)
Table of contents :
)),
pallor, depression,
and many other manifestations may occur. When cachexia is a
prominent feature, it is called hypophysial or pituitary
cachexia. or surgery
> LH
> FSH
> TSH
> ACTH
> PRL), or
excessive (PRL).
Sometimes there is downward herniation of the optic
chiasm, which leads to defects in the visual field.
=> hemorrhagic
shock
during delivery, and leading to variable patterns of
hypopituitarism
-producing) (60-90% of circulating
growth hormone is in the form of tetramers and
dimers (normal, 14-39% in plasma) and the patients'
GH polymers are abnormally resistant to conversion
into monomers by urea)
due to increased LDL-Ch and
decreased HDL-Ch => premature atherosclerosis => bone fracturs (RR = 3)]plasma after
challenge < 3 ng/mL]plasma : a single
low value is useless; lack of nocturnal peak]plasma
and
[IGFBP3]plasma
reduced or normal (depending on sex and age)]plasma (i.v. injection 1 mg/kg) + L-Arg (30 g (adults) or
0.5 g/kg (babies)) => sampling at 0, 15', 30',
45', 60', 120' => normal if [GH]plasma >
20 ng/mL (i.v. injection of 0.05-0.15
IU/ kg) => sampling at -30', 0, 30', 60', 120'
(insulin-tolerance test (ITT)) =>
glycemia < 40 mg/dL, [GH]plasma > 3
ng/mL (or > 140 pmol/l) (> 10 ng/ml or >
465 pmol/l in babies) (sensitivity = 85-100%) (i.v. injection 1 mg/kg) => sampling at 0,
15', 30', 45', 60', 120' => normal if [GH]plasma > 3
ng/mL]plasma > 3
ng/mL (> 10 ng/ml in babies) (4 ng/kg) => sampling at
60-120' => normal if [GH]plasma > 3
ng/mL (sensitivity = 80%) (p.o. 500 mg (adults) or 10
mg/kg (babies)) => sampling at 0, 30', 60',
120' => normal if [GH]plasma > 3
ng/mL (sensitivity = 56-81%)-
and FSH-producing),
lack of sexual hairs)
=> [LH]plasma
increased by 10 IU/L and [FSH]plasma
increased by 2 IU/L agonists
-producing)
=> [TSH]plasma
increased by 5 mU/L if thyroid hormones are not increased
(0.075-0.15 mg/die)
-producing) (i.v. injection ovine at 8
a.m.) => sampling at 0, 15', 30', 60', 90', and
120' => normal if [ACTH]plasma
increased by 2-4-folds, peak at 20-100 pg/mL]plasma
> 21 mg/dL; [aldosterone]plasma
4 ng/dL above normal level every 8 hrs => [cortisol]plasma
> 21 mg/dL tolerance test (ITT)
(i.v. injection of 0.05-0.15 IU / kg) => glycemia
< 40 mg/dL => sampling at -30', 0, 30', 60,
and 90' => normal if [cortisol]plasma
increase by 7 mg/dL or
> 20 mg/dL (inhibitor of conversion of
11-DOC into cortisol => removal of negative
feedbak on ACTH incretion) (30 mg/kg at 12
p.m.) => normal if at 8 a.m. [cortisol]plasma
< 4 mg/dL,
[11-deoxycortisol (11-DOC)]plasma >
7.5 mg/dL or > 0.22 mmol/L, [ACTH]plasma > 75
pg/mL-producing)]plasma
: as its value increases with stress (also
venipuncture), basal values are taken 15 minutes after
cannulation
(bolus injection to prevent peripheral proteolysis
before crossing the BBB) => [PRL]plasma,
basal > 2 mg/dL
with increase by 200% (side effects : skin rash and
incontinence) (200 mg
i.v.) => [PRL]plasma,
basal < ?,
1 mg/kg CRH,
100 mg GnRH
/
LHRH,
and 200 mg TRH) or receptor
agonist therapy
and one or more of the glycoprotein types
and GH and is presumed to be a stem
cell for both lactotrophs and somatotrophs. and PRL-producing)-increting tumors incretion (< 1%)-increting tumors (98%)ref1,
ref2,
ref3,
ref4 and breast
cancerrefrefref. It is a severe autosomal
recessive dwarfism characterized by complete GH
insensitivity. Genetic and mutation analyses have
attested to the high molecular heterogeneity of
this syndrome, and, to date, more than 30
different GHR mutations including deletion,
frameshift, nonsense, missense and splicing
defects have been described. However, among them,
missense mutations are of particular interest in
potentially providing critical information on the
structure-function relationship of the GHR and
related molecules. The study of the recently
described forms of atypical LS is now very
promising. These patients display detectable
plasma GH binding activity associated with
complete or partial GH insensitivity. Molecular
analysis of such a phenotype with positive GHBP
and complete GH insensitivity has revealed the
existence of a missense mutation abolishing
receptor homodimerization, thereby providing in
vivo evidence for the critical role of the
dimerization process in the growth-promoting
action of GH. Similarly, mutations in the
cytoplasmic region, which are expected to be
associated with normal GH binding activity, should
contribute to the identification of other
functionally important domains. Partial GH
insensitivity syndromes may theorically encompass
a wide range of distinct phenotypes with variable
degrees of GH resistance. Missense GHR mutations
and a quantitative GHR mRNA defect have been
identified in some cases belonging to this
heterogeneous group. Interestingly, exclusion of
linkage between the Laron phenotype and the GHR
locus was demonstrated in one affected family.
This latter situation may indicate the existence
of other genes controlling GHR expression or
required at different steps of the signal
transduction pathway. In this regard, the
availability of a possible animal model for LS
should offer new prospects in the identification
of GH-inducible genesref.
Associated anormalities include spinal stenosis,
os odontoideum, degenerative changes of the
atlanto-odontoid joint, and small oropharynxref., snoring, obstructive
sleep
apnea syndrome (OSAS) and thyroid stimulation by GH and IGF-1) (40%) (acromegalic heart
disease) => tachyarrhythmias
=> toothprint on tongue (due to increased PRL and
decreased DA)]plasma (4.6%)]plasma
basal (3-4 dosages separated by 20-30' : doubtful
result if 5 < x < 10 ng/mL) and circadian rhythm]night
urine]plasma
(more important than GH in follow-up)]plasma
:, MRI
to look for SST2 and SST5
expression agonists,
SST2 agonists,
SST3 agonists,
SST4 agonists,
SST5 agonists,
D2 agonists,
GH-R antagonists. Even cases
negative at 111In-DTPA-octreotide
scintigraphy
may respond, so a trial may be attempted for 5-8
months]plasma
basal > 2 ng/ml, the patient can be considered
cured if after 2 hrs from OGTT [GH]plasma
< 1 ng/ml)-producing)]plasma
> 200 ng/mL (directly relates with diameter)
(30% of patiens and 80% of
patients in hemodialysis) excess : hypothyroidismand
oligomenorrhea-hypomenorrhea-mild
menorrhage (50%) => primary or secondary amenorrhoea, none after
menopause ; hypoestrogenism (hot flushes, colpoxerosis,
mastodynia, decreased libido and depression)
test agonists
(bromocriptine, dihydroergocristine, lisuride,
metergoline, cabergoline) : only 33% of patients are
cured-producing)
cells : hypertrophied thyrotrophs found in the
adenohypophysis after thyroidectomy and in severe thyroid
hormone deficiency
-
and FSH-producing)-producing) for Cushing's
syndrome; it is characterized by aggressive
growth of the tumor and diffuse
hyperpigmentation
of the skin
(10-20 mg at morning, 10 mg at evening)
(25 mg at morning, 12.5 mg at evening)
(5 mg at morning; 2.5 mg at evening)
appearance :
and nasal obstruction due to stirring of dura mater over
diaphragma sellae
(rarely hydrocephalus)
(better assessment of posterior fossa and skull base).
Improvements in diagnostic imaging techniques over the last
several years have led to an increasing recognition of
asymptomatic lesions in the pituitaryref1,
ref2.
The management of such pituitary incidentalomas is
controversialref1,
ref2,
ref3,
ref4,
ref5,
ref6,
ref7,
ref8.
Some lesions may increase in size, owing to impaired
pituitary hormone production or compressed optic chiasm,
whereas others will remain unchanged in size and will never
produce tumoral or hormonal symptoms. The type of initial
endocrinological assessment and the required frequency and
length of follow-up for pituitary incidentaloma need to be
carefully determined, taking cost effectiveness into
account. In this setting, it is crucial to obtain precise
information about the natural history of each type of
pituitary lesion. Besides pituitary masses, physiological
enlargement of the pituitary gland is a frequent cause of
incidentaloma and of referrals to endocrinologists for
hormonal evaluation and therapeutic advice. Sex- and
age-dependent variations in size and shape of the pituitary
have been reported. In neuroradiological series, 25–50% of
healthy women, 18–35 yr old, had a convex superior pituitary
contour, but pituitary height exceeds 9 mm in less than 0.5%
of casesref1,
ref2,
ref3,
ref4.
No thorough clinical and hormonal data or long-term
endocrinological and imaging follow-up data are available on
these subjects. The present study was thus designed to
obtain more information, at the time of initial referral and
during follow-up, on the clinical, hormonal, and
neuroradiological characteristics of young women with
incidentally diagnosed pituitary gland enlargement
(height 9 mm) and a suspected pituitary tumor, with
the aim of proposing practical guidelines. 7 eugonadal
nulliparous women, 15-27 yr old, referred between 1989 and
1998 with incidentally diagnosed pituitary gland enlargement
(height > 9 mm) and a suspected pituitary tumor, were
studied. At presentation and at yearly intervals, PRL plasma
levels and corticotropic, somatotropic, and thyrotropic
pituitary function were measured; and pituitary dimensions
and signal on magnetic resonance imaging (MRI), before and
after iv gadolinium-diethylene-triamine-pentaacetic acid
injection, were assessed. PRL plasma levels were normal; and
corticotropic, somatotropic, and thyrotropic pituitary
function was considered normal in all cases. In all the
women, the upper boundary of the pituitary was convex, on
MRI, and touched the optic chiasm in 4 cases. The width and
anteroposterior diameter of the gland were normal. The
pituitary itself seemed normal, with a homogeneous signal,
on plain and dynamic studies with iv contrast injection.
Despite normal initial hormone values, two women underwent
surgery, by the transsphenoidal approach, in another center.
During surgery, the pituitary seemed normal in both cases,
with no evidence of tumoral or inflammatory processes.
Biopsy specimens showed the morphologic characteristics of a
normal, nonhyperplastic pituitary gland. All seven women
were seen at yearly intervals for 2-8 yr (median, 4 yr).
Clinical and hormonal status remained stable, as did the
structure and size of pituitary, on serial MRI. No tumor
formation occurred, supporting the diagnosis of physiologic
hypertrophy of the pituitary gland. In conclusion, these
observations suggest that careful examination of MRI results
may help to distinguish physiologic pituitary hypertrophy
from pituitary tumors and infiltrating lesions. The former
diagnosis is confirmed by normal baseline pituitary function
in extensive hormonal tests. Correct identification of such
patients is important to avoid unnecessary pituitary surgery
and costly MRI surveillanceref.
,
L-T4, and cortisol
acetate
))-producing
cells
: central
or pituitary diabetes insipidus (CDI) ,
desmopressin i.n. 5-20 mg b.i.d. or p.o. 300-600 mg/die
-producing
cells
(closed and penetrating)
=> nausea
and vomiting,
confusion, mild headache, seizures, coma
=> hypouricemia
)), 60% at age 70. 14-40% of
infant nodules are malignant (expecially when male, single
nodule, exposure to ionizing radiations, dysphonia, rapid
growth, adhesion to contigue tissues, cervical adenopathies) or
pink-yellow colour of FNAB) : they are more commonly
degeneration of solid nodules rather than epithelial
cysts, so that 0.5-3% can degenerate into carcinomas.
They should be excised when larger than 4 cm,
containing bloody fluid, or undergo constant refilling
after drainage. detects cysts
> 2 mm and solid nodules > 3-4 mm, calcified amyloid in MTC),
signs of extrathyroid extension
for cold or undeterminated nodules : sensitivity =
65-98%; specificity = 72-100%; accuracy = 95%; false
positives = 2.9%; false negatives = 0.5%; useful also
for cervical lymph nodes, associated with
[thyroglobulin]washing fluid in the needle.
In general, FNAB results are classified as:)
: poor sensitivity and specificity, useless in babies
unless thyrotoxicosis, uncertain cytology (differential
diagnosis with functional adenoma), thyroid agenesis,
neonatal hypothyroidism, ectopic thyroid tissue, follow-up
of differentiated carcinoma
for babies (evaluation of extension and accurate
presurgical topographical planning) due to increased [TSH]plasma
or thyroid-stimulating immunoglobulin (TSI)
,
which inhibits iodide oxidation and incorporation into
thyroglobulin (Wolff-Chaikoff effect). content,
leading to hypoiodemia;
seen in mountainous areas
,
autoimmunity, genetics (tRNA
lysine 1 (TRK1)
rearrangements), ? leading to increased local secretion of
cytokines and growth factors => polyclonal or
monoclonal (selective growth advantage) hyperplasia
=> inspiratory stridor; respiratory failure if obstruct
> 70% of tracheal lumen), recurrent nerve, esophagus
(expecially from retrosternal goitre), or sympathetic trunk (miosis, enophathalmos).
Complications : intragoiter hemorrhage leading to sudden
swelling of the neckref
(monitoring of decreased
vascularization after presurgical treatment with Lugol's
solution) and hashitoxicosis
: dyshomogenous thyroid (cold and hot (hyperthyroid)
areas)
and cytology (< 1% of nodules are malignant)+ FT4]plasma,
including type 1 amiodarone-induced
thyrotoxicosis (AIT) due to increased thyroid
hormone synthesis and secretion in patients with
underlying preclinical Graves' disease or autonomous
nodular goitre (increased vascularization, mild increase
in IL-6)ref
acts on TSHR at high doses
(rare; accompanied by low [TSH]plasma)
acts on TSHR at high
doses) => hyperemesis
gravidarum-induced
thyrotoxicosis (AIT)ref
administration, with little changes in serum T4
levelsref.
However, long-term treatment with OCAs may result in a
high rate of recurrence of hyperthyroidsm due to the
escape phenomenonref1,
ref2.
The use of OCAs for a mixed form of AIT was previously
reported in a case report in association with
thionamides, KClO4 and glucocorticoidsref.
OCAs have been used in combination with thionamides in
the treatment of type II AIT: this therapy was
associated with normalization of both serum free T4
(FT4) and free T3 (FT3)
levels or the occurrence of hypothyroidism after 15–31
wk of treatmentref.
Albeit iopanoic
acid
and prednisone are effective, glucocorticoids are
probably the drug of choice for more rapidly curing type
II AITref.
(80-95%)
with mild steatorrhea (8-33%)
(65-80%)
and hyperreflexia
(39-80%) (rare),
urticaria (10-25%)
(40%)
(50-90%) => hot intolerance,
conjunctival irritation, diplopia)
(50-60%)
(10-40%; more common in patients above age 50, due to
underlying disease)
(28-77%) => systolic
systemic
arterial hypertension
(66%) and vascular murmurs on thyroid (also due to
hypervascularization)
and reduced sexual function in tertiary hyperthyroidism (TRH
also stimulates PRL incretion)
=> hypercalcemia
and hypercalciuria
challenge
(diabetes mellitus) (nodules and cysts > 3
mm)
detects hypervascularization ("thyroid hell")
challenge test : no increase in serum TSH to control adrenergic
symptoms before other therapies work
(propylthiouracil 300-1000 mg/day; methimazole 30-100
mg/day) before surgery or if surgery is refused (e.g. in
newborns, youngs, pregnants). Prolonged remission in 30%
after 8-months course : 15% become hypothyroid. Side
effects from PTU : skin erythema and fever (3-4%) and
agranulocytosis (0.1-0.4%)
=> fibrosis and atrophy (only in patients with age >
18 yy, not pregnant, with small goiter and drug
intolerance)
increase sialylization and decrease clearance)
deficiency,
reduced thyroid hormone metabolic response ]plasma
and increased [FT4]plasma : high
[FT4]plasma, high [FT3]plasma,
normal or decreased [TSH]plasma;
,
nephrotic
syndrome deficiency
(autosomal recessive, only 35 cases reported)
deficiency (autosomal recessive : 1 every 40,000)deficiency
(autosomal recessive)
=> loss of iodine recirculation
(< 5%)]plasma
and decreased [T4]plasma
(Wolff-Chaikoff effect) to treat ... (3-4 months, due to reversible
damages rather than cell destruction)
(rare only if accompanied to natural goitrogenous or
hyposeleniemia; 2-3% of pregnants due to increased
thyroid hormone requirements) in vegetables or milk from
cattle who ate such vegetables
and amiodarone-induced
thyroiditis)
or referred as pharyngodynia or otodynia, dysphagy,
erythema over thyroid, regional lymphadenitis.
Complications : tracheal obstruction, septicemia,
retropharyngeal abscess, mediastinitis,
jugular vein thrombosis.
(ASA 2-3 g/day + antacids) => GR
agonists
as analgesics (prednisone 20-40 mg/day; gradually
reduced in 6-8 weeks until ESR normalized) -induced thyroiditis (type II amiodarone-induced thyrotoxicosis (AIT)
due to lysosomal activation and histiocyte
infiltration => cytotoxic damage, decreased
vascularization, high IL-6)
|
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|
|||
|
|
|
|
||
| macroscopic | consistence |
|
|
|
| lymph node involvement | diffuse | diffuse | asymmetric | |
| adhesion to surrounding structures | no or mild | no or mild | strong | |
| microscopic | microabscesses | present | absent | absent |
| lymphatic infiltration | minimal | diffuse with presence of germinal centres | minima | |
| giant cells | frequent | rare | absent | |
| fibrous tissue | increased | mildly increased | strongly increased | |
]plasma
and decreased [T4]plasma. Upon TRH
challenge test, [TSH]plasma
increases within 1 hour but [T4]plasma
doesn't increase.
]plasma
and decreased [T4]plasma.
Upon TRH challenge test, [TSH]plasma
increases a little (the negative feedback doesn't works) and
hence [T4]plasma increases a
little, too.
(autosomal recessive nongoitrous
hypothyroidism).
deficiency; it is marked by slowing and cessation of
growth, thickening and yellowing of the skin, coarse
facies, delayed puberty, and short stature at maturity]plasma
and decreased [T4]plasma.
Upon TRH challenge test, [TSH]plasma
doesn't increase and hence [T4]plasma
doesn't increase, too.
=> weight gain (despite anorexia)
and rarefaction of hairs on outer thirds of eyebrowns
and hypertriglyceridemia
or myasthenia of respiratory muscles)
(30%),
dementia,
psychosis
=> mixedematous
coma
associated with hypothyroidism occurs due to reduced cardiac
output and subsequent renal hypoperfusionref,
and, in severe cases, acute renal failure secondary to
rhabdomyolysisref.
In most cases, clinical features of hypothyroidism are
apparent and there are associated biochemical abnormalities
such as raised serum creatine kinase concentrationref.
Improvement in renal function following treatment of
hypothyroidism in patients with chronic renal failure has
been previously reported, and it has been suggested that
investigation of unexplained deterioration in renal function
in these patients should include thyroid function testingref.
Reduced T3 and T4 concentrations can
occur in chronic renal failure in the absence of
hypothyroidism, but these are not associated with increased
TSH concentrationref.
CRF may also lead to normochromic
normocytic
anemiaref (nodules and cysts > 3
mm)
(longer half-life than L-T3);
33% of patients experience increased [TSH]plasma
even after [T4]plasma and [T3]plasma
are normalized. Doses cannot be increased as at high
concentrations it has toxic effects.
or Gas in > 90% , K-Ras, N-Ras . Aggressive as tall cell
variant (not in 131I
radiometabolic therapy). Higher incidence in
natives of the Marshall Islands and 62-fold higher
incidence in the children of Belaru, Ukraine and
Bryansk, following the accident at Chernobyl
Nuclear Power Plant on April 26, 1986 : 70% have
mutation in c-Ret vs. 2.5% in Saudi Arabia and
35% in Italy, Gas, and PTEN (in Cowden
syndrome); RET/PTC1:(inv(10q11.2q21),
RET/PTC2:(t(10;17)(q11.2;q23)),
RET/PTC3:ELE1/TK (20-40%), H-Ras, K-Ras, N-Ras, CDKN2A deletion, c-Myc
overexpression, and LOH; multifocal (30-50%; 70-80% if
radioinduced). Individual tumor foci in patients with
multifocal papillary thyroid cancer often arise as
independent tumorsref
|
|
|
|
| stage I | any T, any N, M0 | T1, N0, M0 |
| stage II (80%) | any T, any N, M1 | T2 or T3, N0, M0 |
| stage III | - | T4, N0, M0 any T, N1, M0 |
| stage IV (1%) | - | any T, any N, M1 |
and pulmonary
metastases
(except 131I
radiometabolic therapy)
rearrangements, point mutations in TSHR, Gas, H-Ras, K-Ras, N-Ras, CDKN2A deletion, c-Met
and c-Myc
overexpression, PAX8-PPARg1
translocation, and LOH; 5 years of latency,
multicentricity and lymph node involvement (10-20%) |
|
|
|
| stage I | any T, any N, M0 | T1, N0, M0 |
| stage II | any T, any N, M1 | T2 or T3, N0, M0 |
| stage III | - | T4, N0, M0 any T, N1, M0 |
| stage IV | - | any T, any N, M1 |
,
brain
metastases,
and bone
metastases
to inhibit TSH incretion followed by 131I
radiometabolic surgery of thyroid remnants (this
allow evaluation of 121I total body
scintigraphy (TBS) and [TG]plasma to
assess relapses and metastases), but is associated
in age < 16 years with recurrent nerve injury
(0.3-30%), hypocalcemia (8-24%), and acute
respiratory failure (5%), expecially when there is
extrathyroid invasion, lymph node metastases,
previous surgery, anatomical variants of recurrent
nerve or parathyroids, poor training of the surgeon.
Minimally invasive video-assisted thyroidectomy
has lower mortality reduces relapses, but there is
risk for inferior laryngeal nerve injury for vertebral metastases. (differential diagnosis with primary
lymphomas
(MALTomas)), point mutations in APC,
p21/WAF
overexpression, and LOH.
are marginally beneficial
: as the conventional techniques that are used cannot
distinguish between benign follicular thyroid
adenoma and invasive
follicular carcinoma, all patients with follicular
lesions undergo thyroidectomy.
SAGE analysis identified a combination of 4 genes (DDIT3,
ARG2,
ITM1,
and C1orf24)
that
can be used to identify carcinomas with 83% accuracy, so
this approach might spare patients from unnecessary
surgeryref. to make
differential diagnosis with hemorrhagic cyst
to assess bone
metastases
(10% : risk of injury of recurrent nerve)
for bone
metastases,
it could be due to metastases or uncomplete thryoidectomy
(also ectopic embryological remnants; struma ovarii are
usually nonfunctioning) ,
pulmonary
metastases,
bone
metastases , histaminase, DOPA decarboxylase, NSE,
CGRP,
SST, TG, TSH,
ACTH,
GRP,
5-HT,
chromogranin A, and substance
P.
,
secondary
Cushing syndrome ]plasma agonists
(pentagastrin) > Ca2+ gluconate assessed
at time 0, 2', 5', 15', and 30' (not recommended in
individuals with peptic ulcer) > TRH
> histamine (through H1-receptors,
through nonspecific vascular dilation "washing out"
preformed calcitonin) > PPI (omeprazole
increases endogenous gastrin)
with complete emptying of central lymph nodal
compartment
of CCK2-expressing
medullary thyroid cancers with radiolabeled minigastrin
and chemotherapy are palliative
(1-2%) (pulmonary
metastases
are usually asymptomatic) < multiple endocrine
neoplasia (MEN) IIB / III / Wagenmann-Froboese syndrome /
ganglioneuromatosis of the alimentary tract < anaplastic thyroid carcinoma
) gene or PTH
gene,
MTND6,
or tRNA
glutamine (MTTQ) (hypomagnesemic
hypoparathyroidismref)
during pregnancy
hypoparathyroidism : accidental ablation of parathyroid
tissue gene inherited
from the mother and predicted to interfere with the
parent-specific methylation of this gene activity/protein leading to
the same physical appearance as patients with PHP IA but no
endocrine abnormalities,
obesity,
short metacarpals, and ectopic calcification.
following thyroid surgery is usually transient : if becomes
chronic if persists > 2-3 weeks gene or PTH
gene (autosomal dominant or recessive) gene gene may be more sensitive to
extracellular Ca2+ changes (renal
hyperparathyroidism) => phosphate retention;
inahibility to hydroxylate vitamin D3 => reduced
intestinal calcium absorption => hypocalcemia => parathyroid
hyperplasia and increased serum PTH => bone resistance
=> increased serum calcitonin + calcium)
(MIP) + forearm muscle parathyroid
autograftin
patients
refractory to medical therapyref.
It
is important to remove all parathyroid glands, including
supernumerary glands, at the initial operation and to
choose appropriate and adequate parathyroid tissue for the
autograft to prevent persistent or recurrent 2HPTref.
There is a significant rate of recurrent secondary
hyperparathyroidism (rSHPT), mainly due to the
parathyroid autografts (30% at 7 years after the initial
operationref),
but
in some cases there are previously undetected residual or
ectopic parathyroid glands that can be identified with an
echo-guided approach and treated with echo-guided percutaneous
ethanol
injection therapy (PEIT)
or percutaneous calcitriol injection therapy (PCIT);
however, there is a risk of iatrogenic primary hypoparathyroidism
in patients with non-functioning parathyroid autografts.
As parathyroid autografts consist of multiple nodules,
echo-guided injection of ethanol or calcitriol to each
nodule is almost impossible and therefore resection of the
autograft is indicated for autograft-dependent recurrent
renal hyperparathyroidismref.
A modified Casanova testref
can discriminate between the graft-bearing arm and the
neck as the site of the recurrence : the test measures
intact PTH in blood obtained from the non-graft-bearing
arm before an ischemic period and from the arm bearing the
parathyroid graft during an ischemic period caused by an Esmarch
bandage (application of turniquet to the upper arm).
Graft-dependent recurrence (GDR) is suggested when PTH
levels dropp by > 50% and neck-dominated recurrence
(NDR) whenever the PTH levels dropp to < 20%. Patients
are operated on accordingly. This abbreviated form of the
Casanova test is less time-consuming, satisfactory in an
ambulatory setting, equally effective, and less invasive
than the original Casanova procedureref. agonists
(calcimimeticsref);
they
possess lowering effects not only on serum PTH levels but
also on serum calcium x phosphorus product levels, a
hallmark of an increased risk for cardiovascular death in
dialysis patients with end-stage renal disease (ESRD)
:,
nausea and
vomiting,
peptic
ulcer,
constipation and abdominal
pain
and polydipsia,
psychosis
(15-20%)
=> chronic
pancreatitis
(25%, expecially in premenopausal females or nonhypogonadic
males; it affects mainly bones with high content of compact
bone, eg radius and external third of clavicle, skull and
dental alveoli) => osteolysis => pain and tenderness
of bones and spontaneous fractures or osteitis
fibrosa
cystica generalisata / von Recklinghausen's disease /
osteitis fibrosa osteoplastica / parathyroid osteitis
=> brown tumor (a giant-cell granuloma produced
in and replacing bone in jaw or third finger)
=> hypercalciuria
> 300 mg/24 hr (40%)
=> hypophosphatemia
(40%, due to PTH-induced reduced bicarbonate resorption in
the proximal renal tubule)
of lumbar vertebrae, hips and radium and echocolordoppler
(ECD)
or fine-needle
aspiration
biopsy (FNAB)
(=> PTH dosage) : accuracy depends on diameter,
location, thyroid status (parathyroids may be confused
with enlarged lymph nodes during thyroiditis), devices
and experience-SPECT fusion
to assess relationships with surrounding organs-PETfusion
within the same gantry is an aspecific test to be
practiced after a definite diagnosis or for early
post-therapeutical follow-up
+ MRI 1 mg/dL over
normal value, hypercalciuria > 400 mg/die, creatinine
clearance decreased by 30%) and age < 50 years => surgical
ablation of hyperactive parothydeal gland(s) (minimally
invasive parathyroidectomy
(MIP)) after marking parathyroids with methylene blue or intraoperative
MIBI
g-probe (IMGP) technique at the
time point at which the target-to-background ratio is maximal in
the performance of minimally invasive radio-guided surgery
(MIRS) => evaluation of decreased [PTH]blood
within 20' (normal parathyroid glands are still inhibited by
hypercalcemia) with quick PTH assay (QPTH). False
positivity may occur if parothydeal ischemia prevents PTH from
being released in bloodstream. When all 4 parathyroids are
hyperplastic, 3 are removed, while the fourth is sectioed to let
about 100 mg of parathyroid tissue, assessing good
vascularization and marking it with nonreabsorbable suture or
metallic clip for future surgical explorations. If all 4
parathyroids are normal, the patient should be reevaluated. If
the fourth parathyroid is not found, a hemithyroidectomy should
be performed assuming an intraparenchymal parathyroid. Complications : hemorrhage, recurrent
nerve injury, involvement of superior laryngeal nerve, thyroid
storm, hypoparathyroidism
(more comon in patients with severe bone calcium depletion (hungry
bones)). )
> 140/90 mmHg
> 130/85 or receiving current medication for
hypertension
> 150 mg/dL (or > 1.69 mmol/L)|
|
|
|
| Europids : in the USA, the ATP III
values (102 cm male; 88 cm female) are likely to continue to be used for clinical purposes |
male | >= 94 cm |
| female | >= 80 cm | |
| South Asians : based on a Chinese, Malay and Asian-Indian population | male | >= 90 cm |
| female | >= 80 cm | |
| Chinese | male | >= 90 cm |
| female | >= 80 cm | |
| Japanese | male | >= 90 cm |
| female | >= 80 cm | |
| Ethnic South and Central Americans | use South Asian recommendations until more specific data are available | |
| Sub-Saharan Africans | use European data until more specific data are available | |
| Eastern Mediterranean and Middle East (Arab) populations | use European data until more specific data are available | |
within pacemaker neurons of the hypothalamic suprachiasmatic
nucleus. Homozygous Clock mutant mice have a greatly
attenuated diurnal feeding rhythm, are hyperphagic and
obese, and develop a metabolic syndrome of hyperleptinemia,
hyperlipidemia, hepatic steatosis, hyperglycemia, and
hypoinsulinemia. Expression of transcripts encoding selected
hypothalamic peptides associated with energy balance was
attenuated in the Clock mutant mice. These results suggest
that the circadian clock gene network plays an important
role in mammalian energy balanceref.
|
|
|
|
|
| high |
< 130
|
< 40
|
> 400
|
| borderline |
100-129
|
40-60
|
150-400
|
| low |
< 100 (therapeutic goal)
|
> 60
|
< 150
|
(RR = 4 for fatal ACS, and 2 for total and
cardiovascular mortality)
is significantly elevated in those with metabolic syndrome
(2.36 mg/L vs.1.56 mg/L) and measurement enhanced the
prediction of both CHD and diabetes. gene
mutations leads to apoptosis of >
80% b-cells in pancreas.
(usually accompanied by kidney
transplantation),
affects young women, obesity, hyperandrogenism, severe
hyperinsulinemia, GLUT4, MAPK8IP1,
mitochondrial
glycerol-3-phosphate
dehydrogenase 2 (GPD2), ABCC8 / sulfonylurea
receptor 1 (SUR1)...) do not increase the risk of
developing DM : siblings of children who have DM
-- and are therefore more likely to develop the
condition themselves -- are not more likely to
become diabetics if they are vaccinatedref
levels are increased in the TNF-a-
and dexamethasone-induced modelsref
=> relative insulin resistance in skeletal
muscles and liver (prevalence = 20%; aetiology :
IRS-1 polymorphism => down-regulation of peripheral
InsR
expression and catalytic activity; obesity
=> lipotoxicity, including increased [FFA]serum=Randall
cycle=> decreased [Glc]serum)
=> lack of peripheral glucose usage after meals
(=> induction of ketogenesis =>
increased synthesis of VLDL (liver steatosis) =>
inhibition of hepatic lipase => decreased HDL-Ch,
hyperglycosylated LDL => increased risk of CVD)
=> hyperglycemia=> compensatory hyperinsulinemia
(inversely related to impairment of first phase of
secretion)
amyloid fibrils in Langerhans'
islets or IL-18R, and in mice
transgenic for expression of IL-18BPref.
: gene, with severe insulin
resistance and acanthosis
nigricans as well as thick hair,
abnormalities of teeth and nails, and
hyperplasia of the pineal gland. marked by slow physical and
mental development, the elfin facies suggested
by the name (wide-set eyes, low-set ears, and
hirsutism), and severe endocrine disorders such
as enlargement of the clitoris and breasts in
females and of the phallus in males => deleterious effects of
oxidative phosphorylation inhibition on
pancreatic islet cell function,
middle-age women, hyperandrogenism, autoimmune
disorders
(HAIR-AN) syndromeTherapy :oral hypoglycemizing
drugs are contraindicated in chronic
renal
failure
and liver
failure
(=> shift to insulin
replacement therapy)
activators
agonists inhibitors agonists (side
effect : 70% increased risk of heart
failure,
8.8% vs. 5.5%) agonists
for initial stages
inhibitors
has an anti-diabetic effect on obese patients but also
on non-obese diabetic (NOD) mice) and characterized by b-cell failure,
insulinopenia, insulin resistance, and moderate to
severe hyperglycemia, but without ketosis
(anyway most patients also markers of autoimmune b-cell destruction)
(thiazide diabetes : they inhibit insulin
secretion, possibly through thiazide-induced hypokalemia)
(steroid diabetes / steroidogenic diabetes :
target tissue insulin resistance; it is characterized
by a relatively low incidence of microvascular
sequelae)
(gestational
diabetes mellitus (GDM)) : with onset or first
recognition during pregnancy; this category does not
include diabetics who become pregnant or women who
become lactosuric
have a 48% lower rate of GDM, as it probably acts as a
surrogate for general nutritional deficiency,
estrogens, progesterone, and cortisol) and an increased insulin
degradation by placental insulinase => physiological insulin-resistance
(aimed to shift nutrients to the developing fetus) is
deficiently compensated by maternal hyperinsulinism
(expecially in diabetic pregnants) to obtain a normal
glucose tolerance => maternal hyperglycemia (there is a
risk for ketoacidotic coma if more insulin is not
administered : the lack of increased insulin requirements
in a diabetic pregnant marks placental insufficiency and
fetal risks, expecially when associated with nephropathy
or pre-eclampsia) => fetal hyperglycemia (maternal
insulin doesn't cross blood-placenta barrier) => fetal
hyperinsulinism. Maternal diabetic complications are
increased by pregnant's predisposition to develop urinary
tract infections, neuropathies, nephropathy, and
retinopathy. During last weeks of pregnancy and labor
there is instability in glycemia, with a tendency to
develop acidosis. After delivery instability persists but
carbohydrate tolerance increases abruptly reducing insulin
requirements : during puerperium there is a gradual
increase of carbohydrate tolerance (due to loss of
calories with lactation and loss of placental hormones),
which returns to pre-pregnancy levels within 6 months.
(> 4 kg or > 95th percentile at delivery; normally
sized head, larger than normal trunk) may complicate
delivery due to cephalopelvic disproportion or preeclampsia
/
gestosis / pregnancy induced hyperension (PIH)
;
women who develop GDM had SHBG
levels that were much lower than those of women who remain
diabetes-free throughout pregnancy ,
genetics, oxidative stress, and VEGF SNPs) : hyperglycemia => glucotoxicity
=>
DHAP
=> methylglyoxal (MG) (an a-oxoaldehyde)
=>
methyl glyoxal-derived advanced glycation end products
(MG-AGE) (including hydroimidazolone) => RAGE => inhibition of InsR translocation
& UTIs
: excess of nonreabsorbed glucose => H2O is
recalled into tubule => D[Na+]tubule
< 0 => increased gradient allows Na+
leakage into tubule => further H2O recalling
into tubule and so on (positive feedback)
due to dehydratation
(in type 1 diabetes mellitus)
(in type 2 diabetes mellitus)
due to iatrogenic insulin-induced
hypoglycemiadue
to
impaired aerobic glycolysis
due to nephropathy => inhibition
of GAPDH activityref
to
stimulate
natriuresis => glomerular hypertension => GFR
increases by 20-40%, PRF increases by 10-15%, and
hence filtration fraction increases, too => microalbuminuria
(5-15 years after diagnosis of IDDM or 2-3 years after
diagnosis of NIDDM : incipient or silent diabetic
nephropathy) and renal hypertrophy => macroalbuminuria
(overt diabetic nephropathy : 40% of patients
with IDDM and 15% of patients with NIDDM develop
manifest diabetic nephropathy within 10-25 years;
relates with periodontitis
in patients with NIDDM) and
glomerulosclerosis => GFR decreases by 1
mL/min/month, leading to ESRD
within 4-10 years.,
ABCC8 / sulfonylurea
receptor 1 (SUR1) activators and metformin
=> decreased requirements. due to diabetic autonomic
neuropathy and loss of reflex tachycardia, more difficult vascular access,
rapid progression of retinopathy) (+ non-DHP CCBs)) : overt nephropathy
< 125/75 mmHg and/or as lower as you can (+ non-DHP CCBs)) :
,
but the cause-effect relationship may be bidirectional.
or abdominal
painis the
most debilitating complication alternated to constipation (differential diagnosis with
celiac
disease in type 1 diabetes mellitus) and retrograde
ejaculation. Impaired eNOS function is
associated with erectile dysfunction in DM,
but the exact molecular basis for the eNOS
defect in the diabetic penis remains unclear.
Hyperglycemia increases O-GlcNAc
modification of eNOS in the penis, preventing
phosphorylation at the primary positive
regulatory site on the enzyme and hampering
mechanisms of the erectile response. T1DM was
induced in male rats by alloxan (140 mg/kg,
i.p.). After 5 wk, the diabetic rat penis
exhibited increased O-GlcNAc
modification of eNOS and decreased eNOS
phosphorylation at Ser1177 at
baseline compared with the control rat penis;
eNOS phosphorylation at Thr495, Ser615,
and Ser633 was not affected. In
addition, eNOS phosphorylation at Ser1177
was impaired in the diabetic rat penis
in response to penile blood flow (shear
stress) elicited by electrical stimulation
(ES) of the cavernous nerve and to recombinant
human VEGF165. Phosphorylation of Akt, a
mediator of shear stress-induced eNOS
phosphorylation at Ser1177, was
decreased in the diabetic penis at baseline,
but it was restored by ES. Erectile response
to shear stress elicited by ES and to VEGF was
decreased in diabetic compared with control
rats. eNOS inactivation occurs in the diabetic
penis by a glycosylation mechanism
specifically at Ser1177, by which
the enzyme is rendered incapable of activation
by fluid shear stress stimuli and VEGF
signaling. In vivo penile erection
paradigm supports the physiologic relevance of
O-GlcNAc modification in vascular
disorders associated with diabetesref. with sluggish reaction to
light
(> 50% of newly diagnosed NIDDM cases have CAD;
10-year AMI risk is the same for non-AMI diabetics and
nondiabetic AMI patients; mortality of patients with
new hyperglycemia in both non-ICU and ICU is far
higher than mortality of known diabetes patients; it
relates with periodontitis
in patients with NIDDM; the Hp2
allele of the haptoglobin
gene is highly predictive of adverse cardiac events in
diabetic patients after they undergo PTCA). DM is
considered a CHD
risk
equivalent
(3-fold increase of strokes) : due to myocardial
ischemia (due to atherosclerosis
and systemic
arterial
hypertension)
and dysfunction of cardiomyocytes secondary to chronic
hyperglycemia. (no claudicatio)|
|
|
|
|
|
| A (no infection or ischemia) | ||||
| B (+ infection) | ||||
| C (+ ischemia) | ||||
| D (+ infection and ischemia) |
results from a combination of neuropathy and obliterating
arteriopathy of lower limbs.
=> opportunistic infections
and spongiositis complicated by emphysematous
pyelonephritis
and renal
papillary
necrosis / necrotizing renal papillitis
colonization in skin folds and narices
and pruritus
(RR up to 3) : people with diabetes have a 30-40%
increased chance of developing CRC and tend to have a
higher death rate after being diagnosed. People who
received > 3 years of insulin therapy had 3 times the
risk of developing that cancer compared with patients who
received no insulin. The risk for people on > 5 years
of insulin therapy is 4 times higher than the no-insulin
group
risk due to placental insufficiency associated with IUGR
is higher in F, R, and FR classes
in most patients, severe in 10% vs. < 1% in
non-diabetic pregnants
(20% vs. 3-10% in non-diabetic pregnants)
(favorable in both pregnant and fetus)]blood > 6.1%
(relates to FPG + postprandial glucose (PPG) : monitored at
home with A1cNow®). Measurements reflect
time-averaged glycemia in the past 2–3 monthsref1,
ref2,
ref3,
ref4,
ref5.
Correlations between HbA1c concentration and
average plasma glucose :ref1,
ref2,
ref3
and liver
cirrhosisref,
so you should correct as follows : corrected HbA1c
(%) = measured HbA1c (%) + [0.224 x measured
erythrocyte creatine (mmol/g Hb)] -
0.05 . | HbA1c (%) |
|
|
|
|
| 4.0–5.9 |
|
|||
| 6.0–6.5 | target | |||
| 6.6–6.9 | action | Target Aa | Target | Target |
| 7.0–7.9 | Target Bb | Action | Action | |
| 8.0–8.9 | Target Cc | |||
| > 9.0 | Action | |||
inhibitors
to prevent postprandial hyperglycemia
to prevent glycation
therapies to prevent methylglyoxal formation antagonists inhibitors| Diabetes news
|
,
mental confusion, and disturbances of vision.,
CT,
intraoperatory echography
or KATP activators
; most are islet cell
tumors of non-b cells in the
pancreas, but some are found at sites such as the antrum
of the stomach, duodenum, the hilus of the spleen, or
regional lymph nodes. This is the usual cause of Zollinger-Ellison
syndrome; most are
islet cell tumors, but some are found in the duodenum,
hypokalemia,
and achlorhydria
,
deep
vein
thrombosis (DVT),
diabetes mellitus or IGT,
and hypoaminoacidemia) / CT / MRI, 5-fluorouracil, platin compounds, (if Octreoscan scintigraphy was
positive)
during arterial phase, with slow wash-out
)
(acute tuberculous adrenitis)
(histoplasmosis)
(size, contrast attenuation values)/MRI
(intravascular extension, chemical shift) => adrenal
scintigraphy
(functional evaluation and discordant pattern; sensitive
also for non-secreting pheochromocytomas)|
|
|
P value | |
| maximal diameter > 4 cm | 78% :
> 5 cm : adrenal carcinoma) |
22% | 0.0001 |
| irregular margin | 63% | 53.8% | NS |
| inhomogeneity | 80% | 100% | NS |
| calcifications | 13% | 31% | NS |
| hypodensity | 100% | 100% | NS |
| no cortical uptake at 131I-norcholesterol scintigraphy | 27.7% | 100% | 0.001 |
| cortical uptake at 131I-MIBG scintigraphy | 84.4% | 100% | 0.001 |
)
is
at present restricted to patients with for
all patients with frank or subclinical hormonal incretion,
suspect malignancy based on radiological or scintigraphic
studies
every year for the first 2 years.
deficiency, with normal
production of all other adrenocortical steroids. activity
(PRA)
.
Some affected infants outgrow the need for dietary
salt supplements in early childhood.
and hyperkalemia
but without salt wasting, due to abnormally increased
absorption of chloride by the renal tubules
and 11b-hydroxysteroid
dehydrogenase
2 (HSD11B2) inhibitors
, hypernatriuria
=> dehydration and hyponatremia
=> systemic
arterial
hypotension
(normonatremia and hypertension in Gordon's syndrome !)
(70-90%) (adrenal calcifications are
detectable with Rx in 50% of cases), sore throat,
chills, rigors, weakness, malaise, restlessness,
apprehension, myalgias, arthralgias, and fever. These
symptoms are usually abrupt in their onset. Petechiae
are present in approximately 50-60% of patients (purpura
fulminans).
and subsequent adrenal hyperplasia as well as hyperandrogenism
(in type III and type IV) or hypoandrogenism (in
type I, II, and V)|
|
|
|
|
|
|
|
|
|
|
steroidogenic acute regulatory (StAR) protein : death during childhood |
|
|
|
|
none | all |
|
|
HSD3B2 |
|
|||||
| salt wasting |
|
|
|
DHEA, 17-OH -pregnenolone | aldo, T, cort, estradiol | ||
|
|
|
|
|
DHEA, 17-OH- pregnenolone | aldo, T, cort, estradiol | ||
|
|
|
|
|
DHEA, 17-OH- pregnenolone | - | ||
|
|
CYP21A2 / 21
hydroxylase
(95% : homozygous deficiency causes fetal death due to lack
of cortisol synthesis)
|
|
|||||
|
|
|
|
,
vomiting, hypovolemia
and cardiovascular shock within first weeks of life |
progesterone, 17-OH- progesterone, D4- androstenedione | aldo, cort | ||
|
|
|
|
|
17-OH- progesterone, D4-A | cort | ||
|
|
|
|
|
17-OH- progesterone, D4-A | - | ||
|
|
CYP11B1
/ 11b hydroxylase |
|
|
|
|
11-DOC, 11- deoxycortisol | cort, aldo |
|
|
|
|
|
11-deoxycortisol ± 11-DOC | - | ||
|
|
CYP17A1 steroid 17a-hydroxylase activity |
|
|
|
|
11-DOC, corticosterone | aldo, andro, cort, estro |
| CYP17A1 17,20 lyase
activity |
|
|
|
|
- | DHEA, T, D4-A | |
| multiple deficiency |
incretion
progressing to shock and, if untreated, death,
anorexia,
abdominal pain)
=> hypoglycemic
coma,
anorexia,
abdominal
pain(34%),
diarrhea
(20%), constipation
(19%) => weight loss (97%)
=> systemic
arterial
hypotension
< 110/70 (87%; orthostatic in 12%) => syncope
(16%)
(98% : "black Adddison" vs. "white Addison") on
sun-exposed areas, palmar skin folds, gingivae, and anal
mucosa (82%) (cortisol deficiency
removes negative feedback on a-MSH
secretion)
(9%), alopecia
areata]urineand [cortisol, DHEA, DHEA-S, aldosterone]plasma,
plasma renin activity
(PRA)]plasma
and hypernatriuria
and hypokaliuria
challenge test : reduced response (cortisol peak
< 16-18 mg/dL or <
150% basal value) in primary panhypoadrenocorticism;
normal response in central panhypoadrenocorticism tolerance test (ITT)
: weak ACTH and cortisol response to insulin-induced
hypoglycemia cannot distinguish central from peripheral
Addison disease as hypophysary ACTH pool is limited;
normal ACTH and reduced cortisol response indicates
primary panhypoadrenocorticism
challenge test : in secondary
panhypoadrenocorticism ACTH response < 20 pg/ml (4.4
pmol/l) and cortisol response < 7 mg/dl (200 nmol/l)
(hydrocortisone, cortisol) and MR agonists (9a-fludrocortisone acetate)
.
Suppression of aldosterone with cyproheptadine suggests
a serotonin-mediated aldosterone-stimulating system.
Hyperactivity of this system may be the cause of IHA
associated with adrenal hyperplasiaref,
but actually cyproheptadine is a partial MR
agonist/predominant antagonistref.
and CYP11B1 genes that leads to
ACTH-sensitive mineralocorticoid incretion by zona
fasciculata. (The various hemoglobins Lepore have a
fusion b-type subunit
that is delta globin at the NH2 end and b globin at the COOH end.
This chimeric structure results from nonhomologous
pairing and unequal crossing-over between the
contiguous d and b globin genes. The
hemoglobins Lepore result from d-b fusion because the d globin gene is located
upstream from the b
globin gene. The hemoglobins anti-Lepore, e.g., Hb
Miyada and Hb P(Nilotic), are the reciprocal product
of nonhomologous pairing and unequal crossing-over
between the HBD and HBB genes; they are b-d
fusion globins. In GRA, the 5' portion of the
downstream gene is the 5' portion of the fusion
gene; hence, it is an anti-Lepore fusion). The genes
for CYP11B2 and CYP11B1 are located in close
proximity on 8q and have identical intron-exon
structures. The 2 genes share 95% sequence homology
but are usually only expressed in their respective
adrenal zones under separate regulation by
angiotensin II and ACTH, respectively. Subjects with
GRA have 2 normal copies of genes encoding CYP11B2
and CYP11B1, but they also have an abnormal gene
duplication. This hybrid, or chimeric, gene combines
the ACTH-responsive promoter sequence of the CYP11B1
gene fused to the more distal CYP11B2 coding
sequence. This chimeric gene results from variable,
and unequal, crossing-over between the 2 genesref.
The variability of the crossover site suggests that
these mutations arose independently in each
pedigree, and did not originate from a single
ancestral mutation. As a result, aldosterone
synthase is ectopically expressed in the
cortisol-producing zone of the adrenal cortex under
the regulation of ACTH. The chimerism also results
in the production of the hybrid steroids
18-oxocortisol and 18-hydroxycortisol that can be
used as diagnostic aidesref.
Genetic analysis of GRA kindreds has revealed that
the disorder is inherited as an autosomal dominant
traitref.
Celtic ancestry is frequent among the reported
pedigrees, and no cases have been reported among
blacksref.
0.5 mg x 4 times/day (every 6
hours) x 2-3 days => aldosterone < 4 ng/dl
on day 3 at 8 a.m.ref.
On the other hand, in one study, 10% of 60
patients with elevated aldosterone levels and a
positive dexamethasone suppression study had
negative genetic testingref. is effective by providing
feedback suppression of pituitary ACTH release,
which suppresses the abnormal regulation of
aldosterone secretion (dexamethazone 0.125-0.25
mg/day or prednisolone 2.5-5 mg/day), usually
administered at bedtime. However, iatrogenic
Cushing’s syndrome and impaired linear growth in
children have resulted from glucocorticoid
overdosingref.
The therapeutic goal should be normotension, and
not normalization of biochemical markers, such as
urinary 18-oxosteroid or serum aldosterone levels,
since these remain elevated in the majority of
patients who normalize blood pressureref.
In fact, therapy to normalize laboratory values
may unnecessarily increase the risk of cushingoid
side effectsref.
They normalize aldosterone, ABP, and kalemia have also been used
successfully and ACEIs are less likely to be
efficacious in the setting of a suppressed RAAS.
DHP CCBs can be useful adjunctive treatment to the
above diuretic agents activation
of MR
=> myasthenia (80%), polyuria (72%), hyposthenuria
(72%), polydipsia (46%, nycturia (30%), paraesthesia
(24%), intermittent paralysis (21%), tetania (20%),
asymptomatic (21%), volume-dependent and
vasoconstriction-induced secondary
systemic
arterial hypertension
(1% of all hypertension cases, 5% in referring centres,
20% in drug-resistent patients), orthostatic
systemic
arterial hypotension
without tachycardia, reduced Valsalva's maneuver,
headaches, no edemas. activity
(PRA) < 1 ng/ml/hr => autonomy tests :
(1.25 L in 2 hrs or 2 L in 4
hrs): positive if aldolsteronemia > 6 mg/dl p.o.
test, which in normal patients reduce aldosteronemia
(< 15 ng/dl) after 1 and 2 hrs and increases PRA] 0.5 mg x 4 times/day (every 6
hours) x 2-3 days : test is positive for GRH if
aldosteronuria becomes normal|
|
|
|
| BP | +++ | + |
| [aldosterone]plasma |
> 25 ng/dl | < 25 ng/dl |
| [aldosterone]urine |
> 30 ng/day | < 30 ng/day |
| age | < 50 years | > 50 years |
and MRI have good sensitivity (up
to 80%) only for nodules > 1 cm after suppression of the healthy
adrenal gland with dexamethasone shows early (in the first 24
hours) and persisting (up to day 5-7) uptake of the
tracer in autonomically functioning tissue
in lateral decubitus (side effect : acute pulmonary
edema) after pretreatment with phenoxybenzamine (7
days), propanolol (3 days), and hydroelectrolyte
repletion to precompensate shock after tumorectomy.
Aldosteronemia, PRA, and kaliemia normalize in 100%,
hypertension in 60-70%, type 2 DM in 100%
(100-400 mg/day for aldosterone and 100-200 mg/day for
catabolites; side effects : gynecomastia and sexual
deficits in the male and amenorrhea in females) and epithelial
sodium channel (ENaC) inhibitors and hypovolemia (CHF; cirrhosis, diuretics,
vomiting, salt-wasting nephropathy),
hypocalciuria
,
no edema, insensitivity to the pressor effects of
angiotensin
:-secreting
neoplasms
(reninomas) activity
(PRA)
]plasma
/ plasma mineralocorticoid activity (PMA) >
15 ng/dl in clinostatism and orthostatism]urine
> 10 ng/day (IC95 = 5-20) in clinostatism
and orthostatism]plasma/
PRA ratio (ARR) > 20 h. b-blockers, ACEI and diuretics
should be suspended > 3-4 weeks before testing PRA
! The antihypertensive treatment can be replaced by a
long-acting non-DHP CCBs.
The salt intake should be 60-80 mEq/day (51 g/day) and
potassium intake 40-60 mEq/day
when diet is normosodic (6 g/day for > 1 week in
hospital settings) => muscular weakness, type 2 DM due to b-cell dysfunction (50%), arrhythmias
and metabolic
alkalosis
> 20-25 mEq/day (> 30 mEq/l) => osmotic
polyuria and nycturia due to deficiency of renal
concentration => secondary polydypsia
: U wave, cardiac hypertrophy
: ventricular septal hypertrophy
: metabolic
alkalosis
and adult-onset diabetes mellitus in
postmenopausal women resulting from overproduction of
adrenocortical androgens. (1%) excess (tertiary Cushing's
syndrome) : excess (secondary Cushing's
syndrome) : excess (ectopic ACTH syndrome);
depending on its duration, it may be subtle,
resembling true Cushing's disease, but hypokalemic
alkalosis and weakness are often prominent.
if severe symptoms
(iatrogenic Cushing's syndrome / Cushing's syndrome
medicamentosus)
(side effect : Nelson's
syndrome)
) (50-87%) of the spine (40%) =>
kyphosis and rachialgias (58%), ischemic
necrosis of femur head which are located only on
abdomen. with slow healing (45-65%) (16%)
=> IGT
(55%) => polyuria and polydipsia (23%), diabetes mellitus (15%) (75%) => infections, hypokalemia,
and metabolic
alkalosis => systemic
arterial
hypertension
> 150/90 (75-82%) => benign endocranial
hypertension and edema
(30-62%) => arrhythmias
in 65-80%; acne in 45%; amenorrhoea
in 60-77%, clitoris hypertrophy in 19%)
(in secondary or tertiary Cushing's syndrome) : diffuse
hyperpigmentation
(20%) (14%,
expecially from hypophysary causes) incretion
precedes hypercortisolemia (> 7-8 mg/dL at 12 p.m.; difference <
50% between morning and bedtime values)]pl]pl (FUC) +
17-OH-cortisol]urine
:
challenge test (1 mg/kg
i.v.; samples since -30 to +120 minutes every 30
minutes) : paraneoplastic secondary and tertiary
Cushing's syndromes don't respond with an ACTH peak challenge
test (10 mg i.v.; samples
for ACTH and cortisol since -30 to +90 minutes, every
15 minutes) is positive only in Cushing disease test
(inhibitor of the enzyme steroid 11b-hydroxylase)
: plasma 11-deoxycortisol or urinary
17-hydroxycorticosteroids are measured after the
administration of metyrapone; levels are increased in
patients with Cushing's disease but not in patients
with ectopic ACTH syndrome.
(onset before age 20; multifocal in 20%; not
associated with other endocrinopathies, clinically
malignant in > 50%)
(> 20%; 100% in extraadrenal pheochromocytomas) and adrenalin
(< 80%; 100% in MEN) =>
(15-20% are normotensive; severe and occasionally
malignant (5-10%); 1% of all hypertension in pediatric
age and 0.05-0.1% in adulthood) => vertigo and
hypertensive retinopathy, cardiac or noncardiac acute
pulmonary edema, saralasine, glucagon) (imipramine, desimipramine)
due to down-regulation of vascular a-AR and
vasoconstriction-induced hypovolemia. 71% occur in
previously hypertensive patients, while 29% occur in
normotensive patients.
and mild weight loss => acute
renal failure (ARF) (57%, supraventricular arrhythmias,
and ventricular extrasystoles (palpitations : 64%), angina
pectoris and AMI(myocytolysis) due to increased O2
consumption and coronary spasm, aspecific
alterations of ST tract and T wave, raised U waves,
left ventricular overcharge, left or right bundle
branch block => congestive or hypertrophic
(eccentric or concentric) myocardiopathy (30%)
(80%)
(15-20%) => abdominal
pain
and nausea
and vomiting
=> unexplained orthostatic
systemic
arterial hypotension
or shock during surgery or trauma (also due to hypovolemia)
=> hypercalcemia
(20%) => true
erythrocytosis
(sometimes just relative erythrocytosis due to hypovolemia)
=> secondary
Cushing's syndrome => fever and
increased ESR.
| sensitivity | specificity | |
[total catecholamines]urine, 24h,
beginning collection during hypertensive crisis
> 250 mg/die or > 1480 nmol/die
|
85-100% | 72-99% |
[metanephrine]urine, 24h,
beginning collection during hypertensive crisis >
1.3 mg/die or > 7 mmol/die
|
97-100% | 84-100% |
| [vanilmandelic
acid
(VMA)]urine, 24h, beginning
collection during hypertensive crisis > 7
mg/die or > 35 mmol/die or = 500 - 3,500 mg/hr (normally 240 +/- 120 mg/hr) |
50-75% | 83-88% |
hypercatecholaminemia (66%) : increased
[catecholamines]plasma, during hypertensive
crisis (t1/2 = 2-3' !)
|
75-85% | 75-98% |
| [metanephrine]plasma | 88-100 | 75-88 |
| chromogranine A | 65-85% | 89-98% |
i.v.
=>
if after 2' [noradrenaline + adrenaline]plasma
> 1,500 pg/mL or > 3-folds basal values.
Sensitivity = 81; Specificity = 100% => if negative
you can exclude pheochromocytoma.,
flush, and a brief fall in blood pressure, but those
with pheochromocytoma, after a fall in blood pressure,
experience a marked rise in blood pressure, fear,
excitability, etc. p.o. =>
sampling after 2 and 3 hours => positive if
[noradrenaline + adrenaline]plasma< 500
pg/mL or < 50% basal values. Sensitivity = 97%;
specificity = 67%|
|
|
|
| CT |
|
|
| MRI (hyperintensity in T2wi) |
|
|
| 131I-metaiodobenzylguanidine (MIBG) adrenal
scintigraphy (only when CT gives doubtful
results or multiple localization is suspected) |
|
|
| octreotide scintigraphy |
|
|
| 6-18F-dopamine or 11C-hydroxyephedrine
PET |
,
lymph node metastases, liver
metastases,
brain
metastases,
and pulmonary
metastases.
(phenoxybenzamine 10 mg bid (increase by 10 mg/day up
to 40-80 mg/day), doxazosin or prazosin (1 mg q8h up
to 8-12 mgday) and i.v. phentolamine for 1-2 weeks
before surgery to treat crises =>
(not before a-AR block as
they could cause skeletal muscular ischemia; atenolol
50-100 mg/day or propanolol 0.01-0.1 mg/kg/day) to
treat shunt and reflexed tachycardia
(survival after 5 years > 95% and relapses < 10%) (survival
after 5 years < 50%). (normally-sized adrenals are
seen only in thin patients) => CT
(accuracy = 89%; if < 15 HU, 90% are benign, while when >
15 HU benign or malignant) => MRI or adrenal scintigraphy
)
that is a pinealoma in which the pineal cells are not well
differentiated,
compression of the optic chiasm, and hypopituitarism.)
and FSH)
and FSH) or mixed gonadal dysgenesis) or gonadoblastoma => masculinization) or mixed gonadal dysgenesis)) in males, diffuse renal
mesangial sclerosis (congenital adrenal
hypoplasia and hypogonadotropic hypogonadism) or LH deficiencyor gonadoblastoma)
,
gynecomastia,
normal penis, male psychosexuality, decreased [testosterone]plasma,
increased [estradiol]plasma,
increased [FSH
and LH]plasma,
urine, short height, hypospadia
| Symptoms & signs \ Aetiology |
|
|
| hyalinization of seminiferous tubules |
|
|
| microorchidism (hard testes) |
|
|
| azoospermia |
|
|
| decreased [testosterone]plasma |
|
|
| decreased face hairs |
|
|
| increased [FSH and LH]plasma,
urine |
|
|
| decreased sexual function |
|
|
| gynecomastia |
|
|
| decreased axillary hairs |
|
|
| micropenis |
|
|
| increased [estradiol]plasma due to
increased extragonadal aromatization |
is 20-60-folds higher than in normal males. There is
an association with germ cell tumorsref
and childhood leukemia
may worsen gynecomastia
by increasing substrate for extragonadal
aromatization; fertility via IVF defects
mutations, causing it to be misrouted so that it can
never perform its binding function
or FSH
or both may be deficient
,
a secreted protein that suppresses male sexual
differentiation, is thought to repress the biosynthesis of
gonadal androgen in female mammals : WNT4 appears to be
important in the development and maintenance of the female
phenotype in women, by means of the regulation of
müllerian-duct formation and control of ovarian
steroidogenesisref. => no conversion of testosterone into DHT
in peripheral androgen-sensitive tissues =>
Wolffian ducts develop but urogenital sinus and
external genitalia do not. Severe pseudovaginal
hypospadia,
closed-end pseudovagina opening in urogenital sinus or
urethra, and collecting drainage of ejaculatory ducts.
Female look with normal pubic and axillary hairs, but
without female breast development (as testosterone
inhibits LH,
no gynecomastia
occurs !). Lack of uterus and fallopian tubes.
Variable masculinization at puberty.]plasma = 3.4-31 mIU /
mL]plasma = 6-34
mIU / mL]plasma
= 288-1556 ng / dL]plasma = 8-20 ng / dL not requiring 5a reduction
incretion => increased [LH]plasma =>
increased testicular testosterone and estrogen incretion
(only estrogens can exerct a partial negative feedback
on LH
incretion)
=> Wolffian ducts don't
develop => external genitalia are females
(normally developed breast)occurs in abdomen, along inguinal
canal (simulating inguinal hernia) or in labia
majora. No spermatogenesis and feminizing puberty
with primary
amenorrhea. Patients tend to be tall with
female psychosexual development
,
male psychosexual development
and bilateral uterine tubes, a uterus, and an upper
vagina. When a testis descends the homolateral fallopian
tube and tube maybe located in inguinal canal (hernia
uteri inguinalis) or scrotum. Vasa deferentes are
located in the uterine wall and this increased risk for
sterility during surgery to remove uterus or vagina
to prevent abortion
deficiency,
single kidney in pelvis), skeletal anomalies involving
rachis, limbs or ribs, wedge vertebrae, synostosis, Klippel-Feil
syndrome
(dexamethasone crosses placenta and is used to treat diagnosed
fetuses) suppress adrenal DOC syhnthesis (preventing
hypertension and hypokaliemia) and androgen synthesis
(allowing normal gonadotropin incretion, testes development
and spermatogenesis). MR agonists are
used in type III CAH with salt wasting or increased RPA.
) ]plasma
< 10 ng/mL 5,000-10,000 IU 7
days at day 14)
50-250 mg/day for 5 days (repeated even for 6 months)
works better in MAP-test+ females and suppress the
negative estrogen feedback on hypothalamus. Effective in
70-80% (40% undergo pregnancy, mostly in the first 3
cycles). Side effects : hot flushes (10%),
gastrointestinal disorders (6%), mastodynia
(2%), visual disorders (1.5%), OHSS if > 100 mg/day,
multiple pregnancy = 3-7%
and rLH
in hypogonadotropic hypogonadism.
infusion pump in hypothalamic hypogonadism (low risk of
complications) is administered
when [estradiol]plasma > 1500 pg/mL and
ovarian echography shows 3-4 developed follicles) : ovarian
hyperstimulation
syndrome (OHSS),
multiple pregnancy
/ endometriotic cysts,
diarrhea,
headache, vertigo and
fatigue; dyspareunia; molimen ([L. “effort”] a
laborious effort made for the performance of any normal body
function, especially that manifested by a variety of mild
but unpleasant symptoms preceding or accompanying the
menstrual period) ;
side effects : dry throat)
(33%))refincretion)
(15-30%;
accompanied to galactorrhoea in 30-50%) (deficiency of GH, FSH, ...) or climacterium praecox /
early or premature menopause / premature ovarian
failure (POF) : premature failure of
ovulation before age 40 and/or LH (estroprogestins to prevent
hypoestrogenism); GR
agonists for autoimmune
oophoritis , SHBG, CYP11A1, insulin, InsR, Met196Arg
polymorphism in exon 6 of TNFRSF1B, enhanced peripheral 5a-reductase
activity, lower expression of TIMP-1 in
follicular fluid, increased plasma PAI-1
levels, decreased HOXA10
mRNA in endometrial cells
(reduction of type I of skeletal muscle fibres which are
sensitive to insulin, and the increase of type II fibres
which are resistant to insulin) except than in techal
and hilar ovarian cells => increased ghrelin
on steroidogenesis by granulosa cells via InsR and
IGF-1R and downregulates synthesis of SHBG, but this
interaction may compromise further growth of medium-sized
antral follicles by generation of 'preovulatory'
concentrations of cAMP within the granulosa cell and thereby
leading, prematurely, to terminal differentiation of
granulosa cells => hyperandrogenism =>
levels (with
anticortisol effect) support the development of
abdominal obesity =>
enhanced LH
secretion (approximately one LH pulse per hour), while
FSH is typically in the lower follicular range (reversed
LH-to-FSH ratio > 2.5) even during the
luteal-follicular transition is critical for follicular
development => absence of follicular dominance =>
arrested growth of antral follicles (granulosa
cells from anovulatory women with PCOS hypersecrete
oestradiol due to advanced maturation of medium-sized
antral follicles) => anovulation, the
regulatory IIb-component of
PKA, and hormone-sensitive
lipase
(HSL)
and acanthosis
nigricans (40%)
(association with valproate
?)
or PPARgagonists
(troglitazone), octretotide, a-glucosidase inhibitors, chromium
(III)
with ethinyl
estradiol (EE)
as the estrogen component and as the progestin
component can decrease facial hair and
acne and regulate the menstrual cycle
(flutamide 125-500 mg/day, associated with oral
contraceptive as during pregnancy could cause
feminization of external genitalia in a male fetus)
(finasteride 5 mg/day, associated with oral
contraceptive as during pregnancy could cause
feminization of external genitalia in a male fetus)
preparations, and possibly, GnRH antagonists to prevent
LH surges, chemotherapy. Hematomas
(12.5% in females, 33% in males). 0.01% (13% are
immigrated people who experience catch-up growth,
11.5% myelomeningocele, 10.5% hydrocephalus, 5% dysmorphic
syndromes, 4.3% encephalopathies, 3.7% neurofibromatosis)
and maturation of the gonads in males in Leydig
cells, and patients usually have normal fertility as
adults in females (< 10%) =>
menarche 1.2 +/- 0.8 years after discontinuation
|
|
|
|
| biological | taller than peers but may end up short | short stature but later should achieve normal height; osteoporosis |
| psychological | psychological effects positive in boys (higher self esteem), negative in girls (low self esteem) | low self esteem in boys; no major problems in girls |
| social | different from peers; treated as adolescent while still a child | treated by adults and peers as less mature than real age; difficulty in separating from parents and in getting work |
).
Lines were drawn largely based on mortality statistics from
European and American populations. Some research suggests that
the cut-offs should be higher for elderly populations and Asian
populations don't fit into the existing scale. There are
mounting evidence that Asian populations have a particularly
high risk of type 2 diabetes, cardiovascular disease and
mortality from other causes at relatively low BMIs. That is
thought to be largely due to their higher proportion of body
fat, often hoarded around the waist, relative to other ethnic
groups. For these populations, they found that a BMI of 26-31
was high risk. The panel recommends that intermediate 'public
health action points' be inserted at BMI values of 23.0, 27.5,
32.5 and 37.5. This would allow countries to use disease data on
their own population to decide on BMI targets. The combination
of underweight in children and overweight in adults, frequently
coexisting in the same family, is a relatively new phenomenon in
developing countries undergoing the nutrition transitionref ref,
corticosteroids,
liposuction
with compression, and surgical excision of especially
painful lipomasref1,
ref2.
IFN-a2b
was used to treat chronic hepatitis C in 2 patients with
adiposis dolorosa, and it induced long-term relief of painref.
Several case reports during the past 30 years have described
the use of systemically administered lidocaine (Dercum FX. A
subcutaneous connective tissue dystrophy of the arms and
back, associated with symptoms resembling myxoedema. Univ
Med Mag Phila 1888;1: 140-50)ref1,
ref2,
ref3,
ref4,
but long-term intravenous administration of lidocaine is
impractical and is associated with neurotoxicity. Several
voltage-gated sodium-channel blockers are clinically
available, including the anticonvulsant agents
carbamazepine, oxcarbazepine, phenytoin, lamotrigine,
topiramate, and zonisamide; the antiarrhythmic agent
mexiletine; and the tricyclic antidepressant agent
amitriptyline. Some of these drugs exhibit multiple
mechanisms of action, but even the relatively selective
sodium-channel blockers lack the pharmacologic specificity
that is required to avoid also targeting normal physiologic
activity of the central nervous system and so may be
associated with dose-related adverse effects. The narrow
therapeutic ratio of this class of drugs may account in part
for the inability to show analgesic efficacy consistently in
clinical trials of peripheral neuropathic pain (with the
exception of trigeminal neuralgia)
deficiency deficiency (5%
of severe obesity cases) deficiciency deficiency deficiency (rare) deficiency
(rare)
: chromosomal abnormalities underlying the disease cause
the highest ghrelin levels ever measured in
any humans excess under the control of the
adipocyte-specific promoter FABP4
eat unlimited amounts of high-fat mouse chow, but consume
slightly less oxygen and have about 50% less body fat than
normal mice on a low-fat diet. And despite they produce
half the normal amount of leptin, the insulin sensitivity
and glucose tolerance of transgenic mice on a high-fat
diet was better than that of normal mice on a low-fat diet
: they show no signs of diabetes or other metabolic
disorders, which are common in animals with too little
fat. The mice have underdeveloped mammary glands, an
inability to generate body heat and skin that's twice as
thick as normal.-/-
mice exhibit a profound increase in whole-body energy
expenditure as determined by 10°C increased core
temperature and 30% increased whole-body oxygen
consumption. As a consequence, these mice displayed a 50%
decrease in adiposity, primarily due to a reduction in
cell size despite a 30% increase in food intake. These
changes were accompanied by a significant increase in
activity (2- to 3-fold). In addition, c-Cbl-/-
mice displayed a marked improvement in whole-body insulin
action, primarily due to changes in muscle metabolism,
making it more resistant to type II diabetes. They also
have increased protein levels of the insulin receptor
(4-fold) and uncoupling
protein-3 (UCP-3) (2-fold) in
skeletal muscle and a significant increase in the
phosphorylation of AMPK and acetyl-CoA carboxylaseref.
and elevated ghrelin. These differences in
leptin and ghrelin are likely to increase appetite,
possibly explaining the increased BMI observed with short
sleep duration. In Western societies, where chronic sleep
restriction is common and food is widely available,
changes in appetite regulatory hormones with sleep
curtailment may contribute to obesityref.
Habitual sleep duration below 7.7 h was associated with
increased BMI, similar to findings in other studies
including childrenref1,
ref2,
adolescentsref,
and adultsref1,
ref2.
A significant association of sleep duration with leptin
and ghrelin that is independent of BMI, age, sex, sleep-disordered
breathing
(SDB)
(a pathology associated with increased BMI), and other
possible confounding factors (analysis not shown for SDB
and other confounders) has also been reported. Short sleep
duration was associated with decreased leptin and
increased ghrelin, changes that have also been observed in
reaction to food restriction and weight loss and are
typically associated with increased appetite. These
hormone alterations may contribute to the BMI increase
that occurs with sleep curtailment. Previous studies have
shown that both acute sleep deprivationref
and chronic partial sleep deprivation (sleep restriction)ref
can cause a decrease in serum leptin concentrations. These
studies, however, were performed under highly controlled
laboratory circumstances and results validate the
association of decreased leptin with decreased sleep time
in a large sample of adults under real-life conditions
and, now, indicate a role for ghrelin. Leptin deficiency
increases appetite and produces obesityref1,
ref2.
Leptin administration suppresses food intake and reduces
energy expenditureref1,
ref2.
Importantly, low leptin as observed with sleep loss has a
greater impact on appetite than high leptin levels, which
are associated with leptin resistance, as occurs with
obesityref.
Levels of ghrelin, a potent stimulator of appetiteref1,
ref2,
ref3,
were higher in those with shorter sleep. Ghrelin levels
are also positively associated with hunger ratingsref,
but decrease with increased BMI. In one study, after 3 mo
of dietary supervision, a reduction in BMI of
approximately 5% was associated with a 12% increase in
ghrelin and a 15% decrease in leptinref.
These changes, in participants of similar BMI to our
sample and presumably producing increased appetite, are
comparable to those observed with sleep loss of 2–3
h/night. With sleep loss, however, relatively high ghrelin
and low leptin levels are associated with increased BMI.
These changes can be hypothesized to play a contributory,
rather than compensatory, role in the development of
overweight and obesity with sleep restriction. Hormone
measurements were all performed on a single fasted,
morning sample and may not reflect the 24-h profile. It is
possible that participants with shorter sleep woke up
earlier and that hormone differences may be partially
related to circadian time. Leptin and ghrelin levels rise
slightly during the nightref,
and this could result in higher hormone levels in short
sleepers. This may be an issue for ghrelin, as levels
increased with acute sleep restriction. It is, however,
unlikely to play a role in the leptin finding, since lower
levels were found with chronic but not acute sleep
restriction. Additionally, studies have shown a high
correlation between morning, fasting leptin and ghrelin
levels and 24-h mean profileref1,
ref2.
Ghrelin and leptin changes were unaffected by morningness
tendencies. The fact that studies investigating the
diurnal profile of these hormones found similar hormonal
changes over the entire 24-h period after experimental
sleep restriction also corroborates our resultsref.
The robustness of these findings and similar observations
from smaller controlled studiesref
also suggest that our statistically significant results
are unlikely to be a reflection of the number of analyses
carried out. Animal studies have suggested a link between
sleep and metabolismref.
In rats, prolonged, complete sleep deprivation increased
both food intake and energy expenditure. The net effect
was weight loss and, ultimately, deathref.
Rats fed a high protein-to-calorie diet had accelerated
weight loss, compared to sleep-deprived rats fed
calorie-augmented (fatty) diets. Food consumption remained
normal in sleep-deprived rats fed protein-rich diets, but
increased 250% in rats fed calorie-rich diets. Preference
for fatty foods has also been reported anecdotally in
sleep-deprived humans. Sleep deprivation may thus increase
not only appetite but also preference for lipid-rich,
high-calorie foods. Animal experiments that have found
weight loss after prolonged sleep deprivation have to be
interpreted in the context of a stressful procedure
producing intense sleep debtref1,
ref2,
which may interfere with adequate food intake. From our
study, we hypothesize that the moderate chronic sleep debt
associated with habitual short sleep is associated with
increased appetite and energy expenditure. In societies
where high-calorie food is freely available and
consumption uncontrolled, after milder chronic sleep
restriction, the equation may be tipped towards food
intake for high-calorie food rather than expenditure,
culminating in obesity. Short sleepers may also have more
time to overeat. Sleep loss from a baseline of 7.7 h was
associated with a dose-dependent increase in BMI. This was
the predominant effect in a population increasingly
curtailing sleepref.
Sleep > 7.7 h, however, was also associated with
increased BMI. Patients with SDB may spend a longer time
in bed to compensate for fragmented sleep; however,
controlling for AHI did not change the curvilinear
BMI–sleep association. Another possibility is that in long
sleepers, reduced energy expenditure due to increased time
in bed has a greater impact than reduced food intake. In
favor of this hypothesis, long sleepers exercise lessref.
The odds ratio of high levels of self-reported exercise
(>7 h/wk), based on a single survey question, decreased
with increased sleep time, but controlling for this
variable also did not change our findings. Insulin
resistance with sleep deprivation has been reported in a
laboratory study of young, healthy volunteersref.
When controlling for BMI, we found no significant
correlation between insulin, glucose, or adiponectin
levels and various measures of sleep duration. Also, there
was no significant correlation between QUICKI (or the
homeostatic model assessment HOMAref)
and sleep duration. This may be due to difficulties in
detecting small effects on glucose tolerance under
less-controlled conditions of large population studies.-resistance
and leptin-resistance
.
In vitro, human CRP directly inhibits the binding of
leptin to its receptors and blocks its ability to signal in
cultured cells. In vivo, infusion of human CRP into
ob/ob mice blocked the effects of leptin upon satiety and
weight reduction. In mice that express a transgene encoding
human CRP, the actions of human leptin were completely
blunted. Physiological concentrations of leptin can
stimulate expression of CRP in human primary hepatocytes.
Recently, human CRP has been correlated with increased
adiposity and plasma leptin. Thus, our results suggest a
potential mechanism contributing to leptin resistance, by
which circulating CRP binds to leptin and attenuates its
physiological functionsref. secretion =>
down-regulation of InsR, inhibition of NO
production by endothelial cells => insulin-resistance in
skeletal muscle => increased hepatic
synthesis of haptoglobin and hexokinase,
inhibition of NO production by endothelial cells levels than people of normal
weight, but production increases in people who have lost weight
through dieting. Many think that leptin's main role is
protecting against weight loss in times of deprivation rather
than against weight gain in times of plenty : when a person's
fat stores shrink, so does leptin incretion (in response,
appetite increases while metabolism decreases), but the converse
does not happen (beyond a certain point, increased leptin
production does little to inhibit appetite or increase
metabolism). .
Previous research, however, had only found CRP to be produced in
liver tissue, although Drs. Yeh, Willerson and Paolo Calabro,
MD, discovered in 2003 that the protein also is manufactured in
the walls of blood vessels. But that didn't explain obesity's
connection to high levels of CRP and it also was not clear why
CRP is higher in patients who have metabolic disorders. So the
research team decided to see whether fat cells themselves could
be stimulated by inflammatory cytokines or resistin to
produce CRP. To help find out, plastic surgery patients at M.D.
Anderson donated adipose tissue that would have been discarded,
and the research team then isolated fat cells, cultured them and
stimulated them under a number of different conditions. The
cells produced cytokines that resulted in inflammation and that
this process triggered production of high levels of CRP.
Resistin, produced itself by fat cells, could stimulate
production of CRP. Patients with metabolic syndromes have higher
levels of CRPs, as well as a higher risk of developing heart
disease and stroke, but no one understands why that is. Aspirin,
statins and troglitazone can reduce CRP levels in cultured fat
cells that were producing high levels of CRPsref
,
particularly among participants older than age 50 years,
for use > 90 days, or for diets < 20 g/d of
carbohydrates. Among the published studies, participant
weight loss while using low-carbohydrate diets was
principally associated with decreased caloric intake and
increased diet duration but not with reduced
carbohydrate contentref.
Indeed, a low carbohydrate diet appears to help patients
lose more weight than other diets up until the 6-month
mark. But by 1 year, the difference between
low-carbohydrate and low fat diets disappears. Doctors
should help patients choose a diet that helps them
reduce portion size and that includes a healthy eating
lifestyle they can stick to. Preliminary research on new
internet-based weight loss programs suggests the
technology may be a useful tool for some patients.
Overweight patients who have access to online weight
loss resources lost on average 1.6 kg over 6 months.
Subjects who also submitted calorie and exercise
information to an online bulletin board and received
weekly e-mail counseling and feedback lost considerably
more, or 4.1 kg over the same time periodref1,
ref2.
(atorvastatin 10 mg daily is safe and efficacious in
reducing the risk of first cardiovascular disease events
(acute coronary heart disease events, coronary
revascularisation, or stroke) by 33% (48% for stroke) and
death rate by 27% in patients with type 2 diabetes without
high LDL-cholesterol
(orlistat) interfere with fatty acid hydrolysis and uptake
by the gut, but produces only modest weight loss and may
have unwelcome side effects
allows the body to establish a new, svelter set point
(rimonabant : these receptors support "the munchies", the
food-craving effects of marijuana)ref1,
ref2,
ref3,
ref4.
Recently reported phase III clinical trails show that
2-year treatment with rimonabant reduced weight, reduced
abdominal fat, and improved cardiovascular risk factorsref1,
ref2.
The first in a new class of pharmaceutical agents,
rimonabant is promising as an anti-obesity therapy, but
its clinical value compared with that of existing
therapies must await results of future investigations..
Exendin-4 is a 39–amino acid peptide originally isolated
from the saliva of the Gila Monster that resists
degradation by DPP-IV while retaining GLP-1–like effects
on glucose metabolism and food intakeref.
Activity of GLP-1 is prolonged by conjugation to albumin
(liraglutide) or inhibition of DPP-IV
causes weight loss in diabetic cohorts, but its efficacy
in the general population is uncertain or
alternatively activation of PPAR, as suggested
by studies of OEA action, will await the results of
clinical trials.
=> lipolysis
replacement is effective in the rare cases of human leptin
deficiencyref,
but leptin resistance limits its utility in ordinary
obesity. Increasing leptin action by promoting its
transport into the brain or by antagonizing inhibitors of
leptin signaling pathways might be effective, but the
relevant pharmaceutical targets have proven challenging
acts through leptin-like pathways in the hypothalamus.
Although effective in animal models, human obesity trials
were limited by neutralizing antibodiesref.
blocking antibody not only reduces angiogenesis and tissue
growth but also inhibits preadipocyte differentiation :
part of this inhibition stems from the paracrine
interaction between endothelial cells and preadipocytes
and that VEGF-VEGFR2 signaling in endothelial cells, but
not preadipocytes, mediates this process.
(sibutramine) produce only modest weight loss and may have
unwelcome side effects
patients). ,
hypothalamic center manipulation, liposuction, balloon insertion,
unbanded gastric
partitioning, vagotomy, gastrogastrostomy,
horizontal gastroplasty,
gastric wrap, gastroclip, and any variety of gastroplasty
without a reinforced stoma, intestinal bypass, duodenal bypass
and biliointestinal bypassref.
All bariatric surgical procedures have been performed as open
and laparoscopic procedures.
(fig.A)
(fig.B)
(70% in USA) (fig.D)
(fig.C),
impaired immunocompetence, vitamin deficiency, expecially
thiamine with neuropathy/encephalopathy, hair loss,
gallstone formation; anemia, iron and vitamin B12
deficiency, dumping for gastric bypass
|
|
|
|
| gastric
banding (lap-band) |
|
|
| vertical
banded gastroplasty / silastic ring gastroplasty |
|
|
| gastric
bypass (Roux-en-Y anastomosis) |
|
|
| partial
pancreaticobiliary bypass / biliopancreatic
diversion (with/without duodenal switch) |
|
|
and
25% by pulmonary
embolism.
Laparoscopic gastric bypass is associated with fewer wound
complications, less postoperative pain, less blood loss, and
shorter hospital stays and convalescence periods than does the
open procedure; however, late anastomotic strictures occur
more frequently after the laparoscopic than after the open
procedure.
in premenopausal women
in postmenopausal women-resistance =>
hyperinsulinemia => type II diabetes
mellitus
=>.
Overweight children (age 5-23) are also at risk of heart
attacks : the greater the BMI, the greater the incidence
and severity of left ventricular mass or thickness.
=> gout
=> asthma
& hypercapnia => Pickwick
disease
/ pickwickian or obesity-hypoventilation syndrome
[from the description of Joe, the fat boy in Charles
Dickens' Pickwick Papers] : a complex of obesity,
somnolence, snoring, hypoventilation, and erythrocytosis incretion
(the issue is whether the tumor booster is insulin
resistance or hyperinsulinemia)
in postmenopausal women
=> endometrial
carcinoma
(controversial association; increases the risk for higher
grade prostate cancer and higher recurrence rates after
radical prostatectomy)
(demented women in their 80's are more likely to have an
average BMI of 28 at 70 years of age : each additional point
raises the risk of AD by 36%). Patients with diabetes can
experience anything from short-term memory loss to
Alzheimer's-like symptoms and leptin is the key. An
increasing number of reports show that abnormal levels of
leptin can significantly alter brain cell function :
intrahippocampal injection of leptin increases long-term
potentiation,
which provides a cellular basis for memory and learningref.
From studies of individual neurons isolated in a dish, the
amount of leptin produced by normal food intake in rats
boosts long-term potentiation by 3 times. But increasing the
dose 100-fold abolishes this effect. So could abnormally
high leptin levels in children with weight problems be
hindering their ability to perform in school? Given the
increasing incidence of obesity in the young, researchers
should investigate the potential link. Understanding the
role of leptin secretion in metabolic disorders will help
explain why these illnesses increase the risk of impaired
cognitive function. It may tell us about what goes wrong in
these diseases, which could serve as targets for treatments.