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Blwyddyn 1; Tymor 3 > 128; Adrenal Endocrine > Flashcards

128; Adrenal Endocrine Flashcards

1
Q

What is Cushing’s syndrome?

A

The clinical state of increased free circulating glucocorticoid.

Often due to administration of synthetic steroids or ACTH

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2
Q

What is Cushing’s disease?

A

Increased circulating ACTH from the pituitary

(65% of cases)

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3
Q

What causes Cushing’s syndrome?

A

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
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4
Q

From where is ACTH released?

A

The anterior pituitary gland

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5
Q

What is the role of ACTH?

A

Stimulates secretion of Glucocorticoids from the adrenal gland. ee Cortisol, Corticosterone

(From the Zona fesciculata)

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6
Q

What are the signs and symptoms of Cushing’s disease?

A

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
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7
Q

What investigations should be arranged to diagnose Cushing’s Syndrome?

A

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
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8
Q

How do plasma ACTH concentration measurements at 0900 differe between in the different causes of Cushing’s Syndrome?

A

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
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9
Q

Briefly outline the cortisol synthetic pathway

A

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

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10
Q

How is Cushing’s syndrome treated?

A
  • Metyrapone
  • Adrenalectomy surgery

Metyrapone inhibits steroid 11β-hydroxylase, blocks Cortisol synthetic pathway.

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11
Q

How does Metyrapone treat Cushing’s syndrome?

A

Blocks the synthetic pathway od cortisol

Prevents conversion of 11-deoxy-cortisol to cortisol

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12
Q

What is Congenital Adrenal Hyperplasia?

(CAH)

A

Autosomal recessive deficiency of enzymes in the cortisol synthetic pathway.

Most commonly 21-hydroxylase.

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13
Q

What is the most common type of congenita ladrenal hyperplasia?

A

21-hydroxylase deficiency

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14
Q

How does congenital adrenal hyperplasia affect cortisol and ACTH levels?

A

Cortisol levels are low;

Secretion is reduced leading to reduced negative feedback on pituitary —>

Increased ACTH secretion from pituitary

Acts on adrenals causing hyperplasia

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15
Q

How does the increased ACTH levels affect synthesis of other steroid hormones from the adrenals?

A

Steroid precursors of Cortisol diverted into the androgenic precursor pathway

Causing increased:

  • 17-hydroxy progesterone
  • Androstenedione
  • Testosterone

**** Aldosterone **synthesis mey be impaired**

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16
Q

What are the clinical manifestations of Cong. Adre. Hyperplasia?

A

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

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17
Q

How is CAH treated?

A

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

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18
Q

What would be found on investigation of a patient w/ CAH?

A
  • Increased 17-hydroxyprogesterone
  • Increased Urinary Pregnanetriol excretion
  • Raised basal ACTH levels

LH, FSH, testosterone levels normal

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19
Q

What is Addison’s disease?

A

Primary hypoadrenalism

20
Q

Describe the main hormobe levels affected in Addison’s disease

A

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)

21
Q

List some causes of Addison’s disease

A
  • Autoimmune (90%)
    • Polyendocrine insufficiency syndrome
  • TB
  • Metastatic tumour
  • Lymphoma
  • Amyloidosis
  • Haemochromatosis
  • Bilateral adrenalectomy
  • Adrenal infarction
  • AIDS
22
Q

What is the most common antigen in autoimmune Addison’s?

A

21-hydroxylase

Causes adrenalitis; destruction of adrenal cortex

23
Q

What are the signs and symptoms of Addison’s disease?

A

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
24
Q

What investigations are used to diagnose Addison’s?

A
  • 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
25
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
26
What are the different types of hypertension?
1. Primary/Essential hypertension (no identifiable cause) 2. Renal hypertension 3. Primary Hyperaldosteronism 4. Rare causes
27
What are the causes of Secondary hypertension?
**Renal hypertension** * Renovascular * Renal parenchymatous disease * Primary reninism **Primary hyper**_aldosteron_**ism** * Unilateral adrenal adenoma * Bilateral hyperplasia of Zona Glomerulosa **Rare causes** * Phaeochromocytoma * Cushing's Syndrome * Coarctation of the aorta
28
What is **Conn's** syndrome?
A type of primary hyper**aldosteron**ism; From an aldosterone-producing tumour
29
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
30
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
31
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
32
What investigations are used to diagnose Conn's disease?
Aldosterone:renin ratio Increased CT scan adrenals Adrenal venous sampling
33
What are possible treatments for Conn's disease?
* Adrenalectomy * Low sodium diet * Spironolactone
34
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
35
How are hormone levels altered in a person w/ paeochromocytoma?
Increased levels of **noradrenaline** and, to a lesser extent, adrenaline.
36
What are the signs and symptoms of Phaeochromocytoma?
Headache Flank pain Tachycardia Hypertension & postural hypotension Palpitations Sweating Hyperglycaemia
37
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
38
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.
39
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
40
What signs indicate a paheochromocytoma?
Hypertension * Accelerated * Progressive * Resistant * Paroxysmal (intermittent) * In a young person Paradoxical response to ß-blocker Family Hx
41
What are the associated symptoms of phaeochromocytoma?
* Multiple Endocrine neoplasio Type1 * Multiple Endocrine Neoplasia Type 2a & 2b * (MEN) * Von-Hippel-Lindau syndrome * Phakomatoses * Neurofibromatosis
42
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
43
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)
44
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
45
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
46
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

Blwyddyn 1; Tymor 3 (13 decks)

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