128; Adrenal Endocrine Flashcards
What is Cushing’s syndrome?
The clinical state of increased free circulating glucocorticoid.
Often due to administration of synthetic steroids or ACTH
What is Cushing’s disease?
Increased circulating ACTH from the pituitary
(65% of cases)
What causes Cushing’s syndrome?
ACTH dependent
- Increased ACTH secretion from pituitary (Cushing’s disease)
- Increased ACTH from an ectopic tumour
- ACTH administration
Non ACTH dependent
- Adrenal adenomas
- Adrenal carcinomas
- Glucocorticoid administration
Other causes
- Alcohol induced pseudo-Cushing’s syndrome
From where is ACTH released?
The anterior pituitary gland
What is the role of ACTH?
Stimulates secretion of Glucocorticoids from the adrenal gland. ee Cortisol, Corticosterone
(From the Zona fesciculata)
What are the signs and symptoms of Cushing’s disease?
Symptoms
- Central weight gain
- Depression
- Insomnia
- Amenorrhoea/oligomenorrhoea
- Thin skin/easily bruised
Signs
- Moon face
- Hersutism
- Acne
- *Thin skin & bruising
- *Hypertension
- *Pathological fractures (vertebrae & ribs)
- Central obesity % striae
- *Proximal myopathy
- Oedema
- *Striae
What investigations should be arranged to diagnose Cushing’s Syndrome?
Confirmation requires demonstration of inappropriate cortisol secretion, which is not supressed by exogenous glucocorticoids
- 48H (or over-night) low does dexamethasone test:
- A synthetic steroid
- Normal to supress plasma cortisol to <50nmol/l.
- Cushing’s ptx fail to do this (259nmol/l)
- 24H urinary free cortisol measurements
- Normal values excludes Cushing’s
- Circadian Cortisol
- Normal to be low at 2400H
- Always high in Cusching’s
- CT Adrenals
- CT pituitary
How do plasma ACTH concentration measurements at 0900 differe between in the different causes of Cushing’s Syndrome?
Cushing’s disease
- Mid-range; 50-200 ng/l
Adrenal Tumour
- Very low levels; around 0ng/l
Ectopic ACTH
- Highest measurement, largest range; 100-4000 ng/l
Briefly outline the cortisol synthetic pathway
Cortisol is a steroid hormone, a glucocorticoid, synthesised and released by the zona fesciculata of adrenal gland.
- Cholesterol –>
- Pregnenolone –>
- Progesterone –>
- 17a- hydroxy progesterone –>
- 11-deoxy-cortisol –>
- Cortisol
Synthesis is initiated by ACTH
How is Cushing’s syndrome treated?
- Metyrapone
- Adrenalectomy surgery
Metyrapone inhibits steroid 11β-hydroxylase, blocks Cortisol synthetic pathway.
How does Metyrapone treat Cushing’s syndrome?
Blocks the synthetic pathway od cortisol
Prevents conversion of 11-deoxy-cortisol to cortisol
What is Congenital Adrenal Hyperplasia?
(CAH)
Autosomal recessive deficiency of enzymes in the cortisol synthetic pathway.
Most commonly 21-hydroxylase.
What is the most common type of congenita ladrenal hyperplasia?
21-hydroxylase deficiency
How does congenital adrenal hyperplasia affect cortisol and ACTH levels?
Cortisol levels are low;
Secretion is reduced leading to reduced negative feedback on pituitary —>
Increased ACTH secretion from pituitary
Acts on adrenals causing hyperplasia
How does the increased ACTH levels affect synthesis of other steroid hormones from the adrenals?
Steroid precursors of Cortisol diverted into the androgenic precursor pathway
Causing increased:
- 17-hydroxy progesterone
- Androstenedione
- Testosterone
**** Aldosterone **synthesis mey be impaired**
What are the clinical manifestations of Cong. Adre. Hyperplasia?
Sexual ambiguity & adrenal failure at birth (if severe)
- Hypotension, collapse, hypoglycaemia, hyponatraemia
In females; clitoromegaly (signs may be more difficult to notice in males)
Short stature
Precocious puberty & hirsutism
- Hirsutism befor puberty is a sign of CAH
Later-life presentation; rare, milder
How is CAH treated?
Replacement of glucocorticoid activity, and mineralocorticoid deficiency if deficient
- Fludrocortisone
- Hydrocortisone
- Dexamethasone at night to treat adult hirsuritism
- Corrective surgery
ee Dexomethasone, Oestrogen and Cyproterone
What would be found on investigation of a patient w/ CAH?
- Increased 17-hydroxyprogesterone
- Increased Urinary Pregnanetriol excretion
- Raised basal ACTH levels
LH, FSH, testosterone levels normal
What is Addison’s disease?
Primary hypoadrenalism
Describe the main hormobe levels affected in Addison’s disease
A destruction in entire adrenal cortex causes reduction in:
- Mineralocorticoids (Aldosterone)
- Glucocorticoids (Cortisol)
- Androgens (Testosterone)
Reduction in Cortisol causes increased CRH & ACTH from pituitary
(CRH; corticotropin-releasing hormone
ACTH; Adrenocorticotropic hormone)
List some causes of Addison’s disease
- Autoimmune (90%)
- Polyendocrine insufficiency syndrome
- TB
- Metastatic tumour
- Lymphoma
- Amyloidosis
- Haemochromatosis
- Bilateral adrenalectomy
- Adrenal infarction
- AIDS
What is the most common antigen in autoimmune Addison’s?
21-hydroxylase
Causes adrenalitis; destruction of adrenal cortex
What are the signs and symptoms of Addison’s disease?
Symptoms
- Weight loss
- Anorexia
- Fatigue & malaise
- Amenorrhoa/impotence
- Syncope from postural hypotension
Signs
- *Hyperpigmantation; new scars and palmar tissue (because of ACTH)
- *Postural hypotension
- Dehydration
- Loss of hair
What investigations are used to diagnose Addison’s?
- U&E
- HyperKalaemia, HypoNatraemia
- Random Cortisol measurement
- <100nmol/l is suggestive
- 0900 plasma ACTH levels
- High ACTH and low Cortisol is suggestive
- Blood glucose
- Hypoglycaemic
- Chest/Abdo Xrays
- Evidence of TB or calcified adrenals
- Adrenal Antibodies
- Positive
What is the treatmeny for Addison’s disease?
Acute hypoadrenalism requires urgent treatment
Similar treatment to Congenital adrenal hypertrophy
- Replacement Glucocorticoid & Mineralocorticoid
Prior to results; Dexamethasone
Following:
- Hydrocortisone
- Fludrocortisone
- Education; steroid card; medic alert bracelet
What are the different types of hypertension?
- Primary/Essential hypertension (no identifiable cause)
- Renal hypertension
- Primary Hyperaldosteronism
- Rare causes
What are the causes of Secondary hypertension?
Renal hypertension
- Renovascular
- Renal parenchymatous disease
- Primary reninism
Primary hyperaldosteronism
- Unilateral adrenal adenoma
- Bilateral hyperplasia of Zona Glomerulosa
Rare causes
- Phaeochromocytoma
- Cushing’s Syndrome
- Coarctation of the aorta
What is Conn’s syndrome?
A type of primary hyperaldosteronism;
From an aldosterone-producing tumour
What are the characteristic features of Conn’s disease?
(Investigations)
- Hypertension
- HypoKalaemia
- & Urinary K+ loss
- HyperNatraemia
- Elevated plasma aldosterone:renin activity ratio
- Elevated plasma Aldosterone levels
- Decreased plasma Renin levels
List the steps that lead to hypertension in primary hyperaldosteronism & Conn’s disease?
Adrenal tumour
Increased Aldosterone
- Sodium retention
- Potassium lost
Na retention causes
- Hypertension
- Renin supression
Decreased levels of Angiotensin II
What is the epidemiology of Primary Hyperaldosteronism
60% Bilateral adrenal hyperplasia
40% Conn’s disease, adrenal adenoma
_______________________________
5-10% of Hypertensives
More common in young patient w/o FHx of hypertension
More likely to be Conn’s if severe hypertension
What investigations are used to diagnose Conn’s disease?
Aldosterone:renin ratio
Increased
CT scan adrenals
Adrenal venous sampling
What are possible treatments for Conn’s disease?
- Adrenalectomy
- Low sodium diet
- Spironolactone
What is a Phaeocromocytoma?
Tumour of the sympathetic nervous system;
Vast majority occur in the adrenal medulla
80% unilateral adrenal
10% bilateral adrenal
10% extra-adrenal
How are hormone levels altered in a person w/ paeochromocytoma?
Increased levels of noradrenaline and, to a lesser extent, adrenaline.
What are the signs and symptoms of Phaeochromocytoma?
Headache
Flank pain
Tachycardia
Hypertension & postural hypotension
Palpitations
Sweating
Hyperglycaemia
What investigations are done to investigate Phaeochromocytoma?
Blood glucose level
Catecholamines stimulate glycolysis, increased free fatty acids, decreased glucose uptake in tissues.
24H urine catecholamines
2X higher than normal
24H urine adrenaline
Higher than normal
What is the management for Phaeochromocytoma?
- ß-blockers, à blockade, high salt diet
- Adrenalectomy
à blockade prior to ß blockade (starting with ß can cause paradoxical elevation in blood pressure)
Chronic hypertension has reduced the sensitivity of the RAAS pathway leading to decreased Aldosterone –> increased Na excretion –> H2O loss… High salt diet required.
What are the common features of phaeochromocytomas?
Mainly Right-sided
80% unilateral
10% bilateral
10% extra-renal
10% Malignant
Size is unrelated to symptoms
Malignant if the metastasise to non-chromaffin cells
What signs indicate a paheochromocytoma?
Hypertension
- Accelerated
- Progressive
- Resistant
- Paroxysmal (intermittent)
- In a young person
Paradoxical response to ß-blocker
Family Hx
What are the associated symptoms of phaeochromocytoma?
- Multiple Endocrine neoplasio Type1
- Multiple Endocrine Neoplasia Type 2a & 2b
- (MEN)
- Von-Hippel-Lindau syndrome
- Phakomatoses
- Neurofibromatosis
Summarise the Causes, investigations and treatment of Cushing’s syndrome.
Causes:
- iatrogenic
- pituitary tumour (ACTH)
- adrenal tumour
- ectopic ACTH secretion
Investigations:
- 9 am cortisol after Dexamethasone at midnight
- 9 am ACTH
- 24hr urinary free cortisol
- Radiology
Treatment:
- Metyrapone then Pituitary or adrenal surgery
- Oncology therapy
Summarise the Causes, investigations and treatment of Congenital Adrenal Hyperplasia.
Causes:
- 21 hydroxylase deficiency. Most common type, non classic, late onset
Investigation:
- 17αOH progesterone before and after synacthen
Treatment:
- Dexamethasone (adults)
- Cyproterone and oestrogen
- Fludrocortisone
- Hydrocortisone (salt wasters)
Summarise the Causes, investigations and treatment of Addison’s Disease.
Causes:
- autoimmune
- TB
- adrenal infiltration
Investigations:
- inadequate cortisol response to synacthen
- elevated ACTH
- U & Es
- glucose
Treatment:
- Hydrocortisone
- Fludrocortisone
Summarise the causes, investigations and treatments of Conn’s syndrome
Causes:
- adrenal hyperplasia
- adrenal adenoma
Investigations:
- 9 am rennin (low), aldosterone (high)
- U & Es
- CT/MRI/MIBG scan
Treatment:
- laparoscopic or open adrenalectomy
- Spironolactone
Summarise the causes, investigations and treatments of phaeochromocytoma.
Causes:
- Adrenal tumour
- 10% of patients extra-adrenal tumour
Investigations:
- Elevated 24hr urinary catecholamine levels
Treatment:
- Adrenal surgery after α and ß blockade and high salt diet
