Endocrinology Flashcards
Management of eye disease in graves
- Supportive
Eye care with lubrication
control of hyperthyroidism
- NSAIds, Steroids, diuretics
- Cyclosporin, Azathioprine
- Radiotherapy
- surgical decompression
Outline the pre-op work up for hyperthyroid patients, what are the surgical options?
PRE-OP WORKUP
- confirm diagnosis TSH/ T4/T3
- check TSH - ab for graves
- RAI to differentiate - graves, toxic nodule or TMNG
- CT for retrosternal extension, tracheal compression
- Pre op drugs - betablocker, carbomazole +/- lugol’s
- Vocal cord check
- ECHO/ECG in hyperthyroid patients
- consider US scan to look for suspicious features - biopsy if needed
- Refer to ophthalmology for eye if needed
- Manange in conjunction with endocrinology
SURGICAL OPTIONS
- Graves - total thyroid + lifelong supplement vs subtotal thyroid
- TMNG - total thyroid + supplement
- Toxic nodule - hemithyroid
- Thyroididits (hashitoxicosis, de quervain’s, post partum) - No surgery
Outline the management options for hyperthyroidism with their relative pros and cons
Antithyroids
- carbimazole (or methimazole) first line
- agranulocytosis, hepatotoxicity, teratogenic
- PTU (safe in preg)
- if well tolerated, disease controlled and no high risk features (heart disease, elderly) this can be continued, but is not a definitive treatment.
Adjuncts
- Beta blocker - atenolol (25-50) - helps with palpitation, tachy, tremors
- Glucocorticoid - reduces T4 to T3 conversion
-
Iodine (Lugol’s is Pot Iodide) reduces
- thyroid hormone synthesis (Wolff-Chaikoff)
- thyroid hormone release
- Cholestyramine (4 g/day) - lowers t4, t3
RAI
- definitive treatment
- Not in presence of eye signs, pregnancy
- takes 6-18 weeks to work
- Shouldn’t conceive for 1-2 years after
- complications - salivary gland tumour, oligospermia/oligomenorrhea, increased risk of malignancy, no contact with children for 7 days
- Monitor for persisting hyper/hypothyroidism
Surgery
- definitive treatment
- failure of medical management
- concern about malignancy
- contraindication to RAI (pregnancy, eye signs)
- mechanical compression
- Retrosternal component, difficult to monitor
- Toxic nodules >3cm
Biopsy of neck node shows papillary cells - how can staining / immunohistochemistry help you in finding the primary?
Papillary Thyorid cancer
- Thyroglobulin (Tg) +ve
- TTF1 (thyroid transcription factor 1) +ve
Papillary lung cancer
- Tg -ve
- TTF1 +ve
Other sources (breast, Kidney)
- TG -ve
- TTF1 -ve
Which oncogenes can be mutated in patients with thyroid cancer?
PAPILLARY CANCER
- RET proto oncogene
- BRAF (60%)
- RAS gene (20%)
Follicular cancer
- RAS (50%)
Anaplasic / poorly diffentiated Thyroid cancer
- BRAF
Medullary thyroid cancer
- RET
Describe the Bethesda classification for thyroid lesions along with the their attendant cancer risk and your plan for each category
Bethesda
- Inadequate - (Ca risk - 1-4%) - repeat FNA
- Benign (0-3%) - clinical follow up
- Atypia of indeterminate significance (15%) - repeat FNA
- Follicular lesion - (30%) - hemithyroidectomy
- Suspicious for malignancy - (60%) - Lobectomy –> Total Thyroidectomy
- Malignant (99%) - Total thyroidectomy
Cancer risk in Bethesda 3 is controversial. Traditionally it was quoted to be around 15%. However more recent data suggest the risk may be higher and depends on the type of atypia. For nuclear atypia it can be as high as 46% where as for architectural distortion it is lower at 22%. Due to this some centres advocate a diagnostic hemithyroidectomy for bethesda 3 leisons.
Differentials for rapidly enlarging thyroid lump
PAINLESS
Anaplastic cancer
Lymphoma
PAINFUL
Riedels’ thyroiditis
Suppurative thyroiditis
Haemorrhage into cyst
What are the causes of hyperthyroidism, outline your basic investigation pathway
Causes with normal/increased RAI uptake
- Graves disease (TSH receptor antibody +, eye signs)
- TMNG
- Solitary adenoma
- TSH producing pituitary adenoma
- Thyrotoxic phase of Hashimoto’s
Low RAI uptake
- Thyroiditis (de quervain’s)
- Drugs
- Thyroxine
- Iodine (amiodarone, contrasts) (Jod Basedow effect)
- External thyroxine secretions
- struma ovary
- Metastatic thyroid disease
INVESTIGATION
confirm TSH low>> if nodular disease then progress to RAI uptake. If non nodular disease then TSH -ab to look for graves (if positive then treat as graves), if negative then continue to RAI uptake
Differences between sporadic PHPT and hyperparathyroidism due to MEN1
MEN1 related PHPT usually has the follwing features:
- euqual M:F incidence (c.f. more common in females for non MEN1 PHPT)
- earlier onset (20-40 yrs) c.f. 40-60
- Multigland involvement
- recurrent PHPT after a seemingly successful subtotal parathyroidectomy
When would you perform genetic testing in a patient with pheochromocytoma?
- Paraganglioma
- Bilateral adrenal pheochromocytoma
- Unilateral adrenal pheochromocytoma and a family history of pheochromocytoma/paraganglioma
- Unilateral adrenal pheochromocytoma onset at a young age (eg, <45 years)
- Other clinical findings suggestive of one of the syndromic disorders
Indication for adjuvant radioiodine therapy for thyroid cancer.
Adjuvant Radioiodine therapy is indicated in differentiated thyroid cancer presence of residual disease or high risk features or sometimes in presence of intermediate risk features. The decision is made in MDM setting in conjunction with oncologists and endocrinologists. Common indications include
- Metastatic disease
- Extrathyroidal extension
- Lymph node involvement (usually more than 0.2mm)
- Age >45yrs
- Cancer >4cm
- High risk features
- Tall cell
- columnar cell
- Hurtle cell variant
- insular growth pattern
- Follicular thyroid cancer
- Angio invasive cancer
Outline the main variation in pre-op, surgical approach and post op treatment of Medullary thyroid cancer when compared to differentiated thyroid cancer
MTC arises from parafollicular C cells that secrete calcitonin (reduces serum ca level). It is neuroendodermal in origin (originates from ultimobranchial body) and these cells do not have up-take for radioactive iodine.
These lead to several variation in management compared to DTcC
PRE OP
- Neck US to look for nodes, biopsy and suspicious nodes
- Check for RET mutation - if present check family members and check for MEN2 as below (note - germline mutation of RET will give rise to MEN2 whereas somatic mutation i.e. only in the cells affected, will give rise to MTC without MEN2
- check for MEN
- serum PTH and Calcium -> parathyroid adenoma
- metanephrines -> pheochromocytoma. Treat pheo before treating MTC
- Check serum calcitonin - if >500pcg/ml then check for metastatic disease
- CT neck, CAP
- CT liver triple phase/MRI
- bone scan/ MRI to rule out skeletal mets
SURGICAL APPROACH
- Total thyroidectomy with central node dissection and removal of any lateral compartments that have involved nodes
POST OP
- Thyroxine suppression is not needed, and radioiodine therapy is not beneficial
- Monitor with Calcitonin and CEA 6 monthly. If Calcitonin rises then make a search for metastasis or residual disease with scans
- Replace thyroxine
- Surgery is the main stem of treatment and adjuvant therapies are not very effective. External beam radiotherapy can be used.
- For tumours <2 cm and asymptomatic plus growing <20% per year - may not need any treatment.
- Tumours>2cm, symptomatic or growing >20%
- RET selective inhibitors (tyrosine kinase inhibitors like *nibs
- cytotoxic chemotherapy (Dacarbazine based) is used as next line
What are the causes of multinodular goitre?
- Iodine deficiency
- Goitrogens (cabbage, bressicae)
- Genetics - familial clustering with abnormality in
a. Tg gene
b. TSH receptor gene
c. Na/I symporter gene - Thyroiditis
- Drugs - Iodine, Amiodarone, Lithium
Symptoms relevant to various adrenal tumors
Mineralocorticoids - HTN, headaches, palpitation
Gluco - cushingoid, Wt. gain, lethargy, thin skin, neuropsychiatric symptoms
Sex steroids - Virilization, mood change
Pheo - HTN, sweating, palpitation, impending doom
Outline the pathophysiology and management of carpopedal spasm post thyroidectomy
This is a sign of moderate to severe hypocalcemia. Commonest cause post thyroidectomy is due to partial parathyroid gland devascularization or more rarely complete inadvertent parathyroidectomy. Calcium has memebrane stabilizing properties so in low Calcium states the threshold of action poetential drops (due to continously open Na channels) and an impulse is generated with minimal stimulation
MANAGEMENT PRINCIPLES
- Replace IV calcium (10-20 mls of 10mmol ampoules of Cal gluconate over 10-20 mins with saline)
- Monitor telemetry/involve ICU
- Check Ca, Mg, PTH levels
- Correct Mg
- Follow up IV calcium with slower infuson or oral Ca (1-4 g/day elemental Ca)
- Start Calcitrol (vit D) (25mcg)
- Cont oral Calcium and Vit D until levels normalizes
Note- perioral tingling and numbness are suggestive if mild hypocalcemia hence their treatment should start with Calcium and Mg level check folllowed usually by oral therapy.
