Endocrine Pathology

Question 1

Normal thyroid histology

Answer 1

• Colloid-filled acini lined by follicular epithelial cells
• Vascular organ
• Hormone thyroxine is secreted directly into blood
• Regulates basal metabolic rate

Question 2

**Hypothyroidism **- causes

Answer 2

• Hashimoto’s thyroiditis - commonest
  
  • Auto-immune: production of anti-thyroid antibodies –> lymphocytic destruction of thyroid
  • Females 10:1 Males
• Removal of thyroid
• Radioiodine treatment

Question 3

**Hypothyroidism **- symptoms

Answer 3

• Myxoedema = slowing of mind and body:
  
  • Weight gain
  • Constipation
  • Cold intolerance
  • Tiredness
  • Depression
  • Big tongue, deep voice - deposition of matrix substances in viscera and skin
  • Thin hair
  • Weak heartbeat
  • Slow reflexes

Question 4

**Hyperthroidism **- causes

Answer 4

• Grave’s disease: 85% of cases
• Hyperfunctional multinodular goitre (usually euthyroid)
• Hyperfunctional adenoma (benign follicular tumour) - rare

Question 5

**Hyperthyroidism **- symptoms

Answer 5

• Increased basal metabolic rate:
  
  • _​_Sweating
  • Heat intolerance
  • Weight loss despite increased appetite
  • Diarrhoea
  • Tachycardia, arrhythmias (often AF)
  • Tremor, anxiety, hyperactivity
  • Brist reflexes
  • Staring gaze
  • Lid lag
  • Exopthalmos

Question 6

**Graves disease **- diffuse toxic goitre

Answer 6

• Female 10:1 Male
• Autoimmune - due to thyroid stimulating antibodies
• Symmetrical enlargement of thyroid
• Exopthalmos - due to deposition of connective tissue behind eyeball

Question 7

Multinodular goitre

Answer 7

• Usually euthyroid - if active and –> hyperthyroidism then ‘toxic’
• May be due to uneven responsiveness of areas of thyroid to fluctuating TSH over years
• Development of well circumscribed nodules of various sizes –> irregular hyperplastic enlargement of entire thyroid gland.
• Larger nodules filled with brown gelatinous colloid
• Large goitres may lead to tracheal compression or dysphagia
• Significant cosmetic effect

Question 8

Adenoma (follicular)

Answer 8

• Benign tumour
• Colloid-containing microfollicles and columns of larger cells in alveolar arrangement
• Usually euthyroid
  
  • Rarely hyperfunctional = “toxic” nodule –> thyrotoxicosis

Question 9

Adenoma vs. Hyperplastic Nodule

Answer 9

• Adenoma = solitary follicular nodule with normal background gland
  
  • Treatment - thyroid lobectomy
• Disproportionate nodule = hyperplastic follicular nodule in *nodular *background gland i.e. multinodular goitre
  
  • Treatment - thyroidectomy or no surgery

Question 10

**Papillary adenocarcinoma ** - thyroid cancer

Answer 10

• Well differentiated tumour
• Commoner in younger patients
• Slow-growing, non-encapsulated mass
• Histology
  
  • Epithelial papillary projections +/- calcified spherules between
  • Epithelial cell nuclei large with clear area centrall = ‘Orphan Annie nuclei’
  • Psammoma bodies

Question 11

**Follicular adenocarcinoma **- thyroid cancer

Answer 11

• Well differentiated, single, encapsulated lesion
• Histology
  
  • Similar to papillary adenocarcinoma but with invasion of capsule/blood vessels
• Haematogenous spread to:
  
  • Bone
  • Lungs
  • Brain
• Good uptake of radioactive iodine (¹³¹I) - susceptible to post throidectomy radiotherapy

Question 12

**Anaplastic carcinoma **- thyroid cancer

Answer 12

• Highly malignant, poorly differentiated adenocarcinoma:
  
  • Local invasion
  • Metastases
• Elderly patients - presents as diffusely infiltrative mass
• Very poor prognosis - does not respond to treatment and invades the trachea –> respiratory obstruction
• Histology
  
  • Spindle cell tumour +/- giant cell areas or small cell pattern

Question 13

**Medullary carcinoma **- thyroid cancer

Answer 13

• Rare neuroendocrine tumour
• Arises from parafollicular ‘C’ cells which secrete calcitonin
  
  • Raised serum calcitonin useful diagnostically (no effects)
• Histology
  
  • Amyloid stroma
  • Positive calcitonin staining
• Incidence
  
  • Sporadic - 70%
  • MEN 2A/2B or familial medullary thyroid carcinoma (30%)

Question 14

**Histology of Thyroid **- overview

Answer 14

• Hyperplastic epithelium
  
  • Graves’ disease
  • Iodine deficiency
  • Goitrogen/PUT effect
• Colloid-filled follicles
  
  • ‘Idiopathic’ nodular goitre
• Anaplastic cells
  
  • Cancer
• Lymphocytes
  
  • Hashimoto’s thyroiditis
• Foreign-body granulomas
  
  • DeQuervain’s
• Fibrous tissue
  
  • Riedel’s

Question 15

**Parathyroid Glands **- function

Answer 15

• Four glands - one in each lobe of the thyroid (superior and inferior)
• Parathormone (PTH) is secreted in response to low serum calcium levels by the chief cells
• PTh increases serum Ca²⁺ and decreases serum phosphate by:
  
  • Bone
    
    • Stimulating osteoclastic bone resorption
    • Inhibiting osteoblastic bone deposition
  • Kidney
    
    • Increasing Ca²⁺ reabsorption
    • Decreaseing phosphate reabsorption
    • Activation of Vit D by 1-hydroxylation of 25-hydroxyvitamin D
  • Gut
    
    • Increased Ca²⁺reabsorption

Question 16

**Primary Hyperparathyroidism **- aetiology

Answer 16

• Hypersecretion of PTH and thus elevates serum calcium from
  
  • Adenoma 85-95%
  • Hyperplasia 5-15%
  • Carcinoma <1%
• Usually sporadic causes
• Adenomas and hyperplasia may be related to MEN1, 2A or 2B

Question 17

**Primary Hyperparathyroidism **- symptoms

Answer 17

• Due to effects of PTH and hypercalcaemia
  
  • *Painful bones *-
    
    • osteoporosis
    • osteitis
    • fibrosa cystica
  • Renal stones
  • *Abdominal groans *
    
    • ​Anorexia
    • Constipation
  • *Pyschic moans *
    
    • depression
    • lethargy
    • seizures

Question 18

**Secondary Hyperparathyroidism **- etiology

Answer 18

• Compensatory hyperplasia of the parathyroid in response to chronic low serum calcium or increased phosphate
• Causes:
  
  • Chronic renal failure - most common
  • Vit D or calcium deficiency
  • Malabsorption
  • Low serum magnesium
  • Tissue resistance to Vid D
  • Pseudohypoparathyroidism (genetic resistance to PTH)

Question 19

**Hyperparathyroidism **- investigation

Answer 19

• Ultrasound
• Sestamibi scan
  
  • Radioactive tecnetium-99 injected
  • Taken up preferentially by hyperactive glands
    
    • Just one - implies tumour
    • All four - implies hyperplasia

Question 20

Parathyroid Carcinoma

Answer 20

• Rare
• Causes very high hypercalcaemia >3.5 mmol/l
• Rapid
  
  • Bone disease
  • Kidney stones
  • Metastases
• May damage recurrent larangeal nerve
• Adherent at surgery

Question 21

**Adrenal Gland **- function

Answer 21

• Cortex - produces 3 types of steroids
  
  • Glucocorticoids - mainly cortisol from the zona fasciculata
  • Mineralocorticoids - mainly aldosterone from the zona glomerulosa
  • Sex steroids - oestrogens and androgens from the zona reticularis
• *Medulla - *produces catecholamines mainly adrenaline

Question 22

Primary Adrenocortical Insufficiency (Addison’s disease) - Causes

Answer 22

• Autoimmune destruction
• Tuberculosis - bilateral adrenal (caseous necrosis)
• Surgical remocal
• Metastatic cancer
• AIDs - CMV, Mycobacterium, Kaposi’s sarcoma
• Congenital hypoplasia

Question 23

**Addison’s Disease **- clinical features

Answer 23

• Glucocorticoid insufficiency
  
  • Vomiting and loss of appetite
  • Weight loss
  • Lethargy and weakness
  • Postural hypotension
  • Hypoglycaemia
• Mineralocorticoid insufficiency
  
  • ​Lowered serum Na⁺, raised serum K⁺
  • Chronic dehydration
  • Hypotension
• Increased ACTH secretion
  
  • ​Hyperpigmentation of skin and buccal mucosa
• Loss of adrenal androgen
  
  • Decreased body hair - especially in females

Question 24

**Acute (Addisonian) Adrenal Crisis **- Addison’s disease

Answer 24

• Preciptated by sudden stress demanding raised output from chronically failing glands:
  
  • Infection
  • Trauma
  • Surgery
• Symptoms of:
  
  • Vomiting
  • Abdominal pain
  • Hypotension
  • Coma
• Rapidly fatal! - unless Rx - corticosterioids (IV hydrocortisone) + fluids

Question 25

**Cushing's Syndrome **- Clinical Features

Answer 25

* Clinical feautres due to exposure to raised free cotricosteroid levels: * Central obesity and moon face * Plethora and acne * Menstrual irregularity * Hirsutism and hair thinning * Hypertension * Diabetes/glucose intolerance * Muscle wasting and peakness * Thin skin, easy bruising and striae * Osteoporosis

Question 26

**Cushing's syndrome **- aetiology

Answer 26

* ACTH-dependent * Pituitary adenoma _(Cushing's disease)_ --\> excess ACTH secretion and bilateral diffuse adrenal hyperplasia * Ectropic ACTH (or corticotrophin releasing hormone) production by a non-endocrine neoplasm e.g. small cell lung Ca⁺  * ACTH independent * Iatrogenic steroid therapy - most common cause overall * Adrenal cortical adenoma - majority are non-functional * Adrenal carcinoma - rare * Usually functional * Generally associated with overporduction of glucocorticoids and sex steroids * Virilization common symptom especially in women * Often large and invasive * Nodular hyperplasia

Question 27

**Pheochromocytoma**

Answer 27

* Tumour arising from the adrenal medulla * Produces catecholamines - mostly adrenaline * Rare cause of surgically correctable hypertension * HTN paroxysmal * Diagnosis based on raised level of catecholamines in urine * Rule of 10s * 10% extra-adrenal (paragangliomas) * 10% bilateral * 10% malignant (no histological features predict behaviour * 10% _not_ associated with hypertension

Question 28

**Multiple Endocrine Neoplasia (MEN) Syndromes**

Answer 28

* Genetically inherited diseases * Lead to proliferative lesions of multiple endocrine glands - hyperplasia, adenoma or carcinoma * MEN I (Wermer) --\> parathyoid adenoma/hyperplasia + hyperplasia/carcinoid tumours of other endocrine glands * Caused by abnormal tumour suppressor gene - chromosome 11q * MEN IIa --\> medullary carcinoma of thyroid and/or pheochromocytoma and/or parathyroid adenoma/hyperplasia * Caused by abnormality on chromosome 10q * MEN IIb --\> medullary carcinoma of the thyroid and/or pheochromocytoma * Caused by abnormality of *ret *oncogene - chromosome 10q