Pituitary and Adrenal Disease Flashcards
1
Q
List 3 benign tumours causing a sellar mass
A
Pituitary adenoma Craniopharyngioma Meningioma
2
Q
What are the 2 kinds of pituitary tumours?
A
Primary (very rare) Metastatic tumours
3
Q
List 3 benign tumours causing a sellar masses
A
Pituitary adenoma Craniopharyngioma Meningioma
4
Q
What are the 2 kinds of pituitary tumours?
A
Primary (very rare) Metastatic tumours
5
Q
Which cancers most commonly metastasise to the pituitary?
A
Lung Breast
6
Q
List 3 types of cysts causing a sellar mass
A
Rathke’s cleft Arachnoid cyst Dermoid cyst
7
Q
What is lymphocytic hypophysitis?
A
AI? Headaches, visual symptoms?
8
Q
What are the common presenting symptoms of a space-occupying lesion in the pituitary?
A
Headches (stretching of dura by tumour, rarely hydrocephalus) Visual field defects (most commonly bitemporal hemianopia; Hx of bumping into both sides of door) Cranial nerve palsies Temporal lobe epilepsy CSF rhinorrhoea
9
Q
What are 5 possible presentations of pituitary adenoma, depending on the hormone secreted? Which of these are very rare?
A
Prolactinoma (PLN) Acromegaly (GH) Cushing’s (ACTH) TSH secreting (rare) Gonadotrophin secreting (rare) NB can have a non-functioning adenoma (will present with mass effects but no hormonal derangement)
10
Q
Prolactinoma presentation in women (symptoms of hypogonadism)
A
Galactorrhoea Oligorrhoea or amenorrhoea Infertility or subfertility
11
Q
Prolactinoma presentation in men (symptoms of hypogonadism)
A
Decreased libido Infertility Impotence Gynaecomastia Galactorrhoea (rare)
12
Q
Causes of elevated prolactin
A
Pregnancy Prolactinoma
13
Q
Causes of elevated prolactin
A
Can be loss of inhibitory signal (e.g. via ischaemia, drugs including tranquilisers, antidepressants, antipsychotics, antiepileptics, reserpine, methyldopa)
14
Q
Macroadenoma vs microadenoma
A
Macro >10mm Micro
15
Q
Macroadenoma vs microadenoma (difference in management??)
A
Macro >10mm Micro
16
Q
Prolactinoma treatment
A
DA agonists (bromocriptine, cabergoline) Not necessary to treat if minor symptoms that aren’t bothering the pt
17
Q
2 examples of DA agonists
A
Bromocriptine Cabergoline
18
Q
What is the effect of DA agonists on prolactinoma?
A
Reduce tumour size (can use for large tumours before surgical removal) Reduce PLN secretion
19
Q
Side effects of DA agonists
A
Postural hypotension N + V
20
Q
Gigantism vs acromegaly
A
Gigantism: before epiphyseal closure Acromegaly: after epiphyseal closure
21
Q
Common and rare causes of acromegaly
A
Common: GH secreting pituitary adenoma Rare: GH secreting extra-pituitary adenoma, GHRH secreting tumour
22
Q
Clinical features of acromegaly
A
Growth of many tissues (e.g. skin, connective tissue, cartilage, bone, viscera, epithelial tissues)
23
Q
Biochemical findings
A
Increased GH (failure to suppress OGTT)
Increased IGF1 (somatomedin C)
DM or impaired glucose tolerance
24
Q
3 causes of frontal bossing
A
Paget’s disease
Acromegaly
Thalassaemia
25
List 8 clinical features of acromegaly
Enlarged jaw ("prognathism"), hands, feet (ask about dental problems, tight rings, enlarged shoe size/hat size/glove size)
Coarsening of facial features, including enlarged frontal bones ("frontal bossing") and nose
Thickened skin, skin tags
Enlargement of tongue
Deepening of voice
Goitre
Hepatomegaly, cardiomegaly
Arthritis
26
3 causes of frontal bossing
Paget's disease Acromegaly Thalassaemia
27
Biochemical findings in acromegaly
Increased GH and failure to suppress with OGTT (there is paradoxical stimulation or non-response to GH secretion with OGTT; normally glucose should suppress GH)
Increased IGF-1 (somatomedin C)
Diabetes or impaired glucose tolerance
28
Imaging findings in acromegaly
CT/MRI: large pituitary tumour (more common macroadenoma due to insidious onset of symptoms, prolonged growth)
29
Treatment for acromegaly
Transphenoidal hypophysectomy (1st line)
Radiotherapy
Octreotide (long-acting ?somatostatin analogue)
Bromocriptine
30
Long-term repercussions
GH excess increases risk of bowel cancer, and cardiac hypertrophy and dysfunction (need to do structural imaging)
31
Clinical features of Cushing's
Central adiposity with moon facies, buffalo hump, wasting of buttocks
Skin: atrophy of epidermis (thin skin), plethoric facies, easy bruising, red striae
Neuropsychiatric: depressed mood and crying, decreased concentration and memory, insomnia, decreased libido
Proximal myopathy
Osteopaenia (may present with crush fractures of vertebrae)
Glucose intolerance (75%) or overt diabetes (25%)
Hirsutism
HTN
Menstrual disorders (amenorrhoea, oligomenorrhoea)
32
3 causes of ACTH-dependent Cushing's syndrome
Cushing's disease (pituitary adenoma)
Ectopic ACTH (paraneoplastic syndrome from usually small cell lung cancer)
Ectopic CRF
33
4 causes of ACTH-independent Cushing's syndrome
Adrenal adenoma
Adrenal carcinoma
Micronodular hyperplasia
Macronodular hyperplasia
34
List 4 causes of sellar masses
Tumour (benign and malignant)
Cysts
Lymphocytic hypophysitis
Carotid aneurysm
35
List 4 causes of sellar masses
Tumour (benign and malignant)
Cysts
Lymphocytic hypophysitis
Carotid aneurysm
36
List 6 adrenal problems which may cause Addison's disease
AI associated atrophy
Infections (TB, Pseudomonas, meningococcus, fungi including histoplasmosis and coccidiomyocosis, opportunistic infections in HIV and AIDS)
Infiltration (metastatic carcinoma e.g. lung, breast, stomach, colon, melanoma, lymphoma)
Haemorrhage/infarction (warfarin or heparin use, antiphospholipid syndrome)
Drugs (e.g. ketoconazole, aminoglutethimide)
Adrenoleukodystrophy
37
What 4 findings may be seen in Addison's disease on a U&E and on another simple blood test?
Hyponatraemia
Hyperkalaemia
Moderate metabolic acidosis
Increased urea
Hypoglycaemia
38
List 5 tests used to investigate Addison's disease. What are the expected results for each?
Serum cortisol: low (\>350 is normal if tested in the morning)
ACTH: high
Synacthen test: used to distinguish between adrenal and pituitary causes
Adrenal Abs (17-hydroxylase enzyme Abs) staining: +ive (but more often -ive)
Adrenal imaging: calcification or enlargement of adrenals (TB or infiltration)
39
How is Addisonian crisis treated?
Hydrocortisone 100mg IV 6hrly
IV fluids (normal saline)
Glucose if hypoglycaemic
40
How can Addison's disease be treated in the long term?
Glucocorticoids: cortisone acetate 25mg/12.5mg, dexamethasone 0.25mg BD, prednisolone 5mg daily
Add mineralocorticoids if the cause is adrenal: fluodrocortisone 0.1mg daily
Medic alert and advice on increasing steroid during times of stress
41
List 4 causes of primary aldosteronism
Unilateral aldosterone-producing adenoma (Conn's syndrome; surgical resection may offer a cure here)
Bilateral idiopathic hyperaldosteronism (harder to cure surgically)
Glucocorticoid suppressible hyperaldosteronism
Aldosterone-producing adrenal carcinoma
42
What is the clinical triad seen in primary aldosteronism?
HTN (this is the biggest clue)
Hypokalaemia (may not be present, +/- hypernatraemia)
Metabolic alkalosis
43
How might someone with hypokalaemia present?
5 P's:
Palpitations
Polydipsia
Polyuria
Peeing at night (nocturia)
Pounding headaches
44
How is primary aldosteronism treated, depending on the cause?
Surgical removal for adrenala adenoma
Aldactone (competitive antagonist to aldosterone)
Amiloride (K+ sparing diuretic; blocks Na+ channels in the proximal tubule thus decreasing K+ excretion)
45
When is inferior petrosal sinus sampling performed?
In suspected Cushing's disease
46
Ix for Cushing's syndrome and expected findings
FBE: look at Hb (high normal), WCC (slightly elevated with decreased neutrophils)
Electrolytes: hypokalaemia and metabolic alkalosis in ectopic ACTH
Hyperglycaemia due to insulin resistance
Increased calcium absorption and hypercalciuria
Establish Dx with 24 hr urine free cortisol and overnight dexamethasone suppression test (measure serum cortisol at 8am after 1mg dexamethasone at midnight, should be suppressed if no disease)
ACTH: if suppressed likely cause is adrenal, if normal or slightly elevated likely pituitary dependent, if very high likely ectopic ACTH (e.g. SCLC, medullary carcinoma of thyroid)
Imaging: pituitary (if adenoma, likely Cushing's disease), adrenals looking for tumours
47
Causes of Cushing's syndrome and effect on appearance of adrenals
48
What does these MRI pituitary scans show?
A) Typical appearance of pituitary microadenoma; hypodense lesion is seen in R side of gland (arrow), with deviation of pituitary stalk away from lesion
B) Large macroadenoma (arrow); unlike smaller tumors, large macroadenomas are invariably invasive and recur after surgery
.
49
How is Cushing's syndrome treated, depending on the cause?
Pituitary dependent: transphenoidal hypophysectomy to remove tumour
Adrenal adenoma or carcinoma: adrenal surgery
Ectopic ACTH or CRF: treat tumour associated with hormone production
50
What are the 2 main causes of adrenocortical insufficiency?
Insufficient secretion of ACTH by pituitary (hypopituitarism)
Destruction of adrenal glands (Addison's disease)
51
List 6 causes of Addison's disease
AI associated atrophy
Infections (e.g. TB, fungus including histoplasmosis and coccidiomycosis, HIV and AIDS)
Infiltration (e.g. in metastatic carcinoma)
Haemorrhage/infarction
Drugs
Adrenoleukodystrophy
52
Outline 5 features on examination of Addison's disease
Hyperpigmentation: buccal, palmar creases, lips, nail folds
53
How does presentation of adrenal disease differ depending on whether the cortex or medulla is affected?
Cortex: aldosterone excess (Conn's syndrome)
Medulla: catcholamine excess (phaeochromocytoma)
54
How is primary aldosteronism diagnosed?
24 hr urine collection: document inappropriate K+ wasting in presence of hypokalaemia
Plasma renin activity: suppressed
Plasma or urine aldosterone: increased, and fails to suppress after infusion of 2L NS over 4 hrs or high Na+ intake for 3 days
High aldosterone/renin ratio
CT or MRI scanning
131-I-iodocholesterol scanning
Adrenal vein sampling for aldosterone (risk of non-functioning adrenal tumour or bilateral disease)
55
What is phaeochromocytoma? Where do they most commonly arise? What is the malignancy risk?
Tumour of chromaffin cells located in adrenal medulla and derived from neural crest cells
90% arise in adrenal medulla with 5% bilaterally (esp in childhood or familial cases), 10% are extra-adrenal (e.g. base of brain, testis)
Malignancy risk 3-14%
56
Sx of phaeochromocytoma
Episodic, sudden and severe Sx, usually lasting less than 15mins
Spontaneous or elicited by exercise, bending over, defecation, abdominal pressure or drugs
Paroxysms of pallor, perspirations, palpitations (tachyarrhythmias), and labile blood pressure (causing headache; rarely hypotension, i.e. in the case of epinephrine, dopa or DA secreting tumours)
Suprarenal masses
57
Dx of phaeochromocytoma
Urine (24 hr collection) and plasma (but marked variability) metanephrines/non-metanephrines (DA, adrenaline, NA)
58
How can phaeochromocytoma be localised?
CT/MRI
Meta-iodo-benzyl-guanidine (MIBG) scanning (functional nuclear medicine scan)
Octreotide scanning
Venous samping (not typically)
59
What treatment should be given pre-operatively for phaeochromocytoma?
Alpha adrenergic blockade with phenoxybenamine 40-100mg daily or prazosin FIRST, and increase dose until normotensive with postural hypotension and nasal stuffiness
Give B blockers if necessary to reduce Sx, but always give AFTER alpha blockade to prevent adrenergic crisis
Treat any arrhythmias, cardiac failure and DM as required
60
What is the underlying cause of the very rare polyglandular AI syndrome type 1? How is it inherited?
Caused by AR inherited mutation in AI regulator (AIRE) gene on chromosome 21
61
What 8 endocrine abnormalities are seen in polyglandular AI syndrome type 1?
HypoPTH
Chronic mucocutaneous candidiasis
Adrenal insufficiency\*
Primary hypogonadism\*
Hypothyroidism\*
T1DM\*
Hypopituitarism\*
Diabetes insipidus
\*rarely
62
What 5 non-endocrine abnormalities are seen in polyglandular AI syndrome type 1?
Malabsorption syndromes
Alopecia totalis or areata
Pernicious anaemia
Chronic active hepatitis
Vitiligo
63
64
What is the underlying abnormality in the more common polyglandular AI syndrome type 2 and how is it inherited?
\>50% cases are familial, with varied inheritance patterns (AR, AD, polygenic all reported)
Associated with high titres of Abs to steroid-producing cells (i.e. adrenal, thyroid, testis, ovary)
65
List 5 endocrine abnormalities seen in polyglandular AI syndrome type 2
Adrenal insufficiency
AI thyroid disease
T1DM
Primary hypogonadism
Diabetes insipidus
66
How is MEN1 inherited?
AD (gene located on Ch 11)
67
List 7 on-endocrine abnormalities seen in polyglandular AI syndrome type 2
Vitiligo
Alopecia
Pernicious anaemia
Myaesthenia gravis
Immune thrombocytopaenic purpura
Sjogren's syndrome
RA
68
What does MEN stand for?
Multiple Endocrine Neoplasia syndromes (MEN1, MEN2a, MEN2b)
69
What kind of tumours are seen in MEN1 and what clinical syndromes arise as a result of these?
Parathyroid: primary hyperparathyroidism (most common)
Pituitary: prolactinoma, GH secreting tumours, ACTH secreting tumours, non-hormone secreting tumours
Pancreatic islet tumours: gastrinoma, glucagonoma, VIPoma (secreting vasoactive intestinal peptide, causing malabsorptive Sx and diarrhoea), insulinoma, non-functioning
70
How is MEN2 inherited and what is the underlying cause?
AD
Caused by mutations of the RET proto-oncogene on Ch 10
71
What tumours are seen in MEN2b?
Medullary carcinoma of thyroid (most common)
Phaeochromocytoma
Parathyroid hyperplasia
Mucosal neuromas (typically buccal; can also present with intestinal obstruction)
Intestinal ganglioneuromas (can present with intestinal obstruction)
Marfanoid habitus
72
What tumours are seen in MEN2a?
Medullary carcinoma of thyroid (most common)
Phaeochromocytoma
Parathyroid hyperplasia
