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Flashcards in Endocrinology Deck (130)
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Which hormones does the anterior pituitary gland release ?

- Thyroid stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
- Follicle stimulating hormone (FSH) and luteinising hormone (LH)
- Growth hormone (GH)
- Prolactin


Which two hormones does the posterior pituitary gland release ?

- Antidiuretic hormone (ADH)
- Oxytocin


The hypothalamus releases thyrotropin-releasing hormone (TRH). This stimulates the anterior pituitary to release thyroid stimulating hormone (TSH). This in turn stimulates to thyroid gland to release what ?

Triiodothyronine (T3) and thyroxine (T4)


What effect do T3 and T4 have on the hypothalamus and anterior pituitary? What type of feedback is this ?

They suppress the release of TRH and TSH resulting in lower amounts of T3 and T4. If there are lower levels of T3 and T4 there is less suppression of TRH and TSH thus T3 and T4 levels go up. This is negative feedback.


The hypothalamus releases corticotrophin release hormone (CRH), what other hormones does this stimulate ?

CRH > Adrenocorticotropic hormone (ACTH) > Cortisol


What type of feedback controls the adrenal axis ?

Negative feedback


Cortisol is released in pulses and in response to stressful stimuli (it is a "stress hormone"). It has diurnal variation where it typically peaks in the morning and is at its lowest rate in the evening. Name 5 actions of cortisol within the body ?

-Inhibits the immune system
-Inhibits bone formation
-Raises blood glucose
-Increases metabolism
-Increases alertness


Growth hormone axis ?

Growth hormone releasing hormone (GHRH) is released from the hypothalamus > This stimulates growth hormone (GH) release form the pituitary > Growth hormone stimulates the release of insulin-like growth factor 1 (IGF-1) from the liver.


4 main functions of growth hormone ?

-Stimulates muscle growth
-Increases bone density and strength
-Stimulates cell regeneration and reproduction
-Stimulates growth of internal organs


Parathyroid hormone (PTH) is released form the four parathyroid glands usually in response to what + what else can it be released in response to?

Low serum calcium. It is also released in response to low magnesium and high serum phosphate.


Role of PTH ?

To increase serum calcium concentration


Name 3 ways that PTH increases serum calcium concentration ?

- PTH increases the activity and number of osteoclasts in bone, causing reabsorption of calcium from the bone into the blood thereby increasing serum calcium concentration
- PTH stimulates an increase in calcium reabsorption in the kidney meaning that less calcium is excreted in the urine
- PTH also stimulates the kidneys to convert vitamin D3 into calcitriol, which is the active form of vitamin D that promotes calcium absorption from food in the small intestine


Cholecalciferol is made in the skin following UVB light exposure. How can it end up as calcitriol ?

It is converted into calcifediol in the liver. Then this is converted into calcitriol in the kidneys.


When serum calcium is high this suppresses the release of PTH. This is an example of what type of feedback ?

Negative feedback


Where in the kidney is renin secreted ?

The juxtaglomerular cells that sit in the afferent (and some in the efferent) arterioles in the kidney.


What do the juxtaglomerular cells sense in relation to renin secretion ?

Blood pressure


What is renin ? Explain the RAAS ?

Renin is an enzyme that converts angiotensinogen (released by the liver) into angiotensin I. Angiotensin I is converted to angiotensin II in the lungs by ACE. Angiotensin II acts on blood vessels to cause vasoconstriction and it also stimulates the release of aldosterone from the adrenal glands.


Aldosterone is a mineralocorticoid steroid hormone. It acts on the nephrons of the kidneys to ?

-Increase sodium reabsorption from the distal tubule
-Increase potassium secretion from the distal tubule
-Increase hydrogen secretion from the collecting ducts


Why does increased sodium reabsorption increase blood pressure ?

Water follows it by osmosis. This leads to an increase in intravascular volume and subsequently BP.


What is Cushing's syndrome and what is Cushing's disease ?

Cushing's syndrome is used to refer to the signs and symptoms that develop after prolonged abnormal elevation of cortisol. Cushing's disease is used to refer to the specific condition where a pituitary adenoma (tumour) secretes excessive ACTH. Cushing's disease causes a Cushing's syndrome, but Cushing's syndrome is not always caused by a Cushing's disease.


Features of Cushing's syndrome ?

Round in the middle with thin limbs:
-Round "moon" face
-Central obesity
-Abdominal striae (stretch marks)
-"Buffalo hump" (fat pad on upper back)
-Proximal limb muscle wasting

High levels of stress hormone:
-Cardiac hypertrophy
-Hyperglycaemia (type 2 diabetes)

Extra effects:
-Easy bruising and poor skin healing


Causes of Cushing's syndrome (name four) ?

-Exogenous steroids (in pts on long term high dose steroid medications)
-Cushing's disease (a pituitary adenoma releasing excessive ACTH)
-Adrenal adenoma (a hormone secreting adrenal tumour
-Paraneoplastic Cushing's


What is Paraneoplastic Cushing's and what is the most common cause ?

When excess ACTH is released from a cancer (except in the pituitary) and stimulates excessive cortisol release. ACTH from somewhere other than the pituitary is called "ectopic ACTH". Small cell lung cancer is the most common cause.


Test for diagnosing Cushing's syndrome ?

Dexamethasone suppression test (DST)


Briefly describe how the dexamethasone suppression test works ?

Initially the pt is given the "low dose" test. If the low dose test is normal, Cushing's can be excluded. If the low dose test is abnormal, then a high dose test is performed to differentiate between the underlying causes.

To perform the test the pt takes a dose of dexamethasone (a synthetic glucocorticoid steroid) at night and their cortisol and ACTH are measured in the morning. The intention is to find out whether the dexamethasone suppresses their normal morning spike of cortisol.


Normal response for low dose DST ?

Dexamethasone suppresses the release of cortisol by effecting negative feedback on the hypothalamus and pituitary. This means less CRH and ACTH are produced resulting in a low cortisol level. When the cortisol level is not suppressed, this is the abnormal result seen in Cushing's syndrome


Effects of high dose DST on different causes of Cushings syndrome (include results in table at the end) ?

- In Cushing's disease (pituitary adenoma) the pituitary still shows some response to negative feedback and the high dose (8mg) of dexamethasone is enough to suppress cortisol
- Where there is an adrenal adenoma, cortisol production is independent from the pituitary. Therefore, cortisol is not suppressed, however ACTH is suppressed by negative feedback on the hypothalamus and pituitary gland.
- Where there is ectopic ACTH , neither cortisol or ACTH will be suppressed because the ACTH production is independent of the hypothalamus or pituitary gland

-Pituitary adenoma, ACTH = suppressed, Cortisol = suppressed

-Adrenal adenoma, ACTH = suppressed, Cortisol = not suppressed

-Ectopic ACTH, ACTH = not suppressed, cortisol = not suppressed


Other investigations for Cushing's syndrome ?

24 hr urinary free cortisol can be used as an alternative to the dexamethasone suppression test to diagnose Cushing's syndrome but it does not indicate the underlying cause and is cumbersome to carry out.

Other investigatons:
-FBC (raised WCC) and electrolytes (potassium may be low if aldosterone is also secreted by an adrenal adenoma)
-MRI brain for pituitary adenoma
-Chest CT for small cell lung cancer
-Abdominal CT for adrenal tumours


Treatment of Cushing's syndrome ?

The main treatment is to remove the underlying cause (surgically remove the tumour)
-Trans-sphenoidal (through the nose) removal of pituitary adenoma
-Surgical removal of adrenal tumour
-Surgical removal of tumour producing ectopic ACTH

If surgical removal of the cause is not possible another option is to remove both adrenal glands and give the pt replacement steroid hormones for life


What is Addison's disease + what else is it called?

A specific condition where the adrenal glands have been damaged, resulting in a reduction in the secretion of cortisol and aldosterone. It is also called primary adrenal insufficiency.