Histopath 4: 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?
Other types?
Prolactinoma
GH adenoma - next most (gigantism or acromegaly)
ACTH adenoma - bit less common (Chushings)
What is a microadenoma?
A pituitary adenoma with a diameter < 1 cm
Outline the clinical features of prolactinoma.
Galactorrhoea
Prolactin has inhibitory effect on FSH and LH hence causes:
Amenorrhoea
Loss of libido
Infertility
What are the clinical manifestations of growth hormone adenomas?
Gigantism (in prepubertal children)
Acromegaly (in adults)
What disease is caused by corticotroph cell adenomas?
Cushing’s disease
List some causes of hypopituitarism.
Non-secreting pituitary adenoma (via compression)
Ischaemia (Sheehans, DIC, Shock)
Iatrogenic (e.g. surgery, radiotherapy)
What is the most common cause of ischaemic necrosis of the pituitary gland? What is this?
Other causes?
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.
GH deficiency -> growth failure in children
GnRH deficiency –> amenorrhoea, infertility, impotence, loss of libido
TSH and ACTH deficiency -> Hypothyroidism and Hypoadrenalism
Prolactin deficiency -> failure of post-partum lactation
Which hormones are produced by the posterior pituitary?
ADH and oxytocin
Which clinical syndromes involve ADH?
Diabetes insipidus - deficiency ADH (cranial v nephrogenic)
SIADH - excess ADH (causes euvolaemic hyponatraemia)
NB: This is a diagnosis of exclusion
List some consequences of the local mass effect 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?
Others?
Iodine deficiency
NOTE: brassicas (e.g. cabbages) interfere with thyroid hormone synthesis
It may also be caused by a hereditary enzyme deficiency
Causes of hyperthyroidism?
Primary:
- Graves’ disease (MOST COMMON)
- Hyperfunctioning multinodular goitre/adenoma
- Thyroiditis
Secondary:
- TSH producing adenoma (rare)
Other:
- Exogenous thyroid intake
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 (Anti-TSHr) and thyroglobulin
Describe the effect of TSH receptor-stimulating antibodies.
They stimulate thyroid hormone release and increase proliferation of the thyroid epithelium
List some causes of hypothyroidism.
Primary:
- Iatrogenic - post mx of hyperthyroidism
- Autoimmune (Hashimoto’s) - most in the UK
- Iodine deficiency - most common cause worldwide
Secondary:
- Pituitary failure
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 (H for Hurthle cells / Hashimotos)
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 + feature
Which is most aggressive
Papillary (80%)
Follicular (15%) - middle age
Medullary (5%) - parafolicular C cells
Anaplastic - Most aggressive and mets common
What are some risk factors for thyroid cancer?
Genetic factors (e.g. MEN)
Ionising radiation (mainly papillary)
What is the diagnosis of papillary thyroid cancer based on? What nuclear + histological features
Nuclear features
- Optically clear nuclei
- Intranuclear inclusions (Orphan Annie eye)
- There may also be psammoma bodies (little foci of calcification)
Usually non-functional + mass in neck
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?
Cause of cancer?
Parafollicular C cells - calcitonin producing
NOTE: 80% are sporadic (more in adults 50+), 20% are familial (younger age - associated w/ MEN)
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 intestinal calcium absorption
Increases activation of vitamin D
Increases urinary phosphate excretion
What is hyperparathyroidism usually caused by?
80% solitary adenoma > galnd hyperplasia > carcinoma
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 (OFC)– Thinning of the cortex caused by bone resorption
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.
Convulsions
Arrhythmias
Tetany (Neuromuscular irritability)
Spasms
Numbness in the hands and feet and around the mouth
Cataracts
(CATs go NUMBC)
Which cells types constitute the cortex and medulla of the adrenal gland?
Cortex = epithelial
Medulla = neural
What are the layers of the adrenal cortex + medulla and which hormones do they produce?
Zona Glomerulosa – aldosterone
Zona Fasciculata – glucocorticoids (cortisol)
Zona Reticularis – sex steroids (androgens)
Adrenal Medulla - Stress hormones (adrenaline, noradrenaline)
What is the most common cause of Cushing’s syndrome? what happens to adrenal gland?
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 endogenous causes of Cushing’s syndrome.
- Cushing’s disease - ACTH producing adenoma
- Adrenal causes - adenoma/carcinoma /bilateral hyperplasia
- Ectopic ACTH production - Small cell carcinoma of the lung
Generally all triger some adrenal hyperplasia
What are the causes of hyperaldosteronism?
35% Conn’s syndrome - aldosterone secreting adenoma (More importnat in qs)
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 (Usually 21-hydroxylase) in aldosterone & cortisol synthesis leads to aldosterone + 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%) - most common in the uk
TB - most common worldwide
HIV
Metastatic 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 virilising 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% outside 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.
Tumour 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
amenorrhoea, infertility, impotence, loss of libido
- How to tell difference between prolactinoma and GnRH deficiency causes?
Prolactinoma - visual field defects + lactation which isnt seen in other option
Stimulants and Inhibitors of TRH release from hypothalamus?
Stimulation:
- Cold
- Acute psychosis
- Circadian rhythm
Inhibitors:
- Severe stress
- Thyroxine
Effect of iodine levels on thyroxine production in the thyroid?
Low iodine = stimulant
High iodine (Wold-Chalkoff effect) - Inhibitory
Triad of Graves?
What conditions associated w/?
Thyrotoxicosis, exopthalmos, pretibial myoxedema
Associate w/ other AI conditions - SLE, Pernicious anaemia, T1DM, Addisons
Which type of thyroid cancer is associated w/ MEN? In which patients would you be more likely to suspect this?
Younger patient w/ medullary thyroid carcinoma
Symptoms of cushings?
HTN, Moon facies, Buffalo hump, truncal obesity
Phaeochromocytoma cause release of what?
Catecholamine - adrenaline + noradrenaline
NB- this is because they affect adrenal medulla
Antibody most associated w/ graves?
Anti-TSHr
Type of thyroid cancer associated w/ psammoma bodies?
Papillary thyroid cancer
Most common cause of cushings syndrome? what happens to adrenals?
Exogenous intake of steroids - Adrenal atrophy
Symptoms of congenital adrenal hyperplasia (CAH)?
Aldosterone -Salt losing crisis - hyponatraemia / hyperkalaemia w/ marked depletion of fluids
Hypoglycaemia - lack of cortisol -> raised ACTH -> increased adrenal stimulation (w/ out 21-OH) -> increased androgen production hence females w/ ambiguous genitalia
