Endocrine Lecture

Question 1

What are the three main types of endocrine signalling described?

Answer 1

The three main types are autocrine signalling, paracrine signalling, and endocrine signalling.

Question 2

What brain structures are identified as the major link between the nervous and endocrine systems?

Answer 2

The hypothalamus and the pituitary are the major link and crucial regulators.

Question 3

How do hypothalamic neurosecretory neurons communicate with the anterior pituitary gland?

Answer 3

They secrete compounds directly into the hypophyseal portal veins.

Question 4

Give an example of a hypothalamic hormone, the anterior pituitary hormone it stimulates, and the target gland.

Answer 4

TRH stimulates the anterior pituitary to release TSH, which then finds the thyroid gland. Another example is CRH, which stimulates the pituitary to release ACTH, acting on the adrenal glands.

Question 5

How does the posterior pituitary differ from the anterior pituitary in terms of hormone storage and release?

Answer 5

Hormones like ADH are produced in the hypothalamus and stored in axons that extend into the posterior pituitary.

Question 6

Explain the negative feedback loop in the endocrine system using the hypothalamus-pituitary-adrenal axis as an example.

Answer 6

The hypothalamus produces CRH, stimulating the pituitary to produce ACTH, which stimulates the adrenal cortex to produce glucocorticoids.

Question 7

What are the two broad types of endocrine disease classification from a pathology point of view?

Answer 7

The two types are endocrine effect (underproduction or overproduction of hormones) and mass effect.

Question 8

How is endocrine disease classified based on the location of the pathology in the hypothalamus-pituitary-target gland axis?

Answer 8

If the pathology is in the target gland, it’s primary disease. If it’s in the pituitary gland, it’s secondary disease. If it’s in the hypothalamus, it’s tertiary disease.

Question 9

Name the three different types of cells seen in the anterior pituitary gland based on H&E staining characteristics.

Answer 9

Basophiles, eosinophilic cells, and chromophobes.

Question 10

What is the general term for most tumours arising in the pituitary gland?

Answer 10

Most are benign tumours called adenomas.

Question 11

Are pituitary adenomas typically functional or non-functional?

Answer 11

Many are functional tumours that produce too much hormone, but they are not always functional.

Question 12

What is a tumour derived from a somatotroph cell in the pituitary gland called?

Answer 12

A somatotroph adenoma.

Question 13

If a corticotroph adenoma elaborates excess ACTH, what happens to the levels of glucocorticoids and CRH?

Answer 13

Glucocorticoid levels will go up. CRH levels will go down due to negative feedback.

Question 14

Why are non-functional pituitary adenomas typically larger than functional ones by the time they are diagnosed?

Answer 14

Functional adenomas are detected more quickly due to the systemic effects of excess hormone.

Question 15

What are some specific clinical signs mentioned as being ‘really quite specific for Cushing’s’?

Answer 15

Central obesity, truncal obesity, moon faces, and buffalo hump.

Question 16

What is the diagnosis for an individual presenting with hypertension, weight gain, central obesity, moon faces, buffalo hump, and abdominal striae?

Answer 16

Cushing’s disease or Cushing’s syndrome.

Question 17

When is the term ‘Cushing’s disease’ used specifically?

Answer 17

You only use Cushing’s disease when it is a primary tumour of the pituitary gland elaborating ACTH.

Question 18

What is the most common type/cause of Cushing’s syndrome?

Answer 18

Steroid use (exogenous type).

Question 19

What happens to the adrenal cortex in patients with exogenous Cushing’s due to the negative feedback loop?

Answer 19

The adrenal cortex undergoes atrophy because the circulating steroids downregulate hypothalamus and pituitary hormones.

Question 20

What is the risk if a patient on long-term steroids undergoes rapid withdrawal?

Answer 20

Potential for adrenal crisis because the atrophied adrenal gland cannot respond to stress.

Question 21

What are the two classifications of endogenous Cushing’s syndrome based on ACTH levels?

Answer 21

ACTH dependent and ACTH independent.

Question 22

What are the two main causes of ACTH-dependent Cushing’s syndrome?

Answer 22

A primary pituitary adenoma elaborating ACTH or an ectopic source from other cancers.

Question 23

What are the two main causes of ACTH-independent Cushing’s syndrome?

Answer 23

A primary tumour of the adrenal cortex producing cortisol or nodular hyperplasia of the cortex producing cortisol.

Question 24

Explain the principle behind the dexamethasone suppression test for investigating Cushing’s syndrome.

Answer 24

Dexamethasone inhibits the pituitary gland and hypothalamus, suppressing ACTH secretion.

Question 25

In the low-dose dexamethasone suppression test, what level of cortisol rules out Cushing's, and what level suggests Cushing's?

Answer 25

If cortisol levels are below 50 nm per litre, the patient likely does not have Cushing's. If levels are higher than 50 nm per litre, the patient likely has Cushing's.

Question 26

After a high cortisol result in the low-dose test, what is the next step in the dexamethasone suppression test pathway?

Answer 26

Measure ACTH levels to determine if the Cushing's is ACTH dependent or independent.

Question 27

How is the high-dose dexamethasone suppression test used to distinguish between pituitary adenoma and ectopic ACTH production in ACTH-dependent Cushing's?

Answer 27

Significant suppression of cortisol suggests a pituitary adenoma.

Question 28

Besides cortisol, what other hormones elaborated by the adrenal cortex might contribute to complex clinical scenarios in Cushing's syndrome?

Answer 28

Aldosterone and androgens.

Question 29

Why does abdominal striae occur in Cushing's syndrome?

Answer 29

It's a combination of weight gain and thin skin due to protein metabolism and connective tissue degradation.

Question 30

Name the three layers of the adrenal cortex and the main hormone produced by each layer.

Answer 30

Zona glomerulosa (mineralocorticoids), zona fasciculata (glucocorticoids), and zona reticularis (androgen synthesis).

Question 31

What are the main functions associated with the hormones produced by the four regions of the adrenal gland?

Answer 31

Aldosterone (salt regulation), Cortisol (glucose metabolism), Androgens (sexual hormones), and Catecholamines (stress hormones).

Question 32

Describe the macroscopic appearance of the zona fasciculata and reticularis layers.

Answer 32

They are lipid rich, appearing with more prominent open spaces due to fat accumulation.

Question 33

What condition is suggested by elevated blood pressure and a single functional lesion in the adrenal gland?

Answer 33

Hyperaldosteronism, likely primary.

Question 34

What is the diagnosis for primary hyperaldosteronism caused by a cortical adenoma?

Answer 34

Conn syndrome.

Question 35

What are the expected electrolyte changes and blood volume/pressure changes in primary hyperaldosteronism?

Answer 35

Sodium is retained, water volume increases, potassium is excreted, leading to hypertension.

Question 36

What is the most common cause of primary hyperaldosteronism?

Answer 36

Idiopathic hyperplasia affecting both adrenal cortexes.

Question 37

What percentage of patients with hypertension might have hyperaldosteronism?

Answer 37

About 10%.

Question 38

What clinical signs and symptoms are characteristic of chronic primary adrenal insufficiency?

Answer 38

Easy fatigueability, aggressive weakness, GI disturbances, hyperpigmentation of the skin, and hypotension.

Question 39

What are the typical serum electrolyte findings in chronic primary adrenal insufficiency?

Answer 39

Hyperkalemia and hyponatremia.

Question 40

What is the diagnosis for chronic primary adrenal insufficiency?

Answer 40

Addison's disease.

Question 41

Why does the lack of response to ACTH administration in a patient with low plasma cortisol levels suggest the issue is in the adrenal glands?

Answer 41

A normal adrenal cortex would respond to ACTH administration by producing cortisol.

Question 42

What is the most common cause of Addison's disease?

Answer 42

An autoimmune condition causing destruction of both adrenal cortexes.

Question 43

Besides autoimmune destruction, what are other causes of adrenal destruction mentioned?

Answer 43

Infection or metastatic disease.

Question 44

Explain the mechanism behind the hyperpigmentation seen in Addison's disease.

Answer 44

Low glucocorticoids lead to increased CRH and ACTH production, stimulating melanocytes and causing hyperpigmentation.

Question 45

What is the diagnosis for sudden onset fever, neck rigidity, petechial lesions, hypotension, and bilateral adrenal haemorrhage?

Answer 45

Waterhouse-Friedrichsen syndrome.

Question 46

What is the underlying cause of the bilateral adrenal haemorrhage in Waterhouse-Friedrichsen syndrome?

Answer 46

Disseminated intravascular coagulation (DIC), often triggered by bacterial infection.

Question 47

What are the petechial lesions seen in Waterhouse-Friedrichsen syndrome?

Answer 47

Small microhemorrhages under the skin caused by bacterial damage to capillaries.

Question 48

What type of adrenal cortical insufficiency is Waterhouse-Friedrichsen syndrome classified as?

Answer 48

Acute and primary adrenal cortical insufficiency.

Question 49

What is the diagnosis for a tumour of the adrenal gland presenting with sustained hypertension and episodes of tachycardia and headache?

Answer 49

Pheochromocytoma.

Question 50

Where do pheochromocytomas arise from in the adrenal gland?

Answer 50

The adrenal medulla.

Question 51

What cells are pheochromocytomas derived from, and what hormones do they produce?

Answer 51

Chromaffin cells producing catecholamines.

Question 52

Why does pheochromocytoma tissue turn brown when incubated with chromium salt?

Answer 52

The catecholamines elaborated by the chromaffin cells are oxidised by the chromium salt.

Question 53

Are most pheochromocytomas benign or malignant?

Answer 53

Most are benign, but 10% are malignant.

Question 54

How is malignancy defined in a pheochromocytoma?

Answer 54

Whether there are metastases identified at diagnosis.

Question 55

Describe two key microscopic features of pheochromocytoma mentioned in the source.

Answer 55

Zellballen and salt and pepper nuclei.

Question 56

Pheochromocytomas have a high rate of familial association. What genetic syndromes are associated with an increased risk of developing pheochromocytoma?

Answer 56

VHL, NF1, and RET mutations.

Question 57

What three tumours are associated with MEN 2A syndrome?

Answer 57

Pheochromocytoma, medullary thyroid carcinoma, and parathyroid hyperplasia.

Question 58

What structures are seen in normal thyroid histology?

Answer 58

Follicles lined by follicular epithelial cells surrounding pink substance called colloid.

Question 59

What two components are essential for thyroid hormone synthesis and stored in the colloid?

Answer 59

Iodine and thyroglobulin.

Question 60

What are the terms for conditions of too much and too little thyroid hormone production?

Answer 60

Too much is hyperthyroidism or thyrotoxicosis. Too little is hypothyroidism.

Question 61

Name two important autoimmune thyroid conditions mentioned.

Answer 61

Hashimoto thyroiditis and Graves' disease.

Question 62

What is the characteristic finding on radioactive iodine uptake scan in diffuse hyperthyroidism like Graves' disease?

Answer 62

Diffusely increased radioactive iodine uptake.

Question 63

Based on biochemistry, how can you differentiate primary thyroid disease from secondary or tertiary disease causing hypo- or hyperthyroidism?

Answer 63

In primary thyroid disease, the problem is in the thyroid.

Question 64

What is the diagnosis for primary hypothyroidism caused by an autoimmune condition?

Answer 64

Hashimoto's thyroiditis.

Question 65

What is the diagnosis for primary hyperthyroidism caused by an autoimmune condition?

Answer 65

Graves' disease.

Question 66

What is the diagnosis for primary hypothyroidism caused by an autoimmune condition, characterised by features like enlarged goitre, low T3/T4, and elevated TSH?

Answer 66

Hashimoto's thyroiditis.

Question 67

What is the diagnosis for primary hyperthyroidism caused by an autoimmune condition, characterised by enlarged thyroid, heat intolerance, wide staring gaze, increased T3/T4, and decreased TSH?

Answer 67

Graves' disease.

Question 68

What are the key microscopic findings in Hashimoto's thyroiditis?

Answer 68

Loss of follicles, significant lymphocytic infiltration, germinal centres, and modified follicular epithelial cells called Hurthle cells or oncocytic cells.

Question 69

What are the key microscopic findings in Graves' disease?

Answer 69

Proliferating follicular epithelial cells forming papillary-like structures and colloid scalloping (white space around colloid due to cells absorbing it).

Question 70

What is the difference in antibody action on the TSH receptor between Hashimoto's thyroiditis and Graves' disease?

Answer 70

In Hashimoto's, antibodies can block the TSH receptor. In Graves' disease, antibodies activate the TSH receptor, stimulating hormone production and cell proliferation.

Question 71

What causes the wide staring gaze (exophthalmos) characteristic of Graves' disease?

Answer 71

Autoimmune targeting of fibroblasts in the orbit behind the eyes, which express the TSH receptor, leading to fibrosis, inflammation, and oedema in that area.

Question 72

What is a large nodular swelling in the front of the neck called?

Answer 72

A goitre.

Question 73

What is a common cause of endemic multinodular goitre, particularly mentioned in the context of Nepal?

Answer 73

Iodine deficiency.

Question 74

Explain the pathogenesis of multinodular goitre due to iodine deficiency.

Answer 74

Lack of iodine leads to decreased thyroid hormone. The body signals a need for hormone, stimulating compensatory growth of the thyroid gland to try and produce enough. This involves cycles of expansion and regression. Over time, some follicles become abnormal (atrophy, fibrosis, haemorrhage, rupture), leading to irregular growth and the multinodular appearance.

Question 75

What is the typical endocrine state of an individual with a simple multinodular goitre caused by iodine deficiency?

Answer 75

Euthyroid, as the gland is compensating to produce sufficient hormone. ## Footnote Multinodular goiter can be associated with normal thyroid hormone levels (euthyroid), or, in some cases, can lead to hyperthyroidism (excessive thyroid hormone). While many multinodular goiters don't cause symptoms and are considered non-toxic, some can become toxic, leading to hyperthyroidism.

Question 76

What are potential complications of a large multinodular goitre?

Answer 76

Mass effect (obstructing/compressing structures) and, if nodules become autonomous, potentially becoming toxic (hyperthyroid) or undergoing neoplastic transformation.

Question 77

When evaluating a single nodule in the thyroid, what factors increase the likelihood of it being neoplastic (a tumour) rather than non-neoplastic?

Answer 77

Younger age, male sex, history of radiation exposure, and if radioactive iodine uptake is reduced (cold nodule, as functional nodules are more likely benign).

Question 78

What microscopic feature is crucial for differentiating a benign follicular adenoma from a malignant follicular carcinoma in the thyroid?

Answer 78

Invasion of the capsule or blood vessels.

Question 79

What is the diagnosis for a benign tumour derived from follicular epithelial cells in the thyroid gland?

Answer 79

Follicular adenoma.

Question 80

What is the diagnosis for a malignant thyroid tumour characterised by irregular appearance, cystic areas, and finger-like projections?

Answer 80

Papillary carcinoma.

Question 81

What is the most important diagnostic microscopic feature of papillary carcinoma of the thyroid?

Answer 81

The characteristic clear or empty-looking nuclei known as Orphan Annie eye nuclei.

Question 82

What are Psammoma bodies, and what thyroid tumour are they associated with?

Answer 82

Calcifications that occur when the tips of papillary projections calcify. They are a feature of papillary carcinomas. Microcalcifications seen on ultrasound can correspond to these.

Question 83

What is the cell of origin for medullary thyroid carcinoma?

Answer 83

Parafollicular C cells (neuroendocrine cells).

Question 84

What hormone is produced by medullary thyroid carcinoma?

Answer 84

Calcitonin. ## Footnote Calcitonin is produced by C-cells, also known as parafollicular cells, within the thyroid gland. These cells are derived from neural crest cells and secrete the polypeptide hormone calcitonin. Calcitonin production is regulated by blood calcium levels, with higher calcium levels stimulating calcitonin release.

Question 85

What genetic syndrome is medullary thyroid carcinoma associated with?

Answer 85

MEN 2A.

Question 86

What was the famous historical figure mentioned who is believed to have had Addison's disease?

Answer 86

JFK.