ENDO - Pituitary and adrenal disease Flashcards
What are the causes of sellar (near the depression on the upper surface of the sphenoid bone, lodging the pituitary gland) masses?
- Benign Tumours
•Pituitary adenoma
•Craniopharyngioma
•Meningioma - Malignant Tumours
•Primary (vanishingly rare)
•Metastatic tumours (lung, breast) - Cysts
•Rathke’s cleft
•Arachnoid
•Dermoid - Lymphocytic hypophysitis
- Carotid aneurysm
What are the (4) local effects of pituitary tumours?
- Headaches; due to stretching of dura by tumour or hydrocephalus (rare)
- visual field defects; nasal retinal fibres are compresed by tumour (temporal hemianopia)
- Cranial nerve palsies & temporal lobe epilepsy due to lateral extension of tumour
- Cerebrospinal fluid rhinorrhoea: due to downward extension of tumour
What are the types of pituitary adenomas?
- Prolactinoma: prolactin secreting
- acromegaly: GH secreting
- Cushing’s: ACTH secreting
Very rarely:
- TSH secreting
- Gonadotrophin secreting (FSH & LH)
Non functioning
Px of prolactinoma (in women & men)
In women
•Hypogonadism - infertility, amenorrhea or oligomenorrhea
•galactorrhoea
In men (harder to pick up than women) •Hypogonadism - decreased libido, infertility, impotence, gynaecomastia, rarely galactorrhoea
How do you treat prolactinoma?
Dopamine agonists
•bromocriptine
•cabergoline 0.5mg daily
Dopamine agonists decrease the synthesis and secretion of PRL. It also decreases the rate of tumor cell division and the growth of individual cells.
What are the causes of acromegaly?
Common
•GH secreting pituitary adenoma
Rare
•GH secreting extra pituitary tumour
•GH releasing hormone secreting tumour
Px of acromegaly
•Insidious onset - often helped by looking at old photographs
•Enlarged jaw, hands and feet
–dental problems, tight rings, increased shoe size
•Coarsening of facial features, enlarged frontal bones and nose
•thickened skin
•enlargement of tongue, deepening of voice
Somatic effects - Growth of many tissues •skin •connective tissue •cartilage •bone •viscera •epithelial tissues
Ix of Acromegaly
Biochemistry
•increased growth hormone; failure to suppress with OGTT
•increased IGF1 (somatomedin C)
•diabetes or impaired glucose tolerance
Imaging
•CT or MRI scan may show a large pituitary tumour
What is oral glucose tolerance test (OGTT)?
drinking 75 to 100 grams of glucose solution to see if it lowers blood GH levels to less than 1 nanogram per milliliter (ng/ml), which is normal in healthy people.
In people with GH overproduction, this suppression does not occur. The oral glucose tolerance test is a highly reliable method for confirming a diagnosis of acromegaly.
GH secretion is part of the counter-regulatory defence against hypoglycaemia and physiological GH secretion is inhibited by hyperglycaemia.
In acromegaly, or gigantism, GH secretion is autonomous and does not suppress and may paradoxically rise with hyperglycaemia.
Paradoxical stimulation or non-response of GH secretion following a 75g oral glucose load in an acromegalic patient
How do you treat acromegaly?
First line - transphenoidal hypophysectomy to remove tumour
If not cured surgically, possible treatments:
•radiotherapy
•octreotide - long acting preparation given once/month
•bromocriptine (dopamine agonist)
What are the causes of Cushing’s syndrome (ACTH-dependent & ACTH-independent)?
ACTH-dependent Cushing’s Syndrome (secondary)
•Cushing’s Disease
•Ectopic ACTH
•Ectopic CRF
ACTH-independent Cushing’s Syndrome (primary) •Adrenal adenoma •Adrenal carcinoma •Micronodular hyperplasia •Macronodular hyperplasia
Px of Cushing’s syndrome
- Obesity - redistribution of weight centrally , moon face, buffalo hump, wasting of buttocks
- Skin - atrophy of epidermis; thin skin, plethoric face, easy bruising, striae (esp abdomen)
- Neuropsychiatric - depressed mood and crying; decreased concentration and memory; insomnia and decreased libido
- Proximal myopathy
- Osteopenia - crush fractures of vertebrae
- Diabetes 25%; glucose intolerance 75%
- Hirsutism; hypertension; menstrual disorders
Ix of Cushing’s syndrome
•Full blood examination
–haemoglobin - high normal range
–WCC - slightly elevated; decreased neutrophils
•Electrolytes
–hypokalemia and metabolic alkalosis in ectopic ACTH
•Hyperglycemia - due to insulin resistance
•Increased calcium absorption and hypercalciuria
How do you diagnose Cushing’s syndrome?
(CRH by hypothalamus -> ACTH by a. pituitary -> Cortisol by adrenals)
•24 hour urine free cortisol
•Overnight dexamethasone suppression test (Serum cortisol at 8.00 am after 1mg dexamethasone at midnight should be suppressed in normal)
Establish pathological cause •ACTH –if suppressed - likely adrenal cause –normal or slightly elevated - likely pituitary dependent –very high - likely Ectopic ACTH
•Imaging
–pituitary - if adenoma - likely Cushing’s disease
–adrenal tumours
What are the 4 forms of Cushing’s syndrome depending on the causative origin? What would the adrenal gland look like (hypertrophied/ atrophied)?
- Pituitary Cushing’s syndrome:
- tumour in ant pituitary -> ACTH -> adrenal hyperplasia - Adrenal Cushing syndrome:
- Tumour in adrenal
- Adrenal nodular hyperplasia - Paraneoplastic Cushing’s syndrome
- Lung cancer etc -> ACTH -> Adrenal hyperplasia - Iatrogenic Cushing’s syndrome
- Steroids -> Adrenal atrophy
Compare the MRI appearance & prognosis of pituitary microadenoma & large macroadenomas.
Pituitary microadenoma:
- hypodense lesion
- deviation of the pituitary stalk away from the lesion
- curable by transsphenoidal hypophysectomy
Pituitary large macroadenomas:
- invariably invasive and recur after surgery
Rx of Cushing’s syndrome
Pituitary dependent Cushing’s
•Transphenoidal hypophysectomy to remove tumour
Adrenal adenoma or carcinoma
•adrenal surgery
Ectopic ACTH or CRF
•treat the tumour associated with the hormone production
What are the 2 causes of adrenocortical insufficiency?
- Insufficient secretion of ACTH by pituitary - hypopituitarism
- Destruction of adrenal glands - Addison’s disease
Ix of Addison’s disease. What do you expect to see?
Electrolytes •hyponatremia •hyperkalemia •moderate acidosis •increased urea
Hypoglycaemia
What are the diagnostic tests for Addison’s disease?
- Serum cortisol - low
- ACTH - high
- Synacthen test (ACTH infusion test)
- Adrenal antibodies (17 hydroxylase enzyme antibodies)
- Adrenal imaging- calcification or enlargement of adrenals - TB or infiltration
What is a Synacthen test?
The ACTH test performed to assess the functioning of the adrenal glands stress response by measuring the adrenal response to adrenocorticotropic hormone (ACTH; corticotropin) or another corticotropic agent such as Synacthen.
With ACTH infusion, the adrenal glands are stimulated to release cortisol in normal healthy people. Failure to do so can indicate Addison’s disease.
How do you manage an Addisonian crisis (fatally low cortisol with hypoglycaemia & hypovolaemia)?
- Hydrocortisone 100mg IV 6hrly
- Fluid replacement - IV normal saline
- Glucose if hypoglycemic
Longterm management of Addison’s disease
Glucocorticoids
•Cortisone acetate 25mg/12.5mg
•Dexamethasone 0.25mg bd
•Prednisolone 5mg daily
Mineralocorticoids
•Fludrocortisone 0.1mg daily
Medic alert and advice on increasing steroid during times of stress
What are the causes & (2) conditions involving excessive adrenal hormone production?
Adrenal cortex
•Aldosterone excess - Conn’s syndrome
Adrenal medulla
•Catecholamine excess - phaeochromocytoma
Describe primary aldosteronism subtypes in Conn’s syndrome.
- Unilateral aldosterone producing adenoma (64%)
- Bilateral idiopathic hyperaldosteronism
- Glucocorticoid suppressible hyperaldosteronism
- Aldosterone producing adrenal carcinoma
What is the clinical triad of primary aldosteronism (Conn’s syndrome)?
- Hypertension
- Hypokalemia
–headaches, palpitations, polydipsia, polyuria, nocturia - Metabolic alkalosis
Remember Aldosterone works on Na+/K+/H+ channel on collecting duct; reabsorbs Na+, excretes K+ & H+.
How do you diagnose primary aldosteronism? What ratio is high?
- 24 hr urine collection to document inappropriate K+ wasting in the presence of hypokalemia
- Plasma renin activity - should be suppressed in the disease
- Plasma or urine aldosterone - should be increased in the disease
- Aldosterone fails to suppress after infusion of 2L N Saline over 4 hours or high Na+ intake for 3 days
- High aldosterone/renin ratio
How do you radiologically localise primary aldosteronism?
- CT or MRI scanning
- 131I-iodocholesterol scanning
- Adrenal vein sampling for aldosterone (risk of non functioning adrenal tumour or bilateral disease)
Rx of primary aldosteronism (Conn’s syndrome)
- Adrenal adenoma: adrenal surgery
- Aldactone: competitive antagonist to aldosterone
- Amiloride: blocks sodium channels in the proximal tubule thus decreasing potassium excretion (less Na+ to be exchanged with K+ & H+ in collecting tubule)
Describe Conn’s syndrome
Primary aldosteronism is excess production of the hormone aldosterone by the adrenal glands resulting in low renin levels.
Often it produces few symptoms.
- (most common) high blood pressure which may cause poor vision or headaches.
- muscular weakness, muscle spasms, tingling sensations, or excessive urination.
Complications include CVD such as stroke, myocardial infarction, kidney failure, and abnormal heart rhythms.
Its causes include unilateral aldosterone producing adenoma (64%) & bilateral idiopathic hyperaldosteronism.
Describe phaeochromocytoma
- tumour of which type of cells
- location (which is most common)
- derived from which cells
- % of malignancy
- A tumour of chromaffin cells located in the adrenal medulla
- Derived from neural crest cells
- 90% arise in adrenal medulla
- 5% bilateral
- 10% extra adrenal; base of brain to testis
- Childhood and familial cases tend to be bilateral
- Malignancy 3 to 14%
Px of phaeochromocytoma
Episodic symptoms
•Sudden and severe (usually
How do you diagnose phaeochromocytoma?
- Urine catecholamines (24 hour collection); increased excretion of metabolites of catecholamines
- Plasma catecholamines (marked variability
How do you localise phaeochromocytoma?
- CT scanning
- Meta Iodo Benzyl Guanidine (MIBG) scanning
- Octreotide scanning
- Venous sampling
Pre-operative Rx of pheochromocytoma
- alpha adrenergic blockade: phenoxybenamine (40-100mg/daily). Vasodilates.
- increase dose until normotensive with postural hypotension & nasal stuffiness - Beta blockers if necessary. but NEVER BEFORE alpha-blockade. (ALPHA before BETA)
- Rx of arrhythmias, cardiac failure & diabetes as required
Describe type 1 & 2 polyglandular endocrine autoimmune deficiency syndromes
diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected
Type I: Rare. AIRE gene (Chr 21) defect, autosomal recessive. Affects immune tolerance
Type II: more common. Heterogeneous (c.f. one gene). Higher risks with HLA-DQ2, HLA-DQ8 and HLA-DR4. F»M.
Includes Addison’s, Grave’s, pernicious anaemia, T1D, coeliac disease, myasthenia gravis.
Possible Px of Polyglanduar autoimmune syndrome type I (endocrine & non-endocrine)
Endocrine •Hypoparathyroidism •Chronic Mucocutaneous candidiasis •Adrenal insufficiency •Primary hypogonadism •Hypothyroidism •Type 1 diabetes •Hypothyroidism •Hypopituitarism •Diabetes insipidus
Non Endocrine •Malabsorption syndromes •Alopecia totalis or areata •Pernicious anaemia •Chronic active hepatitis •Vitiligo
Describe polyglandular autoimmune syndrome type I
- very rare
- autosomal recessive
- mutation of autoimmune regulator (AIRE) on Chr 21
Describe polyglandular autoimmune syndrome type II
- more common than type 1
- > 50% familial
- autosomal recessive, autosomal dominant, polygenic reported
- associated w/ high titres of antibodies to steroid producing cells (adrenal, thyroid, testis, ovaries)
Possible Px of Polyglanduar autoimmune syndrome type II (endocrine & non-endocrine)
Endocrine •Adrenal insufficiency •Autoimmune thyroid disease •Type 1 diabetes •Primary hypogonadism •Diabetes insipidus
Non Endocrine •Vitiligo •Alopecia* •Pernicious anaemia •Myaesthenia gravis* •Immune thrombocytopenic purpura* •Sjogrens syndromes* •Rheumatoid arthritis*
*indicates c.f. type I
What is Multiple endocrine neoplasia syndromes?
several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern.
In some cases, the tumors are malignant, in others, benign.
MEN syndromes are inherited as autosomal dominant disorders
Describe multiple endocrine neoplasia syndrome (MEN)1
- Autosomal dominant
- Gene is located on chromosome 11
- Primary hyperparathyroidism (>90%)
- Pancreatic islet tumours (60-70%): gastrinoma, insulinoma, glucagonoma, VIPoma, non functioning
- Pituitary tumours (10-20%): prolactinoma, GH secreting tumours, ACTH secreting, non hormone secreting
What are the 3 organs affected in MEN1 (multiple endocrine neoplasia)?
3Ps
- Pituitary
- Pancreas
- Parathyroid
Describe MEN2 (multiple endocrine neoplasia). Compare compositions of MEN2a & MEN2b
- Autosomal dominant
- mutation of RET protooncogene on Chr10
MEN2a:
- Medullary carcinoma of thyroid (>90%)
- Phaeochromocytoma (40-50%)
- Parathyroid hyperplasia (10-20%)
MEN2b: MEN2a plus: - mucosal neuromas - intestinal ganglioneuromas - Marfanoid habitus
What are the 3 organs affected in MEN2a?
- Thyroid medulla
- Adrenal medulla
- Parathyroid
