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
