Endocrine disorders

Question 1

Describe the negative feedback control of the hypothalamic-pituitary axis

Answer 1

1) Hormone production in the hypothalamus:

• In response to certain signals (like stress, diurnal rhythm, or low levels of certain hormones), the hypothalamus produces and secretes releasing hormones, such as corticotropin-releasing hormone (CRH)

2) Stimulation of the pituitary gland:

• CRH stimulates the pituitary to produce adrenocorticotropic hormone (ACTH)

3) Stimulation of the target gland:

• ACTH acts on the adrenal cortex to stimulate the production and release of cortisol

4) Negative feedback:

• Cortisol inhibits to release of jhypothalamic CRH and pituitary ACTH

5) Return to homeostasis:

• As the levels of the hormone in the bloodstream drop, the inhibitory effect on the hypothalamus and pituitary gland lessens, and they can start producing their hormones again, re-starting the process

Question 2

Describe disorders of the thyroid gland - hyper- and hypothyroidism and understand how laboratory tests of thyroid hormones can diagnose these conditions

Answer 2

Hyperthyroidism:

• is a condition in which the thyroid gland is overactive and makes excessive amounts of thyroid hormone
• When the amount of hormone released into the bloodstream is excessively high, the body’s metabolism increases, which can lead to symptoms such as rapid heart rate, high blood pressure, excessive sweating, heat intolerance, weight loss, increased appetite, irritability, and more frequent bowel movements
• Graves’ disease is the most common cause of hyperthyroidism, an autoimmune disorder where antibodies stimulate the thyroid to secrete too much hormone

Hypothyroidism:

• is a condition in which the thyroid gland is underactive and does not produce enough thyroid hormones
• When the amount of hormone released into the bloodstream is too low, the body’s metabolism decreases, leading to symptoms such as fatigue, cold intolerance, weight gain, constipation, dry skin, depression, and slowed heart rate
• The most common cause of hypothyroidism is Hashimoto’s thyroiditis, an autoimmune condition where the body’s immune system attacks the thyroid tissue

Laboratory Tests:

Involves measuring levels of thyroid hormones in the blood:

Thyroid Stimulating Hormone (TSH):

• Produced by the pituitary gland, TSH stimulates the thyroid to produce thyroid hormones
• Therefore, high levels of TSH can indicate hypothyroidism, while low levels can indicate hyperthyroidism

T4 and T3:

• These are the main hormones produced by the thyroid. In primary hypothyroidism, T4 and T3 levels will be low. In hyperthyroidism, T4 and T3 levels will be high

Question 3

Describe disorders of the adrenal cortex

Answer 3

The adrenal cortex is the outer part of the adrenal gland and produces hormones like cortisol and aldosterone

1) Addison’s disease:

• Also known as primary adrenal insufficiency, Addison’s disease occurs when the adrenal cortex doesn’t produce enough cortisol and, often, aldosterone
• Symptoms include fatigue, weight loss, decreased appetite, darkening of the skin, low blood pressure, salt craving, and worsening tiredness or weakness

2) Cushing’s syndrome:

• when the body is exposed to high levels cortisol for a long time
• It can be due to overuse of corticosteroid medications or the body producing too much cortisol
• Symptoms include a fatty hump between the shoulders (buffalo hump), a rounded face (moon face), pink or purple stretch marks, and skin that bruises easily

3) Congenital adrenal hyperplasia (CAH):

• This is a group of inherited disorders that affect the adrenal glands.
• The most common form causes poor growth, acne, excess body hair, and other symptoms

4) Adrenal cancer:

• overproduction of adrenal hormones or due to the size of the tumour pressing on surrounding organs

5) Hyperaldosteronism:

• This can be primary (also known as Conn’s syndrome) due to a problem with the adrenal gland, or secondary due to a problem elsewhere, often involving the kidney
• Symptoms can include high blood pressure, muscle weakness, and, in severe cases, symptoms of low potassium like muscle weakness or heart palpitations

Question 4

Describe the laboratory tests that can aid differential diagnosis of disorders involving adrenal steroid excess (e.g., Cushing’s syndrome)

Answer 4

Initial Screening Tests:

• 24-hour Urinary Free Cortisol Test: This test measures the amount of cortisol in urine collected over 24 hours. Elevated levels may suggest Cushing’s syndrome.
• Late-night Salivary Cortisol Test: Cortisol levels normally decrease in the late evening. This test measures the level of cortisol in saliva collected late at night. Elevated levels can indicate Cushing’s syndrome.
• Low-Dose Dexamethasone Suppression Test: Dexamethasone is a synthetic glucocorticoid. Normally, taking dexamethasone leads to a decrease in blood cortisol levels. In patients with Cushing’s syndrome, cortisol levels often don’t decrease in response to dexamethasone.

Confirmatory Tests:

• High-Dose Dexamethasone Suppression Test: Similar to the low-dose test, but a higher dose of dexamethasone is used. This test can help differentiate between different types of Cushing’s syndrome.
• CRH Stimulation Test: CRH (corticotropin-releasing hormone) is a hormone that stimulates the production of ACTH. In this test, synthetic CRH is given and then blood cortisol and ACTH levels are measured.

Tests to Determine the Cause:

• ACTH Level: Measuring the level of ACTH in the blood can help differentiate between Cushing’s disease (caused by a pituitary tumor, with high ACTH levels) and other causes of Cushing’s syndrome (usually with low ACTH levels).
• Imaging Tests: If a tumor is suspected, imaging tests such as CT or MRI scans of the adrenal or pituitary glands may be used.

Question 5

Describe the laboratory tests that can aid differential diagnosis of disorders involving adrenal steroid deficit (e.g., Addison’s disease)

Answer 5

Blood tests:

• These are done to measure levels of cortisol, adrenocorticotropic hormone (ACTH), and sodium and potassium in the blood
• Addison’s disease is characterized by decreased cortisol, high ACTH (due to loss of negative feedback inhibition on the pituitary gland), and often altered sodium and potassium levels due to decreased aldosterone

ACTH Stimulation Test:

• This test involves measuring the level of cortisol in your blood before and after an injection of synthetic ACTH
• In healthy individuals, the cortisol level would rise in response to the ACTH. In people with Addison’s disease, the cortisol level would not show a significant increase

Insulin-Induced Hypoglycemia Test:

• In this test, insulin is injected to cause blood glucose levels to fall (hypoglycemia), which should stimulate the release of cortisol
• In individuals with Addison’s disease, the cortisol response would be blunted or absent