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0

What do the adrenal glands produce?

Glucocorticoids (cortisol) affect carbohydrate, lipid and protein metabolism

Mineralocorticoids (aldosterone) control sodium and potassium balance

Androgens (sex hormones) are peripherally converted into testosterone and dihydrotestosterone

1

What controls the release of cortisol from the adrenal glands?

Corticotropin -releasing factor from the hypothalamus stimulates ACTH secretion from the pituitary gland, and it is this that stimulates cortisol release from the adrenal cortex.

The cortisol is excreted as urinary free cortisol and 17-oxogenic steroids

2

What is cushing's syndrome?

Clinical state produced by chronic glucocorticoid excess and loss of the normal feedback mechanisms.

Increased weight, mood changes, proximal weakness, gondal dysfunction, acne.
Plethoric moon face, buffalo hump, supraclavicular fat distribution, skin and muscle atrophy, easy bruising, abdominal striae, osteoporosis, hypertension, glucose tolerance, decreased immunity, poor healing

3

What are the causes of Cushing's syndrome?

Cushing's disease - bilateral adrenal hyperplasia from a ACTH secreting pituitary adenoma.
8mg dexamethasone test may halve morning cortisol

Ectopic ACTH production - small cell lung cancer, carcinoid tumours. Often have increased pigmentation (due to ACTH), hypokalaemic metabolic alkalosis, weight loss, hyperglycaemia.
High dose dexamethosone will fail to suppress cortisol production.

Adrenal adenoma - no dose of dexamethasone will suppress the cortisol

Adrenal nodular hyperplasia - no dose of dexamethasone will suppress the cortisol

Iatrogenic - pharmacological doses of steriods

Rarely - Carney complex, McCune Albright syndrome

4

What is the dexamethasone suppression test?

Overnight suppression test - give 1mg PO at midnight and do a serum cortisol at 8am.
If normal the high dose causes -ve feedback so decrease ACTH and decrease cortisol production to s disease. Any ectopic site of production is not under feedback control so will no be reduced.

5

Which disease causes a reduction in the ACTH?

Adrenal tumour

6

How do you treat Cushing's Syndrome?

Treat the cause

Iatrogenic - reduce oral intake of steroids
Cushing's disease - remove the pituitary tumour
Adrenal adenoma - adenalectomy + radiotherapy if cancer
Ectopic ACTH - surgery if tumour is accessible and hasnt spread.
Metyrapone, ketoconazole and fluconazole can be used in the short term to decrease steroid production pre op

7

How does parathyroid hormone work?

Responds to low calcium.

1. increases osteoclast activity releasing Ca and PO4 from the bone
2. increases Ca and decreases PO4 reabsorption in the kidney
3. active 1,25 dihydroxy - vitamin D3 production is increased.

Overall = increased Ca and decreased PO4

8

What is primary hyperparathryroidism?

Increased release of parathyroid hormone due to adenoma in most cases, can be due to hyperplasia of al the glands or parathyroid cancer.

Causes high Ca with high PTH, low PO4 and high ALP (due to increased bone turn over)

9

What are the indications for surgery in primary hyperparathyroidism?

high serum or urinary calcium
bone disease - osteoporosis
renal calculi
decreased renal function
<50yrs

if only mild disease keep well hydrated, and avoid thiazides and supplementary Ca and vit D

10

What is secondary hyperparathryoidism?

Low calcium with high PTH - appropriate (the PTH is high to try and raise the Ca)
Caused by low vitamin D intake, renal failure.

11

What is tertiary hyperparathyroidism?

High calcium and very high PTH (inappropriate). This is caused by prolonged secondary hyperparathyroidism, the glands begin to act autonomously having undergone hyperplastic or adenomatous change.

Seen in CKD

12

When would your calcium be high but PTH be low?

In malignant hyperparathryoidism - maliginacies can produce parathyroid related protein which causes Ca to increase but it is not picked up in the assay so the PTH appears low.
Squamous cell lung, breast and renal cell carcinomas can cause it

14

What are the clinical signs of hypothyroidism?

Bradycardia
Reflexes relax slowly
Ataxia
Dry thin hair
Yawning (drowsiness etc)
Cold hands
Ascites
Round puffy face
Defeated demeanour
Immobile
CCF

15

What are the causes of hypothyroidism?

Autoimmune:
Primary atrophic hypothyroidism - no goitre as due to diffuse infiltration that leads to atrophy
Hashimoto's - goitre present, more common in women, may have an initial period of hyperthyroidism

Post thyroidectomy or radio iodine treatment
Drug induced - amiodarone, lithium, iodine
Subacute thyroiditis - temporary hypothyroidism after a hyperthyroid phase.
Iodine deficiency
Panhypopituritarism (very rare, causes secondary hypothyroidism)

16

Which conditions are associated with hypothyroidism?

Turners and downs syndrome
Cystic fibrosis
Primary biliary cirrhosis
Ovarian hyper-stimulation
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, m protein band, skin pigmentation)

17

Why does amiodarone cause thyroid problems?

It is rich in iodine and structurally like T4.
Hypothyroidism can result from toxicity from iodine excess.
Thyrotoxicosis can occur due to destructive thyroiditis (hormone release)

18

What is subclinical hypothyroidism?

TSH >4 with normal T4 and T3 and no symptoms.

Need to check TSH in 2-4months
Check history for any symptoms of hypothyroidism - discuss treating to improve QoL
Have a low threshold to treat if: TSH >10, +ve antibodies, past Graves,

19

What are the signs and symptoms of hypercalcemia?

Bones, stones, groans and psychic moans

Abdominal pain, vomiting, constipation, polyuria, polydipsia, depression, anorexia, weight loss, tiredness, weakness, hypertension, confusion, pyrexia, renal stones, renal failure, ectopic calcification, cardiac arrest.
QT interval shortened.

20

What are the differential diagnoses for Hirsutism?

Constitutional
Drugs - ciclosporin, minoxidil
Cushing's syndrome
Congenital adrenal hyperplasia
Androgen - secreting tumour
Hypothyroidism
PCOS

21

What is diabetes insipidus?

The passsage of large volumes (>3L/day) of dilute urine due to impaired resorption by the kidney due to reduced ADH secretion from the posterior pituitary or impaired response of the kidney to ADH

22

What are the causes of diabetes insipidus?

Central:
Idiopathic
Congenital - defects in the ADH gene, DIDMOAD
Tumour - craniopharyngioma, metastases, pituitary tumour
Trauma
Hypophysectomy
Autoimmune hypophysitis
Infiltration - histiocytosis, sarcoidosis
Vascular - haemorrhage (sheehans syndrome)
Infection

Nephrogenic:
Inherited
Metabolic - low K, high Ca
Drugs - lithium
CKD
Post obstructive uropathy

23

How can you differentiate between central and nephrogenic diabetes inspidius?

On the 8 hour water deprevation test central DI results in an urine osmolaity increasing to >600 after desmopressin.
In nephrogenic DI no increase in urine osmolaity

24

What is Addison's disease?
What are the symptoms and signs?

Primary adrenocorticoid insufficiency.
Destruction of the adrenal cortex results in cortisol and mineralcorticoid deficiency

SYMPTOMS:
Lean, tanned, tearful, weak, anorexia, dizzy/ faints, arthralgia's. N+V, abdopain.

SIGNS:
Pigmented palmar creases and buccal mucosa, postural hypotension.
Low Na, high K, low glucose, high calcium, eosinophila, anaemia

25

What is secondary adrenal insufficiency?

It is a condition that occurs due to long term steroid use. The patients own adrenal glands become supressed by the use of exogenous steroids so when the steroids are reduced they have a deficiency of cortisol.

Can occur when patients are weaned off steroids too quickly or when the cortisol requirement becomes increased due to sepsis, cancer etc.

There is no mineralcorticoid effects, as this part of the axis is not interrupted.

26

What is Addison's disease?
What are the symptoms and signs?

Primary adrenocorticoid insufficiency.
Destruction of the adrenal cortex results in cortisol and mineralcorticoid deficiency

SYMPTOMS:
Lean, tanned, tearful, weak, anorexia, dizzy/ faints, arthralgia's. N+V, abdopain.

SIGNS:
Pigmented palmar creases and buccal mucosa, postural hypotension.
Low Na, high K, low glucose, high calcium, eosinophila, anaemia

80% caused by autoimmune disease, +ve for 21, hydroxylase adrenal autoantibodies.

27

What is secondary adrenal insufficiency?

It is a condition that occurs due to long term steroid use. The patients own adrenal glands become supressed by the use of exogenous steroids so when the steroids are reduced they have a deficiency of cortisol.

Can occur when patients are weaned off steroids too quickly or when the cortisol requirement becomes increased due to sepsis, cancer etc.

There is no mineralcorticoid effects, as this part of the axis is not interrupted.

Treating with IV hydrocortisone improves patients when they are in crisis.

28

What is sick euthyroidism?

When patients are systemically unwell TFTs may become deranged. Most commonly everything will be low.
Low TSH, low T4 and Low T3.

Tests should be repeated after recovery

29

What does TPO (antithyroid peroxidase) auto antibody suggest?

That there is an autoimmune process occurring.
Can be +ve in Hashimotos or Graves', but if +ve in Graves there is an increased risk of the patient becoming hypothryroid at a later stage.

30

Who needs to be screened for abnormal thyroid function?

Patients with Atrial Fibrillation
Patients with hyperlipidaemia
Patients with DM, annually
Women with T1DM during 1st trimester and post partum
Patients on amiodarone or lithium - 6monthly
Patients with Downs, Turners or Addisons