WORK SESSION 10: Endocrine Diseases

AIMS

To understand the principal metabolic effects of pancreatic, adrenal, thyroid and growth hormones, and the interactions between them, in relation to endocrine diseases and the control of body weight.

OBJECTIVES

On successful completion of this exercise you will:

• Understand the mechanisms that normally control the release of adrenalin, corticosteroids, insulin, glucagon, growth hormone, leptin and thyroid hormones.
• Appreciate the principal effects of these hormones on target tissues.
• Understand the consequences of the over- or under-secretion of the above hormones, and appreciate the complex secondary and compensatory effects that may follow.
• Understand that hormone assays on blood samples may or may not assist the diagnosis.
• Understand how test doses of some hormones may yield useful diagnostic information.

INTRODUCTION AND PREPARATION

Every hormonal signalling system includes negative feedback loops that regulate hormone output to meet the needs of the organism. Sometimes the 'purpose' of this regulation is obvious (e.g. blood glucose and insulin) but some other physiological systems may be more difficult to understand. There are conspicuous negative feedback loops that regulate the output of all the pituitary hormones, but the benefits to the organism require more thought than for glucose and insulin.

Endocrine diseases are associated with either excessive, inadequate or inappropriate hormone production, but in each case the other parts of the control system continue to operate, and all the interacting feedback loops for other hormonal systems continue to work as well. This can give rise to bizarre "knock on" effects, far removed from the original problem, when other control systems try to compensate for the fault.

It will help you to understand endocrine diseases if you first complete the following table before you come to the Work Session, showing the principal stimuli for hormone production, and also what normally limits hormone output under physiological conditions:

CASE A

A 55 year old woman visited her GP, complaining of feeling "tired and achy all the time". "Maybe it's just my age, doctor, but in the last six months everything seems to have become such an effort". Further questioning revealed that she had lost a bit of weight, but puts this down to missing meals "I don't really feel like eating sometimes, and I don't mind losing a few pounds" Her weight is towards the top of the desirable range. She also says she gets "a bit dizzy sometimes, especially if I stand up too fast".

1. What possible diagnoses might the GP be considering?

A urine test for glucose proves negative. Blood tests reveal mild anaemia which was treated with iron supplements.
Two weeks later, she developed a sore throat and raised temperature. When her partner returned from work he found her in bed, confused, and clearly very ill. She was admitted to hospital. Her blood pressure on arrival was 80/40. Doctors noted areas of dark pigmentation on her hands.

Biochemical analyses of a blood sample revealed the following results:



Measurement	Patient result	Normal range
Sodium	110mmol/L	135 - 145 mmol/L
Potassium	5.7 mmol/L	3.5 - 5 mmol/L
Glucose	3.0mmol/L	4.5 - 5.7mmol/L
Urea	12mmol/l	2.5 - 6.7mmol/L
Cortisol	95nmol/L	*usually > 100nmol/L

* cortisol levels vary at different times of day, and in response to stress

2. What do these results suggest?
3. What immedicate treatment would be given?
4. What additional tests would be performed once the patient's condition was stabilised, and what results might you expect? Explain why these results would be expected.
5. Explain the cause of each of the symptoms observed - i.e. hypotension, electrolyte imbalance, hypoglycaemia, pigmentation.

CASE B

A 42-year-old woman consulted her GP. Her periods had dwindled over several months and had now stopped completely. She had a thin, velvety skin and her hair was fine and thin. She complained that she felt hot all the time, and thought this might be caused by an early menopause.

1. Comments?
2. A pregnancy test proved negative. Why was she unlikely to be pregnant?

"I can't understand it - I am losing weight, but I've been eating like a horse."

3. What possibilities does this suggest?

She had noticed increased bowel frequency, but without diarrhoea. Her stools were not offensive and did not float in the lavatory pan.

4. What does this indicate?

She drank about five cups of tea or coffee each day and did not have any urinary problems.

5. What does this suggest?

She said she felt fidgety and "always on the go". She argued frequently with her husband over silly things like the duvet thickness and leaving the bedroom window open at night. She also said that she was always worried about something "silly things, I know, but I can't seem to stop fretting"

6. Comments?

On examination her temperature was 37.5°C and BP 160/70. She had a rapid irregular pulse, about 120/min at the wrist, although her heart rate seemed to be faster, and grossly irregular. The apex beat was strong and a third heart sound was discernible. Her hands were warm and moist, and a rapid delicate tremor was visible when they were held outstretched. She said that her legs often felt tired, especially climbing stairs, and she worried about her heart: "I sometimes get these dreadful palpitations for no reason at all." Her ankles were not swollen and she had no cough or other respiratory symptoms.

7. Why did her GP check these things and what did he conclude?
8. What condition does this case suggest?
9. What additional symptoms are often seen ?
10. What laboratory tests could be used for confirmation?
11. How does this condition arise?
12. How, in general terms, is it treated?
13. Explain how each of the symptoms is caused, i.e. raised body temperature/heat intolerance, weight loss, cardiac effects, anxiety/restlessness.

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