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13:04 Sunday, 10 February 2019

ACTH TSH FSH\LH GH

GH

1
-

20% GH
GH insulin induced hypoglycemia IGF-1 -
3 GH
stroke
GNRH arginine

GH -
-

-
-

carpal tunnel syndrome

2
-
200 -
100 -

stalk

20 -
sample falsely low 1000 Hook effect -
dilution
falsely elevated Macroprolactinemia -
-

3
functioning pituitary tumors 50% -
10/100,000 30/100,000 -
ACTH GH mixed tumors -
250 1:1 1 20 1 -
-
5% -

4
-
-

200 1

sella 100

MRI 2

MRI 1

2
Dopamine agonists -

20%
Cabergoline
D2 ▪
70-90% ▪
bromocriptine ▪
Bromocriptine


intra-vaginal ▪

GI ▪



5% ▪



Invasive macroadenoma ▪
50% 20% 30%
-

3
15-30% 5% -
-

5
10 -
-
frontal bossing
gigantism
-
-
-
-
-
LVH CVS -
60% Sleep apnea -
-
1/3 -
stroke 3 -
10 -

IGF1 screening -
0.4 GH 75 OGTT -
25% -

-
15%
Somatostatin analouges -


30% GI ▪
pasireotide ▪
Pegvisomant GH receptor antagonist -

lypodystrophy

-
GH

6
-

Non functioning pituitary adenoma


-
-
MRI -
-

7
Diabetes insipidus
19:04 Sunday, 10 February 2019

AVP 75% diabetes insipidus -


300 40 -
-

1-2% -
-

50% -

8
DI 24 -
Primary polydipsia DI -

Water deprivation test 1

primary polydipsia DI
DI

plasma AVP 2

unrestricted fluid intake plasma AVP 3


nephrogenic DI 1 AVP
MRI primary polydipsia central DI 1 AVP
primary polydipsia T1 Bright spot
Central DI bright spot
bright spot nephrogenic DI MRI 4

9
bright spot nephrogenic DI MRI 4

DDAVP -

Central DI -
SC IV DDAVP
V2 DDAVP
flow

Nephrogenic DI -
DDAVP 10
amiloride

indomethacin NSAIDS
30-70% 3
Primary polydipsia -

10
17:23 Friday, 1 February 2019

colloid follicles
Thyroglobulin

TSH TRH -
TSH LH, FSH, hCG TSH -
TSH TRH TRBeta2 (thyroid hormone receptor beta2) -
TSH -

iodinization Tg -
NIS -

congenital hypothyroidism Pendrin NIS


TPO -
T4 T3 coupling Tg
Tg -

-
Cretinism -
-
IQ -
150 -
NIS upregulation -

-
Wolff-Chaikoff effect -
escape -
-

TTR transthyretin TBG 99% -


total thyroid hormones TBG -

SERM tamoxifen

TBG -

NSAIDS TBG -
unbound T4 unbound T3 unbound -

TSH hCG 1
TSH -
hyperemesis gravidarum -
-
TSH -
TBG 2
3
4
45% -
250 5

Deiodinases
T3 20 T4 -
T3 T4 -
Type 1 deiodinase
Type 2 deiodinase
T3 T4 -

T3 T4 -

propanolol PTU
reverse T3 T3 T4 Type 3 deiodinase -
sick euthyroid syndrome
Massive hemangioma

11
-
Pemberton's sign -
thyroglossal cyst -
-

TSH
unbound TSH -
unbound T4 -
unbound T4 TSH 2-5% T3 thyrotoxicosis
TSH -

TSH secreting pituitary tumor


Thyroid hormone resistance
TSH -

TSH
Biotin
T4 TSH Secondary hypothyroidism
TSH ▪

anti TPO Tg TPO -


2% 5-15%
80%
TSH-R TSI -

fetal thyrotoxicosis

Serum Tg
thyrotoxicosis factitia -
-
anti Tg antibodies

Toxic MNG

Subacute viral or post partum thyroiditis 1


thyrotoxicosis factitia 2
3
struma ovarii 4

Whole body scanning -


TSH
thyroid hormone withdrawl protocol ▪
recombinant TSH ▪
whole body scanning

-
3 -
90% -
hypoechoic

isoechoic 5-10% -
3% -

12
3% -
Spongiform

13
19:18 2016 20

-
-
Hashimoto -
-

Congenital hypothyroidism
1:4,000

2 thyroid gland dysgenesis 80-85% -


inborn errors of hormone synthesis 10-15% -
TSH-R antibody mediated 5% -
-

-
-
-
4 -

T4 TSH -
TSH 14 T4 -
IQ -
3 -

Autoimmune thyroiditis
-
Hashimoto's
Atrophic thyroiditis
sub clinical hypothyroidism -
overt hypothyroidism 10 TSH -

14
overt hypothyroidism 10 TSH -

1000 1 1000 4 -
-
60 -
5% 3% subclinical -
TPO 4%

oxyphil metaplasia germinal centers -


end stage thyroid follicles -
IgG-4 plasma cells -
CTLA-4 HLA DR3, DR4, DR5 -
-
pernicious anemia 1 -
-
selenium

alemtuzumab tyrosine kinase inhibitors


anti TPO, anti Tg -

T cell mediated injury

thyroid atrophy 20% TSH-R blocking antibodies -


transient neonatal hypothyroidism
TSH-R blocking antibodies TSI
Thyrotropin binding inhibitory immunoglobulin assay (TBII)
TSH-R antibodies TSI

-
-
-
myxedema
nonpitting pretibial edema Puffy face

-
-
-

TRH
-

30%
sleep apnea
-
Carpal tunnel syndrome -
-
-
tendon reflexes Slow relaxation

15
tendon reflexes Slow relaxation

cingulated cortex PET


Revesible cerebellar ataxia

Myxedema coma
TPO antibodies Hashimoto encephalopathy
EEG
-
5% Thyroid ophthalmopathy -
RA SLE Type 1DM pernicoius anemia -

TSH -
primary T4 TSH
95% TPO ▪
TBII 20% ▪
T4 TSH

16
-

CK

US MNG -
Iatrogenic hypothyroidism -
sub-total thyroidectomy 3-4
TSH unbound T4
cretinism -
-
13%
-

Tyrosine kinase inhibitors


-
Secondary hypothyroidism -
TSH
unbound T4
TSH T4

30 100-150 1.6 -
-
TSH -
AF T4 -
TSH -
TSH 3-6 -
7 T4 -
TSH -
-

17
tyrosine kinase inhibitors PPI SERM

Sub clinical hypothyroidism


-

TSH>10
suggestive symptoms TPO
3 TSH subclinical -
25-50 -
TSH -

pseudotumor cerebri levothyroxine -

-
4
2.5 TSH
45%
12.5-25 20% -
-

Myxedema coma
20-40% -
TSH T4 -
-
-
-
-

MI
GI

Stroke

-
dilutional -
hyponatremia
-
1.6 200-400 levothyroxine IV
IV 25%
IV
8 2.5-10 5-20 liothyronine IV (T3) T3 T4

cardiovascular 30
collapse
6 50 IV hydrocortisone

water retention

18
18:23 Saturday, 2 February 2019

-
-

60-80% -
2% -
20-50 -

PTPN22 CTLA-4 HLA DR -


-
Grave's ophthalmopathy -
3 -
alemtuzumab IRIS HAART -

TSI -

TBII assay
TSI

TSI
80% -
anti TPO
anti Tg
-
T
IL-1 TNF IFNgamma

19
-
-
-
-
-
-
hypokalemic periodic paralysis -
-
SVT
pulse pressure

atrial fibrilation 50


onycholysis Palmar erythema -
40% -
steatorrhea -
-
20% -
firm 2-3 -
-
apathetic thyrotoxicosis

staring lid retraction -


Graves ophthalmopathy -

10%
TPO
75%

US CT
10%

sclera proptosis 1/3


corneal exposure
chemosis scleral injection
5-10%

EUGOGO NO SPECS

20
Thyroid dermopathy
5% -
pretibial myxedema -
-
orange skin indurated -

Thyroid acropathy
clubbing -
1% -
-
clubbing -

TSH -
borderline iodine intake 2-5% T3 T3 toxicosis -
T4 toxicosis -
-

MNG
destructive thyrotoxicosis factitious
thyroiditis
TPO TBII -
MRI CT TSH Secondary hyperthyroidism -
-

21
10-30% -
-
10-15 15% -
-

12-18 3-6
5%

-
1-2

-
-

Thionamides
Carbimazole Methimazole PTU -
-
TPO
thyroid antibodies

T3 T4 deiodination PTU
6-8 100-200 90 PTU -
8-12 10-20 6 -

titration regimn -

22
block-replace regimn -
4-6 -
unbound T4
6-8
TSH
-
12-18 30-60%

-
1-5%

-
PTU

thyroid storm ▪

PTU
Methimazole
drug induced lupus ANCA
1%

Propanolol
6 20-40 -
T3 T4 -
1 -
thyrotoxic periodic paralysis -

-
fixed dose -

-
5-7 -
2-3 -
interval

thyrotoxic crisis 1

3-7 PTU 2-3

radiation thyroiditis 1-2 2


3
5% 10-20%

6-8 tapering 30

23
5

total or near-total thyroidectomy


-
-
thyrotoxic crisis -
potassium iodide

recurrnet laryngeal nerve

2% -

reference range T4

aplasia PTU 14-16


TE fistula choanal atresia cutis
PTU methimazole
TSI
Neonatal thyrotoxicosis -
160 IUGR
26 TSI
1-3
PTU
-
-

Thyroid storm
-
-
30% -
-
DKA stroke

PTU
4 250 500-1000 PZ PR PO IV ▪
T3 T4 ▪
6 SSKI 5 PTU

wolff chaikoff effect ▪
4 IV 2 4 60-80 Propanolol
8 100 300

Cholestyramine
IV

-
-
100 selenium
corneal damage chemosis -
250 6 IV 500 pulse steroids
6 IV
Orbital decompression

24
Orbital decompression
-
rituximab external beam radiation -

-
octreotide -

TSH Secreting pituitary tumor


alpha T3 T4 TSH -
TSH
MRI CT -
Octreotide -

Acute thyroiditis
-
piriform sinus fourth branchial pouch -
-

-
PMN FNA -
PCP -
-
-

Sub acute thyroiditis - de Quervain's thyroiditis- granulomatous\viral thyroiditis


-
- coxsackie mumps
30-50 -
URTI -

25
-
T3 T4 0-6 1
6-12 2
12-18 3
-
-

FNA -
-
NSAIDs 4-6 600

ESR tapering 15-40 ▪

TSH
-

15%

Painless\silent\post partum thyroiditis


3-6 5% -
sub acute -
sub acute -

TPO
-

Drug induced
tyrosine kinase inhibitors IFN-alpha -
-
anti TPO -

Chronic thyroiditis
Hashimoto -
Riedel's thyroiditis -

26
rec. painless
Laryngeal

FNA
compression
IgG-4 related Diseases

Sick euthyroid syndrome - nonthyroidal ilness


IL-6 -
-
T4 TSH low T3 syndrome -

T3
reverse T3
low T4 syndrome -
T4 T3
T3 T4 type 3 deiodinase

T4 TBG
-
TBG total T3 T4

total + unbound T4
T3 T4 HIV
T3
rT3 -
-
-

27
18:01 2016 21

39% -
40 -
6 -
-
T3 T4 deiodinase activity

1
T4 -
Wolff Chaikoff effect -
-
deiodinase
rT3 T4 T3 20 TSH
TSH 3

13% 2
6% 13% -
Wolff Chaikoff effect -
anti TPO -
-
T4 TSH -

Amiodarone induced thyrotoxicosis ( AIT) 3


-
10% 2% -
-

Type 1 AIT -
Nodular goiter pre-clinical graves
Jod Basedow effect


6 200 potassium perchlorate ▪

Type 2 AIT -

destructive drug-induced lysosomal activation


thyroiditis

28
Near total thyroidectomy -

-
-

-
-
-
-
-
QT -
CYP 450 -

Type 1 Type 2
Underlying thyroid disease Yes (Multinodular goiter, Grave s) No
Time after starting amiodarone Short (median 3 months) Long (median 30 months)
24-hour iodine uptake Low-Normal (may be high in iodine deficient Low to Suppressed
regions)
Thyroid Ultrasound Diffuse or Nodular Goiter may be present Normal or small gland
Vascularity on Echo-color Doppler Increased Absent
ultrasound
T4/T3 ratio Usually <4 Usually >4
TgAb / TPOAb/ TSI May be present Usually absent
Circulating interleukin-6 Normal to high Frequently markedly
elevated

29
12:31 2016 21

-
30 US -

1
TSH-R TSI -
TSH -

Diffuse non toxic (simple) goiter 2

TSH -
5% endemic goiter
sporadic goiter

cassava root goitrogens


NIS, TPO, Tg -
TSH

thoracic inlet Sub sternal goiter -


external Pemberton's sign -
jogular vein
diffuse simple goiter -

T4 TSH Sub clinical thyrotoxicosis


AF
50 -
TPO -
US -

-
-

thoracic inlet

30
TSH -

3
3-7% -
US 50% -

Non toxic MNG


12% -
pemberton's -
sign
-

1 US

-
Jod-basedow effect
50%
5% ▪

Toxic multinodular goiter


-

-
T4 T3 TSH
FNA -


hyperfunctioning solitary nodule


TSH-R 90% -
G protein alpha
-
-

3 75% ▪

31

45 10% ▪

32
13:50 2016 21

microfollicular, trabecular, Hurtle -


cell
FNA -
TSH -
6-12 -

-
-

-
65 20 -
MEN2 2 -
Cowden, polyposis, Carney
-

-
-

-
-
TSH -

33
34
80-85% Papillary -
orphan annie eye psammoma bodies

80%
1%

2 ▪
25-30% 2 ▪
5% Follicular -
capsular\vascular invasion FNA

CNS
hurthle cell histology 4 50

35
T1b 1 1
near total 4 1
thyroidectomy
near total thyroidectomy
4 ▪


vasuclar invasion ▪
US
TSH TSH suppression therapy 2

TSH 0.5-2
TSH 0.1-0.5
TSH< 0.1
3

4 ▪


1-2 ▪
recombinant TSH TSH ▪
whole body scanning

multikinase inhibitor Sorafenib 4

serum thyroglobulin -
US -
WBS -

PET CT US Tg

-
stage IV -
-

36
-
-
immune check point inhibitors -

-
-
diffuse large cell lymphoma -
ATC small cell lung cancer -
-
-

Medullary thyroid carcinoma


5% -
Familial MTC MEN 2A MEN 2B -
-
RET mutation -
-
targeted kinase inhibitors -

5% -
US 50 50% -
-

TSH 1
TSH -
US TSH -

US 2
US 15% -
-

US FNA 3
1 -
size cut offs FNA -

US -
AUS\FLUS -

85% 10-30%

37
38
16:55 Friday, 18 January 2019

100,000 1-2 -
-
cushing disease 90% -

90% ACTH Dependent


75% Cushing disease -

1 90%

MEN1
POMC ACTH EFG USP8
15% Ectopic ACTH -
carcinoid tumors
Small cell lung cancer
medullary thyroid carcinoma

10% ACTH independent


5-10% -
1% -
Bilateral macronodular adrenal hyperplasia -

food induced cushing GLP LH


Carney's complex PPNAD Micronodular pigmented -
McCune albright -

-
11betaHSD2 -

-
FSH LH
TSH
-
easy bruising
1

kunckles ectopic ACTH -


ectopic ACTH -

39
ectopic ACTH -
VTE -
-
-

-
-

1
24 1
overnight dexamethasone 2
- false positive
rifampin CYP2A4 Inducers ▪
4-6 total cortisol ▪
diurnal variation 3

4 2 -

ACTH independent ACTH dependent ACTH 2


ACTH ACTH independent -
ACTH ACTH dependent -
-

3
CT ACTH independent -
ACTH dependent -
MRI
40% ▪
T1 ▪
Ectopic ACTH pituitary Cushing 2
CRH test ▪
High dose DEX test ▪
IPSS
MRI inferior petrosal sampling ▪
IPSS ▪
IPSS ▪
Ectopic ACTH production

40
Ectopic ACTH production
high resolution CT ▪
T2 MRI ▪
octreotide ▪
chromogranin A ▪

-
ACTH Independent -
Cushing's disease -
70-80%

Ectopic ACTH -

2

Bilateral adrenalectomy ▪
severe Cushing's -
6 500 11 beta hydroxylase Metyrapone
1200 200 Ketoconazole
adrenolytic agent Mitotan
11 beta hydroxylase Etomidate IV

41
11 beta hydroxylase Etomidate IV
SST5<SST2 Pasireotide 373
GI ▪

-
HPA

-
relapse -
80% Ectopic ACTH
40% adrenal's cushing
60% Cushing's disease

Nelson syndrome
-
ACTH -
-

42
10:52 2016 23

5-12% -
hypokalemic HTN -

1
bilateral micronodular hyperplasia
2 Conn's syndrome
GRA Glucocorticoid-remediable hyperaldosternism
ACTH crossover mutation 

early onset HTN & strokes 

Non aldosterone related 2
Cushing's syndrome
DOC Adrenocortical carcinoma
11-beta-HSD2 SAME
11-beta-HSD2
CAH
17 alpha hydroxylase 11beta hydroxylase 
Deoxy-corticosterone (DOC) 
MR Progesteron-induced HTN
Liddle's syndrome
ENAC 

Hypokalemic HTN -

volume expansion ▪



-
hydrogen depletion ENAC activity
tetany

43
tetany
-
Remodeling

2 -
Connshing syndrome mild autonomous cortisol access MACE -

40
3
ARR aldosterone-renin ratio 1
-

4
FN ACE\ARB FP

confirmation 450 ARR>750 2


140 4 2
oral sodium loading test
fludrocortisone supression test
confirmatory test ARR overt hypokalemic HTN -

CT 3
5 CT -
-
AVS selective adrenal venous sampling -

CT ▪
40 ▪

Vena cava 3
2
GRA -
early onset HTN

Non aldosterone related mineralocorticoid excess 4

urinary steroid metabolite profiling


SAME ▪
DOC-producing ACC CAH ▪
Liddle's syndrome

44
adrenalectomy -
40
AVS
-

AVS CT
postsurgical hypoaldosteronism
- Spirinolactone
400 15-25

Eplerenone

200 25
5-10 Amiloride
GRA

45
46
11:59 2016 24

CT 2-5% -
70 7% 40 1% -

MEN1, MEN2, CARNEY'S, Mc-Cune albright -


benign inactive adenoma -
25% -
5% -
staging 1-2% -
ACC 17OHP DHEA -

-
mild autonomous cortisol excess MACE -

1 -

1
CT 2


60% 80% ▪
tumor density

47
tumor density
HU<10 ▪
HU>20 ACC ▪


lobulated ▪
Intermediate MRI -
-
6-12

UH 10
CT FNA -

1
2
outcome 3
25% -

ACC- adrenocortical carcinoma

1-2 -
90% IGF2 overexpression 25% TP53 -

48
90% IGF2 overexpression 25% TP53 -
ACC 25% Li-Fraumeni syndrome -
FNA -

Weiss score -
60-70% -

GC
Mixed production
-
-
Ki67>10%

-
Mitotane -

8 ▪
Ki67>10% ▪


mitotane
GC
mitotane ▪
CYP3A4 ▪
CBG ▪
-
mitotane cisplatin etoposide Mitotane -
15 5 30-40% -

49
10:29 2016 24

10,000 5 -
10,000 3 Secondary adrenal insufficiency
10,000 2 Primary adrenal insufficiency

CAH ▪
0.5-2% -

Addison's disease - -
isolated autoimmune adrenalitis 30-40%
APS Autoimmune polygalndular syndrome 60-70%
chronic mucocutaneous candidiasis 10% APS1 ▪

T1DM Vitiligo APS2 ▪


pernicious anemia
-
X-linked adrenolekuodystrophy
20,000 1 ▪
very long chain (>24) fatty acids ▪
cerebral ALD 50% ▪
AMN 35% ▪
15% ▪
1% CAH
CMV TB -
-
APLA Waterhouse-friderichsen syndrome -
-
mitotane ketoconazole etomidate -

-
-
Sheehan's syndrome -
-
Isolated ACTH deficiency -

50
-

40% 80%
ACTH
-

SIADH ADH

51
bitemporal hemianopsia
ACTH Alabaster like paleness
GC
GC -

GC TSH

central hypothyroidism TSH ▪
ACTH DHEAS

Adrenal crisis Acute adrenal insufficiency

52
-
GC -
-
acute abdomen -
-
-

GC
adrenal crisis -

Secondary adrenal insufficiency -


ACTH 4
ITT - Insulin Tolerance Test



-
Diurnal cortisol secretion
ACTH

53
Adrenal crisis
1L\h

24 200 100
50

2-3 15-25 -

IV
50%
30



0.025 0.25 0.2 1
fludrocortisone 100-150 -



fludrocortisone 100 40 GC

DHEA 25-50 -

GC
premature ovarian failure -
-

54
13:03 2016 24

-
carotid body -
SDH NF1 VHL MEN2A/B 25-30% -
1 2-8 -
hypertensive patients 0.1% -
40 -
10% 10% 10% -

-
5%
hypertensive crisis
-

flushing





bladder pheochromocytomas ▪
TCA ▪
-

PTH
ACTH
EPO

24 -
fractioned metanephrines and catecholamines
assay 3
-
FP

FP

55

TCA ▪
FP -

MRI CT -
CT T2 MRI

adrenal incidentalomas 5%
MIBG -
PET DOPA -

glial like substebtacular cells chief Zellballen pattern -


SDHB synaptophysin chromogranin S100 -

partial or total adrenalectomy -

-
160/90

volume constricted ▪

prazosin / phentolamine
ACEI CCB
beta2 unopposed alpha ▪
-
intraoperative nitroprusside nitroprusside
-

bilateral adrenal cortex sparing surgery ACTH

5-10% -
-
-
-
-
MIBG nucler medicine therapy
thalidomide sunitinib
30-60% 5 -

15 -
RET MEN2B MEN2A -
MTC MEN2A
multiple mucosal neuromas MTC MEN2B
50% MEN MTC
MTC
PGLs Paraganglioma syndromes -

SDH
VHL -
clear cell RCC retinal and cerebellar hemangioblastomas
20-30%
1% NF1 -
NF1 RET, VHL, SHD -

56
MEN
9:41 Friday, 12 April 2019

Wermer's syndrome MEN-1

MEN1 -
Pancreas Parathryoid Pituitary -
-
60% Pituitary -
90% Parathyroid -
4

total parathyroidectomy 3.5


forearm
50% Gatrinoma Pancreas -
MEN1

20%

57
Sipple's syndrome MEN2

RET -
MEN2B MEN2A -
Medullary thyroid carcinoma -
MEN2
5-10%
RET
flushing
FNA US

PET cold nodule

TKR inhibitors
-
50%
RET 11-16 screeing

fractioned metanephrins MEN2


CT\MRI\PET

58
Autoimmune polyendocrine
Tuesday, 19 March 2019 11:03

59
10:30 Friday, 12 April 2019

-
wheezing 5HT
wheezing flushing
90-100% -
Midgut carcinoid
-
GI

80% Flushing -
flushing -

SSRI

-
30% -

pulmonic stenosis Tricuspid regurgitation


PFO
80%
18% -
25% pellagra like lesions -
tryptophan tryptophan
-
retroperitoneal fibrosis -
Carcinoid crisis -

200 5-HIAA

flushing

60
5-HIAA 24
L DOPA SSRI FP -
synonym -

flushing -
nicotinamide -
loperamide -
-
Pasireotide lanreotide octreotid
5-HIAA

carcinoid crisis
GI

-
Serotonine receptor antagonists
methylsergide 5HT1, 5HT2 receptor antagonists ▪
ondansetron 5HT3 receptor antagonists ▪
H1+H2 receptor blockers
telotristat tryptophan hydroxylase inhibitor
interferon alpha
hepatic artery embolization

61
11:43 2016 18

ESRD 1 -
-
7 -

-
-

HgA1C -
glucose intolerance -

Impaired Fasting Glucose (IFG) -


Impaired Glucose Tolerance (IGT) -

HgA1C FPG

3 45 -
25 BMI -
pre-diabetes -

62
cAMP GIP GLP1 -
fasting level -
-
Alpha cells L cells -

T1DM
70-80% -
T1DM 30 5-10% 20 -
insulin deficient 1-2 honeymoon -
c peptide -
-
40-60% concordance
5-15% 3-4%
IL-2 PTPN22 CTLA-4 HLA DR3, DR4
T -
GAD, insulin Islet cell autoantibodies -
1 85%
15 80% 5 1 70%
5 1 50% 1 1 3-4%
GDM 5% 2 5-10%
-

63
T2DM
-
70-90% -
T2DM 40% -
obese 80% -
-
2 IL-6 CRP -
50% 2 -
GLP1 lipotoxicity glucose toxicity -
- -
-
IGT -
IFG overt diabetes -
10-20 T2DM 35-60% GDM -

-
-
5 Diabetes Prevention Program study
58% 2
31% -
pre-diabetes
35 BMI 60 IFG IGT
GDM
pre-diabetes -

64
65
14:42 2016 18

200 -
-
-

2 1 -

140-180 -

HgA1C
120 RBC 2-3 non-ezymatic glycation -
HgA1C 50% -
28 126 6 -
HgA1C -

0.4%
-
glycated albumin fructosamine -
6.5% HgA1C<7% -
8%
6% HgA1C

1
Intensive insulin therapy -

C peptide 1

66
amylin Pramlintide
-
2 1 -
-
30-60 15 1
120 60 2
-
-
-
HgA1C -
-
-
GI motility
hypoglycemia unawarness

CHF A1C
1-3% Medical nutrition
therapy + physical
activity
GFR<45 - GI - 1-2% -
GFR<45 - FPG
- -
(30 - B12 - cAMP
- -
-
CV -
-
-
-
- - 1-2% Insulin secretagogues SU
- - ATP K Glimepiride -
Glipizide -
- Glyburide -
-

67
-
acrabose ketoconazole
fluconazole
-
glyburide FPG -

repaglinide - - 0.5-1% Non SU Insulin secretagogues Glinides


- ATP K Repaglinide -
Nateglinide -
Mitiglinide -
- - 0.5-1% Insulin secretagogues - glucose GLP-1-agonist
- GI - stimulated insulin secretion Exenatide -
- Liraglutide -
MEN - Insulin secretagogues - victosa
-
- CVS
- -
GI - Semaglutide -
-

- - 0.5-0.8% Insulin secretagogues - glucose ptin DPP-4


- stimulated insulin secretion Sitagliptin -

GLP1

IBD - - 0.5-0.8% - Alpha Glucosidase


- SU - inhibitors
2 - - acrabose -
- migitol -
bila acid -
resins

3-4 CHF - - 0.5-1.5% PPAR- - rosiglitazone, TZD


- CHF - Gamma pioglitazone
CI - -
-
diabetic macular - PCOS -
edema Pioglitazone -
- MI
rosiglitazone LDL -

Pioglitazone -

Rosiglitazone -
CV

insulin - Urinary & genital mycotic - 0.5-1% - flozin SGLT2


deficient infections
Type I -
DM intravascular volume Insulin independent -
3-6 -
-
Euglycemic DKA - Canagliflozin Empagliflozin -
Moderate renal - CVS
insufficiency
CHF
Dapagliflozin -

Canagliflozin -

- Not limited glucose utilization


-
-

68
type 2 DM

250-300 FPG

-
fasting hyperglycemia
NPH Glargine
basal bolus -

69
A1C -
DPP4 inhibitors
acrabose
SGLT2 inhibitors
-

TZD
SU -
-
-
canagliflozin empagliflozin SGLT2 inhibitors
GLP agonist liraglutide
TZD -
-

alpha glucosidase inhibitors


incretins
SGLT2-inhibitors
-
BMI>30

-
-
HgA1C -
-
140-180
110-140
Regular IV -
ICU
SC
1
insulin deficiency 2-4 SC IV -
Basal\bolus -
sliding scale
-

TPN
TPN IV -
SC total enteral nutrition -

Steroid induced diabetes


-

-
steroid induced diabetes 5 -

post prandial period

200

Gestational diabetes mellitus


7% -
-
-
24-28 -
GDM -

2 GDM -
GDM -
-

HgA1C<6.5%
HgA1C

70
DKA HSS
19:54 Saturday, 18 May 2019

DKA
2 1 -
T1DM -
250

captopril FP acetone acetoacetate nitroprusside assay

SGLT-2 Euglycemic DKA


15 high AG -
15 alcoholic ketoacidosis starvation ketosis
-
-
1.6-2.4 100 -
-
CRP -
-
-
3

DKA

71
-
20 1-3 2-3
0.45%

250-500 ▪
5% 250
3-5 24
-
0.1 0.1
0.02-0.1
2-4 IV basal bolus SC
-
5-5.2 20-40 IV
3.5
3.3
potassium phosphate\acetate
5.2
-
PH<7

10 200 sodium bicarbonate 50

7 PH ▪
1 -

DKA -
24 4 1-2 -

precipitating event 1% -
UGIB ARDS VTE -
-

72
HHS
-
2
oral intake

-
DKA -
15% -
DKA

-
MI

water intake

intravascular volume depletion osmotic diuresis -


fluid intake -
-

1000 -
350 -
Pre-renal azotemia -
-
-

-
2-3 0.9% 1-3

0.45 % saline 150 ▪


9-10 ▪
200-300 D5W 0.45% ▪
1-2 9-10 ▪
-
-
-
-
-
0.1 IU/Kg IV
IV 0.1 IU/Kg/Hr
0.02-0.1 250
SC IV

73
74
14:07 Thursday, 7 February 2019

-
2 -
-

2 5000 UKPDS 1 1400 DCCT


-
-
-
HgA1C
10

Legacy effect or metabolic memory ▪
2 -
1 -
-

20-74 -
cotton wool spots blot hemorrhages nonproliferative -
vitreous hemorrhage Proliferative -
3 25% macular edema -
-

6-12 ▪
Laser coagulation
Fenofibrate
Anti VEGF therapy

ESRD CKD 1 Diabetic nepropathy -


20-40% -

75
20-40% -
-
diabetic nephropathy -
-

diabetic nephropathy
GFR GFR mesengial expansion GBM GFR glomerular hyperfiltration -
hyporeninism hypoaldosteronism Type IV renal tubular acidosis -
contrast induced nephropathy -
60 GFR Diabetic kidney disease -
-

spot urinary albumin to creatinine ratio ▪


GFR ▪
2
1 5
-

SGLT-2 inhibitors GLP-1 agonist ▪

140/90 ▪
130/80 ▪
CKD 130/80 CKD ▪
ARBS ACEi ▪
0.8
-

20 30 GFR
-

50% -
-
-
BMI

Distal symmetric polyneuropathy 1

76
Distal symmetric polyneuropathy 1

Autonomic neuropathy 2

GI
GU
hyperhidrosis anhidrosis
hypoglycemia unawarness
Mononeuropathy 3
carpal tunnel
CN III
IV, VI, VII
Diabetic radiculopathy 4

diabetic amyotrophy

loss of protective sensation

B12
TCA pregabalin dulexetin

GI\GU
-


radiolabeled C labelled gastric emptying breath test ▪
-
1 -
-
-

retrograde ejeculation erectile dysfunction

foot ulcers & infections


-
repeated minor trauma
claw toe hammer toe charcot
anhidrosis
PAD
MTP -
-
-

10

PAD

Ankle brachial index 50 PAD

Infected ulcer -

wound probe
debridement
arterial bypass
contact casting orthotic devices Off loading

77
contact casting orthotic devices Off loading

-
Rhinocerebral mucormycosis
Emphysematous cholecystitis
Emphysematous cystitis \ pyelonephritis
Malignant invasive otitis externa
TB S.aureus Pneumonia

Post-operative wound infections


MRSA
cell mediated immunity -

-
Pigmented pretibial papules - diabetic skin spot -

Necrobiosis lipoidica diabeticorum -


Acanthosis nigricans -
1 Vitiligo -
lipohypertrophy Lipoatrophy -

78
19:50 Thursday, 15 February 2018

Whipple's
-
70 -
-

-
-
-
GH 4 prolonged hypoglycemia -
-

shift -
shift recurrent hypoglycemia -

-
-
TIA -

2 -
glinides Sulfonylurea -
-

Hypoglycemia associated autonomic failure ( HAAF)

140-180 -
2-3 hypoglycemia unawarness -

79
1
-
Insulin secretagogues -
-

glycogen depletion

quinine NSAIDs ARBS ACE -

Critical ilness 2
-
-
-
-

3
-

-
GH -

Non beta cell tumors 4


adrenocortical carcinoma hepatomas -
Insulin like growth factor II (big IGF-II) -
-
IGF-II\IGF-I IGF-II -
-
bulk -
GH -

1
fasting hypoglycemia -
inappropriately normal C peptide -
IV -

critical sample -

C peptide

circulating oral hypoglycemia agents


IV glucagon -
72 -
-

-
250,000 1
2 99% 90%
3 MEN1 50
C Peptide

70-80% MRI CT ▪
90% EUS ▪
50% ▪

80

US ▪

Diazoxide ▪
Octreotide ▪
Everolimus ▪
intra-gastric ▪

post prandial hypoglycemia Non insulinoma pancreatogenous hypoglycemia -

Functional beta cell disorder - Nesidioblastosis -

alpha-glucosidase inhibitor octerotide Diazoxide

Post gastric bypass -


post prandial
Roux-en-Y

insulin receptor -

-
ectopic insulin secretion
gain of function

Sulfonylureas factitious 2
factitious disorder
C peptide
C peptide SU
SU

15-20 -
IV 25 -
1 IM glucagon -
1
2
SUs Octreotide -
-

81
11:14 Saturday, 9 February 2019

9-11 12 -
-

primary lipid disorder -

1
2

500 TGs -
-
-

1
-
-
-
-

Fibrates 2
PPRAalpha -
-
TG LPL
apoC-III
VLDL TG
-
severe hyper TG LDL

CKD

n-3PUFAs Omega 3 fatty acids 3


-
3-4 DHA EPA -
TG -
-
LDL

LDL-C -
-
Familial hypercholetaterolemia 1
LDL CVD 2
LDL 7.5% 10 CVD 40 CVD 3
CVD lifetime risk 4

-
-
-
LDL

LDL - HMG-CoA - Statins


reductase
6%
▪ TG - LDL -
▪ 400 LDL receptors
▪ 5-10% HDL -

82
▪ 5-10% HDL -
gemfibrozil
CK -
CK -

AST ALT
2-3 ▪

ULN 3 ▪

3 ▪

2

- LDL 18% - - 1/3 - Ezetemibe


- 2/3

HDL TG - sitosterolemia NPC1L1


NPC1L1 ezetemib -

60%
LDL

TG - - Bile acid
sequestran
- ts
ezetemibe (Resins)
- cholestyra
LDL upregulation mine
intolerance LDL colespitol
colesevela
m
injection site reaction - 50-60% LDL - - PSCK9 - PCSK9
Lp(a) - FH inhibitors
LDL receptor

ezetemibe LDL-R

-
2-4

LDL
- apheresis
PSCK9
inhibitors

200 LDL
160

300 LDL

FH
FH LDL -
PCSK9 -
LDL -
last resort -

83
84
18:21 2016 18

5 3

150 o
50 40 HDL o
85 130 o
100 o
88 102 o

85
11:27 Wednesday, June 1, 2016

PTH
MEN1, MEN2A PTHrP
1,25 (OH)2 D

Calcium overload

hyperparathyroidism -
-
Myeloma - lytic 90% -

TB, silicosis, lymphoma


-
-

12
GI -

PUD

-
Tertiary hyperparathyroidism Nephrogenic DI
Recurrent nephrolithiasis
TPN Nephrocalcinosis
-
Adrenal insufficency, pheochromocytoma
Osteitis fibrosa cystica
cancellous

-
Short QT AV
endothelial dysfunction LVH

11.6 -
12.8 -
14 Severe hypercalcemia -

primary hyperparathyroidism -
-
overt

-
-
-
-

-
hemoconcentration

Corrected Ca = Ca + 0.8 * (4.1-albumin) -


-
PTH\PTHrP related
vitamin D realted
-

tertiary hyperpara PTH


inarppropriately normal PTH -

FHH
Ca/Createnine clearance ratio <0.01 ▪
CaSR ▪
PTH -

PTHrP ▪
bone scan CT ▪

occult sarcoidosis 1,25(OH)2 D


A D

inappropriately normal PTH

86
inappropriately normal PTH

1
1% 60 0.2% -
3-5 -

isolated adenoma 80% -


inferior parathyroid glands
6-10%
20
chief cells
4 15% -

14

MEN syndromes 10% -


ZES MEN1
MTC MEN2A
MEN
Hyperparathyroidism jaw tumor -
secondary hyperpara -
-

PTH -
-

-
-

-
CVS -
-
bone mineral density
PTH
Guidelines -

minimally invasive parathyroidectomy -


SPECT sestamibi
5 PTH
PTH 50% ▪
multiple gland hyperplasia -

forearm Total parathyroidectomy


-

5-6
-
24
3-5

osteitis fibrosa cystica

8 -
-
-
IV -
2-3 IV -

Lithium 2
10% -
-
-
CaSR -
PTH shift
PTH

PTH -

Familial Hypocalciuric Hypercalcemia 3


-
downstream CaSR -
-

87
-
sensing -
inappropriately normal PTH
excessive reabsorption
PHT -
99% 99%
Uca+Pcr\Pca*Ucr<0.01
PTH-dependent
10
PHT PTH

family screening
CaSR FHH -

PTH

1
20% -
-
-
occult tumor -

humoral hypercalcemia of malignancy PTHrP 1


-
-
small cell squamous cell carcinoma
Renal tumors
Head and neck
Urogenital
PHT
true PHT 1,25OH2D -
PTH -
PTHrP -

2
MM
TNF IL-1 Osteoclast activating factor ▪
T cell lymphoma\leukemia

D 2
40,000-100,000 40-100 -
100 25OHD -
inappropriately normal -
-
D

100

TB 3
-
1-25OH2D -
-

High bone turnover 4


1
20%

bone turneover

Paget's high bone turneover


3
Sodium depletion

HPT high bone turneover

A 4
dietary faddism
periosteal calcification A
A

5
Tertiary HPT Severe secondary HPT 1
2

CKD

D
Milk alkali syndrome 3
calcium carbonate

burnett's syndrome
renal calicum retention bicarbonate retention

Jansen's disease 6
PTH PTH -
-
-

12
13

88
13

-
24 4-6
-

extreme diuresis
-
-
6-12 2-8 IV\SC\IM
-
24

-
IV

pamidronate zoledronic acid IV -

multiple myeloma
increased bone turnover
24-48
60-90%
7 pamidronate
pamidronate sustained effect Zolendronate


jaw necrosis ▪
MM ▪
Denosumab -
NFKappa B RANK RANKL

4 1,8,15,29 SC 120

-
3-7 40-60 IV 100-300

1,25(OH)2D mediated hypercalcemia

MM ▪
D ▪
A ▪
FHH CaSR ▪

ketoconazole -

89
11:24 Tuesday, 5 February 2019

-
D -

Protamine, heparin, glucagon

PTH
1
-

APS1
-
autosomal dominant hypocalcemia
G protein CaSR ▪
FHH ▪
Di George syndrome
2
PTH 0.8 -
PTH
-
alcohol abuse -
IV -

secondary hyperpara PTH


Chronic kidney disease 1
FGF 23 -
-
CrCl<30 -
D 2

D
D -
D3 D2

vitamin D binding protein -


-
25(OH)D 25
25(OH)D
2-3
vitamin D binding protein
-
1,25(OH)2D 1alpha hydroxylase 1
CYP450
PTH Inducers
FGF23 repressors
1alpha hydroxylase

24-hydroxylase -
-
D
-
VDR


RANK ligand ▪

PTH ▪

90
D
-
25% -
short bowel syndrome -
-
-
FGF23 -
-
D CYP450 anti-convulsant -

vitamin D binding protein -


-
-
-
hypertrophic chondrocyte layer Rickets -
1 D 1 alpha hydroxylase Type I

D Type II

Pseudo-hypoparathyroidism 3
-
-
PTH -

PTH overwhelmed
1

Tumor lysis syndrome

Osteitis fibrosa 2

-
-
twitching facial Chvostek's sign
circumoral
20 Trousseau's sign
3
Carpopedal spasm

QT

D
-
-
Rickets

Looser's zones radiolucency


pseudo-fractures
-
-
-

-
ionized calcium -
PTH -
inappropriately normal

91

secondary hyperparathyroidism
D ▪

D -
50nmol\L 20ng\ml 25-OHD
bone turnover ALP

1-25 OHD
PTH D ▪
D ▪
1-25 OHD D ▪

5 50 10% 10 calcium gluconate IV -


24 10 -
IV -

-
1000-1500
40,000-120,000 D
D ▪
0.25-2 ▪


urinary calcium reabsorption ▪
1,84 (Natpara) PTH


-
IV
D -

3-12 50,000 pharmacological repletion ▪


800 ▪

100,000 ▪
IV ▪

Impaired 1 alpha hydroxylation


0.25-0.5 ▪
2.5-5 1alpha-hydroxyvitamin D2 ▪
1.5-2 D
3-6 ALKP PTH
D
100-250 24 ▪


-

PTH 100-300

92
17:56 Monday, 8 April 2019

93
94
11:17 Sunday, 19 May 2019

1
PTH\PTHrP
FGF23
2
Shift 3
4

95
Tumor induced osteomalacia
FGF23 -

1,25 (OH)2D
PTH

96
PTH
-
-

Octreotide

nadir 1-2 ▪

cardiac dysfunction

rickets

IV 2 -
IV
6-12
1.5-2.5 -
octreotide Tumor induced osteomalacia -

1
PTH -
-
PTH -
Massive ECF phosphate load 2

97
Klotho
proximal tubule FGF23 co-receptor -
FGF23 Klotho inactivating -

PTH
-
tumor calcinosis
focal hyperostosis

-
tetany

-
Volume expansion -
-
Sevalamer
Aluminium hydroxide antacids
-

98
99
Refeeding
13:43 Tuesday, 9 April 2019

-
TPN 5
-

IV

Zinc
wet beri beri Acute thiamine deficiency
-

Redistributive hypophosphatemia
DKA -

IV -
-
-
EPO leukemia blast crisis -
D Paget -

-
-

100
18:10 2016 29

-2.5 T score DXA BMD -


T score
Z score

-2.5 -1 T score -
50%
BMD 10 FRAX score -
FRAX -
10 20% FRAX
10 3% FRAX
-
50

50% 50 life time -


20% 50 -
30% 5-20% -
-

RANK RANKL -
RANKL Osteoprotegrein -

101
RANKL Osteoprotegrein -
Wnt pathway Sclerostin -

BMD screening

VFA Vertebral fracture assesment


screening -
25-30%

-
-1.5 T Score 70 65
-1.0 T Score 80 70
-


102
-
24 -

75 30 25OHD level -
TSH -
-




20-30% 1000-1200 ▪


1000-2000 D
-

1
-2.5 T Score 2
10 3% FRAX 10 20% FRAX 3

VTE stroke MI - 50% -


- -
- FDA - PO Tamoxifen SERM

-
- FDA - PO Raloxifen SERM
DVT -
Stroke -
-

70 -

- - - Alendronate -
Esophageal irritation pyrophosphate (Fosalan)
- Risedronate -
steroid induced - (Actonel)
Zoledronic acid osteoporosis - Zoledronic acid -
2-3 zoledronic acid (Aclasta)
Zoledronic acid (Aclasta) - Ibandronate -
GFR<30-35 Renal toxicity 28% 15 5 IV -

Osteonecrosis of the jaw (ONJ)






Atypical femoral fracture
shaft subtrochanteric ▪
50% ▪

103
50% ▪

MRI ▪

facial flushing Paget's FDA -

5
-

ONJ - - Denosumab
Atypical femoral fracture fully human
D RANKL
Denosumab -

-
Rebound increase in bone turneover
- -

denosumab
- denosumab - Teriparatide PTH
18 osteogenic sarcoma - (Forteo)- 1,34 PTH
-

denosumab
-
Abaloparatide PTHrP
PTHrP

Romosozumab
Sclerotin

BMD -
6% 4% -
BMD -
30-40% -
Collagen C-telopeptide
osteocalcin P1NP

Glucocorticoid induced osteoporosis

-
-
-

alternate day delivery

3 -
-

24 -
DXA BMD 3 -
spine 60
hip 60

D -
D3 1000 1200 -
-
-
-

zoledronic acid risedronate alendronate -


alendronate recombinant PTH Teriparatide -

104
alendronate recombinant PTH Teriparatide -
Denosumab -

105
12:00 Friday, 12 April 2019

-
-
Copper transporting ATPase ATP7B -

1% 30,000 1 -

-
hepatic decompensation
20

-
20

5 50%
-
sunflower cataract
Kayser-Fleischer
-

Fanconi's syndrome

serum ceruloplasmin -
90%
10%
KF rings -
99%
30-50%

24 -
50-75% -
Gold standard -

FP

106
-
pyridoxine penicillamine
Trientine
-

-
7 9 Nazer prognostic index
Trientine

-
Tetrathiomolybdate

trientine -

107
-
-

6-24
-

108
20:21 Friday, 12 April 2019

3-4
1.5 1

expression
40-60
Hepcidin

20
secondary iron overload -
ineffective erythropoesis

-
-

95%

HCC
30%

1
-

109
-
Bronzing

-
65%

Arthropathy -
25-50%
50
2,3 MCP

-
15%
10%

-
high index of suspicion -
-
-
-
-
MRI -

-
100 1-2 500
100

PO deferasirox IV deferoxamine -

110
PO deferasirox IV deferoxamine -

C -
End stage liver disease -

HCC
-
89% 33%
40%

111

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