disorders of the hypothalamic-pituitary- adrenal axis georgiana cionanca, noemie lemetayer, nada...
Post on 19-Jan-2016
217 Views
Preview:
TRANSCRIPT
DISORDERS O
F TH
E
HYPOTH
ALAMIC
-
PITU
ITARY-A
DRENAL AXIS
GE
OR
GI A
NA
CI O
NA
NC
A, N
OE
MI E
LE
ME
TA
YE
R, N
AD
A H
AK
I MI
Under the supervision of Miklós Jászberényi
TABLE OF CONTENTS
- Introduction-Physiology of the HPA axis
- Discussion -Hypoactivity of the HPA axis-Hyperactivity of the HPA axis
- Conclusion
STRESS SYSTEM
Stressors -> Activation of the sympathetic-adrenal-medullary axis hypothalamic-pituitary-adrenal axis
General Adaptation Syndrome (Hans Selye, 1936)1. Alarm stage
2. Resistance stage
3. Exhaustion stage
PHYSIOLOGY OF THE HPA AXIS
Cerebral cortex
STRESS
Physical EmotionalBiochemicalDiurnal rhythms
Hypothalamus
Corticotropin-releasing hormone
CRH
Parvocellular neurons in the hypothalamus synthesize and secrete
Long portal vessels carry CRH Anterior Pituitary Gland
ACTH
Adrenal Cortex
CORTISOL
Negative feedback
Negative feedback
Short Feedback
CORTISOL EFFECTS
Retrived from S. Melmet, K. S. Polonsky, P. R. Larsen, H. M. Kronenberg, Williams textbook of endocrinology, 12th edition, Elsevier Saunders, 2011
Brain/CNS: Depression Psychosis
Carbohydrate/lipid metabolism: ↑ Hepatic glycogen deposition ↑ Peripheral insulin resistance ↑ Gluconeogenesis ↑ Free fatty acid production Overall diabetogenic effec
Adipose tissue distribution: Promotes visceral obesity
Bone and calcium metabolism: ↓ Bone formation ↓ Bone mass Osteoporosis
Skin/muscle/connective tissue: Protein catabolism/collagen breakdown Skin thinning , Muscular atrophy
Endocrine system: ↓ LH, FSH release ↓ TSH release ↓ GH secretion
Eye: Glaucoma
GI tract: Peptic ulcerations
Cardiovascular/renal: Salt and water retention Hypertension
Growth and development: ↓ Linear growth
Immune system: Anti-inflammatory action Immunosuppression
STRESSOR
Activation of the HPA axis
Antireproductive Antigrowth Catabolic Immunosuppresive
effects
Essential for survival
Hazardous effects on long-term activation
Hypoactivity
Hyperactivity
DISORDERS OF THE HPA AXIS
HYPOACTI
VITY
OF HPA
AXIS
• ADRENOCORT ICAL INSUFF IC IENCY
• CONGENITAL ADRENAL HYPERPL AS IA
Primary Adrenal Insufficiency
(Adrenal Failure)
Chronic(Addison disease)
Acute
- Stress in a chronic PAI history
- Exogenous corticosteroids with acute stress
- Massive adrenal hemorrhage
- Tuberculosis- AIDS- Metastatic
cancers- Autoimmune
adrenalitis (APS1, APS2)
Secondary Adrenal
Insufficiency
Lack of production of
ACTH
Destruction by autoAB of key
enzymes involved in the
steroidogenesis for instance 21-
OH or 17-OH
CLINICAL ASPECT
Glucorticoid and
mineralocorticoid deficiency
Skin pigmentation (sun-exposed
areas and pressure points)
PAI Glucocorticoid deficiency but intact
RAA
No skin pigmentati
on
SAI
Anorexia nausea, vomiting, diarrhea, +/- abdominal pain. +/-Fever and hypoglycemia
TREATMENT- Glucocorticoid
replacement in 2 or 3 divided doses
- +/- Mineralocorticoid
ISSUES…- Mimic the
physiologic cortisol secretion rythm
- Reduce adverse effects
- Adrenal crisis
DIAGNOSIS:- ACTH stimulation test measures of plasma
cortisol level- Radioimmunoassays to detect autoantibodies
CONGENITAL ADRENAL HYPERPLASIASimple Virilizing FormSalt-
Wasting Form
Non classic Form
Mutation CYP21A2
with CYP21A1
P
Retrived from V. Kumar, A. K. Abbas, N. Fausto, J. C. Aster, Pathologic Basis of disease, Robbins and Cotran (2010), 1153
Diagnosis
Treatment- Long-term
glucocorticoid treatment
- Goal: to use the lowest dose of GCC
- Short half-life hydrocortisone preferred but single daily dose ineffective…
- to optimize the treatment and its consequences with the patient’s specificities
Measu
re o
f
eleva
ted
seru
m le
vels
of 1
7-OHP
(>10, 0
00
ng/dL)
Basal measure of 17-OHP and 60 min after Synacthen injection CYP21A2
genotyping
NOVEL TREATMENT, GENE THERAPY?
Single intra-adrenal injection of an adenoviral vector encoding CYP21A2 which may compensate for the biochemical, endocrine and histological alterations in 21OH-deficient mice
Retrieved from: http://fr.dreamstime.com/photo-stock-laboratoire-de-rat-image34061020
HYPERACTI
VITY
OF HPA
AXIS• CUSH ING ’S
SYNDROME• MULT IPLE
ENDOCRINE NEOPL AS IA TYPE 1
CAUSES OF CUSHING’S SYNDROME
Iatrogenic originGlucocorticoids are
routinely used to fight inflammatory diseases
Endogenous origin- Cushing’s disease- Ectopic corticotropin syndrome- Adrenocortical tumors
DEFINITION OF CUSHING’S SYNDROME
Cushing’s syndrome refers to the clinical manifestations induced by chronic exposure to excess glucocorticoids.
from David N. Orth, m.d., Cushing’s Syndrome The New England Journal of Medicine, 1995
CLINICAL FINDINGS• Centripetal fat distribution
• Tissue fragility• Easily scratched skin• Wide and purple striae• Wide ecchymotic lesions
• Protein wasting features• Muscle wasting, great weakness• Osteoporosis
• Immunodeficiency• High blood pressure• Disturbances of the gonadotropic
axis• Psychiatric disorders
From "Adrenal Cortex." In Williams Textbook of Endocrinology. 12th ed.
TREATMENTS
• Surgical removal of the tumor with medical treatments.
• In Cushing’s disease transsphenoidal surgery has very good outcomes
DIAGNOSIS
Cushing’s syndrome24h urinary cortisol
Late night serum or salivary samples
Suppression tests
ACTH-dependentHigh plasma ACTH
level
Cushing’s diseasePituitary
MRI shows adenoma
Ectopic ACTH
secretionLow ACTH level
in petrosal sinus blood
sample
ACTH-independent
Low plasma ACTH level
Adrenal tumorCT scan
MULTIPLE ENDOCRINE NEOPLASIA TYPE 1
Rare autosomal dominant hereditary disease.
Tumors develop in endocrine tissues polyendocrine syndromes
• Parathyroid glands (HPT)
• Pancreatic islets (Gastrinomas)
• Anterior pituitary• Prolactinomas• ACTH adenomas: Cushing’s disease
• Adrenals glands• Cortisol adenomas: Cushing’s syndrome• Aldosterone tumors: Conn’s syndrome
Hyperactivity of HPA axis
TAKE HOME MESSAGES
• The ‘General Adaptation Syndrome’ describes the body’s reaction to a stressor
• The HPA axis mediates the stress response through a chain of hormones
• Adrenocortical insufficiency can be primary or secondary depending on the localization of the impairment.
• Congenital Adrenal Hyperplasia is caused by mutations in key enzymes involve in the steroidogenesis.
• Spontaneous Cushing’s syndrome can be either ACTH-dependent or ACTH-independent.
• MEN1 induce polyendocrine syndromes such as hyperactivity of HPA axis
Thank you for your attention
top related