Endocrine Flashcards
What are the differentials for an adrenal mass?
Neoplastic
Cortex
- adenoma
- adrenal adenocarcinoma
Medulla
- phaeochromocytoma
- ganglioneuroma
- genglioneuroblastoma
Mesenchymal
- Myelolipoma
- Neurofibroma
Developmental
- Hamartoma
- Teratoma
Metastases
- Breast, lung, lymphoma, leukaemia
Non neoplastic
Nodular hyperplasia
Cyst
Haematoma
Amyloidosis
Granulomatosis
Functional tumours - conns, cushings, DHEA secreting
What is the definition of a adrenal incidentaloma?
Asymptomatic mass lesion > 1cm discovered by radiological imaging (CT, MRI) when done for another indication
1-4% (higher in elderly)
Bilateral in 10-15%
20% functional
What is the evaluation aimed at for an adrenal incidentaloma?
1) Is it malignant - radiological phenotype
2) Is it functioning - evidence of hormone overproduction
3) Does the patient have any previous history of malignancy?
What are the main causes for an adrenal incidentaloma?
Non functional adenoma (80%)
Functional adenoma
- cortisol producing (cushings) 5%
- aldosteronoma / Conn’s syndrome 1%
Phaeochromocytoma 5%
Adenocrotical carcinoma 5%
Metastatic disease 2.5%
(Less frequent causes include adrenal cyst, haemorrhage, lymphoma, sarcoma, neuroganglioma)
How is a MRI helpful in adrenal incidentalomas?
Helps to distinguish between adeomas (lipid rich intentisty), phaeochromocytoma (high intensity T2), ACC (central necrosis, haemorrhage, calcification, local invasion, IVC tumour thrombus)
What imaging characteristics are concerning for malignancy of an adrenal incidentaloma?
1) Size - >4cm is high risk of adrenocortical carcinoma (<4cm - 2%, 4-6cm - 6%, >6cm 25%)
2) Irregular shape
3) Heterogenous
4) Calcification
5) Unilateral
6) High attenuation on CT >20HU
7) Delayed washout (<50% after 10mins)
What are the functional tests required to assess for adrenal adenomas?
Phaeochromocytoma - plasma metanephrines (break down products of adrenaline and noradrenaline). >2x normal, then patient has phaeo. If inbetween, discontinue Bblocker/ACE inhibitor and retest. If still doubt, do 24h urine collections of catecholamines, metanephrines.
Cushings
- symptomatic - 24h urinary free cortisol
- asymptomatic - 1mg overnight dexamethasone suppresion test (95% sensitive). cortisol should be < 5 in the morning. If not, confirmatory testing for 24h urinary free cortisol. If confirmed do serum ACTH to confirm from adrenal and not pituitary
Aldosteronism
- Aldosterone Renin ratio
- Lesions are usually small and benign in appearance
- >20 reflects autonomous aldosterone secretion
Adrenocortical carcinoma
- DHEA-S and measures of clinically indicated steroids
What are the indications for adrenalectomy?
Phaeochromocytoma
Adrenocortical cancer (imaging features and size >4cm)
Functioning adenomas
What are the causes of cushings syndrome?
ACTH dependent
- Cushings disease -> pituitary hypersecretion of ACTH 65-70%
- Ectopic secretion of ACTH non pituitary tumours 10-15%
ACTH independent
- Iatrogenic from administration of glucocorticoids 80%
- Adrenocortical adenoma or carcinoma 20%
What investigations would be performed for cushings syndrome?
Initial
- 24h urinary cortisol excretion -> urinary cortisol excretion >3x upper limit of normal -> cushings
- Plasma ACTH concentration -> secretion can be episodic with measurement of 2 seperate days recommended. Low ACTH (ACTH independent disease) and high ACTH (ACTH dependent).
Confirmatory
-CRH stimulation - normally ACTH and cortisol levels increase. WIth adrenal tumours or ectopic ACTH, there is little or no response as pituitary ACTH is suppressed.
- - Low dose dexamethasone suppresion test. Assessment of non suppresible cortisol production by adrenal tumours. Dexamethasone will normally suppress pituitary ACTH secretion with reduction in cortosol. (overnight 1mg dexamethasone)
- High dose dexamethasone suppresion test. Distinguish cushings from ectopic ACTH secretion as cuhsings disease will usually suppress with high dose. Ectopic production non responsive. (overnight 8mg dexamethasone)
Imaging
ACTH-independent -> adrenal CT/MRI
ACTH-dependent -> pituitary MRI
What are the perioperative considerations for cushings syndrome?
Peri-operative hydrocortisone and post operative glucocorticoid replacement therapy
What are some of the causes of secondary hyperaldosteronism and how does this work?
Renal artery stenosis, CHF, cirrhosis, nephrotic syndrome
Low BP -> renin activated -> angiotension -» increase aldosterone
High renin and high aldosterone
What are the screening and confirmatory test for Conn’s syndrome
Screening
- Plasma aldosterone and plasma aldosterone to renin ratio (>20:1). Increase in both of these are required for diagnosis.
Confirmatory
- Saline infusion test - 2L isotonic saline over 4 hours with failure for the aldoserone level to fall results in primary aldosteronism
Subtype classification
- helps to distinguish aldosterone producing adenoma/carcinoma from bilateral hyperplasia
- Adrenal CT - if unilateral >1cm and normal contralateral gland in <40 yo patient (with increased age, increase likelihood, adenoma is non functioning)
- Adrenal vein sampling - IR received serum aldosterone to distinguish unilateral adenoma from bilateral hyperplasia. Measure cortisol sample at the same time to use as a control.
What are the hereditary cancer syndromes and the molecular genetics associated with adrenocortical carcinoma?
**Hereditary cancer syndromes **
1) Li-Fraumeni -> tp53 chromosome 17
2) Beckwith-Wiedemann syndrome -> 11q15
3) MEN1 -> 11q
**Sporadic molecular genetics **
Multistep progression with tp53, LOH and betacatenin mutations
What is the clinical presentation of adrenocortical carcinoma?
Hormone excess
- Cushings (45%)
- Mixed cushing/virilisation (25%)
- Virilisation (<10%)
- Hyperaldosteronism or feminisation <10%
Non functioning tumours
- Abdominal or flank pain
- Constitutional symptoms - weight loss or anorexia
What investigations would you arrange if suspicious for adrenocortical carcinoma?
Bloods
- BSL, K+, cortisol, ACTH, 24h urinary cortisol, 1mg dexamethasone suppresion, adrenal androgens (DHEAS, testosterone), serum oestradiol, plasma aldosterone, plasma metanephrines
Imaging
- CT/MRI - irregular shape, local invasion/mets, heterogenous, calcification, >4cm, high attenuation (>20HU), delayed contrast washout
- CT chest/abdo
- Bone scan
- FDG-PET -> not clear PET sufficietnyl accurate as single staging modality
What is the adjavant management of a adrenocortical carcinoma?
1) Adjuvant mitotane (suppresses adrenal cortex and alters peripheral metabolism of steroids). Improves disease free and overall survival following complete resection.
2) Adjuvant radiotherapy (incomplete resection, stage III, tumour spillage or high grade tumours)
3) Cytotoxic chemotherapy - doxorubicin, 5FU, adriamycin, methotrexate.
What are the sites of paragangliomas (10% of phaeo’s)?
Organ of zuckerkandl - collection of chromaffin cells at the origin of the IMA or aortic bifurcation
Bladder wall
Heart
Mediastinum
Carotid body
What are the causes of a phaeochromocytoma?
Sporadic (80%) -> predominately NA
Familial (15-20%) -> predominately Adrenaline
- MEN2A/2B
- Neurofibromatosis
- Von Hippel-Lindau disease
What is the appearnace of phaechromocytoma on histology?
Arranged in balls and clusters seperated by endothelial lined cystic spaces (zellballen pattern)
What is the clinical presentation of phaeochromocytoma?
1) Classic triad of episoid headache, palpitations and sweating
2) 50% have paroxysmal HTN
3) Complications (HTN crisis, cardiac arrythmias, MI, dilated cardiomyopathy, Pulmonary oedema, intracerebral haemorrhage or stroke)
How would you work up a patient suspicious of having a phaeo?
Screening
- Plasma metanephrines - breakdown of intra tumoural catecholamine metabolism (sensitivity 96%, specificity 85%). First line in high clinical suspicion.
- 24h urinary metanephrines and catecholamines - urinary creatinine to verify adequate collection. First line in low clinical suspicion.
- Medications to cease include TCA, levodopa, amphetamines and EtOH.
Confirmatory
- Clonidine suppresion - to distinguish false positive plasma caetcholamines/fractionated metanephrines
- 0.3mg orally and plasma catecholamines and metanephrines measured before and after 3 hours
Imaging
CT abdomen
- Non con > 20HU
- Marked contrast enhancement
- Bilateral or large size
MRI
- More specific in distinguishing phaeos from other adrenal tumours.
Dotate PET
- Biochemistry positive but imaging fails to demostrate tumour.
- Detect metastasis when MRI/CT positive
**Genetic testing **
History or presentation
- Paraganglioma
- Bilateral adrenal phaeochromocytoma
- Family hx of phaeo or paraganglioma
- Young age < 45 yo
Examination for signs of a genetic syndrome
- Retinal angiomas (VHL)
- Thyroid mass (MEN2)
- Cafe-au lait spots, axillary/inguinal freckling, SC neurofibromas (NF1)
- Neck mass (paraganglioma)
What is the management of phaeo?
Pre operative
- Alpha blocker with phenoxybenzamine 10mg POBD and this is increased 2-3 days until BP 120/80 with 20/10 postural drop. Requires at least 2 weeks and patients are encouraged to have a high Na+ diet to combat volume contraction
- Beta blocker if reflex tachycardia develops. Only started after alpha blockade established. Risk of HTN crisis 2nd to unopposed alpha stimulation after blockade of vasodilatory beta receptors
- Volume expansion with IVF
Operative
- Adrenalectomy. Laparoscopic if solitary, <8cm, no malignant features. Adrenal gland should be removed in sporadic cases. In case of MEN2 require complete bilateral adrenelectomy (require glucocorticoids intra op and life long). VHL require cortical sparing bilateral adrenelectomy
- HTN crisis mgmt with sodium nitroprusside, phentolamine, Nicardipine
Post operative
- Hypotension and hypoglycaemia
- Monitoring with plasma metanephrines annually to assess for recurrence
What are the differentials for a thyroid nodule?
Benign
- multinodular goitre
- thyroid cyst (colloid, simple, haemorrhagic)
- nodular thyroiditis
- follicular adenoma
Malignant
Primary
- Papillary ca
- follicular ca
- medullary ca
- anaplastic ca
- lymphoma
Secondary
- mets from breast, renal cell, others
What are the risk factors for thyroid malignancy?
Medical
- Neck irradiation (lag period of 6-35yeras)
- Autoimmune thyroiditis
Environmental
- Low iodine increases risk of follicular ca
- High iodine increase the risk of papillary ca
Family
- Medullary ca 20% associated with MEN2 syndrome. Familial medullary thyroid ca: AD RET gene, distinguished from MEN2 in that requires a prophylactic thyroidectomy
- Papillary is occasionally familial - AD, genes unknown.
- Follicular is rarely familial
What investigations would you request for a thyroid nodule?
1) Biochemistry
TFTs (hyperfunctioning nodules very low risk of ca)
Calcitonin (raised in meduallry ca and useful to follow up residual disease)
**Thyroglobulin **(raised in differentiated ca but also raised in graves, goitre, adenomas (not specific) as well as not sensitive. Useful in following up residual disease).
2) Imaging
Ultrasound **
- MNG or thyroid nodule
- Info - size and anatomy of thyroid, location and characteristics of nodule/s, lymph nodes.
- Features include Intensity of *echoes (hypoechoic concerning), internal structure* (solid v cystic),* sharpness of border*, Halo (incomplete concerning for malignancy), calcification (microcal - papillary and macrocal - medullary), *taller than wide, central vascularity *
**Thyroid scintigraphy **
- Ix for all nodules with hyperthyroidism
- 123 iodine
- T-99 can be used but not preferred
- WIll concentrate isotope less avidly than surrounding tissue
- Cold nodules require bx as well as intermediate nodules (not enough thyroid hormone to suppress TSH)
- Suppresion scan for follicular neoplasm or indeterminate follicular lesion. Thyroxine given to suppress TSH and scan repeated
3) Biopsy
- US FNA - indication based on TiRADS score. If multiple nodules, need to biopsy all suspicious lesions or at least one on either side
What are the categories of the bethesda criteria?
1 - non diagnostic - repeat FNA (wait 4weeks for haemorrhagic nodules)
2 - Benign (eisk <5%) - macrofollicaular pattern with small uniform non crowded cells smeared in colloid
3 - Follicular lesion or atypia of undetermined significance (FLUS or AUS). Risk of malignancy 10% - mild nuclear atypia and mixed macrofollicular / microfollicular pattern
4 - Follicular neoplasm (20%) - clusters sand clumps of uniform cells with varying pleomorphism. Malignancy is dependent on vascular or capsular invasion (not diagnosed on FNA). Includes Hurthle cell.
5 - Suspicious for malignancy (70%) - papillary, medullary, metastatic or lymphoma
6 - Malignant (97-100%)
What are the histological features of papillary thyroid cancer?
Nuclear holes (Orphan Annie eyes)
Psammoma bodies
Large cells with ground glass cytoplasm
What are the histological features of medullary thyroid cancer?
Spindle cells and nests of neuroendocrine cells
Stromal amyloid (congo red staining)
Calcitonin level measured with wash out fluid
Confirmed with immunohistochemistry
