)
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 concentr