Pathology of Endocrine System 2 Flashcards
Where is the pituitary gland located?
Sella turcica
What is the pituitary gland connected to the hypothalamus by?
Pituitary stalk
What are the 2 distinct components of the pituitary gland?
Anterior pituitary
Posterior pituitary
What is the anterior pituitary also called?
Adenohypophysis
Which componenet of the pituitary gland is the larger?
Anterior pituitary (is 80% of mass)
What does the anterior pituitary secrete?
ACTH
TSH
GH
Prolactin
FSH/LH
What is the secretion of hormones from the anterior pituitary controlled by?
Release factors from hypothalamus
Where does the blood supply to the anterior pituitary come from?
Hypothalamus
What is the posterior pituitary also called?
Neurohypophysis
What does the posterior pituitary secrete?
ADH
Oxytocin
What is the most common cause of pituitary hyperfunction?
Pituitary adenoma (carcinomas are very rare and also some hypothalamic disorders)
What age group does pituitary adenoma usually affect?
35-60 years
Is there a genetic predisposition to pituitary adenoma?
MEN-1
What is the effect of a functioning pituitary adenoma?
- Effects if functioning is hormone excess
- Prolactinoma 20-30%
- Galactorrhoea, menstrual disorders
- GH secreting
- Acromegaly, gigantism
- ACTH secreting
- Cushing’s disease
- Non-functioning 25-30%
- Prolactinoma 20-30%
If a pituitary adenoma is a prolactinoma, what does it cause?
Galactorrhoea
Menstrual disorders
If a pituitary adenoma is a GH secreting, what does it cause?
Acromegaly
Gigantism
If a pituitary adenoma is a ACTH secreting what does it cause?
Cushing’s disease
What can happen if a pituitary adenoma is large?
- If large, can have a mass pressure effect
- Radiographic abnormalities
- Visual field abnormalities
- Elevated intracranial pressure
- Compression damage, such as hypopituitarism
What percentage of pituitary function needs to be los to be considered pituitary hypofunction?
75%
What can cause pituitary hypofunction?
Compression by tumours
Trauma
Infection (rare)
Post partum ischaemic necrosis
What infections can cause pituitary hypofunction?
TB
Sarcoidosis
What are the adrenal glands composed of?
Adrenal cortex
Adrenal medulla
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What classification of hormones does the adrenal cortex secrete?
Steroid hormones
What are the 3 layers of the adrenal cortex?
- Zona glomerulosa secretes mineralocorticoids (aldosterone)
- Zona fasciculate secretes glucocorticoids (cortisol)
- Zona reticularis secretes sex steroids
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What does the zona glomerulosa secrete?
Minerlocorticoids (aldosterone)
What does the zona fasciculate secrete?
Glucocorticoids (cortisol)
What does the zona reticularis secrete?
Sex steroids
What does the adrenal medulla secrete?
Adrenaline/noradrenaline
What cells are found in the adrenal medulla?
Neuroendocrine (chromaffin) cells
What are some examples of the classifications of adrenal pathology?
- Hyperfunction
- Hypofunction
- Mass lesion
- Effect depends on disease process which could be atrophy, normal, hyperplasia or tumour
What are the 3 syndromes for adrenal cortical hyperfunction?
- Hypercortisolism
- Called Cushing’s syndrome
- Hyperaldosteronism
- Called Conn’s syndrome
- Adrenogenital syndromes
What is hypercorticolism called?
Cushing’s syndrome
What is hyperaldosteronism called?
Conn’s syndrome
What is the aetiology of hypercortisolism?
- Exogenous
- Iatrogenic steroids
- Endogenous
- ACTH dependent
- Pituitary adenoma Cushing’s disease 70%
- Ectopic ACTH
- ACTH independent
- Functioning adrenal adenoma 10%
- ACTH dependent
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What is the main cause of ACTH dependent hypercortisolism?
Pituitary adenoma Cushing’s disease 70%
Ectopic ACTH
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What is the main cause of ACTH independent hypercortisolism?
Functioning adrenal adenoma
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How is hypercortisolism diagnosed?
Measuring cortisol, ACTH and response to ACTH suppresion
What is the aetiology of hyperaldosteronism?
Bilateral idiopathic hyperplasia
Functioning adrenal adenoma
What is the clinical presentation of hyperaldosteronism?
Increased sodium retention in nephron
Maybe asymptomatic
May have muscular weakness, tingling, spasms, hypertension, headaches
What are some adrenogenital syndromes?
- Functioning adrenal tumour
- Pituitary tumour such as Cushing’s disease
- Congenital adrenal hyperplasia (due to steroid enzyme deficiency)
What is the clinical presentation of adrenogenital syndrome?
Ambiguous genitalia
Precocious puberty
Failure of puberty
Infertility
What is adrenal insufficiency caused by?
Destruction of the adrenal glands
What can cause acute adrenal insufficiency?
Meningococal septicaemia
What can cause chronic adrenal insufficiency?
- Primary is Addison’s disease
- Caused by
- Autoimmune
- Autoimmune polyendocrine syndromes
- Infections
- TB, fungus HIV related infections
- Replacement
- Metastatic carcinoma amyloidosis
- Atrophy
- Prolonged steroid therapy
- Congenital
- Autoimmune
- Caused by
- Secondary is pituitary failure
What are some causes of Addison’s disease?
- Autoimmune
- Autoimmune polyendocrine syndromes
- Infections
- TB, fungus HIV related infections
- Replacement
- Metastatic carcinoma amyloidosis
- Atrophy
- Prolonged steroid therapy
- Congenital
What do functioning adenomas in the adrenal cortex cause?
Hyperadrenal syndromes
Atrophy of adjacent cortex
What is the histology of adrenal adenomas?
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What are the different kinds of adrenal carcinoma?
Primary adrenocortical carcinoma
Metastatic carcinoma
Are primary adrenocortical carcinomas more likely to be functioning or non-functional?
Functional
How does primary adrenocortical carcinoma often metastasis?
By lymphatics and blood, invades adrenal vein
Is primary adrenocortical carcinoma or metastatic carcinoma of adrenal gland more common?
Metastatic carcinoma
Where do metastatic carcinomas in the adrenal glands often come from?
Lung or breast
What is an example of an adrenal medullary tumour?
Phaeochromocytoma
What does phaeochromocytoma secrete and in turn cause?
Carecholamines causing hypertension
Is there a genetic predisposition to phaeochromocytoma?
Up to 30% is inherited, such as due to MEN2 or SDH
What is the histology of phaechromocytoma?
Nests of polygonal cells in vascular network
Granular cytoplasm containing catecholamines
What are multiple endocrine neoplasia?
Inherited disorders with underlying gentic mutation
What does MEN stand for?
Multiple endocrine neoplasia
What does MEN cause?
Hyperplasia/neoplasms of endocrine organs
When is the term MEN used?
Whe there is two or more distinct endocrine tumours due to one syndrome
What are some different MEN syndromes?
MEN1 (Wermer syndrome)
MEN2 (MEN2A and MEN2B)
What is MEN1 also known as?
Wermer syndrome
What does the MEN1 tumour suppressor gene mutation cause defect in?
Menin protein
What tumours are associated with MEN1 syndrome?
- Parathyroid hyperplasia and adenomas
- Pancreatic and duodenal endocrine tumours (causing hypoglycaemia and ulcers)
- Pituitary adenoma (prolactinoma)
What is the function of the menin protein?
Involved in regulating cell growth
What is MEN2 syndrome caused by?
RET proto-oncogene mutations
What tumours are associated with MEN2?
Medullar carcinoma of thyroid and phaeochromocytoma
What is MEN2A also known as?
Sipple syndrome
What is MEN2A due to?
Extracellular domain auto dimerisation of RET receptor
What tumours are associated with MEN2A?
Medullary carcinoma of thyroid, phaeochromocytoma and parathyroid hyperplasia
Is MEN2A or MEN2B more likely to affect younger patients?
MEN2B
What is MEN2B due to?
Autoactivation of tyrosine kinase pathway
What tumours are associated with MEN2B?
- Causes medullary carcinoma of thyroid, phaeochromocytoma and parathyroid hyperplasia
- Plus neuromas of skin and mucous membrane, skeletal abnormalities
What is the normal function of RET gene?
Provide instruction for producing a protein involved in signalling within cells