Adrenals and Endocrine Pancreas Flashcards
What conditions can cause adrenal hyperfunction?
- Cushing’s syndrome
- Conn’s syndrome
- Adrenogenital syndrome and congenital adrenal hyperplasia
- Adrenocortical neoplasms
Is cushing’s syndrome more common in males or females?
Females
What are features of Cushing’s syndrome?
- Muscle catabolism
- Fat
- Abnormal collagen maturation (can cause stria)
- Hypertension
- Osteoperosis (absorbing more Ca2+)
- Impaired glucose tolerance
- Hirsutism or gyaenacomastia
- Depression / psychosis
What is hirsutism?
Abnormal male-like hair growth on women
What fraction of Cushing’s syndromes are caused by a primary adrenal neoplasm?
~ 1/6
- 50:50 benign to malignant
What fraction of Cushing’s syndromes are related to ectopic ACTH production?
~ 1/6
- Ectopic ACTH or related peptide
- Often part of a paraneoplastic syndrome e.g SCLC
What are the levels of K+ in Conn’s syndrome?
Low (hypokalaemic)
WHat are the features of Conn’s syndrome?
- Hypokalaemia
- Muscle cramps and weakness
- Metabolic alkalosis
- High aldosterone
- Low renin
What gender is affected more by Conn’s syndrome?
Females (4:1)
What percentage of Conn’s syndrome patients have an adrenal adenoma?
80%
What percentage of Conn’s syndrome patients have bilateral hyperplasia of zona glomerulosa but unkown cause?
20%
What enzyme deficiencies can cause congenital adrenal hyperplasia?
- 21 hydroxylase deficiency (CYP21)
- 11-Beta Hydroxylase Deficiency
How common is congenital adrenal hyperplasia?
1 in 15000
Describe the mechanism of congenital adrenal hyperplasia?
Problems in metabolism where one does not get the negative feedback to stop ACTH so you get a drive and hyperplasia
A malignant tumour in the adrenal gland can come from what tissues?
- Lung
- Breast
- Kidney
- Colon
- Melanoma
- Lymphoma
How common are adrenal adenomas on autopsy?
Very common - though to be as high as 5%
- So often not functional therefore not found in life
- Low malignant potential
- Only treated if functional or malignant
Adrenal carcinoma
- Rare
- Poor outlook
- More often secrete sex steriods (Hirsutism)
- Can be quite large (inches)
- Invasive - other organs, fat
What molecular changes can take place in an adrenal carcinoma?
- Proliferation markers increased
- Mutant p53 protein increased
- IGF II increased
- EGFR increased
What gene mutations may cuase adrenal carcinoma?
- p53
- MEN1 (multiple endocrine neoplasia)
What are molecular changes useful for?
- Identifying familial syndrome
- Possibly distinguishing adenoma from carcinoma
What cells do phaeochromocytomas develop from?
Chromaffin cells
How does phaeochromocytoma usually present?
- Intermittent production of catecholamines
- Hypertension
- Sweating
- Collapse
- Glycosuria
- When sympathetic NS activated - symptoms appear, overload of catecholamines
What percentage of phaeochromocytomas are familail?
20%, may be opart of MEN
What percentage of phaeochromocytomas are malignant?
10% (there is a spectrum of benign to frankly malignant)
What is neuroblastoma?
- Rare tumour
- Children
- Can appear late
- Kidney
- N-myc amplification or adrenal site worse prognosis
What can the causes of acute adrenal hypofunction be?
- Meningococcal septicaemia
- Disseminated intravascular coagulation - causes coagulation in organs using upclotting factors leading to haemorrhages and purpuric rashes
What What can the causes of chronic adrenal hypofunction be?
- Addison’s disease (autoimmune adrenalitis)
- Metastasis
- Amyloid
- TB
WHat are some symptoms of Addison’s disease?
- Lethargy
- Weakness
- Anorexia
- Pigmentation of skin and mucus membranes (ACTH build up)
What can the causes of Addison’s disease be?
- Autoimmune adrenalitis > 75%
- TB
- Amyloid
- Metastasis
What are some associations of Addison’s disease?
- Vitiligo
- Diabetes
How can type 2 Diabetes cause B cells not to produce insulin ?
Amyloid deposited late in islets causing loss in islets
How much concordance is there of type 1 diabetes in mono-zygotic twins?
40%
How common is type 1 diabetes?
1 in 500
How can a virus ultimately lead to type 1 diabetes?`
- Viral infection of B cell
- Interferon-alpha expression by B cell
- Islet inflammation
- Class II MHC expression by B cell
- Induction of autoimmunity to B cell
- B cells destroyed
- Diabetes
What are other less common causes of diabetes?
- Pancreatitis
- Cystic fibrosis
- Tumour
What can a G cell Gastrinoma cause?
Zollinger-Ellison syndrome
What can a vipoma (vasoactive intestinal peptide) cause?
Verner-Morrison SYndrome (pancreatic cholera)
What 2 genes can cause multiple different endocrine tumours?
- Multiple endocrine neoplasia 1 (MEN1)
- MEN2
Can be spontaneous or familial
What happens to glucose levels in acute pancreatitis?
Falls - hypoglycaemia
What can happen to the pancreas [macroscopicaly] in pancreatitis?
- Calcification
- Fibrous tissue
Primarrily affects exocrine
How can chronic pancreatitis lead to insulin insufficiency (type 1)?
Fibrotic destruction of islets
What are different neuroendocrine neoplasms?
- Glucagonoma
- Somatostatinoma
- Insulinoma
- Vipoma
- Gastrinoma
Varibale malignant potential
Stomach and SI most malignant
