Histo: Endocrine disease Flashcards
What types of cell are the anterior and posterior pituitary made up of?
Anterior = epithelial cells
Posterior = nerve cells
What is the blood supply to the anterior pituitary?
Pituitary portal system
Where do the nerves that make up the posterior pituitary originate?
Supraoptic nucleus and paraventricular nucleus
Describe the histology of the anterior pituitary.
Made up of epithelial cells derived from the developing oral cavity
How is hyperpituitarism classified?
Based on the hormone produced (this is detected by immunohistochemistry)
What is the most common type of pituitary adenoma?
Prolactinoma
What is a microadenoma?
A pituitary adenoma with a diameter < 1 cm
Outline the clinical features of prolactinoma.
- Amenorrhoea
- Galactorrhoea
- Loss of libido
- Infertility
What are the clinical manifestations of growth hormone adenomas?
- Gigantism (in prepubertal children)
- Acromegaly (in adults)
- Diabetes, Muscle weakness, Congestive HF, HTN
What disease is caused by corticotroph cell adenomas?
Cushing’s disease
List some causes of hypopituitarism.
- Non-secreting pituitary adenoma
- Ischaemia
- Iatrogenic (e.g. surgery, radiotherapy)
What is the most common cause of ischaemic necrosis of the pituitary gland?
Sheehan’s syndrome - the pituitary enlarges during pregnancy and is more susceptible to ischaemia. A post-partum haemorrhage may induce ischaemia.
Other causes: DIC, sickle cell anaemia, shock
List some clinical features of hypopituitarism.
- Pituitary dwarfism
- Gonadotrophin deficiency - amenorrhoea, infertility, impotence, loss of libido
- Hypothyroidism and hypoadrenalism
Which hormones are produced by the posterior pituitary?
ADH and oxytocin
Which clinical syndrome involves ADH?
Diabetes insipidus
SIADH
List some consequences of the local mass effet of pituitary tumours.
- Bitemporal hemianopia (optic chiasm)
- Headaches (raised ICP)
- Obstructive hydrocephalus
Describe the histological appearance of the thyroid gland.
- Arranged into follicles with a small amount of stromal tissue between them
- They are lined by epithelial cells and have a large amount of colloid in the middle
- Parafollicular cells are found between the follicles
Describe the physiological response of the thyroid gland to TSH.
- Stimulating of TSH receptors leads to pinocytosis of the colloid by the thyroid follicular cells and promotes the conversion of thyroglobulin into T3 and T4
- Release of thyroid hormones into the circulation results in a rise in basal metabolic rate
Which hormone do parafollicular cells produce?
Calcitonin - this promotes the absorption of calcium by the skeletal system
What is a non-toxic goitre?
Enlargement of the thyroid gland without overproduction of thyroid hormones
What is the most common cause of non-toxic goitre?
- Iodine deficiency
- NOTE: bassicas (e.g. cabbages) interfere with thyroid hormone synthesis
- It may also be caused by a hereditary enzyme deficiency
List some primary causes of thyrotoxicosis.
- Graves’ disease
- Hyperfunctioning multinodular goitre/adenoma
- Thyroiditis
List some causes of thyrotoxicosis that are not associated with the thyroid gland.
- Struma ovarii - ovarian teratoma with ectopic thyroid hormone production
- Factitious thyrotoxicosis - exogenous thyroid hormone intake
Which antibodies are often seen in Graves’ disease?
Antibodies to the TSH receptor and thyroglobulin
Describe the effect of TSH receptor-stimulating antibodies.
They stimulate thyroid hormone release and increase proliferation of the thyroid epithelium.
List some primary causes of hypothyroidism.
- Post-ablative
- Autoimmune (Hashimoto’s)
- Iodine deficiency
- Congenital biosynthetic defect
Describe the presentation of Hashimoto’s thyroiditis.
Painless enlargement of the thyroid gland with symptoms of hypothyroidism.
Describe the histology of Hashimoto’s thyroiditis.
- There are lots of lymphoid cells with germinal centres
- The epithelial cells become large with lots of eosinophilic cytoplasm (Hurthle cells)
List some features of a thyroid lump that would be suggestive of neoplasia.
- Solitary rather than multiple
- Solid rather than cystic
- Younger patients
- Male more than female
- Less likely to take up radioiodine
List some features of adenomas of the thyroid gland.
- Usually solitary
- Well circumscribed
- Well-formed capsule
- Small proportion will be functional
List the four types of thyroid cancer in order of decreasing prevalence.
- Papillary (80%)
- Follicular (15%)
- Medullary (5%)
- Anaplastic
What are some risk factors for thyroid cancer?
- Genetic factors (e.g. MEN)
- Ionisation radiation (mainly papillary)
What is the diagnosis of papillary thyroid cancer based on?
- Nuclear features
- Optically clear nuclei
- Intranuclear inclusions (Orphan Annie Eye)
- There may also be psammoma bodies (little foci of calcification)
- Usually non-functional
- On histology, they have a papillary structure (central connective tissue stalk with surrounding epithelium)
Where does papillary thyroid cancer tend to metastasise to?
Cervical lymph nodes
Where does follicular thyroid cancer tend to metastasise?
Lungs, bone and liver (via the bloodstream)
Which cells are medullary thyroid cancers derived from?
Parafollicular C cells
NOTE: 80% are spoardic, 20% are familial
What tends to happen to the calcitonin produced by tumour cells in medullary thyroid cancer?
- It is broken down and deposited as amyloid within the thyroid
What are the parathyroid glands derived from?
Developing pharyngeal pouches
List the actions of PTH.
- Activates osteoclasts
- Increased renal absorption of calcium
- Increases activation of vitamin D
- Increases urinary phosphate exretion
- Increases intestinal calcium absorption
What is hyperparathyroidism usually caused by?
- 80% solitay adenoma
- 20% due to hyperplasia of all four glands (sporadic or part of MEN1)
Describe the histological appearance of a parathyroid adenoma.
Very cellular tissue with no fat (whereas the normal parathyroid gland is quite fatty)
What bone change is seen in hyperparathyroidism?
Osteitis fibrosa cystica - caused by bone resorption with thinning of the cortex
What is the most common cause of secondary hyperparathyroidism?
Renal failure
List some causes of hypoparathyroidism.
- Surgical ablation
- Congenital absence
- Autoimmune
List some clinical features of hypoparathyroidism.
- Neuromuscular irritability
- Cardiac arrhythmias
- Fits
- Cataracts
CATs go NUMB
Which cell types constitute the cortex and medulla of the adrenal gland?
Cortex = epithelial
Medulla = neural
What are the layers of the adrenal cortex and which hormones do they produce?
- Glomerulosa - aldosterone
- Fasciculata - glucocorticoids
- Reticularis - sex steroids
What is the most common cause of Cushing’s syndrome?
Administration of exogenous corticosteroids (leads to adrenal atrophy)
What happens to the adrenal glands in Cushing’s disease?
Undergo nodular hyperplasia of the cortex
List some other causes of Cushing’s syndrome.
- Cushing’s disease
- Adernal adenoma/carcinoma
- Adrenal hyperplasia
What are the causes of hyperaldosteronism?
- 35% adenoma (Conn’s syndrome)
- 60% bilateral adrenal hyperplasia
List the two main clinical features of hyperaldosteronism.
Hypertension
Hypokalaemia
What causes virilising syndromes?
- May be associated with neoplasms (more commonly carcinoma than adenoma)
- Congenital adrenal hyperplasia
Describe the pathophysiology of congenital adrenal hyperplasia.
- Autosomal recessive
- Hereditary defect in an enzyme involved in cortisol synthesis leads to cortisol deficiency
- This leads to increased ACTH release from the pituitary gland
- ACTH stimulates androgen synthesis from the adrenal gland
List three causes of acute primary adrenal failure.
- Haemorrhage
- DIC associated with sepsis (Waterhouse-Friderichson syndrome)
- Sudden withdrawal of corticosteroid treatment
List some causes of chronic primary adrenal failure.
- Autoimmune (90%)
- TB
- HIV
- Metastic tumour
What are the two types of adrenocortical neoplasm?
- Adenomas - mostly functional, may be associated with Cushing’s syndrome or Conn’s syndrome
- Carcinomas - rare, more commonly associated with virilisng syndromes than adenomas
What are the two types of tumours of the adrenal medulla?
- Phaeochromocytoma
- Neuroblastoma
What is the rule of 10s regarding phaeochromocytomas?
- 10% associated with a syndrome
- 10% bilateral
- 10% malignant
- 10% oustide the adrenal gland (paraganglioma)
Define multiple endocrine neoplasia.
A group of inherited conditions resulting in proliferative lesions of multiple endocrine organs
Outline the features of MEN.
- Tumours tend to occur at a younger age
- Tumours tend to arise in multiple endocrine organs or may be multifocal within one organ
- Tumours are often preceded by hyperplasia
- Tumours are usually more aggressive than sporadic tumours
