Histopath 4: Endocrine Disease Flashcards by D J

What types of cell are the anterior and posterior pituitary made up of?

Anterior = epithelial cells

Posterior = nerve cells

How well did you know this?

Not at all

Perfectly

What is the blood supply to the anterior pituitary?

Pituitary portal system

How well did you know this?

Not at all

Perfectly

Where do the nerves that make up the posterior pituitary originate?

Supraoptic nucleus and paraventricular nucleus

How well did you know this?

Not at all

Perfectly

Describe the histology of the anterior pituitary.

Made up of epithelial cells derived from the developing oral cavity

How well did you know this?

Not at all

Perfectly

How is hyperpituitarism classified?

Based on the hormone produced (this is detected by immunohistochemistry)

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

What is a microadenoma?

A pituitary adenoma with a diameter < 1 cm

How well did you know this?

Not at all

Perfectly

Outline the clinical features of prolactinoma.

Galactorrhoea

Prolactin has inhibitory effect on FSH and LH hence causes:
Amenorrhoea
Loss of libido
Infertility

How well did you know this?

Not at all

Perfectly

What are the clinical manifestations of growth hormone adenomas?

Gigantism (in prepubertal children)

Acromegaly (in adults)

How well did you know this?

Not at all

Perfectly

What disease is caused by corticotroph cell adenomas?

Cushing’s disease

How well did you know this?

Not at all

Perfectly

List some causes of hypopituitarism.

Non-secreting pituitary adenoma (via compression)

Ischaemia (Sheehans, DIC, Shock)

Iatrogenic (e.g. surgery, radiotherapy)

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Which hormones are produced by the posterior pituitary?

ADH and oxytocin

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

List some consequences of the local mass effect of pituitary tumours.

Bitemporal hemianopia (optic chiasm)

Headaches (raised ICP)

Obstructive hydrocephalus

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Which hormone do parafollicular cells produce?

Calcitonin – this promotes the absorption of calcium by the skeletal system

How well did you know this?

Not at all

Perfectly

What is a non-toxic goitre?

Enlargement of the thyroid gland without overproduction of thyroid hormones

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Causes of hyperthyroidism?

Primary:

Graves’ disease (MOST COMMON)
Hyperfunctioning multinodular goitre/adenoma
Thyroiditis

Secondary:
- TSH producing adenoma (rare)

Other:
- Exogenous thyroid intake

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Which antibodies are often seen in Graves’ disease?

Antibodies to the TSH receptor (Anti-TSHr) and thyroglobulin

How well did you know this?

Not at all

Perfectly

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