Part two - endocrine Flashcards
Adrenal gland anatomy
Cortex derived from mesoderm near gonads
Medulla from ectoderm of neural crest
Right (pyramidal) lower than left (crescenteric)
Right relations - right crus, IVC, bare area liver
Left relations - left crus, aorta, spleen, pancreatic tail
Superior, middle and inferior adrenal arteries from inferior phrenic, juxtacoeliac aorta and renal artery respectively
Left adrenal vein = 2cm into left renal vein after joining inferior phrenic vein
Right adrenal vein = 0.5cm into IVC
Lymph drainage via para-aortic nodes
Myelinated preganglionic sympathetic via aorta and renal plexuses via splanchnic nerves to medulla
Cortical control is by ACTH so not neural
Cortex has three layers:
1 - zona glomerulosa - aldosterone
2 - zona fasciulata - cortisol
3 - zona reticularis - sex steroids
Bethesda categories for thyroid
I - nondiagnostic - <1%
III - atyptia of undetermined significance - 5-10%
IV - Suspicious for follicular neoplasm - 15-45%
V - Suspicious for malignancy - 60-75%
VI - malignant - 97-99%
Define Graves disease
Autoimmune hyperthyroidism caused by thyroid-stimulating antibody.
Most common cause of endogenous hyperthyroidism
Also known as diffuse toxic goitre
Pathogenesis of Grave’s disease
Stimulation of thyroid due to an IgG antibody (thyroid stimulation immunoglobulin/TSH antibody/TRAb) which reacts with and activates the surface receptor for TSH on thyroid epithelium.
Cycic AMP is formed, stimulating hyperplasia of the epithelium and increased formation of thyroid hormone and with its elevation, suppression of TSH.
What is the clinical triad of Graves’ disease?
- Hyperthyroidism with diffuse goitre
- Ophthalmopathy
- Pre-tibial myxoedema - minority
What is infiltrative ophthalmopathy?
Autoimmune induced volume of retro-orbital connective tissue and extra-occular muscles causing exophthlamos with complications of:
- Chemosis
- Conjunctivitis
- Corneal ulceration due to inability to close eyelid
- Ophthalmoplegia causing diplopia
Specific to Graves’ disease
What is the pathophysiology of infiltrative ophthalmopathy?
Orbital fibroblasts express TSH receptors These become target of autoimmune attack Retro-orbital space invaded by T cells Inflammatory oedema Accumulation of ECM components Increased fatty infiltration
What are the non-infiltrative eye signs in hyperthyroidism
Due to sympathetic overactivity and not specific for Graves’ disease
- Upper lid retraction = sclera visible above iris
- Stare - frightened expression
- Infrequent blinking
- Lid lag
Diagnosis of Grave’s disease
Elevated T3 and T4
Depressed TSH
TSAbs positive in 90%
Radioactive iodine uptake showing diffuse goitre
If thyrotoxic with infiltration eye signs, do not need I 123 radio-isotope uptake scan
Causes of thyrotoxicosis
- Graves’ disease - 80%
- Toxic multinodular goitre - 15%
- Solitary toxic nodule - 3%
- Other - 2%
Definition of thyrotoxicosis
Biochemical and physiologic effects of excess thyroid hormones regardless of cause
Define hyperthyroidism
Overproduction of thyroid hormone due to abnormal thyroid gland
What is thyroid storm?
Rare, life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Treatment of thyroid storm
- Propylthiouracil 200mg PO q4h
- Lugol iodine soln 10 drops one hour after above
- Propranalol 60-80mg PO every 4-6 hours
- Glucocorticoids - 100mg IV every 8 hours
What is medullary thyroid cancer?
An uncommon neuroendocrine thyroid neoplasm arising from parafollicular C cells (neural ectoderm)
What is the aetiology of medullary thyroid cancer:
80% sporadic
20% familial
- MEN2A and MEN2B
- Non-MEN familial form = familial MTC
RET proto-oncogene mutation in sporadic and familial cases
MACIS prognostic score for differentiated thyroid cancer
M - metastases, A - age, C - completeness of resection, I - LVI, S - size
MACIS = 3.1 (if aged less than or equal to 39 years) or 0.08 x age (if aged greater than or equal to 40 years), + 0.3 x tumor size (in centimeters), +1 (if incompletely resected), +1 (if locally invasive), +3 (if distant metastases present).
MACIS < 6: 99%
MACIS 6-6.99: 89%
MACIS 7-7.99: 56%
MACIS 8+: 24%
Where do you look for a missing superior parathyroid gland?
Above & lateral to intersection of RLN & ITA - 80%
Behind superior thyroid pole - 14%
Adjacent to ITA behind tubercle of Zuckerkandl - 4%
Retro- pharyngeal or -oesophageal - 1%
Above superior pole thyroid - 0.8%
Intrathyroid - 0.2%
If truly undescended, may be found within any of the 4th arch derivatives - pharyngeal wall, parapharyngeal space, neuromuscular structures within carotid sheath
Where do you look for a missing inferior parathyroid gland?
Behind inferior pole - 46% Thyrothymic ligament - 26% Anterolateral to inferior pole - 17% Just below intersection of RLN & ITA - 6% Above intersection of RLN & ITA - 2.8% Intrathymic - 2% Anterior mediastinum - 2% Intrathyroid - 0.2%
A truly undescended gland may be within the carotid sheath structures and may be found as superiorly as the skull base
Management of hypercalcaemic crisis
Aims are to lower serum calcium and treat the underlying disease.
There is a three-pronged approach
- Volume expansion
- Salmon calcitonin at 4IU/kg
- Bisphosphonate
Other considerations:
◦Correct hypokalaemia and hyponatraemia
◦With-hold exacerbating factors:
▪Milk
▪Alkaline products
▪Oestrogens
▪Thiazides
▪Vitamins A & D
◦Consider frusemide in a well hydrated patient
•Investigate for underlying cause
Bethesda system for reporting thyroid cytopathology
I Non-diagnostic 1-4% (rate of malignancy)
II Benign <1%
III Atypia of undetermined significance 5-10%
IV Suspicious for a follicular neoplasm 15-45%
V Suspicious for malignancy 60-75%
VI Malignant 97-99%
Suspicious features of a thyroid nodule on USS
Hypoechoic
Irregular margin
Central hypervascularity
Micro calcification
Histological features of papillary thyroid cancer
Well-differentiated branching papillae
Orphan Annie eyes = clearing of nuclei
Psoamma bodies = concentrically calcified structures
Nuclear grooving
Define phaeochromcytoma
Catecholamine-secreting neuroendocrine tumour arising from chromaffin cells of the adrenal medulla and certain extra-adrnal sites (paraganglioma)
What is the organ of Zuckerkandl?
Chromatin body derived from neural crest and located at the aorta bifurcation or near the origin of the IMA
Define paraganglioma
Catecholamine-secreting neuroendocrine tumour arising from extra-adrenal chromaffin cells due to failure of involution at birth- e.g. organ of Zuckerkandal, carotid body
Main conditions associated with MEN1
Pituitary adenoma
Parathyroid hyperplasia
Pancreatic neuroendocrine tumours
Main conditions associated with MEN2A
Medullary Thyroid cancer
Parathyroid hyperplasia
Phaeochromcytoma
Main conditions associated with MEN2B
Marfinoid habitus
Mucosal neuromas
Medullary thyroid cancer
Phaeochromocytoma
What are the genetic conditions associated with phaeochromocytoma?
MEN2 - 50%
Von Hippel Lindau syndrome - 20%
Neurofibromatosis type I - 2%
Mutations in the SDH gene in subunits B and D - 10%
How do you clinically diagnose MEN1
2:1 mutation rule
Presence of at least 2 MEN1 tumours in a patient
Presence of 1 MEN1 tumour in patient with MEN1 family history
Identified germline MEN1 mutation
Definition of primary parathyroidism
Autonomous secretion of PTH from one or more parathyroid glands
Causes of primary hyperparathyroidism
Single adenoma 85%
Multiple adenoma 5%
Hyperplasia 10%
Adenocarcinoma 1%
Diagnosis of primary hyperparathyroidism
Elevated (or normal) PTH Elevated corrected calcium Low (or normal) phosphate Serum vitamin D level ALP often elevated Serum chloride to phosphate ratio >33
Ancillary Investigations
- renal function
- bone densitometry +/- X-rays
- renal tract USS
Exclude other diagnoses
- PTHrP
- Serum protein electrophoresis
When is pre-operative localisation important in primary hyperparathyroidism?
Minimally invasive surgery Persistent hyperparathyroidism (after recent surgery) Recurrent hyperparathyroidism (after six months of cure)
Generally USS and sestamibi will suffice
What are the options for preoperative localisation for hyperparathyroidism
USS Sestamibi scintigraphy - planar, SPECT, thyroid subtraction T2-weighted MRI CT MET-PET-CT Angiography Venous sampling
Define secondary hyperparathyroidism
Increased parathyroid hormone in response to low plasma ionised calcium concentration
Aetiology of secondary parathyroidism
Renal failure
Malabsorption
Define tertiary hyperparathyroidism
Autonomous hyperplastic parathyroid gland(s) causing hypercalcaemia, usually occurring after renal transplantation
Treatment of medullary thyroid cancer
EXCLUDE PHAEOCHROMOCYTOMA
Total thyroidectomy + CND
Lateral neck (II-V +/- VII and thumusectomy) dissection if:
- central or lateral nodes involved
- tumour > 2cm
- calcitonin > 400
Test for RET mutation and family members if positive
EBRT if:
- positive margins
- extra nodal soft tissue extension
- extensive mediastinal tumour invasion
Follow-up
- Calcitonin & CEA
When would a grafted parathyroid gland’s function return?
6 weeks
Buzz words for parathyroid surgery
London tan colour
Meticulous haemostasis
Wobble within the capsule
RLN intimately associated with superior parathyroid
Sternotomy not to be undertaken at first operation
Adrenal vein sampling
For cortisol and aldosterone concentrations
Measure at adrenal vein and peripherally
5x indicates successful cannulation
