anaphylactic reactions or suffocation due to oropharyngeal edema is possible. Angioedema may occur with urticaria, which tends to last hours, as opposed to days in bradykinin mediated angioedema
Sarcoidosis is characterized by accumulation of activated macrophages and formation of noncaseating granulomas within the affected tissues. Any organ can be affected, but the lungs are most frequently involved, followed by the skin and eyes. Chest x-ray will show bilateral hilar adenopathy, and diffuse interstitial infiltrates may also be seen. In pulmonary sarcoidosis, the accumulation of CD4+ cells in areas of active disease results in predominance of CD4+ T cells and high CD4+/CD8+ ratio (>2:1) in bronchoalveolar lavage fluid.
True or false: in the absence of microalbuminuria, ACE/ARBs do NOT reduce development of nephropathy but IS protective against retinopathy.
True
In people with XLA, the white blood cell formation process does not generate mature B cells
Hypokalaemia and HTN
- cushing’s syndrome
- Conn’s syndrome (primary hyperaldosteronism)
- Liddle’s syndrome
- 11-beta hydroxylase deficiency (21 hydroxylase deficiency is not associated with HTN)
