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Activate mutations of LH rc
o McCune Albright syndrome early in
development
o GH secreting tumors and acromegaly
occur only in somatotropes
Screening
o Type 2 DM beginning age 45 every 3 years
high risk; FPG 124mg/dl; RPG <200mg/dl
o Hyperlipidemia cholesterol screening every
5 yrs
o Gravess Dse TSH, free T4
o Thyroid nodule/neoplasia PE of thyroid and
FNAB
o PCOS testosterone, DHEAS
o Vit D def 25-OH serum vit D
400 Mechanism of Hormone Action
Classes of Hormones
o Amino acid dopamine, catecholamines, thyroid
hormone
o Small neuropeptide GnRH, TRH, somatostatin,
vasopressin
o Large neuropeptide insulin, PTH, LH
o Steroids estrogen & cortisol
o Vitamin derivative Vit. A & D
Membrane Receptors
o GPCR almost all
o Rc Tyrosine Kinase Insuline
o Cytokine Rc-linked kinase GH, PRL
Hormone precursor
o POMC ACTH
o Pro-glucagon, insulin, PTH
Pro-hormone conversion
o Testosterone dihydrotestosterone
o T4T3
Cholesterol steroid hormones
Stored in secretory granules GnRH, insulin, GH; with
stimulus will be released from the granules
Diffusion as they synthesized steroids stimulated by
StAR protein
Somatostatin - evanescent
TSH long lived
Circulating hormone half-life important to achieve hormone
replacement
o T4 HF:7 days; >1 month to reach steady
state; single daily dose
o T3 HF: 1 day; administered 2-3x a day
o Synthetic glucocorticoids vary
Hormone degradation
o 11B-hydroxysteroid dehydrogenase
inactivates glucocorticoids in renal tubular
cells
o Deiodenases convert tT4 to T4 and
inactivates T3
o Cyp26b1 degrades retinoic acid that
prevents promodial germ cells in male to
enter meiosis female ovary
Functions of hormones
o Growth and differentiation
o Maintenance of homeostasis
o Reproduction
Hormonal rhythms
o Menstrual cycle 28 days; follicular
maturation & ovulation
24 hr urine cortisol
IFG-I - GH action
Table 401e-1
Pituitary Gland
o 600 mg; located within the sella turcica ventral to
diapgragma sella
o bld supply: s/i hypopyseal arteries
o HP portal plexus bld supply of AP
o Inferior hypophyseal art supply posterior
pituitary
o Posterior pituitary innervated by
supraopticohypophyseal and tuberohypophyseal
nerve tracts; so ADH and oxytocin sensitive to
neuronal damage by lesions of pituitary
stalk/hypothalamus
Prolactin
o Analougous to GH and HPL
o Lactotrope hyperplasia pregnancy & lactation
o Transient functional changes in lactotrope
induced by estrogen
o Normal levels:
Men 10-20ug/L
Women 10-25ug/L
spontaneous hypersecretion of
compressice mass lesion on pituitary
stalk
Dopamine management of
hyperprolactinemic d/o
o Stimulants: TRH, VIP, acute stress
o Inhibitors: glucocorticoids and VIP
o Inc 10 fold pregnancy
o Decline rapidly w/in 2 wks of parturition
o Breastfeeding/sucking PRL remains elevated
Action:
Acromegaly high
Stimulates lipolysis
Increase f.a.
induce streoidogenesis
Gonadotropins (FSH & LH)
o 10% of AP cells
o with B-subunits (like TSH and HCG) confers
specificity
o Stimulation: GnRH by brain kisspeptin
402 Hypopituitarism
PANHYPOPITUITARISM
Acquired Causes
o Hypothalamic infiltration disorders sarcoidosis,
histiocytosis X, amyloidosis, and
hemochromatosis may have DI, growth
retardation if GH secretion in puberty, hypogo2
and hyperprolactinemia
o Inflammatory lesions TB, fungal infxns with
AIDS, granulomas and sarcoidosis may mimic
pituitary adenoma
o Cranial irradiation 50Gy (5000rad) develop
hormone insufficiency and ususally hypothalamic
damage GH deficiency most common
o Lymphocytic Hypophysitis postpartum women;
presents with hyperporlactinemia and MRI
evidence of a prominent pituitary mass that
resembles adenoma with mildly elevated PRL
levels; headache and visual disturbance, ESR
elevated
o Pituitary Apoplexy acute intrapituitary
hemorrgagic vascular events; Sheehans
syndrome hyperplastic enlargement of pituitary
normally during pregnancy increases the risk for
hemorrhage and infarction; endocrine emergency
severe hypoglycemia, hypotension, and
shock, Acute s/sx: severe headache w/ signs of
meningeal irritation, bilateral visual changes,
ophthalmoplegia, and CV collapse and LOC. Tx:
high dose glucocorticoids Sx: severe
ophthalmoplegia and visual deficits
o Empty Sella incidental MRI finding; assoc with
intracranial hypertension; pituitary asses undergo
clinically silent infarction and involution w/c devt
of empty sella by CSF filling the dural herniation;
insidious devt of hypopituitarism
Laboratory Investigation:
Table 402 -2
o Low free thyroxine, low or N TSH 2nd hypothyroidism
o Low testosterone w/o inc in gonadotropins hypogo
Pituitary sx
Pit/hypothal tumor/granulomas
Hx of cranial irradiation
Presentation:
o Secondary ACTH (adrenal) def: fatigue,
weakness, anorexia, vomiting, hypoglycemia,
hyperpigmentation, mineralocorticoid def
o Primary ACTH def: no hyperpigmentation, and
mineralocorticoid def
Etiology:
o glucocorticoid withdrawal after tx-assoc.
suppression of HPAdrenal axis.
o Surgical resection of ACTH-secreting pituitary
adenoma
Lab Dx
o Low ACTH levels with low cortisol levels
characteristic diminished ACTH reserve with
ACTH stimulation and insulin-induced
hypoglycemia or testing with metyrapone and
CRH
Presentation:
o Premenipausal: diminished ovarian reserve
oligomenorrhea, amenorrhea, infertility, dec
vaginal secretion, dec libido, breast atrophy
o Men: testicular failure dec libido and potency,
dec muscle mass, reduced body hair, soft testes
Lab Dx:
o Central hypogonadism low gonadotropins, low
sex hormones
o IV GnRH (100ug) stimulates gonadotropes to
secrete LG (peaks w/in 30 mins) and FSH
(plateaus in 60min)
o Normal: LH increase 3fold, FSH inc less
pronounced
o Gonadotropin deficiency: normal response
o Hypothalamic/Pituitary cause: absent reponse
o MRI central hypogonadism
Treatment:
o Males: testosterone IM every 1-4 wks or daily
patches or gels
o hCG or hMG for 12-18 mos restore fertility;
follicular growth and maturation
o pulsatile GnRH therapy: 25-150ng/kg evry 2 hrs
by subq pump for hypothalamic hypogonadism
o premenopausal: cyclic replacement of estrogen
and progesterone
o gonadotropin therapy: ovulation induction
DIABETES INSIPIDUS
Chap 404
403 Anterior Pituitary Tumor Syndromes
Hypothalamic, Pituitary and Other Sellar Masses
children 6mm-8mm
pregnancy/adolescent convex
( pituitary enlargement)
b. pituitary bright spot high phospholipid
content in posterior pituitary
c. Sellar masses incidental findings
Basal PRL
IGF-I
a-FSH and LH
6.
7.
8.
9.
Dopamine agonists
Resection of mass
Prolactinoma
a. Most common pituitary tumor; half of all fxning
pituitary tumors
b. Microadenomas - <1cm; noninvasive; F:M ratio:
1:1
c. Macroadenomas ->1cm; invasive and impinges;
F:M ratio: 20:1
d. Presentation: same with hyperprolatinemia
e.
Symptomatic microadenoma
o Medical: Dopamine agonists
Bromocriptine (0.625-1.25mg at
bedtime w/ snacks; gradual daily
dose of 2.5mg tid short acting;
preferred in pregnancy; restore
fertility in women with
hyperprolactinemia
Immune suppression
Table 403.- 7
c. Lab:
Ketoconazole
Mifepristone
2 hormones:
o AVP acts in renal tubules to reduce water loss
by concentrating the urine
Vasopressin
o regulated primarily by the effective osmotic
pressure of body fluids mediated by osmorc w/c
are sensitive to changes in plasma sodium
(280mosmo/L or 135meq?L
o Action: reduce water excretion by promoting
concentration of urine increasing
hydroosmotic permeability of cellsthat line DT
and MCD of kidney
o Water diuresis lack of reabsorption; excretion of
0.2mL/kg per min of maximmaly dilute urine and
SG -1.000 and osmolarity of 50mosmol/L
o Thirst ensure adequate intake to prevent
dehydration
o Oxytocin
DDX:
o symptoms of urinary frequency, enuresis,
nocturia and persistent thirst in the absence
of glucosuria collect 24hr urine on ad
libitum fld intake
o volume exceeds 50ml/kg/ per day (3500ml in
a 70kg male) and osmolarity is below
300mosml/L
o Fluid Deprivation test effect on urine
osmolality of injecting 2ug of AVP analogue
o
2.
Treatment:
o Central DI: DDAVP (desmopressin) acts on
V2 rc to inc urine concn and decrease urine
flow
o Nephrogenic DI: thiazide diuretic, amiloride,
low sodium diet, prostaglandin synthesis
inhibitor (indomethacin) reduce polyuria
and polydipsia
Hyponatremia due to Inappropriate AntidiuresisDecrease
plasma osmolality/sodium below the normal range
a. Types:
o Hypervolemic hyponat CHF, cirrhosis
o Hypovolemic hypnat diarrhea, diuretic abuse
o Euvolemic hyponat excessive intake with defect
in urinary dilution
b. SIADH
o defect in osmoregulation; decrease volume and
inc concn of urine; excess water retention and
expands dilutes body fluids
o symptoms of water intoxication: mild headache,
confusion, anorexia, n/v, coma, convulsion,
edema (hypervolemic)
o inappropriate secretion of AVP
o ectopic: lung cancer
o eutopic: dse & drugs
o exogenous adm: AVP, DDVP, oxytocin
o Increase in body water of 10% and reduces
plasma osmolarity and sodium by approx. 10%
(~28mosmol/L or 14meq/L
o Wt gain of 4kg
c. SIADH diagnosis of exclusion; hyperglycemia
contribution to the reduction in plasma sodium by
measuring plasma osmololarity for a more accurate
estimate of the true effectivity tonicity
o Corrected Pna = measured Pna + (Pglu -90)/36
o Hypotonic hyponat plasma
osmolarity/corrected plasma sodium are below
limits
o Table 404-3
d. Tx:
o Acute asymptomatic SIADH goal: raise
plasma osmolarity and or/plasma sodium at a
rate approx. 1% an hr until they reach
270mosmol/L or 130meq/L infuse hypertonic
saline at a rate of 0.05 ml/kg body wt per minute
o AVP rc2-agonist (Conivaptan) block the antidiuretic effects of AVP and increase urine output;
restrict fluid intake
d.
e.
2.
3.
4.
5.
6.
7.
f.
Congenital Hypothyroidism
o Prevalence: due to thyroid gland dysgenesis 8085%; common in girls
o Manifestations
g.
h.
No recommended tx
Radiation precautions:
Subtotal/Near-total thyroidectomy
o Option to those with relapse
after ani-thyroid drugs
o Young - very large
o 3 drops SKKI TID; avoid
thytoxic crisis and reduce
vascularity of gland
o
complication: bleeding,
laryngeal edema,
hypoparathyroidism
adults: malignancy
FNAB PMN
Increase in Hcg
Goitrogens
Common in women
Labs
o Iodine def: low t4, normal t3 and TSH, refelecting
enhanced conversion
o Subclinical thyroxicosis: low TSH, normal T3 and
T4 (older pts and undiagnosed graves); elderly
treated to prevent atrial fibr and bone loss
o TPO ab autoimmune
o Low urinary iodine levels (<50ug/L) dx of iodine
def
Asymptomatic, euthyroid
Pembertons
Calcitonin- Medullary TC
PTC most common type of thyroid ca; well- differentiated
Follicular common in iodine deficient regions; WD
Thyroid lymphoma arise in background of Hashimotos
MTC MEN syndrome
Tx: Surgery, TSH suppression
6-11 grams
Dexamethasone test
o Establish Cushingss and ddx of cortisol
excess
o Autonomous(Adrenal nodule) ACTH is
already supressedl dex little effect
o ACTH producing pituitary adenoma dexa
ineffective in low doses but induce
suppression at high doses
o Ectopic source resistant to dexa
suppression
ACTH stimulation
o First line test
o Assess glucocorticoid deficiency
Administer cosyntropin 0.25 mg IV/Im,
collect bld samples at 0,30, 60 min for
cortisol N: >20ug/dl 30-60 min after admin
Insulin tolerance test (ITT)
o Alternative
o Inject insulin to induce hypoglycemia
strong signal that triggers hypothalamic
release and activation of entire HPA axis;
admin reg insulin 0.1U.lg IV & collect bld
samples at 0, 30, 60 120 mins for glucose,
cortisol and GH; then after pt achieved
symptomatic hypogly (glucose <40mg/dl)
give oral or IV glucose; N: cortisol >20ug/dl
and GH >5.1ug/L
o CI: CAD, CVD< seizure
Mineralocorticoid production
o RAAS; release of renin angio I (liver) to
angio II via ACE aldosterone production
and vasoconstriction
o Aldosterone enhance sodium retention and
K excretion; inc arterial perfusion pressure
o Mineralo excess: dec renin; vice versa
o Sodium loading suppress aldosterone;
autonomous mineral exces, absent response
o
e.
Etiology:
o Corticotrope pituitary microadenoma (>1cm
size) 90% of cushings syndrome
o Ectopic ACTH prod carcinoid tumors in the
lung, difficult to locate - small
g. Manifestations
Table 406-2
MRI pituitary
If
positive:
transpeh
noidal sx
If
negative
:
bilateral
adrenale
ctomy
Suppressed <5 pg/ml ACTH
independent
Do CT
o If bilateral
micro/macronodul
ar adrenal
hyperplasia or
unilateral adrenal
mass
adrenalectomy
h. Treatment:
See above
Oral agents:
o Metyrapone inhibits cortisol synthesis at the
level of B-hydroxylase; 500mgTID to 6g
o Ketoconazole inhibits the early step of
steroidogenesis 200 mg TID to 1200
o Mitotane adrenolyric agentl low dose for
adrenocortical carcinoma
o Etomidate severe cortisol excess
o After Surgery: HPA remains suppressed
Hydrocortisone
Mineralocorticoid Excess
e.
Primary Causes:
o Adrenal (Conns) Adenoma
o Bilateral (micronodular) adrenal hyperplasia
o GRH
Clinical Manifestations:
o Potassium depletion and increased Na retention
explansion of extracellular & plasma volume
o Inc ENAC activity hydrogen depletion met
alkalosis
o Direct damage of aldosterone in heart systemic
hpn
o Clinical hallmark of mineralocorticoid excess:
hypokalemic hypertension
Sodium loading
Fludrocortisone suppression
o CT adrenals
<40yo adrenalectomy
If positive:
o Autoiimune adrenalitis
o APS
If negative:
o CXR
o Serum 17OHP
o Adrenal CT
If (+):
adrenal infection (TB)
Infiltration (lymphoma)
Hemorrgae
CAH (17OHP inc)
If (-):
Autoimmune adrenalitis
Adrenoleukodystrophy
(men, VLCFA inc)
If positive: HP mas
lesion
If neg: hx of
exogenous
glucocorticoid tx,
trauma, consider
isolated ACTH def
21 hydoxylase deficiency
Tx:
o hydrocortisone: prevent adrenal crisis
o prednisone: control androgen excess
o dexamethasone: to achieve fertility
o 17OHP useful marker for overtx
o M replacement: renin- regularly monitorer
407 Pheocromocytoma
Etiology:
<140 mg/dl
IGT
100125mg/dl
>140199mg/dl
5.76.4
DM
(Criteria for
Dx)
Symptoms
of DM +
200mg/dl
>126mg/dl
>200mg/dl
HbA1C
<5.6
>6.5
b. Types
Other causes:
o Maturity onset diabetes of the young and
monogenic diabetes early onset of hypergly
<25yo and impaired insulin secretion
o Pancreatic exocrine dse, CF
o Endocrinopathies: acromegaly, Cushings
o Fulminant diabetes rt to virla infections of islets
Epidemiology
o China highest prevalence of DM
o Scandinavia highest Type 1
o Pacific Islands and ME
ADA recommends:
o Screening all individuals >45yo evry 3 hrs
o Screening at early age if overweight BMI>25 and
have additional risk factor for DM
o Risk Factors:
Family hx
Obesity
Physical inactivity
Race/ethnicity
HPN
PCOS
Hx of CVD
Temporal Course:
o With genetic predisposition triggered by
infection initiates autoimmune process
gradual decline in beta cell mass
o Progressive impairment in insulin release when
80% of the beta cell mass destroyed
o Honeymoon phase first 1-2 yrs after onset of
diabetes and insulin reqts
Pathophysiology
o Other islet cell types: spared from autoimmune
destruction
Delta somatostatin
Environmental Factors
o Triggers of autoimmune process: viral (coxsackie,
rubella, enterovirus), bovine milk CHON,
nitrosourea
Type 2 DM
Metabolic Abnormalities:
o AbN muscle and fat metabolism
Mutations in Insulin Rc
o Features: acanthosis nigricans & signs of
hyperandrogenism
o 2 distinct syndromes:
Prevention of Type 2 DM
o Reduce body weight - diet
o Increase physical activity: exercise 30 min/d 5x a
week
o Metformin with high risk of progression, IFG and
IGT, + risk factors
Approach to Patient with DM
History:
o wt, family hx, risk factors
o s/sx: polyuria, polydipsia, wt loss, fatigue,
weakness, blurring of vision, frequent superficial
infections
PE:
o Wt, BMI, BP, foot exam, peripheral pulses, and
insulin injection sites, periodontal dse
o Distal symmetric neuropathy; test of loss of
protective sensation
Classification:
o Type 1: onset before 30yo, lean, insulin as initial
therapy inc risk for autoimmune do and
ketoacidosis
o Type 2: onset after 30yo, obese, not require
insulin initially, with insulin resistance, hpn, cvd,
dyslipidemia, PCOS
Normal lifestyle
o Symptoms resolve when plas,a glucose is <200mg/dl
o Comprehensive diabetes care
Quarterly BP monitoring
Influenza/pneumo/hep b vaccines
Antiplatelet therapy
o Treatment Goals
Glycemic control
o HbA1c <7%
o Preprandial plasma gluc 80-130mg/dl
o Peak PP plasma gluc <180mg/dl
BP <140/90
Lipids
o LDL <100mg.dl
o HDL women >50mg/dl, men >40mg/dl
o Trigly <150mg/dl
o Nutritional recommendations for adults with
diabetes/prediabetes
Individualized; pt approach
Insulin regimens:
o Long acting insulins (NPH, glargine, detemir) basal
insulins
o Short acting insulins (regular, aspart, lispro, glulisin)
prandial insulin; inhected before <10min or just after a
meal. Regular insulin 3-45min prior to a meal
o Type 1 DM: require 0.50-1 U/kg per day of insulin into
multiple doses with ~50% of basal insulin
o Generaizations in Glucose Loweing Agents
Osmolality
Ketones
Bicarb
300-320
++++
<15
330-380
+/Normal to slightly
dec
>7.3
Normal
Normal -slightly inc
Arterial pH
6.8-7-3
Pco2
20-30
Anion gap
Inc
Diabetic Ketoacidosis
a. Symptoms: n.v, thirst, polyuria, abd pain resemble
acute pancreatitis/ruptured viscus, SOB
b. Physical Findings: tachycardia, dehydration, hypotension
due to vol depletion, kaussmauls respiration and fruity
odor breath 2 to met acidosis and inc acetone (classic
signs), lethargy, coma, cerebral edema major
nonmetabolic/ serious complication of DKA common in
children
c. Precipitating events: inadequate insulin admin, infection
(pneumonia, UTI, AGE, sepsis), infarction, cocaine,
pregnancy)
d. Pathophysiology:
Replace fluids
o 2-3L 0.9% plain saline over 1-3 hrs
o 0.45% at 250-500ml/hr
o change to 5% glucose and .045% saline at 150250ml/hr when plasma glucose reaches
250mg/dl
Replace K:
o 10meq/L K<5-5.2meq/L, normal ECG, urine
and crea normal
o 40-80meq/L K<3.5 meq or bicarb given
o do not supplement if K>5.2 meq/L until K
corrected.
Tx:
o Fluid losses and dehydration more pronounced
than DKA
o Fluid replacement
o K repletion
o Insulin
419 DM Complications
4 theories:
o Increased intracellular glucose leads to the formation
of advanced glycosylation end products, which bind to
a cell surface receptor, via the nonenzymatic
glycosylation of intra- and extracellular proteins,
leading to cross-linking of proteins, accelerated
atheroscle- rosis, glomerular dysfunction, endothelial
dysfunction, and altered extracellular matrix
composition.
o Hyperglycemia increases glucose metabolism via the
sorbitol pathway related to the enzyme aldose
reductase
o Hyperglycemia increases the formation of
diacylglycerol, leading to activation of protein kinase
C, which alters the transcription of genes for
fibronectin, type IV collagen, contractile proteins, and
extracellular matrix proteins in endo- thelial cells and
neurons.
o Hyperglycemia increases the flux through the
hexosamine pathway, which generates fructose-6phosphate, a sub- strate for O-linked glycosylation
and proteoglycan production, leading to altered
function by glycosylation of proteins such as
endothelial nitric oxide synthase or by changes in
gene expression of transforming growth factor
(TGF-) or plasminogen activator inhibitor-1.
o Unifying mechanism: hyperglycemia leads to
increased production of ROS
2 types of retinopathy:
o nonproliferative appears in late in first or early
in 2nd decade marked by retinal vascular
microaneurysms, blot hemorrhages, and cotton
wool spots; pathophy: loss of retinal pericytes, inc
retinal vasc permeability and alteration in retinal
bld flow; DM>20yrs
o Proliferative hallmark: neovascularization in
response to retinal hypoxemia; formed vessels
Renal Complications of DM
DM nephropathy: leading cause of CKD, ESRD
Rt to chronic hyperglycemia
Effects of soluble growth factors (GF, angiotensin II,
endothelin; glomerular hyperfiltrration/hyperperfusion,
increase glomerular capillary pressure
Srtuctural changes in glomerulus: inc ECM, BM
thickeining, mesangial expansion, fibrosis
Smoking accelerates declin in renal fxn
Course
o 1st yrs: glomerular hyperperfusion and renal
hypertrophy; inc GFR;
o 1st 5 yrs: thickening of BM, glomerular
hypertrophy, masangial vol expansion
o 5-10 yrs: albuminuria: microalbumineria 30299mg/dl in 24 hr collection or creatine spt
collection; macroalbuminuria >300mg/24h
o Macroalbuminuria ESRD
Annual microalbuminuria measurement: albumin to
creatinine ratio in spot urine
Tx:
o improved glycemic control, strict BP control and
ACE inhibitor or ARNS
o hemodialysis frequent complications:
hypotension, difficult vascular access, and
progression to retinopathy
o renal transplant preferred byt requires chronic
immunosuppression
o combined pancreas-kidney transplant
nomoglycemia and freedom from diabetes
Neuropathy
due to chronic hyperglycemia
Risk factors: BMI, smoking, CVD, and inc trigly
Polyneuropathy: most common form is distal symmetric
polyneuropathy frequently with distal sensory loss and
pain; senstation of numbness, tingling sensation, and
sharpness, burning pain; neuropathic pain: lower
extremities present at rest and worsens at night; PE:
sensory loss, loss of DTR, abnormal position sense
Diabetic polyradiculopathy- severe disabling pain in the
distribution of one or more nerve roots; intercostal/truncal
pain thorax or abdomen; femoral/lumbr nerve hip
and thigh pain; assoc with diabetic amyotrophy muscle
weakness in hip flexors and extensors
Monneuropathy dysfunction of isolated cranial or
peripheral nerve; pain and weakness in single nerve;
occur at entrapment sites carpal tunnel syndrome; third
cranial nerve -> diplopia
Autonomic neuropathy
o CV: resting tachycardia and orthostatic
hypotension
o Gastroparesis and bladder emptying
abnormalities
o Hyperhidrosis of upper ex and anhidrosis of lower
Tx:
Avoid neurotoxins
Vit B supplementations
Check feet daily; footwear precautions
Painful diabetic neuropathy: duloxetine &
pregabalin
GASTROINTESTINAL/GENITOURINARY DYSFUNCTION
Tx
o ACE, ARBS, ASA
o Metformin stable CHF; not thiazeolinediones
o Antiplatement therapy
CV risk factors
o Dyslipidemia most common pattern in DM:
hypertrygly and reduced HDL, LDL particles in
DM more atherogenic; moderate statin
therapy; HMG-CoA reductase inhibitors agents of
choice for lowerimg LDL; nicotinic acid- raise
HDL; hypertrigly dont use bile acid resins
o HPN: Target BP:<140/80mmHg; Tx: ACE
inhibitors and ARBS
420 Hypoglycemia
insulin (or insulin secretagogue) doses are excessive, illtimed, or of the wrong type; (2) the influx of exogenous
glucose is reduced (e.g., during an overnight fast or after
missed meals or snacks); (3) insulin-independent glucose
utilization is increased (e.g., during exercise); (4)
sensitivity to insulin is increased (e.g., with improved
glycemic control, in the middle of the night, late after
exercise, or with increased fitness or weight loss); (5)
endogenous glucose production is reduced (e.g., after
alcohol ingestion); and (6) insulin clearance is reduced
(e.g., in renal failure)
Risk Factors
Aging - lder than age 50, and at >60 years of age women
are more often affected than men. T
Lipodystrophy
Etiology
Insulin Resistance
o most accepted and unifying hypothesis to
describe the pathophysiology of the metabolic
syndrome is insulin resistance,
o An early major contributor to the development of insulin
resistance is an overabundance of circulating fatty acid
o inhibition of lipolysis in adipose tissue is the most sensitive
pathway of insulin action.
o Leptin resistance - reduces appetite, promotes energy
expenditure, and enhances insulin sensitivity.
Dylipidemia
o Hypertriglyceredemia - excellent marker of the
insulin-resistant condition.
o reduction in HDL cholesterol.
Adiponectins
Proinflammatory cytokines
Clinical Features
o Not assoc with s/sx
o waist circumference may be expanded and blood
pressure elevated.
Drugs
MOA
Biguanide
s
Insuin
Secretago
ues
Affect ATP-sensitive K
channel
Insuin
Secretago
Sample
suffix
Metformin
1 sulfonlyureas
(-mide)
2 sulfonylureas
(Gli-)
Nonsulfonylureas
(-glinide)
Advantage
Reduce FPG and insulin,
improves lipid profile, wt loss
Wt neutrak, no hypogly
Effective in Type 2 DM
recently diagnosed
Reduce both fasting and
prandial glucose
CI/SE
Major toxicity: lactic acidosis,
low B12; not used with renal
insufficiencyw/ GFR
<60mL/min; d/c if npo and
radiographic contrast
Hepatic/kidney dses
DI: warfarin, aspirin,
ketoconazole
ues
GLP-1 rc
agonists
Aglucosidas
e inhibitors
Reduce postprandial
hyperglycemia by delaying
glucose absoption
Thiazoline
diones
NaGlucose
Transporte
r Inhibitor
(SLGT2)
Amylin
agonists
Exanatide
(-tide)
(-glitazone)
No hypogly
Inc insulin secretion,
suppress glucagon, slow
gastric emptying
Pramlintide
regulates hematopoiesis
Nausea
Renal dse
MTC
Diarrhea, flatulence, abdominal
distention
Avoid simultaneous admin with
bile acid resins and abtacids
Ci with IBD, gastroparesis, or
serum crea >2mg/d
Measure LFT prior therapy
Increase lipids
Associate with wt gain,
reduction in hct,
SE: peripheral edema and CHF
Increase urinary glucose:
urinary and vaginal infxns
function.
Estradiol - decrease osteoclast number and decrease
bone resorption.
present. Squamous cell tumors are most frequently associated with hypercalcemia, particularly tumors of the lung,
kidney, head and neck, and urogenital tract.
In patients with sarcoid- osis and other granulomatous
diseases, such as tuberculosis and fungal infections,
excess 1,25(OH) D is synthesized in macrophages or
2
other cells in the granulomas. Indeed, increased
1,25(OH) D levels have been reported in anephric
2
patients with sarcoidosis and hypercalcemia.
Mild hypercalcemia, <3 mmol/L (12 mg/ dL), can be
managed by hydration. More severe hypercalcemia (levels
of 3.23.7 mmol/L [1315 mg/dL]) must be managed
aggres- sively; above that level, hypercalcemia